10 Heart Diseases: Pathological Changes & Illustrated Guide

1. Myocardial Infarction (MI)

Pathological Changes

• Mechanism: Atherosclerotic plaque rupture → platelet aggregation → thromboxane A2/ADP/serotonin release → coronary thrombosis → vessel occlusion
• Sequence: Within 20–40 minutes of sustained ischemia, irreversible coagulative necrosis begins in the subendocardial zone (most vulnerable, last to receive blood), then a "wavefront" of necrosis progresses outward over 3–6 hours
• Biochemical: Aerobic metabolism ceases within seconds → ATP drops → lactic acid accumulates → sarcolemmal membrane disruption → release of troponins, CK-MB into bloodstream
• Gross changes by time:
  • 0–6 h: No gross change (only microscopic)
  • 6–24 h: Dark mottling, pale area
  • 1–3 days: Yellow-tan, softening
  • 1–2 weeks: Hyperemic border, yellow-grey centre
  • 4–8 weeks: White scar (collagen replacement)
• Coronary territories: LAD occlusion (40–50%) → anterior LV, anterior 2/3 septum; RCA (30–40%) → inferior/posterior LV; LCX (15–20%) → lateral LV

Images

Composite autopsy panel: hemopericardium from LV free wall rupture (A), transmural infarct (B–C), coagulative necrosis on H&E (D), LAD cross-section with near-total luminal occlusion (E–F)

Coronal heart section: bright red healthy myocardium transitions to darker necrotic subendocardial region; papillary muscles visible

2. Heart Failure (Congestive Heart Failure)

Pathological Changes

• Left heart failure: Pulmonary venous hypertension → pulmonary edema → "nutmeg lung" (congestive hemosiderosis, "heart failure cells" = hemosiderin-laden macrophages in alveoli)
• Right heart failure (or biventricular): Systemic venous congestion → hepatomegaly (nutmeg liver), peripheral edema, ascites, splenomegaly
• Cardiac remodeling: Myocyte hypertrophy, interstitial fibrosis, ventricular dilation; increased wall stress activates neurohormonal pathways (RAAS, sympathetic nervous system, BNP)
• Compensatory mechanisms (that ultimately worsen failure): Frank–Starling mechanism, neurohormonal activation, ventricular hypertrophy/remodeling
• BNP/NT-proBNP: Released due to ventricular wall stress; key diagnostic biomarker

Images

PA chest X-ray: globally enlarged, globular cardiac silhouette; bilateral perihilar haziness/interstitial edema; blunted costophrenic angles suggesting pleural effusions

Axial CT showing peripheral dependent hyperattenuation in both lungs representing fluid accumulation and interstitial edema in heart failure

3. Dilated Cardiomyopathy (DCM)

Pathological Changes

• Causes: Genetic (20–50%; titin mutations most common, also β-myosin heavy chain, troponin T, dystrophin); viral myocarditis (coxsackievirus B, parvovirus B19); alcohol/toxins (acetaldehyde direct myocardial toxin); peripartum; hemochromatosis; sarcoidosis; doxorubicin
• Gross: Four-chamber dilation and hypertrophy; flabby, poorly contractile walls; mural thrombus at apex of LV (risk of systemic embolism)
• Microscopy: Myocyte hypertrophy (enlarged nuclei) + interstitial fibrosis (collagen blue on Masson trichrome); vacuolar degeneration; no specific cause identifiable in end-stage
• Mechanism of failure: Loss-of-function mutations in cytoskeletal/sarcomeric proteins → impaired contractility → systolic dysfunction → progressive dilation → further pump failure

Images

Panel (a): explanted heart with four-chamber dilation and thin walls; Panel (b): H&E microscopy showing myocyte hypertrophy (yellow arrows) and vacuolar degeneration (black arrows)

Gross pathology: markedly dilated both ventricles with thin flabby walls; thrombus adherent to LV endocardial surface — classic end-stage non-ischemic DCM

4. Hypertrophic Cardiomyopathy (HCM)

Pathological Changes

• Genetics: Autosomal dominant; gain-of-function mutations in sarcomeric proteins: β-myosin heavy chain (most common), myosin-binding protein C, troponin T → account for 70–80% of all HCM
• Pathophysiology: Hypercontractility → increased energy consumption → negative energy balance → myocyte disarray and replacement fibrosis → diastolic dysfunction (impaired relaxation/compliance)
• Gross: Massive hypertrophy without dilation; asymmetric septal hypertrophy in 90% (septal > free wall); ventricular cavity compressed into "banana-like" shape; anterior mitral leaflet contacts septum during systole → left ventricular outflow tract (LVOT) obstruction (SAM - systolic anterior motion)
• Microscopy: Myocyte disarray (whorled pattern), hypertrophied myocytes, interstitial fibrosis
• Risk: #1 cause of sudden cardiac death in young athletes

Images

Gross heart cross-sections: (a) asymmetric septal HCM with crescent-shaped narrow LV cavity; (b) anterolateral focal HCM; (c) dilated cardiomyopathy for comparison

Four-chamber cardiac MRI: interventricular septum massively hypertrophied (blue arrow) with enlarged papillary muscles, leaving only a narrow LV residual cavity (red arrow)

5. Infective Endocarditis (IE)

Pathological Changes

• Microbiology: Acute IE (rapid destruction): Staphylococcus aureus; Subacute IE (smoldering): viridans streptococci; HACEK organisms; fungi (Candida) in IV drug users/prosthetic valves
• Pathogenesis: Bacteremia → seeding of endothelium (especially abnormal/damaged valves) → platelet-fibrin-bacteria aggregates form vegetations
• Vegetations: Friable, irregular, cauliflower-like masses on valve leaflets (usually on mitral and aortic valves, left-sided); contain bacteria, fibrin, inflammatory cells, necrotic tissue
• Gross: Large, bulky, destructive vegetations; leaflet ulceration/perforation; chordae tendineae involvement; valve insufficiency
• Systemic effects (emboli): Osler nodes (fingertip tender nodules), Janeway lesions (painless palm/sole hemorrhages), Roth spots (retinal), splenic/renal infarcts, stroke (septic emboli)
• Duke Criteria: Used for diagnosis (major: positive blood cultures, echocardiographic evidence; minor: fever, predisposing condition, vascular/embolic phenomena)

Images

Intraoperative photos: cauliflower-like, friable vegetations (white arrows) on mitral valve leaflets with hemorrhagic areas and inflammatory thickening of subvalvular apparatus

Explanted heart: tan-pink friable vegetation on mitral valve; markedly elongated edematous chordae tendineae; focal cusp thickening with microabscess formation

6. Rheumatic Heart Disease

Pathological Changes

• Acute phase (rheumatic carditis): Pancarditis (all layers); Aschoff bodies (pathognomonic) — granulomatous foci with Anitschkow cells (caterpillar cells = activated macrophages with characteristic chromatin pattern); MacCallum plaques on posterior LA wall
• Valves: Sterile vegetations (verrucae) along valve closure lines during acute phase; subsequent fibrosis and scarring
• Chronic/late changes:
  • Mitral stenosis (most common, 70%): leaflet thickening, commissural fusion → "fish-mouth" or "buttonhole" orifice; chordal shortening/fusion; calcification
  • Mitral valve area reduced from normal 4–6 cm² to < 1 cm² in severe stenosis
  • Left atrial dilation → atrial fibrillation → mural thrombus → systemic embolism
  • Other valves: aortic > tricuspid > pulmonary (in decreasing frequency)
• Microscopy: Fibrosis, neovascularization, calcification of leaflets

Images

Gross pathology: atrial view of mitral valve showing fish-mouth/buttonhole orifice; marked leaflet thickening, fibrosis, commissural fusion, and yellow-white calcification deposits

TTE: (a) parasternal long-axis: anterior leaflet doming/hockey-stick deformity; (b) parasternal short-axis: commissural fusion (white arrows); MVA planimetry = 0.73 cm² (severe stenosis)

7. Pericarditis

Pathological Changes

• Causes: Viral (coxsackievirus A/B, echovirus, EBV, CMV, HIV); bacterial (TB — constrictive); post-MI (Dressler syndrome); uremia; autoimmune (SLE, RA); neoplastic; post-radiation
• Types by exudate:
  • Fibrinous (most common): Fibrin deposition on pericardial surfaces → "bread and butter" appearance on gross inspection (shaggy, yellow-white, irregular surface replacing normal smooth glistening serosal surface)
  • Serous: Clear fluid (viral, autoimmune)
  • Serofibrinous/hemorrhagic: TB, malignancy
  • Purulent: Bacterial (Staphylococci, gram-negatives)
• Pericardial effusion: Accumulation of fluid; if rapid → cardiac tamponade (Beck's triad: hypotension, raised JVP, muffled heart sounds)
• Constrictive pericarditis: Fibrosis + calcification → rigid pericardium → impaired cardiac filling → diastolic dysfunction; "pericardial knock," Kussmaul's sign
• ECG: Saddle-shaped diffuse ST elevation + PR depression (pathognomonic)

Images

Intraoperative pericardiotomy: epicardial surface covered by thick, shaggy whitish-yellow fibrinous exudate with cobblestone texture — pathognomonic "bread and butter" pericarditis

Autopsy heart: dull brick-red rough granular fibrinous exudate coating the pericardial surface; normal smooth serosal appearance completely replaced; prominent at atrial regions and apex

8. Aortic Stenosis (AS)

Pathological Changes

• Causes by age:
  • Young < 60 y: Congenital bicuspid aortic valve (1–2% population) → accelerated calcification
  • Elderly > 65 y: Calcific (senile/degenerative) AS — most common; active process similar to atherosclerosis (lipid deposition, inflammation, calcification)
  • Any age (less common now): Rheumatic (usually combined MS + AS)
• Pathophysiology: Valve orifice narrows (normal 3–4 cm²; severe < 1 cm²) → LV pressure overload → concentric LV hypertrophy (wall thickness increases to normalize wall stress) → diastolic dysfunction → eventually systolic dysfunction and cardiac decompensation
• Gross: Thickened, irregular, heavily calcified leaflets; nodular calcium deposits; fused commissures (rheumatic) vs. calcified but mobile cusps (degenerative)
• Classic symptom triad (SAD): Syncope, Angina, Dyspnea — with each symptom, prognosis worsens (2–5 years if untreated once symptoms appear)
• Auscultation: Harsh systolic ejection murmur at RUSB radiating to carotids; paradoxical splitting of S2; slow-rising pulse (pulsus parvus et tardus)

Images

Gross pathology: aortic view of bicuspid valve; two fused, thickened leaflets with prominent yellow-white calcified nodules severely restricting valve opening

Surgical specimen: markedly thickened, distorted aortic cusp; large yellow-orange calcified nodules and grain-like white deposits; chronic inflammatory foci (reddish areas)

9. Congenital Heart Disease — Tetralogy of Fallot (TOF)

The Four Components

1. Ventricular Septal Defect (VSD) — large perimembranous defect
2. Pulmonary stenosis/infundibular stenosis — RVOT obstruction
3. Overriding aorta — aortic root displaced rightward over VSD
4. Right ventricular hypertrophy (RVH) — secondary to outflow obstruction

Pathological Changes

• Embryology: Abnormal rotation/migration of conotruncal septum → malalignment of great vessels
• Hemodynamics: RVOT obstruction → RV pressure rises → right-to-left shunting through VSD → deoxygenated blood enters systemic circulation → central cyanosis ("blue baby")
• Degree of shunt: Depends on severity of RVOT obstruction; mild (pink TOF = left-to-right shunt) vs. severe (marked cyanosis)
• "Tet spells": Episodes of sudden hypercyanosis from muscular RVOT spasm; treated by knee-chest position (increases SVR) or morphine/propranolol
• Polycythemia: Compensatory; risk of cerebral thrombosis and abscess
• Gross: RV hypertrophy, hypoplastic pulmonary trunk, overriding aorta, large perimembranous VSD
• Treatment: Complete surgical repair (VSD patch + RVOT reconstruction)

Images

Gross sagittal heart specimen: large membranous VSD (VD), overriding aorta (A) receiving blood from both ventricles, hypoplastic pulmonary trunk (PT), narrow RVOT (black arrow), hypertrophic proximal septum (star)

TTE: (A) PLAX view with large perimembranous VSD and overriding aorta; (B) short-axis with CW Doppler showing severe pulmonary infundibular stenosis pressure gradient of 70 mmHg

10. Restrictive Cardiomyopathy (Cardiac Amyloidosis)

Pathological Changes (Cardiac Amyloidosis as Paradigm)

• Types: AL amyloidosis (immunoglobulin light chains, plasma cell dyscrasias/multiple myeloma) and ATTR amyloidosis (transthyretin; wild-type = senile, or hereditary TTR mutations)
• Gross: Concentric LV and RV wall thickening (hypertrophy); waxy, pale yellowish appearance; nodular deposits on endocardium; biatrial enlargement; thickened interatrial septum; thickened AV valves
• Microscopy:
  • H&E: Pale pink amorphous material infiltrating myocardial interstitium between myocytes
  • Congo red stain: Salmon-pink deposits → diagnostic
  • Polarized light: Pathognomonic apple-green birefringence
  • Immunohistochemistry: TTR-positive (ATTR) vs. κ/λ light chain (AL)
• Cardiac MRI: Diffuse subendocardial late gadolinium enhancement (LGE) with base-to-apex gradient; "inability to null" the myocardium; biventricular wall thickening; atrial dilation
• ECG paradox: Despite massive hypertrophy, shows low-voltage QRS (amyloid replaces conducting myocardium) + pseudo-infarct pattern
• Echo: Restrictive filling (E/A > 2, short deceleration time); "sparkling" granular myocardium on older echo; tissue Doppler shows severe diastolic dysfunction

Images

Panel A: Cardiac MRI with diffuse subendocardial LGE (RV transmural); B: Gross cross-section with concentric LV and RV hypertrophy; C: Congo red — salmon-pink perivascular and interstitial deposits; D: Polarized light — pathognomonic apple-green birefringence

Left: gross heart with massive LV/RV/papillary muscle hypertrophy, waxy deposits, and atrial nodules; Right: H&E, Congo red, polarized light apple-green birefringence, and IHC for TTR and κ light chains

Summary Table