DRx 2 Cardiovascular Module MS 221

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.

Renin-Angiotensin System Drugs

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

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

Losartan blocks AT1 receptors hypertension hyperkalemia, teratogen

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.

Hyperlipoproteinemia Drugs

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

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.

Power of Study

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

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).

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 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.

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).

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.

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.

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.

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.

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

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

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.

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.

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

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.

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).

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

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

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.

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)

Reverse cholesterol transport pathway

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

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.

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

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

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)

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 ++.

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.

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.

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.

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

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.

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).

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.

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

Furosemide block Na/K/Cl transporter in ThAL hypertension, heart failure, edema, hypercalcemia 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.

1. Thiazide Diuretic (oral) Drugs for Hypertension

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

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%.

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

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.

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.

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

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.

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.

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.

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

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.

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

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

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.

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

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.

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.

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

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

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.

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.

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.