DRx 2 Cardiovascular Module MS 221

The goals of cardiac rehabilitation are to identify and modify risk factors,

, which may lead to the progression of atherosclerotic coronary disease; and also restore and maintain an individual's optimal physiological, psychological, social, vocational, and emotional status. When necessary, therapy is directed toward the improvement of functional capacity, alleviation of activity-related symptoms, and reduction of disability. Obviously these are major undertakings for the physician alone and are best achieved through the efforts of a multidisciplinary team. Contemporary cardiac rehabilitation programs are comprehensive secondary prevention programs offering: • lipid management • nutritional counseling and weight management • smoking cessation • psychosocial counseling • exercise training The staff usually includes a physician, nurse, exercise physiologists or physical therapists, nutritionist, social worker, and trained personnel for smoking cessation. Once a patient joins the rehabilitation program, reasonable short and long-term goals are established. Patient participation in setting goals appears to improve subsequent adherence and compliance to the program.

EPIDEMIOLOGY OF CARDIOVASCULAR DISEASE

- 70% illness is preventable -33 mill US CVD (26.6 HD' 6..4 Stoke) -Leading death in all races + sexes (23.5% of all death; 611.1k CVD death) -584.8k cancer death; 149.2 lung death -193 per 100k HD death (1 every 40 sec) -Death rate is declining 31% (307 per 100k 1950 to 235.5 2010 to 193 2013) -3.15 billion burden (doc, hosp, med, home health, produc) whereas cancer 201 billion -Major cause is atherosclerosis (slow over life; control risk factors for atherosclerosis reduces CVD burden) -Primary prevents disease; secondary prevents events -Risk factors of atherosclerosis: age, sex, smoking, family, hypertension, cholesterol, sedentary, obese, diabetes, menopause, left ventricular hypertrophy, stress cause atherosclerosis which trigger events like angina pectoris AP< MI, cardiac death, CHF, stroke, and peripheral vascular disease.

Myo Coronary Artery Supply

- LmCA: left coronary cusp of aortic valve -> LAD + LCx -LAD + branches = left ventricular anterior septum and anterior lateral wall -LCx + obtuse marginals = anterior lateral and inferior lateral left ventricle wall -RCA: right coronary cusp AV groove; RCA + PDA/PLseg cover inferior septum, inferior left ventricle wall. RCA dominance 85% supply inferior septum. RCA covers right ventricle, right atrium, SA, and AV nodes.

Treatment of DCM

- Medical therapy for chronic DCM is similar to the standard treatment for heart failure with reduced ejection fraction. Pharmacotherapy includes a beta-blocker for adrenergic blockade, an ACE-I or ARB for afterload reduction, and aldosterone antagonism (spironolactone) helps prevents diuretic-induced hypokalemia and improves outcomes in these patients. Hydralazine/nitrates in self- described black patients can be added for afterload and preload reduction. Loop diuretics are often used in all of these patients for the prevention and treatment of hypervolemia. Digoxin may also be used to improve myocardial contractility and reduce heart failure symptoms and hospitalizations but does not decrease mortality. Patients with heart failure and LVEF < 35% are at increased risk of sudden death due to ventricular arrhythmia including ventricular tachycardia or ventricular fibrillation. Myocardial scar may increase arrhythmia susceptibility. Implantable cardioverter- defibrillator (ICD) are small cardiac devices that are capable of monitoring for ventricular arrhythmias and are able to deliver a high voltage shock to restore normal sinus rhythm if an arrhythmia is detected. ICDs have been shown to reduce mortality in patients with DCM. It is not uncommon that patients with DCM also have left bundle branch block (LBBB) - due to stretching and changes of the conduction system due to ventricular remodeling. This results in delayed electrical excitation of the left ventricle as conduction propagates rapidly down the intact right bundle branch to the right portion of the heart and then slowly spreads leftward. Delayed electrical excitation leads to heterogenous (dyssynchronous) left ventricular contraction and further reduces cardiac output in an already compromised heart. Cardiac resynchronization therapy (CRT) uses a pacemaker to improve the synchrony of left ventricular contraction by simultaneous pacing different regions of the heart with two leads. Large clinical trials have shown that in patients with LBBB and LVEF < 35%, CRT improves heart failure symptoms and quality of life, reduces hospitalizations for heart failure, and reduces overall mortality.

CAT lab Transcatheter aortic valve replacement (TAVR)

- Surgical valve replacement involves excising the defective valve and replacement of the valve with either a biologic or mechanical prosthesis. This is performed via thoracotomy and on cardiopulmonary bypass. With TAVR, a prosthetic valve is deployed and expanded over the native heart valve, similar to how a stent is deployed to treat a coronary artery stenosis. TAVR is minimally invasive and may be the treatment of choice in older-adults patients with high surgical risk.

clinical presentation Acute Myocardial Infarction

- early morning w/ symp nerves + -high MI due to high platelet age, catechol. cortisol in morning -MI in surgical procedures, extreme emotional or physical stress, extreme metabolic derangements, hypertensive crises, coronary vasospasm, or vasospastic agents such as cocaine.

Computed Tomographic (CT) Angiography

-64 slice CT scanners have brought CT coronary angiography -intravenous injection of contrast, instead of the intra-arterial constrast injections that are used in standard coronary angiography -outpatient procedure and only requires a few minutes - evaluate the coronary artery lumen and wall or presence of obstructive coronary stenoses -Data to date demonstrate a high negative predictive value of this technique, and thus a normal coronary CT angiogram is highly reliable in excluding the presence of hemodynamically relevant coronary artery stenosis. - CT coronary angiography may be reasonable to use in ruling out coronary stenoses among symptomatic patients with a low to intermediate likelihood of coronary artery disease, and may help avoid the need for invasive coronary angiography -high radiation doses; not recommended to detect occult CAD in asymptomatic persons.

Power of Study

-Causality determined by conjecture, retrospective, prospective, experimental pathophysiology, small intervention, large RCTs. -Strength, consistency, temporality, biologic gradient, plausibility, coherence, experiment, analogy.

BMI + waist circumference predict risk (35in F 40in M; 25BMI)

-Central Fat Male cardiac apple most linked CRF > Peripheral fat - Central Fat assoc with visceral ectopic fat -> systemic disease via release of cytokines -Possible in normal BMI too! - waist-to-hip ratio (WHR) best predicts future heart attack risk (M > .9; W > .85) -Asses Risk: BMI, Abdomen fat, Waist circumference, other CRF. If high risk = aggressive treatment. -Obesity independent and confounding CFR. -High risk: Coronary heart disease, atherosclerotic disease, diabetes mellitus, sleep apnea.

Ischemia Painful + Silent (if no angina) Angina, Dyspnea, Fatigue, Echo wall motion issue, ECG change, latest is Angina

-Chest pain or high risk ASCAD = evaluate for MI -Diagnosis CorAD via just history -Classic angina: chest, arm, neck, back, nausea, minutes: relieved by rest/nitroglycerin. Chest pain w/ heart origin but not classic: atypical angina. -Unstable angina: increasing, platelet aggregation of fixed stenosis or CorA spasm on lesion, high short-term death.

Coronary artery disease is most common form of heart disease and death in US

-CorAD-RF: high LDLc/c, hypertension, cig, DM, sedentary, obese, family CorAD -CorAD Pathophysiology: MI if Ó in heart cell overdemands. -Myocardial Ó demand: 1. HR, Systolic blood pressure (rate-pressure product)* index 2. Left ventricular contractility (myocardial shortening) 3. Left ventricular wall stress (LVpressure, LVdiameter, LVthickness law of LaPlace s = PR/T). -Myocardial Ó supply via coronary arteries

Pharmacologic Stress Testing (if pt can't exercise due to deconditioning, peripheral vascular disease, orthopedic disabilities, neurologic disease, and concomitant illness,)

-Dobutamine stress echocardiography (DSE) Beta agonist rises HR/Myocontract. Incremental to 40-50 ug/kg/min till end point. -Adenosine or Persantine (dipyridamole ) nuclear stress scintigraphy -Est. diagnosis CAD (myocardial viability prior to revascularization) -Prog post MI/angina -Cardiac risk preoperatively -End point: new or worsening echocardiographic wall-motion abnormalities, adequate heart rate response, arrhythmia, angina, significant ST depression, intolerable side effects, and significant increase or decrease in blood pressure. -Atropine: if HR not reached end point at peak dobutamine. (ECG, HR, BP, echo measures). -A new or worsening wall motion abnormality constitutes a positive test for ischemia. CORONARY PERF + Nuclear imaging agent: vasodilators adenosine,. dipyridamole + thallium or technicium. Cause maximal coronary vasodilation in normal epicardial arteries, but not in stenotic segments. -a coronary steal phenomenon occurs, with a relatively increased flow to normal arteries and a relatively decreased flow to stenotic arteries. -Nuclear perfusion imaging under resting conditions is then compared with imaging obtained after coronary vasodilation.

Excersise Testing

-Duke Prognostic score: single score ex capacity in angina, ST segment depression in test to predict 5-yr CV death. -Ex test post MI before discharge (4 day after) for assess, Rx, and activity require. -Ex testing determine Fx capacity for activity cousneling/ex prescrip, disability assessment to lower contraindications for adverse events during testing. Recent MI, Reduced LVSF, extortion MIsch, and Ventarrhyth risk of death (death in exercise testing is 1/10,000; adverse event is 5/10,000).

Angina Coronary Artery Disease Exercise Testing Sensitivity = 70% Specificity = 70% of obstructive CAD (75+% coronary stenosis)

-Exercise increase myocardial Ó demand + ischemia. -Graded ex test monitor ECG, hemodynamic, symptoms for MI, electrical or abnormal. -Diagnostic testing: good for int. risk CAD. -Asymptomatic Indiv. nonDM noRF = low CAD = no ex tests. -Exercise in asymptomatic if many CARF (10yr CVE) prior to Ec program or occupation public safety. -Pt w +CaRF: typical angina, prior coronary stent, or MI = residual ischemia rather than diagnosis. -Exc test in woman less accurate, sensitivity ok. -Ischemia via lesion = amount of ST depression, # ECG leads involved, duration of depression in recovery. -Ischemia via lesion inverse to ST slope, rate-pressure product of ST depression, max HR, Sys BP, and peak exercise level.

Aquired Hyperlipidemia

-Hypercholesterolemia RF: high cholesterol with age, diabetes, alcohol, hypothyroid, kidney failure, diuretics, cortifcosrteroids, amiodarone, olanzapine raise LDL CP: High cholesterol/LDL increase CVD/death. HDL high is protective. Rx: Statins for all 180+ LDL cholesterol or CRF -Hypertriglyceridemia RF: TAG rise with obese, alcohol, kidney failure. TAG rise with low fat, high carb! CP: TAG + 400 = pancreatitis Rx: Unless sole: statins,if too high: fenofibrate/gemfibrozil, pancreatitis (insulin -> LPL -> TAG cleave fast)

Familial hypercholesterolemia

-LDL receptor mutation prevent liver LDL uptake so it builds up in blood, binds scavenger receptors on VEC, and increases risk for premature atherosclerosis. -Familial Hyperlipoproteinemias by Fredickson Classification type IIa: elevated total cholesterol, normal TAGS, HETEROZYGOUS (1/500), premature coronary disease in 30s/40s, homozygous (1/mill: coronary disease in childhood). -TREAT FHC WITH HIGH DOSE STATIN -LDL apheiesis/liver transplant for homozygous ppl. -PCSK9 promotes LDL receptor degradfation (Evolocumabn PCSK9 antibody for familial hypercholesterolemia) blocks attachment of PCSK9 to LDL receptor for degradation so LDL can be uptaken by liver. -Evolocumab increases LDL receptors on Liver to lover LDL blood levels

When to add other lipid lowering agents Niacin, fenofibrate, gemfibrozil

-LDL still high after high intensity statin -If statin not tolerated due to rhabdomyolysis, transaminitis, etc -Teratogenic statins (use diff in pregnant) -Gemfibrozil/femnofibrate if TAG> 500

Lipid Stuff

-Lipoprotein: lipid + apoprotein move in blood and surface LP determine designation. -Chylomicron: Apo B-48, A, C-II, E -VLDL: Apo B-100, C, E -IDL: Apo B-100, E -LDL: Apo B-100 -HDL: Apo A-1 Gut: B-48 Liver: B-100 LPL: C-II Lecithin cholesterol acyltransferase (LCAT): C-1 A-1 A-IV Cholesterol ester transfer protein (CETP): D LDL receptor: B-100, E Remnant receptor: E HDL receptor: A-1 A-II Inhibition of recognition with hepatic E: C-I, C-II, C-III

Metabolic Syndrome higher prev. in obese, older, 80% overweight.

-Metabolic syn: 2x atherosclerotic heart disease -5x risk diabetes -RF for metabolic syndrome is abdominal obesity, insulin resistance (also sedentary, age, hormone issue, ethnic, genetic; hyperinsulinemia/resistance). -More fat = more bw = hyperinsulinemia-insulin resistance (but 1/4 metabolic syndrome in non-obese people i.e. metabolically obese normal-weight individuals.). -Also assoc w high CRP, pro-thrombotic PAI-1 fibrinogen but not used to define -3 of 5 criteria: -102cm/88cm Abdominal Obesity waist circumference, -150 or Rx TG, --40/50 low HDL, -130s/80d+ bp or Rx bp, -100 or Rx Elev fasting Glu. No specific Rx; lipid, hypertension, diabetes, weight loss to lower MRF 7-10% in Y1, 30min mod exercise, low Sat fat, low sugar. 5-10% weightloss = reduces risk of diabetes in insulin resistant pts (improves insulin, endothelial, TG, BP, heart fx). -Dont gain weight; 3-5% 3year success, low fat diet (behavior, exercise, surveillance). -Weight loss drug BMI 30+ no risk, 27+ w/ risk (hypertension, dyslipid, CHD, DM, OSA) -Orlistat (lipase inhibitor flow 1/3 fat intensive +4% weight loss) oily stool -Phenteramine not for kids of +12 week, not hypertensive or CHD -Lorcaserin Belviq: Serotonin 2CR agonist -Topiramate + Phentermine Qsymia: Anti-seirzure/GABA-Rmod. Withdrawn *Sibutramine NE/Sert Reuptake Inhib increase MI/Stroke, Rimonobant psych, Fenfluamine/dexfenfluarmine PHT). GI surgery failing WL or treatment: BMI 35 w/issues or 40+ (banding, bypass): 60-70% weight loss (gain weight plate is 30% weightloss). Also + hypertension. diabetes, TG, HDL, Chol. Only weight loss intervention to reduce MI risk and life span for obsese.

SG Report Obesity prevalent rapid; DM, hypertension, CVD (BMI 25-29..9 or 30+).

-NHANES: 64% overweight; 20% kids overweight. Poor diet + sedentary: 400k prevent death (second to tobacco). -Obseity: hypertension, diabetes, high TAGs, low HDL, high LDL, OSA, impair lung, gall bladder, gout, joint disease, cerv/uter/breas/pros cancer. 70% type-II DM link obesity. -Obesity own RF for coronary heart disease CHD. -Heart issues w/obesity: Cardiac hypertrophy, diastolic dysfunction (bad relaxation), systolic dysfunction (low LVEF, low after load), vascular endothelial issue, premature coronary artery plaques due to high perfusion body demand and fat into heart tissue being toxic. 1kg/m BMI rise: HF 5% rise M, 7% rise FM. -Daily mod act lower CHD in sedentary (vigorous aerobic + lung/heart fx)

Most important CRF

-Non-modifiable: age, male, family history -Modifiable Strong: smoking, hypertension,. high cholesterol, sedentary. -Modifiable Suggestive Evidence: obesity, diabetes, hormone replacement, left ventricular hypertrophy, stress -Others: Homocysteine, lipoprotein A, triglycerides, hyper coagulability (fibrinogen, factor VII, low antithrombin III, platelet aggrebility, PAI-1, inflammation CRP, ounce of prevention = lots of cure.

Mod intensity statin Rosuvastatin 5-10mg Atorvastatin 10-20mg Simvastatin 20-40mg

-Over 75y/o high coronary disease, PVD, stoke -All other DM -NonDM 10yr 5-7.5% if LDL not less than 70 on other Rx -Cannot tolerate high statin due to CK, muscle ache, ALT>3x upper -High CRP, family coronary disease, coronary calcium score

Classifying hyperlipidemia

-Primary (familial); Secondary (etc) -Type of lipid: hypercholesterolemia, hypertiglyceridemia, or Chol+TAG= hyperlipidemia'

When should one use cardiac imaging with ET:

-Resting ECG abnormal -+ diagnosed. accuracy after ok ECG ET -Ischeia in pt with coronary arteriography to look at vascular territory

Epidemiology Terms leading cause of M/F US death 246 CRF

-Risk factor (assoc w disease occur), Risk marker (reflects other RF), confounding variable, adjustment (account for RF), relative risk -RR (RR = Ie/Iue; RR+1 risky) -Attributable risk (AR = Ie - Iue absolute effect -Population attributable risk (PAR etiologic fraction % of disease in pop attributed to risk i.e. % eliminated in pop if RF eliminated taking into account prevalence and RR) -Prevalence: % disease at point in time (affected by incidence and mortality) -Incidence: new cases during time interval -primary prevention: without clinical disease -secondary prevention: prevent events and deaths in diseases -observational studies (FHS, PHS, NHS impact of CRF but less precise in est. due to healthy cohort effect more healthy less prone also who took extra prevention measures -RCT help see if treating CRF prevents CVD and death; CRF efficacy data is not available -Meta analysis: pool result to resolve conflict, reduce false negative/false positive, and explain variations via stats -Indiv CRF mod personalize patient risk modification (higher risk; better CRF benefit. CHD risk due to angina, claudication, MI, CRFs, and diabetes.

Excersise Testing Devices + Protcols

-Treadmill (walking; higher peak VÓ HR than cycle), cycle ergometer (cheaper, less noise/space, if freaked help up workload less movement of arm/thorax = better ECG/BP measurements, not normal exercise so hard to get to end point). -Protocol: purpose of test, outcome, patient. Bruce treadmill test: large unequal increments METs/stage 3min so overestimate ex capacity. Larger work-rate increments ok for young; small increment for older or issued. -HR/BP measure prior/during/following graded ET. Percepted response. Symptom complaints (chest pain, burning, discomfort, dyspnea, leg pain). ECG. ST segment changes. -Terminate ET if mod angina,. fatigue, ischemic ECG, drop in systolic bp, complex ventricular dysrhythmia.

Coronary angiography is the current "gold standard" for the detection of coronary artery disease.

-catheter via femoral/brachial to coronary -radiopaque dye finds filling defects (coronary artery stenoses) -confirm hidden tests; Rx plans -issues: bleeding at the arterial and venous access site; vessel or cardiac perforation; stroke; myocardial infarction; and rarely deat

Coronary flow supply limited by plaque in lumen degree varies via

-degree of obstrx -length of obstrx -#/size of fx collateral vessels -magnitude of supply dependent muscle mass -shape + prop of stenosis -autoreg capacity of vasc. bed -resistance to flow in steoniss = residual area + length -50-70% stenosis of diameter impairs peak reactive hyperemia in exertion -90% stenosis reduce resting flow -90% of vascular resistance are arterials (can dilate 4x) so tone changes = ischemic threshold -IT: HR/rate pressure when ischemia is called - variable flow reserve to dynamic arteriole. -Change in coronary tone via neuromodulation + endothelia, local thrombosis increases obstruction Other corflow issues: -Coronary vasospasm (w or w/out fix stenosis) -coronary vasculitis: CVD, radiation vasculitis. -anomalous coronary arteries (alt path of artery lower flow) Myo Supply issues w conditions: -Anemia -hypoxemia -hypovolemia

ACC AHA treat blood cholesterol to lower Athero CRF

-healthy life -statins initial -intinsity Rx = LDL baseline + CRF -ASCVD Risk 10yr pooled cohort equation set risk.

Exercise Nuclear Imaging (w/ ECG) ET Perfusion defects only w/ exercise not at rest = ischemia. Perfusion defects ET AND REST = previous MI or scar. Sensitivity = 90% Specificity = 80%

-thallium or technicium radioactive agent injected 1 min prior to end exercise = images 1 hr later. -reinject for rest image 3-4 hour before or after ET -Technetium-99m agents permit higher dosing with less radiation exposure than thallium (sharper image) -Technetium-99m agents good for single photon emission computed tomography (SPECT). w 180 degree gamma camera (thing slice heart images 3D; prevent overlap from thallium planar). -Issue: ionized radiation; more stuff and people -Good: 3D plane specific

Infarct Expansion Effect on Left Ventricular Function Acute Myocardial Infarction w

. This is called infarct expansion. Infarct expansion is associated with a higher mortality and a higher risk of congestive heart failure and aneurysm formation. Rupture of the ventricle, which is generally a fatal event, is considered to be the end result of severe infarct expansion. Elevated left ventricular pressure, by increasing wall stress, increases the risk of infarct expansion, whereas a patent coronary artery leads to the early formation of an adequate myocardial scar thereby reducing the risk of expansion. In general, the larger the area of myocardial damage, the more likely the patient is to develop heart failure, manifested by increased pulmonary congestion or cardiogenic shock, which is manifested by an inability to adequately perfuse the major organs (brain, kidneys) and is often fatal.

ECG Workshop

1. 2. 3. 4. 5. 6. 7. 8. 9. Calibration Rate Rhythm QRS axis Intervals P-wave abnormalities QRS abnormalities ST-segment, T-wave or Q-wave abnormalities Clinical relevance

In clinical practice, patients with heart failure are sometimes classified into one or more broad categories that reflect the underlying cause or the temporal acuity of the symptoms.

1. Acute versus chronic heart failure. The clinical manifestations of heart failure depend on the rate at which the syndrome develops, and whether enough time has elapsed for compensatory mechanisms to become operative or interstitial fluid to accumulate (Table 1). Examples of acute heart failure include massive myocardial infarction, sustained tachyarrhythmia, and acute bacterial endocarditis with valve rupture. Symptoms are due to the sudden reduction in cardiac output with poor organ perfusion and/or marked congestion. When reduction in cardiac output occurs gradually (e.g., remodeling post-MI), compensatory mechanisms allow the patient to tolerate hemodynamic abnormalities with fewer signs and less symptoms.

Stuff released by adipocytes causing CV damage

1. Angiotensinogen (AII vasoconstrictor high bp) 2. FFA (toxic to bv + insulin resistance) 3. C-reactive protein (proinflam vascular dysfx) 4. Plasminogen activator inhibitor-1 PAI-1 (pro-thrombus increase clot) 5. Interleukin-1 & TNF-a cause inflam 6. Resistin inc insulin resistance Good stuff for BV from fat: Adiponectin: vasculoprotective (weight loss increases this!; low blood adiponectin = bad arteries).

Disorders of Impulse Propagation A failure of an impulse to propagate normally through the conduction system may result in bradycardia. The two most common types include:

1. Atrioventricular block (AV block) While first degree AV block does not cause bradycardia, higher degrees of AV block including second degree Mobitz type I & type II, 2:1, and 3rd 2nd degree AV block - Mobitz Type I degree AV block may cause bradycardia or asystole. "Wenckebach phenomen a. Second degree Mobitz type I or Wenckebach: There is 1) Progressive delay in PR interval with eventual Defini on: gradual prolongation of the PR interval prior to occurrence of AV non-conducted or "blocked" beat block. The PR interval after the non- conducted beat is shorter 2) The return PR interval is shorter that of the beat preceding blocked beat than the PR interval prior to the non-conducted beat. The block • Typically "grouped bea ng" is observed. almost always occurs in the AV node and is not indicative of • Block is usually physiologic and occurs within the AV node intrinsic conduction system disease or a need for a pacemaker. (conduc on through His-Purkinje system is usually normal). Atropine or exercise usually improves the block. b. Second degree Mobitz type II: The PR interval of conducted beats is constant before and after spontaneous AV block. The block is usually in the His-Purkinje system and represents conduction system disease. Mobitz type II block is generally an indication for implantation of a permanent pacemaker. c. 2:1 AV block: Since there is only one PR interval prior to AV block it is neither Mobitz type I or II. Clinically, 2:1 AV block is most often due to conduction system disease and a pacemaker is indicated.

Indications for cardiac catheterization Diagnostic cardiac catheterization is used to assess cardiac hemodynamics, physiology and/or to image coronary arteries, heart chambers and aorta through the technique of angiography

1. Coronaryarterydisease a. Stable angina (NO!)-revascularizationhasnotbeenshownto improve MI-free survival (COURAGE trial). Cardiac catheterization may beneficial in: • Class I-II angina patients who are intolerant of anti- anginal medication or who have a specific high-risk occupation (i.e. pilot) • Class III-IV angina patients in whom revascularization with either PCI or coronary bypass is recommended in addition to medical therapy, particularly with: • a change in pattern of angina • ischemia on noninvasive stress testing • new left ventricular dysfunction (reduced ejection fraction) • diabetes b. Acute coronary syndrome-Unlikestableangina,forunstable angina the data support early intervention to reduce risk of death or myocardial infarction. c. Postmyocardialinfarctionangina d. Acute myocardial infarction (ST elevation infarction) - Data supports PCI over fibrinolysis therapy alone with reduction in death, myocardial infarction, recurrent ischemia, and stroke. PCI salvages more myocardium and reduces risk of left ventricular dysfunction. e. "Markedly"positivestresstest f. Rule out coronary artery disease when clinical suspicion is high and/or non-invasive studies are ambiguous 2. Valvularheartdisease-definetheseverityofpathologyanddefine coronary anatomy to determine need for coronary artery bypass at the time of surgical valvular repair 3. Cardiomyopathy a. Dilatedcardiomyopathy-toruleoutcoronarydiseaseascause of myopathy, to assess hemodynamics, and in some patients to obtain myocardial biopsy (i.e amyloid, sarcoid) b. Restrictivecardiomyopathy-toassessphysiologytodistinguish restriction from effusive constrictive and tamponade c. Hypertrophic cardiomyopathy - to assess physiology and to define coronary anatomy as many of these patients have exertional chest pain and may have concomitant coronary disease 4. Congenital heart disease - to diagnosis and define anatomy, to assess physiology

E. Physical Signs of Heart Failure

1. General appearance. Depend on the severity and chronicity of failure. Patients with compensated heart failure may appear well nourished and comfortable at rest, while patients with decompensated failure may appear anxious, dusky in color, and diaphoretic. Other findings that suggest severe LV failure include cool extremities, cyanosis, scleral icterus and a malar flush. 2. Vital signs. a. Manypatientswithdecompensatedheartfailurehaveresting sinus tachycardia due to increased sympathetic activity. The pulse may be irregular if atrial fibrillation is present, or alternatingly strong and weak (pulsus alternans) if severe ventricular dysfunction is present b. TachypneamaybepresentintheclassIVpatientorsecondaryto pleural effusions or ascites. Advanced heart failure may also be associated with Cheyne-Stokes respiration. c. Thebloodpressuremaybeelevated(diastolicheartfailure), normal (compensated heart failure), or low (end-stage systolic failure). The pulse pressure narrows when cardiac output is critically reduced..

1. Incidence and Prevalence. of HF

1. Incidence and Prevalence. In the U.S. prevalent cases of heart failure exceed 5.8 million and each year >550,000 new cases are diagnosed. HF is the leading discharge diagnosis in Medicare patients (i.e., over age 65). Blacks have higher hospitalization rates and mortality compared with whites. Despite steady decrease in incidence of CAD and stroke due to better control of risk factors such as hypertension and smoking, the incidence of heart failure continues to rise. This may be due in part to the aging of the population and the improved survival of patients with cardiovascular diseases such as myocardial infarction. Enormous economic impact due to direct medical costs, as well as disability and loss of employment (estimated annual treatment costs $40 billion).

The evidence for a causal relationship between beta-hemolytic streptococcal infection and ARF rest on three observations:

1. MostpatientswithARFhavehadstreptococcalpharyngitisonetothree weeks before the onset of ARF. 2. TheincidenceofARFinagivencommunityparallelstheincidenceofbeta streptococcal pharyngitis. Approximately 0.3% of individuals with endemic acute streptococcal pharyngitis develop ARF: during well-studied epidemics at military bases, the incidence may rise to 3%. 3. PatientswithARFshowahighorrisingtitreofantibodiesagainst Streptococcus, such as anti-streptolysin O (ASLO).

Mechanisms of arrhythmogenesis AF may be caused by one (or a combination) of three established mechanisms.

1. Multiple random propagating wavelets Multiple independent propagating electrical wave fronts (wavelets) are occurring simultaneously and randomly throughout the right and left atrium. The number of wavelets at any time point is dependent on atrial conduction velocity, refractory period and atrial mass. ***Slow atrial conduction, short refractory period, and large atrial mass promotes and perpetuates AF.*** 2. FocalTriggers Focal electrical discharges trigger the initiation or act as the driver to maintain AF. These triggers arise most commonly from the orifices of the pulmonary veins or near the superior vena cava. Ablation of these triggers has been shown to reduce and or eliminate AF recurrence. 3. Localized reentrant activity with fibrillatory conduction There is increasing evidence that local reentrant circuits or rapidly spinning/spiraling sources in an around the pulmonary veins and posterior wall of the left atrium may promote AF. Ablation of these circuits/ sources has been shown to reduce and or eliminate AF recurrence.

Definition of Acute MI - MI may be diagnosed clinically or at autopsy. Either one of the following criteria satisfies the diagnosis for an acute, evolving or recent MI:

1. Rise and gradual fall (troponin) or more rapid rise and fall (CK-MB) of biochemical markers of myocardial necrosis with at least one of the following: -ischemic symptoms -development of pathologic Q waves on the ECG - changes on ECG indicative of ischemia or infarction (ST segment depression or elevation) - need for coronary artery intervention 2. Pathologic findings of an acute MI at autopsy.

Acute Coronary Syndrome (ACS): an ischemic myocardial event that is a direct consequence of atherosclerotic plaque activation and acute local thrombus formation. (3 syndromes)

1. ST Elevation myocardial infarction (STEMI): no blood flow 100% -> . Transmural injury and infarction -> revascularization with percutaneous intervention 2. Non-ST elevation myocardial infarction (NSTEMI: 1.ACS 2. unstable angina 3. NSTEMI): Coronary stenosis without total occlusion -> subendocardial infarction or ischemia. -UA and NSTEMI, as well as ST elevation MI = unstable coronary lesions/plaque rupture. - acute but subtotal thrombosis of a coronary artery, acute thrombosis of a vessel that supplies an area with collateral blood supply, or embolic occlusion of a small distal part of a vessel (plaque embolus or thromboembolus). -Type II NSTEMI or demand-mediated infarction is myocardial necrosis that occurs as a result of in adequate coronary blood flow in the setting of increase myocardial oxygen demand (supply demand mismatch due to a fixed coronary stenosis). underlying CAD who experience an episode of severe hypertension or tachycardia that suddenly increases myocardial oxygen demand and they are unable to increase their supply across a fixed coronary stenosis. 3. Unstable angina (UA): unstable plaque causes dynamic thrombus formation and intermittent high-grade occlusion of a coronary artery.; duration and severity of this occlusion have not been significant enough to cause myocardial necrosis. ; Unstable angina (UA) and non- ST elevation (non-Q wave) myocardial infarction (NSTEMI) differ primarily in whether the ischemia is severe enough to cause sufficient myocardial damage to release detectable quantities of a marker of myocardial injury. . Unstable angina is considered to be present in patients with ischemic symptoms suggestive of an ACS and no elevation in troponin, with or without ECG changes indicative of ischemia (e.g., ST segment depression or transient elevation or new T wave inversion).

Acute MI ST Depression or T wave Inversion

1. ST depression or T wave inversions without ST elevation is usually seen in an evolving subendocardial infarction (non-ST elevation MI or unstable angina) where the area of necrosis is limited to a small area or to the subendocardium. Following the acute coronary event the ST segment and T-wave return to normal over subsequent weeks.

Pharma of MI Drug

1. Short-acting nitrate (1min:15min): Nitroglycerin/Isosorbide dinitrade (SL) Release NO, high cGMP, relax vasc. SM Use: Acute angina pectoris; ACS Bad: tachycardia, orthostatic hypotension, headache 2. Int-acting nitrate (2-4hr): Nitroglycerin/Isosorbide dinitrate (ol) NO, cGMP, act.metabol.dinitroglycerin, Use: prophylaxis of angina. Bad: tachycardia, orthostatic hypotension, headache 3. Long-acting nitrate (24hr->10hr dur) Transdermal nitoglycerin Release NO, high cGMP, relax vasc. SM Use: prophylaxis of angina. Bad: tachycardia, orthostatic hypotension, headache, low response tachyphylaxis 4. B-blockers Metoprolol (oral; duration 6-9h) selective β1-blocker; block symp. on heart; low CO; + renin release Use: angina pectoris; hypertension, arrhythmias, migraine Bad: asthma broncho, cardiac depression, sedation, erectile issue, sleep issue (less than propranolol) 5. Calcium Channel Blockers Verapamil, Diltizem (oral,6-8h) L-type C blocker, vasc- ++cardiac effect Use: angina (atherosclerosis/vaso), AV node arrhythmia Bad: cardiac depression (less with diltiazem), constipation, flushing, dizziness, hypotension Amiodipine (oral; 6-8hr) L-type Ca blocker More vasodilator effect Use: angina hypertension Bad: like verapamil, less constipation; less cardiac depression Sodium Channel Blocker: blocks late Na+ current in myocardium to limit cardiac work Use: angina Bad: QT elongation on ECT

AF Therapy Focus is on 2 aspects:

1. Stroke prevention AF increases a patient's risk of thromboembolism and stroke. Non- uniform and poorly contracting atrium results in stasis of blood. Blood stasis coupled with endothelial dysfunction and activation of coagulation cascade increases the risk of thrombus formation, particularly within the left atrial appendage. Patients with mitral stenosis from rheumatic heart disease or prior history of stroke are at greatest risk of thromboembolism. A patient's risk of stroke is clinically determined by the CHÁDS2-VASc score and this helps guide the use of aspirin or anticoagulant (vitamin K antagonist, Xa inhibitor, or direct thrombin inhibitor) in patients with non-valvular AF (AF that is not due to mitral valve disease). Patients with CHÁDS2-VASc score ≥2 require anticoagulation for adequate stroke prevention. All patients with valvular AF (AF due to mitral valve disease) are treated with warfarin for stroke prevention.

4. Treatment of Acute Coronary Syndrome - Emergency Department phase Acute treatment of ACS should be started immediately in parallel with the initial workup. The primary therapeutic goals include:

1. restore myocardial perfusion 2. reduce myocardial oxygen demands 3. relieve ischemic pain/anxiety These goals are achieved with multiple, initial pharmacologic interventions.

Despite its low incidence in the US, it is important to study ARF because:

1. thepreciseimmuno-molecularmechanismslinkingstreptococcalsore throat to chronic heart disease remain a mystery. 2.chronicrheumaticheartdiseasecontinuestoafflicthundredsofthousands of patients in this country. 3.preventionofARFandchronicrheumaticheartdiseaseistheprimary justification for antibiotic therapy of pediatric sore throats. 4.rheumaticheartdiseaseremainsamajorworldhealthproblem 5.ARFmay,atsometime,becomearecrudescentproblemintheUS.

2. Changing etiology of HF

2. Changing etiology. Framingham Study, 1971: 75% of patients with heart failure had hypertension; coronary artery disease was present alone in only 10%. SOLVD Registry Data, 1989: 74% of patients with ejection fraction <45% had ischemic heart disease as the underlying cause of LV failure; hypertension was considered to be the primary cause in only 4%, although is likely contributes in a majority. 3. Prognosis and effect of treatment. Mortality rate for all patients with HF is about 50% over 5 years. Patients with end-stage heart failure (NYHA class IV) have a 1-year mortality rate of 30-40%. Over 90% of deaths are due to cardiovascular causes, most commonly progressive heart failure or sudden cardiac death. Sudden death is often due to ventricular tachycardia or fibrillation, but bradycardia and asystole may occur.

AF Prevention

2. Control of symptoms related to atrial fibrillation Treatment of symptoms related to AF may be accomplished with one of two strategies: A. Rhythm control focuses on restoring and maintaining sinus rhythm. To restore sinus rhythm a DC cardioversion (electrical shock) is performed. Once sinus rhythm is restored, a patient may be prescribed an appropriate anti- arrhythmic drug such as amiodarone, flecainide, dofetilide, or sotalol for maintenance of sinus rhythm. Surgical or catheter ablation may also be performed to modify the atrial substrate and reduced pulmonary vein triggers for AF. B. Rate control focuses on preventing a rapid ventricular rate. The electrical activation of the atria during AF occurs at a frequency of < 200 milliseconds (>300 beats per minute). The AV node modulates atrial input and generally protects the ventricles from excessively fast activation (> 200 bpm). With rate control strategy, a patient may be prescribed AV node modulating drugs like beta-blockers, calcium channel blockers and digoxin to slow impulse transmission in the AV node and thereby slow ventricular rate in atrial fibrillation. These drugs are generally titrated to achieve a resting heart rate of < 110 bpm. The choice of rate versus rhythm control does not impact the decision to anti-coagulate. The risk of stroke is not altered by rhythm control strategy (i.e. duration or frequency of AF is not a factor attributed to stroke risk).

Acute MI ST Elevation

2. ST elevation is usually seen in an evolving transmural MI and usually indicates a more extensive necrosis where the electrical integrity of the cell membranes is affected, and currents of injury develop. The injury pattern on ECG during evolution of a classic transmural infarction consists of ST segment elevation. With ST elevation MI, tall or peaked T waves may be observed in early stages. The T waves subsequently invert. As the period of active injury resolves (or evolves) the ST segments return to baseline, but the inverted T waves may persist indefinitely. Pathologic Q waves and loss of R wave amplitude are late manifestations of more extensive, transmural necrosis.

Sys vs Dys HF

2. Systolic versus diastolic heart failure (also see section above). The clinical syndromes resulting from systolic versus diastolic myocardial failure are in many ways similar, and likewise, they share some types of therapy. However, some forms of therapy for systolic failure (e.g., the use of positive inotropic agents) are not useful, and may even be detrimental, in patients with diastolic heat failure. While systolic and diastolic heart failure can be easily distinguished by echocardiography (low ejection fraction = systolic heart failure; normal or elevated ejection fraction = diastolic heart failure), there are some clinical features that can provide clues (Table 2).

3. Atrioventricular nodal reentrant tachycardia (AVNRT)

3. Atrioventricular nodal reentrant tachycardia (AVNRT) has a similar in mechanism to AVRT. A second route of conduction is present within the AV node itself, but unlike normal AV nodal tissue, the second route does not exhibit decremental conduction and is termed the "fast pathway". The "fast pathway" has a longer refractory period than the normal AV nodal tissue. An atrial premature beat can block in the fast pathway, conduct slowly down normal AV nodal tissue "slow pathway", reenter and conduct back to the atrium up the fast pathway. In this manner, AVNRT is established. ECG demonstrates a regular, narrow QRS complex tachycardia with no discernable P-waves or retrograde P-waves immediately following the QRS complex. The ECG below shows a magnified V1 lead. An upright P-wave is discernable at the terminal portion of the QRS. Acute treatment or termination of AVNRT may be achieved with maneuvers that increase vagal tone such as carotid sinus massage. Increased parasympathetic tone transiently slows conduction through the AV node and terminates reentry. Alternatively AV nodal blocking agents like adenosine, beta-blocker or calcium channel blocker may be administered. AVNRT is a recurrent arrhythmia that is cured with ablation.

HF ECG ECHO

3. Electrocardiogram. Common findings include sinus tachycardia, atrial fibrillation, evidence of prior myocardial infarction, ventricular ectopic activity, and left bundle branch block. In restrictive / infiltrative cardiomyopathy (e.g., amyloidosis) low voltage may be seen. 4. Echocardiogram. Very useful non-invasive tool to assess right and left ventricular size and function, examine valvular morphology and function, rule out congenital abnormalities, intracavitary thrombi and pericardial effusion, and obtain hemodynamic information such as cardiac output, pulmonary artery pressures, and valve area (e.g., in aortic or mitral stenosis). In patients with poor echocardiographic windows, cardiac MRI may be used to define cardiac structure and function. 5. Cardiac Catheterization. Provides direct assessment of hemodynamics and valvular disease, and is used to rule out intra-cardiac shunts and define coronary anatomy (see lectures on Hemodynamics). Provides direct assessment of left and right heart filling pressures, cardiac output, and systemic and vascular resistance that can aid in making therapeutic decisions.

Physical Sign of LSHF

3. Left-sided heart failure. Examination of the lungs may reveal rales, rhonchi or wheezing due to pulmonary congestion. On cardiac exam, the LV impulse may be diffuse and laterally displaced (if heart is dilated), or sustained (in pressure-overload states such as aortic stenosis). If pulmonary hypertension has developed in the setting of chronic left heart failure, a loud P2 may be heard. An S3 gallop in an adult is a relatively specific but insensitive finding in LV systolic failure. Conversely, an S4 gallop is often present in patients with diastolic dysfunction and reduced ventricular compliance. A holosystolic murmur of mitral regurgitation may be present in patients with mitral regurgitation which most often secondary due to mitral annular dilation.

Acute MI Q Pathologic

3. Pathologic Q waves are the late manifestation of transmural MI on ECG and are the result of an electrical silent region of myocardium. See figure. A pathologic Q wave must be ≥ 0.04 seconds in duration (width) and have a depth greater than 25% the amplitude of the succeeding R-wave. Note in the figure there is no R-wave. Pathologic Q waves must be present in two contiguous leads for diagnosis of myocardial infarction.

3. Right-sided versus left-sided heart failure.

3. Right-sided versus left-sided heart failure. According to the "backward failure" hypothesis (Hope 1832), fluid accumulates behind the ventricle that is initially affected. Thus, patients with left-sided failure initially develop pulmonary congestion. With time, however, fluid accumulation becomes generalized and patients develop signs of right-sided failure including lower extremity edema, tender hepatomegaly, and pleural effusions. Pure right- sided failure may occur secondary to primary pulmonary hypertension, chronic pulmonary emboli, or chronic lung disease (i.e., cor pulmonale).

4. Low-output versus high-output heart failure.

4. Low-output versus high-output heart failure. Low cardiac output at rest, or in milder cases during exercise or stress, characterizes most etiologies of heart failure. Peripheral vasoconstriction may result in cold, pale extremities, a narrow pulse pressure, and a widened arterial-venous oxygen (A-V Ó) difference. High-output states in which the pumping function of the heart is unable to meet the abnormally high metabolic demands of the body may less commonly lead to heart failure. Examples include thyrotoxicosis, anemia, A-V fistula, and vitamin C deficiency (beri beri). The extremities are warm and flushed, the pulse pressure normal or widened, and the A-V Ó difference narrowed.

RSHF Physical

4. Right-sided heart failure. Elevated systemic venous pressure may manifest as jugular venous distention, hepatojugular reflux (increased jugular venous pressure with compression of the right upper quadrant), an enlarged/tender liver, ascites, and/or lower extremity pitting edema. The lungs may be dull to percussion at the bases secondary to pleural effusions. Massive, generalized edema, known as anasarca, may accompany end- stage right-heart failure. Tricuspid regurgitation, which may result from pulmonary hypertension, causes prominent V-waves in the neck veins, a right-sided holosystolic murmur that increases with inspiration, and a pulsatile liver.

BBB ECG MI

4. The development of a bundle branch block may be seen in more extensive MI's involving the septum where ischemia and/or necrosis to elements of the conduction system occur. Left bundle branch block may mask ST-elevation and make it difficult to determine whether acute and complete coronary artery occlusion is present. For this reason, a new left bundle branch block is treated similar to ST-elevation myocardial infarction with emergency revascularization.

Normal ECG Acute MI

5. No changes (normal ECG) or non-specific ECG changes (T-wave flattening) may be seen in a minority of patients with acute MI and usually indicates an infarct involving a territory of the heart that is not well represented on the ECG (left circumflex artery territory) or one that is small and likely uncomplicated.

B. Diastolic heart failure, also referred to as "HF with preserved ejection fraction" or HFpEF:

: Diastolic heart failure results from a stiff left ventricle resulting in poor diastolic filling. Impaired LV filling occurs because a high end-diastolic pressure is reached at a low end-diastolic volume. The end-diastolic pressure volume relationship (EDPVR) is shifted upward (figure). Diastolic pressures are elevated leading to pulmonary vascular congestion. Abnormal diastolic function may be dues to impaired relaxation (active process), increased stiffness of the ventricle (passive property) or both. Causes include ischemia (example of active), left ventricular hypertrophy (LVH) or restrictive cardiomyopathy (example of passive). Typical causes include: chronic hypertension with resultant LVH, senile changes with aging, infiltrative diseases (e.g., amyloidosis or sarcoidosis), hypertrophic cardiomyopathy, a genetic disease. Diastolic heart failure is the most common form of heart failure in women.

E. Pharmacologic treatment of acute heart failure in the hospital a. Diuretics ("wet to dry"):

: Hypervolemia is corrected acutely with IV loop diuretics, which are dosed 1-3 times daily or given as an IV drip. Loop diuretics inhibit the Na/K/2Cl- transporter in the loop of Henle, resulting in loss of fluid intravascular volume. This improves symptoms, and also decreases preload, allowing the mobilization of interstitial fluid and resolution of peripheral edema and ascites. The most commonly used loop diuretic is furosemide (Lasix). Dosing is individualized and based on establishing an effective diuresis. The threshold dose varies considerably from patient to patient, and even for the same patient depending on their physiologic status, and therefore the initial dose is determined by titrating with careful monitoring of urine output. Excessive diuresis may decrease cardiac function by moving the patient leftward on the Starling curve, and may lead to decreased renal perfusion, kidney dysfunction, and hypotension. Other side effects include depletion of potassium, calcium and magnesium, leading to arrhythmias.

3. Causes of Myocardial Dysfunction

A large number of structural abnormalities that affect the peripheral and coronary vessels, myocardium, pericardium, or cardiac valves can lead to the hemodynamic burden or myocardial or coronary insufficiency responsible for heart failure. • Loss of myocardium: myocardial infarction, right ventricular dysplasia • Decreased contractility: myocardial ischemia, dilated cardiomyopathy, myocarditis, toxins (alcohol, cocaine, chemotherapy) • Pressure overload: aortic stenosis, uncontrolled hypertension, aortic coarctation • Volume overload: mitral or aortic regurgitation, atrial or ventricular septal defects, patent ductus arteriosus • Restricted filling: left ventricular hypertrophy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis or pericardial tamponade • Miscellaneous: mitral stenosis, arrhythmia, endocrinopathies

E. Pharmacologic treatment of acute heart failure in the hospital b. Vasodilators and positive inotropes ("cold to warm"):

A low cardiac output may be corrected acutely with the administration of intravenous positive inotropes and/or vasodilators. Vasodilators may act on the arteries, veins or both (mixed or balanced vasodilator). Commonly used vasodilators in the acute setting include nitroglycerin, nitroprusside and nesiritide. Nitroglycerin and nitroprusside both work by releasing nitric oxide (leading to increased cGMP in the vascular smooth muscle cell), while nesiritide is a recombinant version of BNP, which acts on the BNP receptor to generate cGMP. Nitroprusside, though very potent, consists of NO-complexed to cyanide, and therefore may have serious side effects particularly when there is compromised renal or hepatic function. Nesiritide, which is recombinant BNP, is less potent but much safer and easier to use and has largely replaced nitroprusside. The arterial dilator effect of these agents decreases arterial peripheral resistance, thereby increasing cardiac output by lowering left ventricular afterload (see figure at right). The venous dilator effect of these agents increases venous capacitance, which can be quite large, thereby decreasing cardiac filling pressures, much the way a diuretic would (so-called 'internal diuresis'), and decreasing congestive symptoms.

Pericardial effusion

A pericardial effusion is an abnormal accumulation of excessive fluid within the pericardial space. Any condition that causes pericarditis can cause an effusion but it may also occur in non-inflammatory conditions including congestive heart failure, nephrotic syndrome, and myxedema (swelling due to severe hypothyroidism). The nature of the fluid depends on the etiology and may be: serous (protein-rich water) - congestive heart failure, infection or radiation serosanguinous (serum and blood) - neoplasm, post myocardial infarction, infection with necrotizing bacteria, tuberculosis, trauma, or uremia chylous (lymph) - neoplasm or myxedema Patients may have pain similar to pericarditis, or have shortness of breath from compression of the lung parenchyma. If the fluid accumulates slowly, patients may have no symptoms even with large effusions. In contrast to pericarditis, which is a clinical diagnosis, pericardial effusion is a laboratory diagnosis made using echocardiography or another imaging modality. The classic finding on chest x-ray is an enlarged, globular heart shadow with "water bottle" appearance. On echocardiogram there is an "echo-free space" between the myocardium and parietal pericardium as fluid causes little acoustical reflection. Doppler echocardiogram may also be used to gauge the intrapericardial pressure and its hemodynamic effect on cardiac output. The electrocardiogram may show decreased QRS voltage due to attenuation of electrical current by the fluid. With large effusions electrical alternans may be present. This is where the QRS complexes in the same ECG lead have alternating voltage and axis due to the to-and-fro oscillation of the free-floating heart within the enlarged pericardial space. V3 lead Treatment The management includes treating the underlying cause of the effusion and observing for progression to pericardial tamponade. Pericardiocentesis to remove fluid is indicated if there is hemodynamic compromise (cardiac tamponade) or if fluid is needed for diagnosis of suspected bacterial, tuberculous or neoplastic etiology.

HF Clinical Features

A. Clinical syndromes. "Heart failure" is a clinical syndrome that is most commonly cause by myocardial dysfunction, or cardiomyopathy. Patients with myocardial dysfunction may be free of any clinical signs and symptoms, in which case they would not have heart failure, but rather, "asymptomatic myocardial dysfunction". However, most of the time, cardiomyopathy leads to characteristic signs and symptoms, and the patient is said to have heart failure.

5. Compensatory Mechanisms for Myocardial Dysfunction

A. Frank-Starling mechanism: Cardiac output and ventricular performance may be maintained within normal limits by an increase in preload. This response occurs very rapidly from beat-to-beat. In severe heart failure, the Frank-Starling curve may be flat at higher diastolic volumes; thus, little augmentation in cardiac output is achieved by increased filling, and marked elevation in end-diastolic pressure may result in pulmonary congestion. B. Neuro-hormonal activation: Reduced cardiac output and elevated filling pressures lead to activation of several neuro-hormonal systems, which results in increased systemic vascular resistance and sodium/water retention. This response occurs very rapidly over minutes to hours. During the initial compensatory phase, these compensatory events help to maintain cardiac output, blood pressure, and vital organ perfusion. In contrast, chronic neuro-hormonal activation is detrimental due in part to the adverse effects of vasoconstriction, volume retention, arrhythmias and adverse myocardial remodeling.

Determinates of Normal Myocardial Function Preload

A. Preload: Preload is the ventricular wall tension (stress) at the end of diastole and it corresponds to the end-diastolic volume (EDV) or end-diastolic pressure (EDP). With normal physiology, the higher the preload the greater the force of ventricular contraction, and the greater the stroke volume. Wall stress is approximated by the Law of Laplace, in which tension chamber pressure chamber radius / chamber wall thickness For the heart, preload (ventricular end diastolic pressure) (ventricular end diastolic radius) / (ventricular wall thickness) An increase in venous return with subsequent increase in left ventricular filling during diastole results in an increase in preload by distention of the ventricle and elevated end diastolic pressure. For clinical purposes, venous return and end diastolic volume are both considered loosely synonymous with the preload.

A. Systolic heart failure, also referred to as "HF with reduced ejection fraction" or HFrEF:

A. Systolic heart failure, also referred to as "HF with reduced ejection fraction" or HFrEF: Systolic heart failure typically arises from a weakened left ventricle with reduced left ventricular ejection fraction so that the ventricle fills to a higher end-diastolic volume and pressure, but due to reduced contractile function ejects a smaller than normal fraction of that blood. Ejection fraction = stroke volume / end-diastolic volume Normal EF = 50-55% Reduced EF < 50% With systolic heart failure, the end systolic pressure volume relationship (ESPVR) is shifted downward (figure). As stroke volume falls the symptoms of decreased cardiac output develop. Elevated end-diastolic pressures is transmitted back to the pulmonary veins and capillaries resulting in transudation of fluid into the pulmonary interstitium resulting in symptoms due to pulmonary congestion e.g., dyspnea). Systolic dysfunction may be caused by loss of myocytes (e.g. myocardial infarction), chronic volume overload, or decreased contractility (e.g. dilated cardiomyopathy). Systolic heart failure is the most common form of heart failure in men, who have a higher incidence of myocardial infarction.

Vasodilating Agents (Direct Acting Hydra, ACE Inhibit Linino, ARB Losarton, NV Isosorb, ANP) ACE

ACE inhibitors Linsinopril (oral) reduces Angiotensin II synthesis arteriolar and venous dilation; reduces aldosterone secretion; increases CO; reduces cardiac remodeling, reduces mortality Use: chronic heart failure; hypertension; diabetic renal disease Bad: hyperkalemia, cough,

Chronic ACS + HF ACE Angiotensin Converting Enzyme (ACE) Inhibitors STEMI (ARB if intolerant)

ACE inhibitors reduce left ventricular dysfunction and dilatation, improve hemodynamics and slow the progression to congestive heart failure during and after myocardial infarction. Clinical trials suggest these benefits are greater among those with anterior infarctions, large infarctions or in patients who have poor left ventricular function or clinical congestive heart failure. Recent studies suggest that the use of ACE inhibitors also reduces the risk of suffering a future MI in patients with known coronary artery disease. ACE inhibitors should be started within the first 24 hours of STEMI to patients with anterior infarction, pulmonary congestion, or LVEF less than 40 %, in the absence of hypotension (systolic blood pressure less than 100 mm Hg). An angiotensin receptor blocker (ARB) should be administered to STEMI patients who are intolerant of ACE inhibitors. Patients should be given sublingual nitroglycerine to take in case they experience chest pain or angina. Often, specific instructions are given to the patient to take 0.4 mg of nitroglycerin sublingually every 5 minutes for up to 3 doses for ongoing chest pain. If the pain does not resolve, the patient should seek emergency care. Finally the patient should be referred to cardiac rehabilitation for graded exercise and education on nutrition and other lifestyle changes including smoking cessation.

6. Treatment of ACS without ST elevation - Beyond the emergency room

ACS without ST elevation is often treated pharmacologically for 48 hours with continued dual antiplatelet therapy (aspirin and thienopyridine), anticoagulation (heparin or LMWH), nitrates and a beta-blocker. Many patients may require PCI but this does not need to be performed emergently as ischemia from a non-occlusive thrombosis can often be treated medically. In moderate-to-high-risk UA/NSTEMI patients, routine early PCI improves survival and prevents MI compared to medical therapy alone. A well- validated tool for deciding whether a UA/NSTEMI patient should undergo PCI is the TIMI risk score. Generally a score 3 or higher identifies a higher risk patient and PCI is recommended within the first 48 hours of hospitalization. In low risk patients, an exercise stress test is useful for further risk stratification. Patients with inducible ischemia despite medical therapy should undergo PCI. Patients who do not have ischemia on stress testing should continue with medical treatment (See next section).

Defining AF

AF is classified by the pattern and duration of the arrhythmia. This scheme reflects in part the initiating mechanism and the degree of adverse electrophysiologic and anatomic remodeling of the atrium that promotes perpetuation of the rhythm. The longer the duration of AF (i.e. long standing persistent AF or permanent AF) the greater the degree of adverse atrial remodeling such that restoring and maintaining sinus rhythm becomes more clinically challenging

Atrial fibrillation (AF)

AF is disorganized supraventricular electrical activity that results in a chaotic and non-uniform contraction of the atria. AF suppresses normal sinus node impulse generation (overdrive suppression). The diagnosis is established by ECG. AF is identified on ECG by two features: 1. Irregular RR intervals and 2. No distinct P waves. The QRS complexes occur at irregular intervals (irregularly, irregular rhythm) and the baseline is course and without discrete P-waves (arrows).

CAT lab Closure of Atrial Septal Defect (ASD) or Patent Foramen Ovale (PFO) -

ASDs and PFOs may be closed percutaneously by deploying an umbrella-like device to seal the defect and avoiding need for thoracotomy and surgical repair. Not all ASD and PFOs require closure and there are certain indications

Smoking Qs ASK ADVISE ASSIST ARRANGE

ASK About Smoking @ Every Encounter A.1. "Do you smoke?" A.2. "How much do you smoke?" B.1. "Are you interested in stopping smoking?" B.2. "What are you reasons for wanting to stop?" C.1. "Have you every tried to stop smoking before?" C.2. "What happened? What got you started again?" D.1. "How soon after waking do you have your 1st cigarette" D.2 "Did you experience withdrawal (restlessness, concentration ...)? A. "I'm concerned about your health and your family's health if you continue to smoke" B. Refer to smoker's personal health concerns, reasons for cessation, smoking history, family history, personal interests or social roles (e.g. parent). Include benefits for smoker. A. Brainstorm strategies for handling major triggers/urges B. Tailor materials to smoker's needs. Provide list of referral C.1. Ready to Quit: Set a quit date, help smoker pick a date w/in next 4 weeks, acknowledge NO time is ideal C.2. Highly Nicotine-dependent smoker: Develop a tapering program, consider nicotine replacement Rx C.3. Smoker Not Willing to Quit: Encourage smoker to consider quitting; Ask about smoking next visit. A.1. Smoker with Quit Date-visit within 1-2 weeks after date Smoker w/o Quit Date-visit w/in 4-6 weeks after initial contact A.2. First f/u visit a) assess smoking status, address problem areas. Develop prevention strategies A.3. Set a 2nd f/u visit in 1-2 months. Set f/u visits as needed

Screening for hyperlipidemia

ATP III (NCE): screen lipid at 20y/o+ every 5 years low risk (shorter if high risk for coronary disease). Fasting lipoprotein protein, total cholesterol, HDL cholesterol, TAG, LDL (calc from lipoproteins). LDLc = TC - HDLc - TAG/5 -CoronaryHD or DM = Goal LDLc treatment via CV 10yr risk Framingham Risk Calc (age, sex, TC, HDL, systolic bp., smoker: -10%, 10-20%, 20+% CV risk in 10yr). Hrisk20: -100 mg/dl LDL,Rx@130 MHrisk1020: -130LDL,Rx@130 Mrisk10: -130LDL,Rx@160 Lrisk: -160LDL,Rx@190

Abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) is a focal dilation (>3 cm) of the abdominal aorta, usually just above the bifurcation of the left and right common iliac arteries. The cause is most commonly due to pathologic remodeling from atherosclerosis, but may be rarely due to connective tissue disorders (Marfan's or Ehlers Danlos syndrome) or vasculitis (Takayasu's or Kawasaki's disease). Major risk factors are smoking, hypertension, male gender, age > 55 years, and genetics (more common in white patients and those with 1st degree relatives). Smoking in particular conveys significant risk. AAAs are most commonly asymptomatic but they may cause abdominal or lower back discomfort. A pulsatile abdominal mass may be found on exam or AAA may be incidentally discovered on radiographic imaging. Screening guidelines conflict, but the 2005 USPSTF recommend that men over the age of 65 years who have ever smoked should be screened for AAA with an abdominal ultrasound. Whereas 2005 AHA guidelines recommend screening men older than 60 years who have a family history of AAA (class I level recommendation) or men between the age of 65 and 75 years who have a history of smoking (class IIa level of recommendation). The natural history of an AAA is to progressively dilate usually at a rate of about 0.5 cm per year. A positive feed forward mechanism promotes progressive dilatation. Wall tension is proportional to its radius (law of Laplace: tension pressure radius/wall thickness); therefore dilatation increase wall stress and further dilatation. AAAs that are greater than 5-6 cm in diameter have a substantial risk of spontaneous rupture. This risk increases exponentially with increasing size. Rupture of the AAA typically is fatal due to abdominal exsanguination but some patients may developed contained ruptures (pseudoaneurysm). Surgical repair is recommended when risk of rupture outweighs the risk of surgery (AAA > 5.5 cm in diameter), when the AAA is a source of atheroemboli, or when it threatens to occlude branch vessels or surrounding structures. Surgery consists of replacement of the dilated section of aorta with a synthetic graft. Perioperative mortality is 3-5% for elective surgery, but goes up tenfold in emergency procedures in patients who presented with a contained ruptures. An alternative to open repair is deployment of a graft via a minimally-invasive percutaneous approach. This endovascular approach decreases perioperative morbidity and mortality but may have a higher rate of delayed complications.

Acute mitral regurgitation

Acute mitral regurgitation usually results from loss of valve integrity due to rupture of chordae, ischemic injury to the papillary muscle, or infective perforation of leaflets. Acute mitral regurgitation exposes a small, non- compliant left atrium to systemic pressures, which are directly transmitted to the pulmonary capillary bed. This acute pressure load results in refractory pulmonary congestion often complicated by lung hemorrhage, and requires urgent surgical intervention. The table below compares and contrasts acute vs. chronic MR.

Acute Pericarditis

Acute pericarditis is a syndrome characterized by acute inflammation of the pericardium. Most cases are idiopathic and probably represent an unidentified viral infection. Infectious etiologies include viral, bacterial, fungal, and rickettsial agents. When a virus is identified, common agents include: Coxsackie B virus, echovirus, adenovirus, Epstein Barr virus, cytomegalovirus, influenza, HIV, or parvovirus B19. Viral infection is confirmed with antibody titers. Bacterial infection is less common but is most commonly seen in conjunction with pneumococcal pneumonia. Other pathogens include Staphylococcus, meningococcus, and Haemophilus influenzae (pediatric patients). Tuberculosis pericarditis is a frequent cause of pericarditis outside the United States or in immunocompromised patients with AIDS. Another common etiology of pericarditis is post myocardial infarction. Pericarditis within the first few days after a myocardial infarction is most often due to localized inflammation over an area of transmural infarction and may be seen in up to 7% of patients. Pericarditis may occur a few weeks after myocardial infarction. This is called Dressler's syndrome and is thought to be autoimmune mediated from anti-myocardial antibodies. Classically, it is associated with fevers, leukocytosis and pleural effusion. A Dressler's like syndrome is observed with post-pericardiotomy syndrome that may occur a few weeks after cardiac surgery, and pericarditis following myocardial contusion form blunt chest trauma. Pericarditis can also be seen in rheumatoid arthritis, systemic lupus erythematosis, or drug-induced lupus (which can be caused by procainamide or hydralazine). Uremic pericarditis can be seen in end stage renal disease and is an indication for urgent dialysis. Neoplastic pericarditis is most often metastatic in origin. Lung cancer accounts for 30%, breast cancer for 25%, hematologic malignancies (leukemia, lymphoma) for 15% and melanoma for 5% of malignancies that cause pericarditis. Finally, external beam radiation therapy for cancer can cause acute pericarditis.

Diagnos ARF Major criteria carditis polyarthritis chorea erythema marginatum subcutaneous nodules Minor criteria fever arthralgias previous ARF rheumatic heart disease positive acute phase reactants (ESR, CRP) prolonged PR interval

Acute rheumatic fever has many varied manifestations and any given patient experiences only some of them. In the absence of pathognomonic signs or laboratory tests, T. Duckett Jones defined a set of criteria which, since modified, are used to substantiate the diagnosis of ARF. A conclusive diagnosis requires laboratory evidence of recent streptococcal infection plus either a) two major criteria, or b) one major and two minor criteria.

INTRODUCTION

Advances in contemporary cardiac care of the patient with myocardial infarction, which include the use of beta adrenergic blocking agents, aspirin, angiotensin converting enzyme inhibitors, thrombolytics and early coronary revascularization, have led to marked improvements in survival. Accordingly, major emphasis is now placed on the reduction of subsequent adverse cardiac events (secondary prevention) as well as the reduction in disability imposed by compromised LV function, post-infarct complications and co-morbidities (rehabilitation). Successful cardiac risk reduction and rehabilitation programs must be comprehensive, innovative, and affordable to meet the needs of a broadening population.Contemporary cardiovascular care entails an increased focus on preventive programs, which incorporate lipid management, smoking cessation, exercise, and weight management. Tailoring exercise prescription, risk factor modification and education to meet the individual needs and goals of each patient is most important, yet is most challenging in the current fast-paced, cost-conscious health care environment.

BPS

Alb: 3.5-5.5 gm/dl Calcium: 9-11 mg/dl CPK: 50-200 u/ml Creat: .7-1.5 mg/dl Na: 135-145 mEq/l Cl: 96-106 K: 3.8-5 HCǑ: 24-28 Glu: 80-120 mg/dl Post: 285-295 mOs Phos: 3-4.5 mg/dl BUN: 10-20 mg/dl Uric Acid: Male 2.5-8 mg/dl; Fem: 1.5-6 mg/dl

Weight Management

All individuals entering a cardiac rehabilitation program should have their height and weight measured. Body mass index and waist circumference ratio should also be calculated. These anthropometric measurements are easily obtained and provide a gauge for determining levels of obesity and distribution of body fat. Evaluation by a nutritionist is essential to the weight management program. Individuals should be assessed for total daily caloric intake, fat and cholesterol intake, and adequate nutrient and fiber content of their diet. Individualized recommendations for dietary modification should be made with consideration of reasonable goals and likelihood of compliance. Spousal or living-partner involvement in nutritional counseling sessions is important to foster compliance, particularly if this person is primarily involved with food shopping and meal preparation. The loss of 1-2 pounds per week is usually recommended through caloric restriction and increased energy expenditure. The exercise program should be designed to promote at least 300 kcals expended per session, aiming for 1,000-2,000 kcal/week. This may be difficult to attain in cardiac patients who may have a low exercise capacity, therefore supplemental exercise sessions may be useful in these patients. The choice of exercise modalities is particularly important for the individual aiming to lose weight. Weight bearing activities provide the greatest caloric expenditure and should be recommended whenever possible after considering any musculoskeletal limitations.

Escape Rhythms

All myocardial cells have some degree of automaticity Nodal cells and myocardial cells that comprise the His-Purkinje system have the greatest degree of automaticity. When bradycardia occurs because of sinus node dysfunction or AV block, subsidiary pacemakers are no longer overdrive suppressed. A subsidiary pacemaker arising from the AV node is called a junctional rhythm and typically manifests as a narrow QRS complex rhythm with superior axis P waves (negative in inferior leads) as the impulse simultaneously travels down the His- Purkinje system to the ventricle and up to the atrium. P-waves may be slightly before or after the QRS. A subsidiary pacemaker arising from one of the fascicles of the left bundle branch is called a fascicular rhythm and typically manifests as a wide QRS complex rhythm with right bundle branch block pattern (rSR') in V1. A pacemaker arising from the ventricle is called a ventricular rhythm and manifests as a very wide QRS complex rhythm. Ventricular escape rhythms are the slowest of the escape rhythms because ventricular myocytes have very little pacemaker current. They are the least stable (i.e. likely to fail and cause asystole) and often require emergent pacemaker. See next page for examples of various rhythms.

7. Chronic therapy following ACS

All patients who have suffered an ACS or MI should be continued on aspirin and Thienopyridine for minimum of one year. All patients should be treated chronic beta blockers and high-intensity statin (see hyperlipidemia lecture). Patients with reduced left ventricular ejection fraction (LVEF <40%) or heart failure symptoms an ACE-I or ARB should be started early in the hospital course and continued chronically.

Primarily III, Amiodarone I,II, IV

Amiodaraone Oral IV blocks INa, IK, ICa channels; nonselective β-blocker; marked prolongation of AP and refractory period; slows conduction velocity; prolongs phase 3 repolarization Use: Used for atrial and ventricular arrhythmiasparticularly in patients with underlying structural heart disease. BAD: thyroid abnormalities, deposits in skin and cornea, pulmonary fibrosis, neuropathy, hepatotoxicity

RCM

Amyloidosis is a group of disorders where insoluble amyloid fibrils are produced and deposited within tissues of various organs resulting in their dysfunction. For example amyloid deposition in the kidneys causes nephrotic syndrome and chronic renal failure, peripheral nerves causes neuropathy, gastrointestinal system causes malabsorption or impaired motility, liver causes hepatomegaly and liver failure, and muscles causes weakness and macroglossia. Amyloid fibrils may also be deposited in the heart resulting in RCM. Late in the course of the disease heart failure and arrhythmias develop. Amyloidosis is most commonly diagnosed with a fat pad biopsy from the abdomen or biopsy of the effected organ. The characteristic pathology finding is amyloid fibrils with apple-green birefringence under polarized light when stained with congo red stain. Amyloid fibrils may be produced through various mechanisms that distinguish the various types of amyloidosis. AL amyloidosis is caused by excess immune-globulin light chain AL fragments that are secreted in conjunction with a hematologic malignancy such as multiple myeloma or Waldenström's macroglobulinemia. Men are more commonly affected the women (3:2) and it usually develops around the sixth decade of life. Cardiac involvement is common ~ 60% of patients. AL amyloidosis can have an aggressive natural history and with the development of heart failure, the median survival is about 4 months. In addition to heart failure, conduction abnormalities (heart block) and arrhythmias (atrial tachycardias and atrial fibrillation) may develop. Cardiac death is due to progressive heart failure or arrhythmias. Urine or serum protein electrophoresis (SPEP) and a blood test for serum free light chains confirm the diagnosis. Treatment focuses on treating the underlying hematologic malignancy with chemotherapy and/or hematopoietic stem cell transplantation. Cardiac injury is not reversible and heart failure symptoms are treated with diuretics. For selected patients, cardiac transplantation in conjunction with stem cell transplantation can be offered for those with significant cardiac involvement. Transthyretin-related (TTR) amyloid is a hereditary form of amyloidosis that is most commonly found in African-Americans who are over 60 years of age. It primarily affects the heart rather than other organ systems. Wild-type transthyretin amyloidosis (ATTR-wt, previously known as senile amyloidosis) is age- related and is characterized by transthyretin deposits in the aorta, heart, brain, pancreas, lung, liver, and kidney. It usually affects men over the age of 70 years. Extensive deposition can lead to significant heart failure; although, the disease course is less aggressive than AL amyloidosis.

2a. Atrial septal defect (ASD)

An ASD results in shunt from the LA into the RA, chronically volume overloading the right heart if the defect is large enough. ASDs are classified by location. Most common are secundum ASDs (defect in septum secundum) a central defect, while primum ASDs are located in the inferior part of the septum (persistence of the ostium primum). A sinus venosus septal defect is located adjacent to the insertion of the vena cava, and may be associated with an anomalous right pulmonary vein that drains to the right side of the heart. If the defect is hemodynamically important, treatment is closure. Most secundum defects can be closed in the cardiac catheterization lab with a trans- catheter device. Primum ASDs and sinus venosus defects require surgical closure when intervention is warranted. Exam findings of ASD include: right-sided murmurs (systolic ejection murmur at ULSB (pulmonary valve region) from increased flow across the pulmonic valve (relative pulmonary stenosis, diastolic rumble at lower sternal border from increased flow across the tricuspid valve) fixed splitting of S2 (the shunt corrects for the asymmetries in preload created by respiration that usually cause inspiratory splitting of S2). If RVH is present, there may be a parasternal heave. Note that 20% of the population has patent foramen ovale. These are different from ASDs in that they are persistence of a normal fetal structure, generally result in very little left to right shunting, do not create right ventricular volume overload or Eisenmenger's syndrome. However, PFOs can still present a risk for embolic stroke, since DVTs can shunt right-to-left through the PFO and embolize to the brain. PFOs are generally not repaired.

4. Treatment of Acute Coronary Syndrome - Analgesia/Sedation

Analgesia/Sedation - Patients with the severe pain of acute MI are often in a hyperadrenergic state. Catecholamine surges cause an increase in heart rate, blood pressure and myocardial contractility, which are all major determinants of myocardial oxygen demand. Morphine sulfate, which blocks CNS sympathetic efferent activity remains the standard drug for relieving pain and anxiety from acute ischemia. Small intravenous doses are administered every 5-10 minutes while the level of discomfort, heart rate, blood pressure and respiration rate are monitored. Care must be taken, as morphine can cause hypotension, respiratory depression and vomiting.

Angiotensin Receptor Blockers (ARBs) vasodilation

Angiotensin Receptor Blockers (ARBs) Losarton blocks AT1 receptors arteriolar and venous dilation; reduces aldosterone secretion; increases CO; reduces cardiac remodeling, reduces mortality Use: chronic heart failure; hypertension; diabetic renal disease but for pt not tolerant to ACE-I Bad: hyperkalemia, teratogen

Renin-Angiotensin System Drugs

Angiotensin converting enzyme ACE Inhibitors: Lisinopril Angiotensin II receptor blockers ARB: Losartan

PHARMACOLOGY OF ANTITHROMBOTIC AGENTS I & II

Antiplatelet Agents COX inhibitors Aspirin ADP receptor antagonists Clopidogrel Glycoprotein IIB/IIIa inhibitors Abciximab Anticoagulants Factor IXa and/or Xa inhibitors Heparin Enoxaparin Fondaparinux Vitamin K antagonist Warfarin Direct Xa inhibitor Rivaroxaban Direct Thrombin Inhibitor Dabigatran Fibrinolytic Agents Plasminogen activators Alteplase (r-tPA)

Antithromobotic Drugs:

Antiplatelet Agents (3) COX Inhibitor: Aspirin ADP receptor antagonist: Clopidogrel Glycoprotein IIB/IIIa inhibitors: Abciximab Anticoagulants (4) Factor IXa/Xa inhibitors: Heparin, Enoxaparin, Fondaparinux Vitamin K antagonist: Warfarin Direct Xa inhibit: Rivaroxaban Direct Thrombin Inhibitor: Dabigatran Fibrinolytic agent (1) Plasminogen activators: Alteplase (r-tPA)

Aortic dissection

Aortic dissection is a tear in the intima of the aorta into the medial layer of the vessel wall. This separation forms a false lumen that may propagate distally as the flow of blood causes further shearing. Risk factors for dissection include chronic hypertension, advanced age, smoking, cocaine use, bicuspid aortic valve, collagen vascular disorders (Marfan's or Ehlers- Danlos syndrome), and aortitis. Chest x-ray is insensitive but classically shows a widened mediastinum. Diagnosis is usually made by contrast CT of the thorax showing the false lumen and dissection flap (white arrow). Transesophageal echocardiogram and MRI can also be used to diagnose aortic dissection. Aortic dissection is classified as Stanford type A (involving the ascending aorta) and Stanford type B (involving the descending aorta) dissections. (See Figure 15.3 on page 344 of the Lilly text). The prognosis and treatment is quite different for the two types. Type A dissection carries a high mortality and emergent surgical repair is required. Uncomplicated type B dissections involving the descending aorta distal to the left subclavian artery are managed medically by controlling rate-pressure product with beta-blockers and controlling blood pressure with nitroprusside, ACE-inhibitors and calcium channel blockers. Pain is treated with narcotics. Type B dissection is potentially life threatening but the risk of surgery outweighs the benefits unless there is compromised blood flow to vital organs or limbs. Complicated type B dissection involves branch vessels of the descending aorta (i.e. mesenteric arteries, renal arteries, vertebral arteries etc.) causing ischemia to vital organs and emergent surgical repair is necessary. Patients classically present with severe, tearing chest pain that radiates to the back. Other associated signs and symptoms are specific to the location of the dissection. If the dissection occludes the left subclavian artery there may be asymmetric upper extremity blood pressures or radial pulses. If it blocks a carotid artery the patient may present with stroke-like symptoms. If the dissection extends to the aortic root, cardiac tamponade may be present or if it involves the aortic valve, acute aortic insufficiency and heart failure may be present. Extension of the dissection to a coronary artery may cause acute myocardial infarction. Mesenteric ischemia or renal failure may be present if there is a compromised of blood to the gut or kidneys. Acute management includes stabilization of hemodynamics and obtaining necessary imaging for definitive diagnosis and characterization of the extent of the dissection. The type of dissection will direct surgical versus medical management as outlined above. Chronic management of aortic dissections involves regular surveillance with MRI or CT angiography for stability.

Aortic Regurg Hemodynamics

Aortic regurgitation In aortic regurgitation, the valve is incompetent and there is leaking of blood during diastole. The hemodynamic tracing shows continuous rise in LV diastolic filling pressure (black arrow) and a gradual decline in aortic diastolic pressure (gray arrow).

Aortic Regurgitation.

As with mitral regurgitation, the time course of developing aortic regurgitation dramatically influences the natural history of the disease. Acute severe aortic regurgitation complicates dissection of the ascending aorta, connective tissue disease involving the ascending aorta, and infective endocarditis. Florid acute regurgitation overwhelms the non-compliant LV during diastole preventing adequate emptying of the left atrium, raising left atrial pressure, and sometimes causing premature closure of the mitral valve. Although vasodilator and inotropic therapy may prove helpful in stabilizing these patients acutely, the ultimate therapy is surgical. Chronic aortic regurgitation occurs with polyvalvar rheumatic disease, congenitally abnormal valves, and many rare conditions that cause dilatation of the aortic root with stretching of the aortic annulus and secondary loss of effective coaptation of the valve leaflets. The resulting pathophysiology is mild to moderate chronic LV volume overload, which causes LV dilatation, secondary hypertrophy and peripheral vasodilation. Physical examination discloses a bounding pulse, wide pulse pressure, hyperkinetic LV apex, and a blowing diastolic murmur at the base of the heart, which may be quite subtle, requiring careful auscultation with the patient sitting forward at end expiration. The ECG shows generous voltage, and the chest film and echo both confirm left ventricular volume loading with dilatation. Quantitation of severity of regurgitation remains difficult and inexact. The timing of surgical intervention in aortic regurgitation involves striking a delicate balance between 1) exposing someone who will tolerate his or her lesion well for years to the risk of aortic valve replacement, and 2) delaying operation so long that irreparable LV dysfunction occurs due to chronic volume loading. Serial echocardiograms are useful in following asymptomatic patients with chronic regurgitant lesions, and the demonstration of progressive LV enlargement with an end systolic dimension over 55 mm probably constitutes an indication for surgical intervention. The symptomatic patient with aortic regurgitation as the cause of symptoms should be surgically corrected.

Pressure-volume loops

As you may remember from physics, work is the integral of pressure over volume. The pressure and volume inside a piston can be plotted over its cycle of compression and expansion, and the area inside that loop is equal to the work performed by the system. We can plot LV pressure versus LV volume to determine the work it performs for a single cardiac cycle (see figure).

Confirming MI Cardiac Serum enzyme - AST

Aspartate transaminase (AST) is a serum aminotransferase enzyme, which was utilized in the diagnosis of MI for many years, but has now fallen out of favor because of lack of tissue specificity and its time course of elevation is intermediate between CK and troponin, thus offering little advantage.

4. Treatment of Acute Coronary Syndrome - Aspiring

Aspirin - All suspected ACS patients get high-dose aspirin. The goal of aspirin therapy is to rapidly block formation of Thromboxane Á in platelets by cyclooxygenase inhibition, and thereby inhibit platelet aggregation. Accordingly, aspirin should be given within the first hour to all patients with suspected MI at a dose of 160 to 325mg. Aspirin reduces mortality from MI by 25% and, in unstable angina patients, it reduces incidence of MI by 70%. Aspirin therapy should be continued indefinitely as the use of aspirin in MI patients has been shown to significantly reduce future risk of reinfarction, non-fatal stroke, and vascular death. Aspirin is typically chewed and held under the tongue for rapid absorption.

Psychosocial

Assessment of psychosocial issues after myocardial infarction is necessary to achieve successful rehabilitation of the cardiac patient. Evaluation of emotional status should raise the following questions: Is there evidence of post-traumatic-stress-disorder? What is the patient's perception of their health status and family attitudes toward their illness? Is the patient mourning the loss of a previous, albeit perceived healthy heart or is the patient clinically depressed? Of note, moderate to severe depression occurs in 10-20% of post MI patients and anxiety disorders are manifest in 5-10% of patients. A decrease or cessation of sexual activity occurs in approximately 1/4-1/2 of patients. Work-related concerns including those of the patient, family and employer as well as issues regarding disability should be addressed. Many of these issues can be managed by designated and experienced program staff, however complex and/or unresolved issues should be referred for more thorough therapy or counseling as needed. Stress management and quality of life should be addressed during the outpatient cardiac rehabilitation program as well.

Atheroembolism - "blue toe syndrome"

Atheroembolism occurs when small fragments of atherosclerotic plaque break off and embolize to small distal microvessels, where they cause a local inflammatory reaction leading to occlusion of the vessel. This may happen spontaneously or as a complication of endovascular procedures (i.e. cardiac catheterization). Classically the atheroemboli deposit in the toes, causing a gray-blue discoloration and livedo reticularis but emboli may occur throughout the vascular system causing small infarctions in the brain, retina (Hollenhorst plaque), kidneys, or digestive organs. Treatment is primarily with antiplatelet agents.

1. Statins (oral) Atorvatatin Drugs for Hyperlipidemias

Atorvatatin MOA: Inhibit HMG Co-A Reductace, Reduce hepatic cholesterol synthesis, lower LDL/TAG, raises HDL Rx: ASCVD, 1* 2* prevention, coronary syndomes CP: myopathy, hepatic dysfx, teratogen

Determining Needs Afterload

B. Afterload: Afterload is the ventricular wall stress during systole and is the force that must be overcome for the ventricle to eject blood. afterload (LV systolic pressure) (LV systolic radius) / (LV wall thickness) Afterload determines the extent of fiber shortening and therefore the end-systolic volume. An increase in afterload reduces fiber shortening and increases end- systolic volume. Because LV systolic pressure is almost the same as the systemic blood pressure, for clinical purposes mean arterial pressure is considered loosely synonymous with the afterload.

B. Precipitating Factors for Clinical Heart Failure.

B. Precipitating Factors for Clinical Heart Failure. Patients with myocardial dysfunction may be asymptomatic or mildly symptomatic either because the cardiac impairment is mild or because compensatory mechanisms help to normalize cardiac function. However, symptoms of heart failure may develop or worsen when precipitating factors increase cardiac workload and disrupt the balance in favor of decompensation. Specific factors may be identified in the majority of hospital admissions and include: 1. Increased metabolic demand: fever, infection, anemia, tachycardia, pregnancy, hyperthyroidism, prolonged exertion, emotional stress 2. Increased preload: excess sodium or fluid intake (dietary indiscretion); excess fluid administration (iatrogenic) or retention (renal failure, NSAIDs); inadequate diuretic regimen or compliance 3. Increased afterload: uncontrolled hypertension, pulmonary embolism 4. Impaired contractility: myocardial ischemia or infarction, negative inotropic agents (e.g., calcium blockers), alcohol 5. Non-compliance: failure to take prescribed heart failure drugs and/or adhere to dietary restrictions 6. Other: atrial or ventricular arrhythmias, bradycardia, under-treatment by physician

Revascularization of CAD After a diagnostic cardiac catheterization is performed, the physician determines whether revascularization is indicated and if so, what is the best means for revascularization (percutaneous intervention or coronary artery bypass graft surgery). In general a coronary stenosis of greater than 70-75% is considered significant.

Balloon angioplasty In balloon angioplasty, a high-grade stenosis of a coronary artery is crossed with a thin wire. A deflated-balloon is advanced over this wire and positioned in the region of the stenosis. The balloon is inflated and compresses the plaque against the arterial wall and stretches the underlying media. The limitation of balloon angioplasty is that there is a high rate of restenosis. For this reason, it is most commonly performed in conjunction with coronary stent placement.

STEMI Treatment Percutaneous Coronary Intervention (PCI)

Because of several limitations of thrombolytic therapy, including failure to reperfuse (i.e. failure to dissolve clot), reocclusion and risk of serious bleeding, urgent coronary angiography followed by early PCI of the occluded artery (called "primary" PCI) has a number of theoretical advantages. It offers the opportunity to confirm the diagnosis and achieve reperfusion without the bleeding risk of thrombolysis. Several trials have shown that primary PCI can be performed with high coronary perfusion rates and low rates of stroke, reinfarction and mortality, provided it is performed in a timely fashion by experienced personnel. Primary PCI can also be used as an alternative reperfusion strategy in patients who are at high risk of bleeding with thrombolytic agents. With PCI, tubes are inserted into the coronary artery. The clot may be aspirated from the coronary vessel and the plaque lesion opened with ballooning. A metal or polymer coated stent is deployed in the vessel at the site of occlusion to buttress open the vessel and prevent re-occlusion. In most regions of the country, PCI is standard of care for reperfusion therapy in patients with STEMI rather than thrombolytic therapy. Most hospital have staff and physicians "in-house" or immediately "on-call" allowing for emergent PCI and restoration of coronary perfusion within 90 minutes of the patient presenting to the emergency room. If a 90-minute, "door-to balloon" time is unachievable, thrombolysis therapy is recommended. Following PCI, patients with STEMI are monitored in the cardiac care unit (CCU) for possible complications. (See complication section). Chronic medical therapy is begun (See chronic therapy following ACS).

4. Treatment of Acute Coronary Syndrome - Beta Blockers

Beta Blockers - All hemodynamically stable ACS patients should also be given a beta blocker. By reducing heart rate, blood pressure, and myocardial contractility beta blocking agents reduce myocardial oxygen demand and thus have the potential of preserving injured but not irreversibly damaged myocardial cells. Therefore, patients most suited for early treatment with beta blockers are those who have sinus tachycardia and hypertension. Several clinical trials have demonstrated that beta blocker therapy in acute MI limits infarct size and reduces the risk of death from recurrent ischemia and sudden death. Furthermore, the long-term use of beta blockers has been shown to be effective in reducing future reinfarction and cardiac death. All patients with acute MI without a clear cut contraindication to beta blockers (e.g. bradycardia, hypotension, pulmonary congestion, significant bronchospastic disease) should be treated with these agents within the first few days and have them continued indefinitely. A history of asthma is NOT a contraindication to giving a beta-blocker in a patient with ACS.

Myocardial Ischemia Drugs

Beta blocker - metoprolol Nitrovasodilators: Isosorbide dinitrate, nitroglycerin Cá+ channel blockers: verapamil, diltiazem, amlodipine

C. Combined Systolic and Diastolic heart failure

C. Combined Systolic and Diastolic heart failure: Often heart failure will be caused by a combination of systolic and diastolic dysfunction. For example, with due coronary artery disease, there may be systolic dysfunction due to chronic loss of myocardium by infarction and 2) diastolic dysfunction due to chronic replacement fibrosis (increased stiffness) and/or ischemia (active process). While it is common to have both systolic and diastolic dysfunction, clinically patients are characterized by the ejection fraction (<45% = HFrEF; >55% = HFpEF

Determine Needs Contraction

C. Contractility: Contractility (or inotropic state) is a fundamental property of cardiac tissue that determines the strength of contraction. It reflects the level of activation, resulting in formation and cycling of actin and myosin cross-bridges independent of preload and afterload. Increased contractility results in increased extent and velocity of shortening. Factors that enhance contractility include catecholamines (circulating or from nerve terminals in heart), inotropic agents (e.g., digoxin, beta-adrenergic agonists). Factors that reduce contractility include loss of myocytes (e.g., an infarction), drugs (e.g., Cá+ channel blockers, beta- adrenergic antagonists, and acidosis. Frank-Starling law of the heart: Starling's law states that LV stroke volume increases proportionate to increased preload. This is roughly analogous to the first law of thermodynamics for cardiology, since it ensures that the amount of blood that enters the heart will roughly equal the amount of blood ejected out of the heart. The Frank-Starling mechanism describes the properties of actin and myosin in cardiomyocytes. When tension is low, actin and myosin do not overlap optimally and therefore have a limited mechanical advantage for contraction. As wall tension (preload) increases, actin and myosin are pulled into a more favorable orientation increasing their mechanical advantage for contraction. Wall tension also makes actin and myosin more calcium-sensitive which further increases force generation. During normal physiologic conditions there is a roughly linear increase in contractility (and stroke volume) with preload.

C. Vasoconstriction: in Cardiac Dysfx.

C. Vasoconstriction: Constriction of arteries and veins occurs rapidly, over minutes to hours, and is driven primarily by neuro-hormonal systems (above) and by reduced intrinsic vasodilator function due to decreased endothelial function. Both systemic and pulmonary vasoconstriction occur in heart failure and are part of a compensatory response to reduced cardiac function that attempts to redistribute regional blood flow to the most vital areas (e.g., brain, heart, kidneys). In addition to shunting blood away from the skin, gut and kidneys, systemic vasoconstriction increases LV afterload and may further depress systolic function. Increased pulmonary vascular tone contributes to right-sided heart failure and reduced exercise tolerance. Increased production of endothelin, a potent vasoconstrictor peptide with growth promoting effects, contributes to pulmonary hypertension and myocardial remodeling.

Antithrombotics Study Guide Table Antiplatelet Drugs: COX Inhibitor, GP IIb/IIIaR Inhibitor, ADP Receptor Antagonists

COX Inhibitor: Aspirin Oral nonselective, irreversible COX inhibitor; reduces platelet TXÁ, a potent platelet aggregator Use: low dose aspirin is used for prevention and treatment of arterial thrombosis Adverse Effects: GI, bleed, hypersensitivity Glycoprotein IIb/IIIa Receptor Inhibitors: Abciximab Parenteral inhibits platelet aggregation by interfering with GPIIb/IIIa binding to fibrinogen and ligands Use: used during percutaneous coronary intervention to prevent restenosis; acute coronary syndrome Bad: Bleeding, thrombocytopenia with long use ADP Receptor Antagonists: Clopidogrel Oral prodrug; converted to active metabolite that irreversibly inhibits platelet ADP receptor Use: acute coronary syndrome (unstable angina, acute myocardial infarction), prevention of percutaneous coronary intervention, prevention and treatment of aterial thrombosis.

CRFs are pathogenetically interrelated, frequently cluster in individuals and behave synergistically. Pre-contemplation Contemplation Ready for action Action Maintenance

CRF treated by diet, exercise, no smoking, or drugs. CRF that work = increase aggressiveness. Of 73% smokers seeing Dr in MASS; only 46% told to quit (ask, plan, re-assess)

Assessment of cardiac function from pressure measurements

Cardiac output The cardiac output (CO) is the volume of blood in liters ejected from the left ventricle per minute. It is used as a measure of left ventricular function. CO is decreased when the left ventricle is compromised from underlying cardiomyopathy or myocardial infarction. There are two methods for calculating CO:

Changes on Electrocardiogram for Acute MI

Changes on Electrocardiogram - As soon as the patient arrives in the ER, electrocardiographic monitoring should be initiated in order to detect any arrhythmias. The initial 12 lead ECG is very important for helping establish the diagnosis of acute MI and for determining the initial course of action. Three pathophysiologic events occur in acute MI: ischemia, injury and infarction. These three events may occur in sequence or simultaneously. The ECG manifestations of these events include: inversion or depression of the T-waves or ST segments (ischemia), ST segment elevation (injury), and development of Q wave (infarction). The terminology describing the ECG pattern of an acute MI is somewhat confusing. All three ECG patterns may be observed with an acute MI even though a Q wave on ECG is referred to "infarction" pattern.

5. Bile-Acid Binding Resin Cholestyramine Drugs for Hyperlipidemias

Cholestyramine Prevent bile acid reabsorption from GI Rx: high LDLc, pruritis CP: constiptation/bloating

NYHA Angina Classification

Class I: Mark exertion Class II: Mod exertion Class III: Mild exertion Class IV: Rest 1+ RF of CAD has CAD until ruled out. Premeno with no CorRF with non-anginas or atypical not CAD -CAD Physical exam: not much info: hypertension, xanthoma, xanthelasma, corneal Marcus, obesity, vascular bruit, reduced peripheral pulse. -CAD ECG; Resting is normal. ST segment depression/elevation in episode. Sign. Q ways = prior MI = CAD ++.

Diagnostic Workup for PAD

Common exam findings in PAD are diminished peripheral pulses (especially dorsalis pedis and posterior tibial pulses), bruits on auscultation of the femoral artery or other vessels, and shiny, atrophic, hairless skin in distal extremities. Late findings include foot ulceration or dry gangrene. The diagnosis of PAD is confirmed by calculating the ankle brachial index (ABI), which is the ratio of ankle blood pressure to brachial (arm) blood pressure. PAD is defined as ABI <0.9 and ABI <0.4 indicates severe disease. A negative resting ABP does not rule out PAD. If ABI is normal but the clinical suspicion remains high, exercise ABI should be performed. The patient exercises until claudication occurs, then ankle pressure is measured. A decrease in ABI of 15%-20% is diagnostic of PAD. In patients with severe PAD and those who are being considered for revascularization, Doppler ultrasound, magnetic resonance angiography (MRA) or computed tomography angiography (CTA) may be used to localize the site of stenosis, extent of disease, and feasibility of revascularization with surgical bypass or percutaneous stenting.

1. Fetal heart formation

Congenital cardiac malformations are the most common type of birth defect (affecting just under 1 in 100 babies born). An understanding of the geometry of how the fetal heart is formed is essential to understand why certain congenital defects arise. (The University of New South Wales has a great tutorial: tinyurl.com/pnop9hn) a. Heart tube forms During gastrulation when a trilaminar embryo has just formed, the mesoderm gives rise to left and right endocardial tubes (day 18). As the trilaminar embryo undergoes folding, the tubes are pushed together at the cranial/ventral aspect of the embryo. The tubes merge to form the heart tube, a primitive single-chamber heart. The future ventricles will be derived from the point where the tubes came together. The caudal inflow end of the tubes will form the future atria while the cranial outflow end will form the future aorta and pulmonary artery. The primordial ventricle thickens and organized contractions begin (day 22). b. Heart tube undergoes looping Next, the single chamber heart loops itself into a convoluted sigmoid shape (around day 28) that mimics the spatial orientation of chambers in the adult heart. First it kinks in half so that the primitive ventricle protrudes ventrally, then it twists so that the inflow and outflow vessels all emerge from the cranial end and the ventricles are caudal (just like in an adult). At this stage the heart is still just one long tube without septation, even though everything is positioned correctly now. Session 33 Congenital Heart Disease 2 c. Septation of chambers and division of outflow tract Next, the heart forms septations to separate the four chambers from one another (4-5 weeks). First the common atrio-ventricular canal is divided into a left and right canal (future mitral and tricuspid valve areas) by formation of two endocardial cushions that grow and fuse. Next, the atria are divided as first the septum primum forms and later the septum secundum develops. A hole called the foramen ovale remains in the septum secundum allowing shunting of blood from the right atrium to left atrium to occur during embryonic development. The septum primum acts as a one-way valve that can flap closed over the foramen ovale, so that blood will be able to shunt right-to-left but not vice versa. Abnormalities in this process result in an ASD (atrial septal defect). Finally, the interventricular septum forms. As both sides of the primordial ventricle grow and dilate, their medial walls fuse, forming the interventricular septum. A foramen is left between the cranial portion of the new interventricular septum and the endocardial cushions. This foramen normally closes by the end of the seventh week with formation of a membranous septum. Abnormalities in this process result in a VSD (ventricular septal defect). At this point, the left and right sides still pump into a common outflow tract (truncus arteriosus), which normally will septate into the aorta and pulmonary arteries. In the bulbus cordis, a population of neural crest cells thickens into two opposing ridges called the bulbar ridges. Similar ridges are present in the truncus Session 33 Congenital Heart Disease 3 arteriosus. The bulbar ridges will fuse in a spiral fashion with the ridges in the truncus arteriosus (6 weeks). As a result of this spiral orientation the aorta and pulmonary artery twist around each other. If bulbar ridges do not form the baby will have persistent truncus arteriosus, and if the geometry of the twist is wrong, transposition of the great vessels may result.

Acute MI Continue ECG

Continuous ECG monitor - All patients with a suspected myocardial infarction should be placed on a continuous electrocardiographic monitor system that is near a defibrillator device. Since the development of the Coronary Care Unit in the 1960s, there has been a 50% decrease in the mortality rate associated with acute MI. Much of this decrease is secondary to rapid arrhythmia detection and treatment. An intravenous line should be immediately established for access and rapid administration of cardiac medications. Chest x-ray should be obtained to assess for pulmonary congestion and to rule out non-cardiac etiologies of chest pain (e.g. rib fractures, pleuritis, aortic dissection, pneumonia). Blood laboratories - Routine screening blood work is obtained to detect evidence of myocardial necrosis (cardiac enzymes), infection, anemia, electrolyte imbalance or renal insufficiency. If the patient appears short of breath, arterial blood gas should be obtained to determine level of hypoxemia. Frequently the initial lab screening in a patient presenting with MI will only non-specific signs of inflammation, such as a mildly elevated WBC. Blood laboratories require some time for analysis and reporting; therefore, the immediate diagnosis in the emergency room is primarily based on ECG, history and physical exam.

3. Cyanotic cardiac defects

Cyanotic lesions (truncus arteriosis, transposition of the great vessels, tricuspid atresia, tetralogy of Fallot, total anomalous pulmonary venous return) are not covered in the lecture or on the exam, but we will cover them here because they are tested on Step 1.

D. Inflammation and oxidative stress:

D. Inflammation and oxidative stress: Circulating levels of pro- inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1beta are elevated in heart failure. In addition, myocardial production and activity of TNF-alpha are increased in ischemic and dilated cardiomyopathy. Cytokines, acting in part through the increased production of nitric oxide, may attenuate myocardial beta-adrenergic responsiveness and depress contractility. Cytokines may also directly stimulate ventricular hypertrophy and adverse myocardial modeling. Anti- cytokine therapy is currently undergoing clinical investigation. Reactive oxygen species are also toxic to the myocardium. While increased oxidative stress has been documented in heart failure, the role of antioxidant therapy is unknown.

Complications of Cardiac Catheterization - less likely to occur in experienced centers with experienced operators

Death Myocardialinfarction Injurytocoronaryartery Strokeairembolismordisruptionofplaqueinaorticarch Perforation Coronaryarterydissection Anaphylaxistointravenouscontrastagent Acuterenalfailureduetonephrotoxiccontractagents Vascularcomplication:ischemiclimb,pseudoaneurysm,AVfistula, bleed requiring transfusion, hematoma

Constrictive pericarditis

Dense fibrous scarring of the pericardium causes it to constrict around the heart and physically impede cardiac filling. The most common worldwide etiology is tuberculosis but in the United States may be due to effects of radiation therapy, infection, or after cardiac surgery. As in tamponade the diastolic pressures of the right and left ventricle are equal. Right and left heart filling pressures become markedly elevated and in mid diastole the maximum filling volume is reached (impaired filling). Cardiac output is reduced because of low end-diastolic filling volume. Clinically, patients with mild to moderate constrictive pericarditis present with symptoms of right-sided heart failure with leg edema, abdominal bloating, and pain from hepatic congestion. Those with severe constriction may have left heart failure with pulmonary congestion, orthopnea, and fatigue. Physical exam will show signs of right heart failure and possibly left heart failure. The jugular veins are distended and do not collapse with inspiration (Kussmaul's sign). With inspiration a negative intra-thoracic pressure increases venous return, but with constriction the right atrium and right ventricle are unable to accommodate the increased venous return and the jugular veins do not empty. With auscultation, a pericardial knock may be heard. This sound is due to the rapid deceleration of blood entering a volume-constricted left ventricle, as the elastic limit of the pericardium is reached. Imaging with chest x-ray, computerized tomography or magnetic resonance imaging may show a thickened, calcified pericardium. Treatment It is important to distinguish constrictive pericarditis from a restrictive cardiomyopathy (like cardiac amyloid). Once constrictive pericarditis is confirmed, treatment involves use of diuretics for control of symptoms, and if medical therapy is unsuccessful, surgical removal of the pericardium.

4. Rx of ACS Calcium Channel Blockers NO for MI

Despite the fact that CCBs also effectively reduce heart rate and blood pressure and increase myocardial blood flow by dilating coronary arteries, clinical trials have been unable to show a clear benefit in the treatment of MI.

DiagnosisTamponade

Diagnosis The physical exam is characterized by: 1) elevated jugular venous pressure, 2) hypotension with reflex tachycardia and 3) pulsus paradoxus, which is an exaggerated inspiratory fall in systolic blood pressure (> 10 mmHg). Under normal physiologic conditions, inspiration increases venous return to the right ventricle (vacuum effect of inspiration). With tamponade, the heart is constricted by the large effusion and a less compliant pericardium such that during filling the right ventricle is only able to expand into space that would otherwise be occupied by the left ventricle (i.e. ventricular interdependence) resulting in reduced left ventricular filling during diastole and reduced systolic blood pressure. Echocardiogram will show a pericardial effusion as well as collapse of the right atrium and right ventricle in diastole. If the diagnosis is uncertain and the patient is fairly stable, invasive hemodynamic monitoring (right and left heart catheterization) may be performed to confirm diagnosis. The signature finding is equalization of diastolic filling pressures of the right and left ventricle.

Ddx Acute MI

Differential Diagnosis - As with any patient, consideration should be given to other diagnoses, which can also cause these presenting symptoms and signs. Unstable angina- Myocardial ischemia may not be severe enough to cause myocardial damage, but may still cause many of the above symptoms and warrant hospitalization. Unstable angina is differentiated from NSTEMI by the cardiac enzymes. Pericarditis, pleuritis - Pain is usually localized and described as sharp and intensifies with deep inspiration or with positional changes. A rub is frequently heard. Aortic dissection- Pain is often described as sharp pain in the mid- chest radiating to the back. Clues to this diagnosis are diminished pulse in one or more extremities, a widened mediastinum on chest x- ray and lack of ECG changes. Aortic dissection of the ascending aorta is treated emergently with surgery. Pain can mimic an MI. Costchondritis /musculoskeletal pain - Usually reproducible with palpation Gastrointestinal causes - Cholecystitis, hiatal hernia, esophageal reflux, peptic ulcer disease can all cause chest pain. Often the quality of the pain will indicate a gastrointestinal etiology. Anxiety can sometimes cause a sensation of fullness in the chest. Pulmonary embolus - Causes shortness of breath, hypoxemia, and chest pain (usually pleuritic) and can mimic MI.

B. Dilated cardiomyopathy (DCM)

Dilated cardiomyopathy is characterized by a weakening of the systolic contraction of myocytes in association with dilation of the ventricles. Impaired contraction results in a low ejection fraction and high end-systolic volume. Initially, cardiac output is maintained through progressive dilatation in order to preserve stroke volume. Signs and symptoms of DCM The diagnosis of DCM is made by careful history, physical examination, and non- invasive testing. Clinical symptoms reflect a combination of inadequate forward perfusion and excessive congestion of pulmonary and systemic venous circulations. The insidious onset of left ventricular failure due to elevated left ventricular end- diastolic pressure may be manifested by dyspnea on exertion, cough, and ultimately pulmonary edema (congestive features). Other symptoms reflect inadequate cardiac output (poor perfusion), such as easy fatigability and somnolence. Some patients with DCM may present with an arrhythmia (i.e. ventricular fibrillation arrest) or thromboembolism and their myopathy is only discovered during work-up of their presenting symptom. The findings on physical examination that suggest ventricular dilation include a diffuse apical impulse that is displaced far to the left. On auscultation, mitral or tricuspid regurgitation murmurs may be present as ventricular dilatation distorts the valve annulus leading to poor leaflet coaptation and valve incompetency. Signs of heart failure may also be present. These include a third heart sound (S3), elevated jugular venous pressure, pulmonary rales or effusions, and peripheral edema.

Vasodilating Agents (Direct Acting Hydra, ACE Inhibit Linino, ARB Losarton, NV Isosorb, ANP)

Direct Acting Agents Hydralazine (oral) releases NO from endothelial cells; decreases release of intracellular Ca; opening of K+ channels arteriolar dilator; reduces BP and afterload & increases CO; reduces mortality when used with isosorbide dinitrate Use: chronic HF in African Americans; used alone/with Isosorbide dinitrate bad: tachycardia, headache

Heart Failure Drugs

Diuretics (3): Thiazides: Hydrochlorothiazide Lopp diuretic: Furosemide Potassium-sparing: Spironolactone Inotropic Gents (3): Glycosides: Digoxin Beta-agrenergic agonists: Dobutamine Phosphodiesterase inhibitors: Milrinone Vasodilating Agents (5): Direct-acting agents: Hydralazine ACE inhibitors: Lisinopril ARBs: Losartan Nitrovasodilators: Isosorbide dinitrate Natriuretic peptides: Nesiritide Inhibit Cardiac Remodeling (3): Beta-blockers: Metoprolol ACE inhibitors: Lisinopril Mineralocoricoid antagonists: Spironolactone

Class III: K+ Channel

Dofetilide Oral selective block of IK channels; prolongs AP and QT interval USE: Used for atrial arrhythmias (treatment and prophylxis) Bad: torsades de pointes

E. Adverse remodeling: Left ventricular hypertrophy and adverse remodeling

E. Adverse remodeling: Left ventricular hypertrophy and adverse remodeling occur slowly, over weeks to months. Increased ventricular wall stress due to LV dilation or increased afterload stimulates the development of myocardial hypertrophy. The resulting increase in wall thickness helps to normalize wall stress and thereby helps to maintain ventricular contractility. Cellular events include increases in mitochondrial and myofibrillar mass, myocyte hypertrophy, and interstitial collagen content. When the primary stimulus is LV chamber dilation due to chronic volume overload (e.g., mitral regurgitation), increased diastolic wall stress leads to replication of sarcomeres in series. The radius of the ventricle enlarges in proportion to a mild increase in wall thickness ("eccentric" hypertrophy). By contrast, chronic pressure overload (e.g., due to hypertension or aortic stenosis) results in new synthesis of sarcomeres in parallel, and a moderate to severe increase in wall thickness ("concentric" hypertrophy). Unfortunately, hypertrophy of either type is associated with the reappearance of fetal gene expression leading to decreases and unfavorable changes in contractile proteins. If additional chamber dilation occurs or if the increase in wall thickness is insufficient, systolic and diastolic wall stresses remain abnormally elevated. The tension causes myocyte apoptosis and impaired calcium handling that leads to further chamber dilation and hemodynamic failure. Angiotensin and catecholamines play an important role in this pathological remodeling by activation of matrix metalloproteinases that degrade interstitial collagen and by inducing myocyte apoptosis.

Rx for Acute Heart Failure in Hospitals

E. Pharmacologic treatment of acute heart failure in the hospital Patients are admitted to the hospital for the treatment of heart failure for a variety of reasons. Most commonly they are admitted because symptoms are severe, a situation referred to as 'decompensation', and outpatient therapy has not been effective or would not be safe or practical. A common way to think about treatment of acute decompensated heart failure is that you are taking a patient who is "cold and wet" (poorly perfused and edematous) and making them "warm and dry" (well perfused and euvolemic). After accomplishing this goal during an inpatient admission, the patient is discharged on a set of medications that will prevent them from decompensating again.

3. Evaluation of Patient with Suspected Acute Coronary Syndrome - Emergency Department Phase

ECG - The initial test of all patients presenting to the emergency room with chest pain is an ECG. This is often performed by the triaging nurse prior to the patient being seen and evaluated by the physician. The ECG consists of 12 electrical leads and these leads measure the electrical activity of the heart from 12 different viewpoints. The ECG abnormalities are seen in different leads depending on the location of the myocardial infarction. The electrical location of the infarction can predict the behavior of the infarction. In general, anterior and lateral infarctions are due to occlusion of the left anterior descending artery or the circumflex artery. These infarctions, if left untreated tend to be larger infarctions resulting in mechanical pump failure. Varying degrees of mechanical pump failure can lead to pulmonary edema, and cardiogenic shock. Some MIs may not be observed on the standard 12-lead ECG because the leads do not overlie the region. For example, no observable changes may be seen on ECG with an MI involving the posterior wall as leads are standardly placed on the anterior chest. Placement of leads on the back (posterior leads) will improved detection of MI involving the posterior wall.

Diagnostic tests for DCM

ECG may show left ventricular hypertrophy, intraventricular conductional delay (widened QRS), non-specific repolarization abnormalities and possibly infarct pattern. On chest X-ray a grossly enlarged heart shadow, hilar prominence due to pulmonary vascular redistribution, pulmonary edema and or pleural effusion may be present. An echocardiogram is the diagnostic test that will confirm the diagnosis. LV dilatation is present and all walls will be poorly contracting (global hypokinesis). Ejection fraction will be reduced (LVEF < 45%)

Diagnostic Tests for HCM

ECG shows left ventricular hypertrophy with pseudo-infarct pattern particularly in inferior and lateral leads. Diffuse ST depression and T wave inversion and left atrial enlargement may also be observed. Atrial fibrillation may be present. The diagnosis is confirmed with echocardiography. Asymmetric hypertrophy of the interventricular septum with or without systolic anterior motion (SAM) of the mitral valve may be observed. Doppler demonstrates mitral regurgitation as well as a dynamic obstruction in the LV outflow tract. Cardiac MRI provides accurate assessment of wall thickness, LV mass, and scar burden, which may be useful for assessing a patient's risk of sudden death. The apical variant of HCM is often underappreciated on echocardiogram but better visualized with cardiac MRI. A left heart catheterization may be performed to directly measure pressure gradient across the LV outflow tract; although similar measurements may be made using echo- Doppler. A Holter monitor may be helpful for assessing for atrial fibrillation or ventricular arrhythmias. Finally, genetic testing may have some value for screening family members if a specific mutation has been identified in the affected individual.

8. Complications of MI Electrical Complications

Electrical Complications- Arrhythmias are common during acute MI and are a major source of mortality, especially in the "pre-hospital" phase. Modern Coronary Care Units are designed to quickly detect and efficiently treat life-threatening arrhythmias and have led to a significant decrease in early mortality from acute MI. a. Ventricular fibrillation - Primary ventricular fibrillation occurs suddenly and without warning, usually within the first 12 hours of an infarction. VF requires immediate electric defibrillation. Secondary ventricular fibrillation is a late complication (1-6 weeks after AMI), occurring in patients with severe left ventricular failure. Late VF is more likely to occur in patients with large anterior infarction, patients with conduction defects, patients with persistent sinus tachycardia or atrial arrhythmias.

Endogenous Pathway:

Endogenous Pathway: -TAG and CE (cholesterol esters) put into ApoB-100 hepatocytes of liver to make VLDL -VLDL gives ApoCII and ApoE to HDL to mature -LPL on VEC activated by ApoCII hydrolysis VLDL and frees FA and glycerol for fat/muscle -Hydrolyzed VLDL add density by removing GA/FA to become IDL - taken into liver via APoE/chylomicron remnant receptor -Liver uses hepatic lipase to release more GA/FA -Hydrolyzed VLDL = LDL (cholesterol + apoproteins) -Circulating LDL taken in liver/peripieral cell is via APoB100 binding LDL receptors. -LDL absorbed via VEC low affinity scavenger receptors (leads to ath. plaque + bv disease).

Etiology of DCM

Etiology of DCM - Once the diagnosis of DCM is made, it is important to determine its etiology. These include: Valvular: chronic mitral or aortic regurgitation End-stage remodeling secondary to chronic hypertension (uncontrolled) Chronic ischemic heart disease due to myocardial infarction Infectious myocarditis (usually viral infections, HIV, rare bacterial etiologies) Autoimmune: polymyositis, SLE, scleroderma, etc. or rejection after a heart transplant. Toxin-induced: chronic alcohol abuse, cocaine abuse, heavy metal poisoning (lead), and chemotherapy drugs (anthracyclines - doxyrubicin and daunorubicin and the anti- HÉR/Neu antibody, traztuzumab, which is used in breast cancer). Hormonal and Metabolic causes: thyrotoxicosis, hypothyroidism, diabetes, Cushing's disease, pheochromocytoma, acromegaly, beriberi (a syndrome of low peripheral resistance and high-output heart failure seen in severe thiamine deficiency that is very rare with a modern diet), and Takotsubo cardiomyopathy (catecholamine-mediated myopathy due to acute emotional stress). Genetic: mutations involving the proteins lamin A and C, actin, and dystrophin. DCM is observed in patients with Duchenne's muscular dystrophy, limb girdle muscular dystrophy, and Friedrich's ataxia. Peripartum cardiomyopathy Specific etiology, even with appropriate non-invasive as well as invasive testing, usually is identified in less than 20% of all DCM cases. Genetic testing has only marginally improved the yield but a search for familial etiology may be appropriate if there is a history of DCM in first-degree relatives. Endomyocardial biopsy has a limited yield while a cardiac catheterization is useful for ruling out coronary disease. Depending on the etiology some patients may have recovery of LV function but the rate of such recovery is highly variable depending on the cause. Viral myocarditis, Takotsubo cardiomyopathy and peripartum cardiomyopathy often can have good rates of recovery. Toxic causes and any sort of chronic insult typically have a poor rate of recovery. If LV function does not improve, the five-year survival is below 50%. Etiologies of DCM that warrant specific discussion are listed below.

Exercise The concept of cardiac rehabilitation began in the 1950's when it was determined that chair rest and low level activity after a myocardial infarction (MI) was better than eight weeks of bed rest. Since then, exercise has continued to gain importance for the post-myocardial infarction patient. Exercise training has many benefits, including an increase in functional capacity, reduction in body weight, modest but favorable changes in lipid levels, increase in insulin sensitivity, and reduction in blood pressure.

Exercise Tolerance Testing Upon entrance to an outpatient cardiac rehabilitation program, an initial symptom-limited graded exercise tolerance test (ETT) should be performed. An ETT is a useful tool for risk stratification, exercise prescription, and assessment of baseline functional capacity. Functional capacity is related to the patient's ability to take in, distribute, and utilize O2. This can be measured directly using a metabolic cart, or can be estimated using standard regression equations. Based on the ETT, the intensity of exercise may be prescribed either by measured oxygen uptake (VO2) or heart rate. ETTs should be performed while the patient is taking their usual dose of medication to provide a useful prescription for daily exercise. If VO2 is actually measured, a prescription may be based on 50-85% peak VO2. Heart rates at this range of intensity are determined and a training heart rate range is obtained. Two other methods for exercise prescription are based on heart rates obtained from the initial ETT: 1) 50 - 90 % peak HR 2) Karvonen method: Heart rate range = 50 % (peak HR - rest HR) + rest HR to 90% (peak HR - rest HR) + rest HR If ischemia is present during the ETT, the upper limit of the training heart rate range should be at least 10 beats below the heart rate at the ischemic threshold. Exercise testing also provides information, which is useful to determine the patient's risk of adverse cardiac events during exercise. Individuals with low exercise capacity (<6 METS) [where 1 MET equals the approximate amount on energy used in the awake, resting state], angina or ischemia (particularly at low levels), exercise-induced ventricular dysrhythmias, and exercise-induced hypotension are considered to be at increased risk. Such patients should undergo directly supervised exercise training at least until exercise safety has been determined and the patient understands and practices self-monitoring.

Lipoprotein Metabolism Exogenous Pathway:

Exogenous Pathway: -FA and MAG from gut chyme -> enterocytes -> TAG, pos,chol,cholE put into Apoprotein B-48 nascent chylomicrons then into lymph then thoracic duct then blood. -Blood chylyomicrons transfer App C-11 and App E to HDL. -Apo-C-11 activates Lipoprotein lipase LPL on bv wndo cell to hydrolyze chlyomicrons and release glycerol + FA that then are absorbed by adipose and peripheral muscle for use or storing. -Circulating hydrolyzed chylomicrons, remnants absorbed using ApoE/chylomicron remnant receptor into liver. -Liver uses this stuff for more hydrolysis to release FA and glycerol for self

3. Cholesterol Absorption Inhibitor (oral) Ezetimibe Drugs for Hyperlipidemias

Ezetimibe MOA: lower intensive cholesterol absorption by inhibiting sterol transporter Rx: Treat high LDLc CP: Rare live dysfx.

E. Pharmacologic treatment of CHRONIC heart failure in the hospital

F. Pharmacologic treatment of chronic heart failure The goals of therapy for ambulatory patients with heart failure are to minimize symptoms, prolong life and slow the progression of the underlying disease process. The therapies for systolic (HFrEF) vs. diastolic (HFpEF) heart failure differ. The large majority of patients with chronic heart failure that is due to HFrEF or HFpEF require diuretics to maintain an acceptable intra-vascular volume status that is relatively free of interstitial edema and yet allows sufficient preload for an adequate cardiac output. However, beyond diuretics, the therapies for HFrEF and HFpEF differ. For HFrEF, a large body of placebo-controlled data support the use neuro-hormonal inhibition with RAAS inhibitors (ACE inhibitor, ARB) and beta-blockers which have been shown to improve symptoms, improve survival and slow the progression of disease. These therapies are mandated by standard of practice guidelines in all patients with HFrEF who do not have a contraindication. In contrast, there are no established therapies for HFpEF other than the control of blood pressure and heart rate, which may still involve the use of RAAS inhibitors and beta-blockers, although the benefits with regard to outcomes have not been proven for HFpEF.

d. Fetal circulation

Fetal circulation has a few differences compared to adult circulation, all of which are adaptations for the fact that a fetus gets its oxygen from the systemic circulation via the placenta, not from the lungs. The umbilical arteries arise from the internal iliac arteries. The blood then picks up oxygen and nutrients at the placenta and returns to the fetus via the umbilical vein, which passes though the fetal liver and drains via the ductus venosus into the inferior vena cava, returning to the right heart. However, the oxygen and nutrients are needed by the systemic tissues. The oxygenated blood is shunted from the right atrium across the foramen ovale to the left atrium by the Eustachian valve which sits at the posterior wall of the right atrium. Systemic venous return from the superior vena cava enters the right atrium, courses across the tricuspid valve to the right ventricle and is ejected into the main pulmonary artery. Because of the high pulmonary vascular resistance of the collapsed lungs, 90% of the RV output is shunted across the ductus arteriosus into the descending aorta. At birth, the infant takes a breath, inflating the lungs and decreasing the pulmonary vascular resistance (PVR) markedly. At the same time the umbilical cord is clamped, increasing the systemic vascular resistance (SVR). With the PVR lower than the SVR, blood will now shunt left to right (aorta to pulmonary artery). The ductus arteriosus normally closes spontaneously within hours to weeks in response to the increased oxygen level and decreased prostaglandin levels. With increased pulmonary blood flow, there is increased pulmonary venous return to the left atrium, which tends to push the septum primum against the septum secundum to seal the foramen ovale

Class IC: Na+ Channel Block

Flencainide Oral blocks INa channels; slows phase 0 depolarization; slows conduction velocity and pacemaker activity; negative inotropic effect USE: Used for atrial arrhythmias but only in structurally normal heart BAD: increased arrhythmias, CNS excitation,aggravates CHF

Valvular Physiology

For all practical purposes, normal adults have two hearts and one lung. The cardiac valves, maintain uni-directional blood flow through this system by opening and closing in response to pressure gradients generated by muscle contraction in the chamber walls. In this arrangement, the right heart functions as a low pressure, volume adapted pump to the lung. The normal lung is a low resistance diffusing bed in which, grossly, distribution of blood flow is of little importance. In contrast, the left heart supplies a high-pressure system where distribution of blood flow to various beds is critically important, the high perfusion pressure permitting differential resistances to regulate local perfusion. Symptoms, subjective complaints arising from deranged physiology, often reflect either high pressures in the low-pressure chambers of the circuit, or low flow to key organs in the high pressure left side.

Differential Diagnosis of RCM

Functionally, RCM may resemble constrictive pericarditis and ruling out the latter is extremely important as constrictive pericarditis may respond to pericardial stripping. The methods for distinguishing restriction from constriction will be discussed in the section on pericardial disease. Treatment of RCM - RCM general has a poor prognosis. Symptoms of heart failure may be treated with salt-restriction and careful use of diuretics. Patients with RCM are preload dependent and excessive reduction in preload may lead to significant drop in cardiac output. Because of this preload dependence and the fact that LV function is usually preserved, vasodilators should not be used. Beta-blockers should be used cautiously, particularly with cardiac amyloidosis, for arrhythmia management. Despite preserved ejection fraction, negative inotropic agents including calcium channel blockers are detrimental and should not be used for arrhythmia management. Digoxin should not be used in patients with cardiac amyloidosis. Digoxin binds to amyloid fibrils and there are reports of an idiosyncratic increased sensitivity to digoxin in patients with cardiac amyloidosis leading to digoxin toxicity that does not appear to be dose dependent. Finally, intracardiac thrombi (~26% in one autopsy study) and atrial fibrillation are common in cardiac amyloidosis and it is recommended that these patients are treated with warfarin.

2. Loop diuretic (oral, parenteral) Drugs for Hypertension

Furosemide block Na/K/Cl transporter in ThAL hypertension, heart failure, edema, hypercalcemia hypokalemia, hypovolemia, ototoxicity

Loop Diuretic

Furosemide Oral PE blocks Na/K/Cl transporter ThAL increased excretion of salt and water; reduces cardiac preload & afterload; reduces pulmonary and peripheral edema Use: severe hypertension; acute and chronic heart failure, acute pulmonary edema, hypercalcemia Bad: hypokalemia, hypovolemia, ototoxicity

4. FIbric acid (oral) Gemfibrozil Drugs for Hyperlipidemias

Gemfibrozyl MOA: PPAR-a agonist allows HDL production, LPL lowers VLDL secretion and helps VLDL breakdown Rx: Hypertriglyceridemia CP: Myopathy, hepatic dysfx.

Inotropic Drugs (Glycosides, B-Agrenergic Asgonists, PDE Inhibitors)

Glycosides Digoxin O/PE inhibits Na+/K+ ATPase; increases intracellular Na+ & decreases Cá+ expulsion; increases intracellular Cá+; increases cardiac contractility Use: Chronic HF, Atrial Fibrillation Bad: Nausea, vomiting, diarrhea, cardiac arrhythmias

Reverse cholesterol transport pathway

HD: moves fat (chol,phos,TAG) out of periphery/arteries back into liver via Apo A-1

4. Pathophysiology of heart failure

Heart failure can be defined as the failure of the heart to pump blood at an output required by the metabolizing tissues or as the ability to pump blood at a required output only at elevated filling pressure (that is, it is only contractile enough when distended by high pressures, such that it generates higher forces - Starling's law). Clinically the failure to pump blood at an output required by metabolizing tissues may lead to end organ dysfunction (e.g., kidney or liver failure) if the depression in function is severe. More commonly, insufficient pump functionshows up as the inability of skeletal muscles to perform work that requires increased blood flow to the exercising muscles (e.g., climbing stairs) The ability to pump adequate blood only at an elevated filling pressure would present as signs of volume overload, since those high filling pressures are transmitted backward though the venous circulation, causing fluid to leak out under higher hydrostatic pressures, accumulating in the lungs or dependent systemic tissues.

Antithrombotics Study Guide Table Anticoagulants: Heparin, LMW heparin, Direct factor X Inhib

Heparin: (parenteral): complexes with antithrombin III; irreversibly inactives coagulation factors thrombin and Xa. Use: venous thrombosis, pulmonary embolism, myocardial infarction, unstable angina, adjuvant to percutaneous, coronary intervention and thrombolytics Issue: aPPT (bleeding;protamine is reversal agent); thrombocytopenia, osteoporosis with chronic use LMW heparin: enoxaparin/ fondparinux(subcutaneous) selective for coagulation factor Xa Use: better pharmacokinetics than unfractionated Issue: Only partial protamine several; less risk of thrombocytopenia than heparin Direct factor X Inhibitor: Rivaroxaban oral fixed dose; bind active site of Xa to inhibit; Use: venous thrombosis; PE; prevent strokes in Afib pt Issue: bleeding no reversal Direct Thrombin Inhibitors Dabigatran oral binds to thrombins active site to inhibit Use: anticoagulation in heparin-induced anticoagulation in heparin-induced Issue: bleeding; monitor with aPPT Vitamin K Antagonist: Warfarin oral inhibits vitamin K epoxide reductase and thus interfers with the production of vitamin-K- dependent clotting factors and anticlotting factors Use: venous thrombosis, PE, prevent thromboembolic cx with atrial fibrillation or cardiac valve replacement Issue: bleeding (monitor with PT), vitamin K is reversal agent), thrombosis early in therapy, due to protein C difficiency teratogenic

1. Thiazide Diuretic (oral) Drugs for Hypertension

Hydrochlorthiazide block Na/Cl transporter in DCT hypertension, mild edema hypokalemia, hyperuricemia, hyerglycemia, hyperlipidemia

Thiazide diuretic heart failure

Hydrochlorthiazide oral blocks Na/Cl transporter in DCT Less effective than furosamide Use: Mild Chronic Heart Failure, Mild-mod hypertension Bad: hypokalemia,hyperuricemia, hyerglycemia, hyperlipidemia

2) Hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common cardiomyopathy in athletes who suffer sudden cardiac death. It is a familial disease characterized by a hypertrophic left ventricle, which is the result of a non-physiologic increase in muscle mass in the absence of cavity dilation. There is myocardial fiber disarray and commonly disproportionate hypertrophy of the interventricular septum and a tendency to have obstruction at the left ventricular outflow tract. Less commonly hypertrophy involves the LV apex. Both systolic and diastolic functions are affected in HCM; however, the hallmark of this disorder is abnormal diastolic filling. Signs and symptoms of HCM Dyspnea on exertion due to elevated left ventricular diastolic pressures and angina due to relative ischemia of the hypertrophic myocardium are the most common symptoms. Heart failure symptoms also are a result of elevated end-diastolic pressures with transmission into the pulmonary vasculature often resulting in congestive symptoms. Syncope is an ominous symptom and may be the result of ventricular arrhythmia or outflow tract obstruction. Palpitation symptoms may be a result of atrial fibrillation or ventricular arrhythmias. However, many patients with HCM may be total asymptomatic as is the case with athletes who are only discovered to have the condition after a sudden death event. On physical examination, an S4 heart sound may be auscultated as this extra heart sound represents the left atrium contracting against a stiff left ventricle. In patients with outflow obstruction, a brisk carotid pulse with a characteristic pulsus bisferiens is observed. This "spike and dome" waveform can be recognized on palpation of the carotid arteries. The contour of the carotid pulse reflects the dynamic events occurring within the left ventricle. The initial rapid and unimpeded ejection from the left ventricle leads to a brisk upstroke of the carotid pulse. The obstruction to outflow that occurs in mid-systole (due to the contact of the hypertrophied upper septum and anterior mitral valve) leads to a sharp cut- off of the pulse. Continued ejection of blood in the presence of obstruction in late systole leads to the dome part of the spike and dome contour. A harsh systolic crescendo-decrescendo murmur is heard on auscultation and this is caused by turbulent flow as the anterior flap of the mitral valve is drawn into the left ventricular outflow tract by high flow Venturi forces. The murmur is best heard at the mid-left sternal border right over the LV outflow tract. The murmur classically gets louder with Valsalva maneuver because decreased venous return reduces preload, leading to decreased end-diastolic volume. As a result, the obstructed outflow tract transiently becomes narrower with a smaller volume in the left ventricle leading to more severe obstruction and a louder murmur. Increasing contractility will also worsen the obstruction and the intensity of the murmur. Conversely, the murmur gets softer with squatting (from standing position) because increased venous return increases left ventricular volume and reduces the severity of the outflow tract obstruction. A second, holosystolic murmur may be heard at the apex and this is due to mitral regurgitation from mitral valve incompetence when the anterior leaflet is drawn by high flow Venturi forces into the left ventricular outflow tract during systole. Finally, S2 will not be appreciably split or will split paradoxically (with expiration not inspiration) due to prolonged ejection against obstruction and resultant late closure of the aortic valve.

Antiarrhythmic Drugs

IA sodium channel blocker: Procainamide IB sodium channel blocker: Lidocaine IC sodium channel blocker: Flecainide II beta-blocker: Metoprolol III potassium channel blocker: Dofetilide IV calcium channel blocker: Verapamil III, I, II, IV calcium channel blocker: Amiodarone

Confirmation of MI

If the diagnosis of MI is not immediately evident on ECG (e.g non-STEMI or UA) the patient is initially hospitalized with the diagnosis of "suspected" MI based on their clinical history. The diagnosis is subsequently confirmed and the extent of myocardial damage assessed using the following diagnostic tests: Cardiac Serum Enzyme Levels - Enzymes are released in large quantities into the blood from necrotic heart muscle following myocardial infarction. The appearance in the serum of cardiac enzymes is considered to be diagnostic of MI. Specific cardiac enzymes differ in the time course for detection and diagnostic importance.

Exercise echocardiography -Echo test is positive if wall motion issues in previously normal areas appear or worsen with exercise. Sensitivity: 90% Specificity: 90%

Imaging modalities (echo) combined with ECG to increase sensitivity and specificity of ST + MI risk of Ischemia extent. Echo at rest vs echo at treadmill or right after ET (1-2 min post since ab wall motion normalized post) -Rest/stress compared in cineloop gated during systole from QRS. -MI contractility rises with exercise -Ischemia causes hypokineses, kineses, dyskimnises in affected parts. -Bette than nuclear imaging bc : no inonizd radiation, shorter time to test. - Limitations to echo: bad echo windows if fat or lung interfere. -The sensitivity of exercise echocardiography is approximately 90% and the specificity is approximately 90%.

Hemodynamic pressure profiles associated with common valvular pathology Aortic stenosis

In aortic stenosis the aortic valve orifice is narrow. There is a large systolic pressure difference between the left ventricle (LV) and the aorta since extra pressure must be generated to overcome the resistance of the stenosis. During a left heart catheterization, the magnitude of the pressure gradient across the aortic valve can be measured. The catheter is passed across the valve into the LV, then pulled back to obtain a pressure tracing. The size of the gradient reflects the degree of the stenosis and helps guide whether valve replacement is indicated.

Aortic Stenosis.

In contrast to the decades long slowly evolving clinical course of mitral stenosis, patients with symptomatic aortic valve stenosis have a brief, dramatic course rapidly culminating in either surgical relief of left ventricular outflow obstruction or death. Understanding the pivotal role of normal mitral valve function, the physiologic basis for these different histories becomes clear. With mitral valve disease the low-pressure pulmonary capillary bed is directly exposed to the hemodynamic disturbance. An increase of 10 mmHg in the pulmonary wedge pressure required to maintain mitral flow doubles the normal low wedge pressure and leads to pulmonary congestion. In contrast, with normal mitral valve function, an increase of 10 mmHg to maintain aortic valve flow increases LV systolic pressure minimally (120 to 130mmHg, for instance) and is not reflected in pulmonary pressure at all. The cardinal symptoms of aortic stenosis include 1) exertional syncope, 2) exertional angina pectoris, and 3) congestive heart failure. In the absence of other disease, the onset of symptoms indicates a) the left ventricle cannot maintain forward flow across the stenotic valve, leading to syncope or b) the need for myocardial oxygen consumption has outstripped supply producing angina, or c) LV systolic pressure loading has now caused severe diastolic dysfunction due to impaired compliance and congestive failure. Clinically, precise etiologic diagnosis matters little. Aortic stenosis in youth may be attributed to congenital disease. In mid-to-late adulthood, male dominated disease involving a congenitally bicuspid valve contributes most of the cases. In the elderly, progressive atherocalcific disease of anatomically trileaflet valves occurs with equal frequency in men and women. Physical findings include a slow-rising low volume arterial pulse (parvus et tardus), a sustained left ventricular apical impulse, occasionally a "thrill" or purring vibratory sensation over the sternum, a soft single S2, and a harsh crescendo- decrescendo (diamond-shaped) systolic murmur. The chest x-ray may demonstrate valvular calcification; the ECG usually shows left ventricular hypertrophy. Echocardiogram shows left ventricular hypertrophy with thickened immobile aortic cusps. Once symptoms begin, prompt evaluation and operation should follow. Patients with angina die within 5 years and those with heart failure within 2 years. Survivors of a syncopal episode are at risk for sudden death at anytime. Surgical replacement of the diseased valve is preferred. In older patients who are deemed to high risk for surgery, transcatheter aortic valve replacement (TAVR) may be considered. With this approach a prosthetic valve is deployed and expanded over the native heart valve using percutaneous approach rather than thoracotomy.

5. Treatment for ST Elevation MI (STEMI) - Emergency Department Phase

In patients with STEMI, emergent reperfusion and opening of the completely occluded vessel is imperative. With STEMI, a common saying is: time is myocardium. Irreversible damage will occur after 20 minutes of anoxic injury. As time from MI onset progresses; however, the benefits of reperfusion decreases with longer ischemic times.

4. Treatment of Acute Coronary Syndrome - Anticoagulation with heparin

In patients with unstable angina or NSTEMI, the use of heparin therapy early in the course significantly reduces the risk of acute MI, recurrent unstable angina and possibly death. All patients presenting with UA/NSTEMI should be treated with intravenous unfractionated heparin (UFH) or subcutaneous Low Molecular Weight Heparin (LMWH) in addition to aspirin for the first 24-48 hours. Patients who survive STEMI particularly those with anterior MI or who have a left ventricular thrombus seen on echocardiography are at high risk of having an embolic stroke. This risk may be reduced by early administration of intravenous heparin. Heparin has also been shown to reduce the rate of coronary reocclusion rate in MI patients treated with the thrombolytic agent TPA. Finally, high dose intravenous heparin is recommended while patients are undergoing primary PTCA to reduce the risk of acute thrombosis of the recently opened vessel.

Revascularization of CAD by coronary artery bypass grafting

In some patients, coronary artery bypass graft surgery (CABG) has been shown to be more effective than PCI and stenting. With CABG, vein or arterial grafts are anastomosed distal to the coronary stenosis. Arterial grafts are superior to vein grafts for maintaining long-term patency; therefore when possible, arterial grafts such as left internal mammary artery are used to bypass arteries that supply larger territories of the heart (i.e. left anterior descending artery). CABG has been shown to have greater efficacy over PCI in patients with: 1. Leftmainstenosis>50% 2.3vesselcoronaryarterydisease(i.e.stenosis in RCA, LCX, AND LAD) 2. 2 vessel disease LAD and low LV contraction (low ejection fraction) 4. Diabetes with multi-vessel coronary disease The risks of CABG are greater than PCI and the decision for surgical versus percutaneous revascularization must be individualized. Ideally, each patient is informed by a Heart Team (cardiologist and cardiac surgeon) where risks and benefits of each procedure are discussed and there is opportunity for shared decision-making with the patient.

2. Atrioventricular reentrant tachycardia (AVRT)

In the presence of an anomalous electrical connection between atrial and ventricular tissue (bypass tract), the requirements for reentry are established. A bypass tract creates two routes of conduction, and the AV node serves as a region of slower conduction. Unidirectional block occurs as a result of different refractoriness of the bypass tract and AV node. Most often unidirectional block occurs in the bypass tract and the sinus impulse propagate normally through the AV node down to the ventricle. However, once the ventricle is activated the impulse may conduct in a retrograde fashion back up to the atrium via the bypass tract and initiate reentry (->AV node -> ventricle -> bypass tract ->atrium -> AV node -> etc.). When the reentry occurs in a direction such that the AV node is activated normally (i.e. impulse coming from atrium) the tachycardia is called orthodromic AVRT. With orthodromic AVRT the QRS is narrow because the ventricles are being activated normally via His-Purkinje network. When unidirectional block occurs in the AV node (rather than bypass tract) the sinus impulse propagates down the bypass tract to the ventricle. Once the ventricle is activated the impulse may conduct in a retrograde fashion back up the His-Purkinje system to the AV node and subsequently reactivate the atrium thereby initiating reentry (-> bypass tract -> ventricle -> AV node -> atrium -> bypass tract -> etc.). When the circus movement involves retrograde activation of the AV node the circuit is called antidromic AVRT. Antidromic AVRT is characterized by tachycardia with a wide QRS complex because the ventricles are not being activated by the His-Purkinje system but rather by the bypass tract.

Infectious myocarditis

Infectious myocarditis is a clinically important cause of DCM. It is usually caused by viruses such as Coxsackie B virus, adenovirus, parvovirus B19, HHV6, VZV, rubella, and enteroviruses. Patients with viral myocarditis often present with symptoms of heart failure a few weeks after a viral illness. HIV cardiomyopathy is more often a late consequence after the patient has developed a high viral load. Myocardial injury is caused by the patient's own immune cells attacking virally infected cardiomyocytes, or due to autoimmune cross-reactivity with myocardial antigens. Bacterial infections can also trigger dilated cardiomyopathy via a similar mechanism, more commonly atypical bacteria like Mycoplasma, TB, rickettsial disease, or Lyme disease. In the acute phase of myocarditis, cardiac biomarkers (troponin, CKMB) will be elevated and a cardiac MRI may show edematous myocardium as well as early contrast enhancement (with gadolinium) suggestive of hyperemia and capillary leakage. Active inflammation may be seen with endomyocardial biopsy, where a bioptome is advanced intravenously into the right ventricle and samples from the interventricular septum are obtained. Pathologic findings on biopsy include myocytolysis and lymphocytic infiltration. In practice biopsy is rarely performed because of limited diagnostic yield (i.e. the biopsy rarely is positive even if disease is present). This is largely because myocardial biopsies are usually only taken from the right side of the intraventricular septum. Samples from the left ventricle are rarely obtained due to risks associated with the procedure. In people from Central America, chronic Chagas disease (caused by the parasite Trypanosoma cruzi) is the most common cause of infectious myocarditis and DCM. Commonly patients with Chagas disease have left ventricular aneurysms with mural thrombus and ventricular arrhythmias. Patients will typically also have digestive symptoms including dilation of the esophagus and resultant dysphagia. Unfortunately, there is no cure for Chagas disease once it has progressed to the chronic stage. When a patient is felt to have active inflammation from infectious myocarditis, therapy should include eradication of the precipitating organism (if it can be identified). Therapy typically also includes bedrest and aggressive control of preload and afterload during the acute period to prevent adverse ventricular remodeling. The use of steroids or intravenous immunoglobulin to reduce inflammation remains controversial.

d Effect on Left Ventricular Function Acute Myocardial Infarction w

Initially, the remaining non-infarcted area of myocardium will become hyperkinetic (exhibit increased systolic contraction). This compensatory hyperkinesis is thought to be secondary to an increase in sympathetic nervous system activity and the Frank- Starling mechanism, and generally subsides within two weeks of the infarction. The viable portion of the myocardium also begins to dilate immediately following the infarction and continues for a period of weeks to years. This compensatory enlargement serves to increase stroke volume via Frank-Starling forces. The increased pressure and volume placed on the non-infarcted ventricle also causes a compensatory hypertrophy. These changes in left ventricular size, thickness and function in the infarcted and non-infarcted regions of myocardium described above are collectively referred to as ventricular remodeling.

Invasive hemodynamic monitoring

Invasive hemodynamic monitoring is the process of measuring pressures in the different chambers of the heart and is used to evaluate cardiac physiology. It also allows for assessing the degree of valvular regurgitation or stenosis and for assessing the degree of intracardiac shunting from abnormal connections between chambers (e.g. ventral septal defect). A catheter (commonly referred to a Swan-Ganz catheter) is inserted into a central vein (internal jugular vein, subclavian vein, or femoral vein) and advanced through the right atrium, right ventricle, and pulmonary artery before "wedging" into a branch vessel of the pulmonary artery. The pressure transducer at the tip of the catheter continuously measures pressure as it passes through each chamber. When the catheter is fully inserted, a balloon is inflated to occlude the lumen of a branch of the pulmonary artery and the pressure distal to the blockage is allowed to drop until it is in equilibrium with the pressure of the left atrium. This pressure is called the wedge pressure, and it is used as an indirect measurement of left- sided filling pressures (left atrial pressure). Pressures inside the left heart are often not directly measured unless a catheter is inserted retrograde into the left ventricle across the aortic valve. The wedge pressure is an indirect measure of left ventricular end-diastolic pressure (LVEDP). LVEDP may rise in conditions that cause pressure or volume overload.

Nitrovasodilators

Isosorbide dinitrate (oral) releases NO from drug molecule activates guanylyl cyclase venodilation, reduces preload & ventricular stretch reduces mortality chronic HF in African Americans; used alone/with hydralazine tachycardia, headache

Intravasular Pressures/Resistances

JVP: < 3cm sternal RA: 1-5mmHg RV: 17-30/1-5 mm Hg PAP: 17-30/5-13 mm Hg PCWP: 5-10 mm Hg LA: 4-12 mm Hg LV: 90-140/6-12 mm Hg Aor: 90-140/60-90 mmHp Card Index: 2.6-4.2L/min/m2 PVR: 100-250 dynes/sec-cm^5 SVR: 1000-1400 dynes/sec*cm^5

High intensity statin Rosuvastatin 20-40mg Atorvastain 40-80mg

LDLc >190 - Less than 75y/o high coronary disease, PVD, stoke -40-75 y/o DM 10yr risk + 7.5% Non-db with 10yr risk +7.5% if LDL not reduced to 70 on another Rx

Pericarditis Lab + ZTreatment

Laboratory findings may include leukocytosis (elevated WBC count), and elevated erythrocyte sedimentation rate (ESR). Specific tests for specific etiologies are obtained depending on the clinical scenario and may include viral titers, rheumatoid factor, purified protein derivative (PPD) test for tuberculosis, and antinuclear antibodies (ANA) for lupus. Treatment Basic treatment is high dose non-steroidal anti-inflammatory drugs (NSAIDS) like ibuprofen or indomethacin and rest until the pain abates. If symptoms fail to improve with NSAIDS a brief course of steroids (prednisone) may be required. Relapsing pericarditis often responds to chronic colchicine, which has an anti- inflammatory effect by inhibiting neutrophil activity. In most cases, pericarditis responds well to NSAIDs and resolves completely within 2-3 weeks, but rarely may be complicated by the development of pericardial effusion, tamponade, or constrictive pericarditis.

Class IB: Na+ Channel Block

Lidocaine IV blocks INa channels (no IK channels); blocks activated and inactivated channels; minimal effect on normal tissue; may shorten AP duration and phase 3 repolarization USE: Used for ventricular arrthmias particularly in setting of ischemia. BAD: CNS effects: sedation or excitation

AF Prevelance

Lifetime risk of developing AF in men and women at age 40 is 26% and 23%, respectively, based on Framingham Heart Study. Risk factors for the development of AF include: increasing age, hypertension, obesity, smoking, low HDL, and diabetes. AF is also associated with obstructive sleep apnea, pulmonary disease, heart failure, left ventricular hypertrophy, valvular heart disease, infiltrative heart disease, and ischemic heart disease. There are also an increasing number of genetic mutations that have been identified in familial cases of AF.

6. ACE inhibitors (oral) RAAS Drugs (ACE Inhib Lisinopril and ARB Losartan) Drugs for Hypertension

Lisinopril reduces AII synthesis hypertension, diabetic renal disease, heart failure yperkalemia, cough, teratogen, angioedema

7. ARBs (oral) RAAS Drugs (ACE Inhib Lisinopril and ARB Losartan) Drugs for Hypertension

Losartan blocks AT1 receptors hypertension hyperkalemia, teratogen

Symptoms of Acute Myocardial Infarction

Many patients with unstable angina have a 1-2 week prodrome of chest discomfort. Initially the chest pain may occur with exertion but gradually becoming more frequent and intense and finally, culminating in the symptoms of an ACS. At the time of presentation most patients complain of chest or upper abdominal discomfort. The duration of the pain is usually between thirty minutes and several hours. Patients who complain of chest pain of very brief duration (several minutes) or of long standing duration (several days) have rarely sustained an acute MI. The pain is often described as crushing, squeezing, constricting, tightness, pressure, or heaviness ("like an elephant on my chest"). The discomfort can be vague and diffuse. The patient will often gesture toward the painful area with an open hand or a clenched fist (Levine's sign), rather than point with a single finger. The most intense discomfort is usually felt in the sternal or parasternal region with radiation into the lateral chest (usually to the left) and often to the neck, jaw, arms, or back. Other associated symptoms may be present, such as shortness of breath (dyspnea), nausea, vomiting, indigestion, sweating (diaphoresis) and weakness. Approximately 20% of patients will have an MI without associated symptoms. This can occur in patients who are confused, demented or who have been under anesthesia. Approximately 20% of patients will present with atypical symptoms rather than chest pain, including shortness of breath, weakness, diaphoresis, indigestion, back pain, nausea, or apprehension or confusion.

Assessment of cardiac function from pressure measurements CO MAP

Mean arterial pressure (MAP) The MAP is the average systemic blood pressure oveSystemic vascular resistance (SVR)

Treatment of PAD

Medical treatment is directed at reducing progression of atherosclerosis, reducing cardiovascular ischemia/mortality and relieving symptoms. Treatment involves risk factor modification including: lipid management with high intensity statin (goal LDL < 100 mg/dl), blood sugar control in patients with diabetes (goal HbA1c < 7), blood pressure control (goal <130/85 mmHg), and smoking cessation. Antiplatelet therapy with clopidogrel or aspirin is recommended for reducing risk of myocardial infarction, stroke and cardiovascular mortality. Treatment to relieve symptoms involves a combination of exercise, medications, and/or revascularization. Aerobic exercise (despite claudication symptoms) promotes the formation of collateral circulation within the ischemic limb and may improve symptoms over time. Medications may extend the exercise time before onset of claudication. Cilostazol is a phosphodiesterase inhibitor that causes arterial vasodilation and platelet inhibition. It has been shown to have a beneficial effect in patients with mild to severe claudication by improving walking distance and functional status. Its use is contra-indicated in heart failure. Pentoxyifylline decreases blood viscosity to indirectly lower peripheral resistance. This drug has been shown to have only a modest effect on walking performance and there is little data on its effect on quality of life or functional status. When claudication becomes incapacitating or disease has progressed to critical limb ischemia where blood flow is inadequate to meet the metabolic demands at rest and the survival of the limb is threatened, revascularization may be considered to improve blood flow to the ischemic limb. Percutaneous angioplasty and stenting may be performed to directly open the stenosis, or surgical modalities such as aortofemoral bypass graft or femoro-popliteal bypass graft may be performed to direct blood around the region of stenosis. Unlike percutaneous revascularization procedures, surgical bypass grafting is associated with a high operative mortality (5-8%) because of the nature of the procedure and the fact that these patients commonly have concomitant coronary disease. Surgical options are reserved for PAD that is not amenable to percutaneous repair.

Class II: -Blockers

Metoprolol Oral selective β -1blocker; slows pacemaker activity prolongs AP duration; slows SA node automaticity and AV nodal conduction velocity; inhibits phase 4 depolarization USE: Used for treatment of supraventricular tachycardia, rate control of atrial fibrillation. and atrial fluter and for supression of some ventricular arrhythmias. BAD: bronchospasm in asthmatics, cardiac depression, sedation AV block, hypotension (fewer adverse effects than propranolol)

Mitral Regurg Hemo

Mitral regurgitation In mitral regurgitation, the mitral valve is incompetent and there is leaking of blood during systole. The PCWP is increase due to increased volume of blood (volume overload). The PCWP tracing also is characterized by a prominent v-wave due to a rise in left atrial pressure during ventricular systole.

Mitral Stenosis Hemo

Mitral stenosis In mitral stenosis the mitral valve orifice is narrow. A pressure gradient exists across the mitral valve such that PCWP exceeds the LV end-diastolic pressure (LVEDP). This is one case where our assumption that wedge pressure is an approximation of the LV end diastolic pressure is very wrong.

Left-sided Valve Lesions A. Mitral Valve Disease Mitral Stenosis:

Mitral stenosis, almost invariably rheumatic, obstructs left ventricular inflow. The process, which more often affects women than men has four distinct phases.

Not all bypass tracts can conduct in both directions.

Most bypass tracts are only able to conduct in the retrograde direction (from ventricle to atrium) and therefore are only capable of causing orthodromic AVRT. Some bypass tract are able to conduct in both retrograde and antegrade direction (from atrium to ventricle). Wolff-Parkinson-White syndrome (WPW) affects 0.03% of the population, and is defined by the presence of an antegrade (and retrograde) conducting bypass tract and associated arrhythmias. The presence of an antegrade conducting bypass tract may be diagnosed on ECG. If the bypass tract conducts antegrade (from atrium to ventricle) the normal AV delay provided by the AV node is short circuited, and an abnormally short PR interval (<120 msec) results. Additionally, since activation of ventricular myocardium is not solely down the septum, the initial portion of the QRS is slurred and wide. The slurring of the QRS is called a delta wave and it is the hallmark of WPW (see above figure). Patients with WPW syndrome may have both othrodromic and antidromic AVRT. The treatment of WPW is catheter ablation of the bypass tract to eliminate the anomalous AV connection.

Natriuretic peptides

Nesiritide (IV) recombinant human brain natriuretic peptide (BNP) secreted by ventricular myocytes; binds BNP receptors and increases cGMP atrial peptide vasodilator diuretic acute, severe decompensated failure renal damage hypotension

2. Nicotinic Acid Preparation (oral) Niacin Drugs for Hyperlipidemias

Niacin MOA: Inhibit lipolysis in fat, lower VLDL production, lower LDL/TAG, raise HDL Rx: Hypercholesterolemia, hypertriglyceridemia, low HDLc CP: GI issue, flushing, hepatotoxicity, hyperuricemia, hyperglycemia (lowers glu tolerance)

4. Treatment of Acute Coronary Syndrome - NG

Nitroglycerin - All hemodynamically stable ACS patients should get nitrates. Nitrates have several beneficial physiologic effects. They reduce myocardial oxygen demand by reducing blood pressure and venous return (via peripheral arterial and venous dilation). They increase myocardial oxygen supply by dilation of coronary arteries and coronary collaterals. Typically patients present with ACS are given sublingual nitroglycerine up to three times, and then are started on a nitrate drip if they continue to have anginal chest pain. Early clinical trials suggest that administering IV nitroglycerin during acute MI limits infarct size, improves left ventricular functioning and reduces the risk of infarct expansion and aneurysm formation. The effect on mortality remains unclear. All patients presenting with acute MI, a large infarct, congestive heart failure should receive Nitroglycerin for 24-48 hours aiming for a reduction in mean arterial pressure of 10%. The most common side effects are headache and hypotension. Finally, nitrates help confirm that chest pain is due to coronary event. If the pain resolves within 5 minutes of nitrate administration the mechanism of the pain is most likely ischemic. In contrast if the patient's chest pain is due to acid reflux, nitrates will not relieve the pain.

Serial ECGs may aid in the diagnosis. Dynamic ECG changes (i.e. changes on ECG that vary with time) may indicate myocardial ischemia or infarction.

Non-Invasive Imaging - The relative portability of echocardiographic equipment makes this technique ideal for the assessment of patients with acute MI in the Emergency Room. In patients with "ischemic sounding" chest pain but a non- diagnostic ECG the finding on echocardiography of an area of myocardium with abnormal contraction supports the diagnosis of MI and localizes the affected region and coronary artery distribution. Echocardiographic estimation of overall left ventricular function is also useful in establishing prognosis. Finally, many of the mechanical complications of myocardial infarction discussed below (pump failure, papillary muscle rupture, acute ventricular septal rupture, right ventricular infarction, infarct expansion) can be rapidly diagnosed by this non-invasive modality.

2. Non-cyanotic cardiac defects

Non-cyanotic cardiac defects are cardiac malformations that do not result in deoxygenation of systemic arterial blood. Many non-cyanotic lesions are inappropriate communications connecting the right and left-sided circulations. As pulmonary vascular resistance decreases compared to systemic vascular resistance, there is increased left to right shunting. Long standing shunts can result in an increase in pulmonary vascular resistance and eventually if the pulmonary vascular resistance exceeds the systemic vascular resistance, the shunt will reverse and become right to left with resultant cyanosis. This phenomenon is called Eisenmenger's syndrome. If an adult presents with new onset of cyanosis, always consider undiagnosed congenital heart disease.

Treatment of HCM

Obstruction with HCM is dynamic and becomes hemodynamically more significant under certain physiologic circumstances. Dehydration or hypovolemia decreases preload and LV volume resulting in increased obstruction. Tachycardia, particularly with atrial fibrillation, decreased diastolic filling time and LV volume and thereby worsens the obstruction. Exercise is thus very dangerous in HCM patient with obstruction as tachycardia, positive inotropy and dehydration may worsen obstruction and result in sudden death. (HCM is the leading cause of sudden cardiac death in apparently healthy young athletes.) Patient should be counseled about limiting exercise and avoiding dehydration. Beta-blockers are useful for decreased outflow tract obstruction by decreasing contractility. Beta-blockers also reduce myocardial oxygen demand and alleviate angina symptoms. Calcium channel blockers have a similar effect. Heart failure symptoms may be improved with diuretics but diuresis should be performed cautiously to avoid significant drop in preload that may worsen the severity of the obstruction. Vasodilators should not be used because of their effect on preload and decrease in afterload, which may lead to increased contractility of the myocardium. In patients with severe outflow tract obstruction refractory to medical therapy, septal myomectomy with open-heart surgery can be performed to widen the ventricular outflow tract. An alternative is septal alcohol ablation where alcohol mixture is injected into the septal perforating branches of the left anterior descending artery using a percutaneous approach (left heart catheterization). This results in a controlled myocardial infarction of the septum, which thins as it remodels, thus decreasing the hypertrophied septum. Both procedures can result in injury to the conduction system rendering the patient pacemaker dependent. Patients with HCM are at risk of sudden cardiac death due to ventricular arrhythmias. Historical features that identify patients at greatest risk of sudden death include syncope, family history of sudden death in first degree relative before the age of 40 years, ventricular arrhythmias on monitoring, and wall thickness > 30 mm. Patients with one or more of these features should undergo ICD for prevention of sudden death. Finally, the first-degree relatives of patients with HCM should undergo screening echocardiogram, ECG and possibly genetic testing if the mutation has been identified usually starting in adolescence. Genetic counseling should be offered to patients who are planning on having children.

4. Treatment of Acute Coronary Syndrome - Ó

Oxygen - The rationale behind Ó therapy stems from the observation that some patients with MI are mildly hypoxemic because of ventilation perfusion mismatch, that hypoxemia hastens myocardial necrosis and that breathing oxygen may limit ischemic myocardial injury. Though it is not proven to reduce myocardial damage or mortality the administration of oxygen by nasal prongs has become standard practice.

6. PCSK9C Inhibitor Drugs for Hyperlipidemias

PCSK9C Inhibitor HumMab inactivates PCSK9c enzyme binds liver LDL increase degradation, LDLR #/LDL-C clearance increased, LDL-C lowered Rx: Diet, Statin in hetero-fam, hypercholesterolemia, ASCVD.

ABG Arterial blood gases CAD Coronary artery disease FA Femoral artery IVC Inferior vena cava PA Pulmonary artery PCW Pulmonary capillary wedge P pressure

PV Pulmonary vein PVR Pulmonary RA vascular resistance RV Right atrium SVC Right ventricle SVR Superior vena cava Systemic vascular resistance

AF episode AF documented on ECG monitoring and has a duration of at least 30 seconds. Subsequent AF episodes requires documentation of intervening sinus rhythm.

Paroxysmal AF recurrent AF (≥2 episodes) that terminates spontaneously within 7 days. Persistent AF continuous AF that is sustained beyond 7 days. Longstanding Persistent AF continuous AF of greater than 12 months duration. Permanent AF continuous AF in which either the patient has failed attempts to restore and maintain sinus rhythm with either catheter or surgical ablation or a decision has been made not to restore sinus rhythm by any means.

Clinical Manifestations of PAD

Patients with PAD are most commonly asymptomatic. Intermittent claudication, an aching pain in the lower extremities that occurs with exertion, has been described as "angina of the legs" and is due to supply-demand mismatch of oxygen to the leg muscles. The pain is usually distal to the vessel stenosis, is precipitated by consistent level of exertion, and resolves with rest. The level of exertion at which the pain develops is a fairly reliable indicator of disease severity. As the severity of the atherosclerosis progresses, symptoms may occur at rest. The development of rest pain is the hallmark of critical limb ischemia. Patients with advanced disease may report nocturnal pain that is relieved by dangling the affected limb over the side of the bed. Other clinical features include ischemic ulceration (non-healing foot ulcers) and gangrene. With critical limb ischemia there is an increased risk of limb loss.

Pericardial tamponade

Pericardial tamponade occurs when pericardial fluid accumulates to the degree that the pericardium becomes less compliant and pressure within the pericardium equals the diastolic filling pressures of the right atrium and right ventricle resulting in impaired ventricular filling, reduced cardiac output and hypotension. When the pericardial pressure exceeds diastolic filling pressures shock and death may occur very quickly. If the fluid accumulates gradually over time the pericardium may adapt and stretch to accommodate large volumes of fluid before a rise in pericardial pressure is observed. However, if there is rapid fluid accumulation, such as in the case of traumatic cardiac perforation or myocardial rupture, the pericardium stretches very little (no chronic adaptation) and pericardial pressures rise quickly to cause acute tamponade. Patients with impending tamponade most commonly have symptoms of dyspnea, orthopnea, or dizziness. Tamponade is characterized by severe hypotension or shock.

Inotropic Drugs (Glycosides, B-Agrenergic Asgonists, PDE Inhibitors) B-ad PDE

Phosphodiesterase Inhibitors Milrinone (IV) decreases cAMP breakdown vasodilation & lowering TPR; increases cardiac contractility Use: acute, decompensated heart failure Bad: Cardiac arrhythmia

4. Treatment of Acute Coronary Syndrome - Glycoprotein IIB-IIIA Inhibitors

Platelet aggregation ultimately depends on the binding of fibrinogen to various glycoprotein (GP) receptor sites on the platelet surface. When the resting platelet comes in contact with agonists such as thromboxane, thrombin, ADP, serotonin and collagen conformational changes occur in the receptor such that it becomes more receptive to ligands such as fibrinogen and von Willebrand factor. Fibrinogen simultaneously binds to two receptor sites on two separate platelets, and therefore mediates platelet cross-linking and aggregation. Unfortunately, agents such as aspirin are weak platelet inhibitors because they only block the effects of one agonist, thromboxane, leaving the platelet vulnerable to stimulation by other agonists. Glycoprotein IIB-IIIA receptor inhibitors are more potent inhibitors of platelet aggregation because they bind directly to the fibrinogen receptor site and prevent platelet cross linking. Over 32,000 patients presenting with acute coronary syndromes or undergoing percutaneous interventions have been studied in randomized trials of GP IIB-IIIA inhibitors. These studies suggest that GP IIB-IIIA inhibitors, when used in conjunction with aspirin and heparin, reduce the risk of recurrent ischemic events and myocardial infarction. Therefore, GPIIB-IIIA inhibitor therapy should be considered for use in all patients presenting with unstable angina or MI without ST- segment elevation. Because these agents are more expensive than standard unfractionated heparin and because they might increase the risk of some bleeding complications, their use should be limited to those patients who undergo PTCA or manifest high-risk features: Continued ischemia despite treatment with aspirin, heparin, beta- blockers and nitrates Persistent ischemic ST changes on ECG Positive serum troponin TIMI risk score of > 3 (see below) GP IIB-IIIA Inhibitors are effective in treating patients with ST elevation who undergo PCI. Beyond this initial treatment, further workup is needed to classify the type of ischemic event that occurred and determine if emergency revascularization therapy is appropriate.

Valvular Disease Prevalence of Valvular Disease

Population studies in the US show that the prevalence of valvular disease increases with age. These studies have shown that its prevalence is < 2% before the age of 65 years and then increases to 13.2% after the age of 75 years.

4. a-blockers (oral) Drugs for Hypertension 5. Renin-Angiotensin Inhibitors

Prazosin decreases TPR, relaxes arterial and venous SM mild hypertension, bengin prostatic hyperplasia reflex tachycardia ST, first-dose syncope, salt/water retention

Peripheral arterial disease (PAD)

Prevalence of PAD is 8-10 million people in the United States. The most common cause of PAD is atherosclerosis, but it can also be caused by rare disorders like large-vessel vasculitis, fibromuscular dysplasia, cystic adventitial disease and entrapment syndromes. Risk factors are generally similar to the risk factors for CAD, but diabetes contributes greater to the risk of developing PAD than it does to the risk of developing CAD (RR for CAD in diabetics is around 1.65 but RR for PAD is 4.05). PAD is a systemic disorder. It is associated with an increased all-cause mortality, which is largely driven by a 6-fold increase risk of coronary heart disease. Narrowing of the vessel lumen results in increased vessel resistance to blood flow. Resistance is proportional to the inverse fourth power so small luminal changes cause large changes in resistance. (Poiseuille's Law: resistance 1/radius4). Because of this high resistance, both blood flow and pressure is reduced distal to the region of stenosis. Vascular response (i.e. arterial dilatation during exercise or in response to nitrogen oxide) is reduced in PAD.

Class IA: Na+ Channel Block

Procainamide oreal PE blocks INa and some IK channels; slows phase 0 depolarization; slows conduction velocity and pacemaker activity; prolongs AP duration and refractory period USE: Rarely used. May be used for pre-excited atrial fibrillation (WPW) or diagnosis of Brugada syndrome. BAD: increased arrhythmias, lupus-like syndrome, CNS effects: depression, hallucinations

Risk Factor Modification

Programs which include only exercise are not synonymous with cardiac rehabilitation. A comprehensive program should include a systematic approach to evaluate and modify risk factors for atherosclerosis. Smoking For individuals with CAD, smoking is associated with increased mortality and morbidity, silent ischemia, and dysrhythmias. Benefits of smoking cessation in the post-MI patient include a reduced risk of re- infarction, sudden death, and total mortality compared to those who continue to smoke. Other benefits include an improvement in the lung's ability to remove phlegm, and easier breathing within 3 days of cessation. The cessation of smoking, although obviously important, is a complex, difficult process. Assessment of the patient's smoking history is an integral component of the overall evaluation. Patients who are currently smoking or who have recently quit should be appropriately counseled regarding the importance of cessation. This can be done on an informal individual basis by program staff, or in a more structured smoking cessation program lead by a trained counselor. The latter method is most useful for those who are actively smoking and are experiencing difficulty quitting, or those in whom relapse is likely, such as: individuals with high levels of dependency; those who have just recently quit; or those with high levels of stress. Nicotine dependency contains both a physiological and psychological component, thus both areas need to be addressed in a smoking cessation program. If a patient is deemed to be physiologically addicted to nicotine (this can be done using a nicotine assessment questionnaire) then nicotine replacement therapy (NRT) is useful. NRT, when prescribed in conjunction with a minimal contact psychological intervention has resulted in quit-rates 1.5 times higher than in placebo controlled studies of psychological intervention alone. Health care professionals must be prudent in prescribing NRT particularly in individuals who just recently experienced a myocardial infarction or those with life threatening dysrhythmias due to the possibility of increased adverse events. Other pharmacological agents, buproprion or Chantix (varenecline), a nicotine receptor blocker, can be used to help reduce the cravings of nicotine, and can be used alone or in conjunction with NRT providing the appropriate counseling and follow-up are provided. As 60-90% of smokers who achieve smoking cessation will resume smoking within one year, it is important to note that relapse is a normal process of behavior modification and should not be treated as a failure. Relapse provides a learning experience for triggers to smoke and coping strategies. As such, relapse can help the individual to understand his/her habit. Smoking cessation efforts should be done in concert with the patient's primary care physician who can serve to reinforce this process.

3. B-blockers (oral) Drugs for Hypertension

Propranolol nonselective b-blocker reduces CO and renin release hypertension, angina pectoris, myocardial infarction, migraine, hyperthyroidism bronchospasm in asthmatics, cardiac depression, sedation, erectile sex dysfunction, sleep issues Metoprolol selective B-1 blocker reduces Co and renin release hypertension, angina pectoris, myocardial infarction, migraine, hyperthyroidism less adverse stuff than propranolol

Right-sided Valve Lesions Disease involving the right-sided valves occurs much less frequently than any of the lesions involving the left-sided valves. Right-sided problems in adults generally fall into one of three categories: a) congenital disease, principally pulmonic stenosis. b) tricuspid regurgitation due to chronic passive pulmonary hypertension, and c) infective endocarditis.

Pulmonic stenosis As with aortic stenosis, symptoms in patients with pulmonic stenosis represent inability to increase forward cardiac output appropriately with impaired exercise tolerance, and even exertional lightheadedness or syncope. Severe pulmonic stenosis may lead to angina but sudden death is unusual. Clinical findings in congenital pulmonic stenosis reflect the pathophysiologic consequences of obstruction to RV outflow, with chronic pressure loading of the right ventricle. Prominent A-waves in the jugular venous pulses, a parasternal lift, and a thrill in the second left intercostal space are typical physical manifestations of RV pressure loading. Auscultatory findings include a normal S1, ejection click, systolic murmur and widely split S2 with a diminished pulmonic component. The ECG shows changes of right ventricular pressure overload with a vertical frontal plane axis and tall R waves in the right precordial leads. The chest x-ray almost always shows post stenotic dilatation of the pulmonary artery. Echocardiogram shows the domed stenotic valve in more than 90% of patients. Balloon catheter valvuloplasty is the preferred therapy for pulmonic stenosis.

WPW

Rarely, patients with untreated WPW may have sudden cardiac death due to an excessively rapid heart beat (>250 bpm). WPW patients are susceptible to atrial fibrillation, where excitation of the atrium may be in excess of 400 bpm. Normally the AV node blocks at least half of these beats so the ventricular rate rarely exceeds 200 bpm. However, in patients with WPW the bypass tract may conduct atrial fibrillation more rapidly than the AV node causing a very rapid ventricular rate (> 250 bpm). Such a rapid heart rate leads cardiac collapse because of inadequate filling time. Treatment of pre-excited atrial fibrillation requires intravenous procainamide, which preferentially slows conduction in the bypass tract, or cardioversion to restore sinus rhythm. AV nodal agents including beta-blockers and calcium channel blockers are contra- indicated for the treatment of pre-excited atrial fibrillation because slowing conduction in the AV node may promote conduction over the bypass tract and increase the ventricular rate. Pre-excited atrial fibrillation may be distinguished from ventricular tachycardia by its irregular rhythm and by the variability in the QRS width.

Antithrombotics Study Guide Table Fibrinolytic Drugs

Recominant human tissue plasminogen activators: Alteplase PE converts plasminogen to plasmin which degrades fibrin in thrombi Use: coronary artery thrombosis, ischemic stroke, PE Issue:bleeding ++ hemorrhage

2. Abnormalimpulseconduction

Reentrant excitation. Reentry requires: 1) two pathways of conduction, 2) slow conduction and short refractory period in one of the pathways, and 3) unidirectional conduction block in the other pathway. In the normal state, cardiac conduction progresses in a smooth homogenous fashion over myocardial tissue. In the presence of an anatomic obstacle, two routes or pathways of conduction may result. Often times, these pathways will have different effective refractoriness, causing conduction to fail over one route (the one with the longer refractory period) because it has not recovered excitability. If the other pathway then conducts in a slow fashion, there may be enough time for the blocked pathway to recover conduction and be activated in a reverse direction, thus establishing a reentrant circuit. This is the most common mechanism underlying the majority of tachyarrhythmias.

3) Restrictive cardiomyopathy

Restrictive cardiomyopathy is the least common of the three major primary cardiomyopathies. It is characterized by abnormally stiffened of the ventricle resulting in decreased compliance and impaired diastolic filling. Typically, the left ventricular ejection fraction is preserved (i.e. normal). Because of this reduced ventricular compliance end-diastolic pressure is reached at a low end-diastolic volume. This causes a reduced stroke volume and cardiac output. Signs and symptoms of RCM RCM may present with symptoms of dyspnea on exertion, fatigue, chest pain or palpitations. RCM may be incidentally diagnosed after a patient presents with the primary disorder, such as amyloidosis. Findings on physical exam that suggest restrictive physiology include an S3 gallop due to abrupt cessation of rapid filling when the stiff myocardium reaches the limit of its compliance in early diastole, positive hepatojugular reflex (JVP goes up markedly when you push on the liver because the stiff RV is not able to receive the extra venous return) and Kussmaul's sign (JVP that goes up with each inspiration for the same reason). Systolic murmurs due to mitral or tricuspid regurgitation may also be present. Finally, the typical findings of heart failure including pulmonary rales, peripheral edema, etc. may also be present. Diagnostic tests for RCM ECG may show low voltage and pseudo-infarction pattern (Q waves that mimic an MI) because of infiltration in the myocardium. Conduction abnormalities such as 1st, 2nd or 3rd degree AV block or bundle branch block are frequently present. On echocardiogram small ventricular cavities with markedly dilated atrial cavities and increased ventricular thickening with a classic granular sparkling pattern is observed. Normal systolic function (i.e. LVEF) is maintained. Cardiac MRI may show late gadolinium enhancement, which indicates myocardial fibrosis.

Chamber Pressures Each chamber has a unique pressure waveform.

Right atrium 1-5 Right ventricle (systolic/diastolic) 17-30/1-5 Pulmonary artery (systolic/diastolic) 17-30/5-13 Pulmonary Capillary Wedge Pressure (PCWP) 6-12 Left atrium 6-12 Left ventricle (systolic/diastolic) 90-140/6-12 Aorta (systolic/diastolic 90-140/60-90

See below table for normal values of Oxygen in Chambers

SVC: 72 ICV: 77 RA: 75 RV: 75 PA: 75 PV: 98 FA: 97 If there is mixing of oxygenated blood with de-oxygenated blood a "step- up" in oxygen saturation is observed in the subsequent chamber. A rise in oxygen saturation by 7% is considered significant and diagnostic for shunt. For example, with a ventricular septal defect (VSD) blood shunts from the high pressure left ventricle into the lower pressure right ventricle. With a saturation assessment, a step up in Ó saturation will be observed moving from the right atrium (75%) to the right ventricle (83%).

Shunt Hemodynamics

Shunts Shunting is the inappropriate flow of blood through an anatomical defect (i.e. atrial septal defect or ventricular septal defect) that allows mixing of oxygenated blood from the left-side of the heart with deoxygenated blood from the right-side. This may cause hypoxia. A shunt may be detected by measuring oxygen saturations in the various cardiac chambers. Normally the oxygen saturations in the superior vena cava, inferior vena cava, right atrium, right ventricle, and pulmonary artery are about the same. See below table for normal values.

Resistance Training

Since many activities of daily living and occupational needs require muscular strength, resistance training is an important adjunct to cardiovascular training during cardiac rehabilitation. Coronary patients have been shown to increase muscular strength, and, to a lesser extent, endurance after resistance training. Resistance training has been demonstrated not to cause adverse outcomes in either low-risk and higher risk patients. In fact, heart rates tend to be lower at the end of three sets of light-moderate resistance exercise than during cardiovascular training. Guidelines for beginning a resistance training program are not vastly different than those for beginning a cardiovascular program. Goals must be determined by the patient and staff. Particular attention should be made in instructing the patient on correct form (i.e. exhaling during the exertion) thereby avoiding the Valsalva maneuver. Moreover, muscle groups should be trained in pairs (e.g. chest/back, biceps/triceps, quadriceps/hamstrings). Resistance training can also provide some aerobic benefit if performed as a circuit, (quicker pace, moderate weight, frequent repetitions); increases muscle strength; improves glucose intolerance; increases bone density (a particularly important benefit for older individuals and women); and can lead to a healthier body composition via increased muscle mass.

Potassium-Sparing Diuretic

Spironolactone oral blocks aldosterone receptor CT increased excretion of salt and water; limit remodeling, lower mortality Use; Chronic HF; aldosteronism Bad: hyperkalemia, gynecomastia

MS Stage 1

Stage 1: Non-critical stenosis. Following an attack of acute rheumatic fever, the mitral leaflets thicken, with commissural fusion laterally, where excursion is diminished. The chodae also thicken and fuse. The mitral valve area (MVA) gradually diminishes from 4-5 cm2 to 1.5 to 2.5 cm2. The patient has no specific symptoms, and sinus rhythm is maintained. The first heart sound is accentuated (closing snap), an opening snap occurs 0.10 to 0.14 seconds after Á, and a low frequency diastolic rumble with pre-systolic accentuation may be heard at the apex, most easily in the left lateral decubitus position. The ECG demonstrates only left atrial enlargement and the chest x-ray and/or barium swallow may confirm left atrial engorgement with a double density and impingement on the esophagus. Echocardiogram shows thickened leaflets with concordant motion, reduced E-F slope and slight left atrial enlargement. Pulmonary symptoms (shortness of breath, cough, pulmonary edema) in this stage result from tachycardia and/or increased mitral flow due to superimposed fever, anemia, thyrotoxicosis, pregnancy, etc.

MS Stage 2

Stage 2: Hemodynamically "critical" stenosis. When the processes of thickening and fusion progress to reduce MVA to 1.0 to 1.5 cm2, patients enter the most symptomatic stage of their disease. In order to maintain cardiac output, the right heart drives blood through the narrowed mitral valve increasing left atrial and pulmonary capillary pressure. The rising pulmonary venous pressure exceeds the level (usually about 25 mm Hg) at which plasma oncotic pressure can retain intravascular volume. Intravascular fluid then transudes into the lungs overwhelming pulmonary lymphatics and leading to acute or chronic pulmonary congestion. Patients in this stage show exquisite sensitivity to elevated heart rate. Since mitral flow occurs in diastole, the insertion of more systolic cycles per unit time reduces time available for diastolic flow, and thus requires a higher transvalvar pressure gradient. Fever, pregnancy, or paroxysmal atrial fibrillation with rapid ventricular response rates commonly cause decompensation and overt pulmonary edema. In addition, the limited ability to increase forward output leads to generalized fatigue and weakness. Chronic interstitial congestion and impaired lymphatic function predispose to prolonged episodes of "winter bronchitis," and often bloody sputum (hemoptysis) ensues. Left atrial obstruction with low forward flow predisposes to development of intra-cardiac thrombus and systemic embolization. Physical examination changes but subtly from stage 1. Patients appear more frail or asthenic. Characteristic "mitral facies" with a malar flush may occur. The interval from aortic valve closure to opening snap shortens with increased LA pressure ("decreased Á-0S interval") P2 intensifies. The ECG may show a rightward QRS axis and a tall R in V1 as the right ventricle remodels and dilates. Late in stage 2, atrial enlargement disrupts the atrial conducting system and sustained atrial fibrillation often develops. The chest film now shows left atrial enlargement, prominent pulmonary arteries, and interstitial edema. Echocardiogram shows further thickening of the mitral leaflets, reduction in E-F slope, and left atrial enlargement.

MS Stage 3

Stage 3: The "Quiescent Phase." Since the advent of modern cardiac surgery, first with mitral commissurotomy and later with prosthetic replacement of the valve and balloon valvotomy, few patients progress through the stormy second stage to enter the paradoxical third stage. In this "quiescent phase," the patient experiences a remission of symptoms. Respiratory distress and pulmonary congestion abate, due to development of intrinsic pulmonary vascular disease with severe pulmonary hypertension. The pre-capillary pulmonary hypertension limits right heart output and protects the pulmonary capillary bed by decreasing mitral valve flow. On examination, a parasternal systolic lift and marked accentuation of P2 indicate pulmonary hypertension; the auscultatory features of mitral stenosis persist. Although surgical risk rises for stage 3 patients, intervention should be undertaken. The active or pre-capillary component of pulmonary hypertension will improve fairly rapidly after surgical relief of inflow obstruction and survivors should enjoy good functional status.

MS Stage 4

Stage 4: Right Heart failure: mitral stenosis with advanced pulmonary vascular disease. At this pre-terminal stage, mitral valve area may be from 0.3 to 1.0 cm2. Pulmonary artery pressure may equal or slightly exceed systemic pressure, and the right ventricle dilates and fails, producing dilation of the tricuspid annulus with tricuspid regurgitation. Physical examination in this stage reflects primarily the right heart findings, with engorged systemic veins, peripheral edema, an enlarged pulsatile liver, and the characteristic systolic murmur of tricuspid regurgitation, which increases with inspiration. ECG, chest x-ray, and echocardiogram all confirm right ventricular pressure overload. Surgical treatment at this stage carries an extremely high risk, but may still be offered, since the alternative is extreme cardiac disability and death.

Hyperlipoproteinemia Drugs

Statins - Atorvastatin Nicotinic Acid Preparations - Nacin Cholesterol Absorption Inhibitor - Ezetimibe Fibric Acids - Gemfibrozil Bile Acid Binding Resin - Cholestyramine PCSK9 inhibitors (gabs)

Diagnosis of Pericarditis

The diagnosis of pericarditis is based on the history, physical exam and electrocardiogram. Patients classically present with insidious onset of retrosternal and left sided sharp chest pain that is pleuritic (increases with inspiration) and is relieved by sitting up or leaning forward. Sitting up reduces the contact between the visceral and parietal pericardium as the heart is suspended more within the chest and relieves pleuritic pain. With lying down the diaphragm is pushed upwards and there is increased contact between the layers along the inferior heart wall. The patient may also complain of dyspnea, fever or malaise. On exam, patients may be tachycardic, and febrile. Cardiac auscultation may reveal a pericardial friction rub. This is a harsh scratchy "velcro" sound that classically has three components: ventricular systole, rapid ventricular filling in early diastole, and atrial systole. A rub is usually best heard along the lower left sternal border using the diaphragm with the patient sitting up, leaning forward, and exhaling. This maneuver brings the pericardium closer to the chest wall for better auscultation. The electrocardiogram often shows depression of the PR segment and concave- up ST segment elevation in all leads (see figures). The depression of the PR segment is very specific for pericarditis and typically resolves within 1-2 days. Over the next few days to a week, the ST segments normalize while the T-waves invert. Over the following weeks to months, the T-waves normalize.

Etiology of RCM

The etiologies or RCM can be divided into four categories. Non-infiltrative disease (scleroderma, idiopathic disease) Infiltrative disease (amyloidosis, sarcoidosis) Storage diseases (hemochromatosis - cardiac tissue becomes overloaded with iron deposits), glycogen storage diseases (especially Pompe's disease), and lysosomal storage diseases (Fabry disease and Hurler disease). Fibrotic, inflammatory disease from radiation therapy, carcinoid syndrome with serotonin-induced fibrosis, Löffler's endocarditis (a rare condition with eosinophilic inflammation of the endomyocardium), or endocardial fibroelastosis (a rare condition of young children). Endomyocardial biopsy is the gold standard for diagnosing which etiology is causing RCM, but it is seldom performed because of its low yield and because less invasive diagnostic modalities are often sufficient. Etiologies of RCM that warrant specific discussion are listed below. Sarcoidosis is a multisystem, granulomatous disease that is characterized by noncaseating granulomas in involved organs. There is increased prevalence in African-Americans compared to Caucasians with a ratio of about 15:1 and it is often more prevalent in women than men. The most common organs involved include lymph nodes, skin, lung, central nervous system, and eye. Cardiac involvement may occur in 20-30% of sarcoid patients in the US but this number may be higher as cardiac involvement is often under recognized. Complete heart block and ventricular tachyarrhythmias are common in patients with cardiac sarcoidosis. Heart failure due to restriction may also develop with extensive infiltration of myocardium by noncaseating granulomas. A definitive diagnosis of cardiac sarcoidosis may be made by endomyocardial biopsy but the sensitivity of the biopsy is poor since the infiltration is patchy it may easily missed during sampling. Instead diagnosis is usually made by presence of sarcoidosis elsewhere in the body (i.e. pulmonary). Sampling of involved mediastinal lymph nodes has a greater yield. Cardiac involvement is then inferred based on conduction abnormality on ECG and/or scar and inflammation on cardiac MRI or PET imaging. Treatment most commonly employs immunosuppressive therapy including corticosteroids to prevent LV remodeling and to improve LV function. Heart block and ventricular tachy-arrhythmias are most commonly managed with pacemakers / ICDs to prevent cardiac death.

Exercise Training

The goals of cardiovascular exercise training in cardiac rehabilitation are many, and include: • increase functional capacity (if impaired), and maintain functional capacity (if adequate) to meet lifestyle and occupational needs • increase the efficiency of the exercising muscles and myocardium • assist in risk factor modification The Centers for Disease Control and Prevention and the American Heart Association recommend that all adults engage in moderate intensity physical activity for 30-60 minutes for 5 days/ week or 20 minutes of vigorous intensity exercise for 3 days/week. However, the minimal exercise prescription for cardiovascular training to improve fitness levels is three times per week, for 30 minutes at a moderate intensity. The variety of training modalities used in exercise rehabilitation of the post- MI patient has been greatly expanded in recent years. A diverse exercise regimen can employ upper and lower body exercises used in complementary fashion to yield a well-rounded, highly effective training program. If weight loss is a goal, then modality, duration, and frequency are particularly important. While exercising, weight bearing activities such as walking and stair climbing provide the greatest caloric expenditure per unit of time. Increasing the frequency and/or duration will promote greater caloric expenditure. Although the length of cardiovascular training is usually 30 minutes of continuous exercise per exercise session, some cardiac patients may be incapable of achieving this. Interval training is often useful in those whose exercise capacity is limited by heart failure, pulmonary disease, or other co-morbidities. Location The exercise program can take place in the supervised setting of a formal cardiac rehabilitation program. Such a setting is most appropriate for initial assessment and training, particularly among those who are determined to be at higher risk for an adverse cardiac event (e.g. American Heart Association Class C - Table 1), or those with co- morbidities that may complicate the performance of exercise (e.g. those with diabetes, morbid obesity, pulmonary disease, orthopedic, or neuromuscular conditions). Lower risk patients (American Heart Association Class B - Table 1) can safely perform exercise training as described above, in less supervised settings such as health/fitness centers , or at home, providing that the patient has been properly instructed and has demonstrated the ability to self-monitor. It is most important that follow-up with the cardiac rehabilitation team or the patient's primary health care provider occurs on a regular basis in order to insure that the exercise training program is continuing in a safe and effective manner. Such follow-up is also important to periodically adjust the exercise prescription in response to changes in fitness levels, symptoms, medications, or intercurrent clinical events.

Acute rheumatic Fever (ARF)

The incidence of ARF peaks between 5 and 15 years of age and is rare over 30 years of age, with approximately 60% of people with ARF in endemic communities subsequently developing rheumatic heart disease (RHD). ARF incidence is similar in males and females but the risk of RHD is 1.6-2.0 times greater in women likely due to several factors including worsening of existing disease during pregnancy, Group A Streptococcus exposure during child rearing, and intrinsic/hormonal factors. The epidemiology of RHD varies by region with a particularly high prevalence in Africa and the Pacific region but a high burden also in Latin America, the Middle East, and Asia. In the United States, ARF is rare because of antibiotic therapy for acute streptococcal pharyngitis. There have been only a few outbreaks of ARF in the past decades among disadvantaged communities in certain US cities. In Hawaii, the relative incidence of ARF is higher than the continental US and this has been attributed to an unusual Group A Streptococcus gene type.

Left-sided Valve Lesions A. Mitral Valve Disease

The mitral valve protects the low-pressure pulmonary bed from the high pressure generated by the left heart. In this critical position, the mitral valve faces the highest pressure gradient of the four valves, probably accounting for its predisposition of disease. The complex mitral apparatus includes: 1. leaflets 2. chordaetendineae 3. papillarymuscles . supportingLVwall 5. posteriorLAwall 6. annulus

In normal subjects without heart failure the use of these potent vasodilators would decrease blood pressure and would not be tolerated. However, in patients with heart failure the resulting increase in cardiac output usually offsets this effect.

The most commonly used inotropes are dobutamine and milrinone. Dobutamine is a beta-adrenergic agonist, which acts to increase cardiac myocyte cAMP levels. Milrinone is a phosphodiesterase inhibitor, which prevents breakdown of cAMP, and therefore also increases cAMP levels. An increase in cAMP leads to increased availability of calcium to the contractile elements thereby increasing the strength of contraction, as reflected by an increase in the slope of the end systolic pressure volume relationship (figure). Milrinone also acts in smooth muscle cells, where cAMP is a vasodilator, and thus is also a mixed vasodilator with effects similar to nitroprusside or nesiritide. Both drugs may also increase heart rate and increase arrhythmias, which can be limiting side effects.

Mitral Regurgitation:

The pathophysiology of mitral regurgitation (inflow regurgitation) reflects primarily the time course of the lesion and the severity of the volume load imposed on the left ventricle. "Pure" or isolated hemodynamically significant chronic mitral regurgitation is often rheumatic, imposes a volume load on the left-sided chambers and results in low forward output with LV systolic dysfunction. Since the left atrium has years to dilate and accommodate the chronic volume load, it becomes compliant, acting as a pressure-volume "sink" to dissipate the regurgitant volume and protect the lungs from back pressure.

Physical Examination of Acute MI

The patient with acute MI is often anxious and distressed. They may have a look of impending doom. Increased sympathetic tone can lead to skin pallor and cold perspiration. Poor cerebral perfusion can result in confusion or disorientation. The vital signs may be normal or abnormal, but the abnormalities are not diagnostic. Heart rate and blood pressure can be elevated in patients with increased sympathetic nervous activity (usually anterior or lateral infarctions). Heart rate can be low in patients with increased parasympathetic nervous activity (usually inferior infarctions). Excessively low blood pressure can be due to intravascular volume depletion in a patient who has been vomiting or due to pump failure/cardiogenic shock in a patient who has suffered a large infarct. The respiratory rate can be elevated secondary to pain, anxiety, agitation, or pulmonary congestion. The temperature may be slightly elevated (ie. up to 101-102°F) as a result of myocardial tissue necrosis. Otherwise, the physical examination is usually unremarkable though signs of other diagnoses, which can mimic MI and signs of complications of MI should be looked for (see below). In addition, a thorough examination should be performed to detect coexistent disease (e.g. cerebrovascular, neurologic, pulmonary, peripheral vascular disease), which may further complicate the patient's hospital course.

The pericardium

The pericardium is a collagenous sac that surrounds the heart. It is tethered superiorly to the great vessels, anteriorly to the sternum, posteriorly to the vertebral column, and inferiorly to the central tendon of the diaphragm. Approximately 25-50cc of serous fluid is contained within the pericardial space and it decreases the friction between the visceral and parietal pericardium. The pericardium has several functions: to prevent excessive motion to prevent spread of infection from the pleural space to promote ventricular interdependence Despite these functions the patients in whom the pericardium is removed or is congenitally absent generally lead normal lives.

The determinants of the size of the loop are as follows:

The position of the top right corner (red dot) is defined by the contractility of the ventricle (the pressure generated in systole for a given preload) and the systemic blood pressure (pressure required for ejection and closure of aortic valve) • The position of the bottom right corner (green dot) is defined by the venous return and stiffness of the ventricle. Both together determine how much the LV fills during diastole.

Pulmonary artery waveform

The pulmonary artery pressure (PAP) waveform is characterized by systolic peak and diastolic trough with a dicrotic notch (arrow) due to closure of the pulmonic valve. This is similar to the aortic pressure waveform where the dicrotic notch correlates with aortic valve closure.

Junctional rhythm

The rate is 65 bpm and the QRS is narrow (86 msec). Negative P Page 1 of 1 waves are seen in the inferior leads (II,III, aVF) prior to QRS. This indicates the origin of the rhythm is arising from the low right atrium or AV node region. A narrow QRS occurs because the origin of the rhythm is just above the His Purkinje system allowing for normal activation of the ventricles.

Systemic vascular resistance (SVR) Assessment of cardiac function from pressure measurements CO

The resistance of the vasculature reflects whether there is vasodilation or vasocontraction. The resistance may change in response to low cardiac output and is helpful in determining the etiology of shock. Calculation of resistance is similar to Ohm's law for flow of electric current (V=IR). The analogous equation is: pressure drop across a vessel bed = (rate of fluid flow) x (resistance to flow) ∆Psystemic = CO x SVR SVR = ∆Psystemic /CO SVR = (MAP - RAP)/CO x 80 to convert to dyn-s-cm-5

Right atrial waveform

The right atrial (RA) pressure waveform is characterized by two positive deflections (v-wave, a-wave) and two negative deflections (y-descent, x-descent). During ventricular systole, the RA passively fills and as the pressure increases the v-wave is inscribed. At the start of ventricular diastole, the tricuspid valve opens and the RA empties into the right ventricle. This causes a drop in RA pressure and the y-descent. Atrial contraction in late ventricular diastole (atrial systole) creates an increase in RA pressure and inscribes the a-wave. RA relaxation causes the RA pressure to decrease and creates the x-descent.

Right ventricular waveform

The right ventricular (RV) pressure waveform is very tall compared to the RA tracing (not to scale). In systole during ventricular contraction, pressure rapidly increases and then falls as blood is ejected into the pulmonary artery. Pressure slowly increases again during diastolic filling. The a-wave correlates with atrial systole ("atrial kick").

Acute limb ischemia

The sudden loss of adequate blood flow to a limb may cause acute limb ischemia. While PAD typically results in a gradual compromise of vascular flow, patients with PAD are at increased risk of acute limb ischemia in the affected limb due to plaque rupture causing thrombosis in-situ or due to distal embolization of a plaque causing acute occlusion of the distal vessel. Patients with PAD typically have concomitant heart disease and are at greatest risk of acute limb ischemia caused by thromboembolism arising from the heart (e.g. left atrial clot in patients with atrial fibrillation or ventricular thrombus in patients with myocardial infarction and region of akinesis). The signs and symptoms of acute limb ischemia include pain and paresthesias, pulselessness, pallor, and poikilothermia (cool temperature). If flow of blood is not restored, it causes infarction of the extremity, which carries 75% mortality (even if amputation of the limb is performed). Treatment of acute limb ischemia is dependent on limb viability. If the ischemic time is > 8 hours and there is paralysis of the limb, the limb is not salvageable and primary amputation is performed. If there is severe sensory or motor dysfunction, emergent surgical embolectomy is performed. If there is mild to moderate sensory dysfunction, patients are treated with thrombolytic therapy and/or percutaneous angioplasty. Ischemic reperfusion injury may occur as a complication following revascularization. Increased microvascular permeability to proteins and the presence of activated neutrophils, reactive oxygen metabolites and proteolytic enzymes may lead to limb swelling and compartment syndrome (where blood flow is impeded by high pressures within tissue compartments). Fasciotomy is often needed to relieve pressure in the limb and allow for improved blood flow. Following the acute management of limb ischemia, patients are treated with anticoagulation chronically.

ARF Correlations

The three features that have a high correlation with cardiac involvement include: (1) Erythema marginatum, a fleeting snakelike rash, (2) chorea or St. Vitus Dance, and (3) subcutaneous nodules with fibrinoid necrosis. ARF is an acute febrile illness, which subsides with rest and anti-inflammatory therapy. PR prolongation, marked tachycardia, and murmurs of mitral regurgitation or stenosis (due to inflammation and edema at this early stage) are manifestations of acute rheumatic carditis. Tachycardia out of proportion to fever suggests sinus node inflammation and inappropriate acceleration of heart rate. Pericardial inflammation (pericarditis) may also occur as part of the pancarditis (inflammation from the endocardium through to the epicardium and pericardium). Not all individuals who develop ARF will have carditis. However, in those who do, repeated episodes of ARF are clearly associated with more valvular injury. Thus, patients with documented ARF are advised to use penicillin prophylaxis against recurrent beta streptococcal infection. Prophylaxis may be either twice daily oral penicillin or a monthly injection of long acting bicillin. This prophylactic program continues into adulthood when the risk of recurrent exposure diminishes, usually around age 40. Patients who have recovered from ARF should be evaluated from time to time with careful physical examination and echocardiogram to assess the presence or absence of valvular disease.

Paroxysmal supraventricular tachycardia (PSVT)

There are three common types: 1. Atrial tachycardia is a rapid regular supraventricular rhythm, resulting most often from abnormal impulse formation (enhanced automaticity or triggered activity) of atrial tissue. ECG demonstrates discrete atrial activity usually at rates between 100 and 250 beats per minute, often with variable AV conduction. In the setting of COPD, hypoxemia and excessive catecholamines, atrial tachycardia can be multifocal (arising from several sites simultaneously) and is known as multifocal atrial tachycardia or MAT. Atrial tachycardia is not dependent on AV nodal conduction for its maintenance; therefore drugs that block conduction in the AV node will not be effective for terminating this arrhythmia.

Stents Revascularization of CAD After or concomitant with balloon angioplasty, a metal stent is expanded in the region of the coronary stenosis and this acts as a scaffold to maintain the patency of the artery.

There are two types of coronary stents. 1. Bare-metalstents 2. Drug-elutingstents Exposed stent struts are a nidus for clot formation until endothelialization of the stent occurs. For bare-metal stents, the process of endothelialization takes approximately 1 month and during this time, patients must be treated with combination antiplatelet therapy (usually aspirin and a second anti- platelet agent) to prevent acute thrombosis of the stent and an acute myocardial infarction in the territory of the coronary artery. (For example, acute thrombosis of a stent in the left anterior descending artery results in an ST-elevation anterior infarction).

Hypertension Drugs

Thiazide diuretics - Hydrochlorothiazide ACE Inhibitors: Lisinopril ARBs: Losartan Ca+ channel blockers: vaso-selective: Nifedipine non-selective: Diltiazem cardio-selective: Verapamil Beta-1 blockers: Metoprolol Alpha-1 blockers: Prazosin

4. Treatment of Acute Coronary Syndrome - Thienopyridines: Clopidogrel,

Thienopyridines: Clopidogrel, Prasugrel or Ticagrelor: inhibit platelet aggregation (P2Y12 receptor blockers) induced by adenosine diphosphate. Combination thienopyridine with aspirin, which block the thromboxane- mediated pathway, has been shown to be superior to aspirin alone for the treatment of ACS. P2Y12 receptor blocker as well as aspirin, which is referred to as dual antiplatelet therapy (DAPT). The choice of the P2Y12 receptor blocker and the timing of administration depends on the choice between invasive ischemia-guided management strategies, as well as patient characteristics. The rationale for the use of early oral DAPT is that platelet adhesion and aggregation are early steps in the formation of occlusive coronary artery thrombus. DAPT is directed at limiting these early steps, which might result in thrombus occlusion of a coronary artery or stent thrombosis in those patients who are stented. One major study randomized over 12,000 patients with ACS without ST elevation to receive clopidogrel or placebo in addition to aspirin and showed significantly lower risk of MI and recurrent ischemia. There was a trend towards reduced stroke and cardiovascular death. Typically, in patients with ACS are loaded with 600 mg of clopidogrel, 60 mg of Prasugrel or Ticagrelor 180 mg in the emergency department and started on daily maintenance the following day. Thienopyridines are often not administered in patients in whom triple vessel coronary disease is suspected because of risk of operative bleeding associated with coronary artery bypass surgery.

Pulmonary capillary wedge pressure (PWCP)

This pressure reflects the left atrial pressure and has a waveform that is similar in morphology to the right atrial pressure tracing (see above).

5. Treatment for ST Elevation MI (STEMI) - Reperfusion

Thrombolysis Thrombolytic agents act by converting plasminogen to plasmin, which then lyses the fibrin-enmeshed clot that is occluded the coronary artery. Currently tissue plasminogen activator (t-PA and r-PA) are commercially available and most commonly used in the United States. The rationale for thrombolytic therapy is based on the following four facts: 1. An acute MI is caused by coronary arterial thrombus formation in 85-90% of cases. 2. Myocyte necrosis does not occur instantly after coronary occlusion. Depending on the degree of collateral flow, irreversible injury requires 20 minutes to several hours of ischemia. 3. Reperfusion of ischemic myocardium can prevent progression to irreversible injury. 4. Intravenous thrombolytic agents can rapidly dissolve such coronary thrombi and permit reperfusion. Numerous clinical trials have shown that the timely restoration of coronary flow by thrombolysis leads to smaller infarcts, improved left ventricular function, reduced incidence of congestive heart failure and reduced mortality. The greatest benefit occurs when thrombolysis is started within 6 hours of the onset of symptoms. Thrombolytic therapy should be considered for all MI patients with ST elevation or left bundle branch block on ECG, presenting within 12 hours of the onset of chest pain. The major toxic effect of thrombolytic therapy is hemorrhage, especially intracranial hemorrhage which occurs in roughly 0.5-1.0% of patients and is fatal in roughly 1/2 of cases. Therefore, patients with a history of hemorrhagic stroke, intracranial neoplasm, active internal bleeding, aortic dissection and severe uncontrolled hypertension should not be given thrombolytic agents. The risk of bleeding is also increased in patients older than 75 years.

Treatment of tamponade

Treatment consists of supportive care pending emergent pericardiocentesis to remove the fluid. The patient should be administered IV fluids even in the setting of elevated jugular venous pressure to maintain a venous diastolic filling pressure in excess of the pericardial pressure. Pressors or inotropic support may be required for severe hypotension and shock. Definitive treatment consists of removal of the pericardial fluid by pericardiocentesis (needle aspiration of the fluid). Just as tamponade can develop quickly with a small accumulation of fluid, dramatic resolution in hypotension can occur with the removal of as little as 50 cc of fluid. It is essential to send the fluid for appropriate diagnostic tests to establish the cause of the effusion. These tests include cell count with cell differential, cytology, protein level, LDH, glucose, pH, Gram stain, acid-fast bacillus stain, and/or cultures. The underlying cause for the fluid accumulation should be treated. If the fluid is likely to reaccumulate, a surgeon may perform a pericardial window, which creates a hole in the pericardium and allows for continual drainage of fluid into the pleural or abdominal space.

Ventricular escape rhythm - The rate is 38 bpm and the QRS duration is over 200 msec.

Treatment of bradycardia When approaching the patient with bradycardia identifying the underlying cause is important. For example, Lyme disease is a common cause of AV block in younger patients and AV block will resolve with treatment of Lyme disease using doxycycline. A second common clinical scenario is a patient presenting with bradycardia after overdosing on a calcium channel blocker. The resulting sinus bradycardia and /or heart block will resolve once the calcium channel blocker is cleared. Finally, a third common example is a dialysis patient developing heart block in the setting of hyperkalemia after missing dialysis. Once hyperkalemia is treated, complete heart block will resolve. A temporary externalized pacemaker may be necessary to treat the bradycardia until the underlying cause is treated. The treatment of symptomatic, irreversible, bradycardia is a permanent pacemaker. Older adults with bradycardia due to age-related sinus node fibrosis require a permanent pacemaker. Implantable pacemakers have been around since the late 1960's and consist of a pacing leads and generator that contains the battery and circuitry. Technologic advances have improved lead design and battery longevity and allowed for more physiologic pacing. More recently, with breakthroughs in micro-technology, leadless miniaturized pacemakers have been introduced. There is also growing research on the use of biologic pacemakers,which do not require leads or batteries and will respond to catecholamine activation.

Tricuspid regurgitation

Tricuspid regurgitation in the US adult population occurs primarily as a manifestation of right ventricular dysfunction, rather than a primary valvular lesion. The most common cause of right-sided dysfunction and right heart failure is secondary to left sided dysfunction and failure. The clinical findings of tricuspid regurgitation will include: 1. Thefeaturesoftheprimaryheartdiseasesuchasmitralstenosis with pulmonary hypertension and secondary RV dysfunction, or congestive cardiomyopathy with four chamber dilatation and pulmonary hypertension, along with: 2. Thepredictableconsequencesoflossoftricuspidcompetencein the face of increased pulmonary pressure. When tricuspid regurgitation occurs, the dramatic symptoms of pulmonary congestion give way to the insidious consequences of rising systemic venous pressure and low cardiac output. Thus, breathlessness and orthopnea abate and peripheral edema may be replaced by visceral congestion: hepatomegaly, jaundice, and rarely protein-losing enteropathy. Chronically impaired cardiac output is manifested by weakness, fatigue, and a peculiarly cancerous appearing cachexia. The neck veins are distended; the liver pulsates, and the legs accumulate edema. A characteristic rocking precordial motion often occurs, as the right atrium and liver expand with systole. Multiple murmurs confuse the examiner in these patients with advanced disease; the typical murmurs of tricuspid regurgitation radiate to the xiphoid area and increase in intensity with inspiration (Carvallo's sign). The chest x-ray usually shows pan- cardiac enlargement, but about half the patients will have clear lung fields, due to the "protective" effect of TR. Two-dimensional echocardiogram shows TR with excellent sensitivity and specificity. Treatment with rest, diuresis, and measures directed toward the primary pathology may give some relief of symptoms, but the prognosis for most patients with advanced severe tricuspid regurgitation is dire unless the left heart pathology can be relieved.

Valvular Pathology

Understanding valvular disease requires integrating a number of dichotomies. The heart, as a pump, can be either pressure loaded or volume loaded. Ventricular dysfunction may involve either systole or diastole. Inflow or outflow valves may be either stenotic (narrowed) or regurgitant (leaky). The table below demonstrates some of the interactions of these different states.

Bare metal stent issue

Unfortunately with bare metal stents, late in-stent stenosis is commonly observed due to hyperplasia of intimal smooth muscle cells within the lumen of the stent. To counteract this hyperplastic response, so-called drug eluting stents were embedded with paclitaxel, a chemotherapy drug that interferes with microtubule function, or sirolimus (or everolimus), which are immunosuppressant agents that inhibit T-cell activation. As these drugs eluted over time, intraluminal smooth muscle hyperplasia is significantly reduced. The limitation of drug-eluting stents is that the protective endothelialization of the stent is delayed and this extends the time during which the stent is prone to thrombosis from 1 month to about 1 year. Therefore, patients with drug- eluting stents must be treated with combination antiplatelet therapy for at least 1 year to prevent acute in-stent thrombosis. Bare metal: less thrombosis; more smooth muscle hyperplasia restensois Drug-eluting: high thrombosis; less SM hyperplasia restenosis Bare metal stent are preferred in patients who may not be compliant with combination antiplatelet therapy for > 1 month or may not tolerate the therapy (e.g. patients with higher risk of recurrent GI bleeds), or who may require non- elective surgery within the year that cannot be performed on antiplatelet agents.

Effect on Left Ventricular Function Acute Myocardial Infarction

Upon cessation of flow in the coronary artery, the zone of myocardium supplied by that vessel loses its ability to relax in diastole (diastolic dysfunction) and contract during systole (systolic dysfunction). Three abnormal contraction patterns may then develop in sequence: 1. hypokinesis, reduction in systolic contraction 2. akinesis, cessation of systolic contraction 3. dyskinesis, paradoxical expansion and bulging during systole

Pulmonary vascular resistance (PVR)

Using the same equation as above but with values corresponding to the pulmonary circulation: ∆Ppulmonary = CO x PVR PVR = ∆Ppulmonary /CO PVR = (mean PAP - PCWP)/CO x 80 to convert to dyn-s-cm-5 Below are the normal values for vascular resistance. SVR: 1000-1400 dynes/seccm^5 Pulm PVR: 100-250

Other interventional procedures performed in the Cardiac Catheterization Laboratory Balloon valvuloplasty -

Valvular stenosis can be treated with balloon valvuloplasty. During this procedure, a balloon is advanced across a stenotic valve and inflated. By fracturing calcific deposits on the valve leaflets, the stenosis is relieved. Valvuloplasty is commonly used to treat rheumatic mitral stenosis; however, it is less effective for aortic stenosis and for these reasons, valve replacement with either a surgical or transcatheter (TAVR) approach is recommended.

VT

Ventricular Tachycardia (VT) most commonly involves a reentrant mechanism within the ventricles. The requirements for reentry are frequently established by the presence of scar tissue, which creates different routes of conduction within the ventricle. Scar may be a result of previous myocardial infarction or the result of remodeling in other forms of dilated or hypertrophic cardiomyopathy. Ventricular tachycardia most often presents with syncope or cardiac arrest, but can present as sustained palpitations if the rate is slow. The rate is often determined by the size of scar tissue (more scar, slower rate). ECG reveals a wide QRS complex rhythm (>120 msec), often with AV dissociation. With monomorphic VT the QRS morphology from beat-to-beat is the same in any given lead and indicates a consistent and regular pattern of ventricular activation. In the above example there is a regular tachycardia at a rate of ~ 170 bpm and the QRS duration is wide (~ 180 msec). In each lead, the morphology of the QRS is the same from beat-to-beat. Restoration of sinus rhythm requires electrical cardioversion or administration of anti- arrhythmic drugs. Patients with ventricular tachycardia caused by the presence of scar tissue have an increased the risk of sudden cardiac death and an implantable cardioverter-defibrillator (ICD) is commonly implanted to prevent death. Recurrent ventricular tachycardia refractory to medical therapy may require ablation to eliminate routes of conduction in and around the scar. Rarely, monomorphic VT occurs in the absence of structural heart disease and is based on a mechanism of enhanced impulse formation (triggered activity). This is termed idiopathic ventricular tachycardia.

8. Calcium Channel Blockers (oral, parenteral) Drugs for Hypertension

Verapamil & Diltiazem prototype L-type Ca ch blocker combine vascular and strong cardiac hypertension, angina, arrhythmias cardia depression (less with Diltiazem) and conspitation Nifedipin l-type Ca Ch blocker, more vasodilator less heart hypertension, angina dizziness, fatigue

Class IV: Ca2+ Channel

Verapamil oral PE slows conduction in AV node and pacemaker activity; inhibits AP in SA and AV node; negative inotropic effect USE: Used for treatment of supraventricular tachycardia, rate control of atrial fibrillation and atrial flutter, and for suppression of some ventricular arrhythmias. BAD:cardiac depression constipation hypotension

Lipid Management

Very strong scientific evidence supports the benefits of lowering serum cholesterol levels in patients with coronary artery disease. Reductions in cardiovascular mortality, recurrent cardiac events, hospitalizations, angiographic progression of atherosclerotic disease and stroke have been well demonstrated. Benefits have also been shown in women and the elderly. The results of these studies justify aggressive cholesterol evaluation and management as early as possible in the post- MI patient. Nutritional counseling is tailored to individual patient needs, but at its foundation emphasizes the American Heart Association Diet that includes a composition of whole grain products, fruits and vegetables, low fat dairy products, nuts and legumes, lean meats and fish. However, dietary intervention should not preclude the immediate use of pharmacologic therapy to appropriately lower lipid levels to the desirable range as outlined by the 2013 American College of Cardiology/ American Heart Association Guidelines on Cholesterol Management Accordingly, the goal is to use high intensity statins and other pharmacotherapies as needed to decrease LDL cholesterol levels to < 70mg/dl. Patients with hyperlipidemia should be identified while in hospital, and institution of lipid lowering therapy should be done prior to discharge among individuals with a stable metabolic status, and LDL> 70 mg/dl. Monitoring of compliance, side-effects, and efficacy needs to be done by the primary care physician or cardiologist on a regular basis after discharge. The cardiac rehabilitation team can play an important complementary role in such monitoring. Effective communication between the primary care provider and the cardiac rehabilitation team (including the nutritionist) is important to ensure optimal lipid management. Referral to a lipid specialist is recommended when the goals of lipid lowering therapy are not readily attained. Although exercise training may favorably benefit the lipid profile, the effects are often only modest. Thus, exercise training can be used to complement dietary and pharmacologic treatment of lipids, but should not be considered appropriate therapy when used alone. It is important to note that the LDL-cholesterol level can be below a patient's true baseline in the setting of an acute event. Thus, if LDL- cholesterol levels are <70mg/dl when measured within 6 weeks after myocardial infarction, a repeat LDL level should be measured 6 weeks post event to establish a true baseline, upon which therapeutic decisions can be made.

Histopathology of Acute MI

Wavy fiber change: 1-3hr Coagulation necrosis: 4-12hr Nuclear pkynosis: 12hr Neutro infiltration: 6-8hr (early) 48hr (peak) Macrophage infiltration: 4days Vessel proliferation: 3 days Fibroblast prolific: 4 days Collagen deposition: 9 days Granulation tissue peak: 2-4 weeks Mature scare: +6 weeks

24hr+ AF Atrial Remodeling

When AF is maintained for at least 24 hours, there are changes in ion channels (potassium and calcium) that occur at the cellular level that alter the electrophysiologic properties of atrial tissue promoting sustained reentry and increasing activity of electrical triggers. Both reentry and electrical triggers support the perpetuation and permanence of atrial fibrillation (AF begets AF). Concomitant heart disease (i.e ischemia, heart failure, valvular, infiltrative, etc.) or pre-existing atrial disease can lead to structural remodeling of the atria that cause further alteration in the atrial substrate (Figure) Symptoms associated with AF Symptoms vary from patient to patient. Some may have no symptoms while others may experience irregular heartbeat, skipping, palpitations, anxiety, fatigue, exercise intolerance, lightheadedness, dyspnea, or angina.

G. Non-pharmacologic treatment of heart failure

While the management of most patients with heart failure involves the use of drugs, there are several non-pharmacologic interventions that can have important effects on symptoms and the need for drug treatment. A. Treat underlying cause. All patients with heart failure should undergo evaluation for treatable causes, including: • Improvement in coronary blood flow in patients with ischemic heart disease with bypass surgery or catheter-based interventions, • Repair or replacement of dysfunctional cardiac valves in patients with chronic volume or pressure-overload lesions (e.g., MR or AS) or acute bacterial endocarditis, • Surgical correction of hypertrophic cardiomyopathy, congenital defects, or LV aneurysm, • Aggressive management of severe hypertension, usually with medical therapy, although surgical correction of renal artery stenosis or pheochromocytoma may be indicated in specific cases • Pharmacologic control or catheter ablation of arrhythmias that may be leading to heart failure (tachycardia-mediated heart failure B. Eliminate precipitating factors. The recognition, prompt treatment, and, if possible, prevention of precipitating factors are crucial to the successful management of heart failure and the restoration of a well-compensated state. Examples include the treating acute infection, discontinuing negative inotropic drugs, reducing excessive alcohol consumption, and improving in medication compliance. C. Reduce cardiac workload. Patients who work full-time may need to reduce their hours or stop working altogether depending on the physical and mental demands of their job. Exercise is not contraindicated in patients with heart failure. Recent studies have shown that supervised cardiac rehabilitation in selected patients may result in improvement in symptoms and functional capacity, normalization of hemodynamics, an increase in LVEF, and possibly a reduction in hospitalizations and death. Based on these findings, most physicians recommend a program of regular, sub- maximal aerobic exercise. Medically-supervised weight loss may be an important part of therapy for obese patients. D. Reduce excessive salt and water consumption. Expanded extracellular volume is one of the most common problems in heart failure and is due in part to avid sodium retention by the kidney. A salt-restricted diet is an important, but difficult, and often inadequately implemented part of outpatient therapy. In general, the degree of sodium restriction should relate to the severity of fluid retention, with asymptomatic patients restricting intake to <4 gm/day and patients with severe symptoms to <2 gm/day is desirable. As table salt contains 1.9 gm of sodium per teaspoon, a no-added-salt diet is an important starting point. Fluid intake should be limited to 2 liters per day, particularly is serum sodium is <135 mEq/l.

2c. Patent ductus arteriosus (PDA)

With a PDA, the flow in the aorta shunts to the pulmonary artery. The extra flow through the lungs returns to the left heart, resulting in left atrial enlargement and chronic overload of the LV. Prematurity is a major risk factor. Treatment options include medical closure with NSAIDS in the neonatal period (inhibits the prostaglandins keeping it patent). If that fails, it can be closed surgically or in older patients with a transcatheter device occlusion. Exam findings include: A continuous "machinery-like" murmur from flow through the PDA A-fib might be present late in life due to chronic LA overload Coarctation of the aorta A stenotic region in the aorta (generally just proximal to the ductus arteriosus) prevents normal flow of blood. Pulses and blood pressures may be asymmetric in the limbs. Associated with bicuspid aortic valve and Turner's syndrome.

Sinoatrial node exit block.

With sinus exit block, the SA node generates an impulse that is not conducted to the surrounding atrial tissue but rather blocked prior to exiting the node. Since the sinus depolarization cannot be seen on the surface ECG, the exit block must be inferred. Just as with AV block, sinus exit block is classified second and third degree. (First degree sinus exit block is not observable on ECG and does not cause bradycardia). With second degree type I sinoatrial exit block (SA Wenckebach) there is progressive delay of the sinus impulse as it exits the nodal tissue until an impulse is block. The ECG demonstrates progressive shortening of the P-P intervals until the sinus impulse is blocked and no P wave is observed. The resultant "sinus pause" is shorter than two of the preceding P-P intervals. With second degree type II sinoatrial exit block there are consistent P-P intervals prior to the blocked sinus impulse. The resultant "sinus pause" is an exact interval of the preceding P-P intervals (usually two times). Third degree sinoatrial exit block refers to complete block of all sinus impulses prior to exiting the surrounding nodal tissue. No sinus P-waves are seen on ECG. Without junctional or subsidiary escape pacemakers there would be asystole.

Effect on Left Ventricular Function Acute Myocardial Infarction w

With the passage of time, edema, cellular infiltration and finally, fibrosis and scar formation increases the stiffness in the infarcted myocardium and this stabilizes ventricular function by preventing paradoxical systolic wall motion. Further improvement in wall motion occurs as myocytes that were initially reversibly ischemic recover. However, if a sufficient amount of myocardium is injured, the ability of the ventricle to pump an adequate volume of blood is compromised, the cardiac output and blood pressure decrease, and the left ventricular pressure and volume increase. As necrotic myocytes slip past each other, the infarct zone thinsand dilates, especially in large anterior infarctions.

ANS in Cardiac Dysfx.

a. Autonomicnervoussystem-Decreasedperfusionpressure sensed by carotid sinus and aortic arch receptors results in increased sympathetic and decreased parasympathetic activity. Circulating catecholamines are elevated and direct sympathetic outflow to the heart, peripheral vasculature and muscles is increased. Short-term consequences include: i. increased contractility and heart rate to augment cardiac output ii. systemic vasoconstriction to increase preload and stroke volume (venous constriction), and to maintain blood pressure (arterial constriction) iii. redistribution of peripheral blood flow away from the skin, muscles, and kidneys to vital organs. The long-term effects of sympathetic over-activity can be deleterious and include: i. adverse myocardial remodeling with myocyte hypertrophy and apoptosis, and interstitial fibrosis ii. cardiac norepinephrine depletion, beta-receptor down- regulation resulting in beta-adrenergic hyporesponsiveness and chronotropic incompetence iii. proarrhythmia iv. excess activation of the renin angiotensin system (see below) v. attenuated response to natriuretic factors (see below) vi. peripheral vascular endothelial dysfunction. Baroreflex control of adrenergic outflow from the central nervous system is impaired in heart failure. Examples include inappropriate reflex tachycardia in response to vasodilators, and hypotension in response to tilting or upright posture. In addition, desensitization of atrial stretch receptors results in a reduced ability to excrete salt and water in response to increased atrial pressures. While the SNS is important for acutely maintaining cardiac output, its chronic effect is detrimental. Thus, an important treatment component for chronic heart failure is the use of beta-blockers to prevent long-term effects of sympathetic over-activity on the heart.

1. Definitions

a. Cardiomyopathyisaprimaryabnormalityordiseaseofthemyocardium. b. Heartfailureoccurswhenanabnormalityofcardiacfunctioncausesthe heart to fail to pump blood at an output required by the metabolizing tissues or when the heart can do so only with an elevated filling pressure. c. Clinical heart failure is a clinical syndrome resulting from cardiac decompensation and characterized by signs and symptoms of interstitial volume overload and/or inadequate tissue perfusion.

Prognoiss and Effect Factors c. Functional capacity. Peak oxygen consumption (VÓ) measured during a cardiopulmonary exercise test is an objective, reproducible measure of functional capacity and carries important prognostic information. Patients with peak VÓ < 10 ml/kg/min (normal: 20-35 depending on age) have a 1-year survival of 35%, which is markedly reduced compared to patients with peak VÓ > 14 ml/kg/min (1-year survival 80-90%). Peak VÓ can be useful in deciding when to list a patient for heart transplant.

a. Clinical factors. In large clinical trials, the following clinical parameters have been associated with a worse prognosis: older age, diabetes, atrial fibrillation, smoking, alcohol, pulmonary disease, and higher NYHA class (SOLVD trial, mean follow-up 41 months, mortality: NYHA class II 35%, III 51%, IV 64%) b. Ventricular function. In patients with HFrEF, resting left ventricular ejection fraction (LVEF) is a predictor of mortality. In patients with reduced LVEF, right ventricular ejection fraction (RVEF) obtained at rest or peak exercise is a strong independent prognostic factor. d. Neuro-hormones. Plasma NE, renin, ANP, BNP and endothelin levels are increased in patients with heart failure and predict survival. Patients with higher neuro-hormone levels have a worse prognosis. Hyponatremia secondary to elevated renin levels also identifies patients with severe heart failure and reduced 1-year survival. e. Arrhythmias. Approximately 50% of patients with HF have asymptomatic non-sustained ventricular tachycardia on a 24-hour Holter monitor, and this confers a three-fold increased risk of death. However, suppression of ectopic activity with anti-arrhythmic drugs has not been shown to improve survival; and in fact, pro-arrhythmic effects of some antiarrhythmic therapies may increase mortality. Patients with reduced ejection fraction are at increased risk of sudden death due to sustained ventricular tachycardia or ventricular fibrillation. LVEF is consisted the best predictor for determining this risk. There is a marked increase in the risk of death when the LVEF falls below 35% particularly in those with heart failure symptoms. Numerous multicenter trials have shown that an implantable cardioverter-defibrillator (ICD) prevents sudden death due to ventricular tachycardia or ventricular fibrillation in patients with LVEF < 35%. These devices monitor for sustained ventricular arrhythmia and delivery a life-saving shock to restore a normal rhythm.

Confirming MI Cardiac Serum enzyme CKMB

a. Creatine Kinase (CK) is the most important and widely used cardiac enzyme for diagnostic purposes. The CK level begins to rise 6-8 hours after the onset of infarction, peaks at 24 hours, and reverts to normal by 3- 4 days. Creatine kinase is also released from non-cardiac tissues such as skeletal muscle and brain, and can be elevated due to causes other than (e.g. stroke, intramuscular injections, muscle trauma, surgery, convulsions, electrical cardioversion, hypothyroidism). Further specificity can be obtained by examining the CK isoenzymes. Creatine kinase is a dimer of two subunits, an M subunit and a B subunit which combine to form three different isoenzymes identified as (MB, MM, BB, by electrophoresis). Creatine kinase in skeletal muscle is primarily MM. Creatine kinase in the brain is predominantly BB. Creatine kinase in myocardial cells is 80% MM and 20% MB. Since the MB fraction is not found in great quantities in other tissues, an elevated serum MB fraction indicates myocardial damage with a high degree of specificity. Serial measurements of CK and MB isoenzymes can also be used to determine MI size clinically. The peak CK or MB provides an approximate estimate of infarct size, and prognosis.

D. Signs and symptoms of Heart Failure 1. Left-sided heart failure - due primarily to failure of the left ventricle

a. Difficulty breathing. The most common symptoms of heart failure involve difficulty breathing including exertional dyspnea, orthopnea, paroxysmal and nocturnal dyspnea. Mechanisms of difficult breathing include pulmonary venous congestion and transudation of fluid into the interstitium leading to decreased lung compliance, increased airway resistance, hypoxemia, and V/Q mismatch. Stimulation of J receptors leading to an increased ventilatory drive and reduced blood flow to respiratory muscles may cause lactic acidosis and the sensation of dyspnea. b. Fatigue and weakness. Leg weakness is due to decreased perfusion of skeletal muscles and inability to increase blood flow with exercise. Impaired vasodilation and altered skeletal muscle metabolism during exercise also play a role. Other causes of fatigue in patients with HF include excess diuresis leading to hypotension, and medications (e.g., beta-blockers). c. Mental dullness and confusion. May result from decreased cerebral perfusion. d. Nocturia. Decreased urine output during the day secondary to renal vasoconstriction may result in nocturia or urinary frequency at night.

F. Diagnostic Evaluation 1. Laboratory.

a. Dilutionalhyponatremiamaybepresentinsevereheartfailure. b. Serumpotassiumlevelsmaybenormal,low(duetothiazideorloop diuretics), or high (due to marked reductions in GFR and/or ACE inhibitor therapy). c. Bloodureanitrogenandcreatininemaybeelevatedduetodecreased renal blood flow and GFR (prerenal azotemia). d. Liverfunctiontestabnormalitiesmayreflecthepaticcongestion. 2. Chest x-ray. The cardiac silhouette may be enlarged (cardiothoracic ratio > 0.5). Pulmonary venous congestion may be manifested by progressive findings of pulmonary vascular redistribution (constriction of lower lobe vessels with dilation of upper lobe vessels), interstitial edema (Kerley B lines), and alveolar edema ("butterfly" pattern). In patients with chronic heart failure, higher pressures can be accommodated with fewer radiologic signs due to enhanced lymphatic drainage. Pleural effusions are common when biventricular failure is present.

F. Pharmacologic treatment of chronic heart failure DIURETICS

a. Diuretics: Euvolemia is usually maintained with oral furosemide. Torsemide or bumetanide may also be used, particularly when GI absorption is an issue. Maintenance of an optimal volume status is important for controlling symptoms due to lung congestion (i.e., dyspnea on exertion) and for preventing hospitalizations due to decompensation, but probably does not affect overall survival. Patients often weigh themselves at home to ensure they are not retaining fluid and take more or less diuretic based on fluctuations in their daily weight, according to their doctor's instructions.

1. Abnormalimpulseformation There are two mechanisms:

a. Enhancedautomaticityoccursinthepresenceofreduced maximum diastolic potential (i.e. more positive resting membrane potential) and enhanced phase 4 spontaneous depolarization. This is seen in areas of diseased tissue with "leaky" membranes unable to maintain normal resting gradients. Spontaneous inward current can achieve threshold activation in these partially depolarized cells, often at fast rates. Enhanced automaticity can be initiated by excessive catecholamines. b. TriggeredactivityisduetothespontaneousreleaseofCá+ from the sarcoplasmic reticulum during phase 4. This small release of Cá+ activates an inward Na+ current via Na+/Cá+ exchanger and this causes a further rise in the membrane voltage, which reaches threshold for activation of the voltage- gated sodium channel. Trigger activity occurs in the setting of intracellular calcium overload (e.g. heart failure, high sympathetic tone, exercise). This mechanism is seen with digitalis intoxication and with agents that prolong repolarization.

Mechanical Complications of MI LVF

a. Left Ventricular Failure - The severity of left ventricular pump failure in the setting of AMI is classically categorized using Killip Classification. Killip class I designates no pump failure. Killip II designates mild pulmonary congestion. Killip III designates pulmonary edema and Killip IV designates cardiogenic shock (systolic BP <90mmHg and evidence of peripheral hypoperfusion). The Killip classification is still frequently used and is predictive of in-hospital mortality. Patients with mild pulmonary congestion are treated with diuretics, oxygenation and vasodilations. Patients with pulmonary edema require more intensive treatment, depending upon the severity. Mechanical ventilation is often required. Diuretics, oxygenation, morphine and vasodilations are standard treatments for pulmonary edema. Cardiogenic shock is a condition of severely depressed cardiac output, hypotension (systolic BP<90mmHg) and inadequate perfusion of tissues that develops when > 40% of the LV mass has infarcted. MI complicated by cardiogenic shock is associated with an in-hospital mortality of 50-80%. It is imperative to maintain adequate systolic blood pressure to ensure adequate perfusion to the coronary, renal and cerebral perfusion beds. Blood pressure and cardiac output can be increased using inotropic agents (eg. dopamine or dobutamine). Such patients can also be stabilized by the insertion of an intra-aortic balloon pump, a mechanical device, which is inserted into the aorta via the femoral artery and consists of an inflatable, flexible chamber. By inflating during diastole and deflating during systole, the balloon pump increases perfusion to the periphery and coronary arteries and aids in the ejection of blood from the failing heart. Emergent revascularization with coronary angioplasty and coronary bypass surgery has been reported to improve hospital survival in MI patients presenting with cardiogenic shock and should be considered.

Other Complications of MI

a. Pericarditis - Transmural myocardial infarction frequently causes epicardial and pericardial inflammation during the healing phases, usually during the first week following acute MI, The inflammation causes sharp pain which is worsened by respiration or position and classically a three component friction rub on physical exam. The quality of the pain and the presence of a rub on exam distinguishes this symptom from post MI angina. Pericarditis is usually effectively treated with anti-inflammatory medications. b. Dressler's Syndrome, or post myocardial infarction syndrome can occur 2- 10 weeks following an AMI. This autoimmune process produces pericarditis resulting in a pericardial friction rub and pleuritic chest pain. It is treated effectively with anti- inflammatory medication. c. Thromboembolism - A mural thrombus forms adjacent to infarcted region and occurs in approximately 1/3 of MI's. It is more common in anterior Q- wave infarctions. Peripheral embolization occurs in approximately 4% of patients. Anticoagulation is generally recommended for 3-6 months in patients with documented thrombus by echocardiography, LV aneurysm or severely depressed LVEF (<20%), unless contraindicated.

2. Right-sided heart failure - although these findings may occur with isolated failure of the right ventricle, most commonly they reflect failure of the left ventricle with passive congestion and/or failure of right ventricle

a. Peripheral edema. The most common sign of heart failure is peripheral edema. Elevated systemic venous pressures may result accumulation of fluid in the extracellular spaces. Due to hydraulic forces, fluid usually accumulates first in dependent areas, most often the legs, which may worsen during the day as the patient is upright and improve overnight when supine. May result in a large increase in weight over a short period of time. b. Ascites and GI tract edema. Venous congestion of GI tract and liver may cause edema of GI tract leading to malabsorption, ascites and liver congestion that may be associated with nausea, bloating, anorexia, early satiety and constipation and right upper quadrant abdominal discomfort as the liver capsule is stretched. As with peripheral edema, may be associated with rapid weight gain.

Ischemic Complications of MI

a. Post MI Angina - Typical angina occurring during the first 1-2 weeks following acute MI generally indicates the need for cardiac catheterization to define the patient's coronary anatomy. Spontaneous episodes of rest angina, or angina at a low workload (either with daily activity or during an exercise stress test) indicate a higher rate of reinfarction or predict refractoriness to medical therapy. Cardiac catheterization is usually performed with a view toward percutaneous (PTCA) or surgical (CABG) revascularization. b. Reinfarction or Infarction Extension-Recurrent prolonged angina associated with further evidence of myocardial damage by cardiac enzymes or ECG is referred to as infarct extension and carries a poor prognosis. Such patients are usually studied with cardiac catheterization with a view toward revascularization.

Commonly encountered clinical conditions that cause shock

a. Septicshock-Withsepsis,vasodilationiscausedbysystemic inflammatory mediators. As a result both SVR and PVR will be very low and cardiac output will be proportionately high to compensate for reduced blood pressure. In patients without heart disease, heart functioning is not compromised, so intracardiac pressures will be essentially normal to low. b. Cardiogenicshock-Cardiogenicshockisaconditionofreduced tissue perfusion because of the inability of the heart to pump an adequate amount or blood. By definition the cardiac output is low. In response to hypoperfusion, vasoconstriction occurs via release of endogenous vasopressors (norepinephrine and angiotensin II); therefore the SVR will be high. The diastolic filling pressure (PCWP) is high because of left ventricular dysfunction. c. Massive pulmonary embolism - A massive pulmonary embolism results in isolated right ventricular failure; therefore the PCWP is normal. The embolism causes "stenosis" of the pulmonary vascular bed therefore the PVR will be high. Cardiac output is low because of right-sided failure and poor left ventricular filling. This causes hypotension. In response to hypotension, vasoconstriction occurs via release of endogenous vasopressors; therefore the SVR will be high. The right-sided pressures including pulmonary arterial pressures are elevated. d. Hypovolemicshock-Withhypovolemicshockallpressure measurements are low. Cardiac output is low because under filling. SVR is high due to compensatory vasoconstriction in response to hypotension. e. Cardiactamponade-Incardiactamponade,fluidaccumulatesin the pericardial space and this restricts ventricular filling in diastole. When the pressure within the pericardium equals the diastolic filling pressures of the right atrium and right ventricle there is impaired ventricular filling, reduced cardiac output and hypotension. The hallmark of cardiac tamponade is equalization of all diastolic pressures (RA pressure = RV diastolic pressure = PA diastolic pressure = PCWP = intrapericardial pressure). CO is reduced. SVR is high due to compensatory vasoconstriction in response to hypotension.

Chronic HF ACEI ARBS

b. ACE inhibitors and ARBs: RAAS blockade with an ACE inhibitor or an angiotensin receptor blocker (ARB) exerts vasodilatory effects (mixed) that decrease left ventricular afterload and preload. While these hemodynamic effects are beneficial with regard to improving myocardial function and symptoms, the most important benefit of RAAS inhibition is to decrease the adverse effects of the RAAS on the progression of myocardial disease due to adverse remodeling. In general, these agents decrease all-cause mortality by about 25%, and these benefits appear to be shared by all agents in this class.

RAAS in Cardiac Dysfx,

b. Renin angiotensin aldosterone system (RAASJ): The RAAS acts in concert with the sympathetic nervous system (SNS) to maintain arterial pressure. Stimuli for renin secretion by the kidney include: i. decreased renal perfusion pressure ii. adrenergic stimulation of beta-receptors in the juxtaglomerular apparatus iii. reduction in sodium (due to salt restriction and diuretics) sensed by the macula densa Angiotensin II, formed by the action of angiotensin converting enzyme (ACE) on angiotensin I, is a potent vasoconstrictor. Elevated levels in heart failure result in systemic arterial and venous constriction, and intravascular volume expansion. Volume expansion is due to both direct hypothalamic stimulation of thirst and increased aldosterone secretion by the adrenal cortex, which in turn increases sodium reabsorption from the distal convoluted tubule of the kidney. Vasoconstriction and volume retention may initially be compensatory in helping to maintain arterial pressure and stroke volume, but over time contribute to clinical decompensation. The retained fluid tends to accumulate as interstitial edema instead of remaining in the circulation. Chronic volume expansion does not maintain improved renal perfusion because of the compromised cardiac output. Persistently impaired renal perfusion leads to chronic RAAS activation and progressive volume overloaded. Greater than 90% of ACE in the body is found in tissues, and less the 10% is in the circulation. Myocardial production of ACE is increased in heart failure, and stimulation of myocardial angiotensin receptors leads to myocyte hypertrophy and fibroblast proliferation. These tissue effects contribute to adverse myocardial remodeling that leads to further cardiac dysfunction. Aldosterone is also a potent stimulus for myocardial hypertrophy and fibrosis, and contributes to ventricular remodeling. Blockade of the renin-angiotensin aldosterone system with ACE inhibitors and angiotensin receptor blockers (ARB), which opposes both the short and long term adverse effects of RAAS activation, is a major part of chronic heart failure treatment.

Mechanical Complications of MI RVI

b. Right Ventricular Infarction usually occurs in with inferior infarctions. The right ventricular failure causes increased right-sided filling pressures characterized by increased jugular venous distension. The right ventricle does not adequately pump blood to the left ventricle. The left ventricle is underfilled resulting in systemic hypotension. Treatment is fluid expansion, which resultsin adequate filling of the left ventricle. In other types of myocardial infarction, fluid expansion is contraindicated. Therefore, recognition of right ventricular infarction is critical in the care of acute MI patients and should be considered in all patients with an inferior MI. Right ventricular infarction can be diagnosed using electrocardiographic leads positioned over the right chest, by echocardiography (which shows an enlarged and hypocontractile right ventricle) or by catheterization (which shows increased right ventricular filling pressures and decreased left ventricular filling pressures).

Confirming MI Cardiac Serum enzyme Troponin

b. Troponin - Quantitative serum assays for cardiac specific Troponin T (c TnT) and I (c TnI) can detect even minor degrees of myocardial necrosis. In patients with acute MI, serum troponin levels begin to rise at 3 hours from the onset of chest pain and remain elevated for 7-10 days. Therefore, the troponin assay is potentially useful in patients who present soon after the onset of chest pain (before the CK level rises), and many days after acute MI (after the CK level returns to normal). Several recent studies have shown that among patients with acute coronary syndromes and normal CK-MB levels, elevated troponin concentrations identify a subset of patients with increased risk of recurrent ischemia or death. Furthermore, the higher the troponin level, the greater the risk for future cardiovascular events.

Ventricular Tachycardia 8. Complications of MI Electrical Complications

b. Ventricular Tachycardia - Occurs in 10-40% of patients with MI. VT usually occurs late in the course of large transmural infarction. VT is a marker of increased mortality. It can be precipitated by electrolyte disturbances, acid- base disturbances, hypoxia, hypotension or digitalis toxicity. If sustained, requires immediate cardioversion and may require antiarrhythmic therapy for suppression. Ventricular tachycardia is more commonly seen as a late complication associated with MI and typical arises from the boarder zone of the infarcted area and normal myocardium. Numerous clinical trials have shown that patients with severe left ventricular dysfunction (EF < 30-35%) are at particular risk for suffering a life threatening ventricular arrhythmia after myocardial infarction. Implantable cardioverter-defibrillators (ICD) have been shown to improved mortality in these patients by delivering a life-saving shock to restore a sinus rhythm.

2b. VSD

b. Ventricular septal defect (VSD) A VSD is a communication between the left and right ventricles which typically allows for left-to-right shunting. Unlike the ASD, the VSD is a volume load on the left ventricle. Since the ventricles contract together, the left ventricle ejects the blood through the VSD directly to the main pulmonary artery. Therefore the extra volume never sits in the right ventricle. The lungs, left atrium and left ventricle receive the extra volume. Shunting is proportional to size of the defect and the differential between pulmonary vascular resistance and systemic vascular resistance. There are 4 major types of VSDs, inlet (associated with trisomy 21), membranous, muscular and outlet. Inlet and outlet VSDs do not spontaneously close. Exam findings of VSD include: A holosystolic murmur made by the defect itself. In general, the higher the pitch of the murmur, the smaller the defect. There may also be an ejection murmur at the ULSB from increased flow across the pulmonic valve. Membranous defects may interfere with the aortic valve, causing murmurs of aortic insufficiency. Large defects may also be associated with a diastolic rumble Large defects are associated with pulmonary hypertension and a single S2 will be heard If RVH is present, there may be a parasternal heave.

8. Complications of MI Electrical Complications2

c. Accelerated Idioventricular Rhythm (AIVR) - Most episodes are short and self- terminated. Enhanced automaticity of ischemic ventricular myocardium is often the mechanism. AIVR is often slow < 110 bpm, hemodynamically tolerated, and usually does not require specific therapy. d. Sinus tachycardia is commonly seen, can increase myocardial oxygen demand and requires treatment. Persistent sinus tachycardia is seen in patients with extensive myocardial damage, and indicates a poor prognosis. e. Supraventricular tachycardia, atrial flutter and atrial fibrillation can be seen in patients with AMI. There is a greater urgency for slowing the heart rate in infarction patients with these arrhythmias, since tachycardia increases myocardial oxygen demand and can worsen myocardial ischemia and damage. Patients with atrial fibrillation and flutter with rapid ventricular response who have evidence of myocardial ischemia (angina) should be treated with immediate electrical cardioversion.

Chronic HF Rx B Block

c. Beta-adrenergic receptor blockers: By blocking the adverse effects of sympathetic stimulation to cause pathological myocardial remodeling, beta blockers can slow or even reverse the progression of the underlying disease process. These benefits are associated with improvements in cardiac size and function, exercise capacity and survival. The survival benefit of beta- blockers is on the order of 35%, and is additive to that of RAAS inhibitors discussed above. While the benefits of beta-blockade are likely a class effect, the agents that have been proven to be of value and are most commonly used in the U.S. are metoprolol (Toprol) and carvedilol (Coreg). Beta-blockers are negative inotropes and therefore may initially decrease cardiac output. Therefore, beta-blockers are initiated only in compensated patients and in very low doses (e.g., 6.25 mg of metoprolol per day). The dose is then gradually increased over several weeks until full therapeutic doses are achieved (e.g., 150 - 200 mg per day of metoprolol).

Mechanical Complications of MI Aneurysm

c. Infarct Expansion, Aneurysm Formation -During the several weeks following an AMI, the myocardium undergoes thinning and regional dilatation. If the thinning is relatively circumscribed, it can result in a ventricular aneurysm. An aneurysm can cause persistent ST elevation on the electrocardiogram and can be diagnosed by echocardiography or radionuclide ventriculography. Aneurysms can cause refractory congestive failure and ventricular arrhythmias and occasionally require surgical removal.

ANP in Cardiac Dyzfx. d. Argininevasopressin:Circulatinglevelsofthepituitaryhormone arginine vasopressin (antidiuretic hormone) are elevated in patients with LV dysfunction and heart failure. In addition, levels are abnormally responsive to reductions in plasma osmolality or increases in atrial stretch, and thus contribute to the inadequate ability to excrete free water and thereby increasing intravascular volume.

c. Natriureticpeptides:Circulatinglevelsofatrialnatriureticpeptide (ANP) and brain natriuretic peptide (BNP) are elevated in heart failure. ANP is stored mainly in the right atrium and released in response to increased atrial stretch or pressure. ANP release causes vasodilation and natriuresis, inhibition of renin secretion, and angiotensin II antagonism, which counteract potential deleterious effects of SNS and RAAS activation. BNP is stored and secreted by the ventricles in response to strain, and like ANP, also causes vasodilation and natriuresis. Clinically, BNP can be measured with a blood lab test and a high level indicates left ventricular strain, and is consistent with heart failure. This test is helpful when the physical exam is difficult and may help identify the cause of a patient's shortness of breath. Synthetic human BNP (nesiritide) can be administered as a continuous IV infusion to improve hemodynamics and symptoms in patients with decompensated heart failure.

Mechanical Complications of MI Free wall rupture

d. Free wall rupture - Myocardial thinning can progress to disruption of the structural integrity of the left ventricular free wall, the intraventricular septum or of a papillary muscle. Rupture usually occurs 3-5 days following the onset of an acute MI. Rupture of the left ventricular free wall usually is catastrophic and lethal. Free wall rupture often presents as sudden hypotension and shock secondary to LV failure and acute cardiac tamponade.

Spironolactone Chronic HF

d. Spironolactone: Despite optimal use of an ACE inhibitor or ARB, there may still be detrimental levels of aldosterone, so that the addition of aldosterone blockade with spironolactone yields additional benefits in terms of survival. In this setting spironolactone is used in low doses of 25 mg per day or less in order to avoid the complication of hyperkalemia.

Hyrag NG Chronic HF

e. Hydralazine/Nitrates: The combination of hydralazine and long-acting nitrates has been shown to improve survival in self-described black patients by 36% (V-Heft trial). The two meds working together will cause profound vasodilation (the hydralazine) and venodilation (the nitrate), thus decreasing preload and afterload. This medication should be started in black patients and patients of any race who cannot tolerate an ACE-I or ARB (patients with bilateral renal artery stenosis, etc.).

Mech Comp MI IV Sept Rupture

e. Rupture of the intraventricular septum is usually diagnosed by a new murmur on physical exam. It is important to carefully examine acute MI patients daily. A ventricular septal defect produces a harsh holosystolic murmur heard best over the precordium and radiating to the back. The diagnosis is confirmed by echo/Doppler or by catheterization. The defect results in shunting of oxygenated blood from the left ventricle to the right ventricle, resulting in right ventricular overload. Initial therapy includes vasodilator therapy to reduce the left to right shunting and intra-aortic balloon counterpulsation. Ventricular septal rupture usually require urgent surgical repair.

Digoxin Chronic HF

f. Digoxin: Digoxin inhibits the Na/K ATPase leading to increased calcium levels in the cardiac myocyte thereby increasing contractility. In addition, digoxin decreases sympathetic tone and increases parasympathetic tone. While these effects are beneficial and are associated with improvements in symptoms, they do not appear to improve survival. Thus, although digoxin was the traditional mainstay of HF treatment, it has been supplanted by RAAS inhibitors and beta-blockers. Digoxin is reserved as a second line agent for patients who remain symptomatic despite optimal standard therapy.

Mechanical Complications of MI Pappily

f. Rupture of a papillary muscle also causes a holosystolic murmur on physical examination and acute pulmonary edema secondary to severe mitral regurgitation. It is distinguished from a septal rupture by echo/Doppler or by catheterization. Similar to septal rupture, rupture of a papillary muscle is treated with vasodilator therapy, intra- aortic balloon counterpulsation and urgent surgical repair.

8. Complications of MI Electrical Complications3

f. Sinus bradycardia occurs commonly during the early phase of AMI. Often occurs in inferior MI due to increased vagal tone. Usually does not require specific treatment, though rarely treatment with atropine or temporary transvenous pacemaker is necessary. g. First and second (Mobitz I) degree heart block commonly occur in patients with AMI. Often due to increased vagal tone and does not require specific treatment. The block is at the level of the AV node and usually responds to Atropine. Drugs, which might worsen AV block (beta blockers, verapamil, digoxin), should be used with caution. h. Mobitz II second degree heart block, third degree heart block, and bundle branch block often indicate damage lower in the ventricular conduction system and have worse prognostic implications. Third degree block associated with hypotension is an indication for temporary and perhaps permanent cardiac pacing. Temporary pacing should be used in patients with a high risk of developing complete AV block, i.e. patients with Mobitz II block, with alternating bundle branch block and with bilateral bundle branch block. Patients with a combination of first degree AV block and either right or left bundle branch block should be monitored closely and an external pacing device should be made available.

Cardiomyopathy

is a primary abnormality of the myocardium. It usually results in congestive heart failure when heart function is compromised to the point that the cardiac output is insufficient to meet the metabolic needs of tissue or when an elevated filling pressure is needed to achieve this cardiac output. Many patients may have cardiomyopathy but no overt signs of heart failure early in the disease process. There are three main types of cardiomyopathy: Dilated cardiomyopathy Hypertrophic cardiomyopathy Restrictive cardiomyopathy

Polymorphic VT (PMVT)

is a type of ventricular tachycardia that has a complex mechanism reflected in a chaotic, rapid ventricular rate. The QRS morphology of each beat is variable with a rapidly changing axis (see example). This rhythm is most often the result of acute ischemia from a highly stenotic or blocked coronary artery. In the setting of a prolonged QT interval, this tachyarrhythmia is known as "torsade de pointes" or twisting of points due to the rapidly changing axis. QT interval prolongation may be congenital as the result of a membrane channel mutation, or acquired as the result of a metabolic abnormality (hypokalemia, hypomagnesemia) or QT prolonging drug (Class IA or Class III anti- arrhythmic drug). PVMT most often causes cardiac arrest and emergent defibrillation is required to restore sinus rhythm. The inciting cause should be corrected to prevent recurrent PMVT.

Atrial Fibrillation

is the most common sustained tachyarrhythmia in man. Multiple reentrant circuits circulating simultaneously in both atria produces a rapid and chaotic atrial rhythm marked by irregular rapid undulations on surface ECG. (See Session on atrial fibrillation)

Arrhythmias (both bradycardic and tachycardic) result from disorders of: 1. Impulseformation 2. Impulsepropagation Disorders of Impulse Formation Sinus node dysfunction/Sick sinus syndrome (SSS

manifest as failure of the sinus node to generate impulses at a rate appropriate to the physiological situation. Examples are: Inappropriate resting bradycardia Chronotropic incompetence - The sinus node fails to increase frequency of impulse generation appropriately with exercise or sympathetic nervous system stimulation. Tachy-brady syndrome - Tachyarrhythmias (most commonly atrial fibrillation) overdrive suppress sinus node impulse formation and there is a physiological recovery period of the sinus node when the tachyarrhythmia terminates. This recovery period is very prolonged when the sinus node is diseased. A period of prolonged asystole (>5 seconds) after sudden termination of the tachyarrhythmia may result in lightheadedness or syncope. This sinus pause is also called an offset pause. Tachy-brady syndrome may also manifest as resting sinus bradycardia and paroxysmal tachycardia (usually atrial fibrillation). The resting bradycardia prevents treatment of tachycardia with antiarrhythmic therapy because these agents will further impair sinus node function and cause more profound bradycardia. There are numerous intrinsic and extrinsic factors that cause sinus node dysfunction. The most common intrinsic etiologies are age-related fibrosis, ischemia due to coronary artery disease, surgical trauma, or infiltration with amyloidosis or sarcoidosis. The most common extrinsic factors are drugs that suppress the pacemaker current (beta-blockers, calcium channel blockers) and metabolic causes. Channelopathies that effect impulse formation are rare familial causes of sinus node dysfunction.

Sinus Tachycardia

results from enhanced automaticity of the sinus node. Sinus tachycardia is most often a reflection of vagal withdrawal and enhanced catecholamine secretion. The presence of sinus tachycardia is normal in the setting of physiologic stress including exercise, fever, hypovolemia, hypoxia, anemia, low cardiac output, pain, anxiety, and pregnancy. Sinus tachycardia can be the presenting sign in pathological states such as thyrotoxicosis or pheochromocytoma. Rarely, an underlying cause of sinus acceleration cannot be determined despite extensive evaluation and this is termed inappropriate sinus tachycardia.

Atrial Flutter

results from reentry within atrial tissue. Most commonly seen in the setting of structural heart disease and enlarged atria from aging, hypertension, or valvular heart disease. The most common type of atrial flutter is a single reentrant circuit that circulates in a counterclockwise direction in the right atrium. This produces a characteristic atrial rate of 300 beats per minute with a negative saw tooth pattern in the inferior ECG leads. The AV node characteristically blocks every other impulse creating a ventricular response of 150 beats per minute. Treatment is with AV nodal blocking agents or ablation. Patients with atrial flutter are at increased risk of thromboembolism and their CHA2DS2-VASc score determines the need for anticoagulation to prevent stroke. (See Session on Atrial Fibrillation)

A very contractile heart

will "get ahead" of the venous return by ejecting large volumes, resulting in a low end-diastolic volume before the next beat, and resultant decreased end diastolic wall tension. Lower wall tension causes a corresponding drop in the LV contractility (via the Frank-Starling mechanism). The heart thus reaches an equilibrium wherein the blood volume coming in is equal to the blood volume going out.However, the equilibrium occurs at a lower end-diastolic pressure because the LV is contractile enough that blood volume never builds up.

Conversely, a failing heart will

will "get behind" on the venous return by ejecting smaller volumes, which results in increased end-diastolic volume and wall tension before the next beat. The high wall tension from the blood that wasn't ejected increases the contractility of the LV via the Frank-Starling mechanism until equilibrium is reached between the blood volume coming in and the blood volume going out. The fact that the LV must be distended and tense before equilibrium is reached implies that the heart operates at a higher end-diastolic pressure. This elevated pressure is transmitted backward though the venous circulation causing many of the symptoms of heart failure. This equilibrium between venous return and cardiac output can be demonstrated graphically by plotting the venous return curve against the starling curve.

Takotsubo cardiomyopathy

y is an uncommon cause of DCM that has an increased prevalence in women. Under acute emotional stress, excessive catecholamines and hyperactivation of the RAAS system can causes sudden pathological stunning and remodeling of the left ventricle. Classically, a pattern of "apical ballooning" is observed on echocardiogram or left ventriculography. The basal segments tend to be hypercontractile while the apex is hypokinetic and even dyskinetic. This condition is also called stress cardiomyopathy or "broken heart syndrome." The inciting trigger or stress may be the death of a loved one, the sudden failure of a personal relationship, or even heated dispute. Takotsubo cardiomyopathy may mimic an MI with chest pain, elevated cardiac enzymes and ECG changes. Often the diagnosis is made when no coronary disease is found in a patient with suspected MI at the time of cardiac catheterization. Treatment for Takotsubo cardiomyopathy includes ACE-I/ARB and a beta blocker. Typically, LV function normalizes over a period of a week to a couple of months.

Inotropic Drugs (Glycosides, B-Agrenergic Asgonists, PDE Inhibitors) B-ad

β-Adrenergic Agonists Dobutamine Oral β1-selective agonist that increases cAMP increases force of contraction Use; Acute Heart Failure Bad: Cardiac arrhythmia

Agents that Inhibit Cardiac Remodeling Bblock ACE I Minteral Spiro

β-Blockers Metoprolol oral B-1 Bad: broncho, cardiac depressions v bock, Brady cardia, acute decomp ACE I Lininospril: lower AII Bad: hyperkalemia, cough, teratogen Mineralcortoid Antagonist: Spironolactone: block aldosterone receptor in CT/ZCD Bad; hyperkalemia ; man boobs effect: limit cardiac remodeling Use: chronic HF

The slope of the Starling curve is affected by factors that increase or decrease contractility:

• An increase contractility increases the slope of the Starling curve • A decease in contractility decreases the slope of the Starling curve The Starling effect ensures that the amount of blood that enters the heart will roughly equal the amount of blood ejected out of the heart but as the graph above shows, this is only roughly true on a beat-to-beat basis. At a given preload, the heart can eject larger or smaller stroke volumes based on intrinsic or extrinsic factors that affect its contractility. From this principle we will conclude that how contractile the heart is determines the equilibrium diastolic pressure at which it operates.

Assessment of cardiac function from pressure measurements CO • Fick principle

• Fick principle is based on the assumption that the amount of oxygen used by peripheral tissues is equal to the amount of oxygen extracted from the blood. To do a Fick calculation you must measure the oxygen saturation in the venous blood (by using the Swan to draw a blood sample from the PA) and also the total body oxygen consumption or VÓ (extrapolated from minute ventilation and end tidal CÓ, which are measured by having the patient breathe into a spirometer). The calculation is as follows: VÓ = CO x (ÓSatarterial - ÓSatvenous) CO = VÓ/(ÓSatarterial - ÓSatvenous) This method is most accurate for low cardiac output states and irregular rhythms.

Assessment of cardiac function from pressure measurements CO • Thermo dilution

• Thermo dilution is a technique where cold saline injected in a proximal cardiac chamber. The saline is mixed and warmed by blood. The rate at which the temperature of the distal chamber changes is proportional to the CO. This method is most accurate for high-output states but inaccurate with irregular rhythms or with tricuspid regurgitation.