Valvular Heart Disease — Pathology

Valvular heart disease (VHD) is dysfunction of one or more cardiac valves producing either stenosis (failure to open, obstruction to forward flow) or regurgitation/insufficiency (failure to close, backward flow). From the pathology angle, NEET PG loves the morphology — Aschoff nodules, Anitschkow cells, MacCallum patch, vegetation characteristics, Janeway lesions and Osler nodes. These notes drill those facts cold.

Definition & classification

A valve lesion is described by which valve, which functional defect, and the underlying disease. Pure stenosis or pure regurgitation may coexist as mixed disease (common in rheumatic mitral valve).

Functional defect	Mechanism	Common causes
Stenosis	Valve fails to open fully → pressure overload upstream	Rheumatic (MS), calcific degeneration (AS), congenital bicuspid
Regurgitation	Valve fails to close → volume overload	Rheumatic, IE, MVP, aortic root dilatation, papillary muscle rupture

Stenosis is almost always a chronic process (scarring, calcification). Regurgitation may be acute (chest pain, ruptured chordae, IE perforation) or chronic.

High-yield: The single most common valve lesion overall in the developed world is calcific (degenerative) aortic stenosis. In India and developing nations, rheumatic heart disease (RHD) remains the leading cause of VHD, and the mitral valve is the most commonly affected.

Most common valve affected in RHD: Mitral (almost always involved) → Mitral + Aortic → rarely tricuspid; pulmonary valve is least involved.

Rheumatic heart disease (RHD)

Etiology & pathophysiology

RHD is the chronic sequel of acute rheumatic fever (ARF), an immunologically mediated multisystem disease following group A β-haemolytic streptococcal (Streptococcus pyogenes) pharyngitis (NOT skin infection — that causes glomerulonephritis).

Mechanism is molecular mimicry: antibodies and CD4+ T cells raised against streptococcal M protein cross-react with cardiac self-antigens (myosin, laminin, vimentin). This produces a type II hypersensitivity plus T-cell mediated injury. Latent period after sore throat is 2–4 weeks.

High-yield: ARF is diagnosed by the revised Jones criteria — 2 major, or 1 major + 2 minor, PLUS evidence of preceding strep infection (raised ASO titre, anti-DNase B, positive throat culture).

Jones criteria mnemonic — major = "JONES" / ♥CASES":

• J – Joints (migratory polyarthritis)
• ♥ (O) – Carditis (pancarditis)
• N – Nodules (subcutaneous, over extensors)
• E – Erythema marginatum
• S – Sydenham chorea (St. Vitus dance)

Minor criteria: fever, arthralgia, raised ESR/CRP, prolonged PR interval on ECG.

Pathology — the classic morphology

ARF causes a pancarditis (endocardium + myocardium + pericardium).

Aschoff body (Aschoff nodule) — the pathognomonic lesion of rheumatic fever. It is a focus of granulomatous inflammation found in the interstitium of the myocardium (perivascular), and in the subendocardium/valves.

Aschoff body component	Description
Central zone	Fibrinoid necrosis of collagen
Anitschkow cells	Activated macrophages; abundant cytoplasm, central slender wavy chromatin bar → "caterpillar cells" / "owl-eye" nuclei in cross-section
Aschoff giant cells	Multinucleated cells derived from Anitschkow cells
Surrounding	T lymphocytes, plasma cells, occasional eosinophils

High-yield (the recurring one-liner): The cell characteristic of the Aschoff nodule is the Anitschkow cell (modified macrophage) with "caterpillar / owl-eye" nucleus. Multinucleated forms = Aschoff giant cells. These are NOT derived from myocytes.

Endocardial / valvular lesions:

• Verrucae (vegetations): small (1–2 mm), warty, sterile nodules along the lines of closure of valve leaflets. They are firmly attached, do not embolise readily, and do not destroy the valve acutely.
• MacCallum patch: map-like area of subendocardial thickening in the left atrium (posterior wall), caused by regurgitant jets in chronic mitral disease.

Chronic RHD morphology (years later):

• Leaflet thickening, fibrosis and calcification
• Commissural fusion
• Thickening, shortening and fusion of chordae tendineae
• Result in mitral stenosis: "fish-mouth" / "buttonhole" valve appearance.

High-yield: Mitral stenosis from RHD classically gives a mid-diastolic rumbling murmur with opening snap and a loud S1. It causes left atrial enlargement → atrial fibrillation, mural thrombus (left atrial appendage is the favourite site), pulmonary hypertension and right heart failure. The LV is characteristically normal in pure MS.

Stepwise rheumatic mitral disease:

1. Strep pharyngitis → 2. Molecular mimicry, ARF → 3. Verrucae + Aschoff bodies (acute) → 4. Healing with fibrosis → 5. Commissural fusion + chordal shortening → 6. Mitral stenosis → 7. LA dilatation, AF, pulmonary HTN, right heart failure.

Infective endocarditis (IE)

Definition & classification

Microbial (usually bacterial) infection of the endocardial surface, characteristically forming bulky, friable vegetations of fibrin, platelets and organisms on valves.

Feature	Acute IE	Subacute IE
Organism virulence	High	Low
Classic organism	Staphylococcus aureus	Streptococcus viridans
Valve status	Often normal valve	Previously damaged valve (RHD, MVP)
Course	Days–weeks, destructive	Weeks–months, indolent
Vegetations	Large, bulky	Smaller

High-yield: Overall most common cause of IE today is Staphylococcus aureus (especially with IV drug use, prosthetic valves, healthcare-associated). Strep viridans classically affects previously damaged native valves (subacute). Strep gallolyticus (bovis) → think colon carcinoma; enterococci → GU/GI procedures.

Special associations:

• IV drug users → right-sided IE, tricuspid valve, often S. aureus → septic pulmonary emboli.
• Prosthetic valve, early (<60 days) → Staphylococcus epidermidis (coagulase-negative staph).
• Culture-negative IE → HACEK group (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella), Coxiella, Bartonella.
• Marantic + then think malignancy; prosthetic + fungal → Candida/Aspergillus (large vegetations, embolise).

Pathology of vegetations

IE vegetations are bulky, friable, destructive masses on the valve leaflets (atrial surface of AV valves, ventricular surface of semilunar valves). They contain fibrin, inflammatory cells, and colonies of organisms. Because they are friable they embolise (septic emboli) → infarcts and metastatic abscesses (brain, kidney, spleen).

Valve destruction → perforation, ring abscess, chordal rupture → acute regurgitation.

High-yield: The modified Duke criteria diagnose IE. Major criteria: (1) positive blood culture with typical organism (≥2 separate cultures), (2) echocardiographic evidence of vegetation/abscess/new dehiscence, or new valvular regurgitation. TEE (transoesophageal echo) is more sensitive than TTE for vegetations. Diagnosis = 2 major, OR 1 major + 3 minor, OR 5 minor.

Peripheral / immunological signs (very testable)

Sign	Nature	Pathophysiology
Janeway lesions	Painless, erythematous macules on palms/soles	Septic (embolic) microabscesses
Osler nodes	Painful, raised nodules on finger/toe pulp	Immune complex vasculitis ("Ouch! = Osler")
Roth spots	Retinal haemorrhages with pale centre	Immune-mediated
Splinter haemorrhages	Subungual linear streaks	Microemboli
Petechiae, clubbing, splenomegaly	—	Chronic immune stimulation/emboli

High-yield mnemonics: "Osler = Ouch (painful, immune)"; "Janeway = no pain, on the way (palms/soles, embolic, flat)." Glomerulonephritis in IE is immune-complex (type III) mediated.

Non-infective endocarditis

Non-bacterial thrombotic endocarditis (NBTE) — "marantic endocarditis"

• Sterile deposits of fibrin and platelets on valve leaflets along the line of closure.
• Vegetations are small (1–5 mm), bland, loosely attached, with NO inflammation and NO organisms → but they embolise easily.
• Associated with hypercoagulable states: mucinous adenocarcinoma (pancreas), other malignancies, DIC, sepsis, indwelling catheters (Trousseau syndrome / paraneoplastic).
• Causes little valve damage itself; danger is systemic embolisation.

High-yield: Think mucin-secreting adenocarcinoma (pancreas, GI, lung) → marantic (NBTE) endocarditis → bland sterile vegetations that embolise. Migratory thrombophlebitis with this = Trousseau syndrome.

Libman–Sacks endocarditis (LSE)

• The endocarditis of systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome.
• Sterile, verrucous vegetations, classically small-to-medium, occurring on either surface of the leaflets (i.e., both sides — the distinguishing feature) and extending onto chordae and mural endocardium.
• Mitral and tricuspid valves favoured; underside of the valve is characteristically involved.
• Microscopically: fibrinoid necrosis, haematoxylin bodies of Gross, mononuclear infiltrate.

High-yield (classic distractor): Libman–Sacks vegetations occur on both surfaces of the valve and can be on the undersurface — this is the buzzword that separates it from rheumatic (line of closure) and IE (atrial surface of AV valves). Associated with SLE / antiphospholipid syndrome.

Comparison of vegetations — the master table

Type	Size	Sterile?	Location	Destruction	Embolise	Association
Rheumatic (verrucae)	Small (1–2 mm)	Sterile	Line of closure	Minimal acutely	Rarely	RHD/ARF
Infective endocarditis	Large, bulky	Infected	Valve surface	Severe	Yes (septic)	S. aureus, S. viridans
NBTE (marantic)	Small (1–5 mm)	Sterile	Line of closure	Minimal	Yes (bland)	Adenocarcinoma, DIC
Libman–Sacks	Small–medium	Sterile	Both surfaces	Mild	Occasionally	SLE, APLA

Calcific (degenerative) aortic stenosis

• The most common valve disease in the elderly / developed world.
• "Wear and tear" plus inflammation: lipid deposition, inflammation, dystrophic calcification of the cusps from the base outward.
• Calcific masses pile up in the sinuses of Valsalva, splaying the cusps; commissures are NOT fused (helps distinguish from rheumatic AS, which does fuse commissures).
• Bicuspid aortic valve accelerates this by ~1–2 decades (presents in 50s–60s vs 70s–80s).

High-yield: Calcific AS = no commissural fusion; rheumatic AS = commissural fusion + nearly always coexistent mitral disease. AS produces LV concentric hypertrophy (pressure overload), angina, syncope, exertional dyspnoea (mnemonic "SAD"), and a harsh ejection systolic murmur radiating to the carotids with a slow-rising pulse (pulsus parvus et tardus).

Mitral valve prolapse (MVP) — myxomatous degeneration

• One or both mitral leaflets are enlarged, redundant and "floppy", prolapsing into the LA during systole.
• Histology: myxomatous degeneration — expansion of the spongiosa layer by mucopolysaccharide (proteoglycan), attenuation of fibrosa.
• Association: Marfan syndrome (fibrillin-1 / FBN1 mutation), Ehlers–Danlos.
• Classic auscultation: mid-systolic click ± late systolic murmur.

High-yield: MVP is the most common valve lesion in the developed-world young/general population and a cause of chronic mitral regurgitation. Complications: IE, chordal rupture (acute MR), arrhythmias, rarely sudden death.

Clinical features (consequence by valve)

• Mitral stenosis: dyspnoea, haemoptysis, AF, loud S1, opening snap, mid-diastolic rumble; LA enlargement (dysphagia, hoarseness = Ortner syndrome).
• Mitral regurgitation: pansystolic murmur to axilla, LA + LV dilatation.
• Aortic stenosis: angina, syncope, dyspnoea; ESM to carotids, slow-rising pulse.
• Aortic regurgitation: early diastolic murmur, wide pulse pressure, Corrigan/water-hammer pulse, de Musset, Quincke signs; LV volume overload (cor bovinum).

Complications

• Cardiac: heart failure (pressure vs volume overload), arrhythmias (AF), pulmonary hypertension.
• Embolic: systemic emboli (LA thrombus in MS; septic emboli in IE; bland emboli in NBTE).
• Infective: IE superimposed on any abnormal valve.
• From IE specifically: valve perforation, ring/myocardial abscess, mycotic aneurysm, immune-complex glomerulonephritis, septic infarcts (brain, spleen, kidney).

Key differentials (morphology buzzwords)

• Aschoff body / Anitschkow caterpillar cells → rheumatic fever.
• Vegetations on line of closure, small, sterile → rheumatic OR NBTE (clinical context: malignancy → NBTE).
• Bulky destructive infected vegetations + fever → IE.
• Vegetations on both surfaces of valve + SLE → Libman–Sacks.
• No commissural fusion + elderly + calcified cusps → calcific AS.
• Floppy redundant leaflets + Marfan + click → MVP (myxomatous).

Recently asked / exam angle

• "Cell characteristic of Aschoff nodule?" → Anitschkow cell (modified/activated macrophage) — the single most repeated VHD one-liner. Beware the distractor "myocyte."
• "Caterpillar / owl-eye nucleus belongs to?" → Anitschkow cell.
• Pathognomonic lesion of rheumatic fever → Aschoff body.
• MacCallum patch location → posterior wall of left atrium.
• Painful vs painless lesions in IE → Osler (painful, immune) vs Janeway (painless, embolic).
• Most common organism of IE in IV drug users → S. aureus, tricuspid valve.
• Strep gallolyticus (bovis) IE → screen for colon carcinoma.
• Vegetations on both surfaces of valve → Libman–Sacks (SLE).
• Sterile vegetations + mucinous adenocarcinoma → NBTE / marantic.
• Commissural fusion present → rheumatic; absent → degenerative calcific AS.
• Most commonly involved valve in RHD → mitral.
• Antibody target in RHD molecular mimicry → streptococcal M protein vs cardiac myosin.

Rapid revision

1. Aschoff body = pathognomonic of rheumatic fever; contains Anitschkow ("caterpillar/owl-eye") cells = activated macrophages; multinucleate form = Aschoff giant cell.
2. RHD mechanism = molecular mimicry, M protein vs cardiac myosin, type II hypersensitivity, 2–4 weeks after strep pharyngitis.
3. Mitral valve is most affected in RHD → fish-mouth/buttonhole stenosis with commissural fusion and chordal shortening.
4. MacCallum patch = subendocardial thickening, posterior left atrium.
5. Rheumatic verrucae = small, sterile, on line of closure, don't embolise.
6. IE most common organism = S. aureus overall; S. viridans = subacute on damaged valves; IVDU = tricuspid, S. aureus.
7. IE diagnosis = modified Duke criteria; TEE most sensitive for vegetations.
8. Osler nodes = painful, immune-complex; Janeway lesions = painless, embolic (palms/soles).
9. NBTE (marantic) = sterile, bland, on line of closure, embolise, linked to mucinous adenocarcinoma/DIC (Trousseau).
10. Libman–Sacks = SLE/antiphospholipid; sterile verrucae on both surfaces of valve; haematoxylin bodies.
11. Calcific AS = commonest VHD in elderly; no commissural fusion; bicuspid valve presents earlier; symptoms = angina, syncope, dyspnoea.
12. MVP = myxomatous degeneration (spongiosa expansion), Marfan/FBN1, mid-systolic click; commonest cause of chronic MR in the young.