Amboss Cardiology

Hypertensive crises ypertensive crises refer to acute increases in blood pressure (generally defined as > 180/120 mm Hg) that cause or increase the risk of end-organ damage, i.e., damage to the brain (e.g., encephalopathy, stroke), eyes (e.g., retinopathy), cardiovascular system (e.g., ACS, pulmonary edema, aortic dissection), and/or kidneys (e.g., acute renal failure). They can be due to primary hypertension or precipitated by underlying conditions (e.g., pheochromocytoma, pre-eclampsia, drug toxicity). Management consists of rapidly identifying end-organ damage with patient history, physical examination, and focused testing, and determining whether the rapid lowering of the blood pressure with IV antihypertensives is required. The ideal IV antihypertensive agent should be chosen based on the underlying disorder, end-organ systems affected, and other patient factors. In the absence of end-organ damage, hypertensive crises should be managed with rapid follow-up and oral antihypertensives, as the prognosis is poor if they are left untreated.

Approach Approach to management Confirm blood pressure manually and on bilateral upper extremities. Determine if there are signs of end-organ damage. Focused history/physical (see "Clinical features" below)Select screening tests (see "Diagnostics" below) For hypertensive emergenciesABCDE approachAdmit patients (ideally to ICU).Lower the blood pressure acutely using IV agents and aim for targets based on the affected end-organs (see "Treatment" below).Evaluate and treat underlying disorders. For hypertensive urgencySelect, reinstitute, or modify oral antihypertensive therapy.In patients with a new diagnosis, evaluate for secondary causes of hypertension.Arrange follow-up, monitoring, and counseling. Red flags for hypertensive crisis Dyspnea Chest pain Altered mental status Focal neurologic symptoms Definition Preferred terminologyHypertensive crisis (acute severe hypertension): an acute increase in systolic blood pressure > 180 mm Hg and/or diastolic blood pressure > 120 mm Hg [1]Hypertensive urgency: hypertensive crisis without symptoms and with no signs of organ damageHypertensive emergency: hypertensive crisis with signs of end-organ damage, mainly in the cardiovascular, central nervous, and renal systems (see "Clinical features" below) Historical terminology Accelerated hypertension: identical to Malignant HTN Malignant hypertension: severe hypertension that occurs with retinopathy (flame hemorrhages, papilledema) Clinical features Hypertensive urgency Asymptomatic or nonspecific symptoms Although commonly associated with high blood pressure, isolated findings of nonspecific headache, dizziness, or epistaxis do not constitute end-organ damage. Hypertensive emergency Signs and symptoms of end-organ dysfunctionCardiacHeart failure exacerbation, pulmonary edema: dyspnea, crackles on examinationMyocardial infarction: chest pain, diaphoresisAortic dissection: chest pain, asymmetric pulsesNeurologicHypertensive encephalopathy: headache, vomiting, confusion, seizure, blurry vision, papilledemaIschemic or hemorrhagic stroke: focal neurological deficits, altered mental statusRenalAcute renal failure: azotemia and/or oliguria, edemaOphthalmicAcute hypertensive retinopathy: blurry vision, decrease in visual acuity, retinal flame hemorrhages, papilledemaOtherMicroangiopathic hemolytic anemia: fatigue, pallor Additional clinical features that may be present Signs of sympathomimetic drug toxicity In pregnant patients (in the second or third trimester ): signs of pre-eclampsia or eclampsia (see "Clinical features" in hypertensive disorders of pregnancy) Signs of catecholamine-secreting tumors (see "Clinical features" of pheochromocytoma) Diagnostics Evaluate for signs of end-organ damage [5][6] Laboratory studies CBC: signs of microangiopathic hemolytic anemiaBMP: altered electrolytes and/or elevated creatinine and urea, which suggest kidney failureBNP: elevated in heart failureTroponin: elevated in myocardial ischemiaUrinalysis: signs of glomerular injury (e.g., proteinuria, hematuria) ECG: left ventricular hypertrophy, signs of cardiac ischemia (e.g., ST depressions or elevations) Chest x-ray: cardiomegaly, pulmonary edema Additional evaluation to consider Urine pregnancy test Toxicology screen CT chest with IV contrast if chest pain is concerning for aortic dissection (see also "Diagnostics" in aortic dissection) Consider TTE if clinical features suggest pulmonary edema (see also "Diagnostics" in congestive heart failure). Consider CT head if neurological symptoms are present. Treatment Hypertensive urgency [1][4] Outpatient treatment is recommended. Move patient to a quiet room for 30 minutes. Reinstitute or increase the dosage of existing oral antihypertensive therapy. For patients with nonspecific symptoms that do not constitute end-organ damage (e.g., isolated headache, nonspecific dizziness, and epistaxis), consider a rapid-acting oral antihypertensive agent prior to discharge. [7]Clonidine Captopril Labetalol Prazosin Monitor patient for a few hours to ensure BP is improving. For patients with a first diagnosis of hypertension, consider evaluation for secondary hypertension. Discharge and follow-up Ensure close follow-up with an outpatient provider.Long-term treatment goals: See "Treatment" of hypertension.Sodium restriction diet Hypertensive urgency is usually caused by nonadherence to antihypertensive therapy. Aggressive intravenous antihypertensive therapy is not required. Hypertensive emergency [1][4] General principles ICU admission and immediate initiation of intravenous antihypertensive therapy (see table below) Continuous cardiac monitoring Consider intra-arterial blood pressure monitoring. Identify and treat any contributing comorbidities (e.g., chronic renal failure). IV fluids if signs of volume depletion Monitor BMP every 6 hours. Rate and target of blood pressure reduction General goalReduce BP by max. 25% within the first hour to prevent coronary insufficiency and to ensure adequate cerebral perfusion pressure.Reduce BP to ∼ 160/100-110 mm Hg over the next 2-6 hours.Reduce BP to patients baseline over 24-48 hours. Special casesIndications for the rapid lowering of systolic BP (usually to < 140 mm Hg) in the first hour of treatment include severe pre-eclampsia or eclampsia, aortic dissection, and pheochromocytoma with hypertensive crisis. [1]See "Treatment" in hypertensive pregnancy disorders.See "Treatment" in aortic dissection.See "Treatment" in pheochromocytoma. Mean arterial pressure should not be lowered by more than 25% within the first hour, except in special cases. Reducing the blood pressure too rapidly can lead to hypoperfusion and ischemia in certain organs (e.g., brain, kidney, heart). Choice of intravenous antihypertensive drug Consider the following factors when choosing an antihypertensive: Desired rate of decrease in blood pressureEnd-organ system affectedUnderlying disorderPresence or absence of comorbidities (e.g., heart failure, COPD)Pharmacokinetics and adverse effects of the agent Intravenous antihypertensives [1] Calcium channel blocker: NicardipineClevidipine Nitric-oxide dependent vasodilators: Sodium nitroprussideNitroglycerin Direct arterial vasodilators: hydralazine Antiadrenergic drugsSelective beta-1 antagonist: esmolol Nonselective beta blocker with alpha-1 antagonism: labetalol Nonselective alpha antagonist: phentolamine D1 agonist: fenoldopam ACE inhibitor: enalaprilat The response to and duration of action of IV hydralazine can be unpredictable. It should, therefore, be used with caution. Because prolonged use of sodium nitroprusside carries a risk of cyanide toxicity, it should be limited in dose and duration of use. Associated conditionPreferred intravenous antihypertensive [1]Additional considerationsAortic dissectionFirst-line Esmolol Labetalol Adjunctive: Sodium nitroprusside NicardipineBeta blockers should be administered before vasodilators (e.g., nicardipine, nitroprusside). Pulmonary edemaClevidipine Sodium nitroprusside Nitroglycerin Nitroglycerin is contraindicated if the patient has received a phosphodiesterase inhibitor(e.g., sildenafil, tadalafil) within the past 48 hours.Beta blockers are contraindicated if the patient has acute pulmonary edema, bradycardia, 2nd/3rd-degree heart block, or cardiogenic shock. Acute coronary syndromeNitroglycerin Esmolol Labetalol NicardipineEnalaprilat is contraindicated in acute coronary syndrome. Acute renal failureClevidipine NicardipineFenoldopamNitroprusside and esmolol should be avoided. Catecholamineexcess Clevidipine NicardipinePhentolamine Benzodiazepines are the first-line treatment for sympathomimetic drug toxicity.Beta blockers should be avoided. Acute ischemic stroke/Acute intracerebral hemorrhage Labetalol Clevidipine NicardipineFenoldopam, nitroprusside, and nitroglycerin should be avoided. These drugs can increase intracranial pressure and reduce cerebral perfusion. Eclampsia/severe pre-eclampsiaHydralazine Labetalol NicardipineACE inhibitors (e.g., enalaprilat), ARBs, renin inhibitors, and nitroprusside are contraindicated. The drugs most commonly used to treat hypertensive emergencies are nitroprusside, labetalol, and nicardipine. Prognosis If left untreated, hypertensive emergencies are associated with a 1-year mortality rate of > 80% and a median survival of 10-11 months. [1]

Chest pain Nontraumatic chest pain is one of the most common causes of emergency department visits and is common in both inpatients and outpatients. The differential diagnosis is broad and includes cardiac (e.g., acute coronary syndrome, pericarditis), gastrointestinal (e.g., GERD, gastritis, PUD), musculoskeletal (e.g., costochondritis), and psychiatric (e.g., generalized anxiety disorder, panic attack) etiologies. Any life-threatening causes of chest pain, such as acute coronary syndrome and pulmonary embolism, should be immediately evaluated and assessed. Once life-threatening causes have been ruled out (either by patient history, examination, or rapid diagnostics), a more thorough history and examination should be performed to narrow the differential diagnosis and guide further diagnostic workup and therapy. Traumatic causes of chest pain are not addressed here.

Approach to management [1] ABCDE survey Obtain 12-lead ECG: If ECG shows STEMI, see "Treatment" in acute coronary syndrome. Establish IV access. Continuous telemetry and pulse oximetry Initiate supplemental O2 if there is evidence of hypoxemia. Perform a focused history and physical examination. Perform targeted diagnostics (see "Diagnostics" below) and further tests as required. Treat the underlying cause. Red flags for chest pain Sudden onset Exertional chest pain Substernal or left-sided pain Radiation to the left arm, jaw, and/or back Associated shortness of breath Quality of chest pain: crushing, pressure (e.g., "an elephant sitting on my chest"), tearing, or ripping New murmur Diaphoresis, nausea, or vomiting Chest wall crepitus Distant heart sounds Difference > 20 mm Hg in systolic blood pressure between arms [2] Pulsus paradoxus Hypotension Hypoxia Immediately life-threatening causes Acute coronary syndrome (STEMI, NSTEMI, unstable angina) Pulmonary embolism Aortic dissection Tension pneumothorax Cardiac tamponade Esophageal rupture Diagnostics The diagnostic workup should be guided by the pretest probability of the diagnoses under consideration. The following list includes some commonly used diagnostic tools that can be helpful in diagnosing or ruling out possible etiologies in patients with undifferentiated chest pain. Laboratory studies Troponin [3] D-dimer CBC ESR/CRP BMP LFTs Lipase, amylase BNP Type and screen Coagulation studies (e.g., INR, PTT) Lactate Cultures (e.g., blood cultures, sputum cultures) Procalcitonin Toxicology screen Respiratory virus panel Hepatitis panel Imaging 12-lead ECG X-ray of the chest FAST bedside ultrasound X-ray of the abdomen (upright) X-ray of the ribs CT chest with contrast CT pulmonary angiogram CT abdomen and pelvis with IV contrast Right upper quadrant ultrasound TTE and/or TEE Lung ultrasound V/Q scan Duplex of the extremity Cardiovascular causes STEMI [4]Heavy, dull, pressure/squeezing sensationSubsternal pain with radiation to left shoulderNausea, vomitingDiaphoresis, anxietyDizziness, lightheadedness, syncopePain may improve with nitroglycerin.ECG: ST-segment elevation/depression, T-wave inversions, Q waves ↑ Troponin TTE: hypokinesis, regional wall motion abnormalitiesNSTEMI/UA [5]ECG: nonspecific changes, including T-wave inversions, ST-segmentdepressions Increased or normal troponinTTE: Regional wall motion abnormalities may be present.Aortic dissection [6][7][8]Sudden onset of severe, sharp tearing chest or abdominal pain that radiates to the back Hypotension, syncope, neurological symptoms Asymmetrical blood pressure, pulse deficit New diastolic murmur Symptoms of myocardial ischemia Elevated D-dimer ECG: nonspecific ST-segment changesCXR: widening of the aorta CT angiography of chest/abdomen/pelvis: intimal flap with false lumen TEE: proximal aortic dissection, tamponade, aortic regurgitation Cardiac tamponade[9]Tachypnea, dyspneaTachycardiaPulsus paradoxusCardiogenic shockBeck triad: hypotension, elevated JVD, muffled heart soundsECG: low voltage, electrical alternans CXR: enlarged cardiac silhouette TTE: circumferential fluid layer, collapsible chambers , high EF, dilated IVC Inspiration: Both ventricular and atrial septa move sharply to the left.Expiration: Both ventricular and atrial septa move sharply to the right. Pericarditis [10][11]Sharp, pleuritic, retrosternal chest painExacerbated by lying down; improved by leaning forwardNot relieved with nitratesHigh-pitched pericardial friction rub ↑ ESR, ↑ CRP, leukocytosis↑ Troponin [10]ECG: diffuse, ST-segment elevations without reciprocal ST-segmentdepression, PR-segment depression, or T-wave inversionsCXR: normalTTE: Pericardial effusion may be present.Heart failureexacerbation [12][13][14][15]Chest pressureCough, dyspneaHypoxemiaCrackles, JVD, peripheral edemaClinical diagnosisLabs: ↑ BNP, ↑ troponin, hyponatremiaCXR: diffuse opacities, Kerley B linesTTE: global or focal wall abnormalities, systolic and/or diastolic dysfunction, decreased LVEF Gastrointestinal causes Noncardiac chest pain is most commonly due to gastrointestinal and musculoskeletal disorders. [16] Esophageal perforation [17][18]Retrosternal chest pain, neck pain, epigastric pain with radiation to the back Dyspnea, tachypnea, tachycardiaDysphagiaSigns of sepsisMackler triad (chest pain, vomiting, subcutaneous emphysema)Mediastinal crepitusHistory of recent endoscopy or severe emesis (Boerhaave syndrome)CXR, upright AXR: mediastinal air and/or subdiaphragmatic air, pleural effusion, pneumothorax Lateral neck x-ray: subcutaneous emphysemaContrast esophagography (gold standard): contrast leak [19]CT chest (with oral contrast) : extraluminal air, esophageal thickeningGERD and erosive esophagitis [20][21]Postprandial substernal chest pain, pressure, burning, reflux symptomsAggravated by lying in the supine position and certain foods (e.g., coffee, spices)Epigastric tendernessClinical diagnosisDefinitive diagnosis requires EGD and/or 24-hour esophageal pH monitoringPeptic ulcer disease [22][23][24]Epigastric painDuodenal ulcer: pain relieved with food; weight gain Gastric ulcer: pain exacerbated by food; weight loss Signs of GI bleedHistory of NSAID intakeAnemia, positive FOBT (in cases of bleeding ulcer)Urea breath test for H. pylori: positive in most cases of PUD EGD: mucosal erosions and/or ulcers Acute pancreatitis [25][26][27]Severe epigastric pain that radiates to the backNausea, vomitingEpigastric tenderness, guarding, rigidityUpper abdominal painHypoactive bowel sounds History of gallstones or alcohol use↑ Lipase, amylase Abdominal ultrasound: pancreatic edema, peripancreatic fluid, gallstonesAbdominal CT with IV contrast : pancreatic edema, peripancreatic fat stranding, gallstonesMallory-Weiss syndrome[28][29]Epigastric pain that radiates to the backRepeated episodes of severe vomitingHematemesis Melena, dizziness, syncope CBC: anemiaEGD: longitudinal mucosal tears, typically at the gastroesophageal junction Pulmonary embolism [30] Pleuritic chest painAcute onset dyspnea, hypoxemiaCough, hemoptysisUnilateral leg swelling or history of DVTHypotension, shock (if massive PE)Elevated D-dimer ↑ Troponin, BNP ECG: normal sinus rhythm (most common), sinus tachycardia, signs of right ventricular strain CTA chest: pulmonary artery filling defect V/Q scan: perfusion-ventilation mismatch TTE: right ventricle hypokinesis with normal apical movement Wells criteria for pulmonary embolismTension pneumothorax [31][32]Severe, sharp chest painDyspnea, hypoxemiaHistory of traumaHyperresonance, decreased breath sounds, tracheal deviationTachycardia, hypotensionClinical diagnosisCXR: absent lung markings, tracheal deviation, pneumomediastinumPneumonia [33]Fever, chillsCough, dyspneaHypoxemiaCrackles, egophonyLabs: leukocytosis, ↑ ESR/CRP, ↑ procalcitoninPositive sputum cultureCXR: consolidation, pleural effusionCT chest with IV contrast: hyperdense consolidation Spontaneous pneumothorax [34][31][35]Sudden, sharp unilateral chest pain Acute dyspneaHypoxemiaHyperresonance, decreased breath sounds on affected sideCrepitusHistory of lung disease or trauma CXR (in inspiration): increased lucency, displaced lung markings, subcutaneous emphysemaUltrasound: absent lung slidingAsthma exacerbation [36]Dyspnea, coughTachycardiaTachypnea, hypoxemiaDiffuse wheezing, decreased or absent breath soundsIncreased work of breathingABG: ↓ pH, ↑ PaCO2, ↓ PaO2 (respiratory acidosis) Peak expiratory flow: decreased from predicted or personal bestPleural effusion [37][38]Unilateral, pleuritic chest painDyspneaDry, nonproductive coughDullness to percussion, decreased breath sounds, decreased tactile fremitusPleural friction rubCXR: homogeneous opacity with blunting of the costophrenic angle Ultrasound: hypoechoic space between the parietal and visceral pleura Other causes Costochondritis [39] Clinical features Sharp, well-localized pain that is reproducible on palpation of costal cartilageHistory of recent exercise/exertion/chest wall trauma Diagnostics: Clinical diagnosis [39]CXR: normal Treatment: Pain managementAcetaminophenNSAIDs (e.g., naproxen, ibuprofen)Supportive care: reduction of activities that provoke symptoms, cough suppressants, heat or ice packs Acute herpes zoster [40][41] Clinical features Severe burning or throbbing painThoracic dermatomes most commonly affectedMaculopapular rash that develops into a vesicular rash in a dermatomal distributionImmunocompromised status Diagnostics: Clinical diagnosisPCR of vesicle fluid positive for varicella-zoster virus DNA [41] Treatment: Antivirals Panic disorder [42] Clinical features: Chest tightness, palpitations, tachycardiaTachypneaDiaphoresis, dizzinessParesthesiasAnxious appearanceRecent stressful exposure Diagnostics: Clinical diagnosis Treatment: Breathing exercisesConsider benzodiazepines for an acute episode (e.g., lorazepam, diazepam).Assess for suicidal ideation. [42][43]Psychiatry consult and/or referral for cognitive behavioral therapy Functional chest pain [20][44] Clinical features: Retrosternal chest pain or discomfortNo associated esophageal symptoms (e.g., no heartburn, dysphagia) Diagnostics: Diagnosis of exclusionRome IV criteria for functional chest pain Treatment: Reassure the patient.Referral to psychologist [44]Consider initiating medical therapy with one of the following: TCA (e.g., amitriptyline)SARI (e.g., trazodone)SSRI (e.g., sertraline) SNRI (e.g., venlafaxine) Rome IV criteria for functional chest pain A set of criteria used to evaluate functional chest pain. Criteria include 1) retrosternal chest pain or discomfort not attributed to a cardiac cause, 2) the absence of esophageal symptoms (e.g., heartburn, dysphagia), 3) absence of gastroesophageal reflux and eosinophilic esophagitis, and 4) absence of esophageal motor disorder. Differential diagnoses CardiacAcute coronary syndromeCardiac tamponadePericarditisMyocarditisEndocarditisTakotsubo cardiomyopathyAortic dissectionValvular disease (e.g., aortic stenosis, mitral regurgitation, aortic regurgitation)Stable anginaVasospastic anginaHypertensive crisisHeart failure exacerbationPostcardiac injury syndromePostmyocardial infarction syndromePostpericardiotomy syndrome PulmonaryPulmonary embolismTension pneumothoraxPneumothoraxPneumoniaBronchitisAsthma exacerbationCOPD exacerbationHemothoraxPulmonary edemaPleural effusionPleuritisFibrinous pleuritisRheumatoid pleuritisLupus pleuritisPulmonary sarcoidosisLung contusionPulmonary infarctLung abscessLung cancer MusculoskeletalCostochondritisChest traumaChest wall painRib fractureRib contusionOsteoarthritis of the sternoclavicular or manubriosternal jointOsteoarthritis of the shoulder jointsFibromyalgiaSlipping rib syndromeTietze syndromeOveruse myalgiaThoracic outlet syndrome GastrointestinalEsophageal perforationBoerhaave syndromeMallory Weiss syndromeGastroesophageal reflux diseaseAcute erosive gastritisAcute erosive esophagitisEosinophilic esophagitisDyspepsiaPeptic ulcer diseaseEsophageal motility disorder AchalasiaDistal esophageal spasmHypercontractile esophagusEsophageal hypersensitivitySliding hiatal herniaBiliary colicCholelithiasisCholedocholithiasisCholecystitisAcute pancreatitisAcute hepatitisLiver abscessFitz-Hugh-Curtis syndrome RenalRenal infarctRenal capsular hematoma DermatologicalAcute Herpes zosterPostherpetic neuralgia Hematologic/OncologicAcute pain crisisAcute chest syndromeMalignancyMalignant pleural effusionSplenic infarct RheumatologicRheumatoid arthritisSLEFibromyalgia Functional chest pain PsychiatricGeneralized anxiety disorderPanic disorderMajor depressive disorderSomatic symptom disorderSubstance use disorders (e.g., cocaine, methamphetamines, alcohol)Illness anxiety disorder See also differential diagnosis of increased troponin and differential diagnosis of ST-elevations on ECG.

Syncope Syncope is a sudden, completely reversible loss of consciousness secondary to an acute reduction of cerebral perfusion, which may last from several seconds up to minutes. The most frequent form is vasovagal syncope, which is triggered by emotional stress or prolonged standing, and may be diagnosed with the tilt table test. Orthostatic syncope may occur upon suddenly standing up after prolonged sitting or lying down. It is caused by a drop in blood pressure. This relatively benign cause may, however, lead to life-threatening injuries as a result of falls. A thorough medical investigation is necessary as syncopes may also be the result of a serious cardiovascular disorder (e.g., cardiac arrhythmia or valvular stenosis). The treatment strategy is dependent on the cause of the syncopes.

Cardiac syncope Heart's inability to meet an increased oxygen demand (e.g., during exertion)→ reduced cerebral perfusionArrhythmogenic syncopeBradycardia/tachycardia → ↓ ejection fractionSick sinus syndromeVentricular tachycardiaAtrioventricular blockSupraventricular arrhythmiasAdams-Stokes syndromeTorsades de pointes Cardiovascular syncopeStructural outflow obstructionMassive MIAortic stenosisMitral valve prolapseAtherosclerosisPulmonary embolism Pulmonary hypertensionHypertrophic cardiomyopathySevere asymmetric septal hypertrophyCardiac tamponade Reflex syncope(Most common cause) Neurally mediated syncope that can be due to parasympathetic hyperactivity(cardioinhibitory response), sympathetichypoactivity (vasodepressor response), or a combination of both → vasodilatation (vasodepressor response) and/or bradycardia (cardioinhibitory response) → reduced BP → reduced cerebral perfusion Neurocardiogenic syncope (subtype of vasovagal syncope)Prolonged standing (and no compensatory heart rate acceleration)Common in younger patients(unusual to have first episode after age 40)Can be recurrent Emotional syncope (subtype of vasovagal syncope)Pain or emotional stressPainFearSight of bloodInjury Carotid sinus syndromeIncreased carotid sinus sensitivity(frequently associated with arteriosclerotic changes in the carotid sinus) → ↓ systolicblood pressure when pressure is applied to the carotid sinusPressure on the carotid sinuses (e.g., during a massage, when shaving, tightening a necktie) Other situational syncopesVagotonic, peripheral vascular dilationCoughSwallowMicturition syncopes(commonly seen in males with prostatichyperplasia) Orthostatic syncope(postural hypotension)Standing up/postural change→ insufficient counterregulation due to autonomic dysfunction (e.g. decreased baroreceptor sensitivity in the elderly)→ reduced cerebral perfusionSympathotonic orthostatic hypotensionWhen standing up: ↓ systolic blood pressure despite excessive sympathotonic counter regulation (significant heart rate increase) → reduced cerebral perfusionHypovolemia(dehydration, hemorrhage, use of diuretics such as thiazides),Medications(vasodilators such as alpha-blockers, and ganglionic blocking agents)Prolonged bed rest Asympathotonic orthostatic hypotensionWhen standing up: ↓ systolic blood pressure without sympathotonic counterregulation (steady or even reduced heart rate) → reduced cerebral perfusionDiabetic autonomic neuropathiesParkinson's autonomic dysfunction Postural tachycardia syndrome (PoTS, orthostatic intolerance)When standing up: no significant drop in blood pressure, but massive heart rateincrease within 10 minutes of standing up Clinical features Prodrome: presyncopeVasovagal: impairment of senses, nausea, pallor, warmth, diaphoresis, lightheadedness, and hyperventilationOrthostatic: lightheadedness, nausea, and dizzinessCardiac: no prodrome; often sudden fall Rapid onset loss of consciousnessAccompanied by complete loss of muscle toneLast seconds to minutes followed by spontaneous recoveryConvulsive syncope: common form in which loss of consciousness is accompanied by myoclonic movements Thorough neurological and cardiopulmonary assessments, including pulse and blood pressure measurement in the supine, standing, and sitting positions, are crucial for identifying the underlying etiology! Diagnostics Patient history: Determine triggers, ask witnesses how patient behaved during event, and medication/medical/family history. Routine investigationsECG (for all patients!) CBC (↓ serum Hb) Additional tests Cardiac origin suspected (see also cardiac arrhythmia) Cardiac monitoring (If ECG is not diagnostic and a cardiac cause is strongly suspected): sinus bradycardia< 40/min, sinus pauses > 3 seconds, atrioventricular (AV) or bundle branch blocks Stress ECG (ischemia)Echocardiography: if structural heart disease is suspected or ECG is abnormalCardiac enzymesCarotid ultrasound with dopplerPulmonary origin suspected : chest x-ray (suspected pneumonia, lung mass) and ventilation/perfusion scanning (suspected pulmonary embolus)Neurological origin suspected : head imaging (CT, MRI, or MRA showing ischemia or hemorrhage) and EEG(seizure)Other laboratory tests : abnormal electrolytes, abnormal urinalysis ↑ BUN/creatinine ratio (assess for signs of hypovolemia in orthostatic hypotension), stool occult blood testManeuvers Testing for orthostatic hypotension or vasodepressor syncopePatient is asked to stand after being in supine position for at least 5 minutes → Blood pressure is measured each minute for at least 3 minutes.If systolic BP decreases by ≥ 20 mm Hg and the diastolic BP decreases by ≥ 10 mm Hg, or BP < 90 mm Hg→ orthostatic hypotensionCoinciding bradycardia → vasodepressor syncope Tilt table testDetermines if vasovagal or orthostatic syncope is presentProcedure The patient is strapped onto a tilt table in a supine position for 15 minutes, and then is raised passively to an angle of around 70°.Positive: reflex hypotension (systolic blood pressure < 90 mm Hg) and bradycardia (vasovagal) or slow progressive hypotension (orthostatic) with presyncope or syncopeNegative (normal): increased heart rate along with barely changed blood pressure and no clinical signs of syncope or presyncope Differential diagnoses Non-syncopal eventsMedical history and clinical featuresDiagnosisSeizureEpileptic symptoms (e.g., aura, postictal state, lateral tongue biting, bladder/bowel incontinence)Abnormal EEGBrain lesions visible in imaging (CT, MRI)Subclavian steal syndromeOccurs when straining the ipsilateral armRare: complete loss of consciousnessFocal-neurological signs during an attack (e.g., double images, dysarthria)Duplex ultrasound of the carotid and subclavian arteries showing stenosisVertebrobasilar insufficiency"Drop attacks" can be seen with a TIA in the vertebrobasilar circulation.Other neurologic deficits will be seen as well.CT/MRIHypoglycemiaDiabetesClinical symptoms: symptoms of autonomic counterregulation (e.g., restlessness, sweating, pale skin)↓ Blood glucoseCraniocerebral injuryConsiderable head trauma (e.g., from falling) leading to traumatic brain injuryIsolated eventPathology on imaging (CT, MRI)HeatstrokeThe body is unable to regulate the core body after it becomes elevated.Syncope can precede exertional heatstroke.Elevation in: Creatinine kinaseCBCAST/ALTNormal ECGHyperventilationCan occur when stressedOften occurs in patients with panic disordersArterial blood gas: respiratory alkalosisCryptogenic drop attacksThe cause of many falls, especially in older patients, remains elusive despite extensive diagnostic testing. These falls/attacks are called cryptogenic drop attacks. Treatment Treat underlying conditionArrhythmogenic syncopes may require a pacemaker or treatment with antiarrhythmic drugs.Patients with carotid sinus syndrome should be advised to avoid tight collars and remain hydrated. Vasovagal syncopesPhysiological counterstrategies: Crossing the legs, tensing muscles, lying down, and elevating the legs can reverse the syncope.Avoid triggers Orthostatic syncopesSufficient intake of sodium and fluidsCompression stockingsAdjust medications (e.g., diuretics)Fludrocortisone if unable to manage episodes with nonpharmacological interventions Complications Depends on the underlying condition Cardiac syncope is associated with one-year mortality rates of up to 33%. Fall injuries

Beta blockers Beta blockers are a group of drugs that inhibit the sympathetic activation of β-adrenergic receptors. Cardioselective blockers (e.g., atenolol, bisoprolol) primarily block β1 receptors in the heart, causing decreased heart rate, cardiac contractility, cardiac workload, and AVN conduction. Nonselective beta blockers (e.g., pindolol, propranolol) inhibit all β receptors and may cause bronchoconstriction, peripheral vasoconstriction, and metabolic imbalances (e.g., hypoglycemia and hyperglycemia, hypertriglyceridemia) in addition to cardiac effects. Cardioselective beta blockers have a lower side-effect profile and are preferred in the management of coronary heart disease, compensated heart failure, acute coronary syndrome, and certain types of arrhythmias. Propranolol, a nonselective beta blocker, is the first-line drug in the management of essential tremor, portal hypertension, migraine prophylaxis, and thyroid storm. Beta blockers are contraindicated in patients with symptomatic bradycardia, AV block, decompensated heart failure, and asthma. Initiation and cessation of beta-blocker therapy should always be gradual to avoid side effects or symptoms of withdrawal (e.g., rebound tachycardia, hypertension, acute cardiac death).

Cardioselective beta blockers(β1 selective)With ISAAcebutololCeliprololWithout ISAAtenololMetoprololEsmololBisoprololBetaxololBevantololNebivolol Selectively bind to and block β1receptors, which are primarily found in the heart Decrease HR, contractility, and AVNconductivity Nebivolol is the only beta blocker that causes NO-mediated vasodilation Bradycardia Bradyarrhythmia Cardioselectivity is dose-dependent: β2 receptor blocking activity increases with higher doses Generally do not cause bronchoconstriction or vasoconstriction Generally do not interfere with glycogenolysis; safe in diabetics Coronary heart disease Compensated heart failure Acute coronary syndrome Cardiac arrhythmias (e.g., AF, PSVT) Nonselective beta blockers(β1, β2, and β3receptors)With ISAPindololPenbutololOxprenolol Without ISAPropranololNadololSotalolTimololTertalol Block β1, β2, and β3 receptors Sotalol also blocks cardiac potassium channels (antiarrhythmic effect). Cause bronchoconstriction: may exacerbate asthma/COPD Cause vasoconstriction: avoid in patients with peripheral vascular disease Can cause hypo- and hyperglycemia Can cause bradycardia and syncope Alternative to cardioselective beta blockers PropranololEssential tremorPortal hypertensionMigraineprophylaxisThyroid storm Sotalol: cardiac arrhythmias Timolol: glaucoma With additional α-blockingactionLabetalolBucindololCarvedilolPotent vasodilatorsBecause of their α-blocking action: vasodilation → ↓ peripheral vascular resistance, ↓ preload, ↓ afterload, and improved renal blood flowImprove endothelial function and vascular remodeling Same as side effects of nonselective beta blockers(both with and without ISA)Orthostatic hypotensionPregnancy-inducedhypertension (e.g, labetalol) With the exception of nebivolol, all cardioselective beta blockers begin with the letters A to M (B1 = first half of the alphabet). Except for beta blockers with alpha-blocking action, all noncardioselective beta blockers begin with the letters N to Z (B2 =second half of the alphabet). Effects of β-adrenergic blockade β1 Heart Anti-ischemic effect: β1 blockade → ↓ heart rate and ↓ cardiac contractility → ↓ BP and ↓ oxygen consumption by the heart → anti-ischemic effect Antiarrhythmic effect: β1 blockade → ↓ AVN conduction, ↑ AVN refractory time, and ↓ heart rate → anti-arrhythmiceffectAnti-remodeling effect Kidneysβ1 blockade of the juxtaglomerular cells → ↓ renin release → ↓ angiotensin II conversion → ↓ H2O resorption → ↓ BP β2Smooth muscleVasculature: vasoconstriction Bronchioles: bronchoconstrictionCiliary body of the eye↓ Aqueous humor production → ↓ intraocular pressure [11]Pancreatic beta cells↓ Insulin release → hyperglycemia and new-onset diabetes Skeletal muscle↓ Glucose uptake (↓ insulin sensitivity) Liver↓ Hepatic glycogenolysis → hypoglycemia (esp. in diabetics)Lipoprotein lipaseenzymeInhibits lipoprotein lipase → ↑ triglycerides and ↓ HDL → hyperlipidemiaβ3Adipose tissue↓ Lipolysis → weight gain Beta blockers competitively inhibit adrenergic substances (e.g., adrenaline, noradrenaline) at β receptors! A rule to remember the main effector organs for β receptors: There is 1 heart - β1 blockers act on the heart; there are 2 lungs - β2 blockers affect bronchial smooth muscles. Intrinsic sympathomimetic activity (ISA) [7] Mechanism of action: partial agonist activity Beta blockers with ISA bind to and stimulate the β-adrenergic receptor (agonistic effect) while competitively inhibiting the binding of epinephrine and norepinephrine to β-adrenergic receptors (antagonistic effect).Produce partial sympathetic activity while inhibiting the normal and activated sympathetic activity EffectsCause less bradycardia and less peripheral vasoconstriction because of their mild agonistic action.Have a favorable effect on lipid profile (esp. pindolol and acebutolol): preferred in patients with metabolic syndrome [9]Not recommended in patients with congestive heart failure, ischemic heart disease, and tachyarrhythmias Agents: pindolol, acebutolol, carteolol, alprenolol Beta blocker adverse effectsNonselective beta blockers and cardioselective beta blockers (β1-receptor and β2-receptor blockade)CardiacBradycardia Bradyarrhythmia Ventricular tachyarrhythmia (Torsades de pointes) Worsened heart failure (HF) Orthostatic hypotension (esp. in elderly patients) CNS Drowsiness, sleep disorders, nightmaresFatigue/lethargyDepression, hallucinationsCholesterol levelsHypertriglyceridemia, ↓ HDL levels with beta blockers without ISA CutaneousPsoriasis Nonselective beta blockers (β2-receptor blockade) PulmonaryBronchoconstriction (esp. patients with asthma and reactive airwaydisease) DyspneaBronchospasmExacerbation of asthma and COPDPeripheral vasculaturePeripheral vasoconstrictionErectile dysfunctionSecondary Raynaud phenomenonCold extremitiesMetabolicHyperglycemia and new-onset diabetes Hypoglycemia Weight gain Beta-blocker withdrawal Caused by the sudden termination of beta blockers Clinical features: tachycardia, tachyarrhythmia, hypertension, acute coronary syndrome, sudden cardiac death Prevention: Taper dose over 7-10 days before discontinuing. Beta-blocker overdose Clinical features: bradycardia/bradyarrhythmia, cardiogenic shock (hypotension; cold, clammy extremities), hypoglycemia, hyperkalemia, wheezing (bronchoconstriction), neurological symptoms (seizure, delirium, coma) [17] TreatmentSecure the airways.Correct cardiovascular decompensation (hypotension, bradycardia, and cardiogenic shock). IV fluids and vasopressors (e.g., epinephrine)IV atropine: to correct bradycardiaIV glucagon: antidote for beta-blocker poisoning IV calcium salts: to improve cardiac contractilityIV high-dose insulin with glucose: If cardiovascular decompensation is refractory to all of the above-mentioned agents, high-dose insulin is given for its positive inotropic effect. Prevent further absorption of beta blocker: activated charcoal/gastric lavage , IV lipid emulsions (esp. useful in lipophilic beta-blocker overdose). Indications Cardiovascular indications Hypertension (β blockers lower BP by ↓ cardiac output and ↓ renin secretion) [33] Coronary artery disease Acute myocardial infarctionβ-blockers should be initiated early in all patients (without contraindications) and continued long-term if tolerated.β-blockers decrease the size of the infarct and also reduce early and delayed mortality rates in patients with acute MI.Angina pectoris: first-line treatment for stable angina pectoris in addition to ACE inhibitors or angiotensin-receptor blockers [33] Heart failure: cardioselective β blockers (preferred) in combination with ACE-I/ARB and spironolactone (slows progression of CHF) [33][10] Atrial flutter/fibrillation, PSVT, VT, and premature ventricular contractions: β-blockers are class II antiarrhythmic agents (e.g., metoprolol, esmolol, propranolol).[34] Specific indications for propranolol Essential tremor Migraine prophylaxis [35] Portal hypertension Hyperthyroidism and thyroid storm Infantile hemangioma Miscellaneous Hypertensive crises (e.g., malignant hypertension): IV labetalol (rapid onset of action) Glaucoma: topical β blockers (timolol, betaxolol) Pregnancy-induced hypertension: Labetalol is a first-line drug. Absolute contraindications Symptomatic bradycardia Sick sinus syndrome (without a pacemaker); heart block greater than first-degree Cardiogenic shock and hypotension Pheochromocytoma Decompensated heart failure Combination with calcium channel blockers (diltiazem or verapamil): can precipitate AV block Relative contraindicationsAsthma and COPD Psoriasis Raynaud phenomenon, peripheral artery occlusive disease Pregnancy (except labetalol, which is used to treat pregnancy-induced hypertension)

Antiarrhythmic drugs Antiarrhythmic drugs are used to prevent recurrent arrhythmias and restore sinus rhythm in patients with cardiac arrhythmias. These drugs are classified based on their electrophysiological effect on the myocardium. Antiarrhythmic drugs do not improve the survival of patients with non-life-threatening arrhythmias and may increase mortality, particularly in patients with structural heart disease. They are associated with severe adverse effects, primarily due to their proarrhythmic effects on the myocardium. Patients who have received an intravenous antiarrhythmic should be monitored closely with serial ECGs. Several classes of antiarrhythmics, including beta blockers, calcium channel blockers, amiodarone, cardiac glycosides, and lidocaine, also have other medical uses, which are discussed in their respective learning cards.

Class IA antiarrhythmicsFast sodium channel blockers Reduce conduction velocity (negative dromotropy), particularly in depolarized tissue (e.g., during tachycardia) State-dependent: The faster the heart rate, the greater the effect.Decreases the slope of phase 0depolarizationStabilize membrane Categorized into 3 subgroupsbased upon their effects on the Na+ channel and the action potential (AP) durationModerate blockade of Na+ channels(intermediate association/dissociation)Prolong AP duration(right shift)Slow conduction velocity Prolong effective refractory period (ERP)Weak blockade of the K+ channel QuinidineProcainamideDisopyramideAjmalineParoxysmal supraventricular tachycardia (PSVT): AVNRT and AVRTAntidromic AVRTand WPW(procainamide)Atrial fibrillation(AFib) and atrial flutterVentricular arrhythmiasQT prolongation → torsade de pointesThrombocytopeniaQuinidine: cinchonismProcainamideDrug feverDrug-induced lupus erythematosus(reversible)Disopyramide: anticholinergic effects Class IB antiarrhythmicsWeak blockade of Na+ channels (fast association/dissociation)Shorten AP duration Slow conduction velocityNo effect on or slight prolongation of ERPStrongest effect on ischemic myocardiumLidocaineMexiletinePhenytoinVentricular arrhythmias(especially post-MI)CNS: dizziness, nausea, seizuresCardiovascular: AV conduction block, ventricular extrasystoles Class IC antiarrhythmicsStrong blockade of Na+ channels (slow association/dissociation) → QRS prolongationNo to minimal effect on AP duration (no shift) Slow conduction velocityProlong ERP in AV nodeand accessory tractERP unaffected in Purkinje and ventricular tissueFlecainidePropafenonePSVTAFib (cardioversion)Atrial flutterProarrhythmogenic: contraindicated post-MI Class II antiarrhythmic drugsBeta blockersInhibit β-adrenergic activation of adenylate cyclase → ↓ cAMP → ↓ Ca2+ → ↓ SA and AVnode activity Decrease slope of phase 4 in pacemaker cellsSlow conduction velocityProlong AV node repolarizationProlong PR intervalMetoprololEsmololPropranololAtenololTimololCarvedilolSotalolAFib (rate control)Atrial flutterPSVTPremature ventricular contractionsVentricular arrhythmiasAtrial premature beats [3]Causes: AV block, bradycardiaSedation, CNSdepressionExacerbation of asthma, COPDDyslipidemia(metoprolol)Hypoglycemia HyperkalemiaAvoid in patients with concurrent cocaine use and/or pheochromocytoma: unopposed α1 agonism → ↑ blood pressure, coronary and systemic vasoconstriction(except labetalol and carvedilol ) Class III antiarrhythmic drugsPotassium channel blockersInhibit delayed rectifier potassium currents Prolong QT intervalProlong AP duration (reverse use dependence) and ERP No effect on conduction velocityAmiodarone DronedaroneSotalolBretyliumIbutilideDofetilideAFib (cardioversionand rhythm control)Atrial flutterVentricular arrhythmias (not bretylium)SotalolSupraventricular arrhythmiasVentricular arrhythmiasQT prolongation → torsades de pointes(TdP)AmiodaroneLowest risk of ventricular arrhythmiacompared to other drugs in its class [2]Reversible corneal depositsSkin photosensitivityPulmonary fibrosisLiverdysfunctionPeripheral neuropathyThyroiddysfunctionSotalol: see beta blocker adverse effects Class IV antiarrhythmic drugsCalcium channel blockersInhibit slow calcium channels Decrease slope of phase 0 and 4 → slower conduction velocity → increased ERPProlong AV node repolarizationProlong PR intervalVerapamilDiltiazemNifedipine AFib (rate control)Atrial flutterPSVTMultifocal atrial tachycardiaHypertension(nifedipine)VerapamilAV blockBradycardiaConstipationNifedipineHeadache, flush, pitting edemaReflex tachycardiaDiltiazem: adverse effects similar to those of both verapamil and nifedipine, but less prominent Class V antiarrhythmic drugsVariable mechanismsSee "Other antiarrhythmic drugs" below for details.Adenosine (drug)DigoxinMagnesium sulfateSee belowSee below All antiarrhythmic drugs are also potentially proarrhythmic! Intravenous administration should only be performed with continuous cardiac monitoring! Other antiarrhythmic drugs Adenosine (drug) [1] Mechanism of action: activates Gi protein → inhibition of adenylate cyclase → ↓ cAMP → deactivation of L-typeCa2+ channels and activation of K+ channels → ↓ Ca2+ and ↑ K+ entry → hyperpolarization → transient AV node block→ acute termination of supraventricular tachycardia IndicationsDiagnosis and termination of certain forms of paroxysmal supraventricular tachycardias (e.g., AVNRT and orthodromic AVRT)Diagnosis of underlying AFib in supraventricular tachyarrhythmias Adverse effectsChest pain, flushing, hypotension, bronchospasmSense of impending doomAV blockAsystole ContraindicationsPre-excitation syndromes: antidromic AVRT, WPW AV blockAsthma Avoid adenosine in patients with suspected pre-excitation tachycardia (e.g., WPW), because it may exacerbate the tachycardiavia accessory pathway routes! Digoxin Mechanism of action: inhibits Na+/K+-ATPases → higher intracellular Na+ concentration → reduced efficacy of Na+/Ca2+ exchangers → higher intracellular Ca2+ concentration → increased contractility, decreased heart rate IndicationsAFibAtrial flutterChronic systolic heart failure See cardiac glycosides. Magnesium sulfate [9][1] Mechanism of action: decreases calcium influx → prevents early afterdepolarizations (EAPs) IndicationsTorsade-de-pointesRefractory ventricular tachyarrhythmias (e.g., polymorphic VT)EclampsiaConstipationTocolysis Adverse effectsHypotensionAsystoleDrowsinessFlushLoss of reflexesRespiratory depression If-channel blocker Drug: ivabradine Mechanism of action: selectively inhibits If channel in the pacemaker cells of the SA node → prolongs slow depolarization (phase 4) → slows heart rate Indications: symptomatic stable coronary heart disease and congestive heart failure (NYHA II-IV) in patients who cannot tolerate beta blockers Adverse effectsVision changesBradycardiaHypertension

Overview of cardiac arrhythmias Cardiac arrhythmias are accelerated, slowed, or irregular heart rates caused by abnormalities in the electrical impulses of the myocardium. Bradyarrhythmias include sinus node dysfunction and atrioventricular block, and are characterized by a resting heart rate < 60/minutes. Tachyarrhythmias (heart rates > 100/minute) are classified as supraventricular arrhythmias or ventricular arrhythmias. Supraventricular arrhythmias originate between the sinus node and the atrioventricular node. Ventricular arrhythmias originate below the atrioventricular node, on the ventricular level. This learning card provides an overview of cardiac arrhythmias based on the heart rate and site of origin of the arrhythmia. For details of the individual arrhythmias, see the corresponding learning cards. For the medical treatment of arrhythmias, see the learning card on antiarrhythmic drugs.

Classification Bradyarrhythmias Definition: heart rates of < 60/min Types: see bradyarrhythmias below Tachyarrhythmias Definition: heart rate of > 100/min Supraventricular arrhythmias Definition: arrhythmias that originate in the sinoatrial node, atrial myocardium, or atrioventricular node (regular QRS complex) Types: see supraventricular tachyarrhythmias below Ventricular arrhythmias Definition: arrhythmias that originate below the atrioventricular node (wide QRS complex) Types: see ventricular tachyarrhythmias below Bradyarrhythmias Respiratory sinus arrhythmiaPhysiological, particularly in youths Minor changes in the R-R interval during respiration: reduction during inspiration and increase during expiration Sinus bradycardia Physiological, particularly in athletesSinus node dysfunction (see sick sinus syndrome)Drugs: beta blockers, calcium channel blockersRate < 60 bpmNormal P wave before every QRS complex Sinoatrial pause or arrestMay occur in healthy individualsUnderlying cardiovascular disease (see sick sinus syndrome)Transient absence of the P wave Tachycardia-bradycardia syndrome Abnormal supraventricular impulse generation and conductionSee sick sinus syndrome for detailsIntermittent tachyarrhythmias and bradyarrhythmias AV node origin Atrioventricular blockFirst-degreeblock Physiological responseIncreased vagal toneDrugs: beta blocker or calcium channel blocker PR interval > 200 ms Second-degreeblock Drugs: digoxin, beta blocker, calcium channel blockerIncreased vagal toneSinoatrial conduction diseaseRight coronary infarctionMobitz type I/Wenckebach: progressive lengthening of the PR interval until a beat is dropped Mobitz type II: irregular dropped beats w/ constant prolonged PR interval Third-degreeblock Complete block: no communication between the atria and ventricles AV dissociation: no relationship between P waves and QRS complexes Tachyarrhythmias Supraventricular arrhythmias Supraventricular premature beats Physiological response in healthy individualsElectrolyte imbalancesUnderlying cardiovascular diseaseP wave abnormalities or absent P waves Sinus tachycardia Sympathetic activation or vagal withdrawal on the SA node Gradual onsetRegular rhythmRate: max. rate usually 180 bpmP wave: normal morphology Narrow QRS complex Atrial flutterMacroreentrant rhythms within the atriaRegular rhythm Rate: atrial 250-350; ventricular < 200 P wavesOccur before every QRS complexSawtooth appearance of regular P waves (flutter waves) especially in leads II, III, and aVF Narrow QRS complex Atrial fibrillation Multiple mechanisms which are not completely understoodRhythm: irregularly irregularRate: 350-450 bpm; < 200 P-waves are indiscernibleNarrow QRS complex Atrial tachycardia(∼ 5%) Focal atrial tachycardiaDischarge from a single ectopic focus in the atriumVery abrupt onset Regular rhythmRate: 150-250P wave: morphology varies depending on the site of the ectopic focusOccurs before the QRS complexNarrow QRS complex Multifocal atrial tachycardia(MAT) Discharge from multiple ectopic foci in the atriumAssociated with pulmonary disorders (e.g., COPD exacerbation, pulmonary embolism), cardiac conditions (CHF exacerbation), and treatment with theophyllineVery abrupt onset with rate variationRhythm: irregularly irregularRate: 150-250Discernible P waves with ≥ 3 differentP wave morphologies; no single morphology is predominant Narrow QRS complex AV node originAtrioventricular reentry tachycardia (AVRT)A form of paroxysmal supraventricular tachycardia Tachycardia caused by an accessory pathway between the atria and ventriclesVery abrupt onset Regular rhythmRate: 150-250P waveInverted (downgoing in II, III and aVF and/or upright in aVR) Occur after the QRS complexRP interval is shorter than PR intervalQRS complexOrthodromic AVRT: narrow QRS complexAntidromic AVRT: wide QRS complexwith delta waves AV nodal reentry tachycardia(AVNRT) A form of paroxysmal supraventricular tachycardiaA dysfunctional AV node that contains two electrical pathways Regular rhythmRate: 150-250P waves occur during (i.e. are not visible) or after the QRS complexRP interval is shorter than PR intervalNarrow QRS complex Junctional tachycardia The AV node takes over the pacemaker function Digitalis toxicity Myocarditis Myocardial infarction Regular rhythm Rate: 100-130 P waves occur before, during, or after the QRS complex P waves are inverted AV dissociation may occur Narrow QRS complex Ventricular arrhythmias Premature ventricular beats Ectopic beat that originates from a ventricular focusDue to hypoxia, hyperthyroidism, electrolyte abnormalitiesPremature, wide QRS complex that is not preceded by a P waveCompensatory pause after the premature beat Ventricular tachycardia Coronary artery diseaseMyocardial infarctionStructural heart diseasesRegular, rapid rhythmWide QRS complexes (≥ 3 consecutive premature ventricular beats) Monomorphic VT (most common): single QRS morphologyPolymorphic VT: multiple QRS morphologiesAV dissociation (P waves may or may not be discernible) Torsade de pointestachycardia Associated with Long QT syndromeProarrhythmic drugsElectrolyte abnormalities (hypokalemia)Polymorphic ventricular tachycardia with QRS complexes that appear to twist around the isoelectric line Ventricular fibrillation Myocardial infarction Structural heart diseases Arrhythmic, fibrillatory baseline, usually > 300 bpm Erratic undulations with indiscernible QRS complexes

Hypertension Hypertension is a common condition that affects one in every three adults in the United States. The AHA/ACC guidelines define it as a blood pressure of ≥ 130/80 mm Hg and by JNC 8 criteria as ≥ 140/90 mm Hg. Hypertension can be classified as either primary (essential) or secondary. Primary hypertension accounts for approx. 95% of cases of hypertension and has no detectable cause, whereas secondary hypertension is due to a specific underlying condition. Typical underlying conditions include renal, endocrine, or vascular diseases (e.g., renal failure, primary hyperaldosteronism, or coarctation of the aorta). Clinically, hypertension is usually asymptomatic until organ damage occurs, which then commonly affects the brain, heart, kidneys, or eyes (e.g., retinopathy, myocardial infarction, stroke). Common early symptoms of hypertension include headache, dizziness, tinnitus, and chest discomfort. Hypertension is diagnosed if blood pressure is persistently elevated on two or more separate measurements. Further diagnostic measures include evaluation of possible organ damage (e.g., kidney function tests) and additional tests if an underlying disease is suspected. Treatment of primary hypertension includes lifestyle changes (e.g., diet, weight loss, exercise) and pharmacotherapy. Commonly prescribed antihypertensive medications include ACE inhibitors, angiotensin receptor blockers, thiazide diuretics, and calcium channel blockers. Management of pediatric patients and pregnant women differs from that of nonpregnant adults because some of these drugs are contraindicated in these patient groups. To treat secondary hypertension, the underlying cause needs to be addressed. See also hypertensive crises.

Definition AHA/ACC 2017 definition: persistent systolic blood pressure of ≥ 130 mm Hg and/or diastolic blood pressure ≥ 80 mm Hg JNC 8 definition: persistent systolic blood pressure of ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg Definition of hypertension in children < 13 years: blood pressure ≥ 95th percentile to < 95th percentile + 12 mm Hg OR systolic blood pressure ≥ 130 mm Hg and/or diastolic blood pressure ≥ 80 mm Hg (whichever is lower) [1][2] Epidemiology PrevalenceOne in three adults in the US is affected.Prevalence increases with age (∼ 65% among those ≥ 60 years of age). African Americans are more commonly affected than Asian American or white individuals. 60-75% of obese and overweight patients are affected. Sex: ♂ > ♀ below age of 45; the sex ratio is almost balanced at > 45 years of age (i.e., after menopause) Most common risk factor for cardiovascular disease Etiology Primary (essential) hypertension No specific cause; multifactorial etiology including epigenetic/genetic and environmental factors Accounts for 85-95% of cases of hypertension in adults Accounts for 15-20% of cases of hypertension in children < 12 years of age Age at onset: 25-55 years (prevalence is increasing in adolescents) Risk factors Nonmodifiable risk factorsPositive family historyEthnicityAdvanced age Modifiable risk factorsObesityDiabetes Smoking, excessive alcohol or caffeine intakeDiet high in sodium, low in potassium Physical inactivityPsychological stress Secondary hypertension Caused by an identifiable underlying condition Accounts for 5-15% of cases of hypertension in adults Accounts for 70-85% of cases of hypertension in children < 12 years of age Age at onset < 25 years or > 55 years Causes Endocrine hypertensionPrimary hyperaldosteronism (Conn syndrome): most common cause of secondary hypertension in adultsHypercortisolism (Cushing syndrome)HyperthyroidismPheochromocytomaPrimary hyperparathyroidismAcromegalyCongenital adrenal hyperplasia Renal hypertension Renovascular hypertension (e.g., due to renal artery stenosis)Polycystic kidney disease (ADPKD)Renal failure (renal parenchymal hypertension) GlomerulonephritisSystemic lupus erythematosusRenal tumors Coarctation of the aorta Obstructive sleep apnea Medication: sympathomimetic drugs, corticosteroids, NSAIDs, oral contraceptives Recreational drug use: amphetamines, cocaine, phencyclidine Isolated systolic hypertension: See "subtypes and variants" below for details. Clinical features Hypertension is usually asymptomatic until:Complications of end-organ damage arise (see "Complications" below)Or an acute increase in blood pressure occurs (see hypertensive crisis below) Secondary hypertension usually manifests with symptoms of the underlying disease (e.g., abdominal bruit in renovascular disease, edema in CKD, daytime sleepiness in obstructive sleep apnea). Nonspecific symptoms of hypertension Headaches, esp. early morning or waking headache Dizziness, tinnitus, blurred visionFlushed appearanceEpistaxisChest discomfort, palpitations; strong, bounding pulse on palpationNervousnessFatigue, sleep disturbances Since hypertension is often asymptomatic, regular screening is necessary to prevent end-organ damage! Subtypes and variants White coat hypertension (white coat effect) Definition: arterial hypertension detected only in clinical settings or during blood pressure measurement at a physician's practice Etiology: anxiety experienced by the patient Clinical features: consistently normal blood pressure measurements and normalization of elevated blood pressure outside of a clinical setting Diagnostics: 24-hour blood pressure monitoring Isolated systolic hypertension (ISH) Definition: increase in systolic blood pressure (≥ 140 mm Hg) with diastolic BP within normal limits (≤ 90 mm Hg) EtiologyISH in elderly: decreased arterial elasticity and increased stiffness → decreased arterial complianceISH secondary to increased cardiac outputAnemiaHyperthyroidismChronic aortic regurgitationAV fistula Clinical features: Often asymptomaticSigns of increased pulse pressure: e.g., head pounding, rhythmic nodding, or bobbing of the head in synchrony with heartbeatsSymptoms of hypertension (see "clinical features" above) Diagnostics: See "diagnosis of hypertension" below. Treatment: thiazide diuretics or dihydropyridine calcium antagonists Prognosis: high risk of cardiovascular events (MI, stroke, renal dysfunction) Diagnostics General approach Blood pressure monitoring Repeated measurements on both arms : Hypertension is diagnosed if the average blood pressure on at least two readings obtained on at least two separate visits is elevated. Long-term measurement of blood pressure (24 hours) See "Blood pressure measurement" for the basic approach to measurement. AHA/ACC 2017 BP categoriesBP categorySystolic blood pressure (mm Hg)Diastolic blood pressure (mm Hg)Normal blood pressure< 120and< 80Elevated120-129and< 80Stage 1 hypertension130-139or80-89Stage 2 hypertension≥ 140or≥ 90 JNC 8 BP categoriesBP categorySystolic blood pressure (mm Hg)Diastolic blood pressure (mm Hg)Normal blood pressure< 120and< 80Prehypertension120-139or80-89Stage 1 hypertension140-159or90-99Stage 2 hypertension≥ 160or≥ 100 Initial evaluation of newly diagnosed hypertensive patients Stratification of cardiovascular risk: fasting blood glucose, lipid profile (HDL, LDL, and triglycerides levels) Evaluation of end-organ damage and underlying causesComplete blood countRenal function tests: serum creatinine and eGFRSerum Na+, K+, and Ca2+Urinalysis TSH Electrocardiogram (ECG) Approach to diagnosing secondary hypertension General indicators of secondary hypertensionYoung age (< 30 years) at onset of hypertensionOnset of diastolic hypertension at an older age (> 55 years)Abrupt onset of hypertensionEnd-organ damage that is disproportionate to the degree of hypertensionRecurrent hypertensive crisesResistant hypertension: hypertension that is resistant to treatment with at least three antihypertensivesof different classes including a diuretic Specific indicators (For details regarding individual diagnostic procedures, see the individual learning cards.) Diagnostic findingsUnderlying condition HypokalemiaConn syndrome Renal artery stenosis Metabolic alkalosis and ↑ aldosterone-to-renin ratioConn syndrome Difference in blood pressureIn both armsTakayasu arteritisAortic dissectionAortic arch syndrome Subclavian steal syndromeOf upper and lower limbsCoarctation of the aorta distal to the left subclavian artery Daytime sleepiness (Epworth scale, Berlin questionnaire) Nondipping in 24-hour blood pressure monitoring Obstructive sleep apnea Increased 24-hour urinary metanephrinesPheochromocytoma ↑ Serum calcium, ↑ PTH level, ↓ serum phosphatesHyperparathyroidism ↑ Serum cortisolExcess of glucocorticoids (e.g., Cushing syndrome)↓TSH, ↑ free T4Hyperthyroidism Screening for hypertension (USPSTF recommendations) [36] Individuals 18-39 years of age with normal blood pressure (< 130/85 mm Hg) and without other risk factors: Screen every 3-5 years. Individuals > 40 years of age or who are at increased risk for high blood pressure : Screen every year. Treatment Nonpharmacological measures (lifestyle changes for managing hypertension) Intervention (in order of effectiveness)TargetApproximate systolic BP reduction in hypertensive patientsWeight lossIdeal body weight1 mm Hg per kg reduction in body weight in overweight individualsDASH dietDiet rich in fruits, vegetables, and whole grains; low in saturated and trans fats11 mm HgDecrease dietary sodiumDaily sodium intake < 1500 mg/day5-6 mm HgExerciseAerobic90-150 minutes per week65-75% of maximum heart rate (e.g., brisk walk)5-8 mm HgDynamic resistance (e.g., weight training)50-80% of maximum strength6 exercises with 3 sets per exercise and 10 repetitions per set90-150 minutes per week4 mm HgIsometric resistance (e.g., hand grip exercise)30-40% of maximum strength4 repetitions/session, 3 sessions/week for 8-10 weeks5 mm HgIncrease dietary potassiumDaily potassium intake 3.5-5 g4-5 mm HgDecreased alcohol intake♂: ≤ 2 drink daily♀: ≤ 1 drink daily4 mm HgSmoking cessationCompletely quit smoking3-5 mm Hg after 1 year; 6-7 mm Hg after 3 years [43] Nonpharmacological measures should be pursued in any patient with a systolic BP > 120 mm Hg or a diastolic BP > 80 mm Hg! GuidelineIndication for pharmacological therapyTreatment goalAHA/ACC 2017BP ≥ 140/90 mm HgBP ≥ 130/80 mm Hg with a 10-year-risk of cardiovascular death ≥ 10% (e.g., patients with age ≥ 65 years, diabetes mellitus, chronic kidney disease, heart failure, stable ischemic heart disease, peripheral artery disease, and/or previous stroke)Age < 65: BP < 130/80 mm HgAge ≥ 65: systolic BP < 130 mm Hg For patients with significant comorbidities or limited life expectancy, the BP goal is determined based on clinical judgment and the patient's preference.JNC 8Adults without diabetes mellitus or chronic kidney diseaseAge ≥ 60 years: BP ≥ 150/90 mm HgAge < 60 years: BP ≥ 140/90 mm HgAdults with diabetes mellitus and/or chronic kidney disease: ≥ 140/90 mm HgBP less than threshold for initiating pharmacological therapy Initiation of treatment Number of antihypertensivesNewly diagnosed hypertension with BP < 150/90 mm Hg: Begin therapy with one primaryantihypertensive.Newly diagnosed hypertension with BP > 150/90 mm Hg: Begin therapy with two primaryantihypertensives. Choice of antihypertensive drug Non-African American patients (including individuals with diabetes): thiazide-type diuretic, calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACE-I), or angiotensin receptor blocker (ARB)African American patients (including individuals with diabetes): thiazide-type diuretic or CCB In adults with chronic kidney disease: initial (or add-on) treatment should include an ACE inhibitor orARB to improve kidney outcome. Follow-upReassess within one month of initiating or changing pharmacological therapy. If the treatment goal is not reached with one drug, increase the dose of the initial drug or add a second drug.If the treatment goal cannot be reached with two drugs:Add a third drug. Evaluate for secondary causes of hypertension.If blood pressure is controlled: Reassess after 3-6 months and annually thereafter. First-line drugsACE inhibitors (e.g., lisinopril, captopril, enalapril) Preferred as a first-line drug in patients with diabetes mellitus, renal disease (nephroprotective), ischemic heart disease, and heart failureACEi and ARBs should not be used in combination.Dry cough, angioedema ↑ K+TeratogenicAngiotensin-receptor blockers (ARB)(e.g., losartan, valsartan) ↑ K+Teratogenic Thiazide diuretics (e.g., hydrochlorothiazide, chlorthalidone)Preferred as a first-line drug in African Americans, salt-sensitivepatients, and patients with isolated systolic hypertension↓ K+, ↓ Na↑ Glucose and cholesterol Calcium channel blockersDihydropyridines (e.g., nifedipine, amlodipine)Preferred as a first-line drug among African Americans and patients with isolated systolic hypertensionNondihydropyridines are not commonly used.Nondihydropyridines are contraindicated in patients with reduced ejection fraction.HeadacheConstipationGastroesophageal refluxPedal edemaBradycardia(nondihydropyridines)Nondihydropyridines(e.g., diltiazem, verapamil) Second-line drugsBeta blockers (e.g., propranolol, metoprolol, labetalol)Should be avoided in hypertension due to aortic regurgitationOften used as a primary drug in patients with any of the following comorbidities: Ischemic heart diseaseHeart failureAtrial fibrillationThoracic aortic disease (e.g., dissection, aneurysm)ThyrotoxicosisMigraineEssential tremorBronchoconstriction with noncardioselective beta blockersIncreased triglycerides Loop diuretics (e.g. furosemide, torsemide)Used in symptomatic heart failure and CKD (if GFR < 30 mL/min)↓ K+, ↓ Na↑ Glucose↑ Cholesterol Aldosterone antagonists (e.g., eplerenone, spironolactone)Used in hypertension due to primary aldosteronismCan be used as add-on therapy in resistant hypertension↑ K+Gynecomastia(spironolactone) Direct renin inhibitors (e.g., aliskiren)Should not be used in combination with ACEi or ARBs↑ K+ Alpha-1 blockers (e.g., prazosin, doxazosin)Used in hypertension due to pheochromocytomaMay be used as an adjunct in patients with benign prostatichypertrophyPostural hypotensionHeadache Alpha-2 agonists (e.g., clonidine)Rarely usedCNS depressionBradycardiaRebound hypertension Direct arteriolar vasodilators (e.g., hydralazine)Hydralazine is a first-line treatment in pregnancy.Sodium nitroprusside is used only in hypertensive emergencies.Reflex tachycardia Sodium and water retentionCyanide toxicity with long-term use of sodium nitroprusside Treatment of hypertension in pregnancy First-line treatment: methyldopa , labetalol, hydralazine (vasodilator), and nifedipine (CCB) Second-line treatment: thiazides, clonidine (alpha-2 agonist) Contraindicated: furosemide, ACE-I, ARB, renin inhibitors (aliskiren) Treatment of hypertension in children Treat the underlying cause (e.g., surgical correction of coarctation of the aorta) Lifestyle changes in children with elevated BP (see nonpharmacologic measures in the treatment section below) Pharmacologic management is indicated for symptomatic hypertension, diabetes mellitus, CKD, and end-organ damage, as well as if there is an insufficient response or no response to lifestyle changes. Goal: BP < 90th percentile (BP < 50th percentile in children with DM or CKD)Drugs: ACE inhibitor, ARB, or calcium channel blockerIn children with CKD or diabetes mellitus, ACE inhibitors or ARBs are preferable. Hypertensive emergency: labetalol, nicardipine, or sodium nitroprusside Beta blockers are not recommended for initial treatment of hypertension in children due to their metabolic side effects (e.g., impaired glucose tolerance) and the fact that they exacerbate asthma! Complications Arterial hypertension leads to changes in the vascular endothelium, particularly of the small vessels, and can therefore affect any organ system. See also hypertensive crises. Cardiovascular system Congestive heart failure, dilated cardiomyopathy, hypertrophic cardiomyopathy Coronary artery disease and myocardial infarction Atrial fibrillation Aortic aneurysm Aortic dissection Carotid artery stenosis Peripheral artery disease Atherosclerosis Brain Stroke , TIA Cognitive changes such as memory loss Kidneys Hypertensive nephrosclerosis Pathophysiology: chronic hypertension → narrowing of afferent arterioles and efferent arterioles→ reduction of glomerular blood flow → glomerular and tubular ischemia → arteriolonephrosclerosis and fibrosis (focal segmental glomerulosclerosis) → end-stage renal disease Typical findingsInitially microalbuminuria and microhematuriaWith disease progression, nephrosclerosis with macroalbuminuria (usually < 1 g/day) and progressive renal failure occur.Biopsy: sclerosis in capillary tufts, arterial hyalinosis Eyes Hypertensive retinopathyArteriosclerotic and hypertension-related changes of the retinal vessels Fundoscopic examination: Cotton-wool spotsRetinal hemorrhages (i.e., flame-shaped hemorrhages)MicroaneurysmsMacular star (results from exudation into the macula)Arteriovenous nicking Marked swelling and prominence of the optic disk with indistinct borders due to papilledema and optic atrophy (end-stage disease) Presence of papilledema in a hypertensive patient may indicate a hypertensive crisis and warrants urgent lowering of the blood pressure (see hypertensive crises) Classification system according to Keith-Wagener-BarkerFindingsSymptomsGrade IVessel diameter variation: arteriolar constriction and tortuosityUsually asymptomaticGrade IIGunn sign and marked constriction of vessels and sclerosis of arteriolesGrade IIICotton-wool exudates, hard exudates, retinal hemorrhage, retinal edema, macular star formationDecreased and/or blurred vision, headaches Grade IVPapilledema, optic atrophy

Pericarditis Pericarditis is inflammation of the pericardium that may be acute or chronic. Acute pericarditis is most commonly caused by viral infection; however, a number of conditions can cause an inflammatory response in the pericardium. Acute inflammation typically manifests with fever, pleuritic chest pain, and a pericardial friction rub on auscultation. The diagnosis is established based on clinical findings, although diffuse ST segment elevations on ECG and imaging may support the diagnosis. Acute pericarditis is usually self-limited, lasting days to weeks, and is therefore managed symptomatically. If pericarditis lasts longer than three months, it is described as chronic pericarditis. Chronic pericarditismay either be constrictive or effusive-constrictive. Constrictive pericarditis is characterized by thickening and rigidity of the pericardium, resulting in both backward and forward failure. Patients typically present with fatigue, jugular vein distention, peripheral edema, and a characteristic pericardial knock on auscultation, which is caused by a sudden stop in ventricular diastolic filling. Effusive-constrictive pericarditis is characterized by a thickened pericardium with an effusion; this can lead to cardiac tamponade. It may manifest with symptoms similar to constrictive pericarditis, symptoms of pericardial effusion, or cardiac tamponade. In both constrictive and effusive-constrictive pericarditis, imaging is used to confirm the diagnosis. Management consists of treatment of heart failure (e.g., diuretics) and pericardiectomy.

Definition Acute pericarditis: inflammation of the pericardium that either occurs as an isolated process or with concurrent myocarditis (myopericarditis). [1]Perimyocarditis: condition predominantly affecting the myocardium with pericardial involvement Transient constrictive pericarditis: constrictive pericarditis that lasts < 3 months Chronic pericarditis: inflammation of the pericardium that lasts > 3 months [2][3]Constrictive pericarditis is characterized by compromised cardiac function caused by a thickened, rigid, and fibrous pericardium secondary to acute pericarditis.Effusive-constrictive pericarditis: Pericardial effusion occurs in addition to a thickened pericardium, which can lead to tamponade. [4] Etiology Idiopathic InfectiousMost commonly viral (e.g., coxsackie B virus) [5]Bacterial (e.g., Staphylococcus spp., Streptococcus spp., or M. tuberculosis) FungalToxoplasmosis Myocardial infarctionPostinfarction fibrinous pericarditis: within 1-3 days as an immediate reactionDressler syndrome: weeks to months following an acute myocardial infarction Postoperative (postpericardiotomy syndrome): blunt or sharp trauma to the pericardium Uremia (e.g., due to acute or chronic renal failure) Radiation Neoplasm (e.g., Hodgkin lymphoma) Autoimmune connective tissue diseases (e.g., rheumatoid arthritis, systemic lupus, scleroderma) Clinical features Acute pericarditis [6] Chest painPleuritic chest painAcute, sharp retrosternal pain caused by inflammation of the parietal pleuraTypically aggravated by coughing, swallowing, or deep inspirationOther causes of pleuritic chest pain include pulmonary embolism, myocardial infarction, and pneumothorax.Improves on sitting and leaning forwardCan radiate to the neck and shoulders (most commonly to the left side) Pericardial friction rub: high-pitched scratching on auscultationIndicates friction between the visceral and parietal pericardial tissue [7]Best heard over the left sternal border during expiration while the patient is sitting up and leaning forward [8]Occurs in atrial and ventricular systole, as well as early diastole [9]Present in 85% of patients with acute pericarditis. [10] Pericardial effusionFaint heart soundsEwart sign Low-grade intermittent fever, tachypnea, dyspnea, nonproductive cough Chronic pericarditis Constrictive pericarditis [6][5] Symptoms of fluid overload (i.e., backward failure)Jugular vein distention, ↑ jugular venous pressureKussmaul sign Hepatic vein congestion: hepatomegaly, painful liver capsule distention, hepatojugular refluxPeripheral edema or anasarca, ascites with abdominal discomfort Symptoms of reduced cardiac output (i.e., forward failure)Fatigue, dyspnea on exertionTachycardia Pericardial knock: sudden cessation of ventricular filling during early diastole that is heard best at the left sternal borderPulsus paradoxus: ↓ blood pressure amplitude by at least 10 mm Hg during deep inspiration Effusive-constrictive pericarditis [4] Effusive-constrictive pericarditis is characterized by symptoms of chronic constrictive pericarditis, pericardial effusion, or a mixture of both. Diagnostics Acute pericarditis [5] Diagnostic criteria for acute pericarditis [4] At least two of the following four criteria must be present for a diagnosis of acute pericarditis: Characteristic chest pain Pericardial friction rub Typical ECG changes (see below) New or worsening pericardial effusion ECG Not all patients go through all stages and manifestations may vary. In particular, pericarditis due to uremia may not involve characteristic ECG changes. [11] Stage 1: diffuse ST elevations, ST depression in aVR and V1, PR segment depression Stage 2: ST segment normalizes in ∼ 1 week. Stage 3: inverted T waves Stage 4: ECG returns to normal baseline (as prior to onset of pericarditis) after weeks to months. In contrast to myocardial infarction, pericarditis is characterized by a diffuse distribution of ST elevations on ECG. Imaging [4][5] The goal of imaging is to identify any new pericardial effusion and rule out alternative etiologies. EchocardiographyIndications: considered first-line to evaluate for pericardial disease [4][5]Findings: pericardial effusion may be present, often normal Cardiac MRIIndications: Consider if diagnosis is uncertain; preferred imaging modality to assess pericardium. [4]Findings Thickened pericardium, pericardial enhancement, pericardial effusion [12]May show associated myocarditis [12] CT scan with IV contrastIndications: Consider if the diagnosis is uncertain.Findings: thickened pericardial layers, pericardial effusion Chest x-ray: usually normal; may show an enlarged cardiac silhouette Laboratory studies Elevation of inflammatory markers may support the diagnosis of pericarditis but are not considered to be a part of the diagnostic criteria. [4] CBC: leukocytosis ↑ Troponin I ↑ ESR ↑ CRP ↑ Creatinine kinase Additional diagnostic evaluation Pericardiocentesis with pericardial fluid analysis [10]Indications: large effusion, tamponade, suspected malignant or purulent pericarditis [5]Investigations depend on suspected etiology. Gram stainBacterial cultureAcid-fast bacilli and culturePolymerase chain reactionCytology Additional workup based on suspected etiologyUremic pericarditis: BUN, creatinine, electrolytesBacterial pericarditis: blood cultures (2 sets)Tuberculous pericarditis: interferon-γ release assay, HIV testAutoimmune pericarditis: ANA, rheumatoid factor Chronic pericarditis The diagnostic approach and findings for chronic pericarditis are similar to acute pericarditis but ECG, echocardiography, and imaging findings may vary. Constrictive pericarditis [6][5] The diagnosis of constrictive pericarditis is based on characteristic imaging findings (most commonly echocardiographybut MRI and CT may be used). Echocardiography↑ Pericardial thickness Abnormal ventricular filling with sudden halt during early diastoleVariation in ventricular filling with inspiration Across the tricuspid valve: The velocity of blood flow increases. Across the mitral valve: The velocity of blood flow decreases. Moderate biatrial enlargement [15]Excludes right ventricular hypertrophy and cardiomyopathy ImagingCT and cardiac MRIPericardial thickening > 2 mm CalcificationsNormal cardiac silhouetteChest x-ray (PA and lateral views) [14]Heart size: normal or slightly increasedPericardial calcifications Clear lung fields Cardiac catheterizationIndications: if noninvasive methods have failed to provide a definitive diagnosis [4]Findings [16]Similar pressures in the left and right atria and right ventricle at the end of diastole (e.g., "equalization of pressures")Normal pulmonary artery systolic pressure < 40 mm Hg Mean right arterial pressure > 15 mm HgSquare root sign [4]Also known as dip-and-plateau waveformSudden dip in the right and left ventricular pressure in early diastole followed by a plateau during the last stage of diastole ECGNo conclusive findings: generalized flat/inverted T waves, low QRS voltageAtrial fibrillation can occur in severe disease. [17] Effusive-constrictive pericarditis The diagnostic findings of effusive-constrictive pericarditis are similar to those of pericardial effusion, with the exception that in addition to pericardial effusion, pericardial thickening may also be seen. Elevation of right atrial pressures despite pericardiocentesis is strongly suggestive of effusive-constrictive. [18] Treatment The mainstays of therapy include anti-inflammatories to control pain and prevent a recurrence, and treatment of the underlying cause (if found). Medical therapy Acute pericarditis is often self-limited but NSAIDs can alleviate symptoms and prevent a recurrence. Consider anti-inflammatory therapy also for chronic pericarditis (transient constrictive pericarditis may respond). [10] NSAID therapy AspirinIbuprofenIndomethacin Consider colchicine in combination with NSAIDs or as a monotherapy. [4] Consider prednisone only in severe cases or in pericarditis caused by uremia, connective tissue disease, or autoreactivity. Gastroprotective therapy (e.g., omeprazole ) in patients at risk for GI bleeding Additional considerations Treat any known underlying causes. Antibiotics for bacterial causesAntitubercular therapyImmunosuppressants in autoimmune diseaseDialysis (in the case of uremia) Restricted physical activity in acute pericarditis [4][22]Nonathletes: until symptoms have resolved and CRP has normalizedAthletes: until symptoms have resolved, CRP has normalized, and ECG and echocardiogram findings have normalized Surgical therapy Pericardiocentesis: indicated for cardiac tamponade, large pericardial effusion, acute management of effusive-constrictive pericarditis [4] Pericardiectomy: complete removal of the pericardium Complications Constrictive pericarditis Cardiac tamponade

Atherosclerosis Atherosclerosis is the most common type of arteriosclerosis, or thickening and stiffening of the arterial wall. Major risk factors include smoking, diabetes mellitus, arterial hypertension, dyslipidemia, family history of early heart disease, and advanced age. The pathogenesis is a complicated process precipitated by endothelial damage, which leads to an invasion of inflammatory cells into the tunica intima and adhesion of platelets to the disrupted endothelium. Invading smooth muscle cells (SMCs) and macrophages take up cholesterol from oxidized low-density lipoprotein (LDL) in the vessel wall. They then become foam cells, which accumulate in early atherosclerotic lesions (fatty streaks), triggering the production of extracellular matrix (e.g., collagen). This leads to the formation of fibrous plaques (foam cells, extracellular matrix, free cholesterol, and cellular debris), which may rupture and lead to thrombosis. Common sites of atherosclerosis include the abdominal aorta, coronary arteries, popliteal arteries, and carotid arteries. Depending on the location, atherosclerosis may lead to a variety of conditions, such as arterial aneurysms, dissection, coronary heart disease (CHD), peripheral artery disease (PAD), intestinal ischemia, subcortical vascular dementia (Binswanger's disease), thrombosis (e.g., acute coronary syndrome and stroke), and renovascular hypertension.

Definition Arteriosclerosis: arterial wall thickening (hardening) and elasticity loss with variable pathogenesisAtherosclerosis (most common type of arteriosclerosis) Multifactorial inflammatory disease of the intima, manifesting at points of hemodynamic shear stressCharacterized by a build-up of cholesterol plaques in the intimaAffects elastic arteries and large/medium-sized muscular arteriesMönckeberg arteriosclerosis (less common)Dystrophic calcification of the media and internal elastic lamina causes stiffening of the arteries (intima is not involved) There is no blood flow obstruction.Mainly affects medium-sized arteriesX-ray: pipestem appearance Arteriolosclerosis: hardening of the small arteries and arterioles Hyaline arteriolosclerosisDeposition of proteins below the endothelium due to leakageH&E: pink amorphous deposits (hyaline) within the arteriolar walls Causes: chronic essential hypertension, chronic diabetes, and normal agingHyperplastic arteriolosclerosisProliferation of subendothelial smooth muscle cells in response to very high blood pressureH&E: "onion-skin" appearance of the arteriole Cause: malignant hypertension Epidemiology Leading cause of vascular disease worldwide Sex: ♂ > ♀ Etiology Modifiable risk factorsSmoking Diabetes mellitus Arterial hypertension DyslipidemiaHigh homocysteine levels (homocystinuria) Obesity High fibrinogen levelsHyperphosphatemiaStressIncreased alcohol consumption Nonmodifiable risk factorsFamily history: cardiovascular events in first-degree relatives below the age of 55 (♂)/65 (♀)Age: males ≥ 45 years, females ≥ 55 years (postmenopause) The term metabolic syndrome refers to the presence of at least 3 of the following risk factors: obesity, elevated triglycerides, low high-density lipoprotein (HDL), diabetes mellitus, and arterial hypertension. Pathophysiology Pathogenesis of atherosclerosis Chronic stress on the endothelium Endothelial dysfunction, which leads toInvasion of inflammatory cells (mainly monocytes and lymphocytes) through the disrupted endothelial barrierAdhesion of platelets to the damaged vessel wall → platelets release inflammatory mediators (e.g., cytokines) and platelet-derived growth factor (PDGF)PDGF stimulates migration and proliferation of smooth muscle cells (SMC) in the tunica intima and mediates differentiation of fibroblasts into myofibroblasts Inflammation of the vessel wall Macrophages and SMCs ingest cholesterol from oxidized LDL and transform into foam cells. Foam cells accumulate to form fatty streaks (early atherosclerotic lesions). Lipid-laden macrophages and SMCs produce extracellular matrix (e.g., collagen) → development of a fibrous plaque(atheroma) Inflammatory cells in the atheroma (e.g., macrophages) secrete matrix metalloproteinases → weakening of the fibrous cap of the plaque due to the breakdown of extracellular matrix → minor stress ruptures the fibrous cap Calcification of the intima (the amount and pattern of calcification affect the risk of complications) [11][12] Plaque rupture → exposure of thrombogenic material (e.g., collagen) → thrombus formation with vascular occlusion or spreading of thrombogenic material Common sites (in order of increasing frequency) Circle of Willis Carotid arteries Popliteal arteries Coronary arteries Abdominal aorta Atherosclerotic diseases Weakening of vessel wall: arterial aneurysm or dissection Demand-supply mismatch: coronary heart disease (CHD), peripheral artery disease (PAD), intestinal ischemia, and subcortical vascular dementia (Binswanger disease) Thrombosis and thromboembolism: acute coronary syndrome, stroke Renovascular hypertension: atherosclerosis of the renal artery → activation of the renin-angiotensin-aldosteronesystemPrimary and secondary prevention of atherosclerosis Lifestyle modificationsWeight reductionDietary modification Moderate aerobic exercise Smoking cessationModerate consumption of alcohol (about 1-2 glasses of wine or beer per day) presumably has a protective effect. Medical treatment: Treat hypertension, diabetes and hyperlipidemia The most significant therapeutic step patients with vascular disease can take is stopping smoking!

Congestive heart failure Congestive heart failure (CHF) is a clinical condition in which the heart is unable to pump enough blood to meet the metabolic needs of the body because of pathological changes in the myocardium. The three main causes of CHF are coronary heart disease, diabetes mellitus, and hypertension. These conditions cause ventricular dysfunction with low cardiac output, which results in blood congestion (backward failure) and poor systemic perfusion (forward failure). CHF is classified as either left heart failure (LHF) or right heart failure (RHF), although biventricular (global) CHF is most commonly seen in clinical practice. LHF leads to pulmonary edema and resulting dyspnea, while RHF induces systemic venous congestion that causes symptoms such as pitting edema, jugular venous distension, and hepatomegaly. Biventricular CHF manifests with clinical features of both RHF and LHF, as well as general symptoms such as tachycardia, fatigue, and nocturia. In rare cases, high-output CHF may occur as a result of conditions that increase cardiac output and thereby overwhelm the heart. Acute decompensated heart failure (ADHF) may occur as an exacerbation of CHF or be caused by an acute cardiac condition such as myocardial infarction. CHF is diagnosed based on clinical presentation and requires an initial workup to assess disease severity and possible causes. Initial workup includes measurement of brain natriuretic peptide levels, chest x-ray, and an ECG. Management of CHF includes lifestyle modifications and treatment of associated conditions (e.g., hypertension) and comorbidities (e.g., anemia), along with pharmacologic agents that reduce the workload of the heart. ADHF requires hospitalization and more intensive measures, such as hemodialysis.

Definition Congestive heart failure (CHF): a clinical syndrome in which the heart is unable to pump enough blood to meet the metabolic needs of the body; characterized by ventricular dysfunction that results in low cardiac output Systolic dysfunction: CHF with reduced stroke volume and ejection fraction (EF) The ejection fraction is the percentage of blood being pumped by the left ventricle during each contraction (stroke volume divided by end-diastolicvolume); normally ∼ 55% Diastolic dysfunction: CHF with reduced stroke volume and preserved ejection fraction Right heart failure (RHF): CHF due to right ventricular dysfunction; characterized by backward heart failure Left heart failure (LHF): CHF due to left ventricular dysfunction; characterized by forward heart failure Biventricular (global) CHF: CHF in which both the left and right ventricle are affected, resulting in simultaneous backward and forward CHF Chronic compensated CHF: clinically compensated CHF; the patient has signs of CHF on echocardiography but is asymptomatic or symptomatic and stable (see "Diagnostics" below) Acute decompensated CHF: sudden deterioration of CHF or new onset of severe CHF due to an acute cardiac condition (e.g., myocardial infarction) Epidemiology Prevalence1-2% of the population (∼ 5.7 million individuals) in the US has CHF. The incidence is higher among African Americans, Hispanics, and Native Americans.Increases with age: ∼ 10% of individuals > 60 years old are affected. Systolic heart disease is the most common form of CHF overall. General causesCoronary artery disease, myocardial infarctionArterial hypertension Valvular heart diseaseDiabetes mellitus (diabetic cardiomyopathy) Renal diseaseInfiltrative diseases (e.g., hemochromatosis, amyloidosis) Further risk factorsObesitySmokingCOPDHeavy drug (recreational and prescription) and alcohol abuse Systolic dysfunction (reduced EF) Cardiac arrhythmias Dilated cardiomyopathy (e.g., Chagas disease, chronic alcohol use, idiopathic) Myocarditis Diastolic dysfunction (preserved EF) Constrictive pericarditis Restrictive or hypertrophic cardiomyopathy Pericardial tamponade The three major causes of heart failure are coronary artery disease, hypertension, and diabetes mellitus. Patients typically have multiple risk factors that contribute to the development of CHF. Pathophysiology Cardiac output, which is stroke volume times heart rate, is determined by three factors: preload, afterload, and ventricular contractility. Underlying mechanism of reduced cardiac output Systolic ventricular dysfunction (most common) due to: Reduced contractility: Damage and loss of myocytes reduce ventricular contractility and stroke volume. Increased afterload: increase in mean aortic pressure, outflow obstruction Increased preload: ventricular volume overload Cardiac arrhythmiasHigh-output conditions (see "High-output heart failure" below) Diastolic ventricular dysfunction due to:Decreased ventricular compliance: increased stiffness or impaired relaxation of the ventricle → reduced ventricular filling and increased diastolic pressure → decreased cardiac output Increased afterload: increase in pulmonary artery pressure Increased preload: ventricular volume overload Consequences of systolic and diastolic dysfunction Forward failure: reduced cardiac output → poor organ perfusion → organ dysfunction (e.g., hypotension, renal dysfunction) Backward failureIncreased left-ventricular volume and pressure → backup of blood into lungs → increased pulmonary capillarypressure → cardiogenic pulmonary edemaReduced cardiac output → systemic venous congestion → edema and progressive congestion of internal organsResulting macroscopic findings: nutmeg liver Compensation mechanisms Aim: maintain cardiac output if stroke volume is reduced↑ Adrenergic activity → increase in heart rate, blood pressure, and ventricular contractilityIncrease of renin-angiotensin-aldosterone system activity (RAAS): activated following decrease in renal perfusion secondary to reduction of stroke volume and cardiac output ↑ Angiotensin II secretion → vasoconstriction → ↑ systemic blood pressure → ↑ afterloadKidney: vasoconstriction of the efferent arterioles and, to a lesser degree, the afferent arterioles → ↓ netrenal blood flow and ↑ intraglomerular pressure to maintain GFR↑ Aldosterone secretion → ↑ renal Na+ and H2O resorption → ↑ preload Brain natriuretic peptide (BNP): ventricular myocyte hormone released in response to increased ventricular fillingand stretching↑ Intracellular smooth muscle cGMP → vasodilation → hypotension and decreased pulmonary capillary wedge pressure CHF is characterized by reduced cardiac output that results in venous congestion and poor systemic perfusion! General features of heart failureNocturia [9]FatigueTachycardia, various arrhythmias Heart sounds: S3/S4 gallop Pulsus alternans Clinical features of left-sided heart failure Pulmonary symptoms dominate Dyspnea , orthopnea Pulmonary edema in severe cases or acute decompensated heart failure (see below) Bilateral basilar rales may be audible on auscultation. Paroxysmal nocturnal dyspnea: nocturnal bouts of coughing and acute shortness of breath Cardiac asthma: increased pressure in the bronchial arteries results in airwaycompression, leading to bronchospasm [10] Laterally displaced apical heart beat(precordial palpation beyond the midclavicular line)Forward failure: cool extremities, cerebral and renal dysfunction, sweating (NYHA IV) Clinical features of right-sided heart failureSymptoms of fluid retention (backward failure) dominate Peripheral pitting edema Signs of increased central venous pressure (CVP) Jugular venous distention: visible jugular venous congestion , also seen in biventricular heart failure Hepatojugular reflux: jugular venous congestion induced by exerting manual pressure over the patient's liver → ↑ volume load on the right side of the heart → right heart is unable to pump additional blood volume → visible jugular venous distention persists for several seconds Hepatic venous congestionHepatosplenomegalyAbdominal pain JaundiceAscites Congestion of other organs, e.g., congestive gastritis or gastropathy (nausea, loss of appetite), renal congestion In clinical practice, biventricular heart failure with features of left and right heart failure is more likely than isolated failure of one ventricle! Subtypes and variants High-output heart failure Definition: heart failure secondary to conditions associated with a high-output state, in which cardiac output is elevated to meet the demands of peripheral tissue oxygenation Etiology: conditions that lead to increased cardiac demand (high-output state) AnemiaSystemic arteriovenous fistulas SepsisHyperthyroidismMultiple myelomaGlomerulonephritisPolycythemia veraWet beriberi (vitamin B1 deficiency)Physiological causes: pregnancy, fever, exercise Clinical featuresSymptoms of low-output CHF; particularly tachycardia, tachypnea, low blood pressure, and jugular distention with an audible hum over the internal jugular veinPulsatile tinnitusBounding peripheral pulsesLaterally displaced apical heart beatMidsystolic murmur, S3 gallop (indicates rapid ventricular filling) DiagnosticsPrimarily a clinical diagnosisX-ray and echocardiography: cardiomegaly TherapyManage heart failure: symptom relief, hemodynamic stabilizationTreat underlying condition NYHA classCharacteristicsClass INo limitations of physical activity; no symptoms of CHFClass IISlight limitations of moderate or prolonged physical activity (e.g., symptoms after climbing 2 flights of stairs or heavy lifting); comfortable at restClass IIIMarked limitations of physical activity (symptoms during daily activities like dressing, walking across rooms); comfortable only at restClass IVConfined to bed, discomfort during any form of physical activity; symptoms present at rest StagesObjective assessmentCorresponding NYHA functional classStage AHigh risk of developing heart failure (e.g., pre-existing arterial hypertension, CAD, diabetes mellitus); no structural cardiac changesNo corresponding NYHA classStage BStructural damage to the heart (e.g., infarct scars, dilatation, hypertrophy), without signs or symptoms of heartfailureNYHA IStage CStructural damage to the heart + signs or symptoms of heart failureNYHA I, II, III, IVStage DHeart failure at its terminal stageNYHA IV Diagnostics Heart failure is primarily a clinical diagnosis. Laboratory tests and imaging tests, including a chest x-ray and echocardiogram, are useful for evaluating the severity and cause of the condition. Diagnostic approach [22] Medical history, including pre-existing conditions and history of alcohol and recreational or prescribed drug use Initial evaluation involves a range of routine laboratory tests and a test for BNP level, ECG, and chest x-ray. Echocardiography is the gold standard tool for assessing cardiac morphology and function, as well as investigating the underlying cause of CHF. Other procedures (exercise testing, angiography) may be required for further investigation. Initial evaluation [22] Laboratory analysis Elevated BNP and NT-pro BNP High levels of BNP in patients with classic symptoms of CHF confirm the diagnosis (high predictive index). [23] CHF unlikelyCHF likelyBNP (pg/mL)< 100> 500 NT-pro BNP (pg/mL)< 300> 450 Elevated atrial natriuretic peptide (ANP): Complete blood count: may show anemia Serum electrolyte levels: hyponatremia → indicates a poor prognosis Kidney function tests: ↑ creatinine, ↓ sodium Urine analysis: rule out concurrent renal impairment Fasting glucose: to screen for diabetes mellitus, which is a common comorbidity Fasting lipid profile: to detect dyslipidemia associated with a higher cardiovascular risk Electrocardiogram (ECG) ECG abnormalities in CHF are common, but are mostly nonspecific and nondiagnostic. Signs of left ventricular hypertrophy ↑ QRS voltage (in the left chest leads and limb leads I and aVL) → positive Sokolow-Lyon index↑ QRS duration (incomplete or complete left bundle branch block)Left axis deviation Assessment of prior or concurrent heart conditions Previous or acute MI: see ECG changes in STEMIArrhythmias (e.g., atrial fibrillation, ventricular arrhythmias, sinus tachycardia or bradycardia, AV block) Signs of pericardial effusion and tamponade: low voltage ECG Chest x-ray Useful diagnostic tool to evaluate a patient with dyspnea and differentiate CHF from pulmonary disease Signs of cardiomegalyCardiac-to-thoracic width ratio > 0.5 Boot-shaped heart on PA view (due to left ventricular enlargement) Assess pulmonary congestion (see x-ray findings in pulmonary congestion) Transthoracic echocardiogram Gold standard for evaluating patients with heart failure Assess ventricular function and hemodynamicsAtrial and ventricular sizeInterventricular septum thickness: > 11 mm (normal 6-11 mm) indicates cardiac hypertrophySystolic function: left ventricular ejection fractionNormal EF: > 55%Reduced EF: 30-44%Extremely reduced EF: < 30%Diastolic function (diastolic filling, ventricle dilation) Investigate etiologyValvular heart diseaseWall motion abnormalities (indicate prior or acute MI) Right ventricular strain Tissue Doppler: ↑ PCWP in left-sided heart failure Further tests Cardiac stress test (exercise tolerance test): to assess the functional impairment due to CHF or other conditions (particularly CHD!) Radionuclide ventriculography : indicated to assess left ventricular volume and ejection fraction (LVEF) Cardiac MRI: particularly useful for assessing cardiac morphology and function Cardiac size and volumes, wall thickness, valvular defects, wall motion abnormalities Coronary angiography (left heart catheterization): indicated to detect/confirm CHD and possible percutaneous coronary intervention Right heart catheterization: if pulmonary hypertension is suspected, to assess the severity of systolic dysfunction, and/or to differentiate between types of shockSvO2: will be low in decompensated heart failure Endomyocardial biopsy: may be performed if a specific diagnosis is suspected in patients with rapidly progressive clinical CHF or in case the results would alter the management of the patient, e.g., in amyloidosis Treatment General measures [22] Lifestyle modifications Salt restriction (< 3 g/day) Fluid restriction in patients with edema and/or hyponatremiaWeight loss and exercise Cessation of smoking and alcohol consumptionImmunization: pneumococcal vaccine and seasonal influenza vaccine Patient education Self-monitoring and symptom recognitionDaily weight check Weight gain > 2 kg within 3 days: consult the doctor Monitoring of potential side effects (e.g., hypotension caused by ACE inhibitors, hyperkalemia caused by aldosterone-antagonists, sensitivity to sunlight caused by amiodarone) Treat any underlying conditions and contributing comorbidities. First-line drugsDiuretics (loop diuretics and thiazide diuretics)(✓)(✓)✓✓Begin treatment with loop diuretics(furosemide) to treat volume overloadThiazides may be added for a synergistic effectMonitor for hypokalemiaand hyponatremia, weight gain, and volume statusImprove symptomsACE inhibitors ✓✓✓✓Initiate treatment with ACE inhibitors to reduce preload, afterload, and improve cardiac outputIf the patient does not tolerate drug (e.g., dry cough develops) → substitute with AT2-receptor blockerMonitor for hyperkalemia, hypotension, ↑ creatinine(renal impairment)Improve symptoms and prognosisBeta blockers(✓)✓✓✓Add a beta blocker once the patient is stableon ACE inhibitor Particularly beneficial for patients with hypertension and post-myocardial infarctionContraindicated in acute decompensated heart failure!Improve symptoms and prognosisAldosterone antagonists(✓)✓✓In select patients, an aldosterone antagonistmay be beneficial.If EF < 35%, and after myocardial infarctionSpironolactone; eplerenone as an alternativeMonitor for hyperkalemia Second-line drugsIvabradine(✓)(✓)(✓)If the highest tolerable dose of beta blocker is reached and the patient is still symptomatic or if the patient has a contraindication to beta-blocker useIf EF < 35% and the patient has a sinus rhythm with a resting heart rate > 70/minContraindicated in severe bradycardiaImproves symptomsReduces hospitalization rate Hydralazine plus nitrate(✓)(✓)If EF < 40%; particularly beneficial for African-American patients Alternative if ACE inhibitors and AT1 blockers are not tolerated Monitor for volume depletion and hypotensionImproves symptoms; may improve prognosis Digoxin (✓) (✓)(✓)In heart failure with reduced ejection fractionIf symptoms persist despite treatment with beta blocker, ACE inhibitor, diuretics, and aldosterone antagonistsMay be given to control ventricular rate in atrial fibrillation (if beta blockers are contraindicated)Contraindicated in severe AV blockImproves symptomsReduces hospitalization rate ARNI (angiotensin receptor-neprilysininhibitor)(✓)(✓)(✓)(✓)Persistent or worsening symptoms despite adequate treatment regimen with first-linedrugsAdministered as combination valsartan-sacubitril Angioedema, hypotension, hyperkalemia, and progression of chronic renal disease (↑ creatinine)Improves prognosisReduces hospitalization rate Nesiritide (BNPderivative)Acute decompensated heart failureRarely used today due to side effects and longer half-life compared to other vasodilators (e.g., nitroglycerin) Contraindicated in patients with hypotension and/or cardiogenic shockAdverse effects include hypotension and decrease in pulmonary capillary wedge pressure Drugs that improve prognosis: beta blockers, ACE inhibitors, and aldosterone antagonists! Drugs that improve symptoms: diuretics and digoxin (significantly reduce the number of hospitalizations)! Conducting regular blood tests to assess electrolyte levels (potassium and sodium) is mandatory if the patient is on diuretics! Contraindicated drugs NSAIDsWorsen renal perfusion (see "Side effects" of NSAIDs)Reduce the effect of diureticsMay trigger acute cardiac decompensation Calcium channel blockers (verapamil and diltiazem): negative inotropic effect; worsen symptoms and prognosis Thiazolidinediones: promote the progression of CHF (↑ fluid retention and edema) and increase the hospitalization rate Moxonidine: increases mortality in CHF with reduced ejection fraction (systolic dysfunction) Invasive procedures Implantable cardiac defibrillator (ICD): prevents sudden cardiac deathPrimary prophylaxis indications CHF with EF < 35% and prior myocardial infarction/CHDIncreased risk of life-threatening cardiac arrhythmiasSecondary prophylaxis indications: history of sudden cardiac arrest, ventricular flutter, or ventricular fibrillation Cardiac resynchronization therapy (biventricular pacemaker): improves cardiac functionIndications: CHF with EF < 35%, dilated cardiomyopathy, and left bundle branch blockCan be combined with an ICD Coronary revascularization with PCTA or bypass surgery may be indicated if CAD is present. Valvular surgery if valvular heart defects are present Ventricular assist devices: may be implanted to support ventricular function; may be indicated for temporary or long-term support (e.g., to bridge time until transplantation) of decompensated CHF Cardiac transplantation: for patients with end-stage CHF (NYHA class IV), ejection fraction < 20%, and no other viable treatment options Complications Acute decompensated heart failure (see section below) Cardiorenal syndrome Cardiac arrhythmias Central sleep apnea syndrome Cardiogenic shock Stroke; increased risk of arterial thromboembolisms (especially with concurrent atrial fibrillation) Chronic kidney disease Cardiac cirrhosis (congestive hepatopathy): Cirrhosis due to chronic hepatic vein congestion in patients with right‑sided heart failure. Venous stasis, leg ulcers Acute decompensated heart failure Cardiac decompensation is the most common reason for hospital admissions and is the most important complication of congestive heart failure. Etiology ADHF typically occurs in patients who have a history of CHF or other cardiac conditions in which an acute cause precipitates the deterioration of cardiac function. Exacerbation of congestive heart failure (e.g., through pneumonia, anemia, volume overload, medication noncompliance) Acute myocardial infarction Atrial fibrillation, severe bradycardia, and other arrhythmias Myocarditis Hypertensive crisis Pulmonary embolism Pericardial tamponade Aortic dissection Cardiotoxic substances Renal failure Cardiodepressant medication (e.g., beta blockers, CCBs) Clinical features Rapid exacerbation of symptoms of CHF (see symptoms of left heart failure and symptoms of right heart failure) Pulmonary congestion with: Acute, severe dyspnea and orthopnea; worse when supineCough (occasionally with frothing, blood-tinged sputum)Cyanosis Auscultation of the lungs: rales accompanied by wheezing Flash pulmonary edema: rapid, life-threatening accumulation of fluid associated with the risk of acute respiratory distress Weakness, fatigue, and cold, clammy skin Diagnostics X-ray findings in pulmonary congestionCardiomegalyProminent pulmonary vessels and perihilar alveolar edema (butterfly or "bat's wings" appearance of the hilar shadow) Kerley B lines: visible horizontal interlobular septa caused by pulmonary edemaBasilar edemaBilateral pleural effusions Sputum analysis: heart failure cells (hemosiderin-containing cells) ThoracentesisIndicated if the etiology of the pleural effusion is unclear Pleural fluid analysis: Transudate effusions are typical of cardiogenic causes The radiologic signs of pulmonary congestion can be remembered with "ABCDE": A = Alveolar edema (bat's wings), B = Kerley B lines (interstitial edema), C = Cardiomegaly, D = Dilated prominent pulmonary vessels, and E= Effusions! Differential diagnosis of pulmonary edema and respiratory distress Noncardiogenic pulmonary edema due to ARDS, pulmonary embolism, transfusion-related acute lung injury, high altitude Asthma Pneumonia Treatment Sufficient oxygenation and ventilation ; assisted ventilation as needed (e.g., CPAP). Fluid management: Aggressive diuresis (e.g., IV furosemide) to reduce volume overloadVasodilators: (e.g., IV nitroglycerine) can be considered as adjunct treatment in patients without hypotension. Hemodynamic stabilization: inotropes (e.g., dobutamine) in case of systolic dysfunction Treat the cause of decompensation. Hemodialysis if volume overload is symptomatic (pulmonary edema, pleural effusion, ascites) and resistant to treatment ECLS may temporarily substitute pulmonary function. Ventricular assist devices (see "Treatment of heart failure" above) Beta blockers must be used cautiously in decompensated heart failure! Management of ADHF can be remembered with "LMNOP": L = Lasix (furosemide), M = Morphine, N = Nitrates, O= Oxygen, P = Position (with elevated upper body). Beta-blocker therapy should NOT be initiated at the time of presentation in patients who are not already taking a beta blocker. Cardiorenal syndrome Cardiorenal syndrome is a complication of acute heart failure and CHF. Definition: a complex syndrome in which renal function progressively declines as a result of severe cardiac dysfunction; occurs in ∼ 20-30% of cases of ADHF PathophysiologyCardiac forward failure → renal hypoperfusion → prerenal kidney failureCardiac backward failure → systemic venous congestion → renal venous congestion → decreased transglomerular pressure gradient → ↓ GFR → worsening kidney functionRAAS activation → salt and fluid retention, hypertension → hypertensive nephropathy Diagnosis: ↓ GFR, ↑ creatinine that cannot be explained by underlying kidney disease Treatment: treat heart failure; manage renal failure (see treatment of acute renal injury) Prognosis: CHF with reduced GFR is associated with a poor prognosis. Prognosis The prognosis depends on the patient, type and severity of heart disease, medication regimens, and lifestyle changes. The prognosis for patients with preserved EF is similar to or better than for patients with decreased EF Risk stratification scales may be used to evaluate the prognosis (e.g., CHARM and CORONA risk scores). Factors associated with worse prognosisElevated BNPHyponatremiaSystolic BP < 120 mm HgDiabetesAnemiaWeight loss or underweightS3 heart soundImplantable cardioverter-defibrillator useFrequent hospitalizations due to CHF 1-year survival according to NYHA stageStage I: ∼ 95%Stage II: ∼ 85%Stage III: ∼ 85%Stage IV: ∼ 35%

Rheumatic fever Rheumatic fever is an inflammatory sequela involving the heart, joints, skin, and central nervous system (CNS) that occurs two to four weeks after an untreated infection with group A streptococcus (GAS). The pathogenic mechanisms that cause rheumatic fever are not completely understood, but molecular mimicry between streptococcal M protein and human cardiac myosin proteins is thought to play a role. Because of the structural similarities between the two proteins, antibodies and T cells activated to respond to streptococcal proteins also react with the human proteins, causing tissue injury and inflammation. In addition to nonspecific symptoms (e.g., fever, malaise, and fatigue), patients present with symptoms involving the heart (pancarditis), joints (migratory polyarthritis), skin (subcutaneous nodules, erythema marginatum), and/or CNS (Sydenham's chorea). The diagnosis of acute rheumatic fever is primarily a clinical one, and is based on the Jones criteria. Diagnostic evaluation in acute rheumatic fever typically shows elevated inflammatory markers, positive antistreptococcal antibodies, and valvular damage on echocardiogram. The first-line treatment is penicillin, and is combined with symptomatic anti-inflammatory treatment, typically with salicylates or glucocorticoids (if salicylates are not effective). Acute rheumatic fever may be complicated by progressive, permanent damage to the heart valves (especially the mitral valve), resulting in chronic rheumatic heart disease. Preventing the cardiac complications of rheumatic fever is the goal of both primary prophylaxis (i.e., antibiotic therapy for GAS pharyngitis) and secondary prophylaxis (antibiotic administration following an episode of acute rheumatic fever.

Definition Delayed inflammatory complication of group A β-hemolytic streptococcal (GAS) pharyngitis that usually occurs within 2-4 weeks of acute infectionOne of the nonsuppurative complications of GAS pharyngitis Rheumatic heart disease refers to two clinical entities: Acute pancarditis as a sequela of GAS infectionChronic cardiac valvular changes as a complication of acute rheumatic fever Epidemiology Peak incidence: 5-15 years PrevalenceDeveloping countries: the most common cause of cardiovascular disease in children and adolescents Developed countries: rare Etiology Most commonly accepted mechanism : Group A β-hemolytic streptococcus (Streptococcus pyogenes) (GAS): acute tonsillitis or pharyngitis ("strep throat") without antibiotic treatment → antibodies develop against streptococcalM protein → cross-reaction of antibodies with nerve and myocardial proteins due to molecular mimicry → type II hypersensitivity reaction → acute inflammatory sequela Rheumatic fever is not associated with streptococcal skin infections (e.g., erysipelas, impetigo, cellulitis). The symptoms of acute rheumatic fever can be remembered with the JONES criteria, written with a heart-shaped O (see also "Diagnostics" above): J = Joints, ♥ = Pancarditis, N = Nodules, E = Erythema marginatum, S = Sydenham chorea Constitutional symptoms: fever, malaise, fatigue Joints (∼ 75% of cases): migratory polyarthritis Heart (30-60% of cases) Pancarditis (endocarditis, myocarditis, and pericarditis)Valvular lesions Mitral valve (∼ 65% of cases) Early mitral regurgitation or prolapseLate mitral stenosis: Rheumatic fever is the most frequent cause of mitral stenosis.Mixed mitral stenosis/regurgitation also possibleAortic valve (∼ 25% of cases) Aortic regurgitationAortic stenosisTricuspid valve (∼ 10% of cases) Dilated cardiomyopathy due to severe valvular disease, myocarditis CNS (up to 25% of cases) Sydenham choreaOccurs 1-8 months after the inciting infection Involuntary, irregular, nonrepetitive movements of the limbs, neck, head, and/or face, sometimes asymmetrical or confined to one side (hemichorea) Additional motor symptoms (e.g., ballismus, muscle weakness) and speech disorders (slurred or "jerky" speech)Neuropsychiatric symptoms (e.g., inappropriate laughing/crying, agitation, anxiety, apathy, obsessive-compulsive behavior)Pathophysiology: Streptococcal antigens lead to antibody production → antibodies cross-react with structuresof the basal ganglia (particularly the striatum) and cortical structures → reversible dysfunction of cortical and striatal circuits Skin (∼ 10% of cases) Subcutaneous nodules Erythema marginatum Centrifugally expanding pink or light red rash with a well-defined outer border (erythema marginatum → marginated rash) and central clearing. Location: The trunk and limbs are affected; the face is spared. May rapidly appear and disappear at different locations.Painless and nonpruritic Rheumatic heart disease tends to involve the high-pressure valves, i.e., the mitral and aortic valves! Diagnostics Diagnosis of acute rheumatic fever is based on the Jones criteria, which primarily describe the clinical findings of the condition. Evidence of a preceding GAS infection is also preferred (unless carditis or chorea are present). Laboratory tests and imaging may be necessary to assess any outstanding Jones criteria. Jones criteria Interpretation: two major OR one major plus two minor criteria are required for diagnosis. Major criteriaArthritis (migratory polyarthritis involving primarily the large joints)Carditis (pancarditis, including valvulitis)Sydenham chorea (CNS involvement)Subcutaneous nodulesErythema marginatum Minor criteriaArthralgiaFever↑ Acute phase reactants (ESR, CRP)Prolonged PR interval on electrocardiogram Additional findings Normochromic, normocytic anemia of chronic inflammation Leukocytosis Confirmation of GAS infection↑ Antistreptolysin O titer (ASO): antibodies against metabolites of GAS Positive rapid streptococcal antigen test or throat culture for GAS Echocardiogram (may show mitral or aortic regurgitation) Pathology Myocardial findingsAschoff bodies: Granuloma of rheumatic inflammationCentral area of fibrinoid necrosisSurrounded by characteristic multinucleated giant cells (Aschoff's cells) and other inflammatory cells(mononuclear cells, plasma cells, and T lymphocytes)Anitschkow cells: Cardiac histiocytes (mononuclear cells) appearing in Aschoff bodiesLarge and elongated cellsLongitudinal section: ovoid nucleus containing wavy, caterpillar-like bar of chromatin ("caterpillar cell")Transverse section: owl-eye appearance Treatment General measures: bedrest (especially important in patients with carditis) Antibiotics: to eradicate GAS Drug of choice: oral penicillin VAlternatives AmoxicillinBenzathine IM (in patients unable to complete oral therapy)Cephalosporins (in penicillin hypersensitivity without anaphylaxis)Macrolides (in patients with severe hypersensitivity to beta-lactam antibiotics) Therapy for arthritis and feverNonsteroidal anti-inflammatory drugs (NSAIDs) Preferred: salicylates (e.g., aspirin)Alternatives (particularly for children): ibuprofen and naproxenGlucocorticoids (if NSAIDs fail) Therapy for heart failure: diuretics and conventional therapy (see congestive heart failure) Therapy for myocarditis: monitoring and treatment for arrhythmias (see myocarditis) Damage to the cardiac valves: Surgery or interventional reconstructive measures may be considered at least one year after the acute inflammatory phase. Prognosis Cardiac involvement is the most important prognostic factor. Early death in rheumatic fever is usually due to myocarditis rather than valvular defects.Patients with a history of carditis during an initial rheumatic fever episode are at high risk of developing valvular heart defects with recurrent episodes → rheumatic heart disease Prevention Primary prevention: prompt antibiotic treatment (e.g., penicillin V) of GAS tonsillopharyngitis diagnosed by throat culture or rapid strep test Secondary preventionAntibiotic prophylaxis to prevent recurrenceDrug of choice: IM penicillin G benzathineIn patients with a penicillin allergy: oral macrolidesUsually administered every 28 days Immediately follows antibiotic treatment of acute rheumatic fever (see "Treatment" above)Duration depends on risk and severity of original episode Rheumatic fever without carditis: 5 years or until the patient is age 21 (whichever is longer) Rheumatic fever with carditis: 10 years or until the patient is age 21 (whichever is longer)Rheumatic fever with carditis and permanent valvular heart defects: 10 years or until age 40 (whichever is longer)

Thoracic aortic aneurysm Thoracic aortic aneurysm (TAA) is a focal dilatation of the thoracic aorta to more than 1.5 times its normal diameter. TAAs are classified by location as either ascending or descending aneurysms or aneurysms of the aortic arch. Male patients of advanced age are at a higher risk of forming TAAs; other risk factors include trauma, connective tissue disorders, and hypertension. TAAs are frequently asymptomatic and therefore detected incidentally. If symptomatic, they may present with a feeling of pressure in the chest, thoracic back pain, and signs of mediastinal obstruction (e.g., difficulty swallowing). Whereas a chest x-ray is the best initial test and may show a prominent aortic arch, a CT with contrast is used to confirm the diagnosis and to determine the extent of the aneurysm. Observation, close follow-up, and reduction of cardiovascular risk factors are indicated for small aneurysms, whereas pronounced or rapidly expanding aneurysms require surgery. Surgical treatment involves open resection of the aneurysm with graft placement or, increasingly, endovascular stent placement. The prognosis is markedly worse if dissection or free rupture of the aneurysm occurs. In manifested rupture presenting with severe chest pain and possible loss of consciousness, there is no time for detailed assessment and emergency surgical repair must be performed to prevent cardiac tamponade, hemothorax, and death.

Definition Dilation of all three layers of the aortic wall (intima, media, and adventitia) to > 50% of the normal diameterDiameter: > 3.5 cm (see also aneurysm) Epidemiology Less common than abdominal aortic aneurysm (AAA) Peak incidence: 60-65 years Sex: ♂ > ♀ (∼ 3:1) More common in white populations Etiology Risk factorsSmokingAdvanced ageArterial hypertensionTraumaTertiary syphilis (due to obliterative endarteritis of the vasa vasorum) [4]Connective tissue diseases (e.g., Marfan syndrome, Ehlers-Danlos syndrome)Bicuspid aortic valve [5]Positive family historyRare: vasculitis/infectious diseases with aortic involvement (e.g., Takayasu arteritis) Classification Ascending aorta (most common location) Descending aorta (thoracoabdominal) Aortic arch The ascending aorta extends from the aortic annulus to the innominate artery. Pathophysiology Ascending thoracic aortic aneurysm: most often due to cystic medial necrosis Descending thoracic aortic aneurysm: typically a result of atherosclerosis Inflammation and proteolytic degeneration of connective tissue proteins and/or smooth muscle cells in high-risk patients → loss of structural integrity of the aortic wall → widening of the vessel The aneurysmatic dilatation of the vessel wall may cause disruption of the laminar blood flow and turbulence. Possible formation of thrombi in the aneurysm → peripheral thromboembolism Clinical features Aortic aneurysms are mostly asymptomatic or have nonspecific symptoms. Therefore, they are often incidental findings on ultrasound or CT scan. Rupture or dissection of the aneurysm is a life-threatening condition (see "Complications" below). Feeling of pressure in the chest Thoracic back pain Features of mediastinal compression/obstruction Cough, wheeze, stridor (trachea)Difficulty swallowing (esophagus)Upper venous congestion (superior vena cava syndrome)Hoarseness (recurrent laryngeal nerve)Horner syndrome (sympathetic trunk), with the classic triad of ptosis, miosis, and hemifacial anhidrosis(with or without apparent enophthalmus) Diagnostics Chest x-ray: may be useful as an initial test in TAAs Bulging of the aorta: "aortic knob" (prominent shadow of the aortic arch)Widened mediastinumTracheal deviationCalcification of the aortic wall CT with contrast: best confirmatory test for TAAsDetermines the extent, length, angulation, and diameter of the aneurysmCan detect a thrombus in the aneurysmCan detect free or contained rupture in the chest wallUseful for preoperative planningDisadvantages: exposure to radiation and contrast material; costly, time-consuming process; not suitable for hemodynamically unstable patients Other imagingMRI: similar findings as on CT scan Transthoracic or transesophageal echocardiography Arteriography Treatment Conservative Reduction of cardiovascular risk factorsOptimal blood pressure levels (< 120-80 mm Hg)Cessation of smoking Surgical Whether elective surgical repair is undertaken in asymptomatic patients depends on the size and expansion rate of the aneurysm. In symptomatic patients, the risks and benefits of aneurysm resection should be weighed carefully. In acutely symptomatic patients (e.g., in the case of rupture), an emergency operation is inevitable. Indications for repairAsymptomatic patients if the aneurysm is: Increased in diameter: ascending aneurysm ≥ 5.5 cm; descending aneurysm ≥ 6.5 cm Expanding rapidly: ≥ 1 cm per yearSymptomatic patients (e.g., patients with back pain or hoarseness); acutely symptomatic patients (e.g., in the case of rupture) require emergent surgery Procedure: open or endovascular stent grafting repair Complications Embolism: from thrombotic material of the aneurysm Aortic valve regurgitation: due to aortic root dilation Aortic dissection RuptureRisk factors: large diameter, rapid expansion, traumaClinical features of rupture Severe chest pain indistinguishable from acute MIPossible loss of consciousnessPossible hemoptysisDiagnosis No time for detailed assessmentImmediate surgery may be the investigation of choiceTherapy: emergency surgical repair (prosthetic graft placement)Complications: bleeding into the mediastinum → cardiac tamponade (rapidly fatal); left hemothoraxPrognosis: high mortality rate

Abdominal aortic aneurysm Abdominal aortic aneurysm (AAA) is a focal dilatation of the abdominal aorta to more than 1.5 times its normal diameter. AAAs are classified by location as either suprarenal or infrarenal aneurysms. Men of advanced age are at increased risk for their formation; smoking and hypertension are also major risk factors. AAAs are frequently asymptomatic and therefore detected incidentally. Symptomatic AAAs can manifest with lower back pain, a pulsatile abdominal mass, and a bruit on auscultation. Abdominal ultrasound is the best initial and confirmatory test to diagnose AAAs and determine their extent. Observation, close follow-up, and reduction of cardiovascular risk factors are indicated for small aneurysms, whereas pronounced (> 5.5 cm) or rapidly expanding aneurysms require surgery. Surgical treatment involves open resection of the aneurysm with graft placement or, increasingly, endovascular stent placement. The prognosis is markedly worse if dissection or aneurysm rupture occurs. AAA rupture typically presents with sudden onset of severe tearing back or abdominal pain, a painful pulsatile mass, and hypovolemic shock, and should be managed with emergent surgery. All men between 65 and 75 years of age with a history of smoking should be screened once with an ultrasound to exclude an AAA. See also thoracic aortic aneurysm for more information.

Definition Localized dilation of all three layers of the abdominal aortic wall (intima, media, and adventitia) to ≥ 3 cm pidemiology Peak incidence: 60-70 years (rare in patients < 50 years) Sex: ♂ > ♀: ∼ 2:1 Etiology Risk factorsAdvanced ageSmoking (most important risk factor) AtherosclerosisHypercholesterolemia and arterial hypertensionPositive family historyTrauma Classification LocalizationInfrarenal: below the renal arteriesMost common location [2]One-third of aneurysms extend into the iliac arteries. [1]Suprarenal: above the renal arteries ShapeSaccular (spherical) [3]Fusiform (spindle-shaped) Pathophysiology Inflammation and proteolytic degeneration of connective tissue proteins (e.g., collagen and elastin and/or smooth muscle cells) in high-risk patients → loss of structural integrity of the aortic wall → widening of the vessel → mechanical stress (e.g., high blood pressure) acts on weakened wall tissue → dilation and rupture may occur. The aneurysmatic dilatation of the vessel wall may cause disruption of the laminar blood flow and turbulence. Possible formation of thrombi in the aneurysm → peripheral thromboembolism Clinical features Aortic aneurysms are usually asymptomatic or have nonspecific symptoms. They are often discovered incidentally on ultrasound or CT scan. Rupture or dissection of the aneurysm is a life-threatening condition (see "Ruptured AAA"). Lower back pain Pulsatile abdominal mass at or above the level of the umbilicus Bruit on auscultation Peripheral thrombosis and distal atheroembolic phenomena (e.g., blue toe syndrome and livedo reticularis) Decreased ankle brachial index Diagnostics The diagnosis of AAA is confirmed by imaging showing aortic diameter > 3 cm. Unstable patients should be taken directly to the OR for emergency surgery if ruptured AAA is suspected (see ruptured AAA). There are no laboratory findings specific to AAA. [1] Imaging [6][7] Duplex ultrasoundIndications Best initial and confirmatory test in: Asymptomatic patientsPatients with abdominal pain and no known AAA or risk factors for AAATo determine the presence, size, and extent of an aneurysmScreening and surveillanceSupportive findings Dilatation of the aorta ≥ 3 cm [1]Thrombus may be present (hyperechoic)Disadvantages: Abdominal ultrasound has low sensitivity for aneurysmal leaks, branch arteryinvolvement, and suprarenal involvement, and its findings are insufficient for procedural planning. [8][1] If a large (> 5.5 cm) aneurysm is seen on ultrasound in a patient presenting with abdominal pain, refer the patient for treatment immediately. CT angiography abdomen and pelvis with IV contrastIndications Imaging modality of choice in symptomatic patients and for preintervention planningTo help confirm the diagnosis when ultrasound is not possible in asymptomatic patientsMore detailed evaluation of the location, size, and extent of the aneurysm, involvement of branch vessels, and presence of thrombus or ruptureSupportive findings Dilatation of the aorta ≥ 3 cm and possibly branch vessels [1]Thrombus may also be present (hypodense, nonenhancing) MR angiography abdomen and pelvis with and without IV contrastIndications Preintervention planning when CT angiography is not possibleTo help confirm diagnosis when ultrasound and CT angiography are not possible in asymptomatic patients Supportive findings: similar to CT angiography Arteriography (aortography abdomen) Indications To help confirm diagnosis or for preintervention planning if the patient has significant contraindications to CTA and MRAMore detailed assessment of the aortic lumenSupportive findings: contrast column in the lumen of the aneurysm and branch vessels [6]Disadvantage: may mask the actual diameter of the aneurysm (because a mural thrombus does not appear on arteriography) Abdominal aortic aneurysm Below the renal arteries (most common) Advanced age Predominantly men More common than TAA Smoking (most important risk factor) Atherosclerosis Hypercholesterolemia and arterial hypertension Pulsatile abdominal mass Bruit on auscultation Lower back pain Abdominal ultrasound (best initial and confirmatory test) Thoracic aortic aneurysm Ascending aorta (most common) Advanced age Predominantly men Arterial hypertension Bicuspid aortic valve Tertiary syphilis [9] Connective tissue diseases (e.g., Marfan syndrome, Ehlers-Danlos syndrome) Trauma Smoking Feeling of pressure in the chest Thoracic back pain Chest x-ray and CTA of chest Treatment Approach [1] Unstable patients (e.g., in case of rupture): emergency repair within 90 minutes (see "Ruptured AAA") Symptomatic patients with impending rupture or leaking AAA: urgent aneurysm repair within hoursConsider optimizing conditions for a successful outcome: If this delays surgery for a few hours, the patient should be monitored in an ICU in the meantime.Ensure blood product availability.Management of comorbidities (e.g., heart failure, acute kidney injury) Asymptomatic patients: elective aneurysm repair or aneurysm surveillance All patients: reduction of cardiovascular risk factors [1]Appropriate medical management of other atherosclerotic risk factors (e.g., hypertension, diabetes, hyperlipidemia)Smoking cessation Invasive treatment: AAA repair Indications [1]Emergency repair: unstable patientsUrgent repair: impending rupture or leaking AAAElective repair Fusiform aneurysm with maximum diameter ≥ 5.5 cm and low or acceptable surgical riskSmall fusiform aneurysm expanding ≥ 1 cm per yearSaccular aneurysm [1]Aneurysm with maximum diameter 5.0-5.4 cm in women Small aneurysm (4.0-5.4 cm) in patients requiring chemotherapy, radiotherapy, solid organ transplantation: individual approach Procedures [1] The long-term survival and complication rates of endovascular and open surgical repair are similar, and these procedures each have their advantages and disadvantages. Endovascular aneurysm repair (EVAR)Indications: minimally invasive procedure that is preferred over open surgical repair for most aneurysms, especially in patients with a high operative risk Procedure: Under fluoroscopic guidance, an expandable stent graft is placed via the femoral or iliac arteries intraluminally at the site of the aneurysm.Disadvantage: Reintervention rates are higher for EVAR than for OSR. Open surgical repair (OSR)Indications Mycotic aneurysm or infected graftPersistent endoleak and aneurysm sac growth following EVARAnatomical contraindications for EVAR Procedure: A laparotomy is performed and the dilated segment of the aorta is replaced with a tube graft or Y-prosthesis (bifurcated synthetic stent graft). Elective AAA repair postoperative mortality risk score [10]ParameterPointsPlanned interventionEVAR0OSR (infrarenal)2OSR (suprarenal)4Aneurysm size (mm)< 650≥ 652Age≤ 75 years0> 75 years1SexMale0Female1ComorbiditiesHistory of MI or cerebrovascular disease1COPD2Serum creatinine (mg/dL)< 1.50≥ 1.5 Preoperative management of comorbid conditionsCardiac consult in patients with cardiac diseases Optimize heart failure therapy.Consider coronary revascularization.12-lead ECG in all patientsEchocardiography in patients with worsening dyspnea or dyspnea of unknown originPulmonary function studies, including ABG, in patients with COPD, tobacco use, exertional dyspnea Additional considerations: Life expectancy should also be considered when planning elective repair. Perioperative care IV antibiotic prophylaxis [1]First-generation cephalosporin, e.g., cefazolin If the patient is allergic to penicillin: vancomycin Anticipate and treat acute blood loss anemiaEnsure blood product availability.Indications for blood transfusion [1]Hemoglobin is ≤ 7 g/dLHemoglobin is < 10 g/dL and there is ongoing blood loss Central venous access and arterial line monitoring during the procedure Consider postoperative admission to ICU: In patients with significant cardiac, pulmonary, or renal comorbiditiesIn patients requiring mechanical ventilationAfter significant arrhythmia or hemodynamic instability during procedure Multimodal pain managementE.g., morphine Consider epidural analgesia after OSRSee also acute pain management. VTE prophylaxis Surveillance after repair [1][7] Postoperative surveillance following EVAR is important because it can help to detect possible endoleaks, sac growth, device migration, and device failure. Because of the risk of an anastomotic aneurysm or aneurysmal dilation in the visceral aorta or iliac arteries, regular follow-up is recommended after OSR. CT angiography abdomen and pelvis with IV contrast After 1 month, 12 months, then annuallyAfter 6 months if an abnormality is seen on the 1-month scan MR angiography abdomen and pelvis without and with IV contrast Indication: contraindications to CT angiography, avoidance of radiationArtifacts might be visible depending on stent material and orientation. Duplex ultrasoundIndication: may be used for annual follow-up if the 12-month scan is unremarkableAbdominal and pelvic CT angiography with IV contrast should still be performed every 5 years. Conservative treatment: AAA surveillance without repair Small (< 5.5 cm), asymptomatic AAA can typically be observed with interval surveillance ultrasound. [12]To identify the expansion rate and thus decrease the risk of ruptureFrequency depends on the size of the aneurysm. Follow-up frequency for AAA surveillance [1]Maximum diameter of the abdominal aortaRecommended follow-up interval 2.5-2.9 cmRepeat ultrasound after 10 years. 3-3.9 cmUltrasound every 3 years4-4.9 cmUltrasound every 12 months5.0-5.4 cmUltrasound every 6 months Regular monitoring is essential because aneurysm size and expansion rate are strong predictors for the risk of rupture. Complications Abdominal aortic aneurysm rupture Embolism: caused by thrombotic material from the aneurysm Aortic dissection Postoperative complications [13]Ischemia of the bowel, kidneys, and spinal cord Anterior spinal artery occlusionProsthetic graft infectionAortoenteric fistula Complications following EVAR [1]EndoleakAccess site complications, e.g., bleeding, hematoma, false aneurysmGraft limb thrombosis Abdominal aortic aneurysm rupture Risk factorsRapidly expanding aneurysmLarge diameter aneurysmSmoking, tobacco use Clinical featuresHypovolemic shock (especially in free ruptures) Sudden onset of severe, tearing back or abdominal pain with radiation to the flank, buttocks, legs, or groinPainful pulsatile massGrey Turner sign and/or Cullen sign (if there is an extensive retroperitoneal hematoma) Nausea, vomitingSyncope Hematuria Diagnostics [1]Ruptured AAA is a clinical diagnosis; consider imaging only if the diagnosis is uncertain and the patient is hemodynamically stable UltrasoundDilatation of the aorta ≥ 3 cmPeriaortic fluidFree intra- or retroperitoneal fluid (depending on location of rupture)CT angiography abdomen and pelvis with IV contrast: only indicated if an alternative diagnosis seems more likely Sign of impending rupture: high-attenuation crescent within mural thrombus [14]Signs of rupture: retroperitoneal hematoma, retroperitoneal stranding, indistinct aortic wall, extravasation of contrastLaboratory findings that may be seen: CBC: ↓ hemoglobin, ↓ hematocrit, ↓ red blood cell countMetabolic acidosis in cases of shock Treatment: emergency EVAR or OSR [1]Hemodynamic support: IV fluid resuscitation with permissive hypotension (e.g., SBP 70-90 mm Hg) [1] Prognosis: high mortality rate (∼ 81%) [15] Unstable patients should be taken to the OR immediately for emergency surgery if ruptured AAA is suspected. Prevention Primary prevention [1] The following measures are thought to reduce the risk of developing an AAA: Eating nuts, fruits, and vegetables more than three times a weekExercising more than once a weekSmoking cessation Secondary prevention [1][15] Screening for abdominal aneurysm with abdominal ultrasound One-time screening in men aged 65-75 years with a history of smoking [1][15]Also consider one-time screening for the following groups: [1][15]Individuals aged 65-75 years with a positive family historyIndividuals aged > 75 years in good health with a positive family historyWomen aged 65-75 years with a history of smokingIndividuals aged > 75 years in good health with a history of smokingConsider rescreening after 10 years if the aortic diameter was > 2.5 cm but < 3 cm in the initial assessment. [1] Tertiary prevention [1] Elective repair to prevent rupture (see "Treatment") Aneurysm surveillance Smoking cessation

Metabolic syndrome Metabolic syndrome describes a constellation of medical conditions which increase the risk for several health problems, primarily cardiovascular disease, type 2 diabetes, and fatty liver.These conditions include insulin resistance (considered the main risk factor), hypertension, dyslipidemia, and abdominal obesity. The primary goal in treating metabolic syndrome is therefore to initiate lifestyle changes, which include dietary modifications and physical exercise. These measures often result in lowered blood pressure and triglyceride levels, as well as increased insulin sensitivity. Symptoms that do not respond sufficiently to these changes, such as persistent hypertension or hyperglycemia, are treated with drugs (e.g., ACE inhibitors, metformin).

Definition Metabolic syndrome Presence of ≥ 3 of the following conditions (or already receiving medical treatment for them) Insulin resistance: fasting glucose ≥ 100 mg/dLElevated blood pressure: ≥ 130/85 mm HgElevated triglycerides: ≥ 150 mg/dL Low HDL-C: in men < 40 mg/dL; in women < 50 mg/dLAbdominal obesity: waist circumference ≥ 102 cm in men; ≥ 88 cm in women Weight StatusBody Mass Index (BMI) Underweight< 18.5Normal or Healthy Weight18.5-24.9Overweight≥ 25-29.9Class I Obesity30-34.9Class II Obesity35-39.9Class III Obesity≥ 40 Treatment First-line: lifestyle modificationsDietary changes: calorie restriction, healthy foods (e.g., fruit/vegetables, protein-rich, unsaturated fats, sodium-restricted) Physical activity: minimum of 30 minutes moderate exercise per day (2.5 hours per week) , which increases insulinsensitivity, lowers blood pressure, and promotes weight loss Medical therapy: treat hypertension (e.g., ACE inhibitors), diabetes mellitus, and dyslipidemia (e.g., with statins) Bariatric surgery: if BMI ≥ 40 and no success with dietary and lifestyle changes Sleeve gastrectomy (most common): large part of the greater curvature is removed, so that the remaining stomachresembles a sleeveRoux-en-Y gastric bypass (2nd most common): Roux-en-Y Complications Metabolic syndrome is associated with increased risk of: Cardiovascular disease Type 2 diabetes Non-alcoholic steatohepatitis → increased risk of developing liver cirrhosis and hepatocellular carcinoma

Acute coronary syndrome Acute coronary syndrome (ACS) refers to acute myocardial ischemia and/or infarction due to partial or complete occlusion of a coronary artery. There are three clinical entities grouped under ACS: unstable angina pectoris, non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI). These conditions are often difficult to distinguish from one another based on clinical symptoms alone and require ECGand cardiac biomarker measurement to diagnose. Typical cardiac chest pain is substernal in nature, often described as a feeling of pressure, and is relieved with rest and/or nitrate use. The pain may radiate to the left jaw, neck, epigastrium, upper back, and/or left arm. Additionally, autonomic symptoms such as diaphoresis, nausea, and vomiting are common. ECG and laboratory tests are important diagnostic tools in the initial evaluation. In contrast to angina pectoris, NSTEMIand STEMI are characterized by the destruction of cardiac muscle tissue, which results in elevated cardiac enzymes in the blood (i.e., the elevation of troponin after 3-4 hours). Unlike unstable angina and NSTEMI, STEMI results in specific ECGchanges (e.g., ST-segment elevation), which can help to determine the location and stage of the infarct. The need for revascularization with either fibrinolysis or cardiac catheterization should be evaluated immediately, as revascularization significantly affects the prognosis of patients with myocardial infarction. Cardiac catheterization should be performed as soon as possible in STEMI and electively within 2-72 hours in high-risk NSTEMI and/or unstable angina. Medical management of ACS includes anticoagulation, analgesics, and antiplatelet agents. Complications of ACS include congestive heart failure, papillary muscle rupture, arrhythmias, and sudden cardiac death. Subsequent management and secondary prevention of ACS depends on the presence of comorbidities, but most patients should be started on indefinite aspirin and statin therapy.

Definition Myocardial infarction: myocardial cell death caused by prolonged ischemia [1][2] Acute coronary syndrome: suspicion or confirmed presence of acute myocardial ischemia and/or myocardial infarctionFurther classified as unstable angina, NSTEMI, and STEMI Sudden cardiac death (SCD): sudden, unexpected death caused by loss of cardiac function (most commonly due to lethal arrhythmia, e.g., ventricular fibrillation) Angina at rest or with minimal exertion New-onset angina Severe, persistent, and/or worsening angina (crescendo angina) Autonomic symptoms may be present: diaphoresis, syncope, palpitations, nausea, and/or vomiting Unstable angina Acute myocardial ischemia that is not severe enough to cause detectable quantities of myocardial injury biomarkers or ST-segmentelevations on ECG Partial occlusion of coronary vessel → decreased blood supply → ischemic symptoms (also during rest) No elevated cardiac biomarkers Anticoagulation, aspirin, ADP receptor inhibitor Invasive management depends on risk stratification (TIMI score). Non-ST-segment elevation myocardial infarction(NSTEMI) [5] Acute myocardial ischemia that is severe enough to cause detectable quantities of myocardial injury biomarkers but without ST-segment elevations on ECG Classically due to partial occlusion of a coronary artery Affects the inner layer of the heart(subendocardial infarction) Elevated cardiac biomarkers (e.g., troponin) Normal or nonspecific (e.g., ST depression, loss of R wave, or T-wave inversion) No ST elevations ST-segment elevation myocardial infarction(STEMI) Acute myocardial ischemiathat is severe enough to cause ST-segmentelevations on ECG Classically due to complete occlusion of a coronary artery Affects full thickness of the myocardium(transmural infarction) Cardiac biomarkersusually elevated (e.g., troponin)ST elevations (in two contiguous leads) or new left bundle branch block Immediate revascularization Anticoagulation, aspirin, ADP receptor inhibitor Epidemiology Incidence∼ 1.5 million cases of myocardial infarction per year in the US♂ > ♀ (3:1) Risk factors: See atherosclerosis.Increasing ageMale genderPersonal history of angina and/or known coronary artery diseaseFamily history of CADDiabetes mellitusSystolic hypertensionTobacco useHyperlipidemia Etiology Most common cause: coronary artery atherosclerosis Less commonCoronary artery dissectionCoronary artery vasospasm (e.g., Prinzmetal angina, cocaine use)Takotsubo cardiomyopathyMyocarditisThrombophilia (e.g., polycythemia vera)Coronary artery embolism (e.g., due to prosthetic heart valve, atrial fibrillation)Vasculitis (e.g., polyarteritis nodosa, Kawasaki syndrome)Myocardial oxygen supply-demand mismatch HypotensionSevere anemiaHypertrophic cardiomyopathySevere aortic stenosis Pathophysiology ACS is most commonly due to unstable plaque formation and subsequent rupture. Plaque formation and rupture For plaque formation, see coronary artery disease and atherosclerosis. Stable atherosclerotic plaque: manifests as stable angina (symptomatic during exertion) Unstable plaques are lipid-rich and covered by thin fibrous caps → high risk of rupture Inflammatory cells in the plaque (e.g., macrophages) secrete matrix metalloproteinases → breakdown of extracellular matrix → weakening of the fibrous cap → minor stress → rupture of the fibrous cap → exposure of highly thrombogenic lipid core → thrombus formation → coronary artery occlusion Coronary artery occlusion Partial coronary artery occlusionDecreased myocardial blood flow → supply-demand mismatch → myocardial ischemiaUsually affects the inner layer of the myocardium (subendocardial infarction) Typically manifests clinically as unstable angina and/or NSTEMI Complete coronary artery occlusionImpaired myocardial blood flow → sudden death of myocardial cells (if no reperfusion occurs)Usually affects the full thickness of the myocardium (transmural infarction)Typically manifests clinically as STEMI Clinical features Classic presentation Acute retrosternal chest painTypically described as dull, squeezing pressure and/or tightness Commonly radiates to left chest, arm, shoulder, neck, jaw, and/or epigastriumPrecipitated by exertion or stressSee also angina.The peak time of occurrence is usually in the morning (8-11 a.m.). [10]Dyspnea (especially with exertion)PallorNausea, vomitingDiaphoresis, anxietyDizziness, lightheadedness, syncope Other findingsTachycardia, arrhythmiasSymptoms of CHF (e.g., orthopnea, pulmonary edema) or cardiogenic shock (e.g., hypotension, tachycardia, cold extremities)New heart murmur on auscultation (e.g., new S4) Specific to inferior wall infarctionEpigastric pain Bradycardia Clear lung fields Atypical presentation: minimal to no chest painMore likely in elderly, diabetic individuals, and womenAutonomic symptoms (e.g., nausea, diaphoresis) are often the chief complaint.In patients with diabetes, chest pain may be completely absent (e.g., silent MI) due to polyneuropathy. Diagnostics ECG should be performed immediately once ACS is suspected, followed by measurement of cardiac biomarkers. Further diagnostic workup (e.g., echocardiography) depends on the results of initial evaluation and further risk stratification (e.g., TIMI score). ECG 12-lead ECG is the best initial test if ACS is suspected. Dynamic changes require serial ECG evaluation. Compare to prior ECGs (if available). ECG changes in STEMI [16] Acute stage: myocardial damage ongoing Hyperacute T waves ("peaked T wave") ST elevations in two contiguous leads with reciprocal ST depressions Intermediate stage: myocardial necrosis present Absence of R waveT-wave inversions Pathological Q waves Chronic stage: permanent scarring Persistent, broad, and deep Q wavesOften incomplete recovery of R wavesPermanent T wave inversion is possible. The sequence of ECG changes over several hours to days: hyperacute T wave → ST elevation → pathological Q wave → T-waveinversion → ST normalization → T-wave normalization An acute left bundle branch block accompanied by symptoms of acute coronary syndrome is also considered an ST-elevationmyocardial infarction (STEMI) because ST elevations cannot be adequately assessed in the setting of an LBBB. ECG changes in NSTEMI/unstable angina No ST elevations present Nonspecific changes may be present.ST depressionInverted T waveLoss of R wave Localization of the myocardial infarct on ECG V1-V6 Extensive anterior (Leads aVL and I can also be affected.)Proximal left anterior descending artery (LAD) V1-V2(Antero)septalLADV3-V4(Antero)apicalDistal LADV5-V6(Antero)lateralDiagonal branch of LADDistal LADLeft circumflex artery (LCX)In rare cases, can also be caused by right coronary artery (RCA) infarct I, aVLLateralProximal LCX II, III, aVF InferiorRCA (more common) Distal LCX (less common)V3R-V6R V7-V9 Posterior/posterolateralPosterior descending artery (from RCA or LCX)Reciprocal ST depressions in V1-3 may also be seen Infarction of the anterior wall is caused by obstruction of the LAD or its branches. Depending on the extent of anterior wall infarction, it results in ECG changes in the anterior wall leads (V1-6) and/or I and aVL. Infarction of the inferior wall is caused by obstruction of the LCX or RCA or their branches, and ECG changes are seen in leads II, III, and aVF. To remember the ECG leads with maximal ST elevation in anterior MI, think "SAL": "Septal (V1-2), Apical (V3-4), Lateral (V5-6). In severe transmural posterior wall infarction, there may not be any ST elevation on a standard 12-lead ECG. Troponin T/I6-8 h12-24 h7-10 daysCardiac-specific with high sensitivity for myocardial ischemia The degree of elevation often correlates with the size of the infarct.High sensitivity troponin assays (HscTn) may detect an increase in serum troponin level as early as 90 to 180 minutes after myocardial ischemia has occurred [20]Can also be elevated in other cardiac and noncardiac conditions: See differential diagnosis of increased troponin below.Myoglobin∼ 1 h4-12 h24 hNonspecific marker that is no longer commonly usedCK-MB∼ 4-9 h12-24 h2-3 daysCK-MB is more specific to cardiac tissue than total CK.Can be helpful for evaluating reinfarction because of its short half-life but is no longer commonly usedThe degree of elevation often correlates with the size of the infarct. Serum troponin T is the most important cardiac-specific marker and may be measured 3-4 hours after the onset of myocardial infarction. CK-MB values correlate with the size of the infarct, reach a maximum after approximately 12-24 hours, and normalize after only 2-3 days, making CK-MB a good marker for evaluating reinfarction. Additional findings [21][22] Elevated inflammatory markers: ↑ WBC, CRP Elevated BNP: especially in heart failure Elevated LDH Elevated AST (SGOT) Coronary angiography Best test for definitive diagnosis of acute coronary occlusion Can be used for concurrent intervention (e.g., PCI with stent placement) Can identify site and degree of vessel occlusion Indications includeAcute STEMIOther high-risk ACS (see TIMI score below)See also cardiac catheterization. The most commonly occluded coronary arteries (descending order): left anterior descending artery, right coronary artery, circumflex artery. Additional studies Transthoracic echocardiogramIdentification of any wall motion abnormalities and to assess LV functionImportant for risk assessment: In STEMI, the best predictor of survival is LVEF.Evaluation for complications: aneurysms, mitral valve regurgitation, pericardial effusion, free wall rupture Cardiac CTMay be considered as an alternative to invasive coronary angiography in patients with an intermediate risk of ACS(based on TIMI score)Allows for noninvasive visualization of the coronary arteriesContraindication: arrhythmias, tachycardia [23] Risk stratification TIMI score for unstable angina/NSTEMI [29] Method for calculating the risk of mortality in patients with unstable angina or NSTEMI Can be used to determine recommended therapeutic regimen and timing for revascularization Interpretation An increasing score is associated with a higher risk of mortality, new or recurrent myocardial infarction, and need for urgent revascularization (e.g., progression of unstable angina to STEMI)Risk score ≥ 3Early angiography recommendedConsider addition of glycoprotein IIb/IIIa inhibitor and treatment with enoxaparin (rather than UFH) CharacteristicsPointsAge ≥ 65 years1Three or more CAD risk factors (e.g., premature family history, DM, smoking, HTN, hyperlipidemia, PAD, abdominal aortic aneurysm)1Known CAD (prior stenosis > 50%)1Two or more episodes of severe angina in the last < 24 hours1ASA use in the last 7 days1ST deviation (≥ 0.5 mm)1Elevated cardiac biomarkers1Total points0-7 0-24 hrs Early coagulative necrosis (> 4 hours)Release of inflammatory cytokines from necrotic cells → edema, hemorrhageRecruitment of neutrophils (granulocytes)Hypercontraction of myofibrils → wavy fibers Contraction band necrosis (if reperfusion injury has occurred): release of reactive oxygen species (ROS) → increased influx of Ca2+ into the myocytes → contraction 0-12 hours: no gross changes 12-24 hours: dark mottling 1-3 days Extensive coagulative necrosis (4-72 hours) Neutrophilic infiltrate Inflammation spreads to tissue surrounding infarct. Hyperemia Yellow pallor 3-14 days Macrophage infiltration Granulation tissue surrounds infarct margins (3-10 days) Proliferation of blood vessels into granulation tissue (10-14 days) Hyperemicborder Center: yellow-brown, soft 2 weeks to several months Granulation tissue becomes denser → collagenous scar formation Grayish-whitefibrosis Obstruction of a coronary artery branch due to > 90% stenosis or embolization results in coagulation necrosis of the post-stenotic zone. Cellular changes See "Ischemia" in cellular changes and adaptive responses. Reperfusion injuryTimingCan occur spontaneously or after revascularization (e.g., fibrinolysis or PCI)Typically occurs when reperfusion occurs > 3 hours after the acute coronary artery occlusionMechanism: blood flow restored → damaged myocytes release reactive oxygen species (ROS) → mitochondrialpermeability transition pores are formed → cell swelling → cell death → Ca2+ entry into the cytosol → hypercontraction of myocytes → contraction band necrosis and increase in infarct size [9]Microscopic findings: neutrophilic infiltration, capillary obstruction, and contraction band necrosis of the myocardium ifferential diagnoses See differential diagnoses of chest pain. Differential diagnosis of increased troponin Cardiac causesMyocarditisDecompensated congestive heart failurePulmonary embolism Cardiac arrhythmia, tachycardiaCardiac traumaTakotsubo cardiomyopathy Noncardiac causesRenal failure StrokeCritical illness (e.g., sepsis) Differential diagnosis of ST-elevations on ECG [31] Early repolarization LBBB Brugada syndrome Myocarditis Pericarditis Pulmonary embolism Hyperkalemia Tricyclic antidepressant use Poor ECG lead placement Treatment Any patient with ST elevations on ECG requires immediate evaluation for urgent revascularization. The administration of other therapies should not delay care. All patients [31][5] MonitoringSerial 12-lead ECGContinuous cardiac monitoringSerial serum troponin measurement Pharmacologic therapySublingual or intravenous nitrate (nitroglycerin or ISDN) For symptomatic relief of chest painDoes not improve prognosisContraindications: inferior wall infarct (due to risk for hypotension), hypotension, and/or PDE 5 inhibitor (e.g., sildenafil) taken within last 24 hoursMorphine IV or SC (3-5 mg)Only if the patient has severe, persistent chest pain or severe anxiety related to the myocardial eventAdminister with caution due to increased risk of complications (e.g., hypotension, respiratory depression) and adverse events Beta blockerRecommended within the first 24 hours of admissionAvoid in patients with hypotension, features of heart failure, and/or risk of cardiogenic shock (e.g., large LV infarct, low ejection fraction).Statins: early initiation of high-intensity statin (such as atorvastatin 80 mg) regardless of baseline cholesterol, LDL, and HDL levels Loop diuretic (e.g., furosemide) if the patient has flash pulmonary edema or features of heart failure Supportive careIntravenous fluids (e.g., normal saline): in patients with an inferior MI that causes RV dysfunction Oxygen: only in case of cyanosis, severe dyspnea, or SpO2 < 90% (< 95% in STEMI) Primary interventions of MI treatment include "MONA": Morphine, Oxygen, Nitroglycerin, and Aspirin. But remember: Morphine, oxygen, and nitroglycerine are not necessarily indicated for every patient (see indications above). STEMI [31] Immediate revascularization Revascularization is the most important step in the management of acute STEMI and initiation of further therapies (e.g., DAPT, anticoagulation) should not delay this step in management. Emergent coronary angiography: with percutaneous coronary intervention (PCI) Preferred method of revascularizationBalloon dilatation with stent implantation (see cardiac catheterization)Ideally, door-to-PCI time should be < 90 minutes. It should not exceed 120 minutes. Thrombolytic therapy: tPA, reteplase, or streptokinaseIndications:If PCI cannot be performed < 120 minutes after onset of STEMIIf PCI was unsuccessfulNo contraindications to thrombolysisContraindicationsAny prior intracranial bleedingRecent large GI bleedingRecent major trauma, head injury, and/or surgeryIschemic stroke within the past 3 monthsHypertension (> 180/110 mm Hg)Known coagulopathyTimingSymptom onset was within the past 3-12 hoursShould be administered within < 30 minutes of patient arrival to the hospitalContraindicated if > 24 hours after symptom onsetPCI should be performed even if lysis is successful. Coronary artery bypass graftingNot routinely recommended for acute STEMIIndications If PCI is unsuccessfulIf coronary anatomy is not amenable to PCIIf STEMI occurs at the time of surgical repair of a mechanical defect Medical therapy Dual antiplatelet therapy: start as soon as possible Aspirin loading dose 162 mg-325 mgPLUS ADP receptor inhibitor: prasugrel, ticagrelor, or clopidogrel Dual antiplatelet therapy should be continued for at least 12 months after PCI with DES. GP IIb/IIIa receptor antagonist (e.g., eptifibatide or tirofiban): should be considered in precatheterization setting AnticoagulationHeparin or bivalirudin recommendedContinue until PCI is performed or for 48 hours after a fibrinolytic is given. "Time is muscle": Revascularization should occur as soon as possible in patients with STEMI! Unstable angina/NSTEMI [5] Dual antiplatelet therapy: start as soon as possible Aspirin loading dosePlus ADP receptor inhibitor: clopidogrel or ticagrelorDual antiplatelet therapy should be continued for at least 12 months if PCI with DES was performed. AnticoagulationHeparin or enoxaparinContinue for the duration of hospitalization or until PCI is performed. Immediate vs. delayed revascularizationThe indication for and timing of revascularization depends on the mortality risk (e.g., TIMI score).In patients with therapy-resistant chest pain, a TIMI score ≥ 3, ↑ troponin, and/or ST changes > 1 mmConsider the addition of a GPIIb/ IIIa inhibitor (e.g., tirofiban or eptifibatide)Plan for revascularization within 72 hours (e.g., angiography with PCI or CABG) Fibrinolytic treatment is not recommended in patients with unstable angina or NSTEMI. Subsequent measures See "Prevention" below. Secondary prophylaxis: See prevention of coronary heart disease, therapy of atherosclerotic diseases, and PTCA. See coronary artery surgery.Complications 0-24 hours post-infarction Sudden cardiac death (SCD)Definition: A sudden death presumably caused by cardiac arrhythmia or hemodynamic catastrophe, which occurs either within an hour of symptom onset in patients with cardiovascular symptoms, or within 24 hours of being asymptomatic in patients with no cardiovascular symptoms.[37]Pathophysiology: Fatal ventricular arrhythmia is considered to be the underlying mechanism of SCD. [38]Underlying conditionsCoronary artery disease: present in ∼ 70% of cases in adults over 35 years [39]Dilated/hypertrophic cardiomyopathyHereditary ion channelopathies (e.g., long QT syndrome, Brugada syndrome)Prevention: installation of the implantable cardioverter-defibrillator device [38] Arrhythmias (a common cause of death in MI patients in the first 24 hours)Ventricular tachyarrhythmiasAV blockAsystoleAtrial fibrillation Acute left heart failure: death of affected myocardium → absence of myocardial contraction → pulmonary edema Cardiogenic shock 1-3 days post-infarction Early infarct-associated pericarditisTypically occurs within the first week of a large infarct close to the pericardiumClinical features of acute pericarditis: pleuritic chest pain , dry cough , friction rub, diffuse ST elevations on ECGComplications (rare): hemopericardium, pericardial tamponade 3-14 days post-infarction Papillary muscle rupture Usually occurs 2-7 days after myocardial infarctionCan lead to acute mitral regurgitation Rupture of the posteromedial papillary muscle due to occlusion of the posterior descending artery is most common. Clinical features New holosystolic, blowing murmur over the 5th ICS on the midclavicular line Signs of acute mitral regurgitation: dyspnea, cough, bilateral crackles, hypotension Ventricular septal ruptureUsually occurs 3-5 days after myocardial infarctionPathophysiology: macrophagic degradation of the septum → ventricular septal defect → blood flow from LV to RV following the pressure gradient (left-to-right shunt) → increased pressure in RV and increased O2 content in the venous blood Most commonly due to LAD infarction (septal arteries arise from LAD) Clinical features New holosystolic murmur over the left sternal borderAcute-onset right heart failure (jugular venous distention, peripheral edema)Can progress to cardiogenic shock: tachycardia, hypotension, cool extremities, altered mental status Treatment: emergency surgery and revascularization (often via CABG) Left ventricular free wall rupture Usually occurs 5-14 days after myocardial infarctionGreatest risk during macrophage-mediated removal of necrotic tissueLV hypertrophy and tissue fibrosis from previous MI decrease the risk of free wall rupture. Clinical features: chest pain, dyspnea, signs of cardiac tamponade (e.g., Beck triad) Complications: cardiac tamponade , sudden cardiac death (if the rupture occurs acutely) Left ventricular pseudoaneurysm Usually occurs 3-14 days after myocardial infarctionRefers to the outpouching of the ventricular wall rupture that is contained by either the pericardium, a thrombus, or scar tissueAssociated with mural thromboembolism, decreased cardiac output, and increased risk of arrhythmia 2 weeks to months post-infarction Atrial and ventricular aneurysmsClinical features Persistent (> 3 weeks post-MI) ST elevation and T-wave inversionsSystolic murmur, S3 and/or S4Diagnosis: echocardiographyVisualization of the pathological myocardial wall protrusion Detection of dyskinetic movements of the thinned aneurysmal wall (uncoordinated contraction occurs due to fibrotic changes of the myocardium) Complications Cardiac arrhythmias (risk of ventricular fibrillation)Rupture → cardiac tamponadeMural thrombus formation → thromboembolism (stroke, mesenteric ischemia, renal infarction , acute obstruction of peripheral arteries)Treatment: anticoagulation, possibly surgery Postmyocardial infarction syndrome (Dressler syndrome): pericarditis occurring 2-10 weeks post-MI without an infective cause Thought to be due to circulating antibodies against cardiac muscle cells (autoimmune etiology)Clinical features Signs of acute pericarditis: pleuritic chest pain , dry cough , friction rubFeverLaboratory findings: leukocytosis, ↑ serum troponin levelsECG: diffuse ST elevationsTreatment: aspirin, acetaminophen Complications (rare): hemopericardium, pericardial tamponade Arrhythmias (e.g., AV block) Congestive heart failure (e.g., due to ischemic cardiomyopathy) Can occur at any time after an ischemic eventTreatment: for patients with LVEF < 40% or signs of heart failure, ACE inhibitor/ARB and aldosterone antagonistshave been shown to confer a mortality benefit. Reinfarction Prevention Primary prevention [31] Treatment/avoidance of modifiable risk factors for atherosclerosis (e.g., smoking cessation, treatment of hypertension, etc.) Healthy, plant-based diet [41] Regular physical activity and exercise Low-dose aspirin is beneficial for certain high-risk groups. The choice to prescribe it should be made on an individual basis. Secondary prevention [31] Lifestyle modification and treatment of modifiable risk factors (see "Primary prevention" above and treatment of diseases caused by atherosclerosis) Platelet-aggregation inhibitors Lifelong low-dose aspirin 75-100 mg/day DAPT with the addition of an ADP receptor inhibitor (e.g., prasugrel, ticagrelor, or clopidogrel) is recommended for 12 months for all patients who have undergone PCI. Glycoprotein IIb/IIIa antagonists (e.g., abciximab) may be considered but are not used routinely. Beta blockers: Unless contraindicated, all patients should be started on a beta blocker, which has been shown to confer a mortality benefit. Statin: All patients should be started on a high-intensity statin (e.g., atorvastatin). An aldosterone antagonist and ACE inhibitor/ARB are recommended for all patients with ischemic cardiomyopathyand an LV ejection fraction < 40% or symptoms of heart failure.

Pulmonary hypertension and cor pulmonale Pulmonary hypertension (PH) is elevated pressure in the pulmonary arteries ≥ 20 mm Hg at rest. It can be idiopathic or due to chronic pulmonary (e.g., COPD, chronic sleep apnea) and/or cardiac disease (e.g., mitral valve disease). Over time, the rise in pressure may result in structural changes (e.g., dilation or hypertrophy) or impaired function of the right ventricle. If these changes are secondary to diseases of the lungs or the pulmonary artery system, the condition is referred to as cor pulmonale. While PH and cor pulmonale are often asymptomatic in early stages, symptoms like dyspnea on exertion, fatigue, cyanosis, and syncope appear in later stages. In decompensated cor pulmonale, the risk of arrhythmias and death is high. Echocardiograms are used as an initial non-invasive test to estimate the pulmonary artery pressure and to demonstrate an altered structure of the right ventricle. Right heart catheterization provides the definite diagnosis and the exact mean pulmonary arterial pressure (mPAP). Treatment mainly consists of management of the underlying causes of PHand cor pulmonale. Supplemental oxygen, pulmonary vasodilators, and diuretics may be given to reduce pulmonary artery hypertension and improve blood oxygenation. Lung transplantation is the treatment of last resort in refractory cases.

Definition Pulmonary hypertensionChronically elevated mean pulmonary arterial pressure (mPAP) at rest ≥ 20 mm Hg (normal: 10-14 mm Hg) due to chronic pulmonary and/or cardiac disease or unknown reasonsPlus elevated pulmonary vascular resistance of ≥ 3 Wood units for patients with pre-capillary pulmonary hypertension (e.g., pulmonary arterial hypertension) [1] Cor pulmonale: altered structure (hypertrophy, dilation) or impaired function of the right ventricle caused by pulmonary hypertension resulting from a primary disorder of the respiratory or pulmonary artery system Chronic cor pulmonale: most common form; slow progressionAcute cor pulmonale: sudden overload of the right ventricle, usually due to acute pulmonary embolism; represents a life-threatening condition. Etiology Classification of pulmonary hypertension (WHO) by cause Group 1: Pulmonary arterial hypertension (PAH)IdiopathicHereditary (e.g., BMPR2 mutation)Drug-induced: sympathomimetic appetite suppressants (e.g., diethylpropion), amphetamines, cocaineAssociated conditions: HIV, connective tissue diseases, portopulmonary hypertension, congenital heartdisease, schistosomiasis Group 2: Left heart disease (e.g. valvular heart diseases, left-to-right shunt) Group 3: Chronic lung diseases and/or hypoxemiaCOPD, emphysemaObstructive sleep apneaInterstitial lung disease Group 4: Chronic thromboembolic occlusion of the pulmonary vessels Group 5: Unclear multifactorial mechanisms Pulmonary hypertension can also be classified as pre-capillary or post-capillary. Cor pulmonale Chronic form: diseases of the airway, pulmonary vasculature, and chest wallCOPD Chronic sleep apneaBronchiectasis [6]Idiopathic pulmonary arterial hypertensionKyphoscoliosis Life-threatening acute form is almost always due to acute massive pulmonary embolism. Pathophysiology Increased pulmonary vascular resistanceOcclusive vasculopathy (idiopathic pulmonary arterial hypertension (IPAH) , connective tissue diseases)Perivascular parenchymal changes (e.g., pulmonary embolism, interstitial lung disease)Hypoxic pulmonary vasoconstriction (e.g., COPD, obstructive sleep apnea) Chronic hypoxic pulmonary vasoconstriction → airway smooth muscle hypertrophy and pulmonary vascular bed destruction → increased pulmonary vascular resistanceInflammation (e.g., COPD) → increased inflammatory cell infiltration of intima → thickened endothelial wallPAH associated with endothelial dysfunction: ↑ endothelin → vasoconstriction [12] Increased pulmonary venous pressureVolume or pressure overload from left-sided heart disease (e.g. mitral valve regurgitation) Increased pulmonary blood flowLeft-to-right shunt (e.g., ASD, VSD, PDA)Sickle cell anemia Increased pressure in pulmonary circuit → elevated right ventricular afterload → dilatation and/or hypertrophy of the right heart → right heart failure and arrhythmias → death. Clinical features Often asymptomatic in early stages Fatigue Dyspnea and/or syncope on exertion (due to an inadequate increase in cardiac output during exercise because of increased pulmonary vascular resistance) Cyanosis Chest pain Clinical features of underlying etiology Less common Hoarseness Cough, hemoptysis Physical examination Loud and palpable second heart sound (often split)Parasternal heave Nail clubbingJugular vein distention Symptoms of right heart failure Diagnostics The diagnostic evaluation of cor pulmonale is inseparable from the evaluation of PH. Testing aims at confirming PH with or without cor pulmonale and determining its severity and underlying pathology. Doppler echocardiography (best initial test)Hypertrophy and/or dilation of the right heart ventricleDilation of the coronary sinusEstimation of pulmonary arterial pressure Right heart catheterization (confirmatory test)mPAP ≥ 20 mmHg at restPulmonary capillary wedge pressure: ≥ 15 mmHg in PH due to left heart diseaseIn pre-capillary PH: pulmonary vascular resistance ≥ 3 Wood units [1] Electrocardiography: right axis deviation due to right ventricular hypertrophy Chest x-rayPronounced central pulmonary arteriesRight heart hypertrophy (prominent right heart border)Signs of underlying cause (e.g., nodular opacities in interstitial lung disease, barrel chest in COPD) Treatment Initial therapy should be directed at the underlying cause of PH or cor pulmonale. Patients with persistent pulmonary hypertension and cor pulmonale despite treatment of the underlying cause should be evaluated for pulmonary vasodilator therapy in a specialized center. Treatment of the underlying cause Prior to the initiation of vasodilator therapy, a vasoreactivity test is performed. Patients, whose vasculature responds to calcium channel blockers(CCB) are considered vasoreactive. CCBs are the first-line treatment because they have fewer side effects than alternative second-line vasodilators (e.g. prostacyclins, endothelin receptor antagonists).) Additional treatmentDiuretics Physical exercise Oxygen therapy Pulmonary vasodilator therapy Calcium channel blockersLong-acting synthetic prostacyclin (epoprostenol) or prostacyclin analogs (e.g., iloprost, treprostinil): bind to prostacyclin receptors Endothelin receptor antagonists (e.g., bosentan, macitentan, and ambrisentan): inhibit endothelin-1receptors Phosphodiesterase 5 inhibitors (e.g., sildenafil; see PDE-inhibitors) Patients who are refractory to medical treatmentAtrial septostomy (right-to-left shunt) orHeart-lung/bilateral lung transplantation In acute cor pulmonale: see treatment of "Pulmonary embolism"Maintain adequate blood pressure (e.g., IV fluids, vasoconstrictors)Correct primary problem (e.g., anticoagulation, thrombolytic or surgical embolectomy in pulmonary embolism) Over-diuresis may result in under-filling of the right ventricle and a decrease in cardiac output, leading to further complications such as prerenal failure!

Chronic venous disease The most common chronic venous diseases are varicose veins (affecting approx. 23% of the US population) and chronic venous insufficiency (CVI), which affects 2-5% of the population. The condition is most often caused by increased venous pressure due to malfunctioning valves in the veins. Elevated venous pressure results in fluid accumulation in the lower extremities, leading to alterations in the skin and veins. Depending on the severity of hemodynamic changes, clinical manifestations may include superficial tortuous veins, edema, skin changes (e.g., stasis dermatitis), and ulcer formation. Diagnosis is established based on duplex ultrasonography. In complicated cases, magnetic resonance venography (MRV) may be performed as well. Treatment may be conservative (e.g., compression stockings) or involve ablation therapies (e.g., sclerotherapy, surgical excision).

Definition Varicose veins: cylindrical extension and dilation of superficial veins (diameter > 3 mm) with development of knots and tortuous veins Chronic venous insufficiency: increased venous pressure resulting in alterations of the skin and veins Epidemiology Prevalence: CVI affects 2-5% of individuals in the US. Varicose veins affect approx. 23% of individuals in the US. Peak incidence: CVI ♀: 5th decade♂: 8th decade Sex: ♀ > ♂ (∼ 2:1) Etiology Risk factors for chronic venous disease Increasing age and female sex (see "Epidemiology" above) Family history of venous disease Ligamentous laxity Sedentary lifestyle and prolonged standing Obesity Pregnancy Smoking Prior thrombosis (postthrombotic syndrome) Prior extremity trauma Congenital abnormalities Pathophysiology In healthy individuals, blood from the superficial leg veins passes through the perforating veins into the deep veins. Varicose veins Elevated venous pressure (see "Risk factors" above) → incompetence of venous valves (superficial or deep veins)→ reflux of blood into superficial veins and back into the extremity → further elevation of venous pressure → formation of varicose veins Chronic venous insufficiency Varicose veins → extravasation of protein and leukocytes → release of free radicals → damage to capillarybasement membrane → leakage of plasma proteins → edema formation → ↓ oxygen supply → tissue hypoperfusion and hypoxia → inflammation and atrophy → possibly ulcer formation Clinical features Chief complaints: generalized or localized pain, lower extremity discomfort/cramping, and limb swellingWorsened by heatWorse while standing, relieved by walking and raising of legs Occurs in ∼ 50% of affected individuals Pruritus, tingling, and numbness Skin findingsEdema formation (may be unilateral) that starts in the ankle and may involve the calf later in the disease course (in about half of affected individuals) Telangiectasias (esp. in women)Yellow-brown or red-brown skin pigmentation of the medial ankle; later of the foot and possibly lower legRBC breakdown leads to hemosiderin release → accumulation in the dermis → skin pigmentationMay lead to stasis dermatitis; a scaly, pruritic rashParaplantar varicose veins Lipodermatosclerosis: Localized chronic inflammation and fibrosis of skin and subcutaneous tissues of lower leg Painful, indurated, and hardened skinAtrophie blanche: White, coin- to palm-sized atrophic plaques due to absent capillaries in the fibrotictissue. Diagnostics The diagnosis of varicose veins is based on history and clinical findings. Imaging is only used in the diagnosis of CVI. Test of choice: duplex ultrasonographyPresence of venous reflux confirms diagnosis of CVI Examine patency of deep veinExamine sufficiency of superficial and perforating veins Treatment General treatment principles Elimination of the reflux pathways (via conservative, interventional, or surgical treatment options) → long-term normalization of hemodynamics → prevention/slowing of CVI progression Conservative measures Indications Superficial disease with no correctable cause of refluxPostoperative period Measures Compression therapy with compression stockingsFrequent elevation of the legsPhysical therapy, manual lymphatic drainageAvoid long periods of standing and sitting (with bent legs) and heat Definite treatment Indications: Symptomatic venous disease with correctable cause of refluxIn case of complications such as bleeding, ulcers, or recurrent superficial thrombophlebitis (also see "Complications" below) Technique: vein ablation therapies Interventional: First-line: endovenous thermal ablation (laser and radiofrequency)Alternative: chemical ablation (sclerotherapy) Open surgery with partial or complete removal of a vein: only for veins that are not accessible by interventional techniques Complications Venous ulcers Definition: Chronic defects of the skin that do not heal spontaneously Etiology: usually caused by chronic venous insufficiency Clinical featuresMost frequently occur just above the ankle (gaiter region)Shallow ulcer with irregular bordersUsually only mild pain, pruriticSymptoms and skin findings of chronic venous disease (see "Clinical features" above) DiagnosticsAnkle-brachial index (ABI) to exclude peripheral artery diseaseEvaluate patients for diabetes mellitusBiopsies should be performed in any nonischemic wound that fails to improve after 3 months of treatment.Culture if wound appears infectedSee also "Diagnostics" above. TreatmentTreat underlying disease (see "Treatment" above)Topical wound treatment : debridement, skin care, wound dressingsSystemic antibiotics in signs of infection (see cellulitis and erysipelas) Skin graft in large or refractory ulcers Differential diagnosisArterial ulcerDiabetic foot wounds (Malum perforans)Pyoderma gangrenosumVasculitisUlcerated skin tumors (e.g., basal cell carcinoma) Prognosis: recurrence rate as high as 40% depending on the initial size of the ulcer Further complications Vein hemorrhage Superficial thrombophlebitis Deep vein thrombosis

Calcium channel blockers Calcium channel blockers (CCBs) are drugs that bind to and block the L-type calcium channel. The L-type channels are the predominant calcium channels in the myocardium and the vascular smooth muscles. By blocking these channels, CCBs cause peripheral arterial vasodilation and myocardial depression, which leads to a drop in blood pressure and negative chronotropic, inotropic, and dromotropic effects on the myocardium. The most common indications for CCB use are hypertension, angina, and supraventricular arrhythmias. CCBs are also beneficial in the treatment of cardiomyopathy, thromboangiitis obliterans, Raynaud's phenomenon, and cluster headaches. CCBs are divided into three classes based on their effects: dihydropyridines (e.g., nifedipine, amlodipine) are potent vasodilators, phenylalkylamines (verapamil, gallopamil) are potent myocardial depressants, and benzothiazepines (diltiazem) are moderate vasodilators and myocardial depressants. The main side effects of dihydropyridines are caused by vasodilation (headaches, peripheral edema, reflex tachycardia), and those of phenylalkylamines by myocardial depression (bradyarrhythmias, atrioventricular block). The side effects of benzothiazepines are generally similar but milder compared to those of the other CCB classes. CCBs are contraindicated in patients with pre-existing cardiac conduction disorders (e.g., atrioventricular block, sick sinus syndrome), symptomatic hypotension, and acute coronary syndrome.

Dihydropyridines [1][2]Short-acting : nifedipine, clevidipineMedium-acting : nitrendipine, nicardipine, lercanidipineLong-acting : amlodipinePotent vasodilator Minimal myocardial depressant activity Non-dihydropyridine CCBsBenzothiazepinesDiltiazemModerate vasodilatorModerate myocardial depressant activity PhenylalkylaminesVerapamilGallopamilLess potent vasodilator than dihydropyridinesPotent myocardial depressant Effects CCBs bind to and block L-type calcium channels → decreased frequency of Ca2+ channel opening in response to cell membrane depolarization → decreased transmembrane Ca2+ current Effects of decreased Ca2+ influxVascular smooth muscle relaxation → vasodilation → decreased peripheral vascular resistance → decreased afterload → decreased blood pressure Decreased cardiac muscle contractility (negative inotropic action) → decreased cardiac output → decreased blood pressure Decreased SA node discharge rate (negative chronotropic action) → decreased heart rate (bradycardia) → decreased cardiac output → decreased blood pressure Decreased AV node conduction (negative dromotropic action) → termination of supraventricular arrhythmias Dihydropyridine CCBs (e.g., nifedipine, amlodipine) primarily act on vascular smooth muscles. Nondihydropyridine CCBs(diltiazem < verapamil) primarily act on the heart. Dihydropyridines Effects due to vasodilationPeripheral edema (esp. amlodipine) Headaches, dizzinessFacial flushing, feeling feverishReflex tachycardia (esp. nifedipine) May worsen symptoms of angina Gingival hyperplasia Benzothiazepines Side effects similar to the other classes of CCBs, but milder Phenylalkylamines Reduced contractility/bradyarrhythmia and drug-induced atrioventricular block Constipation Phenylalkylamines (verapamil) primarily affect the calcium channels of the heart and are contraindicated in cases of heart failurebecause of their negative effect on myocardial contractility! Indications Common indications for CCBsArterial hypertension (esp. amlodipine) Angina (all CCBs except for nifedipine)Stable angina (for patients with contraindications or who are not responsive to β blockers) Vasospastic angina (variant or Prinzmetal's angina) Supraventricular arrhythmias (esp. verapamil and diltiazem Supraventricular tachycardiaAtrial fibrillation Less common indicationsCardiomyopathy Raynaud's phenomenonThromboangiitis obliteransCluster headacheAchalasia Contraindications All classes of CCBAllergy/hypersensitivity to CCBsSymptomatic hypotension Acute coronary syndrome Dihydropyridines Hypertrophic obstructive cardiomyopathy (HOCM) Severe stenotic heart valve defects Benzothiazepines and phenylalkylamines Pre-existing cardiac conduction disorders Wolff-Parkinson-White syndrome Sick sinus syndromeSystolic dysfunction (in congestive heart failure) BradycardiaSecond or third-degree atrioventricular blockCombination with beta blockers → risk of AV block

Cardiomyopathy Cardiomyopathies are diseases of the muscle tissue of the heart. There are three major types: dilated, hypertrophic, and restrictive cardiomyopathy. Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy. Although most cases are idiopathic, a number of conditions (e.g., coronary artery disease, wet beriberi), infections (e.g., Coxsackie B virus, Chagas disease), and substances (e.g., heavy drinking, cocaine) have been identified as causes. In DCM, the decreased ventricular contractility of the dilated left ventricle (LV) leads to failure of the left and eventually right heart with decreased ventricular output. Isolated dilation and subsequent decrease in contractility of right ventricle (RV) is rare. Dilation can be seen on echocardiography, the most important diagnostic tool for all cardiomyopathies. Therapy involves management of congestive heart failure and treatment of the underlying condition.Hypertrophic cardiomyopathy (HCM) is the second most common cardiomyopathy. There are two types of HCM: The nonobstructive type is characterized by a thickening of the LV wall and is often asymptomatic, although arrhythmias and even sudden cardiac death can occur. The obstructive type (HOCM) is characterized by a thickening of the interventricular septum and systolic anterior movements of the mitral valve, causing LV outflow obstruction. HOCMmanifests with signs of reduced blood flow (dyspnea, dizziness, syncope). Both types are diagnosed with echocardiography. Even if most individuals are asymptomatic, it is important that they avoid strenuous exercise. Symptomatic patients should be treated with beta-blockers. Restrictive cardiomyopathy (RCM) is caused by the proliferation of connective tissue, with subsequent atrial enlargement (but normal ventricles). Like DCM, RCM causes left and right heart failure. The ejection fraction is usually normal, but diastolic filling is reduced on echocardiography. While a number of drugs offer symptomatic relief, the overall prognosis remains poor. Arrhythmogenic right ventricular cardiomyopathy (ARVC) primarily affects the right ventricle and is characterized by fibrofatty replacement of myocardium, which causes myocardial thinning and subsequent ventricular dilation. Although the hallmark finding is arrhythmia, symptoms are highly variable. Because management depends greatly on individual factors, such as the extent of the disease, there is no single best course of treatment. All patients should avoid strenuous exercise.

Dilated cardiomyopathy Pathophysiology ↓ Ventricular contractility due to dilation → ↓ leftventricular ejectionfraction (LVEF) Distinctive clinical featuresSigns of left heart failureand right heart failureS3 gallop EchocardiographyLV cavity sizeSignificantly increased EFSignificantly decreased Wall thicknessNormal or decreased Additional findingsLeft ventricular (and atrial) dilationWall movement abnormalitiesNormal diastolic function Other characteristicsMost common cardiomyopathy Hypertrophic cardiomyopathyHypertrophy of the left ventricle → ↓ ventricular relaxation → ↓ diastolic fillingand systolic output → ↓ myocardial and peripheral perfusion LV outflow obstruction due to hypertrophy of the interventricular septum and systolic anterior movement (SAM) of the mitral valve in obstructive typeFrequently asymptomatic Signs of left heart failure (dyspnea, syncope, dizziness) Arrhythmias S4 gallop Sudden deathOutflow tract obstruction (SAM, interventricular septum hypertrophy)Second most common cardiomyopathy Most common cause of sudden heart failure in athletes and teenagers Restrictive cardiomyopathy Proliferation of connective tissue → ↓ Elasticity of cardiac tissueAtrial enlargement and severe diastolic dysfunction Signs of left heart failure and right heart failure EF Normal or increasedReduced diastolic filling but (nearly) normal EF Dilated atria, nondilated ventriclesPoor prognosis without heart transplant Dilated cardiomyopathy Epidemiology Most common cardiomyopathy Incidence: 6/100,000 per year Sex: ♂ > ♀ (approx. 3:1) Etiology Idiopathic (∼ 50%) Genetic predisposition [2]Gene mutations with familial incidence Hemochromatosis Duchenne muscular dystrophy Secondary causes Coronary heart disease (ischemic cardiomyopathy)Arterial hypertensionPeripartum cardiomyopathy InfectionCoxsackie B virus myocarditisRheumatic heart diseaseChagas diseaseHIVSystemic lupus erythematosus, sarcoidosis Toxic substances Alcohol use disorderCocaineCardiotoxic drugs (anthracyclines such as doxorubicin/daunorubicin, AZT, and trastuzumab)Inhalation of organic solvents (e.g., glue sniffing) MalnutritionThiamine deficiency (wet beriberi)Selenium deficiencyChronic tachycardia (e.g., atrial fibrillation)RadiationEndocrinopathies (e.g., pheochromocytoma, hyperthyroidism, acromegaly)Valvular heart disease Aortic valve stenosisAortic valve regurgitationMitral valve regurgitation To remember some high-yield secondary causes of dilated cardiomyopathy, think ABCCCDD: A = Alcohol use, B = Beriberi, C = Cocaine, C = Coxsackie B virus, C = Chagas, D = Doxorubicin/Daunorubicin Causative factors decrease the contractility of myocardium → compensatory mechanisms (Frank-Starling law) are activated to maintain cardiac output → ↑ end-diastolic volume (preload) → myocardial remodeling → eccentric hypertrophy and dilation of the ventricle → reduced myocardial contractility → systolic dysfunction and ↓ ejection fraction → heart failureEccentric hypertrophy: sarcomeres added in seriesCaused by an increase in preload, which can be due to DCM and aortic regurgitation, among others ↓ LV contractility due to dilation leads to left-sided heart failure and eventually right-sided heart failureLeft-sided heart failure: decreased LV output leads to clinical features of left-sided heart failure via the following mechanisms: Diminished systemic perfusion → decreased perfusion of end organs → renal and cerebral dysfunction, cold extremities, etc. (forward failure)↑ Pressure within the pulmonary circulation → pulmonary circulation congestion → impaired gas exchange and fluid extravasation into the interstitium and alveoli → dyspnea, orthopnea, cardiac asthma (backward failurewith predominant pulmonary congestion)Right-sided heart failure : decreased rRV output → systemic circulation congestion → clinical features of right-sided heart failure (backward failure with predominant systemic congestion) Clinical features Exertional dyspnea Angina pectoris Palpitations Diffuse abdominal and peripheral edema Jugular venous distention Left ventricular impulse displacement Relative mitral valve regurgitation or tricuspid valve regurgitation S3 gallop Rales over both lung fields Diagnostics Approach Diagnostic approach to DCM aims to: Investigate the underlying cause with confirming either the secondary cause or idiopathic diseaseAssess cardiac functionAssess structural remodeling Specific investigations are guided by suspected underlying cause or complications Investigations [3] ECG: The following findings may be present but are not specific for DCM. Disorders of conduction (e.g. AV-block , left bundle branch block)Atrial fibrillation, arrhythmias Reduced QRS voltage Change of cardiac axis LaboratoryBNP: ↑ in concomitant heart failureTroponin and CK-MB to rule out myocardial infarction Echocardiography: used mainly for assessment of cardiac remodeling and function as it has a limited role in establishing etiology Atrial and/or ventricular dilation↓ Left ventricular ejection fraction (LVEF)Wall motion abnormalities (e.g., inferolateral hypokinesis is seen in muscular dystrophy and acute myocarditis) Chest x-rayCardiomegaly: left-sided hypertrophy with a balloon appearance Signs of left heart failure decompensation: pulmonary edema Pathology Treatment Treatment of the underlying disease Avoid cardiotoxic agents.Abstain from alcohol. Treat endocrine disorders (e.g., beta blockers for the treatment of hyperthyroidism).Treat infection (e.g., benznidazole for treatment of Chagas disease). Treatment of heart failureSodium restrictionACE inhibitors, beta blockers, diuretics, digoxinSee "Treatment" in CHF. Anticoagulation (e.g., warfarin): in case of mechanical valves, intraventricular thrombus and/or atrial fibrillation Surgical treatment If LVEF < 35%: ICD to prevent sudden cardiac death caused by ventricular fibrillationIf medical therapy fails: heart transplantation Complications Progressive LV failure → global heart failure Systemic thromboembolism → stroke, pulmonary embolism, acute mesenteric ischemia Ventricular tachycardia → ventricular fibrillation Sudden cardiac death Hypertrophic cardiomyopathy Epidemiology [9] Second most common cardiomyopathyObstructive type/hypertrophic obstructive cardiomyopathy (HOCM): ∼ 70% of casesNonobstructive type: ∼ 30% of cases Alongside myocarditis, HCM is one of the most frequent causes of sudden cardiac death in young patients, especially young athletes. Etiology [9][10] Primary HOCM: a genetic condition characterized by otherwise unexplained left ventricular hypertrophy. Most common hereditary heart disease: (60-70% of HCM cases)Autosomal dominant inheritance with varying penetrance (familial occurrence in > 50% of cases)Most commonly due to mutations in genes encoding myosin heavy chain → causes disorganized myocytearchitecture characterized by myofibrillar disarray and fibrosis Less commonly due to a mutation in cardiac sarcomeric proteins such as troponin and tropomyosin Secondary HCM: associated with certain conditions (e.g., chronic hypertension, Friedreich ataxia, Fabry disease, Noonan syndrome, amyloidosis) Pressure related hypertrophy: Cardiac hypertrophy is caused by chronic pressure and volume overload. Chronic hypertension → increased afterload → increased myocardial wall tension → changes in myocardial geneexpression → sarcomeres laid down in parallel → increased left ventricular thickness → decreased left ventricular size → diastolic dysfunction Pathophysiology [11] Obstructive type (HOCM): Greater hypertrophy of interventricular septum compared with the LV wall → obstruction of LV outflow [12]Concentric hypertrophy: increased LV wall thickness and decreased LV size, as sarcomeres are added in parallelCaused by an increase in afterload, which can be due to chronic hypertension (most common), aortic stenosis, and HOCMDuring systole: Accelerated blood flow through ventricular outflow tract causes negative pressure (Venturi effect) → anteriorleaflet of the mitral valve is drawn against the septum (systolic anterior motion, SAM) → ↑ outflow tract obstructionEjection flow pushes against abnormally placed and elongated MV leaflets → creates drag forces on a portion of the mitral valve leaflets → the leaflets are dragged into the outflow tract → ↑ outflow tract obstructionIncreasing mitral regurgitation Obstruction is exacerbated by factors that lead to increased heart contraction force and cardiac output : Physical exercise/stressReduction of preload or afterload Positive inotropic drugs (e.g., digoxin) Nonobstructive type involves hypertrophy of the left (possibly also the right) ventricle resulting in: Reduced diastolic compliance of the ventricle → reduced diastolic filling volume → reduced systolic output volumeImpaired cardiac contractility with reduced systolic output → reduced peripheral and myocardial perfusion (myocardial ischemia) → can cause disruption of electrical impulses → cardiac arrhythmia Clinical features [13] Symptoms: worsen with exercise, dehydration, and use of certain drugs (e.g., diuretics, hydralazine, ACEIs/ARBs, digoxin) Frequently asymptomatic (especially the nonobstructive type)Exertional dyspneaAngina pectoris Dizziness, lightheadedness, syncopePalpitations, cardiac arrhythmiasSudden cardiac death (particularly during or after intense physical activity) Physical examinationSystolic ejection murmur (crescendo-decrescendo) Increases with Valsalva maneuver, standing, inotropic drugs (e.g., digitalis) Decreases with:Hand grip, squatting, or passive leg elevationDrugs that decrease cardiac contractility (e.g., beta blockers) Possible holosystolic murmur from mitral regurgitationSustained apex beatS4 gallopParadoxical split of S2 Pulsus bisferiens: LV outflow obstruction causes a sudden quick rise of the pulse followed by a slower longer rise (biphasic pulse). Diagnostics [13][14][15] ApproachEchocardiography is the best initial and confirmatory test.Additional tests (ECG, CXR, exercise testing) are used to assess cardiac function and complications of cardiomyopathy. EchocardiographyFindings Asymmetrically thickened left ventricular wall ≥ 15 mm [16]In obstructive type Asymmetrically thickened interventricular septum Systolic anterior motion: protrusion of the anterior mitral valve cusp towards the septum → dynamic obstruction of blood flow↑ LVOT pressure gradient via doppler echocardiography [17]Provocation tests (see below) are obligatory if no obstruction is discernible at rest. ECGCan be normalSigns of left ventricular hypertrophy (see "Sokolow-Lyon criteria" in "Interpretation of the QRS complex" in ECG)Possibly nonspecific ST-wave and/or T-wave changesCommonly in obstructive type: abnormally deep Q waves, particularly in the inferior (II, III, and aVF) and lateral(I, aVL, V4-6) leads Left bundle branch block Ventricular tachycardia or atrial fibrillation CXRThe heart can be normal or enlarged.Left atrial enlargement is commonly seen in mitral regurgitation.Possibly signs of pulmonary congestion (e.g., pulmonary edema) in severe forms of CHF Exercise testingUsed for risk assessment and evaluation of LVOTTreadmill or bicycle exercise test Clinical observation for development of symptoms (e.g., dyspnea, palpitations)Blood pressure monitoring , ECG , and echocardiography Additional diagnostic proceduresCardiac MRIFor evaluating ventricular morphology if echocardiographic results are ambiguousFor detecting areas of fibrosis and necrosis Cardiac catheterization including levocardiography Possibly genetic testing and/or pedigree analysis Pathology Treatment [14][18][15] All patients should avoid strenuous exercise. Asymptomatic patients usually do not require further treatment. Symptomatic patients Medical therapyBeta blockers (first-line) or verapamil (second-line)Treat possible ventricular tachycardia or atrial fibrillation.Diuretics in nonobstructive HCM onlyAvoid diuretics in HOCM as well as digoxin and spironolactone in both typesInterventional therapy: Implantable cardioverter defibrillator (ICD): in case of a high risk of sudden cardiac death Transcoronary ablation of septal hypertrophy (TASH) indications: HOCM in persistent symptomsNYHA III/IV heart failureHigh-grade obstruction Surgery: myectomy (Morrow procedure) Indications: HOCM if symptoms persist despite nonsurgical treatmentCases of NYHA III/IV heart failureHigh-grade obstruction ) [17] Positive inotropic and afterload-reducing or preload-reducing drugs (e.g., digitalis, glyceryl trinitrate, calcium channel blockers of the dihydropyridine class, ACEIs) are contraindicated in patients with obstructive hypertrophic cardiomyopathy! Restrictive cardiomyopathy Epidemiology Least common cardiomyopathy Prevalence: 1:500 [4] Etiology Idiopathic Systemic diseases (Infiltrative cardiomyopathy) Amyloidosis (most common cause) Sarcoidosis Hemochromatosis Systemic sclerosis Other causes Endomyocardial fibrosis: a disorder with unknown etiology characterized by focal or diffuse endomyocardial thickening Proposed causative factors include: [23]Exposure to earth element ceriumChronic eosinophiliaViral and parasitic infectionsMagnesium deficiencyOccurs mainly in tropical countries with a low standard of health care Affects mainly children and adolescents [24][25]Löffler endocarditis: a condition characterized by eosinophilic infiltration of endocardium and myocardiumoccurring in diseases accompanied by eosinophilia Endocardial fibroelastosis: a condition characterized by diffuse thickening of the left ventricular endocardium due to proliferation of fibrous and elastic tissue Can be primary (with unknown etiology) or secondary (associated with various congenital heart conditions such as aortic stenosis, aortic atresia, coarctation of the aorta, patent ductus arteriosus, etc.)Most commonly occurs in the first 2 years of life [26] Iatrogenic causes of myocardial fibrosisChemotherapy: anthracyclines (e.g. doxorubicin), alkylating agents (e.g. carboplatin, cisplatin), tyrosine kinase inhibitors (e.g. imatinib, sorafenib), monoclonal antibodies (trastuzumab)Radiation of the chestAfter open heart surgery Etiology of restrictive cardiomyopathy: Puppy LEASH: P = Postradiation/Postsurgery fibrosis, L = Löffler endocarditis, E = Endocardial fibroelastosis, A = Amyloidosis, S = Sarcoidosis, H = Hemochromatosis Pathophysiology Proliferation of connective tissue → ↓ elasticity of myocardium → ↓ ventricular compliance → ↓ diastolic filling → atrial congestion → atrial enlargement and severe diastolic dysfunction → systemic venous congestion Clinical features Most common: dyspnea Symptoms of right heart failureJugular venous distentionPeripheral edema, ascitesHepatomegaly See "Clinical features" in CHF. Kussmaul sign Possibly S4 heart sound Diagnostics ApproachEchocardiography is the best initial test, as it can confirm restrictive cardiomyopathy.Further investigations aim to: Establish the etiologyAssess the possible complications EchocardiographySigns of diastolic dysfunctionNormal or decreased ventricular volume Rapid early but reduced diastolic fillingNear normal or elevated EF Atrial enlargement and dilationWall thickening is possible (usually symmetric ). ECGNonspecific abnormalities in S and T wavesLow voltage (especially in amyloidosis )Left bundle branch block and other conduction disorders CXRSigns of pulmonary congestion (e.g., pulmonary edema, pleural effusion)Can reveal signs of underlying disease (e.g., hilar lymphadenopathy in sarcoidosis) Cardiac catheterizationHigh atrial pressureAbnormal ventricular pressure: diastolic pressure is usually slightly higher in the left ventricle compared to the right [27] Endo/myocardial biopsyHistology classically shows fibrosis.Diagnosis of underlying cause if other tests are inconclusive (e.g., amyloid or iron depositions, eosinophilic infiltrates in Löffler endocarditis) Treatment Treatment is generally limited and often only palliative. Treatment of underlying condition (e.g., phlebotomy for hemochromatosis) Symptomatic treatment Maintenance of sinus rhythm: beta blockers↑ Ventricular filling time, ↓ sympathetic activity: cardioselective calcium channel blockers↓ Preload: ACE inhibitorsException: ACEIs are poorly tolerated in amyloidosis.For fluid overload: diuretics Anticoagulation (e.g., warfarin) to prevent embolism in patients with a history of atrial fibrillation Heart transplant (in patients with refractory symptoms) Arrhythmogenic right ventricular cardiomyopathy (ARVC) Epidemiology Most common in young adults (mean age at diagnosis: ∼ 30 years) [30] Prevalence: 1:1000-2000 [31] Etiology Mutations of various genes (e.g., JUP gene) Autosomal recessive or autosomal dominant inheritance [31][32] Pathophysiology Right ventricular myocardial cell death (due to myocyte apoptosis, inflammation, and fatty/fibrotic tissue replacement) → thinning of the ventricular wall → dilation of the right ventricle → ventricular arrhythmia and dysfunction [30] The left ventricle can also be affected, but consequences are usually less severe. Clinical features Highly variable; many patients remain asymptomatic Angina pectoris Dyspnea Peripheral edema, ascites, hepatic and splenic congestion Palpitations, syncope, possibly sudden cardiac death (particularly during or after exercise) Diagnostics [31][30][33] Approach ARVC is diagnosed based on the AHA criteria which include five groups of features: Dysfunction and structural abnormalities of RV (can be revealed by echocardiography, MRI, or RV angiography) Histological characteristics (require myocardial biopsy) Abnormal repolarization (diagnosed with ECG) Depolarization/conduction abnormalities (diagnosed with ECG) Arrhythmias (diagnosed with ECG) Family history (confirmation of ARVC in a relative either by criteria, pathological examination in surgery or autopsy, or by genetic testing) Findings ECGRepolarization disturbances in the right precordial leads (V1-3) → possibly epsilon wave (at the end of a widened QRS complex) Highly specific for ARVC but only occurs in about one-third of patientsIncreased QRS durationVentricular tachycardia Ventricular extrasystoles Echocardiography and cardiac MRIRV enlargementRV wall motion abnormalities↓ RV EFLocalized RV aneurysms Endomyocardial biopsy: fibrofatty replacement of myocardial tissue Genetic testing: Multiple genetic abnormalities that can cause ARVC have been identified (e.g., plakoglobin (JUP), desmoplakin (DSP), plakophilin-2 (PKP2), desmoglein-2 (DSG2), desmocollin (DSC2)). [32] Management [33] Avoid intense physical exertion. Antiarrhythmic treatment Pharmacologic: beta blockers (e.g., sotalol), amiodarone, calcium channel blockersInvasive ICD implantation (in high-risk patients, e.g., patients with left ventricular involvement)Radiofrequency ablation (only as ancillary treatment) Heart transplant (in severe cases refractory to all other treatments) Screening and genetic counseling for 1st-degree relatives Unclassified cardiomyopathies Takotsubo cardiomyopathy Definition: acute, stress-induced, reversible dysfunction of the left ventricle that can mimic acute coronary syndrome Epidemiology: especially postmenopausal women > 60 years Pathophysiology: emotional/physical stress → massive catecholamine discharge → cardiotoxicity, multi-vessel spasms and dysfunction → myocardial stunning Clinical findings: similar to ACSAcute retrosternal chest painDyspneaSyncopeArrhythmiasSigns of heart failure and/or cardiogenic shock (e.g., hypotension) DiagnosticsECG: ST elevation (or, less commonly, ST depression), QT interval prolongation, T wave inversion, abnormal Q wavesLaboratory: slightly ↑ troponin T, ↑ BNPEchocardiography: apical left ventricular ballooning , ↓ LVEFCoronary angiography: usually no pathological findings (e.g., no obstruction of coronaries by plaque rupture); a minority of patients have noncritical stenoses ManagementAvoid triggers of physical and/or emotional stress.Symptomatic: beta blockers , ACE inhibitors Management of complications (e.g., heart failure, ventricular tachycardia) Prognosis: spontaneous recovery if stressors are avoided Left ventricular noncompaction Definition: rare inherited cardiomyopathy which is associated with structural abnormalities of the left ventricular myocardium (prominent trabeculations and deep intertrabecular recesses) Clinical findingsSigns of heart failure and arrhythmia (e.g., dyspnea, edema, chest pain, palpitations, syncope)Thromboembolisms Diagnostics: echocardiography and/or cardiac MRI: LV wall thickening, prominent trabecular meshwork, detection of abnormal flow (within the deep intertrabecular recesses) Treatment: no causal treatment available Avoid intense physical exertion Symptomatic treatment of complications (e.g., heart failure)Prevention of thromboembolismICD Heart transplant Family and genetic counseling Arrhythmia-induced cardiomyopathy Definition: recurring or persistent atrial or ventricular arrhythmias causing structural cardiac changes and left ventricular dysfunction (potentially reversible) EtiologyAtrial tachycardia, atrial fibrillation, atrial flutter, supraventricular reentry tachycardiaVentricular tachycardia (less commonly than supraventricular tachyarrhythmias)Atrial or ventricular ectopy (with or without tachycardia) Clinical features Signs of underlying arrhythmia (e.g., palpitations, syncope)Signs of left-ventricular CHF (e.g., dyspnea, chest pain, pulmonary edema) DiagnosticsECG: tachyarrhythmia, ectopic fociCardiac monitoring (e.g., Holter monitor)Echocardiography and/or cardiac MRI: to evaluate cardiac structure and function (e.g., LVEF measurement)To exclude other causes (e.g., coronary heart disease via coronary angiography) TreatmentBeta blockers: management of CHF, rate control in tachyarrhythmiasAntiarrhythmics (e.g., amiodarone): rhythm control in tachyarrhythmiasCatheter ablation: rhythm control in tachyarrhythmias, ectopic foci

Sympathomimetic drugs Sympathomimetics are substances that mimic or modify the actions of endogenous catecholamines of the sympathetic nervous system. Direct agonists directly activate adrenergic receptors while indirect agonists enhance the actions of endogenous catecholamines. Sympathomimetics stimulate alpha-1 adrenergic receptors, beta-adrenergic receptors, and dopamine (D) receptors in various target tissues, such as the eyes, heart, and vascular smooth muscle. The clinical indications for sympathomimetics are broad and include asthma, heart failure, shock, and anaphylaxis. Side effects include hypertension, sinus tachycardia, and skeletal muscle tremor.

Direct sympathomimetics Direct sympathomimetics stimulate adrenergic and dopaminergic receptors directly. Beta-adrenergic agonists: predominantly act on the adrenergic beta-receptors (e.g. isoproterenol)Alpha-adrenergic agonists: predominantly act on the adrenergic alpha-receptors (e.g. norepinephrine)Dopaminergic agonists: predominantly act on the D1 receptor (e.g., fenoldopam) Albuterol (salbutamol), salmeterol, terbutaline β2 > β1 Acute asthma COPD Preterm labor: Terbutaline is a tocolytic used to delay preterm labor for up to 48 hours. Clonidineα2HTN ADHDDrug withdrawalDobutamineβ1 > β2, αHeart failure Cardiogenic shockCardiac stress testingDopamineD1 = D2 > β > αHeart failureShockUnstable bradycardia Epinephrineβ > α AnaphylaxisCardiac arrestSeptic shockPostbypass hypotensionAsthmaOpen-angle glaucomaFenoldopamD1Hypertensive crisisPostoperative hypertension Isoproterenolβ1 = β2Bradycardia or heart block Cardiac arrest from heart block when pacemaker therapy is unavailableMethyldopaα2HTN, especially in pregnancyMidodrineα1Autonomic insufficiency and symptomatic orthostatic hypotensionMirabegronβ3Urinary urge incontinence or overactive bladderNorepinephrineα1 > α2 > β1Septic shock Neurogenic shock Oxymetazolineα1 > α2EpistaxisRhinitis, sinusitis (topical decongestant)RosaceaPhenylephrineα1 > α2Hypotension RhinitisAllergic conjunctivitisOpen-angle glaucoma Ischemic priapism (high-dose intracavernosal phenylephrine injection) Indirect sympathomimeticsDrugsActionIndicationsIndirect general agonistReuptake inhibitorReleases catecholaminesAmphetamines✓✓✓ADHD [1]NarcolepsyObesity Cocaine✓✓Local anesthesiaVasoconstriction Ephedrine✓✓Anesthesia-induced hypotensionUrinary incontinence Nasal decongestant (pseudoephedrine) Eyeα1Mydriasis (↑ pupillary dilator muscle contraction)Distant accommodation (↑ ciliary body contraction)α2↓ Aqueous humor productionβ2↑ Aqueous humor production Blood vessels α1 ↑ Vascular smooth muscle contraction of arterioles → ↑ peripheral resistance → ↑ afterload Venoconstriction → ↑ venous return → ↑ preload α2 ↑ Platelet aggregation β2 Peripheral vasodilation → ↓ peripheral resistance → ↓ afterload Heart β1 ↑ Heart rate ↑ Contractility ↑ Automaticity and conduction velocity Bronchi β2 Bronchodilation Gastrointestinal tract α1 Sphincter contraction β2 ↓ Peristalsis Liverα1↑ Glycogenolysisβ2 Pancreasα2↓ Insulin releaseβ2↑ Insulin release Kidneysβ1↑ Release of reninBladderα1Sphincter contraction → urinary retention β2Detrusor relaxationβ3Female reproductive organsβ2↓ Uterine tone (tocolysis) Male reproductive organsα1Ejaculation from vas deferensSkeletal muscleβ2↑ Contraction↑ Glycogenolysisβ3↑ Thermogenesis in skeletal muscleAdipose tissueα2↓ Lipolysisβ1-3↑ Lipolysis Side effectsα1-agonists [6]Hypertension (due to peripheral vasoconstriction) and reflex bradycardiaPiloerectionUrinary retention Ischemia and necrosis, especially of the fingers or toes α2-agonistsThe side effects of α2-agonists are mainly due to their sympatholytic effects. [2] [1]CNS depression (e.g., sedation)Respiratory depressionBradycardia and hypotensionMiosisRebound hypertension Dry mouth α-Methyldopa side effects [7]Autoimmune hemolytic anemiaSLE-like syndromeβ1-agonistsTachycardia and arrhythmiasCan precipitate angina or myocardial infarction in patients with coronary artery diseaseβ2-agonists [3]Tremor (most common side effect), agitation, insomnia, diaphoresisHypotension (due to peripheral vasodilation) and reflex tachycardiaMetabolic disturbances: hyperglycemia, hypokalemia Side effectsAmphetaminesSee intoxication in amphetamine use disorder.CocaineSee intoxication in cocaine use disorder.EphedrineHypertensionReflex bradycardia (due to hypertension) or tachycardiaDizzinessNausea, vomiting Catecholamines (e.g., epinephrine, norepinephrine, isoproterenol, dopamine, dobutamine) should only be administered if monitored by an experienced physician! High-dose catecholamine administration requires intra-arterial blood pressure monitoring. Beta blockers should be avoided in any person in which cocaine use is suspected because the interaction between the drugs can lead to unopposed activity of alpha-1 receptors.

Cardiac glycosides Cardiac glycosides are drugs that inhibit the Na+/K+- ATPases found on the outer cell surface. Digoxin is the only drug of this class that is commonly used in clinical settings. The main indications for digoxin treatment are atrial fibrillation and heart failure in treatment-resistent cases. Because cardiac glycosides have a narrow therapeutic index, close monitoring of serum concentrations is necessary. Typical symptoms of cardiac glycoside poisoning are nausea, vomiting, blurry vision, and cardiac arrhythmias. Overdose can quickly become life-threatening and swift treatment is vital. The first-linetreatment for cardiac glycoside poisoning is administration of digoxin-specific antibodies.

Effects Inhibition of Na+/K+-ATPases → higher intracellular Na+ concentration → reduced efficacy of Na+/Ca2+ exchangers → higher intracellular Ca2+ concentration → increased vagal tone→ In cardiomyocytes, this leads to increased contractility (positive inotropic effect), reduced velocity of electric conduction (negative dromotropic effect), and a reduction of the heart rate (negative chronotropic effect). → In neurons (of the vagal nerve), this leads to reduced velocity of electric conduction and reduction of the heart rate (via a reflexive reduction of sympathetic transmission). Cardiac glycosides inhibit Na+/K+-ATPase, increasing cardiac contractility and decreasing AV conduction and heart rate! Cardiac glycoside poisoning EtiologyDigoxin overdose (iatrogenic, by nonadherence to prescribed dosages or by ingestion of plants containing cardiac glycosides) Ouabain poisoining Hypokalemia Renal failureTreatment with verapamil, diltiazem, amiodarone, and/or quinidine Volume depletion (e.g., treatment with diuretics) Clinical features: Nausea/vomiting, diarrhea, abdominal pain, and anorexiaBlurry vision with a yellow tint and halos, disorientation, weakness Diagnostics: ECG: potentially severe cardiac arrhythmiasPremature ventricular beatsT-wave inversion or flatteningDownsloping ST segment depression ("scooped" ST segments)↓ QT interval↑ PR intervalAtrial tachycardia with AV blockLaboratory studiesSerum digoxin concentration (ideally, measure 6 hours after ingestion)Serum electrolyte levels: hyperkalemia Creatinine and blood urea nitrogen to evaluate renal function TreatmentDigoxin-specific antibody (œ) fragments Atropine for symptomatic bradycardiaSlowly normalize serum K+ levelsMg2+Class IB antiarrhythmicsTemporary cardiac pacing Digoxin has a narrow therapeutic index! Serum concentrations of cardiac glycosides must be monitored closely because overdoses can have severe consequences!Cardiac glycoside poisoning EtiologyDigoxin overdose (iatrogenic, by nonadherence to prescribed dosages or by ingestion of plants containing cardiac glycosides) Ouabain poisoining Hypokalemia Renal failureTreatment with verapamil, diltiazem, amiodarone, and/or quinidine Volume depletion (e.g., treatment with diuretics) Clinical features: Nausea/vomiting, diarrhea, abdominal pain, and anorexiaBlurry vision with a yellow tint and halos, disorientation, weakness Diagnostics: ECG: potentially severe cardiac arrhythmiasPremature ventricular beatsT-wave inversion or flatteningDownsloping ST segment depression ("scooped" ST segments)↓ QT interval↑ PR intervalAtrial tachycardia with AV blockLaboratory studiesSerum digoxin concentration (ideally, measure 6 hours after ingestion)Serum electrolyte levels: hyperkalemia Creatinine and blood urea nitrogen to evaluate renal function TreatmentDigoxin-specific antibody (œ) fragments Atropine for symptomatic bradycardiaSlowly normalize serum K+ levelsMg2+Class IB antiarrhythmicsTemporary cardiac pacing Digoxin has a narrow therapeutic index! Serum concentrations of cardiac glycosides must be monitored closely because overdoses can have severe consequences! Indications Congestive heart failure (symptomatic patients with NYHA ≥ II despite pharmacotherapy) Atrial fibrillation Supraventricular tachycardia Contraindications Ventricular fibrillation Use with caution in pregnant women and in patients with: Electrolyte and fluid disorders (e.g., volume depletion, hypokalemia, hypomagnesemia, and/or hypercalcemia )Cardiovascular disorders (e.g., acute coronary syndrome, AV blocks, Wolff-Parkinson-White syndrome, hypertrophic obstructive cardiomyopathy, sick sinus syndrome)Renal failure (can lead to digoxin overdose and, vice versa, digoxin can also cause/worsen renal failure)Certain medications → See "Interactions" below. Interactions K+-depleting diuretics → hypokalemia → arrhythmias Verapamil, diltiazem, amiodarone, quinidine → possible overdose → reduce digoxin dose

Amiodarone Amiodarone is a class III antiarrhythmic agent that blocks voltage-gated potassium channels. It is used in the treatment of acute ventricular tachycardia and persisting ventricular fibrillation (VF) after unsuccessful defibrillation, as well as the long-term treatment of refractory supraventricular arrhythmia (atrial fibrillation). Since amiodarone has a very low negative inotropic effect, it can be used in patients with a reduced ejection fraction (EF). Side effects commonly involve the thyroid, liver, heart, eyes, and central nervous system. Pulmonary side effects, such as lung fibrosis and chronic interstitial pneumonitis, are rare but severe. Because amiodarone is a cytochrome P450 inhibitor, simultaneous administration of other drugs should be considered carefully to minimize the risk of interactions.

Effects Primary mechanism of action: antiarrhythmic effect via blockage of voltage-gated potassium channels → prolongedrepolarization of the cardiac action potential Secondary mechanism of action: inhibits β-receptors and sodium and calcium channels → decreases conduction through the AV and sinus node Special uses: only antiarrhythmic agent with (almost) no negative inotropic effect → use in patients with reduced EF Organ systemSide effectsLungsPulmonary toxicity Pulmonary fibrosis Chronic interstitial pneumonitisOrganizing pneumoniaARDSSolitary pulmonary mass Thyroid May induce hypothyroidism and/or hyperthyroidismMay aggravate pre-existing thyroid conditions LiverAST/ALT > 2x normal If patients experience more than a two-fold elevation, drug therapy should be discontinued. LFTs should be monitored at baseline and every 6 months.Hepatitis and cirrhosis HeartBradycardia and AV block Proarrhythmia EyesCorneal micro-deposits Optic neuritis GI tractNausea, anorexia, and constipationSkinPhotosensitivityBlue discolorationCNSVarious manifestations, esp. peripheral neuropathy (also ataxia, paresthesias, sleep disturbance, impaired memory, and tremor)GU tractEpididymitis and erectile dysfunction "Am-IOD-arone" consists of approx. 37% iodine!Indications Acute treatment (IV administration) Second-line therapy for patients with ventricular tachycardia (VT) who are hemodynamically stable Persistent VT after defibrillationPulseless ventricular fibrillationSupraventricular tachycardia in patients with cardiac failure (LVEF < 40%) Long-term treatment (oral administration) Rhythm control in refractory symptomatic atrial fibrillation (supraventricular arrhythmia) and underlying heartdisease → restoration and maintenance of sinus rhythm Amiodarone is the drug of choice for ventricular arrhythmias in most heart failure patients (LVEF < 40%). Contraindications Severe sinus node dysfunction with marked sinus bradycardia Second- and third-degree heart block (except in patients with a functioning pacemaker) Hyperthyroidism and hypothyroidism Known allergy to iodine Pre-existing lung disease Interactions Amiodarone is an inhibitor of cytochrome P450 enzymes (see principles of pharmacology) → reduced clearance of the following drugs: Warfarin (risk of bleeding!)Simvastatin (increased risk of rhabdomyolysis)DigoxinCyclosporineFlecainide, procainamide, quinidineSildenafil Pharmacokinetics Amiodarone is very lipophilic → accumulation of amiodarone in myocardium and muscles → long duration of action Metabolized in the liver by CYP3A4 with biliary excretion Oral treatmentIV bolusOnset of action2 days to 3 weeksWithin a few hoursTime to peak effect1 week to 5 months15 minutes Half-life elimination40-55 days9-36 days

Renal artery stenosis Renal artery stenosis is the narrowing of one or both renal arteries. It is most commonly caused by atherosclerosis. In young women, fibromuscular dysplasia is an important underlying cause. Decreased renal blood flow due to renal artery stenosis causes activation of the renin-angiotensin-aldosterone system, which in turn results in secondary hypertension. Physical examination may reveal an abdominal bruit. Patients with progressive renal artery stenosis develop renal insufficiency and progressive renal atrophy. Hypokalemia in a newly diagnosed case of hypertension or an abrupt increase in creatinine after initiating ACE inhibitors or angiotensin receptor blockers is suggestive of renal artery stenosis. The diagnosis is confirmed by duplex ultrasonography or angiography. Treatment of mild renal artery stenosis primarily consists of antihypertensive therapy. The antihypertensives of choice are paradoxically ACE inhibitors and angiotensin receptor blockers; calcium channel blockers or beta blockers can also be used. Patients on ACE inhibitors or angiotensin receptor blockers should be closely monitored for an increase in serum creatinine, especially if they have bilateral renal artery stenosis. Patients with severe renal artery stenosis will require renal angioplasty.

Epidemiology Accounts for 1-10% of all hypertension cases. 5-25% of pediatric cases of secondary hypertension cases have a renovascular etiology. Age and sex preponderance depend on the underlying cause (see "Etiology" below). Etiology Atherosclerosis (∼ 90% of cases): occurs more often in men > 50 years of age Fibromuscular dysplasia (∼ 10% of cases): mostly affects women < 50 years of age Pathophysiology Narrowing of one or both renal arteries → obstruction of renal blood flow → ischemia → renin release and activation of the renin-angiotensin-aldosterone system → hyperreninemic hyperaldosteronism → increased sodium retention and peripheral vascular resistance → renovascular hypertension (secondary hypertension) Prolonged renal hypoperfusion → chronic stimulation of the juxtaglomerular apparatus to secrete renin → hyperplasia of the juxtaglomerular apparatus No improvement in renal blood flow → ischemic renal injury → renal insufficiency and progressive renal atrophy Clinical features Abdominal bruits heard over the flank or epigastrium; present during both systole and diastole Hypertension that is often resistant to therapy Features of renal insufficiency (e.g., nausea, edema) Diagnostics Laboratory findings Decreased kidney function (see " Diagnostics" in acute kidney injury) ↑ Serum creatinine > 30% after antihypertensive treatment with ACE inhibitors or angiotensin-receptor blockers is a strong indication of renal artery stenosis. Hypokalemia Imaging (confirmatory test) Indications [12][13]Onset of hypertension before the age of 30 years or after 55 yearsNew onset renal dysfunction or worsening of renal function with ACEi or ARBsUnexplained renal atrophy or asymmetry of > 1.5 cm between kidneysHypertension that is resistant to a 3-drug antihypertensive regimen Imaging modality [12][14][13]First-line: non-invasive imaging Duplex ultrasonographyORCT or MR angiographySecond-line: invasive catheter angiography FindingsTubular stenosis of the proximal renal artery segment → typically atherosclerotic diseaseStenosis of the distal renal artery segment with a "string-of-beads" appearance → typically fibromuscular dysplasia [4][5]Significant renal artery stenosis: > 60% reduction in the diameter of the renal arteryIncreased systolic flow velocity in the renal artery (Duplex) Decrease in kidney size Treatment Patients with atherosclerosis: reduce risk factors by statin therapy and lifestyle modification Antihypertensive therapy: ACE inhibitors, angiotensin receptor blockers, calcium channel blocker, beta blockers [12] Closely monitor serum creatinine especially in patients with bilateral renal artery stenosis. ACE inhibitor or ARBtreatment should be terminated if rapid and/or severe worsening of kidney function occurs. Revascularization procedures [12][16]Indications> 60% unilateral stenosis with any of the following: Patients with heart failure who have recurrent acute decompensationsUnexplained acute pulmonary edemaUnstable anginaFailure of, or intolerance to antihypertensive treatmentAccelerated hypertensionSingle functioning kidney> 60% bilateral stenosisProgressive renal insufficiencyProceduresFirst-line: percutaneous transluminal renal angioplastyAtherosclerotic disease: with stentingFibromuscular dysplasia: typically without stentingSecond-line: aortorenal bypass surgery

Pulmonary embolism Pulmonary embolism (PE) is the obstruction of one or more pulmonary arteries by solid, liquid, or gaseous masses. In most cases, the embolism is caused by blood thrombi, which arise from the deep vein system in the legs or pelvis (deep vein thrombosis) and embolize to the lungs via the inferior vena cava. Risk factors include immobility, inherited hypercoagulability disorders, pregnancy, and recent surgery. The clinical presentation is variable and, depending on the extent of vessel obstruction, can range from asymptomatic to cardiogenic shock. Symptoms are often nonspecific, including chest pain, coughing, dyspnea, and tachycardia. The diagnosis of PE is based primarily on the clinical findings and is confirmed by detection of an embolism in contrast CT pulmonary angiography (CTA). Arterial blood gas analysis typically shows evidence of respiratory alkalosis with low partial oxygen pressure, low partial carbon dioxide pressure, and elevated pH. Another commonly performed test is the measurement of D-dimer levels, which can rule out PE if negative. Empiric anticoagulation with heparin is initiated to prevent further thromboembolisms as well as to promote the gradual dissolution of the embolism and the underlying thrombosis. Blood-thinning therapy must be continued for at least three months with oral anticoagulants such as warfarin. In fulminant PE with shock, resolution of the thrombus with thrombolytic agents or removal in an emergency surgery is attempted.

Epidemiology Accounts for ∼ 100,000 deaths in the US per year. Incidence rises with age. Sex: ♂ > ♀ Etiology Deep vein thrombosis (most common cause)Risk factors: obesity, hypomobility or immobility, malignancy, pregnancy, dehydration , hypercoagulability, use of contraceptives, previous DVT (see risk factors for deep vein thrombosis) Fat embolism during major surgical interventions (e.g., endoprosthesis replacement, osteosynthesis) Others: air embolism, amniotic fluid embolism, tissue embolism, cement embolism, bacterial embolism, tumor embolism Pathophysiology Mechanism: thrombus formation (see Virchow's triad) → deep vein thrombosis in the legs or pelvis (most commonly iliac vein) → embolization to pulmonary arteries via inferior vena cava → partial or complete obstruction of pulmonary arteries Pathophysiologic response of the lung to arterial obstructionInfarction and inflammation of the lungs and pleuraCauses pleuritic chest pain and hemoptysisLeads to surfactant dysfunction → atelectasis → ↓ PaO2Triggers respiratory drive → hyperventilation and tachypnea → respiratory alkalosis with hypocapnia(↓ PaCO2)Impaired gas exchangeMechanical vessel obstruction → ventilation-perfusion mismatch → arterial hypoxemia (↓ PaO2) and elevated A-a gradient (see "Diagnostics" below)Cardiac compromiseElevated pulmonary artery pressure (PAP) due to blockage → right ventricular pressure overload→ forward failure with decreased cardiac output → hypotension and tachycardia Clinical features Acute onset of symptoms, often triggered by a specific event (e.g., on rising in the morning, sudden physical strain/exercise) Dyspnea and tachypnea (> 50% of cases) Sudden chest pain (∼ 50% of cases), worse with inspiration Cough and hemoptysis Possibly decreased breath sounds, dullness on percussion, split-second heart sound audible in some cases Tachycardia (∼ 25% of cases), hypotension Jugular venous distension Low-grade fever Syncope and shock with circulatory collapse in massive PE (e.g., due to a saddle thrombus) Symptoms of DVT: unilaterally painful leg swelling Diagnostics Initial management according to modified Wells criteria Hemodynamically stable patients (systolic BP > 90 mmHg) with high probability of PE (Wells score > 4) → CTA for definitive diagnosisUnless strongly contraindicated (e.g., high risk of bleeding, recent surgery), start empiric anticoagulationbefore conducting a CTA If too unstable for CTA → perform bedside echocardiography obtain a presumptive diagnosis of PE (right ventricle enlargement/hypokinesis or visualization of clot) prior to empiric thrombolysis. In patients with a low or medium probability of PE (Wells score ≤ 4) → measure D-dimer levels (+ ABGevaluation + CXR)If positive (D-dimers ≥ 500 ng/mL) → CTA → evidence/exclusion of PEIf negative → PE unlikely → consider other causes of symptoms (see "Differential diagnosis" below) Wells criteria for pulmonary embolism Wells scorePointsClinical symptoms of DVT 3PE more likely than other diagnoses3Previous PE/DVT1.5Tachycardia (heart rate > 100/min)1.5Surgery or immobilization in the past four weeks1.5Hemoptysis1Malignancy (being treated, in palliative care or diagnosis less than 6 months ago) Modified/simplified Wells criteria (clinical probability) Total score of > 4: PE likely Total score of ≤ 4: PE unlikely Blood analysis Initial test: measure D-dimer levels (if suspicion for PE low) D-dimers: fibrin degradation products detected in the blood after thrombus resolution via fibrinolysis; normal levels < 500 ng/mLIf elevated in patients with low clinical probability of PE → further testing (see below)High sensitivity and negative predictive value: a negative D-dimer test most likely rules out PE Low specificity: positive results in all forms of fibrinolysis ↑ troponin T and B-type natriuretic peptide (BNP): possible elevation from right ventricular pressure overload → poor prognosis Arterial blood gas (ABG) testRespiratory alkalosis : ↓ paO2 < 80 mmHg, ↓ paCO2, ↑ pH↑ Alveolar-arterial (A-a) gradient (5-15) : compares the oxygenation status of alveoli to arterial blood ↓ O2 saturation Imaging Helical spiral CT/CT pulmonary angiography (CTPA): best definitive diagnostic test Contrast-enhanced imaging of the pulmonary arteriesHigh sensitivity, specificity and immediate evidence of pulmonary arterial obstructionVisible intraluminal filling defects of pulmonary arteriesWedge-shaped infarction with pleural effusion is almost pathognomonic for PE Chest radiograph Initially often performed to rule out other causes (e.g., pneumonia, pneumothorax, pericarditis, aortic dissection)Findings that may indicate PE Atelectasis (visible collapse or incomplete expansion of the lung)Pleural effusions Signs of pulmonary embolus (rare) Hampton's hump: wedge-shaped opacity in the peripheral lung with its base at the thoracic wall; caused by pulmonary infarction and not specific for PE Westermark sign: embolus leads to diminished perfusion of downstream lung tissue, which appears hyperlucent on radiograph.Fleischner sign: prominent pulmonary artery caused by vessel distension due to a large pulmonary embolus (common in massive PE)Cardiomegaly Echocardiography: to detect right atrium pressure (RAP) signs Venous reflux with dilation of inferior vena cava (also liver congestion in ultrasound of the abdomen)Tricuspid regurgitation (tricuspid valve insufficiency) ↑ Pulmonary artery systolic pressure Dilatation and hypokinesis of the right ventricle Ventilation/perfusion scintigraphy Indication: alternative to CT angiography in patients with severe renal insufficiency or contrast allergyMethod: detects areas of ventilation/perfusion (V/Q) mismatch via perfusion and ventilation scintigraphyAssessment Perfusion failure in normally ventilated affected pulmonary area (mismatch) suggests PEEvidence of normal lung perfusion rules out PE → ventilation scintigraphy superfluous Pulmonary angiography Indications: only conducted if CT angiography unavailable Procedure: right heart catheterization → insertion of a catheter into a pulmonary artery → radiographafter administration of contrast agent Other diagnostic measures Electrocardiography (ECG)Sinus tachycardia most commonly seenSigns of right ventricular pressure overload SIQIIITIII -pattern New right bundle branch blockBradycardia < 50 or tachycardia > 100 bpmRight or extreme right axis deviation (30% of cases)T negativity in leads V2and V3 (∼ 30%) Compression Doppler ultrasound: diagnosis of potential underlying deep vein thrombosis Diagnostics for underlying causeThrombophilia workupMalignancies Treatment Acute management General measures 45° reclining sitting posture Oxygen supplementation and intubation if respiratory failure IV fluids and/or vasopressors in patients with hypotension Analgesics and sedatives Specific measures Non-life-threatening pulmonary embolism: therapeutic anticoagulation Empiric anticoagulation in patients with no absolute contraindication until definitive diagnosis has been made An absolute contraindication for empiric anticoagulation is a high risk of bleeding (e.g., recent surgery, hemorrhagic stroke, active bleeding)! Initial anticoagulation (0-10 days) Low molecular weight heparin (LMWH) or fondaparinux in stable patients without renal insufficiency, especially in cancer patients Unfractionated heparin (UFH) in patients with renal failure and those who may still require thrombolysis Long-term anticoagulation and prophylaxis (3-6 months) Anticoagulation treatment is indicated for a minimum of three months after PE (see "Therapy" in deep vein thrombosis). The following agents may be used: Warfarin (target INR 2-3)LMWHDirect oral anticoagulants (rivaroxaban, apixaban, edoxaban, dabigatran) Patients with a hypercoagulable state with DVT or PE: heparin followed by 3-6 months of warfarin for the first event, 6-12 months for the second, and lifelong anticoagulation for further events Massive, life-threatening pulmonary embolism: recanalization Thrombolytic therapyIndicationsIn cases of massive PE causing right heart failureIn hemodynamically unstable patients requiring resuscitationAlternative to PTCA for patients with STEMI if PTCA cannot be performed within 90-120 minutes(see "Treatment algorithm based on ECG findings" in the acute coronary syndrome learning card)Procedure: fibrinolysis, preferably with recombinant tissue-type plasminogen activator (tPA), e.g.,alteplaseMost commonly systemic infusion via IV catheterAlternatively, direct infusion of tPA into pulmonary artery via pulmonary arterial catheter Administration of anticoagulants discontinued during thrombolysisComplicationsRisk of hemorrhage during thrombolytic treatment Observe contraindications for thrombolytic therapy EmbolectomyTreatment of last resort when thrombolysis is contraindicated or unsuccessfulSurgical or catheter-based thrombus removal There is no contraindication for systemic thrombolysis if the patient requires resuscitation! Further measures Inferior vena cava filter Indications In recurrent DVTs despite anticoagulationIf anticoagulation is contraindicated (e.g., high-risk of bleeding) in patients with a documented lower leg DVT DVT prophylaxis: (subcutaneous heparin or LMWH for all immobile patients, early ambulation, and compression stockings) Complications High risk of recurrence: without anticoagulant treatment ∼ 10% in the first year, ∼ 5% per year after Right ventricular failure Sudden cardiac death due to pulseless electrical activity Atelectasis (∼ 20% of cases) Pulmonary effusion Pulmonary infarction (∼ 10% of cases) Embolisms of smaller segmental arteries can lead to wedge-shaped hemorrhagic pulmonary infarctions Right ventricular failure, increased bronchial venous pressure, and preexisting pulmonary diseases increase the risk. Pneumonia from pulmonary infarction: peripheral infiltration on chest X-ray (typically wedge-shaped= Hampton's hump) Differential diagnoses See differential diagnosis of acute chest pain and differential diagnosis of acute dyspnea Post-surgery atelectasis Anxiety disorders

Valvular heart diseases Valvular heart diseases can take the form of stenosis, insufficiency (regurgitation), or a combination of the two. These defects are typically acquired as the result of infections, underlying heart disease, or degenerative processes. However, certain congenital conditions can also cause valvular heart diseases. Acquired defects are found primarily in the left heartas a result of higher pressure and mechanical strain on the left ventricle. The type of valvular disease determines the type of cardiac stress and subsequent symptoms. Valvular stenosis leads to a greater pressure load and concentric hypertrophy, while insufficiencies are characterized by volume overload and an eccentric hypertrophy of the preceding heart cavities. Diagnostic procedures typically include ECGs, chest x-ray, and echocardiograms. Management consists of interventional or surgical procedures to reconstruct or replace valves, as well as medical treatment of possible heart failure.

Epidemiology Aortic stenosisMost common valve defect in industrialized countriesMostly degenerative Aortic regurgitationOnset at 40-60 yearsSeverity increases with age Mitral stenosis: symptom onset at 20-30 years Mitral regurgitationOverall prevalence of 0.6 to 2.4 %Second most common valve defect More common in women Tricuspid valve defects occur in < 1% of the population Pulmonary valve defects rare outside of congenital conditions Valve stenosisValve regurgitationLeft heartMitral valveRheumatic fever Rheumatic diseases (e.g., SLE, RA)Mitral valve prolapseDilated cardiomyopathyIschemic heart disease (e.g., following myocardial infarction)Degenerative calcificationAortic valveDegenerative calcification (most common)Rheumatic endocarditisCongenital (e.g., unicuspid, bicuspid, or hypoplastic valve)Acute: infective endocarditis, aortic dissection type A, chest traumaChronic Bicuspid aortic valveConnective tissue diseases (e.g., Marfan syndrome, Ehlers-Danlossyndrome)Rheumatic feverRheumatic diseases (e.g., Behcet's disease, RA, SLE)Right heartTricuspid valveRheumatic feverInfective endocarditis (mostly IV drug abuse)Right ventricular dilation (e.g., in right-sided heart failure)Infective endocarditis (IV drug use)Rheumatic feverConnective tissue diseases (e.g., Marfan syndrome)Pulmonary valveCongenitalPulmonary hypertension (e.g., tetralogy of Fallot, ventricular septal defects)Dilated cardiomyopathy Clinical features All valvular defects can eventually lead to symptoms of heart failure as a result of excessive strain on the ventricles. Aortic stenosis Aortic regurgitation Mitral stenosis Mitral regurgitation Aortic stenosisAortic valve (parasternal 2nd right intercostal space)Erb's pointHarsh crescendo-decrescendosystolic ejection murmur Radiation into the carotidsPossibly ejection click Aortic regurgitationAortic valve (parasternal 2nd right ICS)Erb's pointDiastolic murmur with a decrescendo Possible additional quiet systolicmurmurImmediately following the 2nd heart sound ("immediate diastolic murmur")Austin Flint Murmur Low-pitched diastolic rumble due to anterograde flow from the left atrium and retrograde flow from the aorta. Mitral stenosisHeart apex (midclavicular 5th left ICS)Delayed diastolic murmur with a decrescendo "Tympanic" 1st heart soundMitral opening murmur/opening snap (OS) Mitral valve prolapseHeart apex (midclavicular 5th left ICS)Late-systolic crescendo Mid-systolic high-frequency click Mitral regurgitationHeart apex (midclavicular 5th left ICS)Left axilla Holosystolic murmur 3rd heart sound audibleQuiet 1st heart soundBlowingRadiation into the axilla Pulmonary stenosis Pulmonary valve (parasternal 2nd left ICS) Crescendo-decrescendo ejection systolic murmur Possible radiation into the back Possible early systolic pulmonary ejection clickand/or widely split 2nd heart sound Pulmonary regurgitationPulmonary valve (parasternal 2nd left ICS)Diastolic murmur with a decrescendo Graham Steel murmur: high-frequencydecrescendo diastolic murmur Tricuspid stenosis(extremely rare)Tricuspid valve (parasternal 4th left ICS) Delayed diastolic murmur with a decrescendo Possible pre-systolic crescendo Tricuspid regurgitation(extremely rare)Tricuspid valve (parasternal 4th left ICS)Holosystolic murmur Augmentation of the murmur's intensity with inspiration (Carvallo's sign) Treatment Symptomatic Treatment of heart failure Endocarditis prophylaxis Prevention of thromboembolism (if necessary) Causal Surgery: The choice of procedure is based on the patient's individual risk profile and an evaluation of benefits. Valve reconstruction (annuloplasty)Procedure: ring-shaped device attached to the outside of the valve opening to re-establish shape and function of valveReduced thromboembolic risk compared to mechanical prosthetic valve; but high risk of recurring stenosisLower mortality rate than valve replacements, though replacements are more durableProsthetic valve replacementImmunosuppression not necessary Mechanical prosthetic valve ProsValve has a long lifespan ConsLife-long anticoagulation necessary (warfarin, aspirin) IndicationsYounger patients Previously anticoagulated patients (e.g., with pre-existing atrial fibrillation) Biological prosthetic valve Anticoagulation only necessary for 3 months post operation Short lifespan due to sclerotic degenerationMay need to be replaced every ten years Older patients Patients with a high risk of bleeding Women with a desire to have children Interventional valve replacement via catheter Transcatheter aortic valve replacement (TAVR)Transcatheter mitral valve replacement (TMVR) Percutaneous balloon valvuloplasty for stenoses

Aortic dissection An aortic dissection is a tear in the inner layer of the aorta which leads to a progressively growing hematomabetween in the intima-media space. Hypertensive males between the 4th and 6th decade have the highest incidence of aortic dissection. Patients complain of a sudden onset and severe pain radiating into the thorax, back, or abdomen. Initial chest x-ray shows a widened mediastinum. The diagnosis is confirmed with a contrast-enhanced CT in stable patients and transesophageal echocardiography in unstable patients. Treatment options range from conservative measures (e.g., blood pressure optimization) to surgery (aortic prosthesis), depending on the localization and severity of the dissection. Complete occlusion of branching vessels and aortic rupture are common complications. Even with treatment, mortality rates associated with aortic dissection are high.

Epidemiology Incidence: 40-80 years (Peak incidence: 60-80 years; in Marfan syndrome at the age of 30-50) Sex: ♂ > ♀ (3:1) LocalizationAscending aorta: ∼ 65% of casesDescending aorta, distal to the left subclavian artery: 20% of casesAortic arch: 10% of casesAbdominal aorta: 5% of cases Etiology AcquiredHypertension (most common)Approx. 70% of patients with aortic dissection have elevated blood pressure. This elevated pressure leads to propagation of the dissection and increases the risk of rupture.Exception: in patients < 40 years, less than 40% due to hypertensionTrauma (e.g., deceleration injury in a motor vehicle accident, iatrogenic injury and during valve replacements or graft surgery)Vasculitis with aortic involvement (e.g., syphilis)Use of amphetamines and cocaineThird-trimester pregnancy (or early postpartum period)Atherosclerosis CongenitalConnective tissue disease (Marfan syndrome, Ehlers-Danlos syndrome)Bicuspid aortic valveCoarctation of the aorta Classification Stanford classification Type A (proximal): ascending aorta dissection, including retrograde extension from the descending aorta(independent of the site of origin and propagation) Type B (distal): descending aorta dissection, originating distal to the left subclavian artery Stanford A = Affects ascending aorta; Stanford B = Begins beyond brachiocephalic vessels. Pathophysiology Anatomic site of origin Above (2.2 cm) the aortic root Aortic archDistal to left subclavian artery Transverse tear in the aortic intima ("entry") → blood enters the media of the aorta and forms a false lumenin the intima-media space → hematoma forms and propagates longitudinally downwards→ Rising pressure within the aortic wall → rupture→ Occlusion of every single branching vessel (e.g., coronary arteries, arteries supplying the brain, renal arteries, arteries supplying the lower limbs) → ischemia in the affected areas (see "Complications" below)→ A second intimal tear may result in a "reentry" into the primary aortic lumen. Clinical features Sudden and severe tearing/ripping painLocation Anterior chest (ascending) or back (descending) Interscapular or retrosternal pain Neck and jaw Abdomen or periumbilical, colicky pain Character: migrates as the dissected wall propagates caudally ↑ BP (if the patient is hypotensive, consider shock from blood loss or a cardiac tamponade) Asymmetrical blood pressure and pulse readings between limbs Syncope, diaphoresis, confusion or agitation A heart murmur (an aortic regurgitation in a proximal dissection) Diagnostics Initial imaging: Chest x-ray (AP view) showing a widened mediastinum (> 8 cm) Definitive diagnostic tests (determine the type of lumen, location, and extent of the dissecting membrane) In stable patients → Contrast-enhanced CT angiography (gold standard) High sensitivity and specificity. In unstable patients, renal insufficiency, contrast allergy → Transesophageal echocardiography (TEE) If contrast-enhanced CT is contraindicated in stable patients → Magnetic resonance angiography (MRA) ECG: in all patients, although normal or signs of left ventricular hypertrophy Treatment Stanford A dissections (involvement of the ascending aorta) require immediate surgery, while Stanford Bdissections are generally treated conservatively unless complications (e.g., rupture or occlusion) occur. Conservative treatment Sedation and analgesia (e.g., morphine) Adequate resuscitation Control hypertensionTarget value of the systolic blood pressure is ∼ 90-120 mm HgIV labetalol, esmolol, or propanolol (best initial )Followed by IV sodium nitroprusside (vasodilator) Surgery Open surgery with a polyester graft implantation Possibly, endovascular treatment: aortic stent implantation (only in type B dissections and if the operative risk is too high) Avoid thrombolytic therapy in patients with suspected aortic dissection! Ascending aortic dissection is a surgical emergency! Descending aortic dissection can often be managed medically. Complications Aortic rupture and acute blood loss: acute back and flank pain (tearing pain), symptoms of shock → indication for emergency surgery Complications of Stanford type A dissectionsMyocardial infarction (coronary artery occlusion)Aortic regurgitation (extension of the dissection into the aortic valve): new diastolic heart murmur and (exertional) dyspneaCardiac tamponade combined with cardiogenic shockPericarditis (slow extension of the dissection into the pericardium) Stroke (extension of the dissection into the carotids) Complications of both Stanford type A and B dissections Bleeding into the thorax, mediastinum, and abdomenArterial occlusion followed by ischemia of the: Coeliac trunk, superior/inferior mesenteric artery → acute abdomen, ischemic colitisRenal arteries → acute renal failure (oliguria, anuria)Spinal arteries → weakness of lower extremities or acute paraplegiaComplete occlusion of the distal aorta → Leriche syndrome (aortoiliac occlusive disease) Prognosis In-hospital mortality due to aortic dissection ranges from 9 to 39%, depending on the type of dissection and treatment modality. Prevention Blood pressure control Smoking cessation Screening and repair of rapidly expanding aneurysms (also see "Therapy" and "Prevention" sections in aortic aneurysms)

Coronary artery disease Coronary heart disease (CHD) refers to a mismatch between myocardial oxygen supply and demand. Atherosclerosis is the most important cause. Atherosclerotic changes in coronary vessel walls lead to a narrowing of the lumen and prevent vessels from dilating. As a result, an increase in oxygen demand (e.g., during physical activity) can no longer be satisfied and/or myocardial perfusion at rest is insufficient. Acute retrosternal chest pain (angina) is the cardinal symptom of CHD. Other symptoms include dyspnea, dizziness, anxiety and nausea. If ischemia is severe, myocardial infarction can occur. Coronary heart disease is diagnosed via a cardiac stress test (possibly provoking symptoms and instrumental findings) and/or coronary catheterization (e.g., measurement of coronary blood flow). Management of CHD involves primary and secondary prevention of atherosclerosis (e.g., weight reduction), antianginal treatment (e.g., beta blockers) and, in some cases, revascularization (e.g., PCTA).

Epidemiology Lifetime risk of coronary heart disease Age 40: 49% in men and 32% in women Age 75: 35% in men and 24% in women Cardiovascular disease is the leading cause of death in the US and the world. Etiology Risk factors for atherosclerosis Pathophysiology Plaque formation and coronary artery stenosis For plaque formation, see pathogenesis of atherosclerosis. Stable atherosclerotic plaque → vascular stenosis → increased resistance to blood flow in the coronary arteries →decreased myocardial blood flow → oxygen supply-demand mismatch → myocardial ischemia The extent of coronary stenosis determines the severity of the oxygen supply-demand mismatch and, thus, the severity of myocardial ischemia. Severe ischemia results in myocardial infarction (see acute coronary syndrome for details). Coronary flow reserve (CFR): the difference between maximum coronary blood flow and coronary flow at rest; a measure of the ability of the coronary capillaries to dilate and increase blood flow to the myocardium.In healthy individuals, the CFR can be up to 4 times higher on exertion than at rest.CFR is reduced in individuals with CAD due to vascular stenosis and reduced vascular compliance. Myocardial oxygen supply-demand mismatch Definition: mismatch between the amount of oxygen the myocardium receives and the amount it requires Factors reducing oxygen supplyCoronary atherosclerosis and sequelae, including: Rupture of an unstable atherosclerotic plaque (most common cause)ThrombosisStenosisVasospasms↑ Heart rate Anemia Factors increasing oxygen demand ↑ Heart rate↑ AfterloadAnemia An increased heart rate reduces oxygen supply and increases oxygen demand! Effect of vascular stenosis on resistance to blood flow The resistance to blood flow within the coronary arteries is calculated using the Poiseuille equation: R = 8Lη/(πr4), where R = resistance to flow, L = length of the vessel, η = viscosity of blood, and r = radius of the vessel. Provided the length of the vessel and viscosity of blood remain constant, the degree of resistance can be calculated using the simplified formula: R ≈ 1/r4 Vascular stenosis increases vascular resistance significantly! For example, a 50% reduction in radius results in a 16-fold increasein resistance: R ≈ 1/(0.5 x r)4 = [1/(0.5 x r)]4 = (2/r)4 = 16/r4 Myocardial ischemia Reversible ischemia: Tissue is ischemic but not irreversibly dead and, therefore, still potentially salvageable. Myocardial stunning: acutely ischemic myocardial segments with transiently impaired but completely reversible contractilityHibernating myocardium: a state in which myocardial tissue has persistently impaired contractility due to repetitive or persistent ischemiaPartially or completely reversible when adequate oxygen supply is restored (e.g., after angioplasty or coronary artery bypass grafting)Seen in angina pectoris, left ventricular dysfunction, and/or heart failure Irreversible ischemia: tissue necrosis (myocardial scars) Coronary steal syndrome Definition: a phenomenon of vasodilator-induced alteration of coronary blood flow in patients with coronary atherosclerosis resulting in myocardial ischemia and symptoms of angina BackgroundLong-standing CAD requires maximal coronary arterial dilation distal to the stenosis to maintain normal myocardialfunction.In CAD, the affected coronary artery is maximally dilated distal to the stenosis to compensate for the reduced blood flow If a vasodilator (e.g., dipyridamole) is administered, the subsequent vasodilation of healthy vessels causes these to "steal blood from the stenotic blood vessels, resulting in poststenotic myocardial ischemia Clinical relevance: coronary steal is the underlying mechanism of pharmacological stress testingAdministration of vasodilators (e.g., dipyridamole) → coronary vasodilation → decreased hydrostatic pressure in the normal coronary arteries → blood shunting back to well-perfused myocardium → decreased flow to the ischemic myocardium → myocardial ischemia downstream to the pathologically dilated vessels → angina pectorisand/or ECG changes Chronic ischemic heart disease Progressive heart failure that occurs after many years of chronic ischemic damage to the myocardium. Clinical features Angina Typically retrosternal chest pain or pressurePain can also radiate to left arm, neck, jaw, epigastric region, or back.Pain does not depend on body position or respirationNo chest wall tendernessAngina may be absent, particularly in younger patientsOften gradual progressionCan also present as gastrointestinal discomfort Dyspnea Dizziness, palpitations Restlessness, anxiety Autonomic symptoms (e.g., diaphoresis, nausea, vomiting, syncope) Stable angina Symptoms are reproducible/predictable Complaints often subside within minutes , with rest or after administration of nitroglycerin Common triggersMental or physical stressExposure to cold Unstable angina Symptoms are not reproducible/predictable Usually occurs at rest or with minimal exertion and is usually not relieved by rest or nitroglycerin Every new-onset angina Severe, persistent, and/or worsening angina (crescendo angina) Increasing intensity, frequency, or duration in a patient with a known stable angina Unstable angina is a form of acute coronary syndrome and may progress to myocardial infarction. Most patients with CHD first become symptomatic with acute myocardial infarction or sudden cardiac death! Subtypes and variants Vasospastic angina Description: Angina caused by transient coronary spasms (usually occurring close to areas of coronary stenosis)Unrelated to exertion and may even occur at rest (classically at night) Etiology: e.g., cigarette smoking, use of stimulants (e.g., cocaine, amphetamines) or sumatriptan, alcohol, stress,hyperventilation, exposure to coldThere is an association with other disorders involving vasospasms (e.g., Raynaud phenomenon, migraine headaches) Epidemiology: average onset around 50 years Diagnostics Reversible ST elevation on ECGNo troponin I or T level elevations on serial measurementsCoronary spasms on angiography confirm the diagnosis Treatment Risk factor modificationCalcium channel blockers and nitrates: first-line agent for acute attacks and prophylaxis Avoid beta-blockers! Prognosis: The five-year survival rate is > 90% (with treatment). Persistence of symptoms is common. Diagnostics Patient history and physical exam History of recurrent angina episodes Signs of atherosclerotic vessel disease (e.g., absent foot pulses, carotid bruit) → see also physical exam in cardiology Resting ECG Best initial test for both types of angina (and other types of chest pain) Usually normal in stable angina Treat as unstable angina if abnormalities (of the ST segment or the T wave) occur during an episode of chest pain Cardiac stress test Cardiac stress tests are generally most useful in patients with an intermediate pretest probability of coronary arterydisease. Choosing the most appropriate provocation and detection methods ProvocationAble to exercise (and no contraindications for exercise testing): exercise stress test Unable to exercise (and no contraindications to pharmacologic testing): pharmacologic stress test Detection Resting ECG can be interpreted: ECGResting ECG cannot be interpreted: imaging Example: In a 75-year-old patient with acute aortic dissection, exercise testing would be contraindicated. If he also has atrial fibrillation, imaging would be indicated to monitor the test. Therefore, a pharmacologic stress test with either echocardiography or scintigraphy would be indicated. Provocation methods Both types of stress test can be used with ECG, echocardiography, and/or myocardial perfusion imaging. Clinical features, blood pressure, and heart rate are evaluated/recorded simultaneously. Cardiac exercise stress testThe patient exercises until the target heart rate is achieved (e.g., on a treadmill). Maximum heart rate = 220 - age (in years)Target heart rate = 85% of the maximum heart rateContraindications Acute myocardial infarction with elevated troponin levels and/or ST elevations (in the past 2 days)Unstable angina pectoris or ST depressions at restDecompensated heart failure or severe symptomatic stenosis of one or more heart valvesAcute endocarditis, myocarditis, or pericarditisHemodynamically significant arrhythmiasAcute thromboembolic diseaseAcute aortic dissectionMental or physical impairment to exercise Cardiac pharmacological stress testIV administration of positive inotropic/chronotropic substances (e.g., dobutamine) or vasodilators (e.g., dipyridamole or adenosine) to simulate the effect of exercise on the myocardiumContraindications Adenosine, dipyridamole:Active bronchospasm or reactive airway diseaseFirst-degree heart blockLow systolic blood pressure (< 90 mm Hg)MethylxanthinesDobutamineMyocardial infarction within the last weekUnstable anginaObstructive cardiomyopathy, aortic stenosisTachyarrhythmiasLeft bundle branch blockUntreated hypertensionThoracic aortic aneurysm Preparation If cardiac stress test is done for primary diagnosis, withhold the following:Beta blockers, calcium channel blockers, nitrates (48 hours)Methylxanthines (especially if a pharmacological cardiac stress test is considered): caffeine (12 hours), aminophylline (24 hours), dipyridamole (48 hours) If cardiac stress test is done for treatment evaluation, medication can be continued. Findings in stress-induced ischemia Clinical findings: If one of the following symptoms occurs, the exercise stress should be stopped. New onset/intensification of chest painSevere dyspnea, cyanosis, pallor, ataxia, or altered mental status Decrease in systolic BP below the resting BPSystolic BP > 250 mm Hg or diastolic BP > 120 mm Hg ECGDownsloping or horizontal ST depressions of ≥ 0.1 mV in the limb leads and ≥ 0.2 mV in the precordial leads ST elevations ≥ 0.1 mV (requires immediate test termination!)Excessive or delayed increase in heart rate New onset ventricular arrhythmia ImagingThe goal is to distinguish between: Irreversible ischemia: necrosis (myocardial scars)Reversible ischemia: tissue that is ischemic (but not yet irreversibly dead) and therefore still potentially salvageable Myocardial stunning: acutely ischemic myocardial segments that demonstrate transiently impaired contractility that is completely reversibleHibernating myocardium: persistently impaired myocardial contractility that is partially or completely reversible when adequate oxygen supply is restored (e.g., after angioplasty or CABG)Caused by chronically reduced coronary blood flowSeen in angina pectoris, left ventricular dysfunction, and/or heart failureEchocardiographyRadionuclide myocardial perfusion imaging Patients with new-onset chest pain, ST segment depression, hypotension or arrhythmias should undergo cardiac catheterization! Cardiac catheterization Indications Persistent symptoms of angina despite appropriate therapy orPathological result of the non-invasive examination orNoninvasive procedure with ambiguous results and high clinical suspicion of CHD Gold standard of CHD diagnosis Information on several qualities (e.g., coronary blood flow, pressure within heart chambers, cardiac output, oxygen saturation)Direct visualization of coronary arteries (coronary angiography)Opportunity for direct therapeutic intervention using percutaneous coronary intervention (see "Treatment" below) Additional tests Holter monitoring: can detect silent ischemia and arrhythmias and be used to evaluate heart rate variability and pacemaker/ICD function Coronary magnetic resonance imaging (CMRI) or coronary computed tomography angiography (CCTA) Treatment Approach All patients: risk factor reduction and antiplatelet drugs; see "Prevention" below Mild CHD: pharmacologic therapy Moderate CHD: consider coronary angiography and percutaneous transluminal coronary angioplasty(PTCA)/percutaneous coronary intervention (PCI) Severe CHD: coronary angiography and revascularization or coronary artery bypass grafting Antianginal treatment First-lineBeta-blockers (except in vasospastic angina): can reduce the frequency of coronary events NitratesCan prevent exertional anginaSuitable for relief of acute angina or for long-term treatment Second-lineCalcium channel blockers (CCBs): indicated if there are contraindications to beta-blockers or in addition to beta-blockers (if angina or hypertension persist)Ranolazine: indicated in stable angina that is refractory to first-line treatment Two mechanisms of action to reduce myocardial oxygen demand: 1) inhibit late phase sodium influx into cardiac myocytes → reduced calcium flux (via sodium-calcium channel pump) → reduced wall stress and oxygen demand; and 2) decreased rate of fatty acid beta oxidation (aerobic process) with simultaneous increase in glycolysis (anaerobic process). Combination therapy: indicated if angina persists with monotherapy Beta-blocker + nitratesCalcium channel blocker (nondihydropyridines) + nitratesBeta-blocker + calcium channel blockers (long-acting dihydropyridines, such as nitrendipine) Revascularization Indications In stable angina: activity-limiting symptoms despite optimal medical treatment, contraindications to medical therapy, stenosis of critical (e.g., LCA) or multiple coronary arteriesAcute coronary syndrome Techniques Percutaneous coronary interventionCoronary artery bypass grafting Prognosis Prognostic factors Left ventricular function: increased mortality if EF < 50%Involvement of left main coronary artery or involvement of more than one vessel is associated with a worse prognosis. Stable anginaAnnual mortality rate: ∼ 5%25% of patients will suffer an acute MI within the first 5 years.High-grade stenosis is associated with an unfavorable prognosis Prevention Prevention of atherosclerosis Primary and secondary prevention of atherosclerosis Special considerations in coronary heart disease Antiplatelet drugs indicated in all patients: aspirin or clopidogrel (if aspirin/ASA is contraindicated) → ↓ risk of infarction, ↓ morbidity Treating arterial hypertensionReduce blood pressure to < 140/90 mm Hg in cases of low/moderate risk and to < 130/80 mm Hg in high-riskpatientsBeta-blockers are the first-line therapy for CHD combined with arterial hypertension. ACE-inhibitors patients post-MI, especially those with left ventricular systolic dysfunction. Calcium channel blockers (for indications, see "Antianginal therapy" above) HbA1c of 6.5-7% Risk-adjusted LDL values: see Guidelines for lipid-lowering therapy (ATP III guidelines) for details

Cardiac myxoma Cardiac myxomas are the most common type of primary tumor of the heart. They are usually benign and arise from primary connective tissue. Most cardiac myxomas arise sporadically; however, 10% are hereditary (following an autosomal dominant pattern). Even though they may develop in any chamber of the heart, most (∼ 75 %) cardiac myxomas arise in the left atrium, usually from the interatrial septum, while the rest occur in the right atrium (ventricular myxomas are rare). Clinical features are primarily caused by obstruction of the blood flow through the heart and include dyspnea on exertion, palpitations, syncope, weight loss, or even sudden death. Rarely, life-threatening conditions (e.g., stroke) may result from an embolization from the myxoma. Typical examination findings include abnormal heart sounds, such as a rumbling diastolic murmur over the apex or a characteristic "tumor plop." The diagnosis is not easily established clinically because of the nonspecific nature of symptoms. Echocardiography is the diagnostic procedure of choice. Surgical resection of the tumor is the curative treatment of choice. The prognosis is usually favorable, but tumors can recur after inadequate resection.

Epidemiology Most common primary cardiac neoplasm (usually benign) Most common location: left atrium (∼ 75% of all cases) Sex: ♀ > ♂ (3:1) Peak incidence: 40-60 years Etiology The exact etiology is unknown. Most cases are sporadic. Familial inheritance: ∼ 10% of all casesAutosomal dominant inheritanceCarney syndrome Clinical features GeneralProduction of IL-6 by tumor causes constitutional symptoms (e.g., weight loss, fever, pallor)Clubbing of the fingers Clinical features caused directly by the tumor Symptoms caused by obstructionDyspnea on exertion, paroxysmal nocturnal dyspnea, and/or orthopneaDizziness or syncopePalpitationsAuscultatory findings Low pitched, mid-diastolic rumbling murmur over apex (similar to mitral stenosis)"Tumor plop": a sound related to movement of the tumorPotentially, an additional heart sound (audible just after S2)These sounds may change when the patient changes position.Valve damage may result in mitral regurgitation.Further symptoms of left heart failure; symptoms of right heart failureSymptoms due to embolizationCNS: transient ischemic attack, stroke, or seizureAbdomen: visceral infarction or hemorrhageLungs: pulmonary embolizationDistant recurrence Diagnostics Because of the nonspecific nature of the cardiac symptoms, the diagnosis is often only established much later in the course of the disease. Echocardiography: diagnostic test of choiceThe tumor is visualized as a pedunculated, heterogenous, mobile mass, usually present in the left atrium.Helps assess tumor location, size, attachment, and mobility. Other tests: CT and MRI scans help better visualize the intracardiac mass. Pathology Microscopic appearance: Scattered mesenchymal cells within mucoid, gelatinous materialSurrounded by glycosaminoglycansProduce VEGF Macroscopic appearance: often pedunculated, gelatinous consistency Differential diagnoses Secondary (metastatic) cardiac tumors: ∼ 20-30 times more common than primary cardiac tumorsMost common primary cancers: melanoma, lung cancer, and breast cancer Lipoma: usually an incidental finding Treatment The only definitive treatment of cardiac myxoma is surgical resection. Medical intervention may be required for the treatment of associated conditions like arrhythmias, heart failure, or embolism. Recurrence may occur in cases of incomplete excision of the tumor, growth from a second focus, or intracardiac implantation from the primary tumor.

Atrial fibrillation Atrial fibrillation (Afib) is a commonly seen type of supraventricular tachyarrhythmia that is characterized by uncoordinated atrial activation resulting in an irregular ventricular response. While the exact mechanisms are still poorly understood, associations with a number of cardiac (e.g., valvular heart disease, coronary artery disease) and noncardiac (e.g., hyperthyroidism, electrolyte imbalances) risk factors have been established. Individuals with Afib are typically asymptomatic. However, when symptoms do occur, these usually include palpitations, lightheadedness, and shortness of breath. Physical examination typically reveals an irregularly irregular pulse. Ineffective atrial emptying as a result of Afib can lead to stagnation of blood and clot formation in the atria, which in turn increases the risk of stroke and other thromboembolic complications. The diagnosis is confirmed by an ECG showing indiscernible P waves and a narrow QRS complex with irregular QRS intervals. Echocardiography is used in patients with Afib to rule out structural heart diseaseand detect the presence of atrial thrombi. Immediate synchronized cardioversion is required in hemodynamically unstable patients. In stable patients, treatment involves the correction of modifiable risk factors, rate or rhythm control strategies, and anticoagulation. Rate control therapy typically involves the use of beta-blockers or nondihydropyridine calcium channel blockers. Rhythm control strategies involve elective synchronized cardioversion and/or the use of antiarrhythmics (e.g., flecainide, propafenone, or amiodarone). The need for anticoagulation therapy is determined based on the CHA2DS2-VASc score. Catheter-directed or surgical ablation of the arrhythmogenic tissue is used in refractory or severe Afib. Atrial flutter is another type of commonly seen supraventricular tachyarrhythmia that is usually caused by a single macroreentrant rhythm within the atria. The risk factors for atrial flutter are similar to those of Afib. In atrial flutter, the atrial rate is slower than in Afib and the ventricular rhythm is usually regular. Treatment is similar to that of Afib, consisting of anticoagulation and strategies to control heart rate and rhythm. Atrial flutter frequently degenerates into atrial fibrillation.

Epidemiology Most common sustained arrhythmia Incidence: increases with age The lifetime risk of Afib among individuals > 40 years is 1 in 4.>95% of individuals with Afib are ≥ 60 years Prevalence: ∼ 1% of US population Risk factors for atrial fibrillationCardiovascular risk factorsAdvanced ageHypertensionDiabetes mellitusSmokingObesitySleep apneaIntrinsic cardiac disordersCoronary artery diseaseValvular heart disease (especially mitral valve disease) Congestive heart failure (CHF)Pre-excitation tachycardia. e.g., Wolff-Parkinson-White (WPW) syndrome Sick sinus syndrome (tachycardia-bradycardia syndrome)CardiomyopathiesPericarditisCongenital channelopathiesNoncardiac disordersPulmonary disease: COPD, pulmonary embolism, pneumoniaHyperthyroidism Catecholamine release and/or increased sympathetic activity Stress: sepsis, hypovolemia, post-surgical state (especially following cardiac surgery), hypothermiaPheochromocytomaCocaine, amphetaminesElectrolyte imbalances (hypomagnesemia, hypokalemia)Drugs: e.g., adenosine, digoxinHoliday heart syndrome: irregular heartbeat classically triggered by excessive alcohol consumption, but also sometimes by moderate alcohol consumption, stress, or lack of sleep Chronic kidney disease Approx. 15% of individuals who develop Afib have none of the above mentioned risk factors (idiopathic/lone Afib). Remember PARASITE to memorize the major risk factors for acute Afib: P - Pulmonary disease; A - Anemia; R - Rheumaticheart disease; A - Atrial myxoma; S - Sepsis; I - Ischemia; T - Thyroid disease; E - Ethanol. Hemodynamic stabilityUnstable AfibAfib presenting with signs of hemodynamic instability (e.g., chest pain, altered mental status, acute pulmonary edema, hypotension, or cardiogenic shock)Stable AfibAfib without signs of hemodynamic instabilityHeart rateAfib with rapid ventricular responseAfib with a ventricular rate > 100 bpm (tachycardic Afib)Slow AfibAfib with a ventricular rate < 60 bpm (bradycardic Afib) Onset and duration of AfibNew-onset AfibAfib less than 48 hours in durationParoxysmal AfibAfib that resolves within 7 days of onset either following treatment or spontaneouslyPersistent AfibContinuous Afib for > 7 daysLong-standing persistent AfibContinuous Afib for > 1 year Permanent AfibLong-standing persistent Afib that is not treated unless the patient and the treating physician agree to do so Mitral valveinvolvementValvular AfibAfib in patients with mitral valve stenosis, artificial heart valves, and/or repaired mitral valves Nonvalvular AfibAfib in patients without mitral valve involvement Pathophysiology Atrial fibrillation is a supraventricular arrhythmia. The exact mechanisms of Afib are not well understood. Suggested mechanisms include: Volume overload, hemodynamic stress → atrial hypertrophy and/or dilatationAtrial ischemiaInflammation of the atrial myocardiumAltered ion conduction by the atrial myocardium The new onset of Afib triggers a vicious circle that can ultimately lead to long-standing Afib with atrial remodeling: Afib is triggered by one or both of the following Bursts of electrical activity from automatic foci near the pulmonary veins or in diseased, fibrotic atrial tissue Pre-excitation of the atria as a result of aberrant pathways (e.g., WPW syndrome)Afib is sustained by re-entry rhythms and/or rapid focal ectopic firing Re-entry rhythms are more likely to occur with enlarged atria, diseased heart tissue, and/or aberrant pathways (e.g., WPW syndrome).Atrial remodelingElectrophysiological changes in the atria occur within a few hours of Afib onset (electrical modeling).If Afib persists, atrial fibrosis and dilatation (structural remodeling) occur within a few months.Electrical and structural remodeling increase susceptibility to Afib, resulting in a vicious circle. Effects of Afib The atria contract rapidly but ineffectively and in an uncoordinated fashion → stasis of blood within the atria →risk of thromboembolism and strokeIrregular activation of the ventricles by conduction through the AV node → tachycardia Clinical features Most affected individuals are asymptomatic. Less commonly, affected individuals develop symptoms of arrhythmias such as palpitations, dizziness, syncope, fatigue, and or dyspnea. Signs of underlying disease (e.g., murmurs of mitral stenosis) Tachycardia with an irregularly irregular pulse Apex-pulse deficit: difference between the rate of apex heart beat and that of the peripheral pulseManifests when only some cardiac contractions are strong enough to transmit a pulse wave to the peripheryNumber of cardiac contractions (perceived with stethoscope or palpated on the chest) is higher than the peripheral pulse rate (e.g., radial artery) Complications of long-standing Afib Acute left heart failure → pulmonary edemaThromboembolic events: stroke/TIA, renal infarct, splenic infarct , intestinal ischemia , acute limb ischemiaLife-threatening ventricular tachycardia Individuals with Afib may be asymptomatic for a long time before diagnosis is made. The brain, kidney, and spleen are the three organs most likely to be damaged by emboli! Diagnostics ECG (initial investigation) Irregularly irregular RR intervals P-waves are indiscernible Tachycardia Narrow QRS complex (< 0.12 seconds) Echocardiography Transthoracic echocardiogram (TTE) Indications: all patients with new-onset AfibAssesses cardiac function and rule out underlying structural cardiac disease, e.g., mitral valve stenosis Transesophageal echocardiogram (TEE)Indicated in patients who meet all of the following criteria:Afib or atrial flutter for > 48 hours or unknown durationScheduled electrical or pharmacological cardioversionNo anticoagulation therapy for at least the past 3 weeksVisualizes the atria and the left atrial appendage (hotspots for thrombogenesis) to identify thrombi before attempting cardioversion Further assesses heart function and rules out underlying structural disease Laboratory studies TSH, fT4: to screen for hyperthyroidism Serum electrolytes (Na+, K+, Mg2+, and Ca2+): to identify electrolyte imbalances Troponin levels: to rule out myocardial infarction D-dimer levels: if risk factors (e.g., DVT) or clinical features of pulmonary embolism are present Brain-natriuretic peptide (BNP): to rule out heart failure CBC: to identify anemia, infection BUN, serum creatinine: to identify chronic kidney disease Ethanol levels, digoxin levels, and/or urine toxicology (e.g., cocaine, amphetamines) Differential diagnoses AFib should be differentiated from other supraventricular tachyarrhythmias with a narrow QRS complex. See supraventricular arrhythmias in the overview section of cardiac arrhythmias. Treatment The general principles of treating atrial fibrillation include: Correcting reversible causes and/or treatable conditions (e.g., hyperthyroidism, electrolyte imbalances) Controlling heart rate and/or rhythm Providing anticoagulation Controlling heart rate and/or rhythm Unstable AF: emergent electrical cardioversion Stable AF: rate control or rhythm control strategies to control AF and prevent long-term recurrence (see table below) Rate control Normalizing the ventricular heart rate <80 Elderly patients ContraindicationsAF due to pre-excitation syndromes measures 1st line1st choice: beta blockers (esmolol, propanolol, metoprolol) ORnondihydropyridine calcium channel blockers (diltiazem, verapamil) 2nd choice: digoxin 3rd choice: dronedarone, amiodarone2nd line(ablative procedures)AV nodal ablation and implantation of a permanent ventricular pacemaker Rhythm control Terminating atrial fibrillation and restoring it to sinus rhythm in order to prevent atrial remodeling Failure of rate-control strategy to control symptoms Younger patients CI Long-standing persistent AF 1st choice: elective electrical cardioversion 2nd choice: pharmacologic cardioversion with antiarrhythmic drugs such as flecainide, propafenone, ibutilide, dofetilide See prerequisites for cardioversion of AF below Catheter-based radiofrequency ablation of atrial tissue around pulmonary vein openings (pulmonary vein isolation) Anticoagulation Prerequisites for cardioversion of AF New onset AF (< 48 hours) in patients with:Low thromboembolic risk (see CHA2DS2-VASc score below) → consider anticoagulation directly before or after cardioversionHigh thromboembolic risk → start anticoagulation immediately before or after cardioversionAnticoagulation options: IV heparin or LMWH, direct thrombin inhibitors (e.g., dabigatran), or factor Xa inhibitors(e.g., rivaroxaban, apixaban) AF ≥ 48 hours or of unknown duration in patients with:Unstable AF (require urgent cardioversion): IV heparin or LMWH immediately before cardioversion followed by warfarin for up to 4 weeks after cardioversionTEE to rule out atrial thrombi recommended if anticoagulation has not been administered at least 3 week prior to cardioversionStable AF (do not require urgent cardioversion): warfarin with bridging therapy for 3 weeks before and up to 4 weeks after cardioversion Long-term anticoagulation CHA2DS2-VASc score CHF or left-sided heart failure 1 Hypertension1A2Age ≥ 752 DDiabetes Mellitus1 S2Stroke or TIA or thromboembolism2VVascular disease (prior MI, peripheral artery disease, or aortic plaque)1AAge 65-741ScSex category (female sex)1 Nonvalvular atrial fibrillation: The need for anticoagulation therapy is based on the CHA2DS2-VASc scoreScore = 0: no anticoagulationScore = 1: no anticoagulation OR treatment with oral anticoagulants Score ≥ 2: oral anticoagulation with either warfarin or newer oral anticoagulants (dabigatran, rivaroxaban, apixaban) Valvular atrial fibrillation: anticoagulation with warfarin is required regardless of the CHA2DS2-VASc score Long term anticoagulation for patients with AF in order to prevent thromboembolic complications is indicated if the patient has an underlying valvular disease and/or a CHA2DS2-VASc score ≥ 2 Atrial flutter Atrial flutter is a supraventricular tachyarrhythmia that is usually caused by a single macroreentrant rhythm within the atria. EpidemiologyIncidence: 88 per 100,000 person-years (increases with age) Sex: ♂ > ♀ (5:2) Etiology: similar to atrial fibrillation (see "Etiology" above) Pathophysiology Type I (common; typical or isthmus-dependent flutter): caused by a counterclockwise (more common) or clockwise (less common) macroreentrant activation of cardiac muscle fibers in the right atrium that travels along the tricuspid annulus and passes through the cavotricuspid isthmus Type II (rare, atypical atrial flutter): various reentrant rhythms that do not involve the cardio-tricuspid isthmus, are not well defined, and/or occur in the left atrium Clinical featuresMost patients are asymptomaticLess commonly, symptoms of arrhythmias such as palpitations, dizziness, syncope, fatigue, and or dyspneaSymptoms of the underlying disease (e.g., murmurs of mitral stenosis)Tachycardia with a regular pulse Diagnostics: similar to atrial fibrillation; see "Diagnostics" above Sawtooth appearance of P waves: identical flutter waves (F waves) that occur in sequence at a rate of ∼ 300 bpm Regular, narrow QRS complexesThe rhythm may be:Regularly irregular if atrial flutter occurs with a variable AV block occurring in a fixed pattern (2:1 or 4:1)Irregularly irregular with a variable block occurring in a nonfixed pattern Treatment: similar to atrial fibrillation (see "Therapy" below) ComplicationsFrequently degenerates into atrial fibrillation (see "Clinical features" above)1:1 conduction leading to life-threatening ventricular tachycardia Due to the risk of ventricular fibrillation, avoid digoxin, nondihydropyridine calcium channel blockers, and amiodarone in patients with Afib with pre-excitation.

Aortic valve stenosis Aortic stenosis (AS) is a valvular heart disease characterized by narrowing of the aortic valve. As a result, the outflow of blood from the left ventricle into the aorta is obstructed. This leads to chronic and progressive excess load on the left ventricle and potentially left ventricular failure. The patient may remain asymptomatic for long periods of time; for this reason, AS is often detected late, i.e., when it first becomes symptomatic (dyspnea on exertion, angina pectoris, or syncope). Auscultation reveals a harsh, crescendo-decrescendo murmur in systole that radiates to the carotids, and pulses are delayed with diminished carotid upstrokes. Echocardiography is the gold standard for diagnosis. Patients with asymptomatic aortic stenosis are treated conservatively. Symptomatic patients or those with severe aortic valve stenosis require valve replacement.

Epidemiology Most common valvular heart disease in industrialized countries Prevalence: Increases with age May reach up to 12.4% among individuals ≥ 75 years Classification By location of obstruction Valvular: most common Supravalvular Subvalvular By etiology Congenital: Bicuspid aortic valve: caused by a fusion of two of the three aortic-valve leaflets in uteroMost common congenital heart defect, 3:1 ♂ predominancePredisposes the valve to dystrophic calcification and degenerationPatients present with symptoms of aortic stenosis earlier than in regular aortic valve calcification AcquiredCalcific aortic stenosis: most common cause of aortic stenosisCharacterized by calcification and fibrosis of aortic valve leaflets that occur at an increasing rate as patients age (prevalence is 65% in those aged 75-84 years)Similar pathophysiology to atherosclerosis (see generic risk factors for development of arteriosclerosis)Rheumatic fever is a rare cause of AS in developed countries, but continues to remain a significant cause in developing countries. Pathophysiology Narrowed opening area of the aortic valve during systole → obstruction of blood flow from left ventricle (LV) → increased LV pressure → left ventricular concentric hypertrophy →Increased LV oxygen demand Impaired ventricular filling during diastole → left heart failureReduced coronary flow reserve Initially, cardiac output (CO) can be maintained. Later, the decreased distensibility of the left ventricle reduces cardiac output and may then cause backflow into the pulmonary veins and capillaries → higher afterload (pulmonic pressure) on the right heart → right heart failure (see congestive heart failure) Clinical features The disease may remain asymptomatic for years (particularly with mild or moderate stenosis). Symptoms typically present on exertion, unless AS is severe Dyspnea Angina pectoris Dizziness and syncope Small blood pressure amplitude, decreased pulse pressure Cardiac exam (see cardiovascular examination) Weak and delayed distal pulse (pulsus parvus et tardus)Palpable systolic thrill over the bifurcation of the carotids and the aortaHarsh crescendo-decrescendo (diamond-shaped), late systolic ejection murmur that radiates bilaterally to the carotidsBest heard in the 2nd right intercostal space Hand grip decreases the intensity of the murmur. Valsalva and standing from squatting decreases or does not change the intensity of the murmur (in contrast to hypertrophic cardiomyopathy).Soft S2 S4 is best heard at the apex. Early systolic ejection click Frequently associated with aortic regurgitation (see diagnosis of aortic regurgitation) Additional signs specific to infants: wheezing and difficulty feeding SAD (syncope, angina, dyspnea) Without definite treatment (surgery), more than 50% of the symptomatic patients with severe aortic stenosis will die within the first 2 years of diagnosis! Diagnostics ECGNonspecific for ASSigns of left ventricular hypertrophy (e.g., left axis deviation, positive Sokolow-Lyon index) Chest x-ray Findings of left ventricular hypertrophy, such as left ventricular enlargement and rounded heart apex, usually only in decompensated aortic stenosis, and possibly left atrial enlargement as well Narrowing of retrocardiac space (lateral view)Calcification of aortic valve: signs of more severe disease EchocardiographyTransthoracic (TTE) or transesophageal (TEE): preferred primary test and noninvasive gold standard Findings include concentric hypertrophy, narrowing of the opening of the aortic valve, and increased meanpressure gradient across the aortic valve. Also utilized to determine the severity of stenosis by parameters such as the mean gradient and cross-sectionalarea of the opening of the valve Left-heart catheterization Definitive diagnostic testIndication: inconclusive echocardiogramRisk of cerebral embolization Treatment Conservative management: regular follow-ups indicated for asymptomatic patients with mild aortic stenosis Surgical (see heart valve prostheses) Indications Symptomatic patients Asymptomatic patients with severe AS and either significantly ↓ LV EF or those undergoing cardiac surgeryAortic valve replacement (AVR): 3 possible approaches Surgical AVR: patients with low surgical risk.Transcatheter AVR (TAVR): patients with high surgical risk or contraindicationCatheter balloon valvuloplasty: children without AV calcification The presence of exertional symptoms (dyspnea on exertion, angina pectoris, syncope) is an indication for surgery! Prognosis Asymptomatic patients: The mortality rate is < 1% in a given year. Symptomatic patients: The mortality rate in the first 2 years is > 50%.

Thromboangiitis obliterans Thromboangiitis obliterans (TAO, Buerger disease) is an inflammatory, non-atherosclerotic, vaso-occlusivedisease of both small and medium-sized arteries as well as veins in the upper and lower limbs. TAO most commonly affects adult males with a significant history of cigarette smoking. In susceptible individuals, smoking causes inflammation of the tunica intima of small vessels by an unknown mechanism, which results in thrombotic occlusion of the vessel. Patients initially present with a classic triad of intermittent claudication, Raynaud phenomenon, and migratory thrombophlebitis. Eventually, critical limb ischemia develops and the patient presents with rest pain, absent pulse in the extremities, and/or digital gangrene. Ultrasonography and arteriography are used to localize the site of occlusion and differentiate TAO from other causes of peripheral artery disease. The most important therapeutic measure is the complete cessation of smoking. Additionally, prostaglandin analogs (e.g., iloprost) may be used to improve blood flow and decrease rest pain. Patients with TAO who develop digital gangrene require amputation.

Epidemiology Prevalence: 13-20 cases per 100,000 individuals Sex: ♂ > ♀ (3:1) Age of onset: 20-45 years Ethnicity: Ashkenazi Jews, Indians, Koreans, Japanese Pathophysiology Thromboangiitis obliterans is an inflammatory, non-atherosclerotic vasculitic disease that affects both small and medium-sized arteries as well as the veins. Smoking is the single most important risk factor for TAO. Stages of TAOInflammation of the tunica intima with neutrophilic infiltration and microabscess formation (endarteritis)→ inflammation may also spread to the tunica media but the internal elastic lamina usually remains intact. Unlike in other forms of vasculitis, the rest of the vessel wall is usually relatively spared → development of cell-rich, inflammatory thrombi in the lumen → occlusion of the vesselMononuclear cells, fibroblasts, and giant cells replace neutrophilsReorganization of the thrombus and perivascular fibrosisContiguous extension of inflammatory process to the adjacent vein and nerve, resulting in the encasement of the artery, vein, and nerve in a fibrous sheath Disease localization: distal arteries of the upper and lower extremities Clinical features Patients may present with acute limb ischemia and/or symptoms of chronic peripheral artery disease (see "Clinical features" of peripheral artery disease). Early manifestationsSuperficial thrombophlebitis (which is often migratory) with tender nodules along the course of the veinIntermittent claudication Raynaud phenomenon Late manifestations Rest painCool peripheral extremitiesTrophic nail changesUlceration and/or gangrene of fingertips and/or toes (digits may autoamputate)Normal brachial and popliteal pulses but poor/absent radial, ulnar, anterior tibial, posterior tibial and/or dorsal pedis pulsationsAn abnormal Allen's test may be seen if the ulnar artery is involved. Diagnostics Laboratory findingsESR and CRP are within normal limits. Autoantibodies (e.g., ANA, RF) are absent and the hypercoagulability screen is normal. ImagingDoppler ultrasound (initial imaging): ↓ ankle-brachial index Arteriography (imaging modality of choice): non-atherosclerotic, smooth, tapering, segmental lesions that occlude distal vessels of extremities with corkscrew-shaped collateral vessels around the site of occlusion Although confirmation of the diagnosis requires excisional skin biopsy, biopsies are rarely performed. Treatment General measuresComplete cessation of smoking and the use of tobacco products is the single most important therapeutic measure Protection of fingers and toes from cold to prevent Raynaud phenomenon Medical therapy Iloprost Calcium channel blockers (nifedipine, amlodipine)Hyperbaric oxygen therapy Surgical therapyRevascularization procedures (e.g., bypass grafting, angioplasty) usually cannot be performed because, typically, distal small and medium-sized arteries are involved. Patients with ulcers may require debridement and treatment with antibiotics.Patients who develop gangrene in the extremities will require amputation.

Mitral valve prolapse Mitral valve prolapse (MVP) is caused by a structural defect of the mitral valve that results in /mitral leaflets bulging into the left atrium during systole. In the US, MVP is the most common heart valve abnormality and the most common cause of mitral regurgitation (MR). Although MVP is typically asymptomatic, symptoms (eg., palpitations, fatigue, dyspnea) may arise, especially if associated with MR. A mitral prolapse click is a classic auscultatory finding MVP and diagnosis is made with echocardiography. No specific treatment is needed unless severe, symptomatic MR is present, in which case mitral valve repair or replacement is required.

Epidemiology Prevalence: 2-3 % (one of the most common valvular abnormalities in the US) The most common cause of mitral regurgitation in developed countries Etiology Mostly idiopathic Connective tissue disorders: Marfan syndrome, Ehlers-Danlos syndrome, osteogenesis imperfecta Myocardial infarction Acute rheumatic heart disease Infective endocarditis Autosomal dominant polycystic kidney disease Pathophysiology The most common underlying pathology in the case of mitral valve prolapse is myxomatous degeneration (deposition of glycosaminoglycan such as dermatan sulfate) of the mitral valve due to a primary disease or connective tissue disorderLong, floppy mitral valve leaflets with excessive valvular tissue → the mitral annulus becomes dilated and the chordae tendineae become elongated (and may rupture) → prolapse of one or both mitral valve leaflets into the left atrium during systole The leaflets may also exhibit fibrous thickening at regions where they rub against each other. Mitral valve prolapse sets into motion a vicious cycle of events. If prolapse happens without the rupture of chordae tendineae → mitral valve leaflets billow into the left atrium→ mild to moderate mitral regurgitationIf the papillary muscles become severely ischemic and the chordae tendineae rupture → mitral valve leaflets flail about in the left atrium → severe mitral regurgitation Clinical features Most patients are asymptomatic. Rarely: atypical chest pain and anxiety In case of complications: fatigue, dyspnea, syncope, and palpitations (see "Complications" below) Auscultatory findings Mitral valve prolapse click: high-frequency, midsystolic click that is best heard at the mitral region High-frequency, mid-to-late systolic murmur that is best heard at the mitral region and may radiate to the axilla(squatting diminishes the murmur) Patients with severe MR: S3 may be heard as a result of left ventricular overload (especially in the left decubitus position) Diagnostics ECG: mostly normal Transthoracic echocardiography (test of choice) to confirm diagnosis Echocardiographic definition of MVP: displacement of the mitral valve during systole by more than 2 mm above the mitral valve annulus in the parasternal long-axis view Classical MVP (∼ 60%): leaflet thickness ≥ 5 mmNon-classical MVP (∼ 40%): leaflet thickness < 5 mm Transesophageal echocardiography (TEE) is used as an adjunct to TTE and intraoperatively to guide mitral valve repair procedures. Treatment No treatment is required in most cases. Patients with severe mitral regurgitation : mitral valve repair or replacement (see "Therapy" in mitral regurgitation) Additional treatment is required when complications arise (see "Complications" below) Complications Atrial fibrillation Ventricular ectopics : MVP patients with ventricular ectopics should be asked to avoid caffeine; β-blockers may be used for symptomatic relief. Transient ischemic attacks (TIA) and/or stroke : Patients who experience TIA or stroke will require prophylactic doses of aspirin (also see "Therapy" in stroke) Infective endocarditis : MVP patients with a past history of infective endocarditis require prophylaxis against infective endocarditis (see prophylaxis for endocarditis). Right heart failure

Peripheral arterial disease Peripheral arterial disease (PAD) is characterized by narrowing and, in final stages, occlusion of the peripheral arteries due to atherosclerotic plaques. Smoking is the most important risk factor for developing PAD. PAD is often a silent disease, but patients may present with features of arterial insufficiency (intermittent claudication, reduced temperature and pulse rate in affected limb, skin discoloration, and trophic changes). On occasion, critical limb ischemia is the only presenting complaint. Segmental blood pressures and pulse volume recordings, particularly the ankle-brachial index (ABI), may support the diagnosis. Further imaging may confirm and assess the location and severity of arterial stenosis or occlusion. Treatment focuses on smoking cessation, graduated exercise, avoiding extremely cold temperatures, and modifying other cardiovascular risk factors. If conservative treatment fails, interventional and surgical management is recommended for low-risk patients with potential long-term success.

Epidemiology Prevalence: 8.5 million in the US Prevalence increases with age, starting from the age of 40 US incidence rates are highest among African Americans, followed by Hispanics, who are at a slightly higher risk than non-hispanic whites. Peak incidence: 60-80 years of age Sex: ♂ = ♀ Etiology Insufficient tissue perfusion due to atherosclerosis in the aorta and peripheral arteries Often coexists with coronary artery disease (CAD), stroke, atrial fibrillation, and renal disease See risk factors for atherosclerosis Fontaine Classification of PAD Stage IAsymptomatic PADStage IIPain on exertionIIa: claudication at a walking distance > 200 m IIb: claudication walking distance < 200 m Stage IIIIschemic pain at restStage IVNecrosis/gangrene/ulcersIVa: dry necrosis, trophic disordersIVb: infection of necrotic tissue, humid gangrene Characteristic featuresDescriptionSilent diseaseUp to 20-50% of patients with PAD are asymptomatic!Intermittent claudication (10-35% of patients) Pain, cramps, or paresthesia distal to arterial occlusionFemoropopliteal disease (most common) → calf claudication Aortoiliac disease (Leriche syndrome) Level of the aortic bifurcation or bilateral occlusion of the iliac arteriesTriad of bilateral buttock, hip, or thigh claudication, erectile dysfunction, and absent/diminished femoral pulsesTibiofibular disease→ foot claudicationWorsens upon exertion , completely relieved by rest or lowering affected limbs Reproducible when the patient is asked to walk the same distance as when he/she was symptomatic Absent or diminished pulsesBrachial arteryRadial arteryFemoral artery Popliteal artery Posterior tibial artery Dorsalis pedis artery Trophic changes↓ Skin temperature↓ Perspiration↓ Hair on legsBrittle nails, ↓ nail growthAtrophied muscles Dry atrophic, shiny skin and/or bluish skin discolorationSkin pallor when limb is elevated and reactive hyperemia of dependency → Buerger test for examination Livedo reticularis (advanced disease)Gangrene, ulcers, necrosis (end-stage disease): see also "Arterial ulcer"Rest pain Typically in distal metatarsalsWorse at night Improved when hanging feet over bed or standingCritical limb ischemiaThe presence of any one of the following: Resting painUlcerTissue loss (gangrene)Indicative of limb-threatening arterial occlusion A bruit, suggestive of arterial stenosis, may be heard in > 60-70% of cases with PAD! Diagnostics Ankle-brachial index (ABI) First-line diagnostic test (high specificity and sensitivity) [9] Defined as the ratio of systolic ankle blood pressure (BP) to systolic brachial BP The ABI is calculated for each leg by dividing the higher systolic pressure of either the dorsalis pedis or posterior tibialis of the respective leg by the higher blood pressure of either the right or left arm Right ABI = highest systolic BP in the right ankle/brachial BP in the arm with the highest systolicpressureLeft ABI = highest systolic BP in the left ankle/brachial BP in the arm with the highest systolic pressure Normally, ankle BP and brachial BP are equal (ABI = 1), or ankle BP is only slightly higher because of gravity (ABI > 1) Differences in systolic BP indicate different pathologies: > 1.3 = medial sclerosis with incompressible vascular wall (generally calcified vessels)1.0-1.30 = normal value0.91-0.99 = borderline0.40- 0.90 = mild to moderate PAD → claudication< 0.40 = severe PAD → resting pain, gangrene (critical limb ischemia) Exercise testing may be required if patients have a normal resting ABI Imaging While vascular imaging is not necessarily required for diagnosis, it is useful to determine the site and severity of arterial stenosis or occlusion (especially preoperatively and postoperatively) Color-coded duplex ultrasonography Digital subtraction angiography (DSA): gold standard CT angiography MR angiography Oscillography ABI measurements in diabetic or older patients may be inaccurate because of Monckeberg sclerosis! Differential diagnosis of claudicationPatient characteristicsClinical featuresCauses of arterial occlusionVasculitidesTakayasu arteritisAsian females15-45 yearsFever, malaise, arthralgiaSyncope, angina pectorisImpaired visionObliterative endarteritis20-40 yearsMigratory thrombophlebitisIntermittent claudication, often limited to feet, calves and/or handsRaynaud syndrome(Lower-extremity) fibromuscular dysplasiaMiddle-aged womenGradual onset of symptomsRarely affects the extremities, leading to intermittent claudication, critical limb ischemia, and blue toe syndromePopliteal aneurysmSimilar risk factors as PADChronic lower limb ischemia may manifest like PAD Acute limb ischemia → 6 PsBlue toe syndrome: small vessel occlusion caused by embolusArterial embolismYoung patients without atherosclerotic risk factorsSudden onset of symptoms6 PsPopliteal entrapment syndrome Intermittent claudicationCystic adventitial disease Generally affects men between 30-50 yearsFoot pulses may be present during rest and absent following exercise Mimics of arterial occlusionDeep vein thrombosis> 60 years oldHistory of immobilization, obesity, hereditary thrombophilia or malignancySwellingWarmthErythemaProgressive tendernessDull pain: worsened by walking, improved by restingSpinal stenosisMiddle-aged to older patientsNeurogenic claudicationAccompanied by weakness or numbnessBilateral or unilateral leg and back painImproved by lumbar flexionDiabetic neuropathyMiddle-aged to older patientsHigh BMIProgressive symmetrical loss of or abnormal sensation in the distal lower extremities (glove and stocking sensation)Normal ABINeuopathic diabetic foot: warm, dry skin, palpable foot pulses Treatment Conservative Smoking cessation! Supervised graded exercise therapy Foot care (especially in diabetic patients) Avoid cold temperatures Medical therapy Modify cardiovascular risk factors: see therapy of atherosclerotic diseaseAntiplatelet therapy reduces morbidity and mortalityAspirin: irreversible cyclooxygenase inhibition → decreased thromboxane A2 synthesis → decreased platelet aggregationADP receptor inhibitorsClopidogrel: inhibition of the P2Y12 ADP receptor → decreased platelet activation and platelet-fibrin crosslinkingTicagrelor: reversible inhibition of the P2Y12 ADP receptor (otherwise identical downstream effects as clopidogrel)Lipid-lowering agent (usually statins)Antihypertensive treatmentHyperglycemia control PDE inhibitorsCilostazol (the single most effective medication)It is indicated in patients with lifestyle-limiting intermittent claudication only after 3 months of supervised graded exercise therapy.It is administered as a therapeutic trial for 3-6 months.If no or minimal improvement occurs, consider advanced vascular imaging (see "Imaging" above).Mechanisms Phosphodiesterase 3 (PDE3) inhibition → increased cAMP → increased activity of protein kinase A→ reduced platelet aggregationMyosin light chain kinase inhibiton → vascular smooth muscle relaxation → arterial vasodilation Revascularization IndicationsCritical limb ischemiaFailure of conservative and pharmacologic treatmentInability to perform normal work or activities because of claudicationNo limitations to exercise by other disease (e.g., chronic heart failure) if claudication is improvedAnatomy of the lesion allows low-risk and long-term success of intervention Minimally invasive interventional radiology: percutaneous transluminal angioplasty (PTA) with or without stenting Surgical proceduresOperative vascular reconstruction (bypass surgery): an autologous vein (e.g., great saphenous vein) is used to bypass the stenosis Endarterectomy Amputation Last resort in the event of gangrene Complications Arterial ulcerDefinition: skin defect due to impaired blood flow to the lower extremitiesEtiology: most often seen in peripheral arterial diseaseClinical featuresPunched-out ulcer with well-defined borders Usually involves the foot, particularly pressure points (e.g., lateral malleolus, tips of the toes)Often severe painDifferential diagnosis: venous ulcer Infection of ulcers; sepsis Acute limb ischemia Surgical complications: bleeding, infection of vascular prosthesis, relapse Prognosis Intermittent claudication → good prognosis Rest pain and/or ischemic ulcers → poor prognosis Increased cardiovascular mortality → high risk for secondary MI or stroke A low ABI in PAD is also predictive of an increased risk of all-cause and cardiovascular mortality! Prevention See primary and secondary prevention of atherosclerosis.

Paroxysmal supraventricular tachycardia Paroxysmal supraventricular tachycardia (PSVT) is a type of arrhythmia arising from a defect in atrioventricular conduction, which causes the heart to sporadically beat faster. There are different forms of PSVT, including atrioventricular nodal reentrant tachycardia (AVNRT; about two-thirds of cases), atrioventricular reentrant (or reciprocating) tachycardia (AVRT), and atrial tachycardias. In AVNRT, extra electrical conduction pathways (accessory pathways) within the AV node lead to non-extinguishable, circulating electrical impulses (reentrant circuits). AVRT, on the contrary, is caused by circular depolarizations that travel through ectopic connections between the atria and ventricles. PSVT is characterized by tachycardia attacks that may cause dizziness, dyspnea, chest pain or syncope, and are usually self-limiting. Diagnostic steps for any type of PSVT include obtaining the patient history and a 12-lead ECG, which typically shows tachycardia and narrow QRS complexes. Because most tachycardia attacks subside before an ECG is conducted, continuous recording with a Holter monitor is often needed to confirm the diagnosis. In some cases, invasive electrophysiological studies may be indicated. Patients with a congenital condition known as Wolff-Parkinson-White(WPW) syndrome commonly exhibit AVRT because of the presence of an accessory pathway known as the bundle of Kent. This pathway bypasses the AV node and transmits the sinus impulse directly to the ventricles, resulting in a premature depolarization (pre-excitation) that appears as a delta wave on ECG. Management of PSVT should be tailored to the individual patient: hemodynamically unstable patients should undergo urgent cardioversion, whereas patients who are hemodynamically stable may benefit from vagal maneuvers, e.g., carotid massage. Pharmacologic therapy is indicated if the sinus rhythm cannot be restored by vagal maneuvers. The appropriate drug depends on the conduction pathway in the heart as revealed by ECG findings. Catheter ablation may be performed as a definitive treatment.

Epidemiology Prevalence: ∼ 2.25 per 1000 people Sex: ♀ > ♂ (2:1) Age of onsetAVRT: 23 ± 14 yearsAVNRT: 32 ± 18 years Etiology Atrioventricular nodal reentrant tachycardia (AVNRT): tachycardia caused by a dysfunctional AV node that contains two electrical pathways Atrioventricular reciprocating tachycardia (AVRT): tachycardia caused by an accessory pathway between the atriaand ventriclesWolff-Parkinson-White syndrome (WPW): A congenital condition characterized by intermittent tachycardias and signs of ventricular pre-excitation on ECG, which both arise from an accessory pathway known as the "Bundle of Kent" (an accessory pathway that conducts impulses from the atria to the ventricles)The bundle of Kent connects the atria and ventricles, bypassing the AV node and leading to a pre-excitation of the ventricles. Up to one-third of patients may develop paroxysmal atrial fibrillation.May result in supraventricular tachycardia due to a reentry circuit Atrial tachycardia (AT): The atria respond to impulses from an atrial pacemaker outside of the SA node. Atrial tachycardia is responsible for 10% of sustained PSVT.May occur in patients with or without underlying heart disease.A common cause of AT includes digoxin poisoning which typically presents with concomitant AV block. Atrial fibrillation and atrial flutter: These conditions are types of supraventricular tachycardias, but are usually considered separately (see atrial fibrillation). Permanent junctional reciprocating tachycardia (PJRT) Pathophysiology AVNRT The AV node contains two electrical pathways: one fast and one slow → the electrical impulse circles around the AV node within both pathways → continuous circuit that conducts impulses to the ventricles → tachycardia Approx. 90% of cases are due to anterograde conduction across the slow-conducting pathway and retrograde in the fast pathway (although the reverse is possible) AVRT There are two types of atrioventricular reentrant tachycardia. The direction of the reciprocating impulse helps distinguish between the two: Orthodromic AVRT: most common (90-95%) → narrow QRS complexAntegrade conduction (atrium → ventricle) through AV node; retrograde conduction (ventricle → atrium) through accessory pathwayAntidromic AVRT: least common (5-10%) → delta waveAntegrade conduction (atrium → ventricle) through accessory pathway; retrograde conduction (ventricle → atrium) through AV node Do not confuse atrioventricular reentrant (or reciprocating) tachycardia (AVRT) with atrioventricular nodal reentrant tachycardia(AVNRT)! AVRT is caused by an accessory pathway between the atrium and ventricle, while in cases of AVNRT, there are two functional pathways present within the AV node! Clinical features Palpitations, dizziness, chest pain, dyspnea, syncopes Urinary urgency Irregularly activated atria contract against a closed atrioventricular valve → ↑ atrial pressures → release of atrial natriuretic peptide (ANP) → ↑ urine output through renal sodium loss Diagnostics ECG A 12-lead ECG should be performed in patients suspected of PSVT. If inconclusive, consider recording the heart's electrical activity for 24 to 48 hours with a Holter monitor or event recorder. Supraventricular: narrow QRS complex (< 120 ms) AVNRT: no P waves or atrial activity AVRT: P wave in the ST segment AT, atypical AVNRT or junctional reciprocating tachycardia : RP interval longer than PR interval ECG findings in AVNRT ECG may be normal During tachycardia: Heart rate of 150-220 bpmNarrow QRS complexesP wave falls in QRS complex → P wave is not visible ("buried" in the QRS complex)Infrequent finding: P wave occurs before or after a QRS complex → abnormal P wave morphology ECG findings in AVRT Orthodromic AVRT:Narrow QRS complexP wave following QRS complex Antidromic AVRT:Shortened PR intervalDelta wave (ECG) = slurred upstroke in QRS complex due to pre-excitation → wide QRS complexThis feature of pre-excitation can not be observed during tachycardia or in a patient with "concealed pathway" (retrograde conduction)Commonly found on ECG in WPWNot visible during tachycardia or in patients with a concealed pathway (retrograde conduction) Differential diagnoses Anxiety disorders or panic disorder Sinus tachycardia: sinus rhythm with heart rate of > 100 bpm. Gradual onset and offset are typical Treatment Hemodynamically unstable patient Cardioversion: fastest and most effective treatment of supraventricular tachycardia Hemodynamically stable patient Goal: re-establish and maintain sinus rhythm Most asymptomatic patients do not require medical intervention, so observation is sufficient Acute Management of PSVT Vagal maneuvers: first step in acute management Carotid sinus massage: pressure must be applied at the level of the carotid bifurcation unilaterally for 5-10 seconds at mostCarotid sinus massage stimulates the baroreceptors → stimulates CN IX (specifically the branch of the glossopharyngeal nerve to the carotid sinus) → nerve impulse transmission to the medulla (nucleus tractus solitarius) → efferent signals from the medulla to the myocardium via the vagus nerve (parasympathetic supply) → ↓ AVN conduction, ↓ heart rate, ↓ contractility, and vasodilation (↓ blood pressure) → termination of arrhythmiaValsalva maneuver: Following deep inspiration, the patient is told to perform an abdominal press and forcefully exhale against a closed glottis.Diving reflex: immersion of head in ice cold water Medical therapy: if vagal maneuvers have failedAVNRT and orthodromic AVRT: First line: IV adenosine: briefly blocks the AV node (↑ refractoriness)Second-lineIV verapamil, IV diltiazem (calcium channel blockers) IV metoprolol, esmolol (beta blockers) For antidromic AVRT: procainamideAV nodal blocking agents are contraindicated! For WPW patients with AF: generally rhythm control (e.g., procainamide) AV nodal blocking agents are contraindicated! AV nodal blocking agents (i.e., adenosine, verapamil, beta-blockers, digoxin, amiodarone) are contraindicated in patients with signs of preexcited tachycardia on ECG (e.g., antidromic AVRT; AF in WPW patient)! ECG should be recorded during acute management to identify and treat other arrhythmias if the treatment was unsuccessful After successful termination of tachycardiaFollowed by a P wave upon termination → AVRT, AVNRTFollowed by a QRS complex upon termination → focal atrial tachycardiaPersisting tachycardia with AV block → atrial flutter, atrial tachycardia A defibrillator should be ready in case new dysrhythmias emerge (especially for AF) Administration of adenosine and calcium channel blockers together may potentiate a bradycardic or hypotensive response! Long-term management of PSVT For the management of well-tolerated, infrequent episodes, the patient may be instructed to perform vagal maneuvers Catheter radiofrequency ablationFirst-line therapy (curative) in AVNRT, AVRT, or drug refractory AT Indicated especially for: Symptomatic patients with concomitant structural heart diseaseSymptomatic patients who want to avoid long-term drug therapy (especially younger patients)Asymptomatic patients with special lifestyle considerations (e.g., pilots) Medical therapy (second line) AVNRTVerapamil, diltiazem (non-dihydropyridine calcium channel blockers)β-blockersDigoxinAVRTFlecainide, propafenone (class Ic antiarrhythmic drugs)SotalolAmiodaroneFor initial management of prolonged tachycardia, the "pill-in-pocket" approach may be useful if vagal maneuversare unsuccessful

Long QT syndrome Long QT syndrome (LQTS) is a congenital or acquired heart condition in which the QT interval (i.e., ventricular depolarization and repolarization) is prolonged. Most patients with LQTS are asymptomatic, but some present with seizures, syncope, or even life-threatening arrhythmias and sudden death. Treatment depends on the underlying cause: Beta blockers and implantable cardioverter defibrillator (ICD) insertion are commonly used for congenital LQTS, whereas treatment of the underlying cause (drug, electrolyte abnormality, etc.) is the first-line therapy for acquired LQTS.

Etiology A prolonged QT interval may be congenital or acquired. Congenital LQTS Congenital LQTS arises from mutations in genes that code for ion channels within myocytes These mutations all cause ventricular action potentials to be prolonged, resulting in a lengthened QT interval on ECG. [1] LQTS type 1Most common type of congenital LQTSDefect: loss of function mutation on the KCNQ1 gene located on chromosome 11p → defective slow delayed rectifier voltage-gated potassium channelSubtypes Jervell and Lange-Nielsen syndrome [2]Associated with congenital deafnessAutosomal recessiveAssociated with ventricular tachyarrhythmiasRomano-Ward syndrome [3]No associated deafnessAutosomal dominantAssociated with ventricular tachyarrhythmias Acquired LQTS Drugs: Usually substances that block potassium outflow during the rapid repolarization phase [4]Antiarrhythmics: especially class IA and class III antiarrhythmicsCompared to other class III antiarrhythmics, amiodarone rarely causes torsades de pointes.Psychiatric medications: especially tricyclic antidepressants and haloperidolAntibiotics (e.g., macrolides, fluoroquinolones)Antihistamines (e.g., diphenhydramine)Antimalarial medicationsAntiparkinson medicationsOpioids Electrolyte imbalances (e.g., hypokalemia, hypomagnesemia, hypocalcemia) Endocrine disorders (e.g., hypothyroidism) Nutritional deficiencies (e.g., anorexia nervosa) Ischemic stroke or intracranial hemorrhage Clinical features Often asymptomatic, especially if the QT interval is only minutely prolonged Some patients present with: PalpitationsDizzinessSyncopeCardiac arrest Diagnostics Diagnosis of LQTS can be difficult because a slightly prolonged QT interval can be a normal variant (i.e., not congenital LQTS), and some patients with LQTS do not have a prolonged QT interval. The primary finding in LQTS is a long QT interval corrected for heart rate (QTc) interval. Males: > 440 msFemales: > 460 ms Other diagnostic criteria take patient history and ECG findings into account. Genetic testing confirms the diagnosis of LQTS. Treatment Both congenital and acquired LQTSAvoid activities that stress the heartAvoid cold temperatures (e.g., swimming, diving, skiing) Congenital LQTSFirst line: beta blockers (e.g., propranolol)Left cardiac sympathetic denervation (stellectomy): patients not responsive to beta blockersHigh-risk patients (recurrent syncope despite medical therapy, survival of cardiac arrest): implantable cardioverter defibrillator (ICD) Acquired LQTS: treat cause (remove offending drug, fix electrolyte imbalances, etc.) Complications Ventricular tachycardia (torsade de pointes) Ventricular fibrillation Asystole Sudden cardiac death

Aortic regurgitation Aortic regurgitation (AR) is a valvular heart disease characterized by incomplete closure of the aortic valve that leads to reflux of blood from the aorta into the left ventricle (LV) during diastole. Aortic regurgitation may be acute (occurring primarily after bacterial endocarditis or aortic dissection) or chronic (due to congenital bicuspid valve or rheumatic fever) and may be caused by valvular disease or an abnormality of the aorta. In most cases, acute AR leads to rapid deterioration of LV function with subsequent pulmonary edema and cardiac decompensation. Frequently, chronic AR may remain compensated for a long period of time, becoming symptomatic only when left heart failure develops. Auscultation reveals an S3 and a high-pitched, decrescendo early diastolic murmur. Another characteristic diagnostic finding is widened pulse pressure. Echocardiography is the most important diagnostic tool, both for confirming the diagnosis and determining the severity of disease. In asymptomatic patients, conservative treatment consists of symptom management and physical activity as tolerated. However, symptomatic patients or those with severely reduced LV function should undergo surgical aortic valve replacement.

Etiology Acute ARInfective endocarditisAortic dissection (ascending aorta)Chest trauma Chronic ARCongenital bicuspid valve: most common cause of AR in young adults and in developed countriesRheumatic heart disease: most common cause of AR in developing countriesDistortion or dilation of the ascending aorta and aortic root Connective tissue disorders (e.g., Marfan syndrome, Ehlers-Danlos syndrome)Tertiary syphilis Also see heart valve disease Pathophysiology GeneralRegurgitation of blood from the aorta into the left ventricle (LV)→ Increased systolic blood pressure and decreased diastolic pressure → Widened pulse pressure → water hammer pulse (see "Diagnostics" below) Acute ARBecause LV cannot sufficiently dilate in response to regurgitant blood, LV end-diastolic pressure increases rapidly → pressure transmits backwards into pulmonary circulation → pulmonary edema and dyspneaDecreased cardiac output if severe → cardiogenic shock and myocardial ischemia Chronic ARInitially, a compensatory increase in stroke volume can maintain adequate cardiac output despite regurgitation (compensated heart failure)Over time, increased left ventricular end-diastolic volume → LV enlargement and eccentric hypertrophy of myocardium → left ventricular systolic dysfunction → decompensated heart failure Clinical features Acute ARSudden, severe dyspneaRapid cardiac decompensation secondary to heart failurePulmonary edemaSymptoms related to underlying disease (e.g., fever due to endocarditis, chest pain due to aortic dissection) Chronic ARMay be asymptomatic for up to decades despite progressive LV dilationPalpitationsSymptoms of left heart failureExertional dyspneaAngina OrthopneaEasy fatigabilitySyncopeSymptoms of high pulse pressure (e.g., head pounding, rhythmic nodding, or bobbing of the head in synchrony with heartbeats- de Musset sign) Diagnostics Physical examination For detailed information about the individual tests, see cardiovascular examination. High pulse pressure Water hammer pulse of peripheral arteries characterized by rapid upstroke and downstrokePulsing of carotid arteries with rapid upstroke and downstrokeVisible capillary pulse (Quincke sign)Nodding of the head with each pulse Point of maximal impulse (PMI): displaced inferolaterally, diffuse, and hyperdynamic Auscultation S3 High-pitched, blowing, decrescendo early diastolic murmur AR due to valvular disease: best heard in the left third and fourth intercostal spaces and along the left sternal border (Erb point)AR due to aortic root disease (e.g., aortic dissection): best heard along the right sternal borderWorsens with squatting and handgrip Austin Flint murmur In more severe stages, possibly a harsh, crescendo-decrescendo mid-systolic murmur that resembles the ejection murmur heard in aortic stenosis Confirmatory tests Transthoracic echocardiogram (TTE)Indicated for suspected AR as well as to monitor confirmed AR to determine the staging and optimal timing of surgeryFindings Abnormal aortic valve leafletsRegurgitant AR jet on Doppler flow tracingIncreased LV size and volumeDilated aortaFluttering of anterior mitral valve leaflet Transesophageal echocardiogram (TEE): indicated if suboptimal or nondiagnostic TTE Screening tests (optional) ECGSigns of left ventricular hypertrophy Chest x-ray Prominent aortic root/arch Enlarged cardiac silhouette Treatment Conservative Indication: asymptomatic patients and symptomatic patients who are not candidates for surgical treatment Treatment of heart failure Physical activity , but without excessive straining Surgical Indications [7]Symptomatic patients with acute severe AR Asymptomatic patients with:Chronic severe AR and EF < 50%Left ventricular systolic diameter > 50 mm Surgical procedure: aortic valve replacement (occasionally valve reconstruction is possible) and long-termanticoagulation therapy for mechanical valve Prognosis Asymptomatic patients with normal EF: progression to symptoms or LV dysfunction at a rate of < 6% per year Asymptomatic patients with decreased EF: progression to symptoms at a rate of > 25% per year Symptomatic patients: mortality rate is > 10% per year

Acute limb ischemia Acute limb ischemia (ALI) is a vascular emergency in which the arterial blood supply to one or more extremities is critically reduced. Arterial thrombosis and cardiac emboli are responsible for the majority of cases. The typical signs and symptoms of ALI include pain, pallor, pulselessness, poikilothermia, paralysis, and paresthesia of the limb distal to the site of vascular occlusion (the 6 Ps). Diagnosis relies on examination and arterial Doppler studies. Clinical findings in combination with Doppler studies are then used to categorize the limb as viable, threatened, or nonviable. Further imaging studies, e.g., digital subtraction angiography, should only be performed if they do not result in treatment delays. Management of viable and threatened limb ischemia begins with intravenous heparin followed by revascularization. Irreversible limb ischemia will inevitably progress to gangrene and requires amputation of the nonviable parts of the limb. Whether long-term anticoagulation and/or further diagnostic studies are required depends on the suspected etiology (e.g., echocardiography in suspected left atrial thrombus formation).

Etiology Arterial occlusion [1][2][3]ThrombosisPeripheral arterial disease Stent or graft thrombosisAneurysmal thrombosis (most commonly popliteal aneurysms)Vasculitis, thrombophilia (rare)Embolism Cardiac emboli Atrial fibrillation (most common) Myocardial infarction Cholesterol embolism (e.g., blue toe syndrome)DVT (paradoxical embolism via a patent foramen ovale)Septic emboli (e.g., from endocarditis)Proximal aneurysms (aortic, popliteal) or atherosclerotic lesionsTrauma leading to transsection, dissection, or thrombosis of a vesselPosterior knee dislocations (e.g., popliteal artery thrombosis)Iatrogenic injury at the site of arterial access (e.g., femoral artery thrombosis)Crush injury of a limbAortic dissectionCompartment syndrome Venous occlusion (phlegmasia cerulea dolens) Clinical features The lower limb is affected in > 80% of cases. Arterial thrombosis: subacute onset; history of claudication pain Embolism: acute onset; history of heart disease (e.g., atrial fibrillation) The 6 Ps distal to the site of occlusion Pain Pallor Pulselessness Paralysis Paresthesia Poikilothermia Subtypes and variants Leriche syndrome (aortoiliac occlusive disease) Occlusion at the level of the aortic bifurcation or bilateral occlusion of the iliac arteries that usually presents with: Pain in both legs and the buttocks Bilaterally absent femoral, popliteal, and ankle pulses Erectile dysfunction Shock Hair tourniquet syndrome Definition: a condition in which a hair or thread becomes wound around an appendage tightly, putting the appendage at risk of ischemic damage Epidemiology: usually affects infants Pathophysiology: hairs or threads inside socks or under bed sheets can become spontaneously tied round a toe and tighten with the child's movement → venous and lymphatic return is impaired → further obstruction may cause arterial occlusion and ischemic injury Clinical features: painful, swollen, reddened appendage with a deep groove proximal to it, in which the constricting fiber may be visible Treatment: prompt removal of the constricting hair or fiber, either by means of a hair-dissolving product or a scalpel Sensory lossMuscle weaknessPainHand-held Doppler signal Arterial Venous ViableNoneNoneMild to moderateAudible flowAudible flowThreatenedMinimalMild to moderateSevereNo flowAudible flowNonviableAnesthetic limbParalysisNo pain No flowNo flow Diagnostics Tests to confirm the diagnosis and identify the site(s) of occlusion Best initial test: arterial and venous DopplerDiminished or absent Doppler flow signal distal to site of occlusion.Confirmatory test: angiography (DSA, CTA, MRA) Digital subtraction angiography (DSA) is the imaging modality of choice.Should only be performed if delaying treatment for further imaging does not threaten the extremity Depending on the suspected etiology, other tests may be indicated (e.g., echocardiography if an arterial embolism is suspected). Treatment Acute limb ischemia due to thromboembolismSystemic anticoagulation with an IV heparin bolus followed by continuous infusion unless a contraindication is presentFurther management depends on the severity of acute limb ischemia. Viable, non-threatened limbUrgent angiography to localize the site of the occlusionRevascularization procedure (open or catheter-directed thrombectomy or thrombolysis) within 6-24 hoursThreatened limb: emergent revascularization procedure within 6 hoursFirst-line: catheter-directed thrombolysis and/or percutaneous mechanical thromboembolectomy(e.g., balloon catheter embolectomy)Second-line: open thromboembolectomyNon-viable limb: limb amputation Acute limb ischemia due to compartment syndrome: fasciotomy (see compartment syndrome) Acute limb ischemia due to a dissecting aneurysm: stenting and/or surgical repair Complications Permanent nerve damage: sensory loss, muscle weakness, paralysis Loss of limb due to irreversible ischemia Reperfusion injury (postischemic syndrome) Following reperfusion, detached metabolites may trigger further complications, especially after prolonged occlusion (more than 6 h).Possible complications Acidosis, hyperkalemia → cardiac arrhythmiaRhabdomyolysis → myoglobinemia → crush syndromeIschemia-reperfusion injury → compartment syndromeMassive edema → hypovolemic shockSevere complications: DIC (disseminated intravascular coagulation), multiorgan dysfunctionSymptomatic treatment, monitoring (amputation of the affected extremity if necessary)

Carotid artery stenosis Carotid artery stenosis (CAS) is an atherosclerotic, degenerative disease of the common carotid artery and internal carotid artery. Risk factors include advanced age, tobacco use, arterial hypertension, and diabetes mellitus. Depending on the extent of stenosis, ischemia in the carotid perfusion territory can result in amaurosis fugax, TIA, or stroke, and a bruit may be auscultated over the stenosis. Carotid duplex ultrasonography is the initial test of choice for evaluating asymptomatic patients. All symptomatic patients should undergo noncontrast CT or MRI to rule out acute or previous cerebral ischemia. Management depends on symptoms and the degree of stenosis. Lifestyle modifications and antiplatelet, antihypertensive, and statin therapy are recommended for all patients. Carotid endarterectomy is recommended for symptomatic patients with a stenosis ≥ 70% and asymptomatic patients with a stenosis ≥ 80%, but may also be considered in highly selected patients with moderate stenosis. Alternatively, if surgery is not feasible, carotid artery stenting may be performed.

Etiology Atherosclerosis Risk factors for cardiovascular diseaseAdvanced ageTobacco use Arterial hypertensionDiabetes mellitus Clinical features Many patients are asymptomatic. Carotid bruit (a pathologic sound heard on auscultation over the carotid artery that is caused by turbulent blood flow) Amaurosis fugax Transient ischemic attack Ischemic stroke Carotid artery stenosis does not typically cause vertigo, lightheadedness, or syncope. Diagnostics First test: carotid duplex ultrasonography (may not detect mild stenosis) Findings: focally increased velocity of blood flow MRA or CTA: indicated for asymptomatic patients with inconclusive ultrasound Noncontrast CT or MRI: indicated for all symptomatic patients (see stroke imaging for details) Digital subtraction angiography (DSA) Treatment Medical management: recommended for all patientsLifestyle modification (see primary and secondary prevention of atherosclerosis) Weight controlSmoking cessationDASH dietRegular aerobic physical activityLimited alcohol consumptionPharmacologic therapy as indicated Antiplatelets drugsStatinsAntihypertensive drugsAntidiabetic drugs Interventional management: decision to pursue intervention depends on the patient's symptoms, degree of stenosis, and risk factors Carotid endarterectomy (CEA): a surgical procedure in which the inner lining of a carotid artery is removed, along with any associated atherosclerotic deposits. Indications Symptomatic patients Carotid artery stenosis ≥ 70%Moderate carotid artery stenosis (50%-69%): depends on patient's age, sex, and comorbidities Asymptomatic patients Carotid artery stenosis ≥ 80%Moderate carotid artery stenosis (60%-79%): depends on patient's age, sex, and comorbiditiesContraindications Life expectancy of < 5 yearsSymptomatic carotid artery stenosis < 50%Asymptomatic complete carotid occlusionPrior ipsilateral endarterectomyPerioperative risk of a stroke/death: ≥ 6% in symptomatic patients; ≥ 3% in asymptomatic patients History of prior neck surgery/irradiation Carotid artery stenting (CAS): angioplasty and stenting as an alternative to CEAMay be considered if surgery is not feasible Increased risk of periprocedural complications compared to CEA Complications Stroke Asymptomatic carotid artery stenosis: annual risk of stroke is 0.5-1% (stenosis > 50%) Carotid artery stenosis is considered an indicator for increased risk of myocardial infarction and cardiovascular death. Complications of CEA (during and after the procedure) StrokeHypertension and hypotension See "Complications" in endarterectomy. Prevention Screening for asymptomatic carotid artery stenosis is only recommended in patients with a high risk of stroke (e.g., age > 65 years, coronary artery disease, dyslipidemia, history of tobacco use) Noninvasive methods (e.g., duplex ultrasonography, MRA)

Subclavian steal syndrome Subclavian steal syndrome (SSS) is a condition in which the subclavian artery proximal to the origin of the vertebral artery narrows or becomes occluded, usually due to atherosclerosis. This blockage results in a lack of blood reaching the ipsilateral arm through the subclavian artery, which can lead to a reversal of blood flow in the affected vertebral artery so that blood from the contralateral side can flow through the circle of Willis to supply the affected arm. The condition is mostly asymptomatic. If symptoms occur, they are mainly caused by ischemia of the affected arm and include limb pain, fatigue, paresthesia, and cold skin. Neurological symptoms such as dizziness or even syncope are rare and usually only occur in the presence of cerebrovascular lesions. A characteristic diagnostic sign is a discrepancy in blood pressure between the arms of > 15 mm Hg. Imaging (e.g., ultrasonography) can identify a reversal of blood flow and/or atherosclerosis that confirms the diagnosis. Endovascular intervention or surgery are used to treat symptomatic SSS.

Etiology Atherosclerosis Takayasu's arteritis Pathophysiology Stenosis of the subclavian artery proximal to the origin of the vertebral artery → hypoperfusion distal to the stenosis → reversal of blood flow in ipsilateral vertebral artery → compensation through collateral arteries → reduced blood flow in the basilar artery → reduced cerebral perfusion upon exertion involving the affected arm Clinical features Most patients are asymptomatic Limb ischemia (on exertion)Pain, paresthesiaPale, cool skinWeak, delayed radial pulseDisparity in BP > 15 mm Hg Neurologic symptoms (rare) Dizziness, vertigoOcular findings (e.g., diplopia)Syncope Subtypes and variants Coronary-subclavian steal syndromeIn patients with an internal thoracic artery (internal mammary artery) bypass Stenosis of the subclavian artery proximal to origin of the internal mammary artery (IMA) → exertion of the ipsilateral arm → flow reversal in the IMA graft → symptoms of angina pectoris Diagnostics Imaging of the cerebral and upper extremity arteries, e.g., via Doppler ultrasound, duplex ultrasound, or magnetic resonance angiography, shows reversal of blood flow and/or atherosclerosis. Treatment Asymptomatic patients usually do not require treatment apart from lifestyle changes to prevent progression of atherosclerosis. Symptomatic patients: angioplasty and stenting or surgical revascularization

Ventricular tachycardia Ventricular tachycardia (VT) is a potentially life-threatening arrhythmia originating in the cardiac ventricles. Usually, VT results from underlying cardiac diseases such as myocardial infarction or cardiomyopathy, but it can also be idiopathic or iatrogenic. Clinical manifestations range from palpitations and syncope to cardiogenic shock and sudden cardiac death. The characteristic ECG findings of VT are broad QRS complexes (> 120 ms) and tachycardia (> 120 bpm). In the acute setting, management of VT may require immediate cardioversion, defibrillation, or administration of antiarrhythmic drugs. Most patients who develop symptomatic, sustained VT require long-term antiarrhythmic therapy involving medication, intracardiac devices, or catheter ablation.

Etiology Cardiac scars (usually due to infarction; also iatrogenic, e.g., postoperative) Conduction disorders Drugs (e.g., digitalis, antiarrhythmics) Long-QT syndrome Congenital long-QT syndrome Acquired long-QT syndromeDrugs AntiarrhythmicsClass Ia (e.g., quinidine, disopyramide)Class III (e.g., sotalol, amiodarone)Antibiotics (e.g., macrolides, fluoroquinolones)Antidepressants (most tricyclic and tetracyclic antidepressants, lithium)Antipsychotics (e.g., haloperidol)Anticonvulsants (fosphenytoin, felbamate)Electrolyte imbalances (hypokalemia, hypomagnesemia, hypocalcemia)Ischemic stroke or intracranial hemorrhage Endocrine disorders (e.g., hypothyroidism)Nutritional disorders (e.g., anorexia nervosa) In rare cases, VT can occur in healthy individuals. Pathophysiology Monomorphic VT (all QRS complexes look similar) Increased automaticityRe-entry circuit Polymorphic VT (dissimilar QRS complexes): caused by abnormal ventricular repolarization (e.g., long QT syndrome, drug toxicity, electrolyte abnormalities) Decreased cardiac output: asynchronous atrial and ventricular beats + rapid ventricular rhythm → ↓ blood flow into the ventricle during diastole → ↓ CO→ hemodynamic compromise → symptoms of syncope, MI, angina Clinical features Often asymptomatic, especially if nonsustained Common symptoms of sustained VT include: PalpitationsHypotensionSyncope In more severe cases: Chest pain/pressure (often in conjunction with MI)Cardiogenic shockLoss of consciousnessProgression to ventricular fibrillationSudden cardiac death Subtypes and variants Torsades de pointes Polymorphic ventricular tachycardia with QRS complexes that appear to twist around the isoelectric line Most severe complication: progression to life-threatening ventricular arrhythmia Cause: prolonged QT interval caused by congenital disease, electrolyte abnormalities , and drugs Treatment If hemodynamically unstable → defibrillationIf hemodynamically stable → IV magnesium sulfate Diagnostics ECG 3 or more consecutive premature ventricular beats (i.e., widened QRS) Heart rate > 120 bpm DurationNonsustained: < 30 sSustained: > 30 s MorphologyMonomorphic: all QRS complexes look similar (identical origin)Polymorphic: QRS complexes are different (multiple origins) Other possible ECG findingsAV-dissociation: no relationship between P waves and QRS complexes (in VT, ventricular rhythm is often faster than atrial rhythm) Fusion complex: atrial and ventricular impulses occur simultaneously Capture beats: Occasionally, a supraventricular impulse may reach AV node and produce a subsequent ventricular beat (similar to a beat in sinus rhythm). Other diagnostic tests Holter monitor: useful for diagnosing intermittent VT which may not be present on a single ECG Patient-activated (manual) event recorder Echocardiography: provides information about possible etiologies of VT (e.g. structural heart disease, prior MI) and is thus a useful tool for evaluation of VT Differential diagnoses Confirming the diagnosis of VT can be challenging and, in some cases, impossible. However, VT accounts for nearly 80% of wide-complex tachycardias. Supraventricular tachycardia with aberrancy (RBBB, LBBB, Wolff-Parkinson-White) It is important to make the distinction between SVT with aberrancy and VT because treatment of the two conditions differs and sometimes the wrong treatment can lead to hemodynamic instability (e.g., using AV-nodalblocking drugs in patient with VT).Signs and symptoms that suggest VT rather than SVT are: Age > 35 (high PPV)History of structural heart defects or past MIAV dissociation, fusion beats, and capture beatsSigns and symptoms that suggest SVT with aberrancy rather than VT are: Bundle branch block on prior ECGHistory of SVTEvidence of WPW (e.g., delta wave) If there is any doubt regarding the diagnosis, assume VT rhythm and treat accordingly. Treatment Initial therapyIf patient is hemodynamically unstable (hypotension, loss of consciousness): VT with pulse → cardioversionVT without pulse → defibrillationSee "Advanced cardiac life support"If patient is hemodynamically stable: Antiarrhythmics (typically lidocaine, procainamide, amiodarone)Cardioversion if medical therapy failsIn all patients, look for and address possible causes of VT such as: Electrolyte abnormalities (e.g., hypokalemia) → correct any electrolyte imbalancesMedication-induced QT prolongation → remove any offending medication, digoxin immune fab (fragment antigen-binding) for digoxin toxicity Long-term therapyIntracardiac devices (ICD) (most effective treatment for reducing mortality): indicated in case of VT that does not respond to therapy Catheter ablation Antiarrhythmics (usually class I or III)

Raynaud phenomenon Raynaud phenomenon (RP) is an exaggerated vasoconstrictive response of the digital arteries and arterioles(e.g., in the fingers and/or toes) to cold or emotional stress. It is termed primary or secondary based on the underlying cause. The etiology of primary RP is poorly understood. Secondary RP, on the other hand, is caused by underlying systemic diseases (e.g., mixed connective tissue disease, vasculitides, hematologic abnormalities). Both types typically present with the sequential discoloration of fingers and/or toes from white (ischemia) to purplish-blue (hypoxia) to red (reactive hyperemia). Episodes of vasoconstriction usually end 15-20 minutesafter the trigger is removed, and last no longer than an hour following adequate warming or stress reduction. Secondary RP may be accompanied by complications of underlying diseases and/or trophic disorders. Management involves the treatment of any underlying conditions, avoidance of situations that may trigger an attack, and calcium channel blockers (e.g., nifedipine, diltiazem). Rubefacients, or vasoactive agents, are indicated in severe cases.

Etiology Cold and emotional stress are common triggers of vasospastic attacks in patients with primary or secondary RP. Occurs more commonly in women. Primary RP (also called Raynaud disease) Idiopathic genesis, without any identifiable organic vascular change, leading to vasospasms of the digital arteries and arterioles. Onset usually < 30 years of age Secondary RP (also called Raynaud syndrome) Organic arterial changes in the fingers (and/or toes) that lead to vasospasm, which may be caused by:Drugs: beta-blockers, ergotamine, bleomycinSmokingOccupational trauma: from handling vibrating tools, typingHyperviscocity: polycythemia, paraproteinemias (plasmacytoma, Waldenstrom's disease), cryoglobulinemia, cold agglutinin diseaseVasculitides: e.g., Buerger's diseaseConnective tissue diseases: e.g., scleroderma , systemic lupus erythematosus, mixed connective tissue disease, Sjögren's syndromeArterial disease: e.g., peripheral artery diseaseFrostbiteNeurological disease: e.g., carpal tunnel syndrome, intervertebral disc diseasePulmonary hypertension Onset usually ≥ 30 years of age Clinical features ManifestationIschemic phase (white): exposure to trigger (e.g., cold) → vasoconstriction of digital arteries and arterioles→ ischemia and pallorSometimes accompanied by pin-and-needles sensation, numbness, or pain Hypoxic phase (blue): low oxygen supply → cyanosis Hyperemic phase (red): rewarming or removal of stressor leads to recovery and reperfusion → erythema Livedo reticularis might occur during attacks Primary Raynaud phenomenon Attacks typically occur symmetrically No ulcerations/necrosis Secondary Raynaud phenomenon Attacks typically occur asymmetrically Evidence of severe pain and ulcerations Possibly systemic manifestations of the primary disease LocationMost commonly the fingers and toesRarely the nose, ears, nipples, and lips Duration: Spasms are usually reversible, typically lasting 15-20 minutes after removing the trigger, but may last for up to an hour. Irreversible ischemia with tissue damage indicates secondary RP and requires further investigation to identify the underlying cause! Diagnostics While primary RP is primarily a clinical diagnosis, additional testing is required to diagnose secondary RP. Differentiating between the two types enables the practitioner to identify and assess the severity of any possible underlying condition. Patient history Assessment of patient history focuses on: onset of symptoms, triggers of attacks, time course, pattern of attacks, accompanying symptoms (pain, paresthesias), and impairment of everyday life. See "Etiology" and "Symptoms/Clinical findings" above. Bedside test Allen test Nailfold capillary microscopy Important means of distinguishing primary from secondary RP Primary RP: normal capillaroscopic patternSecondary RP: abnormal capillaroscopic pattern. Laboratory tests All values typically normal in primary RP In suspected secondary RP, analyses should focus on diagnosis of underlying diseases. Abnormal CBCAbnormal plasma viscosity↑ Infection parameters (CRP, ESR)↑ Antibody serology: e.g., antinuclear antibody (ANA) Differential diagnoses Acrocyanosis Erythromelalgia Peripheral artery disease (PAD) Acute arterial occlusion of an extremity Treatment The general approaches to primary and secondary RP are similar. However, in cases of secondary RP, the underlying condition should also be treated. General measures Avoid triggers: dampness, cold , emotional stress Stop smoking Adjust medication (discontinue drugs that may cause attacks: e.g., beta-blockers, ergotamine, oral contraceptives) Medical therapy First‑line: calcium channel blockers; the drug of choice is nifedipine administered orally Second‑line: Topical agents to increase perfusion (e.g., topical nitroglycerin)Off-label therapy with orally administered vasoactive agents: prostacyclin analog (e.g., iloprost), SSRIs(e.g., fluoxetine), PDE5 inhibitors (sildenafil, tadalafil, vardenafil), endothelin receptor antagonists(bosentan) Complications Trophic disorders (rare in primary RP) Other systemic complications of underlying disease in secondary RP

Thoracic outlet syndrome Thoracic outlet syndrome (TOS) is an umbrella term for conditions involving the compression of neurovascular structures (e.g., the brachial plexus or the subclavian artery or vein) as they pass from the lower neck to the armpit. Causes include trauma, tumors, or the presence of a cervical rib. Neurogenic TOS is the most common type and involves the compression of the brachial plexus, leading to neck pain and numbness and tingling in the fingers. Arterial TOS involves compression of the subclavian artery and presents with pain, pallor, coldness, and pulselessness in the affected arm, especially during overhead activities. Venous TOS results in pain, cyanosis, and swelling of the arm. Imaging techniques such as duplex sonography, X-ray, MRI, or electrodiagnostic testing are used to detect the cause of TOS. Mild symptoms should be treated with pain medication and physical therapy. Surgical resection of the causal structures might become necessary in the case of progressive neurologic dysfunction or acute vascular insufficiency

Etiology Compression of subclavian vessels and the lower trunk Physical trauma (e.g. hyperextension neck injuries) Repetitive motion of the abducted and externally rotated shoulder (e.g. tennis, baseball, swimming, repetitive throwing, carrying heavy objects overhead) Structural abnormalitiesBones: anomalous cervical rib , collarbone fracture, exostoses of the first rib or collarbone Soft tissue: hypertrophic muscles in athletes and weight lifters, poor posture and obesity, hematoma, tumors (e.g., Pancoast tumor) Clinical features Clinical features of TOS depend on the anatomic structure affected by compression and are more pronounced during and after overhead activity. Compression of the subclavian arteryMild arm ache and fatiguePulselessness, pain, pallor, paresthesia and coldness in the affected arm (5 Ps) ↓ Blood pressure of > 20 mm Hg in the affected arm compared with the contralateral arm Compression of the subclavian veinSwellingVenous distentionDiffuse hand or arm painHeavinessRisk of thrombosis of the arm (Paget-Schroetter disease) Compression of parts of the brachial plexusSensory loss or paresthesia Pain in the neck and armAtrophy of hand muscles (Gilliatt-Sumner hand) Swelling and venous distention in the arm may be a sign of venous thrombosis of the arm! Diagnostics Radiographs of the spine, shoulder, collarbone → bony abnormalities CT or MRI imaging mainly to exclude other conditions that present similarly . Other tests depend on suspected underlying pathology Arterial TOS → MR angiographyVenous TOS → duplex ultrasonographyNeurogenic TOS → electromyography/nerve conduction studies Treatment In mild cases: physical therapy , weight reduction, NSAIDs, thrombolytics with continued anticoagulation in the case of venous thrombosis In cases of acute vascular insufficiency or progressive neurologic dysfunction, or if conservative treatment fails: thoracic outlet decompression surgeryTransaxillary resection of the cervical rib or first ribAngioplasty or venous or arterial bypass for severely narrowed vessels

Sinus node dysfunction Sick sinus syndrome (SSS) refers to the dysfunction of the sinoatrial node and is responsible for several types of arrhythmia. It comprises bradyarrhythmias (e.g., sinus bradycardia, sinoatrial pauses, blocks, and arrest), and may alternate with supraventricular tachyarrhythmias, in which case it is referred to as tachycardia-bradycardia syndrome. The most common SSS arrhythmias are sinus bradycardia and non-respiratory sinus arrhythmia. SSS typically occurs in the elderly. Depending on the extent of bradycardia or tachycardia, the condition may be asymptomatic or present with symptoms such as palpitations or dyspnea. More serious manifestations, such as lightheadedness and syncope, are indications for pacemaker placement.

Etiology Degeneration and fibrosis of the sinoatrial node and surrounding myocardium (most common cause) Medications (e.g., β-blockers, digoxin, non-dihydropyridine calcium channel blockers such as verapamil and diltiazem) Clinical features Symptoms vary or may be entirely absent depending on the extent of bradycardia or tachycardia. Symptoms of bradycardiaDizzinessSyncope, presyncopeLack of increasing heart rate during physical activityAdams-Stokes attacks Tachycardia-bradycardia syndrome presents with additional symptoms: PalpitationsDyspneaAngina pectoris Diagnostics Symptoms or ECG findings may be inconclusive if considered on their own. Therefore, it is very important to establish a correlation between the underlying rhythm and symptom manifestation. ECG: Non-respiratory sinus arrhythmia, bradycardia, sinus arrest, sinoatrial pauses, or SA block In cases of tachycardia-bradycardia syndrome: atrial tachycardia, atrial flutter, or atrial fibrillationHolter monitor: detects bradycardic episodes and sinus pauses Exercise stress testing: shows an inadequate increasing heart rate during physical activity (also called chronotropicincompetence) Atropine challenge test: shows an inadequate increasing heart rate after administration of atropine. Electrophysiology studies: may show prolonged sinus node recovery time. Treatment Management depends on the symptoms of each patient, most notably on the length of sinus pauses. All patients: address reversible causes (e.g., side effects of medication) Asymptomatic patients: no pacemaker placement needed Symptomatic patientsInitial therapy for hemodynamically unstable patients First-line: atropineTemporary cardiac pacingLong-term therapy Isolated symptoms of bradycardia : pacemaker placementTachycardia-bradycardia syndrome requires treatment of both tachycardia and bradycardia. In the case of atrial fibrillation or flutter: The need for anticoagulation should be evaluated (see CHA2DS2-VASc score).Pacemaker placementMedical therapy: e.g., ß1-selective (cardioselective) beta blockers (e.g., metoprolol, bisoprolol)

Pericardial effusion and cardiac tamponade Pericardial effusion is the acute or chronic accumulation of fluid in the pericardial space (between the parietal and the visceral pericardium) and is often associated with a variety of underlying disorders. The fluid can be either bloody (e.g., following aortic dissection) or serous (usually idiopathic). As the pericardium is rather stiff, the capacity of the pericardial space is limited. In chronic effusion, the pericardium can stretch to a certain degree, accommodating slightly more fluid. In the acute setting, however, the added volume quickly exceeds the maximum capacity of the pericardial space. In both cases, the end result is often cardiac tamponade: compression of the heart which can lead to a life-threatening reduction in cardiac output. Pericardial effusion is initially asymptomatic, but cardiac tamponade has a distinct clinical presentation, including hypotension, tachycardia, jugular venous congestion, and pulsus paradoxus. Echocardiography is the most important diagnostic procedure and usually reveals an anechoic pericardial space. Treatment depends on hemodynamic stability: unstable patients require quick pericardial fluid drainage, through either pericardiocentesis or surgery, whereas in stable patients, treatment focuses on the underlying disease.

Etiology HemopericardiumCardiac wall rupture (e.g., complication of myocardial infarction)Chest traumaAortic dissectionCardiac surgery (e.g., heart valve surgery, coronary bypass surgery) Serous pericardial effusionIdiopathicAcute pericarditis (especially viral, but also fungal, tuberculous or bacterial)MalignancyPoststernotomy syndromeUremicAutoimmune disordersHypothyroidism Pathophysiology Limited elasticity of the pericardium → ∼ 150-200 mL of fluid → ↑ pressure in pericardial space → compression of the heart, especially of the right ventricle due to a thinner wall → interventricular septum shifts towards the left ventriclechamber → ↓ ventricular diastolic filling → ↓ stroke volume (+ venous congestion) → ↓ cardiac output Clinical features Usually initially asymptomatic Shortness of breath, especially while lying down (orthopnea) Beck's triadHypotensionMuffled heart soundsDistended neck veins Tachycardia, pulsus paradoxus Retrosternal chest pain Apical impulse difficult to locate or nonpalpable Pallor, cold sweats Symptoms of left heart failure and symptoms of right heart failure Cardiogenic shock, asystole Beck's triad for cardiac tamponade: hypotension, muffled heart sounds, distended neck veins! Diagnostics Echocardiography (gold standard) Anechoic space between pericardium and epicardiumReduced ejection fractionReduced wall motion CXR: enlarged cardiac silhouette, clear lungs, in severe cases a globular "water bottle-shaped" heart contour (water bottle sign) ECGLow voltageElectric alternans Pericardial fluid drainage: used to sample the effusion in cases of unclear etiology Echocardiography is a quick and safe diagnostic tool for detecting pericardial effusions and pericardial tamponade! Treatment Hemodynamically unstable Pericardial fluid drainage: ultrasound-guided pericardiocentesis or surgical drainage Subsequent surveillance in an intensive care unit (ICU) Acute pericardial effusion with pericardial tamponade is a life-threatening condition, requiring immediate pericardialdecompression! Hemodynamically stable Treatment of underlying cause Pericardial window: an incision in the pericardium is made that allows continual drainage from the pericardial spaceinto the pleural cavity to prevent a cardiac tamponadeCommonly indicated for effusion due to underlying malignancy Hemodynamic monitoring

Premature ventricular contractions Premature ventricular contractions (PVCs) are extra, abnormal heartbeats caused by ectopic foci within the ventricles. PVCs are very common and most individuals are asymptomatic, but select patients may present with symptoms such as dizziness or palpitations. Typical ECG findings of PVCs include broad QRS complexes, compensatory pauses, and axis deviation, and may be random or have consistent patterns, such as couplets or bigeminy. Most patients do not require treatment. However, any underlying condition, e.g., myocarditis, must be managed appropriately. Patients with frequent PVCs that cause significant symptoms should receive antiarrhythmic drugs or possibly catheter ablation, as they are at risk for sudden cardiac death.

Etiology Idiopathic Cardiovascular disease (e.g., CAD, myocarditis) Electrolyte imbalances (e.g., hypokalemia, hypomagnesemia) Side effect of certain drugs (e.g., digoxin, psychiatric medications) Caffeine, alcohol Classification Monomorphic PVC: Each PVC has the same configuration → identical origin Polymorphic PVC: PVCs have different configurations → multiple foci Clinical features Most patients are asymptomatic. Skipped beat If frequent PVCs, possibly → lightheadedness, dizziness, palpitations, irregular heartbeat Diagnostics If patient suspected of PVCs → evaluate with ECG → if confirmed, rule out underlying disease (e.g., echocardiography, exercise treadmill stress test) with further procedures ECG findings Common ECG characteristics QRS duration ≥ 120 ms with a block-like QRS morphology PVCs are often followed by a compensatory pause May be random or adhere to a specific pattern, including: Single PVCCouplet: two PVCs in a rowTriplet: three PVCs in a rowBigeminy: one extrasystole after every single sinus beatTrigeminy: one extrasystole after every two sinus beats PVCs are a common incidental finding on routine ECGs. The detection of them does not require any further workup in patients who are asymptomatic! Additional procedures Only indicated in case of frequent, symptomatic PVCs 24-hour Holter monitor Exercise stress test Echocardiography Treatment Most patients do not require any treatment Treat any underlying disease (e.g., CAD, myocarditis) Only treat frequent and significantly symptomatic PVCsAntiarrhythmic therapyCatheter ablation if antiarrhythmic therapy fails

Supraventricular premature beats Supraventricular premature beats are atrial contractions triggered by ectopic foci rather than the sinoatrial node. They arise within the atria (atrial premature beats) or, through retrograde conduction, in the atrioventricular node (junctional premature beats). Premature beats may be found in healthy individuals as well as patients with underlying heart disease. Certain triggers, e.g., alcohol, smoking or electrolyte imbalances, may also contribute to the condition. Premature beats do not significantly impair cardiac output on their own; however, they may lead to more severe forms of arrhythmia such as atrial fibrillation. Unless patients exhibit severe symptoms (e.g., tachycardia), those experiencing premature beats do not require treatment.

Etiology Idiopathic Potential triggers: smoking, alcohol, coffee Cardiovascular disease or electrolyte imbalances (e.g., hypokalemia) Classification Atrial premature beats Definition: extrasystole that originates in the atrial myocardium and occurs prior to the expected QRS complex Typical findings on ECGP-wave abnormalities or absent P waves Altered PR interval in the premature beats (compared to the normal beats) QRS complex may be normal, aberrant (widened), or absent No full compensatory pause Junctional premature beats Definition: premature beat that occurs prior to the expected QRS complex and that originates between the atria and ventricles Typical findings on ECGNegative P wave Narrow QRS complex No compensatory pause Clinical features Usually asymptomatic Palpitations Diagnostics ECG: identify supraventricular premature beats (SPBs) Echocardiography: to rule out structural heart disease and evaluate cardiac structure and function if SPBs are identified on ECG or Holter monitor Further work-up: if structural abnormalities are present Treatment Treatment is not required in asymptomatic individuals without underlying structural heart defects. Underlying conditions, e.g., electrolyte imbalances, should be treated. Symptomatic patients Advise patients to reduce potential triggers like caffeine, alcohol, stress and smoking.Beta blockers or catheter ablation in patients with persistent symptoms

Mitral valve stenosis Mitral stenosis (MS) is a valvular anomaly of the mitral valve that leads to obstruction of blood flow into the left ventricle. The most common cause of MS is rheumatic fever. The clinical manifestations depend on the extent of stenosis: reduced mitral opening leads to progressive congestion behind the stenotic valve. Initial dilation of the left atrium (complications: atrial fibrillations, emboli) is followed by progressive congestion of the lungs and subsequent cardiac asthma (coughing, dyspnea). Acute decompensation can cause pulmonary edema. Echocardiography is the main diagnostic tool for evaluating the mitral valve apparatus, left atrial size, and pulmonary pressure. In the event of high grade and/or symptomatic stenosis, percutaneous valvuloplasty or surgical valve replacement is often required.

Etiology Most commonly due to rheumatic fever Autoimmune diseases: systemic lupus erythematosus, rheumatoid arthritis Congenital Some conditions may mimic mitral stenosis: bacterial endocarditis of the mitral valve with large vegetation, left atrial myxoma Degenerative aortic stenosis Pathophysiology Mitral valve stenosis → obstruction of blood flow into the left ventricle (LV) → limited diastolic filling of the LV (↓ end-diastolic LV volume) → decreased stroke volume → decreased cardiac output (forward heart failure) Mitral valve stenosis → increase in left atrial pressure → backup of blood into lungs → increased pulmonary capillarypressure → cardiogenic pulmonary edema → pulmonary hypertension → backward heart failure and right ventricular hypertrophy Clinical features Initially asymptomatic (onset ∼ 10 years after acute rheumatic carditis) Dyspnea (paroxysmal nocturnal dyspnea) and orthopnea, especially when supine Hemoptysis Atrial fibrillation Later stages: signs and symptoms of right-sided heart failure Diagnostics Auscultation (see auscultation in valvular defects) Diastolic murmur typically heard best at the 5th left intercostal space at the mid-clavicular line (the apex)Heard loudest when the patient is lying on his/her left side. Loud first heart sound (S1) Opening snap of the mitral valve after S2: A high-frequency, early-to-mid diastolic sound that occurs when leaflet motion suddenly stops during diastole after the stenosed valve has reached its maximum opening Shorter interval between S2 and opening snap indicative of more severe disease, because left atrial pressure is greater than left ventricular end diastolic pressure (LVEDP) Chest x-rayPosterior-anterior imageLA enlargement with prominent left auricle (left atrial appendage) → straightening of the left cardiac borderSigns of pulmonary congestion (see X-ray findings in pulmonary congestion)Lateral imageDorsal displacement of the esophagus (visible in barium swallow test)Signs of right ventricular hypertrophy ECGP mitraleAtrial fibrillationSigns of right ventricular hypertrophy (Sokolow-Lyon index) Echocardiography: most important diagnostic method for detecting and assessing valvular abnormalitiesAbnormal valve mobilitySubvalvular thickeningLeaflet thickeningCalcification Coronary angiography may be conducted prior to surgical interventions to assess the associated risk of coronary artery disease Treatment Conservative treatmentTreatment of heart failure: only diuretics may be administered!Beta blockers or calcium channel blockers: ↓ heart rate and ↓ cardiac output Endocarditis prophylaxis (see "Infective endocarditis") InterventionalIndication: high grade and/or symptomatic mitral stenosisFirst-line: percutaneous balloon commissurotomy of the mitral valveAlternatives: open commissurotomy and surgical valve replacement (mechanical prosthetic valve or biological prosthetic valve) ACE inhibitors and other afterload-reducing drugs are contraindicated because they cause dilation of peripheral blood vessels, which may lead to cardiovascular decompensation! Complications Atrial fibrillation → thromboembolic events Progressive congestion of the lungs, pulmonary edema, pulmonary hypertension Congestive heart failure Enlarged left atrium (rare) → esophageal compression, recurrent laryngeal nerve palsy

Atrioventricular block Atrioventricular block (AV block) is characterized by an interrupted or delayed conduction between the atria and the ventricles. AV blocks are divided into three different degrees depending on the extent of the delay or interruption. First-degree blocks are identifiable on ECG by a prolonged PR interval. Most patients with first-degree block are asymptomatic, and the condition is usually an incidental finding. Second-degree AV blocks are further divided into two different subtypes. Mobitz type I, or Wenckebach, blocks exhibit a progressive prolongation of the PR interval that culminates in a non-conducted P wave ("dropped beat"). Most patients with Mobitz type I blocks are asymptomatic. The Mobitz type II block generates dropped QRS complexes at regular intervals (e.g. 2:1, 3:1, or 3:2), often leading to bradycardia. Symptoms of patients with Mobitz type II block range from fatigue to dyspnea, chest pain, and/or syncope. This fixed second-degree block frequently progresses to a third-degree block. A third-degree AV block involves total interruption of the electrical impulse between the atria and ventricles. The complete absence of conduction results in a ventricular escape mechanism, which may be dangerously slow and result in life-threatening bradycardia or Stokes-Adams attacks. Therefore, a third-degree AV block is an absolute indication for pacemaker placement.

Etiology Physiological: ↑ vagal tone PathophysiologicalIdiopathic fibrosis of the conduction systemIschemic heart diseaseCardiomyopathy (e.g., due to amyloidosis or sarcoidosis)Infections (e.g., Lyme disease, bacterial endocarditis)Hyperkalemia (> 6.3 mEq/L) IatrogenicSide effect of certain drugs (e.g.,beta blockers, calcium channel blockers, digitalis) Cardiac interventions (e.g., surgery, alcohol septal ablation) First-degree AV block Definition PR interval > 200 ms No interruption in atrial to ventricular conduction Rate of SA node = heart rate Characteristics May be found in healthy individuals, e.g., in athletes with ↑ vagal tone Usually asymptomatic Often discovered incidentally on ECG Treatment Clinical assessment for underlying diseases (e.g., structural heart diseases, electrolyte imbalances) Usually no specific treatment necessary Follow-ups to evaluate progression of the disease Pacemaker If the patient also exhibits wide QRS complexes on ECG → identify the level of AV block (within or below the bundle of His) using intracardiac electrogram → if conduction time from the bundle of His to the ventricles is > 100 ms: pacemaker placement Patients with neuromuscular disease (e.g., Kearns-Sayre syndrome, myotonic muscular dystrophy) Symptomatic patients: unpleasant awareness of the heartbeat due to loss of atrioventricular synchrony (pacemaker syndrome) Second-degree AV block Mobitz type I/Wenckebach Definition Progressive lengthening of the PR interval until a beat is dropped; regular atrial impulse does not reach the ventricles (a normal P wave is not followed by a QRS-complex) Rate of SA node > heart rate; mostly regular rhythm separated by short pauses, which may lead to bradycardia Symptoms/clinical findings Usually asymptomatic May present with symptoms of reduced cardiac output, resulting in hypoperfusion (e.g., dizziness, syncope) and bradycardia Irregular pulse Treatment Asymptomatic patients Clinical assessment for underlying diseases (e.g., structural heart diseases, electrolyte imbalances)Usually no specific treatment necessaryFollow-ups (ECG and cardiac monitoring) to evaluate progression of the disease Symptomatic patients Hemodynamically stable Monitoring with transcutaneous pacing padsIf symptoms not reversible → placement of a permanent pacemakerHemodynamically unstable AtropineTemporary cardiac pacing (if not responsive to atropine) Mobitz type II Definition Single or intermittent non-conducted P waves without QRS complexes The PR interval remains constant. The conduction of atrial impulses to the ventricles follows regular patterns: 2:1 block: regular AV block that inhibits conduction of every other atrial depolarization (P wave) to the ventricles (heart rate = ½ SA node rate)3:1 block: regular AV block with 3 atrial depolarizations but only 1 atrial impulse that reach the ventricles (heart rate = ⅓ SA node rate)3:2 block: regular AV block with 3 atrial depolarizations but only 2 atrial impulses that reach the ventricles (heart rate = ⅔ SA node rate)Symptoms/clinical findings Bradycardia → ↓ cardiac outputFatigueDyspneaChest painDizziness, syncope Treatment Hemodynamically stable patients: Monitoring with transcutaneous pacing padsClinical assessment for underlying diseases (e.g., structural heart diseases, electrolyte imbalances)If symptoms are not reversible → placement of a permanent pacemaker Hemodynamically unstable patients: AtropineTemporary cardiac pacing The second-degree AV block Mobitz type II may progress to a third-degree block and is an unstable condition that requires monitoring and treatment! Third-degree AV block Definition Third-degree AV block is a complete block with no conduction between the atria and ventricles. AV dissociation: on ECG, P waves and QRS complexes have their own regular rhythm but bear no relationship to each other A ventricular escape mechanism is generated by sites that are usually located near the AV node or near the bundle of His. The more distant the site of impulse generation: The slower the ventricular escape mechanismThe wider and more deformed the QRS complexBlock proximal to bundle of His: narrow QRS complexesBlock distal to bundle of His: wide QRS complexesThe worse the prognosis Sudden onset of a third-degree AV block results in asystole, which lasts until the ventricular escape mechanism takes over. This asystole may lead to Stokes-Adams attacks. Symptoms/clinical findings Symptoms depend on: Rate of ventricular escape mechanism Bradycardia (< 40 bpm) with cerebral hypoperfusion (fatigue, irritability, apathy, dizziness, syncope, cognitive impairment), heart failure, dyspnea Length of asystole Nausea, dizzinessStokes-Adams attacks Cardiac arrest Treatment Hemodynamically stable patients: Monitoring with transcutaneous pacing padsClinical assessment for underlying diseases (e.g., structural heart diseases, electrolyte imbalances)No reversible causes → placement of a permanent pacemaker Hemodynamically unstable patients: Temporary transcutaneous or transvenous cardiac pacingIn the event of low blood pressure, administer dopamine.In the event of heart failure, administer dobutamine.

Mitral regurgitation Mitral regurgitation (MR) refers to the leakage of blood from the left ventricle to the left atrium due to incomplete closure of the mitral valve. The most common causes are primary diseases of the valve (e.g., mitral valve prolapse), although damage may also result secondary to other heart conditions such as left ventricular dilation and myocardial infarction. Symptoms such as palpitations or dyspnea appear late in the course of chronic compensated MR in which cardiac outputcan still be maintained. In acute or chronic decompensated MR, pulmonary edema and pulmonary hypertension often cause dyspnea, coughing, jugular venous distention, and pitting edema. Echocardiography is the most important diagnostic tool and allows for assessment of severity. It may also be used for preoperative evaluation. Treatment options include surgical mitral valve repair or replacement and percutaneous reconstruction. Early intervention is favored in most cases of MR with evidence of left ventricular dysfunction, regardless of symptoms.

Etiology Primary MR Degenerative mitral valve disease (mitral valve prolapse, mitral annular calcification, ruptured chordae tendineae)Rheumatic feverInfective endocarditis Secondary (functional) MR Coronary artery disease, prior myocardial infarction causing papillary muscle involvement Dilated cardiomyopathy and left-sided heart failure Pathophysiology Acute MR → ↑ LV end-diastolic volume → rapid ↑ LA and pulmonary pressure → pulmonary venous congestion → pulmonary edema Chronic (compensated) MR: progressive dilation of the LV (via eccentric hypertrophy) → ↑ volume capacity of the LV (preload and afterload return to normal values) → ↑ end-diastolic volume → maintains ↑ stroke volume (normal EF) Chronic (decompensated) MR: progressive LV enlargement and myocardial dysfunction → ↓ stroke volume → ↑ end-systolic and end-diastolic volume → ↑ LV and LA pressure → pulmonary congestion, possible acute pulmonary edema, pulmonary hypertension, and right heart strain Clinical features Acute mitral regurgitationSymptoms of left-sided heart failureSigns and symptoms of pulmonary edemaCardiogenic shock Chronic mitral regurgitation: late onset of symptoms(Exertional) dyspnea, dry cough PalpitationsSymptoms of left-sided heart failure Diagnostics Auscultation See "Auscultation in valvular defects"Quiet first heart sound (S1)S3 gallop in advanced stages of disease Holosystolic murmurRadiates to the left axilla and heard loudest over the apex (5th ICS at the left mid-clavicular line)Intensity increases with increased systemic vascular resistance (hand grip, squatting)Cardiac impulse is often prominent ECGLeft cardiac hypertrophy and P mitraleLater, signs of right heart strain with P pulmonale Chest X-rayPosterior-anterior image LV enlargement: laterally displaced left cardiac border LA enlargement: straightening of the left cardiac border Signs of pulmonary congestion in late stages of disease (see "X-ray findings in pulmonary congestion") Lateral image: Narrowing of the retrocardiac space Echocardiography: most important diagnostic method for detecting and assessing valvular abnormalitiesValve apparatus (e.g., dimensions of valve opening area, calcification, rupture of the chordae tendineae) and mobilityLV and LA size and function Coronary angiography: prior to surgical intervention Myocardial infarction must be ruled out in patients presenting with acute MR! reatment Acute mitral regurgitationHemodynamic stabilization: diuretics, nitrates, antihypertensive drugsIntra-aortic balloon pump if pharmacologic management is insufficientUrgent surgical valve repair or replacement Chronic mitral regurgitationAsymptomatic patients Without evidence of LV dysfunction (EF > 60%): conservative management (regular follow-ups, avoidance of physical exertion), management of underlying and/or secondary diseasesWith evidence of LV dysfunction (EF < 60%): early surgical valve repair or replacementSymptomatic patients Without evidence of severe LV dysfunction (EF > 30%): early valve repair or replacement (mechanical prosthetic valve or biological prosthetic valve)With severe LV dysfunction (EF < 30%): surgical valve repair or replacement only if the patient is hemodynamically stable ;Alternatives for severe LV dysfunction: Percutaneous reconstruction Medical management of heart failure Complications Heart failure, cardiac decompensation, and pulmonary edema Atrial fibrillation and arterial emboli Endocarditis

Deep vein thrombosis Deep vein thrombosis (DVT) is the formation of a blood clot in a deep vein of the legs, thigh, or pelvis. Thrombosis is most often seen in individuals with a history of immobilization, obesity, malignancy, or hereditary thrombophilia. Vascular endothelial damage, venous stasis, and hypercoagulability, collectively referred to as the Virchow triad, are the main factors contributing to the development of DVT. Symptoms usually occur unilaterally and include swelling, tenderness, and redness or discoloration. Pulmonary embolism (PE), a severe complication of DVT, should be suspected in patients with dizziness, dyspnea, and fever. The diagnostic test of choice for DVT is compression ultrasound. In most cases, a negative D-dimer test allows thrombosis or PE to be ruled out, but a positive test is nonspecific. Initial acute treatment of DVT consists of anticoagulation with heparin and, if the thrombus is large or unresponsive to anticoagulation, may also include thrombolysis or thrombectomy. Secondary prophylaxis is achieved with oral warfarin or direct factor Xa inhibitors and supportive measures such as regular exercise and compression stockings.

Etiology Risk factors for deep vein thrombosis History of DVT or PE (30x increased risk) [1] Immobilization: e.g., post-surgery, long-distance flights, trauma (20x increased risk) Age > 60 years Malignancy Hereditary thrombophilia (especially factor V Leiden) Pregnancy, estrogen use (oral contraceptives) Obesity Smoking IV drug use Nephrotic syndrome Insufficient thrombosis prophylaxis, noncompliance with prophylaxis Pathophysiology The Virchow triad The Virchow triad refers to the three main pathophysiological components of thrombus formation. Hypercoagulability: increased platelet adhesion, increased clotting tendency (thrombophilia) Endothelial damage: inflammatory, traumatic Venous stasis: varicosis, external pressure on the extremity, immobilization, local application of heat Clinical features May be asymptomatic Localized unilateral symptoms Typically affects deep veins of the legs, thighs, or pelvisMore common in the left lower extremity May-Thurner syndrome: compression of the left iliac vein between the right iliac artery and a lumbar vertebral spur (occurs in > 20% of adults) [6][7]Swelling, feeling of tightness or heavinessWarmth, erythema, and possibly livid discolorationProgressive tenderness, dull pain Homan sign: calf pain on dorsal flexion of the foot Meyer sign: Compression of the calf causes pain.Payr sign: pain when pressure is applied over the medial part of the sole of the footDistention of superficial veins Distal pulses are normal General symptoms: fever [8] Possible signs of pulmonary embolism: dyspnea, chest pain, dizziness, weakness Subtypes and variants Phlegmasia cerulea dolens Definition: a severe form of phlebothrombosis, characterized by obstruction of all veins of one extremity with subsequent restriction of arterial flow and associated with a high mortality SymptomsSevere swelling, edema, and painColdness, cyanosis, and pulselessness TreatmentEmergency surgery: venous thrombectomy, fasciotomyFibrinolysis if surgery failsAmputation as last resort Complications: shock, gangrene, acute renal failure (due to rhabdomyolysis) Paget-Schroetter disease (upper extremity DVT) Definition: acute thrombosis of a brachial, axial, or subclavian vein EtiologyEffort-induced thrombosis: triggered by repetitive strenuous activity of the upper extremities (e.g., weight-lifting, operation of a jackhammer)Thoracic outlet syndromePresence of a foreign object in veins (e.g., central venous catheter, pacemaker lead) Treatment: anticoagulation, fibrinolysis Diagnostics The diagnostic approach for suspected DVT is determined by the Wells score. Compression ultrasonographyand D-dimer levels are the main diagnostic tests. Wells criteria for deep vein thrombosis Medical historyActive cancer+1Previously documented DVT+1ImmobilizationParalysis or recent (cast) immobilization of lower extremity+1Recently bedridden (≥ 3 days) orMajor surgery (< 12 weeks)+1Clinical symptomsTenderness localized along the deep venous system+1Swelling of the entire leg+1Calf swelling ≥ 3 cm compared to asymptomatic calf+1Unilateral pitting edema in symptomatic leg+1Presence of collateral (non-varicose) superficial veins+1Differential diagnosisAlternative diagnosis at least as likely as DVT-2 Interpretation 2 risk group< 2: DVT unlikely (low risk)≥ 2: DVT likely (high risk) Compression ultrasonography with Doppler (test of choice) DescriptionA combination of ultrasonography (to visualize the vein) and Doppler (to assess blood flow abnormalities) in which the examiner applies gentle pressure to normally compressible veins using an ultrasound probeHigh sensitivity and specificity in the popliteal and femoral veins, but very operator dependent Indications: clinical suspicion of a DVT or pulmonary embolism Findings: noncompressibility of the obstructed vein, visible hyperechoic mass, absent or abnormal flow in Doppler imaging D-dimer testing High sensitivity (∼ 95%), low specificity (∼ 50%) Useful for ruling out DVT (normal D-dimer levels rule out DVT) Elevated D-dimers alone are not proof of DVT. Further diagnostic tests Venography (angiography) Most accurate assessment of calf veins and valvular competency Indications: obesity, severe edema, equivocal results in previous tests CT scan: suspected pulmonary embolism or underlying malignancy Thrombophilia screening (coagulation studies) Indications: young patients, unusual thrombus localization, positive family historyAt earliest, tests should be performed 2 weeks after discontinuing anticoagulation. General tumor screeningIndications: idiopathic thrombosis (esp. patients > 50 years)Tests: CBC, renal function tests, liver function tests, urinalysis, and chest x-rayEnsure that patient is up-to-date on all age-appropriate cancer screening (e.g., colonoscopy, mammogram, digital rectal exam) Differential diagnoses Superficial thrombophlebitis Definition: Inflammation and thrombosis of a superficial vein, most commonly in the leg. It may co-exist with DVT, and it rarely causes PE. Risk factors: same as for DVT (see risk factors for deep vein thrombosis above), but also Varicose veins Venous cannulation, IV drug administrationBehçet diseaseThromboangiitis obliterans [19] VariantsThrombophlebitis migrans (Trousseau syndrome)Superficial thrombophlebitis of the breast (Mondor disease) Clinical features: pain, tenderness, induration, and erythema overlying a superficial vein, often with a palpable cord (the thrombosed vein) DiagnosticsTypically a clinical diagnosisDuplex ultrasoundIndicated if the clinical diagnosis is not clearFindings: A thickened, edematous, noncompressible vessel with or without an intraluminal thrombusTests to diagnose the underlying cause: See "Further diagnostic tests" under "Diagnostics" above. TreatmentSymptomatic: NSAIDs, compression, elevation of the affected limb Anticoagulation (e.g., LMWH, fondaparinux) if larger segments of the vein (≥ 5cm) are affectedDVT treatment if the thrombus is close to the junction with the deep venous system (see "Treatment" below) ComplicationsExtension into the deep veins → DVTInfection (septic thrombophlebitis)Distal embolization (PE) Other differential diagnoses of DVT Muscle or soft tissue injury (i.e., posttraumatic swelling or hematoma) Lymphedema Venous insufficiency Ruptured popliteal cyst Cellulitis Compartment syndrome Treatment Anticoagulation Acute therapyHeparin bolus plus constant heparin infusion for 4-5 daysUnfractionated heparin or low molecular weight heparin (see also parenteral anticoagulation)Alternatively: fondaparinux (factor Xa inhibitor)Target: Achieve and maintain an aPTT of 1.5x-2.5x the mean of the control value or upper normal limit.Simultaneous initiation of warfarin once aPTT is therapeutic Secondary prophylaxisWarfarin with target therapeutic INR of 2.0-3.0 Duration of treatment First thrombosis: usually 3-6 months For confirmed thrombophilia and recurrent thrombosis: indefiniteOR direct oral factor Xa inhibitor (i.e., rivaroxaban, apixaban)Regular monitoring of coagulation parameters not required → improved patient complianceDuration of treatment: at least 3 months Additional therapy ThrombolysisGoal: faster resolution of thrombiIndications Slow response to anticoagulationPulmonary embolism with hemodynamic instabilityCan be considered for acute proximal DVT of the leg Agents: streptokinase, urokinase, tissue plasminogen activatorCatheter-directed thrombolysis: The thrombolytic agent is administered directly at the site of obstruction via a venous catheter. ThrombectomyIntravenous thrombus removal via a catheterIndications Insufficient response to anticoagulation and thrombolysisExtensive thrombusPhlegmasia cerulea dolensLow-dose heparin is required prior to the procedure. Inferior vena cava filter (Greenfield filter): indicated in patients with DVT at high risk of developing pulmonary embolism who have contraindications to anticoagulation, thrombolysis, and thrombectomy (e.g., active bleeding, recent major surgery, recent intracranial hemorrhage) Compression therapy with bandages or compression stockings Early mobilization as early as tolerated, minimize bedrest. Complications Pulmonary embolism Postthrombotic syndrome (chronic venous insufficiency) Prevention Preventive measuresRegular exercise Early mobilization (e.g., post-surgery)Compression stockings and intermittent compression (Postoperative) anticoagulation with LMWH or unfractionated heparin (see parenteral anticoagulation)Avoid certain medications (e.g., OCPs) in patients with thrombophilia (e.g., factor V Leiden) Indications (based on assessment of risk factors; see "Etiology" above) Low thrombosis risk: exercise, compression stockingsMedium and high thrombosis risk: anticoagulation treatment

Ventricular fibrillation Ventricular fibrillation ("VF" or "V-fib") is a life-threatening cardiac arrhythmia characterized by disorganized, high-frequency ventricular contractions that result in diminished cardiac output and hemodynamic collapse. V-fib usually begins with ventricular tachycardia and appears as a very irregular rhythm with indiscernible P waves or QRS complexeson ECG. The most common underlying condition is coronary artery disease, but V-fib may also be caused by other cardiovascular diseases or external factors (e.g., drugs, electricity). V-fib is frequently preceded by ventricular flutter("V-flut"), which features very rapid sinusoidal QRS complexes that can not be distinguished from T waves. Some patients with V-fib may present with early signs, including chest pain, palpitations, and dizziness. However, V-fib usually causes sudden hemodynamic instability that results in loss of consciousness and, ultimately, sudden cardiac death. Therefore, immediate defibrillation and resuscitation are vital for survival.

Etiology Underlying cardiovascular disease Most common: coronary artery disease (CAD)Others: previous myocardial infarction, myocarditis, cardiomyopathy, severe congestive heart failure, heart valve disease Congenital heart defects (e.g., pulmonary atresia) Electrophysiologic disorders Wolff-Parkinson-White syndromeLong-QT syndrome → torsade de pointes Pathophysiology Normal electrical conduction can be disrupted by re-entry → chaotic, circulating excitation of the myocardium (= ventricular fibrillation) → simultaneous contractions at multiple foci → insufficient cardiac output → hemodynamic collapse → loss of consciousness and possibly death (sudden cardiac death) Re-entry can be caused by Changes to the conduction pathway (e.g., unexcitable scar tissue as a result of past myocardial infarction)Abnormal pattern of excitation, for example: If the period of activation and recovery of myocardial cells becomes greater than the duration of an action potential (as in long-QT syndrome)If excitation occurs outside of the normal pattern of activation (premature ventricular complex, PVC ) Clinical features Possible early signs Chest painPalpitationFatigueShortness of breathDizziness Ultimately: loss of consciousness, death Diagnostics ECG findings Ventricular fibrillation Commonly preceded by ventricular tachycardiaGeneral appearance Arrhythmic, fibrillatory baseline, usually > 300 bpmErratic undulations with indiscernible QRS complexesNo atrial P waves Ventricular flutter: ventricular rates of ∼ 240-300 bpmFrequently transitions to V-fib Evaluation of underlying conditions Conducted during or directly after initial management of patients ECG: specific findings may indicate underlying condition (see above) LaboratoryCardiac enzymes Electrolytes TSH Drug levels and toxicology screen Arterial blood gases ImagingCoronary angiography Echocardiography Nuclear imaging Treatment Resuscitation for V-fibAdvanced Cardiac Life Support (ACLS)If V-fib does not respond to the standard ACLS protocol (refractory V-fib), consider administration of lidocaine, procainamide, or magnesium Post-resuscitation careIntensive care monitoring Control/management of vital signs and removal of acute metabolic imbalances (e.g., electrolyte disturbances)Mild therapeutic hypothermia Maintain application of antiarrhythmics that were used during successful resuscitation (usually IV amiodarone or IV lidocaine)Consider administration of beta blockers Treat underlying causes (e.g., treatment of CAD)ICD (implantable cardioverter-defibrillator) in patients without a readily reversible or treatable cause and/or with a high risk of recurrent, hemodynamically significant V-fib

ECG Electrocardiography (ECG) is an important diagnostic tool in cardiology. ECG uses external electrodes to measure the electrical conduction signals of the heart and record them as characteristic lines. These lines allow the axis, rate, and rhythm, as well as the amplitudes of specific parts of the heart (e.g., the P wave, PR interval, QRS complex, ST segment) to be examined-all important interpretive criteria. This learning card provides an overview of the most essential components of the ECG.

General Leads: A 12-lead ECG with six limb leads (I, II, III, aVL, aVF, aVR ) and six precordial leads (V1-V6) is standard. Interpretation of the limb leadsI → left ventricle, lateral wallII, III, and aVF → left ventricle, inferior wall (inferior ECG leads)aVL → left ventricle, high part of the lateral wallaVR → reciprocal of the left lateral side leads (II, aVL, V5 and V6)Interpretation of the precordial leadsV1 and V2 → both ventricles, anterior wallV3 and V4 → anterior wall of the left ventricle and parts of the septumV5 and V6 → lateral wall of the left ventricle and apex of the heart Paper speedA paper speed of 25 mm/s is usually used in the United States: 1 mm = 0.04 s Alternatively, in other countries a paper speed of 50 mm/s is used: 1 mm = 0.02 s Amplitude: 1 mm (vertical) = 0.1 mV If you don't pay attention to the paper speed, it is easy to misinterpret the heart rate or duration of the cardiac cycle! Holter monitor Definition: A continuous, ambulatory battery operated ECG worn by patients for 24-48 hours IndicationsDaily or near-daily symptoms of: SyncopePalpitationsPatients who are unable to use other ambulatory ECG monitoring devicesAssessing effect of new atrial fibrillation rate control medication (e.g., metoprolol)Screening for ventricular ectopy in high-risk patients (e.g., cardiomyopathy, acute coronary syndrome) Common metricsAverage, minimum, and maximum heart rateNumber of premature beatsEpisodes of arrhythmiaLongest RR interval and any pauses > 3 secondsST segment changesPatient-reported symptomsRepresentative (e.g., hourly) ECG tracing samples Interpretation/findings When interpreting an ECG, it is important to keep the individual patient in mind and, if possible, to compare it with previous ECGs. A thorough, algorithmic approach to ECG interpretation that assesses every aspect of the ECG ensures that no abnormalities are overlooked. Determination of heart rate and rhythm Determination of the heart rate The heart rate (i.e., the pulse felt on physical exam) can be calculated by assessing the QRS complexes on ECG (correlating with ventricular systole). The atrial rate is sometimes calculated (e.g., in assessing some supraventricular arrhythmias). ImplementationIf the QRS rhythm is regular (see determination of the heart rhythm below), then the heart rate can be estimated by dividing 300 by the number of large (5 mm) squares between successive QRS complexes, or by counting the number of QRS complexes in 6 seconds and multiplying by 10. Careful! This method is only a rough estimate.Only applies if paper speed is 25 mm/sAlternatively, the heart rate may be estimated by multiplying the number of QRS complexes on the rhythm stripof a standard ECG by 5. Careful! This method of measuring the heart rate is not very precise and only for initial orientation.Only applies to a paper speed of 25 mm/s. A more exact method to calculate the heart rate (HR) If paper speed is 25 mm/s: HR = 150/RR interval in cm The heart rate is often measured with an ECG ruler in clinical settings. InterpretationNormal heart rate: 60-100/minTachycardia: > 100/min (see also tachycardic arrhythmias)Bradycardia: < 50-60/min (see also bradycardic arrhythmias) Determination of the heart rhythm The heart rhythm is assessed by evaluating the frequency, regularity, and relationships between the P waves and QRS complexes. ImplementationP wave assessment Are they visible in any lead? Determine the atrial rate (i.e., PP interval). Determine the morphology of the P waves. Relationship of P waves to QRS complexesA 1:1 relationship of P with QRS is normal. If not present: Determine the atrial and ventricular heart rates.Is there an abnormal number of P waves compared to QRS complexes? A P wave before every QRS, and a QRS after every P are normal. QRS morphology Normal duration: 0.07-0.10 seconds Wide QRS: > 0.12 seconds or 3 small squaresSome arrhythmias have characteristic features which can help in diagnosis (see cardiac arrhythmias).Associate any findings with your patient (e.g., history of heart disease, drug ingestion, etc.) Criteria for a sinus rhythm Normal morphology of the P waves A regular QRS complex follows every P wave. Normal, constant PP and RR intervals Determination of the axis The axis represents the spread of intraventricular electrical activity projected along the frontal plane (determined from limb leads I, II, III, aVR, aVL, aVF). The key here is to evaluate the QRS complex, and specifically whether it is positive or negative. Positive: if the area above the isoelectric line (i.e., the amplitude) is larger than the area beneath Negative: if the area below the isoelectric line is larger than the area above The main QRS vector (position of the electrical axis of the heart) is close to the lead with the highest positive QRS amplitude. The normal axis of the heart is between -30° and +90°. A rapid approximation of the axis may be made by assessing the QRS complexes in leads I and aVF: Left-axis deviation I+ aVF- (-30°)-(-90°)Normal variant (especially with age), LVH, LBBB, LAFB, inferior MI Normal I+ aVF+ (-30°)-(+90°)Normal axis Right-axis deviation I- aVF+ (+90°)-(+180°)Normal variant, RVH, LPFB, lateral MI, RV strain (e.g., PE), chronic lung disease (e.g., COPD) Extreme right-axis deviation I- aVF- (-90°)-(-180°)Severe RVH, lateral MI Interpretation of the P wave The P wave is best evaluated using lead II. Elevation of P ≥ 0.25 mV (2 small boxes height) P pulmonale Effect of right atrial enlargement Pulmonary disease COPDLung fibrosisPulmonary hypertension Other causes of overload of the right atrium (e.g., tricuspid or pulmonary valve stenosis) Biphasic P wave Prolongation of P > 0.10 s (3-5 small boxes length) P mitrale Effect of left atrial enlargement Heart valve defects Mitral valve stenosisSevere mitral insufficiencyAortic stenosis Other causes of overload of left atrium (e.g., cardiomyopathy, myocarditis) Biphasic morphology: elevation (≥ 0.25 mV) and prolongation (> 0.10 s) P biatrial (combination of P mitrale and P pulmonale) Effect of biatrial enlargement Overload of left and right atrium due to global heartstrain Interpretation of the QRS complex The QRS complex represents depolarization of the ventricles and corresponds approximately to ventricular systole. Interpretation of the duration≤ 100 ms = normal100-110 ms = incomplete bundle branch block (BBB)≥ 120 ms = complete bundle branch block (BBB)Signs of right bundle branch block (RBBB) are primarily seen in leads V1,2 Prolonged QRS complexrSR' formation (typical M shape/ "rabbit ear" shape)Wide S wave in lead IT wave inversions and ST-segment depression in V1--V3Final negativity (intrinsicoid deflection) in V1,2 after > 0.03 s Signs of left bundle branch block (LBBB) are primarily seen in leads I, V5,6 Prolonged QRS complexBroad, notched R waveLoss of Q wavesPossible rSR' formation in V5 or 6Deep S wave in V1,2Final negativity (intrinsicoid deflection) in V5,6 after > 0.05 The name William Morrow can help you identify LBBB and RBBB by looking at the QRS morphology in V1 and V6. In LBBB the QRS looks like a W in V1 and an M in V6 (WiLLiaM), in RBBB the QRS looks like an M in V1 and a W in V6 (MoRRoW). Interpretation of amplitudeAmplitude of the QRS complex in the precordial leads is used to assess for ventricular hypertrophy Various grading criteria exist for electrocardiographic determination of ventricular hypertrophy. The Sokolow-Lyon criteria are utilized below: Left ventricular hypertrophy (LVH): SV1 or 2 + RV5 or 6 ≥ 3.5 mVRight ventricular hypertrophy (RVH): RV1 or 2 + SV5 or 6 ≥ 1.05 mV The dominant waves seen in right ventricular hypertrophy can be remembered with the phrase "R1ght 5ignS" (R in V1 and S in V5) Patients with ventricular hypertrophy may not exhibit these signs on their ECG: These may become apparent later in the course of the disease or they may even be absent in some cases (e.g., severe obesity). However, ECG changes associated with clinical signs confirm the diagnosis of hypertrophy! Interpretation of the PR interval (normal 5 small boxes) The time between the beginning of the P wave and the beginning of the Q wave The PR interval represents atrioventricular transmission. PR interval ≤ 0.2 sNormal PR interval > 0.2 s First-degree atrioventricular block PR intervals become progressively longer (but PP intervals remain constant) until a dropped QRS complex occurs after a regular atrial depolarization.Second-degree AV block, Mobitz type I(Wenckebach) Constant PR intervals (which are usually normal but may be prolonged) followed by one or more non-conducted P waves. Second-degree AV block, Mobitz type II P waves and QRS complexes occur independently of each other, but in regular intervals → complete dissociation of P waves and QRS complexes.Third-degree AV block Interpretation of the Q wave Physiological The Q wave represents the beginning of ventricular depolarization. A narrow (≤ 40 ms 1 box wide) Q wave is physiological in: All limb leadsaVRV5 and V6 Pathological Pathological Q waves are characteristically: Abnormally wide (≥ 40 ms) Abnormally deep (2 squares tall ≥ 0.2 mV or > 25% of the R wave amplitude) or, detectable in V1-V3 EtiologyMyocardial injury or replacement Myocardial infarctionCardiac infiltrative disease (e.g., sarcoidosis, amyloidosis)Ventricular enlargement Acute pulmonary embolismHypertrophic cardiomyopathyAltered ventricular conduction Left bundle branch blockWolff-Parkinson-White syndrome ST segment Physiological The ST segment represents the interval between ventricular depolarization and repolarization It is physiologically horizontal on the isoelectric line. Pathological ST elevation An ST elevation is significant if: ≥ 0.1 mV in limb leads, or≥ 0.2 mV in precordial leads! The hallmark ECG finding of myocardial infarction!If significant ST elevations are present in ≥ 2 anatomically contiguous leads (corresponding to occlusion of a specific artery)The ischemia can be localized by which leads show ST elevation: Lateral MI (left circumflex artery occlusion): I, aVL, V5-6 Anterior MI (left anterior descending (LAD) artery occlusion): V1-4 Inferior MI (terminal branches of right or left coronary artery occlusion): II, III, aVF Widespread ST elevations suggest pericarditis LBBB may cause ST elevations due to repolarization abnormalities, therefore ST elevation cannot be used to diagnose MI in the presence of a LBBB. Small, concave ST elevations may be a normal finding in young, healthy adults due to early repolarization. From descending R: The most important cause is a myocardial infarction. From (deep) S: perimyocarditis Brugada pattern Associated with Brugada syndrome: rare autosomal dominant condition that affects sodium channels and disturbs repolarization Epidemiology: most common in Asian males Clinical featuresOften an incidental finding, as patients are mostly asymptomaticSyncopeSudden cardiac death DiagnosisBrugada pattern on ECG: Pseudo-RBBB with ST elevation in leads V1-2Rule out underlying heart disease (e.g., stress test and echocardiography) TreatmentImplantable cardiac defibrillator (ICD) placementScreen all 1st-degree relatives annually with clinical exam and ECG ComplicationsSyncopeSudden cardiac deathIncreased risk of atrial fibrillation ST elevation from a descending R is likely caused by a myocardial infarction! ST depression Differential diagnosisSubendocardial myocardial ischemia (MI) (i.e., NSTEMI) Stress-induced MI (sign of coronary artery disease)Reciprocal change from MI Ventricular hypertrophyLeft ventricular hypertrophy: ST depression with pre-terminal T-wave inversion in V4-6Right ventricular hypertrophy: ST depression with pre-terminal T-wave inversion in V1-3(4)Digoxin effect HypokalemiaLBBB The shape of the ST segment suggests the etiology of the depression. Downsloping ST depression or horizontal ST depression: myocardial ischemiaUpsloping ST depression: mild manifestations may be normal, but may also occur in cases of tachycardia; sign of coronary heart disease if significantly manifestedSagging type ST-segment depression: characteristic of digoxin intake Progression of ST elevation myocardial infarction (STEMI) on ECG The stages of myocardial ischemia are associated with characteristic (but variable) ECG findings: Hyperacute T waves: very early and transient; usually have disappeared by the time ECG is performed ST elevation at the J point: point at which the QRS complex completes and returns to the isoelectric line (i.e., the intersection of the S wave and the ST segment) Progressive ST segment elevation, with added convexity ST merges with T wave, forming a QRS-T segment (i.e., tombstone): usually with associated reciprocal ST depressions(see ST depression) ST segment returns to isoelectric line, Q wave develops, and R wave loses amplitude T-wave inversion Progressive Q wave deepening and R wave shrinkage T wave may or may not return to upright position T wave Physiological The T wave represents the repolarization of the ventricles The T wave is physiologically concordant to the QRS complex: positive if the QRS complex is positive or negative if the QRS complex is negative. Pathological T-wave inversion Small T-wave inversions may be normal in the limb leads Differential diagnosisCoronary heart diseaseVentricular hypertrophyPerimyocarditisMyocardial infarction (STEMI (in the intermediate stage) or NSTEMI)Ventricular aneurysmIntracranial hemorrhageLBBBAcid/base disturbance The shape of the T wave may help to narrow the differential diagnosis. Pre-terminal T-wave inversion: If the T wave is bisected, it points to the left. It may occur in: PerimyocarditisVentricular hypertrophyCoronary heart diseaseTerminal T-wave inversion: If the T wave is bisected, it points either to the right or upwards. It may occur in: Intracranial hemorrhage PerimyocarditisA persistent negative T wave following myocardial infarction may suggest an aneurysm.Myocardial infarction (STEMI (in the intermediate stage) or NSTEMI) Peaked T wave Tall, narrow, symmetrically-peaked Differential diagnosisHyperkalemiaHypermagnesemiaHigh vagal tone Hyperacute T wave Broad, asymmetrically-peaked Differential diagnosisEarly stages of ST (segment) elevation myocardial infarction (STEMI) Prinzmetal's angina Normally, if electric conduction in the heart is pathological (bundle branch block), repolarization is also disturbed → reliable evaluation of the ST segment or T wave is not possible! New occurrence of a left bundle branch block associated with angina chest pain is defined as a STEMI! QT interval Physiological (11 small squares) Measured from the beginning of the Q wave to the end of the T wave Represents the entire duration of ventricular depolarization Varies with heart rate, so correction for the heart rate is necessary (=QTc ) QTc normally < 350-440 ms Pathological Prolongation of the QT interval Possible differential diagnoses include: Hypocalcemia Hypokalemia Inflammatory heart diseases (myocarditis, pericarditis) Bundle branch block High vagal tone Rare congenital syndromes (e.g., congenital long QT syndromes such as Romano-Ward syndrome) Acquired long QT syndrome Hypothyroidism Drug side effect (e.g., antiarrhythmic agents, antidepressants, phenothiazines, 1st-generation antihistamines) Shortening of the QT interval Possible differential diagnoses include: Hypercalcemia Hyperkalemia Digoxin effect Increased sympathetic tone (e.g., hyperthyroidism or fever)

Edema Edema is an abnormal accumulation of interstitial fluid caused by a variety of conditions, including, for instance, generalized fluid retention and localized reactions to trauma and allergies. Edema may manifest with swelling of the extremities (peripheral edema) or with internal fluid accumulation in organs and body cavities (e.g., pulmonary edema, pleural effusion). Patients with peripheral edema usually present with painless swelling of the lower legs. A residual indentation left by pressure on the site of the swelling indicates pitting edema. Bilateral lower limb pitting edema is often a sign of cardiac failure, while generalized peripheral pitting edema with swelling of the eyelids indicates hypoalbuminemia (e.g., in nephrotic syndrome). Nonpitting edema is seen especially in patients with lymphatic disorders and thyroid conditions.

General features Definition: abnormal fluid accumulation in the interstitium due to an imbalance in fluid homeostasis TypesPeripheral edema Mostly swelling of lower legs, feet, and ankles, sparing the toes Usually painless; possibly discomfort and difficulty walking Stasis dermatitis and peripheral polyneuropathy may occur in chronic edema.Either pitting or nonpitting edema (see "Causes" below)Anasarca: extreme generalized peripheral edema Periorbital edema (e.g., nephrotic syndrome) Internal edemaInterstitial pulmonary edemaCerebral edemaAscites Pleural effusion Causes Pitting edema Fluid retentionReduced cardiac stroke volume in cardiac failure → impaired renal perfusion → activation of renin-angiotensin system → increased renal fluid retention → increased hydrostatic pressure → secretion of fluid into the interstitium (edema formation)Pharmaceutical side effects (e.g., calcium channel blockers) Protein deficiency (mainly hypoalbuminemia) : nephrotic syndrome, liver cirrhosis, malnutrition, protein-losingenteropathy Hydrostatic: chronic venous insufficiency , pregnancy, deep vein thrombosis, post-thrombotic syndrome Increased capillary permeability: inflammation, burns, allergic reactions, trauma Nonpitting edema Lymphedema: due to lymphatic obstruction (see below) Myxedema: hypothyreosis (generalized), hyperthyreosis (typically pretibial) GeneralizedAcute Nephrotic syndrome Acute cardiac failure Acute renal failure Chronic Chronic cardiac insufficiency Chronic renal insufficiency Liver cirrhosis Malnutrition LocalizedInflammation Burns Allergic reaction Trauma Thrombosis Lymphedema Chronic venous insufficiency Post-thrombotic syndrome Lymphedema Definition: edema associated with lymphatic obstruction and reduced fluid clearance due to compromised lymphatic vessels or lymph nodes→ Lipid-rich, protein-rich fluid in the interstitial space that has high viscosity EtiologyPrimary lymphedema (rare) Congenital anomaly with poorly developed lymphatic vessels Characteristic finding in Turner syndromeSecondary lymphedemaTumors, operations , inflammation, trauma, radiation therapy Infections Recurrent erysipelas, leprosy, syphilis, granuloma inguinaleLymphatic filariasis (elephantiasis) Clinical findingsSwelling of limbs; characteristically nonpitting edema Swelling of toes and feet with deep flexion creases Stemmer's sign: inability to lift a skin fold on the base of the second toe StagesLatent stage Reversible swelling Gradual fibrosis Irreversible elephantiasis TreatmentConservative Manual compression therapy and compression garmentsElevation of the involved limbExerciseManagement of underlying diseaseSurgical Resection of lymphatic vesselsLymphaticovenous anastomosis and lymphatic vessel graftingVascularized lymph node transfer

Antiadrenergic agents Antiadrenergic agents inhibit the activity of the sympathetic nervous system. They act by blocking adrenergic receptors in target organs or by inhibiting the synthesis, storage, or release of endogenous catecholamines (mainly norepinephrine). This class of medications is most commonly used for the treatment of ischemic heart disease and hypertension, although antiadrenergic agents may also be used for urinary retention secondary to benign prostatic hyperplasia and for psychiatric conditions such as anxiety disorders and post-traumatic stress disorder. Beta blockers are discussed in detail in a separate learning card.

General mode of action All antiadrenergic agents reduce sympathetic tone by inhibiting the production, storage, or release of catecholamines(especially norepinephrine). Alpha blockersInhibit alpha-1 receptors in smooth muscle →↓ Vasoconstriction → ↓ blood pressureRelaxation of bladder neck muscles → ↓ bladder outlet obstruction and easier micturitionUnopposed epinephrine binding to beta-adrenergic receptors →↑ Vasodilation (via beta-2 receptors) → ↓ blood pressure↑ Secretion of renin (via beta-1 receptors) → ↑ water retention → peripheral edema (in some patients)Through unknown mechanisms, alpha blockers can reduce nightmares secondary to PTSD. Beta blockersInhibit mainly beta-1 receptors in the heart →↓ Heart rate, ↓ contractility, ↓ atrioventricular conduction The main benefit of beta blockade is that it reduces myocardial oxygen demand. Some beta blockers suppress aqueous humor production in the eye → ↓ intraocular pressure Inhibition of catecholamine release Alpha-2 adrenergic agonistsActivate alpha-2 receptors in presynaptic sympathetic neurons of the central nervous system → ↑ negativefeedback → ↓ catecholamine release (dopamine and norepinephrine) → ↓ Sympathetic tone → ↓ vasoconstriction → ↓ blood pressureTizanidine, an alpha-2 adrenergic agonist, also inhibits motor neurons → ↑ muscle relaxation↑ Unopposed GABA activity → sedationThrough unknown mechanisms, some alpha-2 adrenergic agonists improve symptoms in ADHD and Tourette syndrome. Monoamine-depleting agentsReserpine: Indole alkaloid used in the treatment of tardive dyskinesia, psychiatric disorders, and hypertension. Mode of actionInhibits uptake of norepinephrine and dopamine into presynaptic vesicles of adrenergic neurons → ↓ catecholamine release (dopamine and norepinephrine) → ↓ Cardiac output → ↓ blood pressure↓ Vasoconstriction → ↓ blood pressureSide effects include parkinson-like syndrome, angina, bradycardia, peripheral edema, and depression All drug groups that directly inhibit the sympathetic nervous system (i.e., alpha blockers, beta blockers, and drugs that reduce sympathetic tone) are treatment options for arterial hypertension! Alpha blockers Doxazosin/Terazosin HypertensionBenign prostatic hyperplasia Tamsulosin/Alfuzosin/Silodosin Benign prostatic hyperplasia Peripheral edemaOrthostatic hypotensionNausea, constipationIntraoperative floppy iris syndrome (IFIS) Complication of cataract surgery characterized by iris prolapse through the surgical incision and intraoperative pupillary constrictionMay lead to retinal detachment and endophthalmitisRetrograde ejaculation Urinary frequency PrazosinHypertensionPTSD-relatednightmares PhenoxybenzaminePheochromocytoma Same as alpha blockers aboveIn addition: pronounced reflex tachycardia Alpha blockers are usually only second-line drugs for the treatment of hypertension, since they do not improve prognosis! Alpha-2 adrenergic agonists ClonidineHypertensionADHDOrthostatic hypotensionSedationDry mouth Rebound hypertension caused by abrupt discontinuation of medication RashBradycardiaMethyldopaHypertension in pregnancyOrthostatic hypotensionSedationPeripheral edema Autoimmune hemolytic anemiaHyperprolactinemia TizanidineMuscle spasticity Orthostatic hypotensionSedationDry mouthBradycardiaGuanfacineHypertensionADHDTourette syndromeOrthostatic hypotensionSedationDry mouthNausea and vomitingDexmedetomidineSedationOrthostatic hypotensionBradycardiaHypertension AgitationConstipationNauseaSedation Sympathetic blockers are usually used in antihypertensive combination regimens!

Cardiovascular examination Cardiovascular examination is a central tool for assessing the cardiovascular system. Examination includes assessment of vital signs and jugular venous pulse, chest inspection and palpation, and, most importantly, auscultation of the heart. For specific auscultatory findings in valvular heart disease, see auscultation in valvular defects. For specific auscultatory findings of heart defects, see congenital heart defects. Details regarding the specific signs and symptoms of cardiovascular disease can be found in the links provided below.

History and general examination History Dyspnea Chest pain Palpitations Syncope Hemoptysis Edema AppearanceLevel of consciousness (altered mental status)Skin and mucous membrane (color changes, temperature, dehydration) Central cyanosis (see features of congenital heart defects and congestive heart failure) Pallor (e.g., anemia)Plethora (e.g., polycythemia)Xanthomas (e.g., dyslipidemia)Syndromic facies (e.g., in trisomy 21, trisomy 18; associated with congenital heart defects)Features of rheumatic fever: migrating polyarthritis, erythema marginatum, subcutaneous nodules Signs and symptoms of left-sided heart failureSigns and symptoms of right-sided heart failureHandsPerfusion (venous obstruction, conditions associated with a decreased cardiac output): TemperatureCapillary refill timeCyanosisPalms: Osler nodes, Janeway lesions (see "Clinical features" of infective endocarditis) Nails: clubbing, splinter hemorrhagesFaceMalar flush (red cheeks, seen in patients with mitral stenosis)Swollen faceEyesSigns of dyslipidemia (xanthelasmas, arcus lipoides corneae)Signs of hypertensive retinopathy (ophthalmologic exam)MouthPoor dental hygieneHigh arched palate (Marfan syndrome)NeckCarotid pulseJugular venous pulse (see clinical assessment of central venous pressure)OtherLung bases: pulmonary edemaLower limbsPeripheral edemaSigns of venous insufficiency (e.g., varicose veins)Signs of stroke Central venous pressure The jugular venous pulse (JVP) can be used to estimate the central venous pressure (CVP) and provides information about fluid status and cardiac function. Approach The patient should be in supine position, torso elevated to 45 degrees, and the head extended backward and turned to the left (the neck veins should not be visible and collapse in this position). Identify the venous pulsation of the internal jugular vein.Determine the height of the internal jugular venous filling pressure.The hepatojugular reflux may be tested if the JVP cannot be visualized properly. Physiological JVP: waveform with the following components a wave → atrial contraction causes a peak in JVP; absent in atrial fibrillationc wave → RV contraction → closed tricuspid valve bulges into atrium → second peak in JVPx descent → atrial relaxation and ventricular contraction → inferior displacement of closed tricuspid valve → a drop in JVP; absent in tricuspid regurgitationv wave → increased right atrial pressure during filling period against the closed tricuspid valve; prominent in tricuspid insufficiency and right heart failurey descent → RA pressure decreases as blood is pumped into the right ventricle; prominent in tricuspic insufficiency, and constrictive pericarditis; absent in cardiac tamponade, and tricuspid stenosis Evaluation of pathological JVP: > 4 cm is considered elevated. Signs of elevated jugular venous pressureJugular venous distentionHepatojugular refluxConditions associated with elevated JVP: e.g., right heart failure, fluid overload, tricuspid valve dysfunction, SVC syndrome, pericardial effusion, tamponade, pulmonary hypertension Blood pressure Approach The patient should be sitting for several minutes before measuring blood pressure. Use correct cuff size. The patient should be asked to rest his/her straight arm horizontally on a surface at heart level. Record the pressure in both arms (and legs) and note any differences. Determine the systolic and diastolic blood pressure value. Repeat measurement. Ambulatory blood pressure measurement (24 hours) may be helpful in establishing the average and peak blood pressure values during daily activities. Pulses A pulse wave is produced by ventricular contraction during systole. Approach Three finger method: palpation with 2nd-4th fingertips Palpation of the common carotid artery, radial artery, abdominal aorta, femoral artery, popliteal artery, tibialis posterior artery, and dorsalis pedis artery. The pulse of the carotid artery should NEVER be palpated bilaterally and simultaneously! Risk of compression of vessels → cerebral hypoperfusion → syncopeRisk of hyperstimulation of the carotid sinus reflex → bradycardia/low blood pressure → cerebral hypoperfusion → syncope The thumb of the examiner should never be used to take the pulse as it has its own strong pulse, which might be mistaken for the patient's pulse! Characteristics of pulse DescriptionPossible causesRateNumber of beats per minute< 60 bpm → bradycardia> 100 bpm → tachycardiaPhysiological variationsBradyarrhythmiasTachyarrhythmiasRhythmRegularPhysiological Regularly irregularAtrial tachyarrhythmias (e.g., atrial flutter) with a fixed AV blockIrregularly irregularAtrial fibrillationAtrial tachyarrhythmias (e.g., atrial flutter) with a varying AV blockVentricular ectopics (premature ventricular contractions)Pulse deficit: difference between the pulse rate measured by cardiac auscultation and the peripheral pulse rate obtained by palpating the radial arteryPulse deficit > 10 → atrial fibrillationPulse deficit < 10 → premature ventricular contractionsObstructive hypertrophic cardiomyopathyPulsus bigeminus: two heartbeats occur in rapid succession (usually a high volume pulsefollowed by a low volume pulse) followed by a long gap (therefore regularly irregular)Severe left heart failureDigoxin toxicityPulse volume (amplitude) Hyperkinetic pulse (pulsus altus): bounding pulseCorrigan sign and water hammer pulse: bounding pulse best palpated on the radial, brachial, or carotid artery Arterial hypertensionHigh cardiac output states: anemia, sepsisPDAAortic regurgitationVSDHypokinetic pulse (pulsus parvus): soft pulse with a low amplitudeLow blood pressurePulsus paradoxus: pathological decrease in the pulse wave amplitude and systolic blood pressure of > 10 mm Hg during inspiration Constrictive pericarditisCardiac tamponadeSuperior vena cava syndromeSevere obstructive airway disease (asthma, COPD)Obstructive sleep apneaTension pneumothoraxCroupReverse pulsus paradoxus: pulse volume increases with inspirationHOCMAV dissociationIntermittent positive pressure ventilation (IPPV)Pulsus alternans: alternation of strong and weak pulses caused by alterations in the stroke volume (cardiac output) Dicrotic pulse: two peaks in the pulse wave occurring in systole and diastole Congestive heart failurePulse wave tensionHigh-tension pulse: The vessel wall feels rigid and cord-like between beats (during diastole) and is not easily compressible. Arterial hypertensionLow-tension pulse: The vessel wall is either soft or not palpable between beats and is easily compressible.Low blood pressureSystemic vasodilatation (e.g., sepsis)Speed of pulseupstroke (wave contour) Fast-rising pulse: rapid upstroke of the pulse Aortic regurgitationLow-rising pulse: delayed peak pressure of the carotid artery Aortic stenosisDelayRadiofemoral delay Coarctation of the aortaVascular obstruction (atherosclerosis)Aneurysms Auscultation For detection of vascular murmurs in the carotid artery, abdominal aorta, renal artery, and femoral artery Causes of vascular murmurs: alteration of local vessels and vascular walls FistulaeAneurysmsVascular stenosis Auscultation of high-frequency, pulse-synchronous sounds proximal to the stenosisHypercirculation and increased cardiac outputE.g., pregnancy, fever, anemia, hyperthyroidismMay occur physiologically in adolescents Chest inspection Approach The patient is initially requested to remove their upper body attire to identify: Scars (e.g., heart surgery, pacemakers) Chest deformities (pectus carinatum or pectus excavatum) Visible apex beat Distended veins on chest (e.g., in SVC obstruction) De Musset sign: head bobbing in time with pulse (seen in aortic regurgitation) Chest palpation Apex impulse The apex impulse (apex beat) is the outermost and lowermost cardiac impulse on the chest wall that is definitely palpable. The examiner places their flat hand on the cardiac apex to locate the apex beat; it is further localized and assessed by palpating with 2-3 fingers. If the apex beat is not initially palpable, the patient should be positioned on his/her left lateral side and the cardiac apex should be palpated during expiration. PositionNormal: 5th left intercostal space in the midclavicular lineAbnormalLateral and downward displacement → left ventricular hypertrophyLateral displacement → right ventricular hypertrophy, right tension pneumothorax, large pleural effusion, chest wall deformities Displacement to the right hemithorax → dextrocardiaQualityNormal: a brief (early systolic) impulse that is felt over an area of 2-3 cm2AbnormalHyperdynamic impulse: a very brief, large-amplitude impulse that is palpable over a diffuse area (> 3 cm2) High cardiac output (e.g., thyrotoxicosis, anemia, sepsis, beriberi)Volume overload: aortic regurgitation, mitral regurgitation, ventricular septal defect, patent ductus arteriosusHeaving impulse: a prolonged (holosystolic), large-amplitude impulse Pressure overload: hypertension, HOCM, aortic stenosisHypodynamic impulse: a weak or absent apex impulse Myocardial infarctionConditions that impair transmission of the apex impulse to the chest wall: obesity, pericardial effusion, left-sided pleural effusion, pneumothorax, COPD (emphysema) Other impulses Parasternal heave: a heaving motion felt over the left parasternal area (palpate with right hand and straightened elbow) Suggests RV hypertrophy (e.g., pulmonary hypertension) Thrills: a palpable murmur, usually over the region where the heart murmur is heard best (see auscultatory locationsbelow) Palpable heart sounds: palpate over valve areas (e.g., palpable P2: see auscultatory locations below) Chest percussion Although cardiac percussion can provide some information about the size and shape of the heart, it is very unreliable and dependent on the examiner and is thus of limited clinical use Chest auscultation Approach Performed in the supine position with slight elevation of the torso Politely ask the patient to refrain from speaking while the heart sounds are being assessed. The pulse should be simultaneously palpated during auscultation (mainly the radial artery). If heart sounds are weakly audible, request that the patient holds their breath for a moment after expiration(respiratory rest position). Assess the following: Location, timing, changes in intensity, and splitting of heart soundsAbnormal heart soundsMurmurs Heart soundOriginTimingOccurrencePrimary heart sounds1st heart sound(S1)Closure of the mitral valve and tricuspid valveBest heard in the 5th left intercostal space in the midclavicular line (cardiac apex) Onset of systoleHeard just before the carotid pulsation is feltAlways2nd heart sound(S2)Closure of the aortic and pulmonary valveTwo components: A2: closure of the aortic valve (louder)P2: closure of the pulmonary valve (softer)Best heard in the aortic region (A2) and pulmonary region(P2)Transition from systole to diastoleHeard immediately after the carotid pulsationAlwaysSee splitting of S2 below. Extra heart sounds (gallops) 3rd heart sound(S3)Ventricular filling soundRapid ventricular fillingSudden deceleration of blood when the ventricle reaches its elastic limit.Immediately after S2 Ventricular gallop: Ken-tuc-key pattern (S1-S2-S3) Physiological: young individuals(< 40 years) or pregnant womenPathological Chronic mitral regurgitationHeart failure (dilated ventricles)Dilated cardiomyopathy4th heart sound(S4)Ventricular filling sound: late diastolic contraction of the atria("atrial kick") against a high ventricular pressureImmediately before S1 Atrial gallop: Ten-nes-seepattern (S4-S1-S2) Physiological: advanced age Pathological: atrial gallopVentricular hypertrophy (e.g., hypertension, aortic stenosis, cor pulmonale)Ischemic cardiomyopathyAcute myocardial infarction Gallops more commonly arise from the left side of the heart. Gallops that originate from the left side of the heart become softer with inspiration while those that originate from the right side become louder! Splitting of heart sounds If the aortic and pulmonary valves do not close simultaneously, an apparent splitting of S2 can be heard upon auscultation. Splitting of S2Physiological split During inspiration: The sound of aortic valve closure (A2) precedes the sound of pulmonary valve closure (P2). The split is especially pronounced among young individuals. Wide split An exaggerated physiological split, i.e., more pronounced during inspiration (A2 precedes P2). Pulmonary hypertensionMassive pulmonary embolismSevere mitral regurgitationWolff-Parkinson-White syndromeConstrictive pericarditisRBBBFixed split A split in S2 that does not change with respiration, i.e., the split is also audible during expiration.Atrial septal defect (ASD) Severe RV failureParadoxical split(reversed split) The split in S2 is audible during expiration but not inspiration. Aortic stenosisLeft bundle branch blockHypertrophic obstructive cardiomyopathy(HOCM; LV outflow tract obstruction)Early excitation of the right ventricle (e.g., RV pacing, Wolff-Parkinson-White syndrome)Absent splitNo splitting of S2Severe aortic stenosis (geriatric) VSD with Eisenmenger syndrome (pediatric) Aortic ejection clickOpening of a stiff aortic valve in aortic stenosisEarly-systolic sound(immediately after S1)Best heard with the diaphragm of a stethoscope at the aortic region with the patient seated and leaning forward Mitral valveopening snapOpening of a stiff mitral valve in mitral stenosisEarly-diastolic sound (immediately after S2) Best heard with the bell of a stethoscope at the mitral region with the patient in a left lateral position Mitral valve prolapse clickMitral valve prolapse into the left atriaduring systoleMidsystolic soundBest heard with the diaphragm of a stethoscope at the mitral region with the patient in left lateral position Mechanical valve clicksS1 and S2 sounds that are produced by prosthetic valves sound like clicks.Appropriate (see S1 and S2 above)With the diaphragm of a stethoscope The presence of an aortic ejection click can be used to differentiate a pathological systolic murmur of aortic stenosis from a flow murmur! The absence of a click in patients with prosthetic valves may indicate valve failure! Functional murmur (physiological or innocent) Non-cardiac or peripheral cause: due to increased blood flow across normal aortic and/or pulmonary valves (ejection murmur) Most commonly occurs in infants and children but also in individuals without cardiac conditions (particularly thin or pregnant individuals) due to e.g., hyperdynamic circulation Cardiac conditions and structural abnormalities (e.g., valvular defects) must be ruled out. Soft (< 3/6 without a thrill) Most commonly mid-systolic or continuous murmurPosition-dependent; murmur varies in intensity or disappears Cervical venous hum: common benign auscultation finding in childrenCaused by turbulent flow in internal jugular veinsContinuous murmur best heard at the infraclavicular and supraclavicular regions; more common on the right sideBecomes softer or disappears with flexion of the head, compression of the jugular vein, or in supine position Still murmur Pathologic murmur Caused by structural defects (valvular disease or heart defects) Typically > 3/6 Thrill may be present Systolic, diastolic, or continuous Murmur rarely disappears For specific auscultatory findings in valvular heart disease, see auscultation in valvular defects. For specific auscultatory findings of heartdefects, see congenital heart defects. Erb's point (cardiology)3rd left parasternal intercostal space Diastolic murmurs: aortic regurgitation, pulmonic regurgitationSystolic murmurs: HCOMAortic area2nd right parasternal intercostal spaceAortic stenosisAortic regurgitationCoarctation of the aortaPulmonic area2nd left parasternal intercostal spacePulmonary stenosisPulmonary regurgitationASDMitral area5th left intercostal space in the midclavicular lineMitral stenosisMitral regurgitationMitral valve prolapseTricuspid area4th left parasternal intercostal space Tricuspid stenosisTricuspid regurgitationGibson's pointLeft infraclavicular regionContinuous murmur of a PDA is heard best at this point. SystolicmurmursDuring ventricular contraction (i.e. occurs with or after S1 and before S2)May be classified as early-systolic, mid-systolic, late-systolic, and holosystolic according to the onset and termination of the murmurFunctional (innocent):ChildrenPregnancyDuring states of excitement or strenuous activityAnemiaFever, sepsisThyrotoxicosisBeriberiArteriovenous fistulaPathological Aortic stenosisPulmonary stenosisMitral regurgitationTricuspid regurgitationVentricular septal defectCoarctation of the aortaHypertrophic obstructive cardiomyopathy(HOCM) DiastolicmurmursDuring ventricular relaxation (i.e., occurs with or after S2 and before S1)May be classified as: early-diastolic, mid-diastolic, late-diastolic, or holo-diastolic according to the onset and termination of the murmurDo not occur physiologicallyNext best step in management: transthoracic echocardiogramMitral stenosisAortic regurgitationTricuspid stenosisPulmonary regurgitation Continuous murmursDuring systole and diastoleHyperdynamic stateCervical venous humPDAArteriovenous fistulas A mid-systolic murmur in an asymptomatic individual is most likely physiological! Unlike systolic murmurs, diastolic murmurs are almost always pathological! Diastolic murmurs may require that certain maneuvers be performed to make them more apparent. Levine grading scaleLoudness of the murmurGrade IThe murmur is heard only upon listening carefully for some time.Grade IIThe murmur is faint but becomes immediately audible when the stethoscope is placed on the chest.Grade IIIA readily audible loud murmur without a thrill.Grade IVA loud murmur with a thrill.Grade VA loud murmur with a thrill. The murmur is audible with just the rim of the stethoscope touching the chest.Grade VIA loud murmur with a thrill. The murmur is audible with the stethoscope hovering above the chest. While most murmurs of grade III and above are pathological, the intensity of a murmur does not always correlate to the severity of the underlying lesion! For example, a larger VSD produces a softer murmur than a small VSD and a murmur of severe aortic stenosis may disappear if a patient develops left heart failure! All diastolic murmurs and any systolic murmurs of grade II and above require further echocardiographic evaluation! Configuration The configuration of a murmur describes the change in intensity of the murmur. Uniform: unchanging intensity Crescendo: increasing intensity Decrescendo: decreasing intensity Crescendo-decrescendo: initial increase, followed by decrease in intensity (rhombus-shaped) Radiation A murmur may be auscultated at a site that does not lie directly over the heart. Aortic stenosis: systolic murmur radiates to carotid arteries Mitral regurgitation: systolic murmur radiates to the left axilla (in the left lateral recumbent position) Pulmonary stenosis: systolic murmur radiates to the interscapular region Response to maneuvers Certain maneuvers may be performed to elicit a change in the intensity of a murmur. ManeuverEffect on cardiac parametersEffect on murmursInspiration ↑ RV preload↓ LV preloadNo effect on LV afterloadCarvallo Sign↑ Intensity of murmurs arising from the right side of the heart↓ Intensity of murmurs arising from the left side of the heart (see "Exception" below)Valsalva maneuver/standing↓ RV preload↓ LV preload↓ LV afterload↓ Intensity of murmurs arising from the left side of the heart (see "Exception" below)MVP: click occurs earlierSquatting/lying down quickly/raising the legs ↑ RV preload↑ LV preloadNo effect on LV afterload(afterload may increase with squatting)↑ Intensity of all murmurs (see "Exception" below)Tetralogy of Fallot: severity of "Tet spells" and the associated murmurs decrease with squatting.MVP: click occurs laterHand grip No effect on RV preloadNo effect on LV preload↑ LV afterload↑ Intensity of murmurs resulting from backward flow of blood in the left side of the heart(e.g., aortic regurgitation, mitral regurgitation, VSD, mitral valve prolapse)↓ Intensity of murmurs associated with forward flow of blood in the left side of the heart(e.g., mitral stenosis, aortic stenosis, HOCM)MVP: click occurs laterSitting leaning forwardNo effect↑ Intensity of murmurs at or near the aortic valve (e.g., AS, AR, coarctation of the aorta, HOCM)Lying down in the left lateral positionNo effect↑ Intensity of murmurs at or near the mitral valve (e.g. mitral stenosis, mitral regurgitation, mitral valve prolapse)Exception: In the following conditions, maneuvers that increase preload decrease the intensity of the murmur.Hypertrophic obstructive cardiomyopathy (HOCM) Mitral valve prolapse (MVP) Diagnostics Imaging Electrocardiography Cardiac stress test Chest x-ray: shows the heart shadow (the transverse diameter of the heart shadow in the PA view should be no greater than one-half of the transverse diameter of the thorax) Heart contour in the lateral view Anterior border: right ventricleInferior border: left ventriclePosterosuperior border: left atriumHeart contour in the PA view Right border (from caudal to cranial): right atrium → superior vena cavaLeft border (from caudal to cranial): left ventricle → left atrial appendage → pulmonary trunk → aortic knuckleInferior border: right ventricle Echocardiography: done as transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE) based on the indication TTE recommended for evaluation of pathological murmurs (e.g., diastolic murmur, late systolic murmur, all symptomatic murmurs, etc)Assess valvular function: allows one to classify the defect (mild, moderate, or severe) Determine the average pressure gradientDetermine the valve area: decreased in case of valvular stenosis Determine the amount of reflux via a color duplex scan: increased in the case of valvular insufficiencyAssess myocardial contractility Detect and evaluate other pathologies (septal defects, aneurysms, thrombi, vegetations, etc.) Cardiac MRI/CT Cardiac scintigraphy (especially in the case of ischemic cardiac disease) Invasive tests Cardiac catheterizationCoronary angiography and possibly a PCIDirect measurement of the ventricular and aortic pressures to determine the degree of valvular stenosisCardiac ventriculography to directly visualize and quantify the reflux of the contrast material in valvular insufficienciesRight heart catheterization Electrophysiological studies (to assess cardiac arrhythmias)The cardiac arrhythmia is often treated (e.g., by ablation) during the test itself. Myocardial biopsySuspicion of cardiomyopathies, myocarditis, or a systemic illness with cardiac involvement (sarcoidosis, amyloidosis, hemochromatosis)Follow-up after a heart transplantation (to rule out the possibility of organ rejection)

Coronary artery bypass grafting Coronary artery bypass grafting (or CABG) is a cardiac revascularization technique used to treat patients with significant, symptomatic stenosis of the coronary artery (or its branches). The stenosed segment is bypassed using an arterial (e.g., internal thoracic artery) or venous (e.g., great saphenous vein) autograft, re-establishing blood flow to the ischemic areas of the myocardium. This may be performed either with the help of a heart-lung bypass machine (traditional CABG, performed via a thoracotomy), or on a beating heart (off-pump CABG, and minimally invasive direct CABG). In addition to general surgical risks, the main complications associated with bypass grafting are bypass occlusion and postpericardiotomy syndrome. The procedure provides more effective symptom relief than medical management and is superior to PCI in multivessel coronary disease.

Indications Indication for CABG is established after careful consideration of the clinical features, coronary catheterization findings, cardiac function, and the patient's general condition. High-grade left main stem coronary artery stenosis Significant stenosis (> 70%) of the proximal left anterior descending artery, with 2-vessel or 3-vessel disease Symptomatic 2-vessel or 3-vessel disease Disabling angina despite maximal medical therapy Poor left ventricular function with myocardium that can return to function on revascularization Postinfarct angina Indications for emergency CABG Non-ST segment elevation myocardial infarction with ongoing ischemia that is unresponsive to medical therapy/PCISTEMI with inadequate response to all nonsurgical therapySignificant ongoing ischemia, traumatic complications, or threatened occlusion in STEMI, after a failed PCI or previous CABG Contraindications There are no absolute contraindications for CABG. Relative contraindications include: Asymptomatic patients with a low risk of myocardial infarction or death Comorbidities (e.g., COPD, pulmonary hypertension, systemic diseases) Advanced age Procedure/application Overview of stepsThoracotomy via a midline sternotomy → cardiopulmonary bypass (heart-lung machine) → cardioplegic arrest of the heart → anastomosis of the bypass vessels distal to the coronary artery stenosis using autologous vessels Types of graftsArterial graft Internal thoracic artery (internal mammary artery)Radial arteryVenous graft (aortocoronary saphenous vein bypass, or ACVB)Great saphenous vein (first choice in vein bypass grafts)Small saphenous vein Types of CABGTraditional CABG Off-pump coronary artery bypass (OPCAB) surgery Minimally invasive direct, or totally endoscopic CABG Alternate procedure: percutaneous coronary intervention (PCI)Advantages: decreased periprocedural morbidity, decreased cost, decreased hospital stayDisadvantages: higher rate of patients requiring reintervention CABG is proven to be a superior long-term form of revascularization in high-risk multivessel disease (diabetics or low LV function), certain cases of severe two-vessel CAD, and in all patients with three-vessel CAD. PCI is preferred in cases with symptomatic low-risk obstruction (single vessel, mild double vessel obstruction). Postoperative long-term treatment with antiplatelet drugs (e.g., 100 mg aspirin 1-0-0) is required to reduce the risk of subsequent myocardial ischemia! Complications Cardiac complications Myocardial dysfunction Postpericardiotomy syndrome: autoimmune febrile pericarditis or pleuritis that may occur 1-6 weeks following cardiac surgeryFeatures Fever, malaiseChest pain, with or without associated dyspneaTachycardiaPericardial friction rubTreatment Anti-inflammatory drugs: nonsteroidal anti-inflammatory drugs (NSAIDs) or prednisonePericardial drainageSurgery: formation of a pericardial window through thoracotomy or by means of a balloon catheter Postoperative cardiac tamponade with cardiogenic shock Bypass occlusion Arrhythmias Mediastinal complications Postoperative acute mediastinitisNasal colonization with methicillin-susceptible Staphylococcus aureus prior to surgery is associated with a higher incidence of postoperative mediastinitisFeatures: fever, chest pain, ↑ WBC, chest x-ray shows mediastinal wideningTreatment: surgical (drainage and debridement), long-term antibiotics (minimum of 4-6 weeks) Mediastinal hemorrhage Features: excessive blood (> 100-200 mL per hour) in chest tube drainage; decreased cardiac output, hemoglobin, blood pressure, or urine output; chest x-ray shows mediastinal wideningTreatment: raising the airway pressure for artificial ventilation; surgical exploration of the mediastinum Other Complications resulting from sternotomy (wound infection, sternal dehiscence, sternal osteomyelitis, etc.) Postoperative renal failure Neurologic deficits and coma Outcome and prognosis Prognosis following CABG depends on a variety of factors, such as anatomical location and severity of the stenoses, presence of comorbidities, patient age, and preoperative levels of activity. Successful grafts typically last 8-15 years and provide an improved chance of survival (decreased 5-year mortality, especially in patients with triple vessel disease). Further progression of arteriosclerosis may still occur after CABG.

Antiplatelet agents Antiplatelet agents are drugs that inhibit enzymes or receptors required for platelet activation, platelet aggregation, and/or thrombus formation. The most commonly used antiplatelet agent is acetylsalicylic acid (aspirin), which is an irreversible cyclooxygenase inhibitor with dose-dependent antiplatelet, antipyretic, analgesic, and anti-inflammatoryactions. Low-dose aspirin is used in the management of cardiovascular events (e.g., acute MI, angina) and for primary/secondary prophylaxis of cardiovascular disease. Adverse effects of aspirin include peptic ulcers, hemorrhage, salicylate toxicity, aspirin-exacerbated respiratory disease, and Reye syndrome. P2Y12 receptor antagonists (clopidogrel, prasugrel, ticagrelor) are mainly used in conjunction with aspirin (dual antiplatelet therapy) in the management of acute coronary syndrome and to prevent stent thrombosis in patients after percutaneous coronary intervention (PCI). Although allergic reactions are more common, P2Y12 receptor antagonists cause fewer hemorrhagic/gastrointestinal complications compared to aspirin. Glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, and tirofiban) are parenterally administered, rapid-acting antiplatelet agents that are only used in high-risk patients in which PCI is planned. Gp IIb/IIIa inhibitors can cause a sudden drop in platelet counts (acute profound thrombocytopenia), necessitating platelet count monitoring. All antiplatelet agents increase the risk of hemorrhage and are contraindicated in patients who have thrombocytopenia or an active/recent hemorrhagic event (e.g., hemorrhagic stroke, major surgery within the past 30 days)

Irreversible cyclooxgenase inhibitors Acetylsalicylic acid(aspirin) Acute coronary syndrome ischemic stroke Primary and secondary prevention of cardiovascular disease Aspirin exacerbated respiratory disease GI upset Salicylate toxicity Reye syndrome Affects the kidneys in a dose-dependent manner: Low doses: uric acid retentionHigh doses: uric acid excretion P2Y12 receptor antagonists (ADP receptor inhibitors) Clopidogrel Prasugrel Ticagrelor Ticlopidine Dual antiplatelet therapy (with acetylsalicylic acid) in STEMIUnstable angina/NSTEMIBefore PCI Alternative to aspirin Allergic reactions Hemorrhage GI upset Glycoprotein IIb/IIIa inhibitors Abciximab Eptifibatide Tirofiban High-risk patients with unstable angina/NSTEMI before undergoing PCI Acute thrombocytopenia Hemorrhage AgentsAcetylsalicylic acid (aspirin)EffectsIrreversible COX-1 inhibition → inhibition of thromboxane (TXA2) synthesis in platelets → inhibition of platelet aggregation (antithrombotic effect) Onset of antiplatelet action: within minutesDuration of antiplatelet action: 7-10 days Irreversible COX-1 and COX-2 inhibition → inhibition of prostacyclin and prostaglandin synthesis → antipyretic, anti-inflammatory, and analgesiceffect IndicationsAcute myocardial infarctionAcute ischemic stroke [3]Angina pectoris (stable and unstable)After revascularization procedures (e.g., PTCA, CABG, carotid endarterectomy) Secondary prevention of cardiovascular disease Primary prevention of CVD and colorectal cancer Symptomatic peripheral arterial diseaseGiant cell arteritis See non-opioid analgesics for indications in pain management and inflammation.Side effectsGastrointestinal (most common): dyspepsia, gastric ulceration, hemorrhage, perforationAspirin blocks COX-1 → inhibits conversion arachidonic acid to PGH2 → ↓ formation of PGE2 → ↓ secretion of mucus and bicarbonate by epithelium → loss of protective layer on mucosa → gastric acid damages tissue → ↑ risk of ulcers, bleeding, and perforationCoagulopathy and bleedingAspirin exacerbated respiratory disease (AERD) Definition: a chronic condition characterized by Samter's triad; exacerbated by a pseudoallergic sensitivity reaction to aspirin and other NSAIDs(NSAID intolerance) Clinical features: Samter's triad (asthma, chronic/recurrent rhinosinusitis, nasal polyps) Diagnosis: NSAID/aspirin challenge test Treatment: avoid NSAIDs; aspirin desensitization Reye syndrome: rare disease in patients < 19 years who have been treated with aspirinPathophysiologyThe liver is dependent on mitochondrial fatty acid oxidation (via the TCA cycle) for ATP production.Salicylates are metabolized by hepatic mitochondria; ↑ concentration of salicylate metabolites cause mitochondrial injury and inhibition of enzymes required for fatty acid oxidation.Viruses alter the metabolism of salicylates → accumulation of salicylate metabolites → hepatic mitochondrial injury → failure of hepatic ATPproduction → hepatic failure → hyperammonemia and metabolic acidosis (and accumulation of fat within hepatocytes)Hyperammonemia → astrocyte edema → ↑ ICP → vomiting and neurological symptomsClinical features: triad of a preceding viral illness , acute encephalopathy , and (fatty degenerative) liver failure Diagnosis: clinical; liver biopsy (in doubtful cases) ; head CT/MRI ; lumbar puncture Treatment: supportive Aspirin should be avoided in patients < 19 years of age, esp. in those who have a febrile illness! The lifespan of a platelet is 7-10 days. If aspirin is held prior to surgery, it should be discontinued one week in advance. Emergency inhibition of the antiplatelet effect of aspirin can only be achieved by administering platelet concentrates! P2Y12 receptor antagonistsAgentsClopidogrelPrasugrelTicagrelorTiclopidineEffectsInhibition of P2Y12 receptor on platelets (ADP receptor) → inhibition of platelet aggregationADP usually binds to P2Y12 receptors, leading to activation of Gp IIb/IIIa receptors and subsequent platelet aggregation.Side effectsAllergic reactions (rash, pruritus, anaphylaxis)Hemorrhage Gastrointestinal complications Neutropenia/agranulocytosis (ticlopidine only)IndicationsAs dual antiplatelet therapy (in combination with acetylsalicylic acid)STEMI Unstable angina/NSTEMI Before PCISecondary prophylaxis against cardiac events in patients post PCI and/or stenting As an alternative to aspirin in cases of intolerance Glycoprotein IIb/IIIa inhibitorsAgentsAbciximab EptifibatideTirofibanEffectsGp IIb/IIIa inhibitors bind to and block glycoprotein IIb/IIIa receptors on the surface of the platelets → prevention of platelets binding to fibrinogen → inhibition of platelet aggregation and thrombus formationSide effectsAcute profound thrombocytopenia HemorrhageIndicationsOnly indicated in high-risk patients with unstable angina/NSTEMI planned for PCI within 24 hours to prevent thrombotic complications (not for routine use) High-risk factors include age > 75 years; diabetics; chest pain lasting > 20 minutes; elevated troponin I(and other markers); ST depression on ECG; development of pulmonary edema, and left ventricular dysfunction. Abciximab and tirofiban are contraindicated in patients with thrombocytes < 100,000/mm3! Contraindications Known allergy against an antiplatelet agent Active/recent hemorrhage within the past 30 days (e.g., gastric ulcers or intracranial bleeding) Major surgery/severe trauma within the past 30 days Severe hypertension Aortic dissection Thrombocytopenia Aspirin: patients < 19 years of age with a febrile illness (risk of Reye syndrome)

Parenteral anticoagulation Parenteral anticoagulants are routinely indicated for the prevention and treatment of venous thromboembolism. Heparinis typically the preferred agent for inpatient parenteral anticoagulation. Serious side effects include bleeding complications and type 2 heparin-induced thrombocytopenia (HIT), which causes arterial and venous thromboembolismdue to an antibody-mediated aggregation of platelets. A drop in platelet count (< 100,000 platelets /μL or decrease of > 50% compared to baseline) may indicate HIT; therefore, the platelet count must be closely monitored in patients on parenteral anticoagulants, especially heparin. If HIT is suspected, treatment involves discontinuing all heparins and beginning nonheparin anticoagulation (usually argatroban).

Low dose: subcutaneous administration every 8-12 hrs High dose: intravenous administration with bolus and continuous application via infusion pump Unfractionated heparin (UFH) Drug: heparin AdministrationProphylaxis: subcutaneousTherapeutic: continuous intravenous infusion Monitoring during therapy: activated partial thromboplastin time (aPTT) , platelet count (including baseline before treatment is started) Clearance: hepatic (preferred agent for patients with renal insufficiency) Antidote: protamine sulfate (a positively-charged protein that can neutralize negatively-charged heparin by forming inactive complexes) In order to detect heparin-induced thrombocytopenia, platelets must be continuously monitored during heparin therapy and a baseline should be established before commencing treatment. Low molecular weight heparin (LMWH) Drugs: enoxaparin, dalteparin, tinzaparin, nadroparin, Administration: subcutaneous Monitoring during therapy: anti-factor Xa activity can be assessed in specific cases; not generally recommended Clearance: renal (therefore, contraindicated for patients with renal insufficiency) Antidote: protamine sulfate (partial reversal) Synthetic heparin Drugs: fondaparinux Administration: subcutaneous Monitoring during therapy: Not generally recommendedAnti-factor Xa activity can be assessed in specific cases Antidote: possibly activated prothrombin complex concentrates (aPCC) Direct thrombin inhibitors Drugs: argatroban, bivalirudin, desirudin, dabigatran AdministrationIntravenous: argatroban, bivalirudin, desirudinOral: dabigatran (see direct oral thrombin inhibitors) Monitoring during therapy: not generally recommended AntidotePossibly aPCC and/or antifibrinolytics (e.g., tranexamic acid)Dabigatran: idarucizumab (monoclonal antibody) [1] Effects Unfractionated heparin (UFH) Enhances the activity of antithrombin Indirect inhibitor ofFactor Xa: antithrombin III potentiation → inhibition of factor Xa → decreased activation of prothrombin → ↓ thrombin→ ↓ fibrinogen activation → ↓ fibrinThrombin (factor IIa): UFH binds antithrombin III and thrombin simultaneously at two distinct binding sites → antithrombin III and thrombin held by heparin in close proximity (complex formation) → ↑ thrombin inhibition → ↓ fibrinogen activation → ↓ fibrin Short half-life: anticoagulant effect quickly ceases once administration is stopped Low molecular weight heparin (LMWH) and synthetic heparin (fondaparinux) Mechanism of action [5][6]LMWH: binds to antithrombin III → inhibition of factor Xa → decreased conversion of prothrombin → ↓ thrombinSynthetic heparin: only binds to antithrombin III → selective inhibition of factor Xa Higher bioavailability than unfractionated heparin Long half-life: 2-4 times longer than unfractionated heparin Direct thrombin inhibitors Directly inhibit thrombin (freely circulating and in association with clots) The effect of most parenteral anticoagulants (except for direct thrombin inhibitors) depends on native antithrombin. In patients with antithrombin III deficiency (e.g., due to nephrotic syndrome), this effect is reduced! AgentsSide effectsUFH and LMWHAllergic reactionsHeparin-induced thrombocytopenia: risk of type 2 HIT LMWH:UFH ≈ 1:10Osteoporosis Drug interactions (e.g., ASS, tetracycline)Synthetic heparinOccasionally low platelet countDirect thrombin inhibitorsAllergic reactions, fever Heparin-induced thrombocytopenia (HIT) Treatment with heparin, especially UFH, can cause thrombocytopenia. HIT can be differentiated into type 1 (asymptomatic), and type 2, which is antibody-related and prognostically worse. Type 1 HIT∼ 10-20%Within the first 5 days after beginning treatmentModerate : > 100,000 platelets/μLDirect interaction between heparin and platelets (e.g., heparin directly induces platelet aggregation) No antibodies involved (nonimmunologic) Continue heparin (plateletsusually return to normal with continued heparinadministration) Monitor platelets Type 2 HITMore commonly occurs with UFH ∼ 1-5% for UFH∼ 0.1-1% for LMWH Day 5-14 Massive reduction: < 100,000 platelets/μL (or decrease of > 50% compared to baseline) Heparin and platelet factor 4 (PF4) form a complex → production of IgG antibodies against the heparin-PF4 complex → IgG antibody-heparin-PF4 immunocomplex binds on platelet surface → platelet activation and aggregation → consumption of platelets (thrombocytopenia) and arterial/venous thrombosis Clinically significant Features of thrombocytopenia: Bleeding is rare because platelet nadir (lowest point) is usually > 20,000 platelets/μL. Features of thrombosisVenous > arterial thrombi manifestationsInvolving legs (e.g., DVT), cardiac vessels (e.g., myocardial infarction), and skinOrgan ischemia or infarction Skin necrosis Limb gangreneTreat presumptively as soon as HIT is suspected, and continue treating until confirmatory testingresults. Immediate discontinuation of all heparin-containing products Send confirmatory test (ELISA, serotonin release assay, or functional assay against PF4 autoantibody). Initiate nonheparin anticoagulation Direct thrombin inhibitor (argatroban is first-line) [10]Alternative: synthetic heparin (can be used in patients with hepatic insufficiency) NO warfarin until platelet count has normalized (> 150, 000 platelets/μL) Transition to warfarin or other long-term oral anticoagulants for at least two months (often longer if the patient had thrombosis). Inform patient of their heparin allergy and to never receive any heparin products for life. The significantly increased risk of bleeding is the main side effect of all anticoagulants. Heparin treatment requires regular monitoring of the platelet count, especially for UFH, even before starting treatment. Indications Heparin Low-dose therapy DVT prophylaxis for prolonged bedrest, peri- and postoperative state, immobility High-dose therapy Immediate anticoagulation effect forAtrial fibrillationDVT, acute arterial thrombosis, pulmonary embolismAcute coronary syndrome, myocardial infarctionMechanical heart valve replacementVTE prophylaxis for patients with hemodialysis, heart-lung machine, etc. Low molecular weight heparin [13] Prophylaxis of DVT in orthopedic and abdominal surgery, prolonged immobility Treatment of DVT Acute coronary syndrome Direct thrombin inhibitors Atrial fibrillation Venous thromboembolism Type 2 HIT Use direct thrombin inhibitors (Bivalirudin, Argatroban, Dabigatran) to treat the BAD HIT (type 2 HIT has a worse prognosis than type 1 HIT). Contraindications Recent stroke Uncontrolled hypertension Active bleeding HIT (except for direct thrombin inhibitors which can be used for anticoagulation in HIT) Unfractionated heparin (UFH) Subcutaneous or intravenous administration Therapeutic administration requires infusion pump Low dose: subcutaneous administration every 8-12 hrs High dose: intravenous administration with bolus and continuous application via infusion pump Adequate anticoagulation is achieved sooner due to direct effect on thrombin Protamine (the antidote) antagonizes effect of UFH Short half-life means anticoagulant effect quickly ceases once stopped If used therapeutically, PTT levels have to be monitored frequently (target range: 1.5-2.5-foldprolongation) In comparison with LMWHType 2 HIT is about 10-fold more commonSevere bleeding is more common Emergencies (more easily titrated, available as IV infusion) For patients with advanced renal failure (e.g., in patients with severe renal insufficiency (CrCl < 30mL/min) or the elderly) Low-molecular-weight heparin (LMWH) Always administer subcutaneously Dosage depends on specific drug used, indication, body weight, and kidney function; adjust to body weight and decreased kidney function Effect of LMWH lasts for about 12 hours Monitoring of anti-factor Xa is only necessary in patients with decreased kidneyfunction (and significant over- or underweight); anti-factor Xa activity is measured 4 hrs after administration Use cautiously in renal failure because of its renal elimination Contraindicated if poor renal function (CrCl < 30mL/min) No full antagonist available DVT prophylaxis, outpatient care (longer half-life → fewer injections) Generally preferred to UFH (fewer side effects, easier handling) as long as there are no contraindications Special patient groups Pregnancy Physiological hypercoagulability (e.g., due to increased levels of clotting factors) leads to increased risk of thrombosis. UFH and LMWH can be used during pregnancy: neither cross the placenta nor are they transferred through breastmilk LMWH has fewer side effects. Patients with decreased renal function In severe renal failure: accumulation of LMWH → increased bleeding risk → adjust dose or switch to UFH

Diuretics Diuretics are a group of drugs that induce increased production of urine. Depending on the class, diuretics act on different renal structures and lead to varying changes in the volume and composition of urine as well as electrolyte balance. Some of these effects can be used to treat disorders like hypercalcemia, hypocalcemia or hyperaldosteronism. The most commonly used diuretics with a pronounced diuretic effect are thiazides, loop diuretics, and potassium-sparingdiuretics. Osmotic diuretics and carbonic anhydrase inhibitors are used in acute settings to lower intracranial and/or intraocular pressure (e.g., cerebral edema, acute glaucoma). The most important side effects of most diuretics include volume depletion and excessive changes in serum electrolyte levels (particularly of sodium and potassium) which increases the risk for cardiac arrhythmias.

Main characteristics and mechanisms Effects on serum Thiazide diureticsInhibition of Na+-Cl--cotransporters in the early distal tubuleEffects compared to loop diureticsGreater loss of potassiumReduced effectiveness if GFR < 30 mL/min Water elimination pH Na+ K+ Ca2+ ↑↑↓*↓↑ Loop diuretics Inhibition of Na+-K+-2Cl--cotransporters in the thick ascending loop of Henle ↑↑↑↓*↓↓ Potassium-sparing diuretics Inhibition of expression of Na+-channels in the collecting duct (aldosterone receptor antagonists) or Blocking of Na+-channels in the distal convoluted tubule and the collecting duct(epithelial sodium channel blockers) Leads to ↓ reabsorption of sodium and ↓ secretion of potassium in the distal convoluted tubule and proximal collecting duct (↑)↓↓*↑↔︎ Osmotic diuretics Effect the entire tubule, but predominantly act on the straight segment of the proximal tubule and the descending loop of Henle ↑ Blood and tubular fluid osmolarity → ↑ urine flow, ↓ intracranial/intraocular pressure ↑↑ Carbonic anhydrase inhibitors Inhibit carbonic anhydrase in the proximal convoluted tubule (small diuretic effect) → ↑ elimination of bicarbonate (↑) ↓(↓)(↓)↔︎ Thiazide diuretics Agents Hydrochlorothiazide (HCTZ) Chlorthalidone Chlorothiazide Mechanism of action Inhibition of Na+-Cl- cotransporters in the distal convoluted tubule → ↑ excretion of Na+ (saluresis) and Cl- → ↑ excretion of potassium (kaliuresis) → diuresis Increased reabsorption of Ca2+ Hyperpolarization of smooth muscle cells → vasodilation Hyperpolarization of pancreatic beta cells → decreased insulin release Side effects Hypokalemia and metabolic alkalosis Hyponatremia, hypomagnesemia Hypercalcemia Hyperglycemia Hyperlipidemia (↑ cholesterol, triglycerides) Hyperuricemia Thiazide diuretics may be combined with potassium-sparing diuretics (e.g., aldosterone receptor antagonists) to avoid hypokalemia! Indications Hypertension Chronic edema secondary to congestive heart failure, cirrhosis, and kidney disease Sequential nephron blockade Prevention of calcium kidney stones Nephrogenic diabetes insipidus Contraindications Hypersensitivity Anuria Severe hypokalemia InteractionsGlucocorticoids → increased hypokalemiaCarbamazepine → increased hyponatremiaACE inhibitors → hypotension (especially first-dose hypotension)Propranolol → increased hyperlipidemia and hyperglycemiaNSAIDs → ↓ diuretic effect ↑ Effects of digitalis , methotrexate, and lithium Loop diuretics Agents Sulfonamides: furosemide, torsemide, bumetanide Other: ethacrynic acid Mechanism of action Blockage of Na+-K+-2Cl--cotransporters in the thick ascending loop of HenleConcentration gradient between renal medulla and cortex diminishes over time → urine cannot be concentrated any more → diuresis↓ Reabsorption of Ca2+ and Mg2+ ↑ PGE releaseDilation of renal afferent arterioles → diuresisGeneral venodilation (rapid venous pooling) → ↓ cardiac preload Loops lose calcium! Side effects Metabolic imbalances Hypokalemia, hypomagnesemia, hypocalcemia, hypochloremia, hyponatremia (moderate) Metabolic alkalosisHyperuricemia/gout Hyperglycemia Ototoxicity (potentially permanent hearing damage) Dehydration/hypovolemia Sulfonamide hypersensitivity (except ethacrynic acid) → rash, interstitial nephritis Hypokalemia and/or hypomagnesemia can lead to life-threatening arrhythmias! Indications Hypertension Edema treatmentCardiac (acute and congestive heart failure, peripheral edema, lung edema)Renal (nephrotic syndrome)Hepatic (liver cirrhosis) Renal failure(acute and chronic) Forced diuresisDefinition: massive diuresis for forced renal elimination of (toxic) substancesImplementation: IV administration of large amounts of fluids in combination with loop diureticsIndications: hypercalcemic crisis, severe hyperkalemia, rhabdomyolysis, intoxication (e.g., lithium) Sequential nephron blockadeUsed to overcome resistance to diuretic treatment Method: combination of loop diuretics and thiazides → restoration of diuretic effects FurosemideTorsemideBumetanideEthacrynic acidAnuria YesYesYesYesSulfonamide hypersensitivityYesYesYesNoHepatic coma or severe electrolyte depletionNo No YesNo History of severe watery diarrhea (caused by the drug) NoNoNoYes Potassium-sparing diuretics Agents Aldosterone receptor antagonists: spironolactone, eplerenone Epithelial sodium channel blockers: triamterene, amiloride To memorize potassium-sparing diuretics, Keep your SEAT: K+ is kept by Spironolactone, Eplerenone, Amiloride, and Triamterene! Mechanism of action Although the molecular pathways differ, both types of potassium-sparing diuretics have very similar clinical effects. Aldosterone receptor antagonists (spironolactone, eplerenone): Competitively bind to aldosterone receptors in the late distal tubule and the collecting duct → inhibit effects of aldosterone → decreased Na+ reabsorption and K+ excretion → diuresisSpironolactone also acts (nonspecifically) on sex hormone receptors → endocrine side effects Epithelial sodium channel blockers (triamterene, amiloride): direct inhibition of the epithelial sodium channels in the distal convoluted tubule and the collecting duct → reduced Na+ reabsorption and reduced K+ secretion → diuresis Side effects Metabolic and electrolyte imbalances : hyperkalemia, hyponatremia, metabolic acidosis Gastrointestinal disturbances (nausea, vomiting, diarrhea) Endocrine disturbances Men: gynecomastia, impotenceWomen: amenorrhea Indications Hypertension (especially if hypokalemia is also present) Ascites/edema due to congestive heart failure, nephrotic syndrome or cirrhosis of the liver Hyperaldosteronism SpironolactoneEplerenoneTriamtereneAmilorideAnuria/renal insufficiencyYesYesYesYes Pre-existinghyperkalemiaYesYesYesYesAddison's diseaseYesYesNoNoOtherCreatinine clearance< 30 mL/minConcomitant use of strong CYP3A4 inhibitors Patients with hypertension and type II diabetes mellitus and microalbuminuriaCreatinine clearance< 50 mL/minCombination with other potassium-sparing diuretics or other medications containing triamtereneCombination with other potassium-sparing diuretics or potassium supplements Elevated serum creatinine (> 2 mg/dL in men, > 1.8 mg/dL in women)Combination with eplerenone, other potassium-sparing diuretics or potassium supplements Osmotic diuretics Agents Mannitol Urea Mechanism of action No absorption into cells → intravascular binding of water → ↓ intracranial/intraocular pressure Glomerular filtration throughout the entire tubule without reabsorption → ↑ tubular fluid osmolarity → ↑ urine flow No saluresis Side effects Dehydration Initial cardiac volumetric strain Metabolic and electrolyte imbalances Effective glomerular filtration → hypernatremiaIneffective glomerular filtration or administration of very high doses → ↑ plasma osmolality → ↑ extracellular fluid volume → pulmonary edema, potassium fluctuations, hyponatremia, metabolic acidosis Indications Cerebral edema Acute glaucoma Prevention of acute renal injury in cases of oliguria Forced renal excretion of substances (e.g., drugs or toxins) Contraindications Anuria Progressive heart failure Severe pulmonary edema Severe dehydration Carbonic anhydrase inhibitors Agents Acetazolamide Mechanism of action Inhibition of carbonic anhydraseKidney: in the proximal convoluted tubule → ↑ H+ reabsorption and inhibition of Na+/H+ exchange → ↑ NaHCO3 diuresis and ↑ HCO3- elimination Eyes: ↓ production of aqueous humorBrain: ↓ CSF production Side effects Hyperammonemia with paresthesias Proximal renal tubular acidosis → hyperchloremic, non-anion gap metabolic acidosis Hypokalemia Sulfa allergy Indications Acute glaucoma Pseudotumor cerebri , altitude sickness Metabolic alkalosis Prevention of cystine kidney stones Contraindications Hyponatremia, hypokalemia Hyperchloremic metabolic acidosis Adrenocortical insufficiency Severe renal insufficiency Hepatic disease or insufficiency Long-term use in glaucoma

Nitrates Nitrates are a class of medications that increase the release of nitric oxide (NO) in vascular smooth muscle cells, leading to smooth muscle relaxation and subsequent vasodilation. Veins are affected more than arteries, and most therapeutic effects of nitrates result from venous pooling and subsequently decreased preload. Rapid- and short-acting nitrates are primarily used in the symptomatic treatment of acute angina pectoris and hypertensive urgency. Side effects may include headache (nitrate-induced headache), gastroesophageal reflux, and hypotension with syncope. Prior intake of PDE-5 inhibitors significantly increases the risk of hypotension.

NitroglycerinOralSublingualShort2-5 minutes15-30 minutesTransdermal patchLong30 minutes8-14 hoursIsosorbide dinitrateSublingualShort2-5 minutes1-2 hoursOralLong1 hour4-6 hoursIsosorbide mononitrateOralLong30-45 minutes6-24 hoursSodium nitroprussideIntravenousUsed primarily for hypertensive crises (see "Indications" below) Effects Exogenous supply of nitric oxide (NO) through nitrate → activation of guanylyl cyclase → ↑ cyclic guanosine monophosphate (cGMP) → activation of protein kinase GIncreases SERCA activity → ↓ intracellular calcium → ↓ recruitment of contractile units → vasodilationIncreases myosin light chain phosphatase activity → ↓ phosphorylated myosin → smooth muscle relaxation → vasodilationPeripheral vasodilationDecreased preload through venous dilation (venous pooling) → reduces myocardial wall tension → improved myocardial perfusionDecreased afterload → reduces contraction effort → ↓ myocardial oxygen demand Dilates veins >>> arteriesCoronary dilation → improved myocardial perfusion In patients with atherosclerotic CAD, arterioles are already dilated to maximize cardiac blood flow (due to flow-limiting stenosis) → difficult to dilate coronary vessels further → limited effect of nitrates Anginal pain relief: ↓ preload through venous pooling → ↓ heart size → ↓ oxygen demand → ↓ pain Side effects Circulatory dysregulation: hypotension, reflex sympathetic activity → reflex tachycardia → nitrate syncope Nitrate-induced headache: vasodilation of the cerebral arteries Gastroesophageal reflux: relaxation of the lower esophageal sphincter Development of tolerance Prevention: intermittent therapy with nitrate-free intervals of at least 8 hours Cyanide toxicity after sodium nitroprusside infusion (see cyanide poisoning) Methemoglobinemia "Monday disease": Industrial workers who are exposed to nitrates during the work week develop a tolerance over the course of the week; no exposure during weekends leads to loss of tolerance. Reexposure on Monday causes dizzinessand headache. Indications Angina pectorisShort-acting nitrates such as sublingual nitroglycerin, isosorbide dinitrate, or nitroglycerin spray for treatment of acute attacks.Long-acting nitrates such as isosorbide mononitrate can be taken regularly (2-3 times daily) for anginalprophylaxis: unlike some other nitrates, isosorbide mononitrate does not undergo first-pass metabolism by the liver and thus has ∼100% bioavailability. Hypertensive crisis: short-term reduction of blood pressure Hypertensive pulmonary edema Chronic heart failure Contraindications HypotensionRisk of life-threatening hypotension if taken within 24 hours of a PDE-5 inhibitor (e.g., patients with angina pectoris) Stenosis of the left ventricular ejection tract (aortic stenosis, hypertrophic obstructive cardiomyopathy) Myocardial infarction with right ventricular failure Increased intracranial pressure

Phosphodiesterase inhibitors Phosphodiesterase inhibitors (PDE inhibitors) are a class of drugs that inhibit phosphodiesterase enzymes (PDEs). PDEsnormally break off phosphate groups and decrease cAMP or cGMP in target cells. PDE inhibitors are classified according to which enzyme(s) they act upon as nonspecific, PDE5, PDE4, and PDE3 inhibitors. PDE5 inhibitors cause pulmonary vasodilation and penile smooth muscle relaxation, and are used for pulmonary hypertension and erectile dysfunction. PDE4 inhibitors enable bronchial dilation in severe COPD. PDE3 inhibitors have positive inotropic, vasodilator, and antiplatelet effects, which are used in acute heart failure and in peripheral vascular disease. PDE3 inhibitors are not recommended for long-term use in patients with heart failure because of their strong cardiostimulatory effects. Nitratesor alpha-blockers are strongly contraindicated in patients taking PDE5 inhibitors because of the risk of life-threateninghypotension.

Nonspecific phosphodiesteraseinhibitors (inhibitors of PDE3, -4 and -5) Theophylline COPD Asthma Nonspecific PDE inhibition → ↓ hydrolysis of cAMP → ↑ cAMPlevels Inhibition of proinflammatory mediators Deceleration of fibrotic changes in the lung Relaxation of the bronchial musculature Phosphodiesterase type 5 inhibitor (PDE5 inhibitor) Sildenafil(Viagra®) Tadalafil Erectile dysfunction Pulmonary hypertension Benign prostatic hyperplasia (tadalafilonly) PDE5 inhibition → ↓ breakdown of cGMP → ↑ cGMP → ↑ smooth muscle relaxation in reaction to NOactivation → Pulmonary vasodilation→ Penile smooth muscle relaxation Decrease in pulmonary vascular resistance ↑ Blood flow in the corpus cavernosum→ increase in penis size during an erection Inhibition of proinflammatory mediators Deceleration of fibrotic changes in the lung Relaxation of the bronchial musculature Phosphodiesterase type 4 inhibitor (PDE4 inhibitor) Roflumilast Severe COPD PDE4 inhibition → ↑ cAMP in neutrophils, granulocytes, and bronchial epithelium Inhibition of proinflammatory mediators Deceleration of fibrotic changes in the lung Relaxation of the bronchial musculature Phosphodiesterase type 3 inhibitor (PDE3 inhibitor) Milrinone Amrinone Acute treatment of decompensated cardiac failure with cardiogenic shock Cilostazol Dipyridamole Intermittent vascular claudication Antiplatelet (anti-angina, TIA/strokeprevention) Prevention of coronary stentrestenosis PDE3 inhibition → ↑ cAMP In the myocardium: ↑ cAMP → activation of calcium channels → cardiostimulatory effects (e.g., ↑ contractility)In peripheral vessels: ↑ cAMP → smooth muscle relaxation → vasodilation with reduced cardiovascular preload and afterloadIn platelets: ↑ cAMP → inhibition of platelet aggregation Increase cardiac inotropy acutely in cardiac failure Vasodilation and antiplatelet action in intermittent claudication Inhibition of platelet aggregation for angina prophylaxis, TIA/strokeprevention, and deceleration of restenosis in coronary stents Side effects Nonspecific phosphodiesterase inhibitorsCardiotoxicity: arrhythmias, tachycardiaNeurotoxicity: dizziness, headache, insomnia, irritability, lightheadedness; at high levels, seizuresGastrointestinal (GI) upset: nausea, diarrhea Phosphodiesterase type 5 inhibitors. Headaches, cutaneous flushing LightheadednessVisual deficits: blue-tinted vision, or cyanopiaRunny nose, nasal congestionExanthemaDyspepsiaRarely: myocardial infarction, stroke, hearing loss, optic neuropathy Phosphodiesterase type 4 inhibitorsGI upset (nausea, abdominal pain) Weight lossMental disorders: sleep disturbances, anxiety, depression Phosphodiesterase type 3 inhibitorsTachycardia, ventricular arrhythmias (most common and severe side effect! )HeadachesHypotensionCutaneous flushingGI upset: nausea, abdominal pain Contraindications Because of their vasodilatory and arrhythmogenic effects, PDE inhibitors have a number of contraindications: Phosphodiesterase type 5 inhibitorsNitrates: Use of PDE5 inhibitors with nitrates can result in life-threatening hypotension. Both nitrates (e.g., sublingual nitroglycerin) and PDE-5-inhibitors (e.g., vardenafil) function by increasing cGMPconcentration → cGMP leads to activation of myosin-light-chain phosphatase (MLCP) → dephosphorylates light chains of myosin → smooth muscle cell relaxation in blood vessels → vasodilationAlpha-blockers: Use of PDE5 inhibitors with alpha-blockers can also result in hypotension Phosphodiesterase type 3 inhibitorsSevere obstructive cardiomyopathy or ventricular aneurysmHypovolemiaTachycardia Patients being treated with PDE5s should not receive nitrates in unstable angina pectoris, acute coronary syndrome, and myocardial infarction because of the risk of a life-threatening decrease in blood pressure!

Cyanotic congenital heart defects Cyanotic heart defects are congenital cardiac malformations that commonly affect the atrial or ventricular walls, heart valves, or large blood vessels. Common causes include genetic defects (e.g., trisomies), maternal infections (e.g., rubella), and maternal consumption of drugs or alcohol during pregnancy. Pathophysiologically, cyanotic heart defects are often characterized by a right-to-left shunt, which results in deoxygenated blood entering the systemic circulation. The resulting hypoxemia manifests clinically as cyanosis, which may occur as acute, life-threatening episodes. Further symptoms include failure to thrive, characteristic heart murmurs, and symptoms of heart failure. The diagnosis is confirmed through visualization of the defect on echocardiography. Further diagnostic findings include low oxygen saturation and characteristic x-ray findings (e.g., decreased pulmonary markings). Heart defects requiring treatment are repaired via catheter procedures or surgery. Supportive medical therapy is required in cases of heart failure (e.g., diuretics, inotropic agents) or if surgery cannot be performed (e.g., prostaglandin). If untreated, most cyanotic heart defects are fatal within the first year of life.

Overview of cyanotic congenital heart defects General pathophysiological processes Heart defects may lead to the formation of connections between the right and the left heart (see "Pathophysiology" in acyanotic congenital heart defects). Right-to-left shunt: blood flows from the right to the left heart via a shunt → deoxygenated blood enters the systemic circulation → cyanosis General clinical features "Blue babies": pale gray or blue skin color caused by cyanosis Nail clubbing Exertional dyspnea, tachypnea, and fatigue Squatting for relief during hypoxemic episodes Poor weight gain, failure to thrive Characteristic heart murmurs Features of underlying genetic syndromes For specific features, see "Clinical features" in the subsections below. Treatment Infusion of prostaglandin (PGE1) to prevent closure of the ductus arteriosus in ductal-dependent defects (see "General treatment concepts" in acyanotic congenital heart defects) In cases of heart failureDecrease fluid volume and lower pulmonary vascular resistance: diuretics or ACE-I inhibitorsInotropic agents to improve contractility of the heart (e.g., digoxin) Antibiotic prophylaxis for bacterial endocarditis for all patients with unrepaired cyanotic congenital heart disease The "5 Ts" of cyanotic CHDs: Tetralogy of Fallot, Transposition of the great vessels, Tricuspid atresia, Total anomalous pulmonary venous return, and Truncus arteriosus Tetralogy of Fallot Definition Tetralogy of Fallot is defined as the simultaneous occurrence of the following four defects: Right ventricular outflow obstruction (RVOT) due to pulmonary valve stenosis Right ventricular hypertrophy Ventricular septal defect (VSD) Overriding aorta (above the VSD) Epidemiology Most common cause of cyanotic CHD (∼ 4/10,000 live births in the US) Etiology Typically sporadic; sometimes associated with genetic defects (e.g., Down syndrome, DiGeorge syndrome) Associated with other cardiac anomalies in ∼ 40% of patients Pathophysiology The extent of right ventricular outflow tract obstruction and central pulmonary hypoplasia determines the severity of hemodynamic dysfunction.Mild obstruction → left-to-right shunt via VSD more pronounced → no cyanosisSevere obstruction → right-to-left shunt via VSD more pronounced → severe cyanosis Clinical findings Mild cyanosis Tet spells Intermittent hypercyanotic, hypoxic episodes with a peak incidence 2-4 months after birthAssociated with psychological and physical stress (e.g., crying, feeding, defecation) Untreated young children tend to squat. Auscultatory finding: harsh systolic murmur that is best heard over Erb's point and left upper sternal border Diagnostics Pulse oximetry: ↓ SpO2 Hyperoxia test: to distinguish cardiac from pulmonary causes of cyanosis ECG: right axis with right heart hypertrophy; P pulmonale with increasing age ImagingEchocardiography: detection of the main features of TOF, quantification of right ventricular outflow tract pressure gradient (supplementary cardiac catheterization may be performed)Chest x-ray: absent pulmonary artery segment, decreased pulmonary vasculature, small "boot-shaped" heart Treatment Severe RVOT: IV prostaglandin (PGE1) until surgery Acute hypoxia (tet spells) Administer oxygenKnee to chest position, squattingIV morphine for sedation and fluidsIf above measures fail: IV beta blockers Heart failure: See "Treatment" in "Overview" section above. Long-term managementSurgery: performed within the first year of life, if possible VSD repair: patch closure of the ventricular septal defect; ensuring correct aortal positioning above the left ventricleEnlargement of the RVOT: resection of the obstructive infundibular musculatureFollow-up care: to prevent long-term complications such as heart failure, arrhythmias, and neurodevelopmental impairment Transposition of the great vessels (TGV) Definition Anatomical reversal of the aorta and the pulmonary artery Epidemiology Accounts for ∼ 20 % of all cyanotic CHD Often associated with VSD, left ventricular outlet obstruction, and abnormal valves and coronary arteries Etiology Intrauterine risk factorsInfants born to diabetic mothersMaternal alcohol consumption/poor nutritionMaternal age > 40 yearsRubella infection or other viral illness Rarely associated with genetic syndromes or extracardiac malformationsDiGeorge syndrome Down syndrome, Edward syndrome, Patau syndrome Pathophysiology Failed spiraling of the aorticopulmonary septum → pulmonary circulation and systemic circulation function as completely separate parallel circuits → oxygenated blood cannot pass into systemic circulation → incompatible with life unless mixing occurs via an intracardiac shunt across a PFO, VSD, or ASD or via an extracardiac connection (e.g., PDA) Clinical findings Postnatal cyanosis (not affected by exertion or supplemental oxygen) Tachypnea Auscultation Single loud S2If concurrent VSD is present: systolic murmur at the left sternal border Diagnostics Echocardiography: (confirmatory test) demonstrates transposition of the great arteries and shunts Pulse oximetry: ↓ SpO2 X-rayHeart with an "egg on a string" appearance ↑ Pulmonary vascular markings Treatment Initially: infusion of prostaglandin (PGE1) to prevent closure of the PDA Definite repair: surgical correction within the first two weeks of life with arterial switch procedure Balloon atrial septostomyIndications: if surgery cannot be performed or if hypoxia is severe despite IV PGE1 administration prior to surgeryProcedure: right heart catheterization with creation or enlargement of an existing ASD Without treatment, 90% of patients with transposition of the great vessels die within the first year of life! Hypoplastic left heart syndrome Definition High-grade stenosis or atresia of the aortic and/or mitral valve in conjunction with severe hypoplasia of the left ventricle, ascending aorta, and aortic arch Epidemiology Rare congenital heart defect, but most common heart-related cause of death in neonates Etiology Mostly occurs sporadically Associated with trisomy 13, trisomy 18, and Turner syndrome Pathophysiology Nonfunctional hypoplastic left ventricle → The neonate's survival is dependent on the patent ductus arteriosus(right-to-left shunt) and a PFO or ASD supplying the systemic circulation with blood. Clinical findings May be asymptomatic at birth if the open PDA provides adequate systemic perfusion Aggravation of symptoms following closure of the PDA Postnatal cyanosis Dyspnea and metabolic acidosis ↓ BP, ↓ peripheral pulses, and cool extremities Heart failure and cardiogenic shock, if untreated Diagnostics Postnatal echocardiography: (confirmatory test): visualization of the defects Pulse oximetry: ↓ SpO2 Treatment Initially: continuous infusion of PGE1 prior to heart surgery Definite therapyStaged surgical correction in three steps Alternative: heart transplant Prognosis Most children reach adult age. Without treatment, 95% of patients with hypoplastic left heart syndrome die within their first month of life! Tricuspid valve atresia Definition Absent or rudimentary tricuspid valve, resulting in no blood flow between the right atrium and the right ventricle Epidemiology Third most common cyanotic heart defect Almost always accompanied by ASD, VSD, and right ventricular hypoplasia Pathophysiology Functional univentricular heart; the right ventricle is usually hypoplastic → dilatation of left atrium and ventricle due to volume overload Circulation depends on the patency of the ductus arteriosus and ASD. Clinical features Central cyanosis occurring within days after birth Auscultation: if a concurrent VSD is present → rough holosystolic murmur over lower left sternal border Diagnostics Echocardiography: (confirmatory test) absent tricuspid valve, atrial septal defect, and RV hypoplasia Pulse oximetry: ↓ SpO2 Chest x-ray: decreased pulmonary markings ECG: left axis deviation due to LVH; tall P waves (right atrial enlargement); minimal R waves in precordial leads Treatment Initially: infusion of prostaglandin (PGE1) Definitive treatment: three-staged surgical procedure to separate the pulmonary and systemic circulation Without treatment, about 75% of patients with tricuspid atresia die in early childhood! Total anomalous pulmonary venous return Definition Malposition of pulmonary veins, in which the four pulmonary veins drain into the systemic venous circulation instead of the left atrium Epidemiology 5th most common cause of cyanotic CHD Etiology Exact cause unknown; found in 20% of children with Down syndrome Pathophysiology The four pulmonary veins drain abnormally into the systemic venous circulation (most commonly the left brachiocephalic vein) instead of the left atrium. Oxygenated pulmonary venous return mixes with the systemic venous system → partially oxygenated blood is shunted right-to-left through an ASD, PFO, or PDA into the systemic arterial circulation → cyanosis Clinical features In severe cases: cyanosis, dyspnea, cardiogenic shock Over time, symptoms of right heart failure Systolic and diastolic murmur Diagnostics Echocardiography (confirmatory test): malposition of pulmonary veins, enlarged right heart, right-to-left interatrial shunting Pulse oximetry: ↓ SpO2 ECG: right axis deviation due to RVH Chest x-ray: ↑ pulmonary vascular markings, right heart enlargement Treatment Improve cardiac function in patients with heart failure (see "Treatment" in "Overview" section above) Surgical repair Without treatment, about 80% of patients with total anomalous pulmonary venous return die within the first year of life! Ebstein anomaly Definition Malformed and displaced tricuspid valve leaflets causing tricuspid valve regurgitation and right heart enlargement Epidemiology Age of onset depends on the severity of the Ebstein anomaly. Usually associated with PFO, ASD, and other cardiac malformations Etiology Prenatal lithium exposure Isolated genetic defects Pathophysiology Incomplete undermining process during cardiac septation → right AV valve does not separate normally from the ventricular myocardium Displaced valve reduces the ventricular volume → regurgitation into the right atrium (tricuspid regurgitation) → atrial dilatation; poorly functioning, small RV (atrialization of the right ventricle); functional pulmonary valve atresia ; obstruction of the RV outflow by the large, sail-like anterior leaflet → blood flows through the patent foramen ovale(right-to-left shunt) → cyanosis Clinical findings Prenatal: in-utero heart failure → ascites (non-immune hydrops fetalis), pleural effusions, pericardial effusions Postnatal Cyanosis AuscultationTricuspid regurgitation: wide split S2, holosystolic murmur at the left sternal border Diagnostics Prenatal: sonography PostnatalPulse oximetry: ↓ SpO2Echocardiography (confirmatory test): enlarged RH, tricuspid regurgitation MRI: in patients with nondiagnostic echocardiography and before surgical tricuspid valve intervention; shows apical displacement of the septal and posterior tricuspid leafletX-ray: mild to severe cardiomegaly with RA enlargement ECG: right axis deviation due to RVH Treatment IV PGE1: in infants with acute symptoms of heart failure SurgeryIndication is individually assessed based on the cardiac function and severity of symptoms.Surgery typically occurs in stages and involves the creation of a systemic-pulmonary shunt, repair of the tricuspid valve, and reconstruction of the right ventricle. Cyanosis usually worsens as the ductus arteriosus closes; IV prostaglandins should be administered to keep the ductus arteriosus open! Persistent truncus arteriosus Definition Failed separation of aorta and pulmonary artery during development → single trunk that receives output from both ventricles Epidemiology Rare, but accounts for 4% of all critical CHD cases Often associated with VSD, PDA, coronary artery anomalies Etiology Failure of cardiac neural crest cell migration, leading to a lack of aorticopulmonary septum formation Associated with DiGeorge syndrome Clinical features Cyanosis Symptoms of heart failure Accentuated and bounding peripheral pulses Harsh systolic murmur at lower left sternal border, loud S2 Diagnostics Echocardiography (confirmatory test): single overriding great vessel arising from the heart Pulse oximetry: ↓ SpO2 ECG: signs of cardiomegaly Chest x-ray: ↑ pulmonary vascular markings, right aortic arch, no pulmonary artery Treatment Initial stabilization of cardiopulmonary function (e.g., diuretics, dopamine, ventilation, and correction of metabolic acidosis) Surgical repair during the neonatal period Without treatment, 85% of patients with persistent truncus arteriosus die within the first year of life! Double aortic arch Definition Embryonic malformation resulting in a double aortic arch (vascular ring anomaly) with subsequent constriction of the trachea and esophagus Pathophysiology The right and left pharyngeal arch arteries persist postnatally → formation of a vascular ring (double aortic arch) → constriction of the trachea and esophagus Clinical findings Typically manifests within the first weeks of life, especially in cases of tracheal compression Tracheal constriction: inspiratory or expiratory stridor, dyspnea, respiratory arrestAcute episodes of severe constriction and/or apnea with cyanosis may occur → possibly life-threatening!Hyperextension of the head to improve airflow Esophageal constriction: dysphagia, choking, retching, vomiting Diagnostics Chest x-ray (anteroposterior and lateral): shows anterior tracheal bowing and narrowing MRI scan of the thorax: imaging method of choice; visualization of the defect Treatment Surgical division of the minor arch

Acyanotic congenital heart defects Acyanotic heart defects are congenital cardiac malformations that affect the atrial or ventricular walls, heart valves, or large blood vessels. Common causes include genetic defects (e.g., trisomies), maternal infections (e.g., rubella), or maternal consumption of drugs or alcohol during pregnancy. Acyanotic heart defects are characterized pathophysiologically by a left-to-right shunt, which causes pulmonary hypertension and right heart hypertrophy. The symptoms depend on the extent of the malformation and the resulting impairment of cardiac function. Infants may be asymptomatic or present with exercise intolerance, failure to thrive, and symptoms of heart failure. Characteristic heart murmurs are important clues for establishing the diagnosis, which is typically confirmed by visualizing the defect on echocardiography. A chest x-ray, MRI, or cardiac catheterization may also be required to determine the indications for surgery and plan the procedure. Acyanotic heart defects requiring treatment are repaired via catheter procedures or surgery. Supportive medical therapy is needed in cases of heart failure (e.g., diuretics, inotropic agents) or if surgery cannot be performed (e.g., prostaglandin). Common complications include arrhythmias, embolisms, and infective endocarditis, especially if treatment is delayed.

Pathophysiology General pathophysiological processes The left chambers of the heart are a high-pressure pump system and the right chambers of the heart are a low-pressure pump system. Heart defects may lead to the formation of connections between the two systems (shunts), allowing blood to flow along the pressure gradient from high to low pressure. The shunts are classified according to the direction of blood flow as left-to-right shunts or right-to-left shunts. Left-to-right shunt: Oxygenated blood from the lungs is shunted back into the pulmonary circulation via an ASD, VSD, or PDA → pulmonary hypertension and right ventricular pressure overload → right-sided hearthypertrophy (cardiomegaly on x-ray) and heart failure, but no cyanosis Eisenmenger syndrome Prolonged pulmonary hypertension due to a left-to-right shunt causes reactive constriction with permanent remodeling of pulmonary vessels → irreversible pulmonary hypertensionRight ventricle hypertrophies to compensate for pulmonary hypertension → right ventricular pressure becomes higher and eventually exceeds left ventricular pressure → reversal of blood flow, associated with onset of cyanosis either at rest or during exercise Right-to-left shunt: blood flows from the right to the left heart via a shunt → deoxygenated blood enters the systemic circulation → cyanosis Untreated left-to-right shunts (acyanotic heart defects) may progress to right-to-left shunts (cyanotic defects) if right ventricularpressure exceeds left ventricular pressure due to pulmonary arterial hypertension (Eisenmenger reaction). Overview of acyanotic congenital heart defects General clinical features Nonspecific symptomsNormal skin tone Exercise intolerance FatigueExertional tachycardia, pallor, and diaphoresis (sweating)Exertional dyspnea, tachypnea Recurrent bronchopulmonary infections Failure to thrive Heart failure in larger defects TachycardiaRight-sided heart failureHepatic venous congestion with hepatomegalyPeripheral edema is rarely seen in infants. Left-sided heart failureTachypnea, pulmonary edemaLow cardiac output: ↓ BP, pallor, sweating, cool extremities, poor growth, syncope Differential cyanosis: cyanosis in the lower extremities when the Eisenmenger reaction occurs For specific features, see "Clinical features" in the subsections below. General treatment concepts Administration of IV prostaglandin/PGE1 (e.g., alprostadil) Indicated in ductal-dependent CHDs until surgery can be performedMechanism: prostaglandin prevents the ductus arteriosus from closing → creates intentional shunt to allow mixing of deoxygenated with oxygenated blood Ductal dependent CHDsPDA needed for systemic circulation Critical aortic valve stenosis Coarctation of the aorta Transposition of the great arteries Hypoplastic left heart syndrome PDA needed for pulmonary circulation Critical pulmonary valve stenosis Tetralogy of Fallot Tricuspid atresia In cases of heart failureDecrease fluid volume and lower pulmonary vascular resistance: diuretics or ACE-I inhibitors Inotropic agents to improve contractility of the heart (e.g., digoxin) Antibiotic prophylaxis: not generally recommended before procedures; given for 6 months after surgical correctionprocedures and if small defects remain after repair Nutritional support and immunoprophylaxis If the Eisenmenger reaction has occurred: heart-lung transplant or lung transplant The "3 Ds" of acyanotic CHDs: VSD, ASD, PDA. Atrial septal defect (ASD) Epidemiology Prevalence: ∼ 2/1000 live births Etiology Down syndrome Fetal alchohol syndrome Holt-Oram syndrome Pathophysiology Impaired growth or excessive resorption of the atrial septa in utero leads to atrial septal defects. Ostium primum atrial septal defect (ASD I): (∼ 15-20%)Ostium secundum atrial septal defect (ASD II): (∼ 70%) Typically a low-pressure, low-volume, minor left-to-right shunt → patients are asymptomatic In larger defects, the shunt may lead to: right heart failure, supraventricular arrhythmias, pulmonary hypertension, cor pulmonale, and/or the Eisenmenger reaction Clinical findings Depend on defect size and shunt volume Small defects: usually asymptomaticLarge defectsSee "Nonspecific symptoms" and "Heart failure" in the overview above.Palpitations ASDs typically manifest with advancing age. AuscultationSystolic ejection murmur over the left second ICS sternal border Widely split second heart sound (S2) over the left second ICS, which is fixed (does not change with respiration ), normal S1Soft mid-diastolic murmur over the lower left sternal border Diagnostics Echocardiography (confirmatory test): to visualize the defect, its extent, and shunt volume ECG: vertical or right axis, P pulmonale, right bundle branch block (complete or incomplete), signs of right hearthypertrophy, PR prolongation Chest x-ray: enlarged right atrium, ventricle, and pulmonary arch; increased pulmonary vasculature Treatment In childhood, spontaneous closure may occur. Patch repairIndicated in symptomatic children with significant left-to-right shuntSurgical or via percutaneous transcatheter procedure Complications Paradoxical embolism → risk of stroke Ventricular septal defect (VSD) Epidemiology The most common congenital heart defect (4/1000 live births) Occurs as an isolated heart defect or in combination with others Etiology Genetic syndromes: Down syndrome, Edward syndrome, Patau syndrome Fetal alcohol syndrome Intrauterine infection (e.g., TORCH) Pathophysiology Localization: most commonly in the membranous part of the ventricular septum (pars membranacea) Defect in ventricular septum → left-to-right shunt with the following consequences:RV volume overload → right ventricular hypertrophyExcessive pulmonary blood flow → increased pulmonary artery pressures → pulmonary hypertension and right-sided heart hypertrophyDecreased cardiac output Possibly an Eisenmenger reaction in late stage of disease due to irreversible pulmonary hypertension Clinical findings Small defects: usually asymptomatic Medium-sized or large defectsLead to cardiac failure in the first 2-3 months of lifeSome VSDs can present after the first weeks of life because pulmonary vascular resistance (PVR) is high at birth and decreases thereafter. ↓ PVR → ↓ right ventricular pressure → ↑ left-to-right shunt → presence of symptomsSee also "Nonspecific symptoms" and "Heart failure" in the overview section above. Palpation: Hyperdynamic precordium may be detected in hemodynamically relevant defects. Auscultatory findingsHarsh holosystolic murmur over the left lower sternal border; typically louder in small defects Becomes louder with maneuvers that increase left ventricular afterload (e.g., handgrip) because of increased left-to-right shuntingMid-diastolic murmur over cardiac apex Systolic thrill Loud pulmonic S2 (if pulmonary hypertension develops) Diagnostics Doppler echocardiography: confirms diagnosis; evaluation of defect size and shunt volume; exclusion of other anomalies ECG: signs of right heart hypertrophy Chest x-rayEnhanced pulmonary vascular markingsLeft atrial and ventricular enlargementIn later stages, enlarged right ventricle and pulmonary artery (due to elevated PVR) Treatment Small VSDs: rarely require surgical interventions → small to moderate defects often heal spontaneously; follow-upechocardiography recommended Symptomatic and large VSDs See treatment of "Heart failure" in the overview section above.Surgical (patch) repair in children < 1 year of age with signs of pulmonary hypertension and older children who did not improve with medical therapy Closure of a VSD results in a decrease in right ventricular and left atrial pressures and an increase in left ventricular pressure when compared to pre-treatment valuesHeart-lung transplant or lung transplant with concurrent VSD repair if Eisenmenger's reaction has occurred Complications Arrhythmias Right heart failure Eisenmenger's reaction Infective endocarditis Aortic regurgitation Patent foramen ovale (PFO) Definition Persistence of the foramen ovale beyond 1 year of age Epidemiology Prevalence: 25-30% of the general population Pathophysiology The foramen ovale in the atrial septum does not close after birth. → mild left-to-right shunt A shunt reversal may be induced by certain maneuvers that induce an increase in right atrial pressure (e.g., Valsalva maneuver, coughing). Clinical findings Patients are usually asymptomatic until complications occur (see below). Diagnostics Often an incidental finding If ischemic stroke occurs, specific work-up for suspected PFO is needed:Contrast echocardiography (best initial and confirmatory test): shunt identification; assess structure and function of the heart Complications Paradoxical embolism Systemic embolisms (e.g., renal infarction) Stroke Treatment Asymptomatic PFO: The majority of cases do not require any treatment. Ischemic infarction in patients with confirmed PFO: medical therapy with antiplatelet agents or anticoagulation and surgical or percutaneous closure of the defect Patent ductus arteriosus (PDA) Definition Failure of the ductus arteriosus to completely close postnatally Epidemiology Sex: ♀ > ♂ (2:1) Etiology In 90% of cases, PDAs occur as isolated defects; in 10% of patients, PDAs occur with other congenital heart defects. Premature infants Infants born at high altitude Maternal rubella infection during pregnancy Maternal prostaglandin administration Trisomies (Down, Patau, and/or Edwards syndrome) Pathophysiology Failure of the ductus arteriosus to close after birth results in a left-to-right shunt → volume overload of the pulmonary vessels (see also in the "Overview" above) Eisenmenger's reaction may occur with shunt reversal and present with differential cyanosis. Clinical features Small PDA: asymptomatic with normal findings on physical examination Large PDANonspecific symptoms (e.g., failure to thrive) and symptoms of heart failure in infancy (see overview section above)Physical examination Heaving, laterally displaced apical impulse Bounding peripheral pulses, wide pulse pressure (pulsus celer et altus)Auscultatory findings: loud continuous murmur ("machinery" murmur) ; best heard in the left infraclavicular region Diagnostics Echocardiography (confirmatory test)Shows left cardiac enlargement (in larger PDAs)Doppler: assesses degree of shunt and pulmonary artery pressureColor Doppler: demonstrates blood flow from the aorta into the pulmonary artery ECG: normal in small PDA; left axis deviation due to LVH in large PDA Chest x-ray: prominent pulmonary artery and aortic knob along upper left heart border; increased pulmonary markings Cardiac catheterization and angiography: only necessary prior to repair or in more complex CHDs Treatment Observation: Regular evaluation of the heart and pulmonary vasculature is indicated in patients with a small PDAwithout evidence of left-sided heart volume overload. Elective ductal closureIndications for closureSymptomatic PDAsLeft heart enlargement or mild to moderate pulmonary hypertension Techniques Pharmacologic closure (in premature infants): Infusion of indomethacin or ibuprofen (pharmacologic closure) can induce the closure of the ductus. In infants > 5 kg: percutaneous catheter occlusion or surgical ligation Administer prostaglandin (PGE1) if the PDA is needed for survival (e.g., in transposition of the grand vessels, tetralogy of Fallot, hypoplastic left heart). Complications Heart failure in infancy Infective endocarditis Common cause of pulmonary hypertension and Eisenmenger syndrome in adolescents and adults Coarctation of the aorta Definition Narrowing of the aorta at the aortic isthmus Epidemiology Prevalence: 4/10,000 live births Sex: ♂ > ♀ Usually associated with bicuspid aortic valve , VSD, and/or PDA Etiology Associated with Turner syndrome Pathophysiology Genetic defects and/or intrauterine ischemia → medial thickening and intimal hyperplasia form a ridge encircling the aortic lumen → narrowing of the aorta → ↑ flow proximal and ↓ flow distal to the narrowing Compensatory mechanismsMyocardial hypertrophy and collateral blood flow (e.g., intercostal vessels , scapular vessels) develop in cases of discrete stenosis to compensate for the left ventricular outflow tract obstruction (common) → onset of symptoms usually later in childhoodIn long segment stenosis, there is no time for development of compensatory mechanisms → closure of PDAafter birth → left ventricular pressure and volume overload → hypoperfusion of organs and extremities distal to the stenosis, heart failure, cardiogenic shock Clinical findings NewbornsAsymptomatic if PDA is present or aortic narrowing is only mildCyanosis in lower extremities (differential cyanosis)Weak femoral pulses (brachial-femoral delay) In larger stenosis: See "Nonspecific symptoms" and "Heart failure" in the overview section above.In severe stenosis: shock and multi-organ failure, when ductus arteriosus closes Childhood Chest pain, cold feet, and lower-extremity claudication on physical exertion↑ BP in upper extremities and ↓ BP in lower extremities Auscultation: systolic ejection murmur over left paravertebral region and/or continuous murmur below left clavicula and between the shoulder blades Palpation of strong displaced apical impulse to the left AdultsHypertensionVariability in blood pressure in the upper and lower extremities Headache, epistaxis, tinnitus Claudication of the lower extremities with exertion Diagnostics Best initial test: upper and lower extremity blood pressure measurement and search for brachial-femoral delay Pulse oximetry: ↓ SpO2 Echocardiography with doppler (confirmatory test): location and extent of stenosis; concurrent anomalies X-rayCardiomegaly and ↑ pulmonary vascular markings"Figure of 3" sign Rib notching (on inferior border of the ribs) Genetic testing for Turner syndrome Treatment Initial management: infusion of PGE1 (alprostadil) Surgery Should be performed as soon as possible in critical cases.Techniques: surgical correction or balloon angioplasty Follow-up and monitor for restenosis, aortic aneurysm and aortic dissection Complications Secondary hypertension and/or cerebral aneurysms in adulthood→ Intracranial hemorrhage Heart failure, aortic dissection, coronary artery disease, endocarditis, ischemic stroke, myocardial infarction Endocardial cushion defect Definition Defect of atrioventricular valves (i.e., mitral and tricuspid valves) as well as the atrial septum and/or ventricular septumComplete form: ASD and VSD, common AV valvePartial form: only ASD and minor atrioventricular valve abnormalities Etiology Strongly associated with Down syndrome Maternal diabetes and obesity Pathophysiology Complete form (ASD and VSD) → atrial and ventricular left-to-right shunt → excessive pulmonary blood flow and biventricular volume overload → pulmonary hypertension and heart failure Partial form (only ASD) → atrial left-to-right shunt → symptoms may remain minimal until adulthood In both forms: abnormal AV valve → AV valve regurgitation → in severe cases, in utero heart failure (nonimmune hydrops fetalis) Clinical features Complete form: See "Nonspecific symptoms" and "Heart failure" in the overview section above. Partial form: See "Clinical features" of ASD. Heart murmurs according to underlying characteristic septal and valvular defects Diagnostics Antenatal echocardiography: diagnosis of endocardial cushion defect in first trimester → screening for Down syndrome Echocardiography (confirmatory test): assessment of size, function, and shunt volume ECG: left axis deviation due to LVH Chest x-rayComplete form: global cardiomegaly, ↑ pulmonary markings Partial form: enlarged right heart and pulmonary artery Treatment Improve cardiac function in patients with heart failure (see treatment of "Heart failure symptoms" in the overview section above) Surgical repair

Summary Shock is a life-threatening circulatory disorder that leads to tissue hypoxia and a disturbance in microcirculation. There are many different causes of shock, which are classified into cardiogenic shock (e.g., as a result of acute heart failure or cardiac tamponade), hypovolemic shock (e.g., following massive blood or fluid loss), and shock due to a disturbance in the fluid distribution in the body (septic, anaphylactic, and neurogenic shock). The common clinical findings are hypotension and tachycardia, accompanied by specific symptoms related to the cause of shock. Hypoxia can result in organ damage and complex metabolic disorders such as kidney failure, DIC (disseminated intravascular coagulation), ARDS (acute respiratory distress syndrome), and circulatory collapse. Management of shock involves circulatory support and the treatment of the underlying cause. Shock is associated with a very high mortality rate.

Pathophysiology Shock is a life-threatening disorder of the circulatory system which results in inadequate organ perfusion The causes for inadequate organ perfusion may differ, but they all ultimately result in tissue hypoxia: Loss of intravascular fluid → hypovolemic shockInability of the heart to circulate blood → cardiogenic shockRedistribution of body fluid → distributive shock Generalized tissue hypoxia causes life-threatening metabolic disturbances and ultimately irreversible organ damage Stages of shock Non-progressive phase (stage of compensation): activation of compensatory neurohumoral reflexes in order to maintain vital organ perfusion → Peripheral vasoconstriction → cold, clammy extremities and increased capillary refill time Decreased capillary hydrostatic pressure → increases absorption of interstitial fluids into intravascularspace to help maintain blood pressureTachycardia/Patients with neurogenic shock may present with bradycardia! Oliguria Progressive phaseWorsening hypotensionHypoperfusion of peripheral tissues → generalized tissue hypoxia → anaerobic metabolism in the underperfused organs → lactic acidosis → Worsening tachypneaPrecapillary dilation and postcapillary constriction of the blood vessels → pooling and stasis of blood in the capillary bed → decreased cardiac output and formation of microthrombi in the capillaries → DIC and further hypoxic injury to tissuesAcidosis, cerebral hypoperfusion → altered mental status Irreversible phase (stage of decompensation): irreversible tissue damage sets inCerebral hypoxia → autonomic dysfunction → worsening of shockMyocardial ischemia → acute coronary syndrome → decreased cardiac output → worsening of shockWidespread cell necrosis → Release of lysosomal enzymes → further tissue injury → worsening of shockActivation of the immune system → release of cytokines → DIC, further tissue damage → worsening of shockBowel ischemia → bacteremic sepsis → worsening of shockThe end result of these vicious cycles is a downward spiral from which there is no recovery (multiple organ failure) These separate stages may not occur in the case of severe insults (e.g., severe hemorrhage from an abdominal aneurysm, cardiac tamponade). These stages may also not be very distinct in the case of septic shock. Hypotension, oliguria, tachycardia, and altered mental status indicate that the patient is in shock! Multiorgan dysfunction (MODS) CNS: stroke, hypoxic brain damage Kidneys: acute tubular necrosis → acute kidney failure Heart: reduced coronary perfusion → acute coronary syndrome Liver: necrosis that begins around the hepatic veins → acute hepatic failure Lungs: acute respiratory distress syndrome Coagulation system: disseminated intravascular coagulation Intestine: ischemic colitis → paralytic ileus Adrenals: hypocortisolism, hypoglycemia Skin and soft tissue: necrosis, gangrene, myositis, and necrotizing fasciitis Hypovolemic shock PathophysiologyLoss of > 20% of intravascular fluid volumeFaster rate of volume loss → poor compensation → higher morbidityPatients with multiple comorbidities → poor compensation → higher morbidity EtiologyHemorrhagic fluid lossBlunt/penetrating traumaExternal hemorrhageInternal hemorrhageMassive hemothoraxInjury to the spleen, liver, and/or intra-abdominal blood vesselsFracture of the pelvis and/or long bones (especially femur)Upper GI bleeding (e.g., variceal bleeding)Postpartum hemorrhageNon-hemorrhagic fluid loss GI loss: diarrhea, vomiting, surgical drainageIncreased insensible fluid loss (e.g., burns, Steven-Johnson's syndrome)Third space fluid lossRenal fluid loss: adrenal insufficiency and other salt wasting nephropathies, osmotic/drug-induceddiuresis Clinical featuresWeak pulse, tachycardia, tachypneaCold, clammy extremities, poor capillary refillHypotension with narrow pulse pressure in the decompensated stageSpecific symptoms corresponding to the cause (e.g., bleeding, melena, hematemesis, diarrhea) Classification of hemorrhagic shockClassIIIIIIIVBlood loss< 15%15-30%30-40%> 40%Heart rate< 100100-120120-140> 140Systolic blood pressureNormalNormal↓↓Pulse pressureNormal or ↑↓↓↓Respiratory rate14-2020-3030-40> 35Urine output> 30 mL/hr20-30 mL/hr5-15 mL/hrAbsentMental statusAnxious Mildly anxiousAnxious, confusedConfused, lethargic DiagnosticsIf occult hemorrhage is suspected FAST scanHemoglobin and hematocrit See also "Diagnostics" below TreatmentFluid resuscitationIn the case of hemorrhagic fluid lossHemostasisPossibly blood transfusion Remember occult sites of hemorrhage in the case of trauma; blood on the floor (external hemorrhage) and four more, i.e., internal hemorrhage in the chest, abdomen (peritoneal cavity), pelvis (retroperitoneum), and thigh! A patient can bleed and yet show a "normal" hemoglobin value (hyperacute bleeding without the compensatory "dilution effect"); in the case of hemorrhage, hemoglobin value will only start to drop after 8-12 hours, when the interstitial fluid shifts into the plasma. Continuous monitoring of the blood pressure and the heart rate is, therefore, more important in the acute setting! Upon suspecting hemorrhage, perform blood grouping and cross-matching and have packed RBC concentrates at hand for transfusion! Cardiogenic shock Definition: systolic BP < 90 mm Hg with urine output < 20 mL/hr and normal or elevated left ventricular filling pressure Pathophysiology: ↓ stroke volume EtiologyNon-obstructive cardiogenic shockMyocardial infarction ArrhythmiasObstructive cardiogenic shockTension pneumothoraxCardiac tamponadeConstrictive pericarditisRestrictive cardiomyopathyPulmonary embolism Clinical featuresWeak pulse, tachycardiaCold, clammy extremities, poor capillary refillDyspnea, fine basal crepitations Elevated JVP and distended neck veinsHypotension with a narrow pulse pressure in the decompensated stageOther clinical features related to the underlying disease: chest pain, abnormal auscultatory findings (e.g., S3, S4) DiagnosticsIdentifying the cause Cardiac markers (e.g., ↑ troponin I, troponin T): to identify acute coronary syndrome ECG: to identify myocardial infarction, cardiac arrhythmiasEchocardiography: to identify valvular lesions, cardiac tamponadePulmonary artery catheterization: to monitor hemodynamic parameters as a guide to therapySee also "Diagnostics" below Treatment Cardiopulmonary resuscitation if necessaryMyocardial infarctionsBP < 70 mm Hg: norepinephrinesBP 70-100 mm Hg: dopamine Reperfusion therapy (PTCA, thrombolysis)If pulmonary congestion: diureticsVasodilators to decrease afterload (e.g., hydralazine, isosorbide dinitrate)Cardiac tamponade: pericardiocentesisPulmonary embolus: thrombolysisTension pneumothorax: needle decompression followed by chest tube insertion Unlike other causes of shock the administration of intravenous fluids in most cases of cardiogenic shock would worsen cardiogenic pulmonary edema! The only accepted indication for fluid therapy in cardiogenic shock is right ventricular dysfunction with a normal RV afterload (e.g., following an inferior wall MI). Such a scenario is seen only in 5% of cases of cardiogenic shock. In such cases, carefully administered fluid boluses may be used to maintain the RV end-diastolic pressure (RV preload) in the optimal range of 8-12 mm Hg in order to maintain the cardiac output! Distributive shock Distributive shock is a collective term for shock that is caused by one or both of the following mechanisms:Capillary leakage → redistribution of fluid from the intravascular to the extravascular compartmentSystemic vasodilation → peripheral pooling of blood Types of distributive shockSeptic shock (most common)Neurogenic shockAnaphylactic shock Septic shock Pathophysiology: abnormal host response to infection → capillary leakage, systemic vasodilation → acute and life-threatening organ dysfunction + circulatory, metabolic, and cellular abnormalities Etiology: see the "Sepsis" learning card Clinical featuresCan be febrile or hypothermicFlushed, warm skinBounding pulse, tachycardiaHypotension with a wide pulse pressure Diagnostics (see also "Diagnostics" in sepsis) Leukocytosis or leukocytopenia↑ ESR and acute phase reactants (e.g., CRP, procalcitonin)Positive blood culturesSee also "Diagnostics" below TreatmentFluid resuscitationVasopressorsFirst-line: norepinephrineSecond-line: epinephrineEarly initiation of broad-spectrum empirical antibiotic therapy in the case of sepsis Surgical therapy may be required in some cases (e.g., peritonitis, necrotizing fasciitis) For more information on septic shock, see the "Sepsis" learning card Neurogenic shock Pathophysiology: loss of sympathetic vascular tone → peripheral vasodilation → pooling of peripheral blood EtiologySpinal cord injury; above the level of T6. Spinal anesthesiaTraumatic brain injuryCerebral hemorrhagePoisoningSevere pain Clinical featuresFlushed, warm skinBradycardiaHypotension with a normal pulse pressureClinical features of the underlying cause, i.e. toxidromes or neurological deficits (e.g., loss of spinal reflexes) TreatmentFluid resuscitationAtropine to treat bradycardiaIf fluid resuscitation fails to increase MAP beyond 90 mm HgIf bradycardia is absent: phenylephrineIf bradycardia is present: epinephrine In a patient who develops hypotension following high-energy trauma, neurogenic shock is a diagnosis of exclusion that is made after hypovolemic and obstructive cardiogenic shock have been ruled out! Anaphylactic shock Pathophysiology: anaphylaxis (type I hypersensitivity reaction) or anaphylactoid reactions → degranulationof mast cells → massive histamine release → systemic vasodilation, increased capillary leakage EtiologyDrug reactionsBee stings, food allergiesContrast medium allergy Clinical features: see anaphylaxisTachycardia, tachypneaHypotension with a narrow pulse pressureFlushed, itchy skinBronchospasm, laryngeal edema → wheeze, stridor, cyanosisAngioedemaVomiting, diarrhea Treatment (see also "Treatment of anaphylaxis") EpinephrineAirway support (e.g., intubation, nebulization with albuterol)Glucocorticoids (e.g., hydrocortisone) Diagnostics Test the patient's responsiveness to check for CNS dysfunction Check skin color and capillary refill time (CRT) Monitor the following parameters continuously: Heart rate and blood pressure Shock index (Allgower's index) = pulse rate / systolic blood pressureShock index greater than 1 (positive shock index) may indicate the presence of shock Oxygen saturation by pulse oximetry Catheterize the bladder to assess the urine output. The following investigations must be performed frequently in a patient with shock: Renal function tests: ↑ BUN and creatinine indicate acute renal failureArterial blood gas analysis: lactic acidosis Clotting parameters: ↓ AT-III, ↓ fibrinogen, and thrombocytopenia, with ↑ FDP (e.g., D-dimer) indicate a consumption coagulopathyLiver function tests: hyperbilirubinemia, ↑ AST/ALT indicate acute liver failureElectrolytes (especially sodium, potassium, and calcium) Insert a central venous catheter to measure central venous pressure Pulmonary artery catheterization: to measure hemodynamic parameters (see cardiac catheterization) Hypovolemic shock Pulmonary capillary wedge pressure/Left ventricular end-diastolic pressure(LVEDP) (PCWP)↓ Cardiogenic shock Pulmonary capillary wedge pressure/Left ventricular end-diastolic pressure(LVEDP) (PCWP) ↑ Septic shock Cardiac output / Cardiac index and Mixed venous oxygen saturation (SvO2) ↑ Neurogenic shock Heart rate ↓ Anaphylactic shock Peripheral vascular resistance ↓ More than one type of shock can occur simultaneously (e.g., with burns), which can make a specific classification impossible!

Cardiopulmonary resuscitation Cardiopulmonary resuscitation (CPR) is a lifesaving procedure that maintains circulation in patients with sudden cardiac arrest until cardiac function can be restored. Sudden cardiac arrest presents with unconsciousness, apnea, and pulselessness. There are two protocols for CPR: Basic Life Support (BLS) for lay rescuers and professionals alike and Advanced Cardiac Life Support (ACLS) for medical professionals. BLS includes checking the patient's responsiveness, calling for help, performing chest compressions and rescue breaths, and, if available, the use of an automated external defibrillator (AED). Advanced Cardiac Life Support includes additional procedures performed by medical professionals, such as drug therapy (especially epinephrine), securing the airways (e.g., endotracheal intubation), and finding and treating reversible causes of cardiac arrest. Immediate initiation of high-quality chest compressions is the most important factor in the success of CPR.

Procedure/application Chain of survival Check responsiveness and call for help Immediate cardiopulmonary resuscitation (CPR) Early defibrillation Early advanced life support Immediate initiation of high-quality chest compressions, minimizing interruption of chest compressions, and early defibrillationare the most important factors in improving patient survival! Minimizing the time elapsed prior to CPR is crucial for avoiding long-term complications! Check responsiveness and call for help Make sure the scene is safe Check for responsiveness (e.g., verbally or by lightly shaking the shoulders) Call for help and make a 911 emergency call Send someone to get an AED Check breathingClear airways by carefully tilting the head back/lifting the chinAbnormal respiratory patterns include apnea, single breaths, or gasping. When in doubt, continue as if respiratory pattern is abnormal. Cardiopulmonary resuscitation30 chest compressions followed by two rescue breaths (30:2) Chest compressionCompression rate: 100-120 per minuteCompression depth: 5-6 cm (2-2.5 inches)Rescue breathingVerify sufficient ventilation by checking for thoracic movement during rescue breathing.If psychological/hygienic factors prevent rescue breathing, perform continuous hands-only CPR.Beginning early is essential!DefibrillationInstall AED (if available) Positioning of the electric pads: Place one pad on the right chest (above the nipple) and the other on the left side of the thorax (below the nipple). Administer shock if indicated Shockable rhythm: 1 shock → continue CPR → analyze rhythm after 2 min → repeatNon-shockable rhythm: continue CPR → analyze rhythm after 2 min → shock if indicated; if not, repeatWhile the defibrillator is charging, CPR must continue!CAUTION: Make sure that everyone stays clear of the patient before defibrillation! Continue CPRContinue CPR until professional help arrives or the patient shows clear signs of life. Early cardiac arrest often presents as gasping respiration, which should be interpreted as abnormal respiration and is therefore an indication for CPR! Advanced Cardiac Life Support Call for helpShoutActivate hospital/institutional emergency response systemProfessionals are allowed to check for carotid pulse for 10 secondsChest compressionsPerform chest compressions as described above in BLS.AirwayIf necessary, secure the airways (e.g., endotracheal intubation). BreathingRescue breathsSecure adequate oxygen supply Artificial ventilation with 100% oxygen (e.g., bag valve mask)Capnography to detect ROSC and monitor the effectiveness of CPRCirculationContinue CPRInstall AED/defibrillator and check rhythmShockable rhythms: ventricular fibrillation (VF), ventricular tachycardia (VT) DefibrillationAs soon as defibrillator is availableEnergy load: biphasic waveforms First shock: 120-200 JAdditional shocks: 200-360 JMedical therapy Epinephrine 1 mg IVAfter 2nd cycle of defibrillationRepeat every 3-5 minAmiodarone 300 mg IVAfter 3rd unsuccessful cycle of defibrillationAn additional dose of 150 mg after 3-5 minNon-shockable rhythms: asystole, pulseless electrical activity (PEA) Continue CPRPharmacotherapyEpinephrine 1 mg IVAs soon as possible without delaying CPRRepeat every 3-5 min Treat reversible causes 5 H's HypoxiaHypovolemiaHypokalemia/hyperkalemia/other metabolic causesHypothermiaHydrogen ion (acidosis) 5 T's Thrombosis (myocardial infarction)Thromboembolism (pulmonary embolism)Tension pneumothoraxTablets and toxinsCardiac tamponade Return of spontaneous circulation (ROSC) Diagnosis Clear signs of life, e.g., breathing, coughingReturn of pulse and blood pressureIncrease in expiratory CO2 measured via capnography All comatose patients who achieve ROSC (return of spontaneous circulation) after cardiac arrest should be subjected to mild hypothermia therapy for at least 24 hours (32-36°C target core temperature)! Shockable rhythm Ventricular fibrillation(VF) Arrhythmic and unsynchronized high-frequencyfibrillation of the ventricles No cardiac output Pulseless ventricular tachycardia Rapid, regular ventricular rate (along with pulselessness)Insufficient cardiac output due to high heart rate → common: peripheral pulselessness along with palpable carotid pulse Nonshockable rhythms Asystole Flatline Lack of ventricular electrical and mechanical activity Pulseless electrical activity (PEA) Rhythmic electrical activity (commonly low rate, wide, distorted QRS-complexes) and nonpalpable carotid pulse Myocardial contraction does not occur or does not generate sufficient cardiact output, which leads to electromechanical dissociation. Special patient groups Newborns and children Ventilation is more important in children and newborns than in adults, as respiratory distress is a common cause of cardiac arrest in children! Newborns5 initial rescue breaths → CPRCompression rate: 100-120/minCompression-to-ventilation ratio → 3:1Technique of chest compressions: tip of two fingers (one emergency rescuer) or two-thumb-encircling hands (≥ 2 emergency rescuers) Children older than 1 year5 initial rescue breaths → CPRCompression rate: 100-120/min Compression-to-ventilation ratio: Medical professionals: 15:2 Lay rescuers: 30:2Further management should follow the guidelines for adults. Defibrillation: monophasic and biphasic waveforms: 2-4 J/kg of body weight

Cardiac catheterization Cardiac catheterization is a procedure used in the diagnosis and treatment of cardiovascular conditions. It involves the insertion of a catheter into a cardiac vessel (coronary catheterization) or chamber by way of a suitable vascular access (usually a femoral or radial artery). Once in position, a cardiac catheter can help evaluate the blood supply to the cardiac musculature (angiography) or open up narrowed or blocked segments of a coronary artery by means of a coronary angioplasty with stenting (percutaneous coronary intervention, or PCI). Additionally, it can be used to perform a cardiac tissue biopsy, open narrowed heart valves via valvuloplasty, examine electrophysiological pathways, or measure pressure and oxygen levels in different chambers (hemodynamic assessment). The procedure is associated with a low rate of complications, with the most common among these being bruising and bleeding at the site of IV access. Rarer, more severe complications include arrhythmias, cardiac arrest, embolization of existing plaques, and infection.

Procedure/overview General Sites of IV access Femoral artery, most common Radial artery Imaging: A contrast dye is injected via the catheter, and is visualized with serial x-ray imaging. Preprocedural investigations ECGLaboratory tests: complete blood count, INR/prothrombin time, serum urea, and creatinine Coronary angiography/ventriculography Contrast-enhanced radiological analysis of the heart cavities (ventriculography) or coronary arteries(coronary angiography). IndicationsCoronary artery disease: to assess the exact location and extent of coronary vessel narrowing before possible PCI/surgeryPatients with unstable anginaPatients with adverse effects from medical therapyPatients in which conservative control of symptoms has failedHigh-risk patients (those with signs of ischemia during stress ECG)Valvular or myocardial diseases with symptoms (e.g., shortness of breath) Recurring chest pain of unidentified causePreoperative evaluation prior to noncardiac and planned cardiac surgery (CABG) in high-risk patientsTo detect and quantify the presence of an intracardiac shunt Coronary angiography is not a screening method for coronary heart disease in asymptomatic patients! Percutaneous coronary intervention (PCI)/percutaneous transluminal coronary angioplasty (PTCA) A therapeutic procedure carried out during cardiac catheterization in which a blocked coronary vessel is opened and appropriate blood flow is restored. A balloon catheter is used to dilate the narrowed section, with/without the placement of a stent to keep it patent. IndicationsAcute and chronic occlusion of coronary arteriesMyocardial infarction (primary revascularization or primary PCI)Occlusion of bypass grafts and stentsRecurrent ischemia after PCI or bypass surgery Types of stentsBare metal stent (BMS): bare-surfaced, metallic stent that provides a mechanical framework to keep the arteryopen. Drug-eluting stent (DES): stents that are coated with antiproliferative substances (immunosuppressant drugs, cytostatic drugs) that prevent excessive intimal hyperplasia Electrophysiological examination Testing of the electrical conduction system of the heart to assess electrical activity and conduction pathways via a cardiac catheter IndicationsDiagnostic: to evaluate various, repeatedly refractory cardiac arrhythmias Therapeutic Radioablation of areas of accessory pathways (areas that generate and conduct the arrhythmias)Placement of intracardiac pacemakers or defibrillators Right heart catheterization The passing of a balloon-tipped, multi-lumen catheter (Swan-Ganz catheter) into the right side of the heart and the pulmonary artery to monitor pressure within the heart (intracardiac pressure) and pulmonary arterial pressure. IndicationsIn heart failure, cardiomyopathy, congenital heart disease, and valvular disease: helps measure pressure, oxygen, and cardiac output of the right heart to assess the severity of dysfunction. Also helps measure pulmonary capillary wedge pressure (PCWP), which can be used to diagnose the severity of left ventricular failure and mitral stenosis. In suspected pulmonary hypertension: helps measure mean pulmonary arterial pressure (mPAP) and central venous pressure (CVP) Contraindications Absolute contraindication: patient refuses to undergo the procedure Relative contraindications: comorbidities in which the risks associated with coronary angiography are greater than the benefits of securing the diagnosis Decompensated heart failureAcute renal failureUncontrolled, severe hypertensionBleeding disorder or anticoagulated stateAllergy to radiographic agents Special consideration: Abnormal results on a modified Allen test are a contraindication for radial access. Complications Periprocedural complications Complications at the site of vascular access Superficial hematoma formation Retroperitoneal hematomaMost common cause of unexpected mortality after diagnostic or interventional cardiac catheterization Clinical featuresOften asymptomatic Suprainguinal tenderness and fullnessSudden flank or back pain with hemodynamic instabilityPrompt diagnosis is a priority: CT with contrast of the abdomen and pelvis in hemodynamically stable patients or sonography in unstable patientsTreatmentPredominantly supportive treatment: careful monitoring, fluid resuscitation, blood transfusion, and normalization of coagulation factors if abnormalSurgical repair Endovascular management options like intra-arterial embolization or stent-grafts to stop the bleedingOpen surgery to control active bleeding and/or to remove a large retroperitoneal hematoma Pseudoaneurysms Arterial injury (can include laceration, arteriovenous fistula formation, or thrombosis) Complications at the cardiac level Myocardial infarction Arrhythmias can be induced by catheter introduction into the right or left ventricle. Spontaneous coronary artery dissection (SCAD) in the artery affected by acute coronary occlusion Injury to coronary vasculature by the catheter (e.g., dissection of coronary artery wall) Other complications Hypersensitivity to contrast media Acute kidney injury (see also contrast nephropathy) Cholesterol embolization syndromeDefinition: embolization of cholesterol released from atherosclerotic plaques or common vessel wall depositsEtiologyUsually after vascular interventions (like PCI) or during anticoagulant therapyCan occur spontaneously in patients with atherosclerosis after plaque ruptureClinical featuresSevere peripheral, muscular, or visceral embolismsAcute renal failure Skin involvement (purpura, necroses, livedo reticularis)Gastrointestinal involvement (e.g., ischemia, pancreatitis)CNS symptoms (transient ischemic attack, stroke)HistopathologyAmorphous, eosinophilic material in the vessel lumenSpindle-shaped vacuoles ("cholesterol clefts") TreatmentSymptomatic treatmentTermination of anticoagulant therapy , initiate statin therapy The prognosis is poor even with optimal treatment. Delayed complications Most common complication: restenosis Stent thrombosis (0.5-5%) Vascular complications Systemic embolisms: stroke due to cerebral emboli (< 1%) Infection (localized or generalized bacteremia) Alternative methods Coronary artery bypass graft (CABG)/aortocoronary bypass (ACB)

Statins Statins are the lipid-lowering drugs of choice. Statins reduce hepatic cholesterol synthesis by inhibiting enzyme HMG-CoA reductase. This leads to a consequent upregulation of LDL receptors on hepatocytes, which, in turn, lowers LDL cholesterol levels and triglycerides while raising HDL cholesterol. Headache and gastrointestinal side-effects are common. Statins carry a risk of hepatic and muscle toxicity. Muscle toxicity may rarely manifest with rhabdomyolysis.

StatinHalf-life in hoursCYP-450BioavailabilityAtorvastatin15-30CYP3A4∼ 10% Simvastatin2-3CYP3A4, CYP3A5∼ 5% Pravastatin∼ 2- ∼ 20% Lovastatin3CYP3A4∼ 5% Fluvastatin0.5-2.5CYP2C9∼20-30% Pitavastatin12Limited CYP2C9∼ 50% Rosuvastatin19Limited CYP2C9∼ 20% Potency (and cost) increases in the following order: fluvastatin → lovastatin and pravastatin → simvastatin and atorvastatin! Effects Competitive inhibition of HMG-CoA reductase → reduced intrahepatic cholesterol biosynthesis → upregulation of expression of LDL receptor gene via sterol regulatory element-binding protein (SREBP) → ↓↓ LDL cholesterol (by ∼ 21-63%) ↑ HDL cholesterol (by ∼ 5-10%) ↓ triglyceride level (by ∼ 10-20%) Pleiotropic effect: ↓ C-reactive protein, ↑ plaque stabilization, ↑ anti-inflammatory effect, antioxidant effect and improved endothelial function of coronary arteries Treatment of hyperlipidemia with statins significantly reduces the risk of mortality! Side effects General (common): headache and gastrointestinal symptoms (e.g., constipation, diarrhea, flatulence) Hepatic (<1% of patients): ↑ LFTs due to the involvement of cytochrome P450 systems (CYP3A4 and CYP2C9) in the breakdown of statins Muscular: Statins decrease the synthesis of coenzyme Q10 and impair energy production within the muscle.Myalgia (muscle pain): continue treatment as long as creatinine phosphokinase (CK) remain normalStatin-associated myopathyMuscle pain and weakness↑ CK May progress to rhabdomyolysis: rare but severe side-effect that may lead to myoglobulinuria → AKI (↑ BUNand ↑ creatinine)Management: discontinue statin therapy for 2-4 weeks; start treatment with a low-dose statin (e.g., pravastatin or fluvastatin) once symptoms have resolved Treatment must be discontinued if myopathy/rhabdomyolysis occurs! Indications Patients with LDL cholesterol elevated ≥ 190 mg/dL Patients with a clinical atherosclerotic cardiovascular disease (includes coronary artery disease (CAD), stroke, and peripheral arterial disease) Patients aged 40-75 with diabetes and LDL levels of 70-189 mg/dL Patients aged 40-75 with an estimated 10-year ASCVD risk ≥ 7.5% and LDL levels 70-189 mg/dL → For details see therapy of atherosclerotic disease and Guidelines for lipid-lowering therapy (ATP III guidelines) Statins are the first-line therapy for hypercholesterolemia! Contraindications Hypersensitivity Active liver disease Muscle disorder Pregnancy, breastfeeding Interactions Other lipid-lowering agents FibratesNicotinic acidBoth agents may also cause myopathy → concomitant use with statins further increases the risk of myopathy! CYP3A4 inhibitors HIV/HCV protease inhibitorsMacrolides (especially erythromycin and clarithromycin)Azole antifungalsCyclosporine Warfarin Guidelines & therapy recommendations Ideally administered in the evenings (especially simvastatin) Combination therapy with bile acid resins has a stronger hypolipidemic effect compared to treatment with statins alone (both groups of drugs increase LDL receptor expression)

Renin-angiotensin-aldosterone system inhibitors Renin-angiotensin-aldosterone system (RAAS) inhibitors are a group of drugs that act by inhibiting the renin-angiotensin-aldosterone system (RAAS) and include angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs), and direct renin inhibitors. ACE inhibitors and ARBs are commonly used in the treatment of patients with hypertension, heart failure with reduced ejection fraction, certain types of chronic kidney disease, and patients who have suffered a myocardial infarction. They are particularly important in the treatment of hypertensive diabetic patients, as they prevent the development of diabetic nephropathy. A common side effect of ACE inhibitors is a bradykinin-inducedcough, which may necessitate switching to an alternative therapy (e.g. ARBs), while angioedema and hyperkalemia may occur in both ARBs and ACE inhibitor use. Direct renin inhibitors may be considered in hypertensive patients if ACE inhibitors or ARBs are not well tolerated; however, they should never be used in combination with other RAAS inhibitors.

The renin-angiotensin-aldosterone system (RAAS) Drops in blood pressure reduce renal perfusion. If the pressure in the renal artery falls by more than 10-15 mm Hg → proteolytic renin is released from thejuxtaglomerular apparatus → renin converts angiotensinogen to angiotensin I → ACE cleaves C-terminal peptides on angiotensin I, converting it to angiotensin II → increases the blood pressure in two ways: (1) vasoconstriction and (2) stimulation of the release of aldosterone, which increases the retention of water and sodium ACE inhibitorsEnalapril, lisinopril, ramipril, captopril, benazeprilArterial hypertensionDiabetes mellitus (type I and type II) with: Nephroprotective indications such as: Arterial hypertensionMicroalbuminuria (especially ≥ 300mg/g) Coronary heart disease Heart failure with reduced ejection fractionSurvival benefit (the exact mechanisms are poorly understood)Any murmur that decreases with amyl nitrite has an etiology that is treatable with ACE inhibitors. History of myocardial infarction Nondiabetic-associated chronic kidney disease with proteinuriaScleroderma-associated hypertensive crisis (even if creatinine is elevated!) ARBsValsartan, candesartan, losartan, irbesartanSame as ACE inhibitors, but second-line treatment (if ACE inhibitors are not tolerated)Direct renin inhibitorsAliskirenArterial hypertension if both ACE inhibitors and ARBs are not tolerated ACE inhibitorsInhibition of ACE → ↓ conversion of angiotensin I to angiotensin II↓ Angiotensin II↓ Vasoconstriction → ↓ blood pressure ↓ Secretion of aldosterone → ↓ reabsorption of Na+ and water → ↓ blood pressureDilation of efferent arteriole → ↑ renal plasma flow → ↓ filtration fraction ↑ Renin secretion (compensatory) → ↑ Angiotensin I↓ Breakdown of bradykinin → ↑ production of arachidonic acid metabolites → ↑ vasodilation → ↓ blood pressureOther effects: ↓ Proteinuria and ↓ progression of proteinuric kidney disease↓ Preload and afterload → ↓ cardiac remodeling after acute myocardial infarction or chronic hypertensive diseaseARBs (sartans)Inhibition of angiotensin II receptor type 1 (AT1 receptors) → ↓ Vasoconstriction → ↓ blood pressure↓ Secretion of aldosterone → ↓ reabsorption of Na+ and water → ↓ blood pressure↑ Renin secretion (compensatory) → ↑ Angiotensin I → ↑ Angiotensin IIOther effects: ↓ Proteinuria and ↓ progression of proteinuric kidney disease↓ Cardiac remodeling after acute myocardial infarction or chronic hypertensive disease irect renin inhibitorsDirect inhibition of renin → ↓ conversion of angiotensinogen into angiotensin I → ↓ angiotensin I and angiotensin II → vasoconstrictioncaused by ↓ angiotensin II↓ Blood pressure↓ Secretion of aldosterone → ↓ reabsorption of Na+ and water → further ↓ blood pressure Side effects ACE inhibitors Dry cough due to increase in bradykinin concentration → Treat by discontinuing ACE inhibitor; consider switching to ARB Angioedema Hyperkalemia Pemphigus vulgaris (unknown mechanism) ARBs Angioedema Hyperkalemia Direct renin inhibitors Rash Diarrhea Acute kidney injury is a potential side effect of all types of RAAS inhibitors, especially in patients with pre-existing kidneydisease or in combination with NSAIDs! Contraindications Contraindications for ACE inhibitors and ARBs Absolute contraindicationsHypersensitivityC1 esterase inhibitor deficiency (due to predisposition to angioedema)Pregnancy Breastfeeding Relative contraindicationsAortic stenosis Renal dysfunction; consider altering dose if GFR < 60 mL/min Bilateral renal artery stenosis or a solitary kidney Drug interactions (see "Interactions" below) Contraindications for direct renin inhibitors Hypersensitivity Drug interactions (see "Interactions" below) Normally, angiotensin II constricts efferent vessels and thereby increases the GFR. ACE inhibitors antagonize the conversion of angiotensin I to angiotensin II, thereby reducing the GFR! Interactions ACE inhibitors and ARBsOther antihypertensive drugs → ↑ hypotensive effectNSAIDs → ↓ antihypertensive effectPotassium-sparing diuretics or other drugs that increase potassium level: ↑ hyperkalemia↑ Level of lithium due to ↓ renal eliminationAllopurinol: ↑ risk of immunological reactions or leukopenia Direct renin inhibitorsP-glycoprotein inhibitors (e.g., ketoconazole, verapamil, clarithromycin, erythromycin, amiodarone): ↑ aliskirenlevelACE inhibitors or ARBs → ↑ hyperkalemia Do not combine direct renin inhibitors with ACE inhibitors or ARBs, especially in patients with diabetes or pre-existing kidneydisease! Guidelines & therapy recommendations Starting with low doses (preferably in controlled setting) is recommended to avoid severe hypotension! Combine ACE inhibitors or ARBs with thiazide diuretics to offset the risks of hyperkalemia and hypokalemia. When starting an ACE inhibitor or an ARB, monitor blood pressure, potassium, and creatinine.

Aneurysm True aneurysms are an abnormal dilation of an artery due to a weakened vessel wall. By contrast, false aneurysms are external hematomas with a persistent communication to a leaking artery. Dissections are a separation of the arterial wall layers caused by blood entering the intima-media space after a tear in the internal layer occurred. Aneurysms are differentiated according to their location. This card discusses the etiology and clinical features of cerebral, external carotid, Ileofemoral, popliteal, and ventricular aneurysms. Symptoms generally depend on the location and size of the aneurysm. There are surgical and endovascular treatment options, the choice of which depends on the specific type of aneurysm and if symptoms or complications are present. For more specific information on individual types of aneurysms, see the learning cards on thoracic aortic aneurysm, abdominal aortic aneurysm, aortic dissection, dissection of the carotid and the vertebral artery, and subarachnoid hemorrhage.

True aneurysm Abnormal dilation of an artery due to a weakened vessel wall Most frequently a consequence of atherosclerosis Inflammation and proteolytic degeneration of connective tissueproteins → Loss of structural integrity of the aortic wall → Widening of the vesselTreatment of atherosclerotic risk factors Open or endovascular stent grafting repair depending on size and growth rate of aneurysm False aneurysm (pseudoaneurysm) Leaking artery leads to a hematoma between the vessel and the surrounding tissue. A persistent communication between the vessel and the hematoma remains. (accumulation of blood between the tunica media and the tunica adventitia) Usually trauma (e.g., deceleration injury, gunshot) or iatrogenic (e.g., after vascular puncture or cardiovascular surgery) Perforation of the vascular wall causing bleeding into the surrounding tissue → Formation of an extravascular (pulsatile) hematoma → Surrounding structures delimit the expansion of the hematoma→ Organization of the hematoma → Formation of a false vascular wall and false aneurysm Typical deceleration injury → contained aortic injury of the thoracic aorta (typical location: distalto the left subclavian artery)Painful and pulsatile mass at the site of trauma Buzzing sensation Bruit on auscultationUltrasound-guided thrombin injection (e.g., to treat iatrogenic postcatheterization pseudoaneurysms that are symptomatic) Surgical managemen Arterial dissection Separation of the arterial wall layersThe wall of a vessel rips (dissects) longitudinally from a tear in the inner layer. Blood subsequently enters the intima-media space Hypertension or trauma In rare cases, Ehlers-Danlos syndrome and Marfan syndrome; for more risk factors see aortic dissection and dissection of the carotid and the vertebral artery.Transverse tear in the arterial intima ("entry") → Blood enters the intima-media space (creates a false lumen) → Hematoma forms and propagates longitudinally downwards → Rising pressure within the aortic wall and rupture, occlusion of branching vessels, and ischemia in the affected areas Aortic dissectionSudden and severe tearing/ripping pain in the anterior chest, interscapular area, the neck, jaw or abdomen depending on the site of dissectionSyncopeAsymmetrical pulse and BP readings Dissection of the carotid artery: ipsilateralheadache, pulse-synchronous tinnitus, stroke Dissection of the vertebral artery: occipital headache, stroke resembling Wallenberg syndrome ortic dissectionControl hypertension (Stanford Bdissections, which do not involve the ascending aorta, are generally treated conservatively)Open or endovascular stent grafting repair(Stanford A dissections, which involve the ascending aorta, require immediate surgery) Dissection of the carotid artery and the vertebral arteryAnticoagulationAngioplasty/stenting or surgical intervention Thoracic aortic aneurysm(TAA)Aortic arch, ascending and descending aortaAtherosclerosis TraumaConnective tissue diseases (e.g., Ehlers-Danlos syndrome and Marfan syndrome)Aortitis (aortic wall inflammation): due to autoimmune disease (e.g., vasculitis, rheumatoid arthritis) or infection (e.g., cardiovascular syphilis) Usually asymptomaticFeeling of pressure in the chestThoracic back painFeatures of aortic regurgitation Abdominal aortic aneurysm(AAA)Commonly below the renal arteries, may be above the renal arteriesUsually asymptomaticPulsatile abdominal mass Bruit on auscultationCerebral aneurysmCircle of WillisDepends on type of aneurysm (berry, fusiform, mycotic, traumatic, or microaneurysms)Usually asymptomaticMass effectsIn case of rupture → subarachnoid hemorrhageVentricular aneurysm∼ 85% in the anterior or apical walls of the left ventricleMyocardial infarction Enlarged heart3rd and 4th heart soundsSystolic murmurPopliteal aneurysmPopliteal arteryAtherosclerosisUsually asymptomatic mass in the popliteal fossa (50% are bilateral)Knee painAcute limb ischemia → 6 PsIleofemoral aneurysmIliac and/or femoral arteryMay be asymptomaticAcute limb ischemia → 6 PsMass effect: sudden pain, weakness, swelling, numbness in the legCarotid aneurysmExternal carotid arteryPulsatile neck massBruitTransient ischemic attacks(TIAs) or stroke Cerebral aneurysm TypesBerry (saccular) aneurysmsMost common type of aneurysm Associated with autosomal-dominant polycystic kidney disease, Ehlers-Danlos syndrome and Marfan syndrome, aortic coarctation, smoking, hypertension, hyperlipidemia, high alcohol consumption, familial aneurysms, estrogen deficiencyFusiform aneurysms Mycotic aneurysms Traumatic aneurysms Charcot-Bouchard microaneurysmsAssociated with hypertension and diabetes.Affect small lenticulostriate vessels in the basal ganglia and thalamus.Their rupture is the most common cause of intracerebral hemorrhage. Location: The majority of cerebral aneurysms occur in the circle of Willis. Clinical features Usually asymptomaticAnterior or posterior communicating artery aneurysms Visual field defectsOculomotor nerve palsyIn case of rupture → subarachnoid hemorrhage →Thunderclap headache: sudden onset of severely painful headache, meningism, impaired consciousness DiagnosisAngiography: determines location, size, and morphology of aneurysmSee subdural hemorrhage for suspected aneurysmal subdural hemorrhage. TreatmentControl BP Surgical clipping and/or endovascular coiling Popliteal aneursym Most common peripheral aneurysm and second most common aneurysm after AAAs Epidemiology♂ > ♀Mean age: 65 years Etiology: multifactorial (i.e., inflammation, immune, genetic, and mechanical factors) Clinical featuresUsually asymptomatic mass in the popliteal fossa (50% are bilateral) If symptomatic Knee painAcute limb ischemia → 6 Ps Chronic limb ischemia DiagnosisDoppler ultrasonography (best initial): excludes Baker's cyst; identifies thrombus and patency of vesselCT angiography: preoperative assessment ComplicationsRuptureDistal embolization: blue toe syndrome (small vessel occlusion caused by an embolus)Chronic thrombosis TreatmentAnticoagulation (e.g., heparin) Surgery with venous bypass graft or surgical aneurysmal excision Indication: symptomatic or ≥ 2 cm in diameter Ileofemoral aneurysm Second most common peripheral aneurysm after popliteal aneurysms Etiology: See risk factors for atherosclerosis. Clinical featuresMay be asymptomaticAcute limb ischemia → 5 PsCompression of nearby nerves or veins: sudden pain, weakness, swelling, numbness in the legPainless, pulsatile swelling with a palpable thrill at the mid-inguinal pointAuscultation of the swelling: loud, harsh, continuous murmurOften associated with other aneurysms, esp. AAA and thoracic aortic aneurysm DiagnosisDoppler ultrasonography (best initial test): identifies thrombus and patency of vesselCT angiography: preoperative assessment ComplicationsRupture: acute groin painBlue toe syndrome TreatmentProcedure: surgery with bypass or surgical excision of aneurysmIndication SymptomaticIAA ≥ 3 cmRapidly expandingCoexistent AAAComplications are present External carotid artery aneurysm Etiology: commonly atherosclerosis, trauma (iatrogenic or penetrating injury), infection (septic emboli) Clinical featuresPulsatile neck mass (below angle of mandible)Associated bruitTransient ischemic attacks (TIAs) or strokeMass effect on adjacent structures (veins and nerves → hoarseness, facial swelling, difficulty swallowing) DiagnosisUltrasound (initial): evidence of swirling blood with a thrombusCT or MR angiography: determines the site and size of the aneurysm, excludes rupture or other pathologies ComplicationsRupture: airway compression, pharyngeal hemorrhage, epistaxisNeck infection: pain, fever Treatment: surgical repair, either in the form of an aneurysm excision and reconstruction or endovascular repair (grafting or stenting) Ventricular aneurysm EtiologyMyocardial infarction (occurs in 8-15% of patients; 2 weeks to months after MI)Risk factors Complete occlusion of the left anterior descending coronary arteryAbsent angina Location: ∼ 85% in the anterior or apical walls, 10-15% in the inferior-basal walls of the left ventricle Clinical featuresEnlarged heart on percussionDiffuse and displaced apical pulse to left midclavicular line3rd and 4thheart soundsSystolic murmur (mitral regurgitation) DiagnosisECG: persistent ST elevationEchocardiography (or CT or MRI ): dyskinetic wall motion and diastolic deformity ComplicationsArrhythmiasVentricular rupture → cardiac tamponadeThrombus formation → thromboembolism (stroke, mesenteric ischemia, renal infarction)Heart failure TreatmentSmall and asymptomatic: conservative treatment with regular follow-upIf large, symptomatic, or there is evidence of a thrombusACE inhibitors AnticoagulationIf not responsive to medical therapy: surgical resection of the aneurysm

Oral anticoagulants Anticoagulants are used for treating and preventing embolic events. The most common oral anticoagulatory agents are vitamin K antagonists such as warfarin and phenprocoumon. Non-vitamin K antagonist oral anticoagulants (NOACs) like dabigatran and rivaroxaban have also gained popularity in recent years. Vitamin K antagonists inhibit the enzyme vitamin K epoxide reductase, thereby blocking hepatic synthesis of the active, reduced form of vitamin K (needed for carboxylation of coagulation factors II, VII, IX, and X, protein C, protein S). This effect can last for several days, which complicates exact dosing and makes regular monitoring necessary. Vitamin K antagonists are also metabolized by C-P450(CYP) enzymes and therefore interact with a broad range of foods and drugs. NOACs act selectively via inhibition of thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban, edoxaban). Because of their comparatively short half-life and fewer interactions, NOACs are easier to control and administer than warfarin and do not require regular monitoring to ensure their efficacy and safety. For all substances, it is important to consider the dose-dependent risk of bleeding, especially when combining different substances that affect hemostasis (e.g., aspirin, clopidogrel, ticagrelor).

Vitamin K antagonists(coumarins)PhenprocoumonWarfarinInhibit hepatic vitamin K epoxide reductase → ↓ hepaticsynthesis (recycling) of the active, reduced form of vitamin K → ↓ γ-carboxylation of glutamate residues on coagulation factors II, VII, IX, and X as well as protein Cand protein SMutations and polymorphisms in gene VKORC1 alter the effect of vitamin K antagonists. Well-known effects and side effectsLow costsIn cases of life-threateningbleeding: Direct reversal by replacement (e.g., with prothrombin complex concentrate, FFP)Indirect/delayed reversal by increasing production of coagulation factors(e.g., with vitamin Ksubstitution)Difficult to manage Long half-lifeRegular monitoring of the PT/INR required (as vitamin Kantagonists affect the extrinsic coagulation pathway) Requires bridgingbefore surgery (see below)Broad range of interactions (see "Warfarin interactions" below)Not suited for acute therapy of pulmonary embolism or deep vein thrombosis Direct oral anticoagulants Direct oral thrombin inhibitorsDabigatranSelective thrombin antagonist For more information about other drugs from this class, see direct thrombin inhibitors under parenteral anticoagulation Direct oral factor Xa inhibitorsApixabanRivaroxabanEdoxabanSelective and direct inhibition of factor Xa Easily manageable (similar to heparins) when administered orally Regular monitoringof coagulation parameters is not required → improved patient compliance Antidotes available in the case of life-threateningbleeding Dabigatran: idarucizumab(monoclonal antibody)Apixaban and rivaroxaban: andexanet alfa Costly Limited clinical experience with these drugs Not recommended, and partially contraindicated, in patients with artificial cardiac valves Not suited for patients with valvular atrial fibrillation General notes regarding oral anticoagulationIndications for all oral anticoagulantsProphylaxis of thromboembolism following: DVT and/or pulmonary embolismProlonged immobilization after surgery (e.g., especially in knee or hip surgery)Nonvalvular atrial fibrillationFor specific indications, see "Indications" below.Expected laboratory changesWarfarin: increased PT/INR, no change to PTT or TT (routinely monitored)Direct thrombin inhibitors: prolonged thrombin time (TT), no change to PTT or PT (not routinely monitored)Direct factor Xa inhibitors: prolonged PT and PTT, unchanged thrombin time (not routinely monitored) The most important side effect of all oral anticoagulants is a dose-dependent increase in bleeding risk. You can memorize the most important oral anticoagulants with DRAW: Dabigatran, Rivaroxaban, Apixaban, and Warfarin. RivaroXaban, apiXaban, and edoXaban are factor Xa inhibitors. WARsaw is an EXTRaordinary Place To check out: WARfarin affects the EXTRinsic pathway; therefore, PT should be regularly checked. HeparinIntravenousSubcutaneousActivates antithrombin → ↓ action of factors IIa and Xa Site of action: bloodRapid onset of actionShorter half time: duration of action is several hoursPTT (effects intrinsic pathway) Protamine sulfate WarfarinOral↓ Synthesis of Factors II, VII, IX, and X (procoagulants)And proteins C and S (anticoagulants)Site of action: liverSlow onset of actionLonger half time: duration of action is several daysPT or INR (effects extrinsic pathway) Vitamin KFFP, PCC (for rapid reversal) Side effects Coumarins Dose-dependent increased risk of bleedingSmall wounds cease to bleed spontaneously and no additional measures are requiredSevere cases of hemorrhage are usually retroperitoneal, intracranial, or gastrointestinal. Countermeasures for extensive or life-threatening bleeding includeStop coumarinsAdminister FFP or prothrombin complex concentrate (PCC) for rapid reversal of warfarin effect Vitamin K: takes longer to take effect than FFP or PCC Warfarin-induced skin necrosis Seen within the first few days of treatment with high doses of warfarinWarfarin inhibits all vitamin K-dependent coagulation factors. Anticoagulants protein C and protein S have a relatively short half-life and are depleted more quickly than procoagulants factors II, IX, and X → increased factor V and VIII activity → initial hypercoagulable state → formation of microthrombi → vascular occlusion, tissue infarction, and blood extravasationIncreased risk in patients with underlying hereditary protein C deficiencyPresentation: painful purpura, hemorrhagic blisters, and large areas of necrosis; mostly affects subcutaneous adipose tissue Immediate management: discontinue warfarin, administer IV vitamin K, unfractionated heparin, and source of protein C (protein C concentrate, FFP); surgical debridement and grafting in therapy-refractory cases Prevention: temporary bridging therapy with heparin for immediate anticoagulation until warfarin has started to act and the initial hypercoagulable state has been bridged Individuals with protein C deficiency are at a higher risk of developing warfarin necrosis. Direct factor Xa inhibitors and direct thrombin inhibitors Dose-dependent increased risk of bleeding Interventional steps to stop the bleeding If life-threatening bleeding occurs, administer PCC General management and specific medication antidotesAntifibrinolytic agents (e.g., tranexamic acid)Oral activated charcoal reduces absorption if anticoagulants were ingested in the past couple of hours.Apixaban and rivaroxaban: andexanet alfa (recombinant modified factor Xa protein) Dabigatran: idarucizumab (monoclonal antibody) RivaroXaban and apiXaban can be reversed with andeXanet alfa. DrugsIndicationsCoumarinsPhenprocoumonWarfarinProphylaxis of thromboembolism (e.g., stroke) in patients with the following: Valvular atrial fibrillation and nonvalvular atrial fibrillationHeart valve replacementHeart failureMyocardial ischemia Standard target INR: 2.0-3.0 (higher in mechanical heart valves or in special high-risk circumstances; usually 2.0-3.5) Direct thrombin inhibitorsDabigatranNonvalvular atrial fibrillation (increased risk of stroke) Direct factor XainhibitorsApixabanRivaroxabanEdoxaban herapy and secondary prophylaxisof:Deep vein thrombosisPulmonary embolism Prophylaxis of thromboembolismfollowing: Total knee or hip replacement, hip fracture surgery Contraindications General contraindicationsCoagulopathies; hepatic dysfunction with impaired hepatic production of coagulation factorsAcute bleedingSuspected vascular lesions, increased risk of severe bleeding Severe arterial hypertension, aneurysmEndocarditisRecent cardiovascular events (e.g., cerebral ischemia)Gastrointestinal bleedingSurgery or interventional procedures (e.g., biopsy)Tendency to fallSevere renal insufficiency Concurrent administration of several anticoagulants Pregnancy and breastfeedingWarfarin crosses the placenta, causing teratogenicity and fetal bleeding Side effects of NOACs during pregnancy and breastfeeding are unknown. Therefore, they are currently not recommended. Specific contraindicationsDabigatran: concurrent administration of ketoconazole, itraconazole, ciclosporin, tacrolimus, or dronedarone P450 inducers: ↓ warfarin levels (Chronic Alcoholics Steal Phen-Phen and Never Refuse Greasy Carbs): C - Chronic alcohol use, S - St. John's wort, P - Phenytoin, P - Phenobarbital, N - Nevirapine, R - Rifampin, G - Griseofulvin, C - Carbamazepine P450 inhibitors can be remembered with "sickfaces.com group": S - Sulfonamides, I - Isoniazid, C - Cimetidine, K - Ketoconazole, F - Fluconazole, A - Alcohol (binge drinking), C - Ciprofloxacin, E - Erythromycin, S - Sodium valproate, C - Chloramphenicol, O - Omeprazole, M - Metronidazole, G - Grapefruit juice Guidelines & therapy recommendations Bridging anticoagulation: the administration of heparin for the duration of the transient hypercoagulable state caused by warfarin therapy. Heparin prevents coagulation by activating antithrombin.Reduces risk of venous thromboembolism and skin necrosisMay also be used during interruptions of warfarin therapy (e.g., surgery) Preoperative bridging therapy Stop coumarin administration 5-6 days before surgery.Administer a therapeutic dose of the bridging drug 3 days before surgery, with the last dose administered 24 hours before the procedure. Resume the bridging drug and warfarin after surgery ; administer the bridging drug for 4-6 days post-surgery.