cardiovascular review and notes (hah)
TRANSCRIPT
Sources
• My lecture notes• Review lecture recordings• Goljan’s cardiovascular lecture• USMLE World cardiovascular questions• First Aid for Step 1
Atherosclerosis• Thickening of artery wall due to build-up of
atheromatous plaque• Major risk factors:– Diabetes (#1 risk factor)– Smoking– Hypertension– Dyslipidemia (high LDL, low HDL)– Obesity– Family history of ischemic heart disease– ↑ serum homocysteine
• Locations: abdominal aorta > coronary artery > popliteal artery > ICA > circle of Willis
Pathogenesis of atherosclerosis: reaction to injury hypothesis
Endothelial injury
↑ blood vessel permeability
Infiltration of intima by LDL, platelets, monocytes
Macrophages & platelets secrete growth factors (e.g. PDGF)Foam cells (LDL phagocytosed by macrophages & SMCs)
Formation of fatty streak (benign; seen in all people aged >10)
SMCs in media migrate into intima and proliferate intimal hyperplasia
SMCs produce collagen
Fibrofatty atheroma (fibrous plaque)
Angina pectoris• Severe chest pain due to ischemia of myocardium• Stable angina: chest pain with exercise, emotional distress, eating
(3 E’s) lasting 30 sec. – 30 min.– Cause: occlusion of coronary artery by stable plaque
• Requires lumen narrowing >75%– ECG: ST segment depression– Relieved by rest & nitroglycerin
• Unstable angina: worsening chest pain at rest– Cause: plaque rupture partial thrombosis– ECG: ST segment depression/elevation
• Variant (Prinzmetal’s) angina: – Cause: coronary artery vasospasm– ECG: ST segment elevation– β blockers can worsen coronary vasoconstriction contraindicated
Myocardial infarction• Irreversible necrosis of myocardial tissue resulting from acute ischemia• Causes:
– #1 cause: atherosclerosis• Sudden plaque rupture total thrombosis
– MI with normal coronary arteries: cocaine abuse• Cocaine causes intense vasoconstriction
• Location: LAD > RCA > circumflex– LAD anterior MI (leads V1 – V4)– RCA inferior MI (leads II, III, aVF)– Circumflex lateral MI (leads I, aVL, V5, V6)
• Symptoms:– Severe chest pain lasting >30 minutes
• May radiate to L arm and/or jaw• NOT relieved by rest or nitroglycerin
– Anxiety/dread (sense of impending doom)
Diagnosis of MI• At least 2 of the following– History: clinical Hx of ischemic-type chest pain lasting >20
minutes– ECG: ECG changes suggestive of MI (ST elevation,
pathologic Q waves)• In the 1st 6 hours post-MI, ECG is the gold standard• If patient has LBBB, MI cannot be diagnosed via ECG
– Enzymes: elevation of serum cardiac biomarkers (most sensitive & specific test for acute MI)• Cardiac troponin (cTnT, cTnI)• Creatine kinase-MB (CK-MB)• Myoglobin• LDH1:LDH2 ratio
Serum cardiac biomarkers• Cardiac troponin (cTnT, cTnI)
– Best marker (highest sensitivity & specificity)
– Rises within 4 – 6 hours– Remains elevated for up to 2 weeks
• Creatine kinase-MB (CK-MB)– Non-specific (also found in skeletal muscle)– Rises within 4 – 6 hours– Remains elevated for up to 3 days can be
used to diagnose re-infarction• Myoglobin
– Non-specific (also found in skeletal muscle)– Rises after 1 hour (1st biomarker to appear)– Remains elevated for 1 day
• LDH1:LDH2 ratio– In normal serum, LDH2 > LDH1– Acute MI LDH1 > LDH2– Non-specific
Management of MI• “MONAH-B”
– Morphine• ↓ pain ↓ anxiety ↓ SNS activity ↓ HR & contractility ↓ cardiac output ↓ myocardial
oxygen demand– Oxygen supplementation
• Optimizes blood’s oxygen carrying capacity– Nitrates
• Dilation of veins & arteries ↓ preload & afterload ↓ cardiac output ↓ myocardial oxygen demand
• Risk of life-threatening hypotension in patients taking sildenafil (Viagra)– Aspirin
• Irreversible COX inhibition ↓ TxA2 ↓ platelet aggregation prevention of recurrent coronary artery thrombosis
• If allergic use clopidogrel (ADP receptor blocker)– Heparin
• Immediate anticoagulation– β-blocker
• ↓ SNS activity ↓ HR & contractility ↓ cardiac output ↓ myocardial oxygen demand
Management of MI• Myocardial reperfusion
– Thrombolytics / coronary angioplasty: only if symptom onset within 12 hours• After 12 hours, risks of therapy > benefits
– Coronary artery bypass grafting (CABG)• Indications:
– Disease of L main coronary artery– 3-vessel disease (LAD, RCA, circumflex)– L ventricular dysfunction
• Vessels used:– Internal mammary artery (best)– Radial artery– Greater saphenous vein
• Post-MI medications: “ABC”– Aspirin– β-blocker– Cholesterol-lowering drug (statin)
• Target LDL: <70 mg/dl
MI complications• 1 – 3 days:
– Arrhythmias: most common complication of MI• Ventricular fibrillation: #1 cause of sudden death in acute MI
– CHF and pulmonary edema– Cardiogenic shock: seen only with large infarcts (>40% of L ventricle)
• Seen with occlusion of all 3 coronary vessels (LAD, RCA, circumflex)• 3 – 7 days:
– Myocardial rupture• Free wall of ventricle hemopericardium cardiac tamponade• IV septum acquired VSD• Papillary muscle acute MR
– Post-infarction fibrinous pericarditis• Patchy (localized to region of pericardium overlying necrotic segment)
• 4 – 8 weeks: – Ventricular aneurysm
• Can lead to– Mural thrombus emboli (most common complication of ventricular aneurysm)– CHF (most common cause of death from ventricular aneurysm)
– Autoimmune fibrinous pericarditis (Dressler’s syndrome)• Diffuse
MI pathology timelineTime after MI Histology Gross pathology
0 – 4 hours Minimal change (normal myocardium)
4 – 12 hours
Early coagulation necrosisEdema
HemorrhageWavy fibers Dark mottling
12 – 24 hours Coagulation necrosisContraction bands
1 – 5 days Coagulation necrosisNeutrophilic infiltrate Hyperemia (red)
5 – 10 days Phagocytosis of dead cells by macrophages Yellow-brown
softening10 – 14 days Granulation tissue
Neovascularization
2 weeks – 2 months Collagen deposition scar formation
Gray-white scar formation
Hypertension
• Definitions– Normal: BP <120/80– Pre-HTN: BP 120 – 139/80 – 89– Stage I HTN: BP 140 – 159/90 – 99– Stage II HTN: BP >160/100
• Types– Primary (essential) HTN: 90% of cases
• May be associated with genetic tendency to retain sodium– Secondary HTN
• Most cases are 2° to renal disease (e.g. renal artery stenosis)
Hypertension• Treatment– DOC for patients w/o diabetes: thiazide diuretics– DOC for patients w/ diabetes: ACE inhibitors
• Thiazide diuretics cause hyperglycemia- exacerbation of diabetes– DOC for chronic HTN in pregnancy : α-Methyldopa, Clonidine– DOC for acute HTN in pregnancy: Hydralazine– DOC for elderly (isolated systolic HTN): CCB (Nifedipine = DHP
type if no CHF [best for vasodilation], Verapamil = non-DHP type if CHF [best for reducing TY and CTY)
– DOC for pt w/ comorbid BPH: α-blocker (-zosin) • Malignant HTN: BP >200/140– DOC: IV sodium Nitroprusside (immediate ↓ of BP)
Congestive heart failure (CHF)• Impaired ability of the heart to meet metabolic demands of the
body• Presentation
– LV failure • Dyspnea on exertion
– Failure of LV output to ↑ during exercise• ↑ pulmonary venous pressure pulmonary edema
– Microhemorrhages from ↑ pulmonary capillary pressure hemosiderin-laden macrophages (heart failure cells) in the lung
• Orthopnea, paroxysmal nocturnal dyspnea– ↑ venous return in supine position exacerbates pulmonary vascular congestion
• Dilated heart on CXR– Due to ↑ LVEDV
– RV failure ↑ systemic venous pressure • Jugular venous distension• Hepatic congestion (nutmeg liver) hepatomegaly• Peripheral edema
Congestive heart failure (CHF)
• NYHA classification– Class I: no impairment of physical activity– Class II: dyspnea with ordinary physical activity– Class III: dyspnea with minimal physical activity– Class IV: dyspnea at rest
Congestive heart failure (CHF)• Treatment
– Lifestyle changes: ↓ sodium & water intake– Medications
• ACE inhibitors / ARBs (DOC)– ↓ angiotensin II ↓ vasoconstriction ↓ TPR ↓ afterload ↓ myocardial
workload– ↓ aldosterone ↓ sodium & water retention ↓ preload ↓ myocardial workload– Remember: ACE inhibitors cause cough & angioedema via ↑ bradykinin
• Diuretics– ↑ sodium & water excretion ↓ preload ↓ myocardial workload– IV furosemide is usually given as 1st step in management, to clear the lungs (treats Sxs)– Oral Spironolactone = only diuretic shown to improve survival long-term
• β-blockers– ↓ HR & CTY ↓ myocardial workload– Carvedilol = β1, β2, and α1-blocker → most likely to ↓mortality, esp. when used w/
spironolactone. – Contraindicated in acute CHF
• Digoxin (digitalis)– ↑ CTY improvement of symptoms– Use only when needed (due to ↑ myocardial workload)
• PDE Inhibitors (Milrinone, Amirinone)– ↑cAMP → ↑CTY + coronary vasodilation.
Aortic dissection• Pathophysiology– Weakening of tunica media tearing of tunica
intima formation of secondary (false) lumen• Causes– Hypertension (#1 cause)– Connective tissue disorders
• Marfan syndrome• Ehlers-Danlos syndrome
– Note: no relation to atherosclerosis• Presentation: tearing chest pain radiating to the
back
Aortic dissection• Histology: degeneration of elastic fibers and
accumulation of extracellular myxoid material (cystic medial necrosis)
• Complication: aortic rupture cardiac tamponade• Diagnosis: transesophageal echocardiography– Note: apparently, the test of choice has been changed to
CT this year• Treatment– Type A (ascending): surgery– Type B (descending): medications
• DOC: β-blockers to prevent propagation of dissection– ↓ HR & CTY ↓ cardiac output ↓ BP ↓ shear stress
Cardiomyopathy• Dilated cardiomyopathy (90% of cases)
– Dilation of all 4 chambers and flabby ventricular walls– Systolic dysfunction (impaired contractility)– #1 cause: chronic ethanol abuse
• Hypertrophic cardiomyopathy– Massive cardiac hypertrophy (esp. IV septum)– Diastolic dysfunction (impaired diastolic filling)– #1 cause: mutation in cardiac sarcomere proteins (most common: myosin
heavy chain)– #1 cause of sudden death in young athletes
• Death is due to ventricular fibrillation– Histology: myocyte disarray (pathognomonic)
• Restrictive cardiomyopathy– Endocardial thickening and non-compliant ventricular walls– Diastolic dysfunction (impaired diastolic filling)
ECG abnormalities• Atrial fibrillation– “Irregularly irregular”– Absent P waves
• Atrial flutter– “Regularly irregular”– “Sawtooth” P waves
• L ventricular hypertrophy– Tall R waves in LV leads (I, aVL, V5, V6)– Deep S waves in RV leads (V1, III)
• R ventricular hypertrophy– Tall R wave in lead V1 (R wave > S wave)
• Normally, S wave > R wave in lead V1
ECG abnormalities• L bundle branch block (LBBB)
– Minimal/absent R wave in lead V1
– RR’ (broad, notched R wave) in LV leads (I, aVL, V5, V6)– QRS duration >120 msec
• R bundle branch block (RBBB)– rSR’ in lead V1
– S wave on leads I & V6
– QRS duration >120 msec• Hyperkalemia
– Peaked T waves• Pericarditis
– ST segment elevation in all leads– PR segment depression in all leads (pathognomonic)
Ventricular action potential• Phase 0: rapid depolarization
– Opening of Na+ channels• Phase 1: early repolarization
– Closure of Na+ channels– K+ channels begin to open
• Phase 2: plateau– Unique to cardiac myocytes– Balance between Ca2+ influx and K+
outflow– Ca2+ influx triggers Ca2+ release from
sarcoplasmic reticulum (calcium-induced calcium release) myocyte contraction
• Phase 3: rapid repolarization– Closure of Ca2+ channels– Opening of K+ channels
• Phase 4: resting potential– High K+ permeability through K+
channels
Pacemaker action potential• Phase 0: upstroke
– Opening of Ca2+ channels• Phase 3: repolarization
– Closure of Ca2+ channels– Opening of K+ channels
• Phase 4: diastolic depolarization– Spontaneous depolarization
by Na+ & Ca2+ conductance through If (funny current) channels
– Slope of phase 4 in SA node determines HR
Class I antiarrhythmics: Na+ channel blockers
• Class IA: quinidine, procainamide, disopyramide– Slows phase 0 depolarization ( → less rapid contraction)– Slows phase 3 repolarization (K+ channel blockade) ↑ AP duration– ADRs:
• Quinidine: cinchonism (headache, tinnitus), thrombocytopenia• Procainamide: drug-induced SLE (ass w/ anti-histone antibodies)• All class IA drugs can cause torsades de pointes
• Class IB: lidocaine, mexiletine– Slows phase 0 depolarization– Speeds up phase 3 repolarization (K+ channel activation) ↓ AP duration– Only useful for ventricular arrhythmias– Use lidocaine for:
• Post-MI ventricular arrhythmia• Digitalis-induced arrhythmia• Torsades de pointes
• Class IC: flecainide, propafenone– Slows phase 0 depolarization only (no effect on AP duration)– Most potent Na+ channel blockers used only as last resort
• Hyperkalemia ↑ toxicity for all class I antiarrhythmics• All cause ↑QRS duration (corresponds to phase 0 depolarization)
Class II antiarrhythmics: β-blockers• Slow diastolic depolarization (phase 4) in pacemaker
cells ( → ↓rate of spontaneous firing, ↓HR)– Sympathetic (β1) stimulation increases the chance that If
channels are open ↑ rate of diastolic depolarization ↑ HR
• AV node is particularly sensitive ↑ PR interval– Useful for ventricular rate control in atrial fibrillation &
atrial flutter• Sotalol has both class II and class III effects• Esmolol: t1/2 = 15 min– Used for hospital emergencies
• Useful for SVT, A-fib, A-flutter (to slow HR)
Class III antiarrhythmics: K+ channel blockers
• Slow phase 3 repolarization ↑ AP duration– Can cause torsades de pointes
• Amiodarone, dronedarone, sotalol, dofetilide, ibutilide– Sotalol has both class II and class III effects– Amiodarone:
• Has class I, II, III, and IV effects because it alters the lipid membrane• ADRs: every organ system can be affected
– Pulmonary fibrosis (need PFTs)– Hepatotoxicity (need LFTs)– Hyperthyroidism / hypothyroidism (need TFTs)– Slate blue skin discoloration
• The only class III drug that does NOT ↑ risk for torsades de pointes• t1/2 = 1 – 3 months
– Because of this, amiodarone is the most commonly used antiarrhythmic• DOC for ventricular arrhythmia that is NOT post-MI
Class IV antiarrhythmics: Ca2+ channel blockers
• Slow upstroke (phase 0) & diastolic depolarization (phase 4) in pacemaker cells
• Verapamil, diltiazem• Uses: atrial fibrillation, any supraventricular
tachycardia• ADRs:– AV block– CHF contraindicated in CHF patients– Verapamil also causes:
• Gingival hyperplasia• Constipation
AV nodal blocking agents: drugs that prolong the PR interval
• β-blockers• Ca2+ channel blockers• Adenosine
– t1/2 < 1.5 sec (only acts for 15 sec)– DOC for acute supraventricular tachycardia– ADRs
• Flushing• Hypotension• Chest pain (due to bronchospasm)
• Digoxin (digitalis)– MOA:
• Inhibition of Na+/K+ pump ↑ [Na+]i ↓ activity of Na+/Ca2+ exchanger ↑ [Ca]i ↑ contractility• Stimulation of vagus nerve slowed conduction at AV node prolonged PR interval
– Uses: CHF, atrial fibrillation– ADRs: very narrow therapeutic window
• N/V/D• Blurry yellow vision• Ventricular tachycardia / fibrillation (cause of death)• Hypokalemia ↑ risk of toxicity! (K+ competes for binding site on Na-K ATPase, so when K+ is decreased,
digoxin is more active. Don’t give digoxin with thiazide or loop diuretics, since they cause ↓ K+!)
Dyslipidemia drugs
• Optimal lipid levels (ATPIII guidelines)– Total cholesterol: ≤150 mg/dl– LDL cholesterol: ≤80 mg/dl– HDL cholesterol: >45 mg/dl– Triglycerides: ≤150 mg/dl
Dyslipidemia drugs• HMG-CoA reductase inhibitors (statins)
– ↓ cholesterol synthesis ↓ cellular cholesterol ↑ LDL receptors ↑ LDL uptake ↓ serum LDL
– 1st line for treating high LDL– ADRs:
• Hepatotoxicity (↑ LFTs)• Myalgias• Rhabdomyolysis (need to monitor CK)
• Niacin (nicotinic acid)– 1st line for treating low HDL– 2nd line for treating high triglycerides– ADRs:
• Cutaneous flushing (mediated by prostaglandins- preventable with aspirin)• Hyperglycemia (use caution in pts w/ diabetes)• Acanthosis nigricans (hyperpigmentation of skin, esp. around skin folds)• Hyperuricemia (exacerbates gout)
Dyslipidemia drugs• Bile acid sequestrants (cholestyramine, cholestipol, colesevelam)
– ↓ intestinal bile acid absorption ↓ bile acids ↑ hepatic production of bile acids from cellular cholesterol ↓ cellular cholesterol ↑ LDL receptors ↑ LDL uptake ↓ serum LDL
– ADRs:• GI discomfort (constipation, bloating, abd pain)• ↓ absorption of fat-soluble vitamins (A, D, E, K)• Cholesterol gallstones (esp. when used with fibrates)• Hypertriglyceridemia
• Ezetimibe– ↓ intestinal cholesterol absorption– 2nd line for treating high LDL
• Fibrates (gemfibrozil, fenofibrate)– ↑ LPL activity ↑ triglyceride clearance– 1st line for treating high triglycerides– ADRs:
• Myositis• Hepatotoxicity (↑ LFTs)• Cholesterol gallstones