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Cardiac Pathology — Robbins, Cotran & Kumar: Pathologic Basis of Disease (Latest Edition, ISBN 9780443264528)

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Overview

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1. HEART FAILURE (CHF)

Compensatory Mechanisms

1. Frank-Starling mechanism — increased filling → myocyte stretch → more forceful contraction
2. Neurohumoral activation — norepinephrine (↑HR, ↑contractility, ↑vascular resistance), RAAS (salt/water retention), atrial natriuretic peptide (counterbalancing diuresis)
3. Myocardial hypertrophy & ventricular remodeling — collective molecular, cellular, and structural changes in response to injury/altered loading

Classification

Left-Sided Heart Failure

• Causes: IHD, hypertension, aortic/mitral valve disease, myocardial disease
• Morphology: left ventricular dilation or hypertrophy; lungs show pulmonary congestion, hemosiderin-laden macrophages ("heart failure cells"), interstitial edema, and ultimately pulmonary fibrosis
• Clinical: dyspnea, orthopnea, paroxysmal nocturnal dyspnea, systemic hypoperfusion causing renal/cerebral dysfunction

Right-Sided Heart Failure

• Usually a consequence of left heart failure; less commonly primary pulmonary disorders
• Morphology: right ventricular dilation; systemic/portal venous congestion → hepatomegaly (nutmeg liver), splenomegaly, pleural effusions, ascites, peripheral edema
• Clinically dominated by peripheral edema and visceral congestion

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2. CONGENITAL HEART DISEASE (CHD)

Frequencies of Common Malformations (Table 12.2)

Key Entities

• VSD: Most common; 90% are membranous; small ones close spontaneously; large → Eisenmenger syndrome (L→R shunt → pulmonary hypertension → shunt reversal → cyanosis)
• ASD: Often asymptomatic for decades; secundum type most common; ostium primum type associated with Down syndrome
• PDA: Failure of ductus arteriosus to close after birth; prostaglandins maintain patency; indomethacin can close it
• Tetralogy of Fallot: (1) VSD, (2) pulmonary/infundibular stenosis, (3) overriding aorta, (4) right ventricular hypertrophy — classical "boot-shaped heart" on X-ray; cyanosis from R→L shunt
• Transposition of Great Arteries: Aorta arises from RV, pulmonary artery from LV — incompatible with life unless a mixing defect (ASD, VSD, PDA) is present
• Coarctation of Aorta: Male predominance; associated with Turner syndrome; causes upper extremity hypertension and lower extremity hypotension/claudication; "rib notching" on X-ray

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3. ISCHEMIC HEART DISEASE (IHD)

Clinical Presentations

1. Myocardial infarction (MI)
2. Angina pectoris (stable, unstable, Prinzmetal's vasospastic)
3. Chronic IHD with heart failure
4. Sudden cardiac death (SCD)

Pathogenesis

• Stable plaque → stable angina
• Disrupted/ruptured plaque → superimposed thrombus → acute coronary syndrome (unstable angina, NSTEMI, STEMI) or SCD
• Non-atherosclerotic causes: coronary emboli, vasculitis, spasm, anomalous origin

Myocardial Infarction

• STEMI: Transmural infarct, complete occlusion; classic ST elevation
• NSTEMI: Subendocardial infarct, often partial occlusion; no ST elevation

• Arrhythmias (most common cause of death in the first 24 hours)
• Cardiogenic shock
• Cardiac tamponade from free wall rupture (days 3–7)
• Interventricular septal rupture
• Papillary muscle rupture → acute mitral regurgitation
• Mural thrombus → systemic embolism
• Fibrinous pericarditis (Dressler syndrome when autoimmune, weeks later)
• Ventricular aneurysm

Sudden Cardiac Death (SCD)

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4. HYPERTENSIVE HEART DISEASE (HHD)

Systemic (Left-Sided) HHD

• Minimal criteria: (1) LV hypertrophy (usually concentric) without other cardiac pathology, and (2) clinical/pathologic evidence of hypertension
• Heart weight may exceed 500 g; LV wall thickness may exceed 2.0 cm
• Microscopy: increased transverse diameter of myocytes; perivascular and interstitial fibrosis
• Complications: diastolic dysfunction, left atrial enlargement, atrial fibrillation, IHD, CHF, SCD
• Effective BP control can cause regression of hypertrophy

Pulmonary (Right-Sided) HHD — Cor Pulmonale

• Right ventricular hypertrophy, dilation, and potential right-sided failure due to pulmonary hypertension
• Caused by: COPD (most common), pulmonary fibrosis, pulmonary embolism, primary pulmonary arterial hypertension

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5. VALVULAR HEART DISEASE

• Stenosis — failure to open completely; almost always chronic (calcification/scarring)
• Insufficiency/Regurgitation — failure to close completely; acute (chordal rupture, IE) or insidious (scarring)

Calcific Valvular Degeneration

• Most common cause of aortic stenosis in adults; calcium deposits in valve cusps at flexion points
• Morphology: focal calcific deposits on the outflow (aortic) side of aortic cusps; no commissural fusion (unlike RHD)
• Bicuspid aortic valve (1–2% prevalence) calcifies earlier (5th–6th decade) vs. tricuspid (7th–8th decade)

Rheumatic Heart Disease (RHD)

• Immune-mediated; follows pharyngeal Group A streptococcal infection
• Aschoff bodies = pathognomonic granuloma-like lesions with central fibrinoid necrosis, surrounded by lymphocytes, plasma cells, and Anitschkow cells (caterpillar cells — macrophages with characteristic chromatin pattern)
• Acute RHD: carditis (pancarditis — endo, myo, peri); small, warty vegetations along the line of valve closure
• Chronic RHD: fibrous thickening, commissural fusion, leaflet calcification; the mitral valve is most commonly affected, followed by aortic, then tricuspid
• "Fish-mouth" or "button-hole" mitral stenosis on gross exam

Endocarditis Comparison (Key Robbins diagram):

Infective Endocarditis (IE)

• Microbial infection of valves/mural endocardium → vegetations of thrombotic debris + organisms + valve destruction
• Acute IE: Highly virulent organisms (S. aureus) on previously normal valves; rapid, destructive; requires surgery
• Subacute IE: Low-virulence organisms (Streptococcus viridans) on deformed valves; indolent; often responds to antibiotics alone

Nonbacterial Thrombotic Endocarditis (NBTE) / Marantic Endocarditis

• Small, sterile, bland vegetations along the line of valve closure
• Associated with: cancer (especially mucin-secreting adenocarcinoma), sepsis, burns, prolonged debilitating illness
• Mechanism: hypercoagulable state

Libman-Sacks Endocarditis (LSE)

• Small-medium vegetations on either or both sides of valve leaflets
• Pathognomonic of SLE; associated with antiphospholipid antibody syndrome

Mitral Valve Prolapse (MVP) / Myxomatous Degeneration

• Most common valvular abnormality (1–2.5% of adults); female predominance
• Morphology: enlarged, floppy leaflets that balloon into the LA during systole; myxomatous change (acid mucopolysaccharide accumulation) weakens the fibrosa layer
• Complication: chordal rupture, mitral regurgitation; small increased risk of IE and SCD

Carcinoid Heart Disease

• Right-sided valvular lesions (tricuspid/pulmonary) due to serotonin and other vasoactive substances released by carcinoid tumors
• Fibrous plaques on endocardial surfaces ("carcinoid plaques")
• Left heart spared because lungs inactivate serotonin; left-sided involvement occurs with pulmonary carcinoid or right-to-left shunts

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6. CARDIOMYOPATHIES

Dilated Cardiomyopathy (DCM)

• Progressive cardiac dilation + contractile failure, usually with hypertrophy
• Familial in up to 50% of cases; autosomal dominant most common
• TTN mutations (titin gene) = 10–20% of all DCM cases
• Other causes: myocarditis (Coxsackie B), alcohol/toxins (acetaldehyde, cobalt, chemotherapy), peripartum, Duchenne/Becker (dystrophin mutations), hemochromatosis
• Morphology: all four chambers dilated; pale, flabby myocardium; mural thrombi common; microscopy shows myocyte hypertrophy, interstitial fibrosis (nonspecific)
• Clinical: progressive CHF, arrhythmias, emboli; transplantation may be required

Hypertrophic Cardiomyopathy (HCM)

• Prevalence: 1 in 500; leading cause of SCD in young athletes
• Autosomal dominant; >400 mutations in 9 sarcomeric protein genes; most common: MYBPC3 (myosin-binding protein C) and MYH7 (β-myosin heavy chain) — together 70–80% of cases
• All are gain-of-function mutations → hypercontractility
• Morphology: massive ventricular hypertrophy (asymmetric septal hypertrophy); banana-shaped LV on cross-section; "subaortic hypertrophy" causing dynamic outflow obstruction (in ~1/3)
• Microscopy hallmark: myofiber disarray (haphazard arrangement of myocytes at odd angles to each other) + interstitial fibrosis
• Systolic anterior motion (SAM) of the anterior mitral leaflet worsens outflow obstruction
• Clinical: diastolic dysfunction, angina, syncope, SCD; novel therapy: mavacamten (myosin inhibitor)

Restrictive Cardiomyopathy (RCM)

• Decreased ventricular compliance → impaired diastolic filling; normal systolic function
• Causes: amyloidosis (most common in adults), sarcoidosis, hemochromatosis, endomyocardial fibrosis (Löffler endocarditis — eosinophilic), glycogen storage diseases, radiation fibrosis
• Morphology: firm, non-compliant myocardium; microscopy depends on cause (e.g., Congo red–positive amyloid deposits, eosinophilic infiltration)

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

• Autosomal dominant with variable penetrance
• Mutations in desmosomal proteins (plakoglobin, desmin) at the intercalated disk
• Naxos syndrome = ARVC + palmoplantar hyperkeratosis (plakoglobin mutation)
• Morphology: right ventricular wall severely attenuated; massive fatty infiltration + focal fibrosis replacing RV myocardium
• Clinical: right-sided heart failure, ventricular arrhythmias, SCD in young adults; can mimic DCM

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7. MYOCARDITIS

Causes (Table 12.12)

• Infections: Viruses (Coxsackievirus A & B most common in the US; also CMV, HIV, influenza; COVID-19 causes focal myocardial necrosis via microthrombi)
• Trypanosoma cruzi → Chagas disease (endemic in South America; acute death 10%; chronic immune-mediated cardiomyopathy in 10–20 years)
• Trichinella spiralis (most common helminth)
• Diphtheria toxin (Corynebacterium diphtheriae)
• Borrelia burgdorferi (Lyme disease — self-limited conduction abnormalities)
• Immune-mediated: Poststreptococcal (RHD), SLE, drug hypersensitivity, transplant rejection, immune checkpoint inhibitor therapies
• Unknown: Sarcoidosis, giant cell myocarditis (idiopathic; rapidly fatal; pathognomonic multinucleated giant cells + extensive necrosis)

Morphology

• Gross: may be normal or show ventricular dilation
• Microscopy: lymphocytic (most common) — interstitial edema + mononuclear inflammatory infiltrate + myocyte necrosis; eosinophilic; giant cell; granulomatous (sarcoid)

Clinical

• Can range from asymptomatic (incidental finding) to fulminant CHF and SCD
• Some cases resolve completely; others progress to DCM

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8. PERICARDIAL DISEASE

Acute Pericarditis

Pericardial Effusion and Cardiac Tamponade

• Slowly accumulating effusions (up to 500 mL) tolerated well; rapidly accumulating effusion of 200–300 mL can cause tamponade (compression of heart, Beck's triad: hypotension, elevated JVP, muffled heart sounds)

Chronic/Healed Pericarditis — Constrictive Pericarditis

• Most commonly follows TB, hemopericardium from cardiac surgery, radiation
• Pericardium replaced by dense fibrous scar or calcification, encasing the heart
• Clinical: mimics RHD or tricuspid stenosis; elevated JVP, ascites, Kussmaul's sign (paradoxical rise in JVP on inspiration)

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9. TUMORS OF THE HEART

Primary Cardiac Tumors

1. Myxoma (most common in adults)
2. Fibroma
3. Lipoma
4. Papillary fibroelastoma
5. Rhabdomyoma (most common in infants/children; strongly associated with tuberous sclerosis)

• ~90% arise in the atria; L:R ratio = 4:1; origin from fossa ovalis
• Sporadic (no consistent genetic alteration) vs. syndromic:
  • McCune-Albright syndrome (GNAS1 gain-of-function mutation — G protein signaling)
  • Carney complex (PRKAR1A loss-of-function mutation — ↑cAMP signaling)
• Morphology: sessile or pedunculated, 1–10 cm; gelatinous or hemorrhagic; histology: stellate myxoma cells in abundant acid mucopolysaccharide matrix + peculiar vessel-like/gland-like structures

• Clinical manifestations: (1) "ball-valve" obstruction of mitral valve orifice (position-dependent symptoms), (2) systemic embolization, (3) constitutional symptoms (fever, malaise — due to IL-6 secretion)
• Treatment: surgical excision — usually curative; rare recurrence if incompletely excised

• Most common primary cardiac tumor in infants and children
• Strongly associated with tuberous sclerosis (TSC1/TSC2 mutations — hamartomas)
• Often regress spontaneously; may cause outflow obstruction or arrhythmias

Secondary (Metastatic) Cardiac Tumors

• Far more common than primary tumors
• Most common sources: lung carcinoma, breast carcinoma, lymphoma/leukemia, malignant melanoma (highest rate of cardiac involvement per primary tumor)
• Reach the heart via direct invasion, hematogenous spread, lymphatic spread, or growth through the vena cava

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Summary Table of Key Cardiac Pathologies

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