9.2 Ischemic Heart Disease & Cardiomyopathy

9.2 Ischemic Heart Disease & Cardiomyopathy

Quick Answer: Chronic coronary stenoses cause demand-related stable angina; plaque rupture with thrombosis drives unstable angina, NSTEMI, and STEMI. Infarct complications follow histology timelines (arrhythmia → coagulative necrosis → macrophage clearing/rupture risk → scarring; Dressler later). Cardiomyopathies separate by remodeling geometry and filling/ejection physiology into dilated, hypertrophic, and restrictive patterns that produce HFrEF or HFpEF phenotypes.

Atherosclerosis Pathogenesis

Atherosclerosis is a chronic inflammatory disease of large and medium arteries initiated by endothelial injury (hemodynamic shear at branch points, hypertension, smoking toxins, hyperlipidemia, diabetes-related glycation stress). Injured endothelium increases permeability to LDL, expresses adhesion molecules, and reduces nitric oxide bioavailability (impaired vasodilation, prothrombotic surface).

LDL accumulates in the intima, becomes oxidized, and is taken up by macrophages via scavenger receptors to form foam cells (fatty streak). Smooth muscle cells migrate from media to intima, proliferate, and synthesize extracellular matrix, evolving a fibrofatty plaque with a lipid-rich necrotic core and fibrous cap. T-cell cytokines and matrix metalloproteinases weaken the cap. Complicated plaques calcify, ulcerate, or rupture.

Stable plaques with thick fibrous caps and smaller lipid cores tend to cause progressive luminal narrowing and demand ischemia. Vulnerable plaques with thin caps and large necrotic cores may be only moderately stenotic yet rupture, exposing thrombogenic material (tissue factor, collagen) that triggers platelet activation and coagulation cascade thrombosis—the dominant mechanism of acute coronary syndromes (ACS).

Stable Angina vs Unstable Angina vs MI

Stable angina occurs when myocardial oxygen demand exceeds supply across a fixed atherosclerotic stenosis, typically with exertion or stress, and relieves with rest or nitroglycerin (↓ preload via venodilation → ↓ wall tension; also coronary dilation). The myocardium is ischemic but not infarcted; troponins remain negative and the rest ECG may be normal or show old changes.

Unstable angina reflects acute plaque disruption with thrombosis and/or vasospasm producing rest pain or accelerating patterns without biomarker evidence of myocyte necrosis. Myocardial infarction implies ischemic necrosis with biomarker elevation (troponin). Pathophysiologically, the continuum is supply disruption from occlusive or near-occlusive thrombus on disrupted plaque, sometimes with embolization of platelet aggregates into the microcirculation.

Oxygen supply–demand mismatch is amplified by tachycardia (less diastolic coronary filling time), anemia, hypoxia, and left ventricular hypertrophy (higher wall stress and diffusion distance).

STEMI vs NSTEMI: Conceptual Injury Patterns

STEMI conceptually corresponds to acute transmural ischemia, classically from total thrombotic occlusion of an epicardial coronary artery, producing ST-segment elevation in an anatomic territory and Q waves if necrosis completes. NSTEMI typically reflects severe subendocardial ischemia/necrosis (subendocardium is most vulnerable: highest wall stress, farthest from epicardial flow) with ST depression or T-wave changes, or even a nondiagnostic ECG, plus positive biomarkers.

These are clinical-ECG-biomarker constructs rather than perfect histology labels, but CBSE stems use the physiology: complete occlusion → larger transmural risk; partial flow → subendocardial injury. Territory maps: LAD → anterior wall/septum; RCA → inferior wall (often), right ventricle; LCx → lateral wall (variable dominance).

Ischemic myocytes switch to anaerobic glycolysis, lose ATP-dependent ion pumps, accumulate lactate, and develop irreversible membrane injury when ischemia is prolonged. Coagulative necrosis evolves over hours; reperfusion can salvage myocardium but also introduces reperfusion injury.

Reperfusion Injury

Restoring flow (thrombolysis or PCI conceptually) is essential to limit infarct size, but reperfusion can paradoxically injure cells via oxidative stress (reactive oxygen species burst), calcium overload, mitochondrial permeability transition, inflammation, and no-reflow from microvascular obstruction. Arrhythmias may appear at reperfusion. The board-level message: earlier reperfusion saves more myocardium; reperfusion injury explains why some cell death continues after flow returns and why microvascular obstruction limits benefit.

Complications of MI by Time

Complications track the histologic evolution of the infarct:

Free wall rupture causes hemopericardium and electromechanical dissociation/tamponade physiology. Papillary muscle rupture (more often posteromedial papillary with RCA-related inferior infarcts because of single blood supply patterns) produces acute MR and pulmonary edema. Septal rupture creates a harsh holosystolic murmur with left-to-right shunt and shock. Dressler syndrome is delayed post-MI autoimmune pericarditis, distinct from early peri-infarction pericarditis.

Mural thrombus over akinetic endocardium can embolize systemically. Progressive remodeling after large infarcts yields dilated cardiomyopathy phenotype and chronic HFrEF.

Cardiomyopathy Mechanisms

Dilated Cardiomyopathy (DCM)

Dilated cardiomyopathy features four-chamber or LV dilation with impaired systolic function (reduced ejection fraction), eccentric hypertrophy pattern, and often functional MR from annular dilation. Mechanisms/associations include genetic cytoskeletal/sarcomere defects, viral myocarditis sequelae, toxins (alcohol, anthracyclines), peripartum cardiomyopathy, tachycardia-mediated cardiomyopathy, and ischemic burn-out. Pathophysiology is reduced contractility → increased ESV → remodeling dilation → worse wall stress (Laplace) → further dysfunction. Forward failure (fatigue, hypoperfusion) and backward failure (pulmonary and systemic congestion) both appear.

Hypertrophic Cardiomyopathy (HCM)

Hypertrophic cardiomyopathy is commonly caused by autosomal dominant sarcomere mutations (classic examples: β-myosin heavy chain, myosin-binding protein C). Myocardial disarray and hypertrophy reduce compliance (diastolic dysfunction); dynamic LVOTO and SAM of the mitral valve produce the classic murmur physiology discussed in Section 9.1. Sudden death risk relates to malignant arrhythmias in disorganized hypertrophied muscle, especially in young athletes with HCM. Concentric hypertrophic geometry from pressure overload (hypertension, AS) is a related but distinct compensatory pattern; familial HCM is the genetic disease prototype.

Restrictive Cardiomyopathy

Restrictive cardiomyopathy is defined by stiff ventricles with impaired filling, biatrial enlargement, and relatively preserved wall thickness early (though infiltrative diseases may thicken walls). Causes include amyloidosis, sarcoidosis, hemochromatosis, radiation fibrosis, and endomyocardial fibrosis. PV-loop thinking: elevated filling pressures at modest volumes (upward-shifted EDPVR). Clinically it can mimic constrictive pericarditis; mechanism questions emphasize decreased compliance rather than primary contractile failure, though systolic function may later decline.

Heart Failure: Systolic vs Diastolic; Forward vs Backward

Heart failure with reduced ejection fraction (HFrEF / systolic HF) is inadequate forward stroke volume from impaired contractility or severe remodeling (ischemic DCM, nonischemic DCM). End-systolic volume is high; neurohormonal activation (sympathetic, RAAS, ADH) initially supports pressure and volume but chronically promotes fibrosis, remodeling, and fluid retention.

Heart failure with preserved ejection fraction (HFpEF / diastolic HF) features elevated filling pressures from decreased ventricular compliance (hypertension with hypertrophy, ischemia, aging, infiltrative disease) despite a normal or near-normal EF. Small, stiff ventricles need higher atrial pressures to fill; pulmonary congestion occurs even when EF looks “normal.”

Forward failure signs: fatigue, cool extremities, prerenal azotemia, confusion from low CO. Backward failure left-sided: pulmonary edema, orthopnea, PND, elevated pulmonary venous pressure. Backward failure right-sided: elevated JVP, congestive hepatomegaly, peripheral edema—often secondary to left disease raising pulmonary pressures or primary right insults (PE, RV infarct, pulmonary hypertension).

Compensatory mechanisms include Frank–Starling recruitment (limited in failing hearts), hypertrophy, and neurohormonal vasoconstriction/volume retention. Decompensation occurs when these raise afterload and preload beyond benefit, worsening edema and myocardial energetics.

Integrating Ischemia with Failure and Cardiomyopathy

Chronic ischemia produces hibernating myocardium and ischemic cardiomyopathy (dilated, reduced EF). Acute ischemia can cause flash pulmonary edema from diastolic stiffening and MR (papillary ischemia). Post-infarct scar yields regional wall motion abnormalities and aneurysm risk. When reading stems, sequence the story: risk factors → plaque biology → syndrome type → territory → time-based complication or remodeling phenotype → HF physiology (EF, forward/backward).

This section’s CBSE core is mechanism chaining: endothelium and lipid inflammation build plaques; thrombosis converts stable disease to ACS; necrosis timelines predict rupture and Dressler; geometry defines cardiomyopathy; EF and congestion patterns define HF phenotypes.