11.2 Cardiovascular & Collagen Pathology: Heart Failure, Congenital, Ischemic, Hypertensive, Valvular, Pericardial & Myocardial Disease

Why this area matters

The TOS lists:

• heart failure (left-sided, right-sided);
• congenital heart disease (left-to-right and right-to-left shunts, obstructive lesions);
• ischemic heart disease (angina, MI, sudden cardiac death);
• hypertensive disease (systemic hypertensive heart disease, cor pulmonale);
• valvular disease (mitral valve prolapse, rheumatic fever, RHD, infective endocarditis);
• pericardial disease;
• cardiomyopathies;
• primary cardiac tumors;
• collagen disorders.

Cardiovascular disease is the leading cause of death in the Philippines, and rheumatic heart disease remains common in young Filipinos.

Heart failure

• Left-sided failure:
  • causes: ischemic heart disease, hypertension, aortic and mitral valve disease, cardiomyopathy;
  • effects: pulmonary congestion and edema (orthopnea, paroxysmal nocturnal dyspnea); alveolar macrophages laden with hemosiderin, the heart failure cells; prerenal azotemia and renin activation from reduced renal perfusion.
• Right-sided failure:
  • usually caused by left-sided failure; when isolated, by cor pulmonale (lung disease or pulmonary hypertension);
  • effects: raised jugular venous pressure, chronic passive congestion of the liver ("nutmeg liver") that may progress to cardiac sclerosis, congestive splenomegaly, dependent pitting edema, ascites and pleural effusions.
• Most patients have both. Hearts fail with reduced ejection fraction (systolic) or preserved ejection fraction (diastolic stiffness, as in hypertension).

Congenital heart disease

Hypertensive and pulmonary heart disease

• Systemic hypertensive heart disease produces concentric left ventricular hypertrophy (wall over about 1.5 cm) without another cause. Myocytes enlarge with "boxcar" nuclei. Diastolic dysfunction comes first, then failure. It also leads to atrial fibrillation and ischemia.
• Cor pulmonale is right ventricular hypertrophy and dilation from pulmonary hypertension due to lung disease (COPD, interstitial fibrosis), chronic hypoxia, pulmonary emboli or sleep apnea. Acute cor pulmonale follows a massive pulmonary embolus.

Cardiovascular Pathology

Atherosclerosis Pathogenesis & Plaque Architecture

Atherosclerosis is a chronic inflammatory and fibroproliferative disease of elastic and large-to-medium muscular arteries, initiated by endothelial injury:

1. Endothelial Dysfunction: Initiated by hemodynamic shear stress (arterial branch points), oxidized LDL, cigarette toxins, and hyperhomocysteinemia. Endothelium displays increased permeability, enhanced leukocyte adhesiveness, and upregulation of VCAM-1.
2. Lipid Accumulation & Oxidation: Circulating low-density lipoproteins (LDL) enter the tunica intima, where they become entrapped in the extracellular matrix and undergo oxidation by free radicals.
3. Foam Cell Generation: Monocytes enter the intima, differentiate into macrophages, and ingest oxidized LDL via scavenger receptors (CD36). As lipid accumulates in their cytoplasm, macrophages transform into foam cells. Aggregations of foam cells form the fatty streak, the earliest visible atherosclerotic lesion (grossly flat, yellow, fully reversible).
4. Smooth Muscle Migration & Cap Formation: Macrophages, endothelial cells, and platelets release platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-$\beta$). These cytokines stimulate vascular smooth muscle cells (VSMCs) to migrate from the tunica media into the intima, proliferate, and synthesize extracellular matrix proteins (predominantly collagen). This forms a protective fibrous cap overlying a necrotic lipid core containing cholesterol clefts, debris, and foam cells.
5. Plaque Vulnerability: Stable plaques have dense fibrous caps and small lipid cores. Vulnerable (unstable) plaques have thin fibrous caps, large lipid cores, and intense macrophage infiltration. Macrophages secrete matrix metalloproteinases (collagenases) that thin the fibrous cap, precipitating plaque fissure, ulceration, intra-plaque hemorrhage, and superimposed acute occlusive thrombosis (acute coronary syndrome).

Myocardial Infarction: Chronologic Histopathologic Evolution

Valvular Heart Diseases: Infective Endocarditis vs. Rheumatic Heart Disease

• Infective Endocarditis (IE): Colonization of heart valves by microbial agents, producing friable, bulky, destructive vegetations composed of fibrin, platelets, inflammatory cells, and bacterial colonies.
  • Microbiology: Staphylococcus aureus is the most common cause of acute endocarditis overall and in intravenous drug users (IVDU), aggressively destroying healthy native valves (specifically the tricuspid valve in IVDU). Viridans streptococci (S. sanguinis, S. mitis) cause subacute endocarditis on previously damaged or abnormal valves (mitral valve prolapse, bicuspid aortic valves). Staphylococcus epidermidis infects prosthetic heart valves within 12 months. Streptococcus gallolyticus (S. bovis) is strongly associated with underlying occult colorectal adenocarcinoma.
  • Peripheral Stigmata: Janeway lesions (painless, flat erythematous macules on palms/soles caused by septic microemboli); Osler nodes (painful, tender erythematous nodules on pads of digits caused by immune complex deposition); Roth spots (pale-centered retinal hemorrhages); Splinter hemorrhages (subungual linear streaks).
• Rheumatic Heart Disease (RHD): Post-infectious autoimmune consequence of Group A streptococcal (Streptococcus pyogenes) pharyngeal infection, mediated by molecular mimicry (anti-streptococcal M protein antibodies cross-reacting with human cardiac myosin and laminin).
  • Pancarditis & Histopathology: Pathognomonic Aschoff bodies (foci of interstitial fibrinoid necrosis surrounded by lymphocytes, plasma cells, and pathognomonic Anitschkow cells ["caterpillar cells": plump activated histiocytes with abundant cytoplasm and slender, wavy ribbons of chromatin]).
  • Valvular Sequelae: Recurrent inflammation causes diffuse fibrous thickening, commissural fusion, and chordal shortening, producing classic "fish-mouth" or "buttonhole" mitral valve stenosis (the mitral valve is involved in $> 95\%$ of cases).

Other valvular lesions

• Mitral valve prolapse: myxomatous degeneration with ballooning leaflets. A mid-systolic click is followed by a late systolic murmur. Seen in Marfan syndrome. Usually benign, but can cause mitral regurgitation and endocarditis.
• Calcific aortic stenosis: age-related dystrophic calcification of a normal valve (after age 70) or of a bicuspid valve (after age 50). Concentric LVH develops, with angina, syncope and heart failure.
• Nonbacterial thrombotic (marantic) endocarditis: sterile vegetations in cancer and hypercoagulable states. Libman-Sacks endocarditis in SLE forms small vegetations on both surfaces of the valves.

Pericardial disease

• Fibrinous pericarditis: after MI (early, or as Dressler syndrome), and in uremia, rheumatic fever and SLE. A friction rub is heard.
• Purulent pericarditis: from bacterial infection.
• Caseous (tuberculous) pericarditis: leads to constrictive pericarditis with a thick, calcified pericardium. This is still a notable cause in the Philippines.
• Pericardial effusion and hemopericardium: after ruptured MI, aortic dissection or trauma, they cause cardiac tamponade (Beck triad, pulsus paradoxus).

Cardiomyopathies

Primary cardiac tumors

• Atrial myxoma: the most common primary cardiac tumor in adults. It is usually in the left atrium at the fossa ovalis. It can cause ball-valve obstruction, a "tumor plop", emboli and constitutional symptoms (IL-6).
• Rhabdomyoma: the most common in children, associated with tuberous sclerosis.
• Metastases to the heart are far more common than primary tumors.

Collagen-vascular (connective tissue) disorders and the heart and vessels

• SLE: pericarditis, Libman-Sacks endocarditis, myocarditis, accelerated atherosclerosis.
• Rheumatoid arthritis: pericarditis, rheumatoid nodules, aortitis.
• Systemic sclerosis: myocardial fibrosis, pulmonary hypertension.
• Vasculitides are classified by vessel size:
  • large: Takayasu arteritis and giant cell arteritis;
  • medium: polyarteritis nodosa (sparing the lungs; associated with hepatitis B) and Kawasaki disease (coronary aneurysms in children);
  • small: ANCA-associated vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis) and IgA vasculitis.