Valvular Heart Disease

Mechanical and Hemodynamic Alterations

• Stenotic lesions create resistance to forward flow, requiring compensatory concentric hypertrophy of the proximal chamber; chronically, the chamber becomes dilated and dysfunction ensues as ventricular wall stress overwhelms myocyte contractility
• Regurgitant lesions allow backward flow during systole (AV valves) or diastole (semilunar valves), imposing eccentric hypertrophy through increased preload on the receiving chamber; the combination of elevated filling pressures and wall stress eventually leads to systolic dysfunction
• Functional/secondary regurgitation develops when geometric chamber remodeling (dilatation) and papillary muscle displacement prevent adequate valve leaflet coaptation despite structurally normal leaflets

Cellular and Molecular Mechanisms

• Endothelial injury from abnormal hemodynamic shear stress and turbulent flow activates expression of adhesion molecules (ICAM-1, VCAM-1) and recruits inflammatory cells
• Valve interstitial cells (VICs) undergo transition to myofibroblasts via TGF-β signaling, promoting excessive collagen deposition, extracellular matrix remodeling, and fibrosis
• In calcific aortic stenosis, oxidized lipids accumulate on valve leaflets, triggering osteogenic differentiation of VICs through alkaline phosphatase and Runx2 expression, resulting in ectopic bone and cartilage formation (metaplasia)
• Inflammatory pathways (NF-κB, MAPK) perpetuate a chronic inflammatory state characterized by macrophage infiltration and release of proteolytic enzymes (matrix metalloproteinases) that degrade elastic fibers and collagen

Morphological Consequences

• Leaflet thickening, calcification, and fibrosis disrupt normal three-dimensional architecture and compromise mobility
• Commissural fusion (characteristic of rheumatic disease) physically restricts leaflet opening; neovascularization and pannus formation further impair function
• Papillary muscle rupture, elongation, or ischemia disrupts the chordal apparatus in functional mitral regurgitation
• Progressive ventricular remodeling includes chamber dilatation, wall thinning, and sarcomeric dysfunction, ultimately culminating in systolic heart failure

Aortic Stenosis

• Degenerative/calcific aortic stenosis (most common; >80% of cases in developed countries): age >60 years, male predominance, hyperlipidemia, hypertension, chronic kidney disease with secondary hyperparathyroidism, bicuspid aortic valve
• Rheumatic heart disease: prior acute rheumatic fever (streptococcal infection), persistent inflammation, predominantly in developing nations and older patients in developed countries
• Bicuspid aortic valve: congenital leaflet abnormality predisposing to premature calcification and stenosis (10-15% of population variant)

Aortic Regurgitation (Insufficiency)

• Primary (organic) causes: calcific aortic stenosis, bicuspid aortic valve, rheumatic disease, infective endocarditis with vegetation or perforation, trauma, aortic root dilatation (Marfan syndrome, Ehlers-Danlos syndrome, syphilis)
• Secondary (functional) causes: aortic root dilatation from hypertension, aortic dissection, atherosclerosis, or inflammatory aortitis (syphilis, Takayasu arteritis, ankylosing spondylitis)

Mitral Stenosis

• Rheumatic heart disease: accounts for >90% of cases worldwide; commissural fusion and progressive fibrosis narrow the orifice
• Rare: congenital abnormalities, cor triatriatum, left atrial myxoma obstructing flow

Mitral Regurgitation (Insufficiency)

• Primary (organic) causes: rheumatic disease (leaflet retraction), myxomatous degeneration/mitral valve prolapse (MVP; degenerative fibroxanthomatous replacement of spongiosa), infective endocarditis, trauma, papillary muscle rupture (acute MI), connective tissue disorders (Marfan, Ehlers-Danlos)
• Secondary (functional) causes: left ventricular dilatation with papillary muscle displacement (dilated cardiomyopathy, prior MI, chronic ischemia), left atrial enlargement from atrial fibrillation, ischemic mitral regurgitation

Tricuspid Regurgitation

• Predominantly secondary/functional from right ventricular dilatation (left heart failure, pulmonary hypertension) or right atrial enlargement (atrial fibrillation)
• Primary causes: rheumatic disease, endocarditis (especially in IV drug users), carcinoid syndrome (serotonin-induced fibrosis), trauma, pacemaker/ICD lead-related

Pulmonary Stenosis

• Congenital: most common; associated with Noonan syndrome, tetralogy of Fallot
• Acquired: rheumatic disease, carcinoid syndrome

Pulmonary Regurgitation

• Often secondary from pulmonary hypertension or left heart failure
• Primary: tetralogy of Fallot (post-surgical), endocarditis, trauma

Global Risk Factors

• Age, male gender, hypertension, hyperlipidemia, chronic kidney disease, connective tissue disorders, pregnancy (increased hemodynamic demands), obesity

Aortic Stenosis

• Cardinal symptoms (late-stage): angina (even without coronary disease, from increased myocardial oxygen demand and reduced diastolic perfusion), syncope (fixed cardiac output during exertion prevents adequate cerebral perfusion), dyspnea (from LV dysfunction and pulmonary congestion)
• Physical exam: harsh, systolic ejection murmur at the right upper sternal border radiating to the carotids; S4 gallop (forceful atrial contraction against stiffened LV); slow, sustained carotid pulse (pulsus parvus et tardus); paradoxical splitting of S2 (prolonged LV ejection time)
• ECG findings: left ventricular hypertrophy with strain pattern (T wave inversions in lateral leads), left axis deviation; conduction abnormalities in calcific disease
• Echocardiography: thickened, calcified leaflets with restricted opening; decreased aortic valve area (<1.0 cm² = severe); elevated transaortic gradients; LV hypertrophy
• Natural history: prolonged asymptomatic phase followed by rapid deterioration once symptoms emerge (high mortality without intervention)

Aortic Regurgitation (Acute vs. Chronic)

• Acute AR (endocarditis, aortic dissection): sudden severe dyspnea, pulmonary edema, hypotension, normal or absent murmur (insufficient time for LV adaptation)
• Chronic AR: early diastolic, high-pitched, blowing decrescendo murmur at the left sternal border; wide pulse pressure with bounding pulses (water-hammer pulse, Corrigan's pulse); systolic flow murmur at the apex (Austin Flint murmur); S3 gallop; diastolic rumble of mitral origin from AR jet
• Physical findings: head bobbing with systolic impulse (de Musset's sign), systolic pulsation of the uvula (Müller's sign), capillary pulsations in nail beds (Quincke's pulse)
• Chest X-ray: marked cardiomegaly with boot-shaped silhouette (LV dilatation)
• Symptoms: gradual onset of exertional dyspnea, orthopnea, and nocturnal dyspnea as LV function declines

Mitral Stenosis

• Cardinal symptoms: dyspnea (most common; from elevated pulmonary venous pressures), orthopnea, paroxysmal nocturnal dyspnea, fatigue, palpitations (often from atrial fibrillation)
• Physical exam: loud S1 (forceful MV closure before it opens fully), opening snap (abrupt halting of MV by fused commissures), low-pitched, rumbling, mid-to-late diastolic murmur at the apex (accentuated with left lateral decubitus position and expiration); right ventricular heave (RV hypertrophy); atrial fibrillation with irregular pulse
• ECG: left atrial enlargement (broad, bifid P wave—P mitrale), right axis deviation, right ventricular hypertrophy
• Chest X-ray: straightening of the left heart border (LA dilatation), double density at the right heart border, pulmonary vascular redistribution, pulmonary edema in severe cases
• Echocardiography: reduced mitral valve area (<1.5 cm² = severe); doming of leaflets; commissural fusion; increased transmitral gradients; LA enlargement

Mitral Regurgitation (Acute vs. Chronic)

• Acute MR (papillary muscle rupture, endocarditis): sudden severe dyspnea, pulmonary edema, cardiogenic shock; systolic murmur may be soft or absent if regurgitation is severe (little pressure gradient)
• Chronic MR: holosystolic (pansystolic), high-pitched blowing murmur at the apex radiating to the axilla; S3 gallop (from rapid LV filling); hyperkinetic, displaced LV apical impulse (eccentric hypertrophy); giant CV wave in JVP if pulmonary hypertension develops
• Symptoms: insidious dyspnea on exertion, orthopnea, fatigue; often asymptomatic until LV dysfunction is advanced
• Chest X-ray: cardiomegaly with left atrial enlargement; pulmonary congestion
• ECG: left atrial enlargement, left ventricular hypertrophy, atrial fibrillation

Mitral Valve Prolapse (MVP)

• Often asymptomatic, discovered incidentally on echocardiography
• Classic murmur: mid-to-late systolic click (best heard with patient standing) followed by a late systolic murmur if MR is present
• Symptoms (if present): atypical chest pain, palpitations, dyspnea, anxiety
• Genetic associations: Marfan syndrome, Ehlers-Danlos syndrome (connective tissue laxity)

Tricuspid Regurgitation

• Often asymptomatic until secondary to other cardiac pathology
• Physical exam: pulsatile hepatomegaly (systolic hepatic pulsation), prominent CV wave in JVP, holosystolic murmur at the left lower sternal border (increases with inspiration—Carvallo's sign)
• Symptoms: fatigue, peripheral edema, ascites (right heart failure manifestations)

Histological Findings

• Rheumatic heart disease: verrucous vegetations along the line of closure composed of fibrin, inflammatory cells, and platelets; Aschoff bodies (pathognomonic for acute rheumatic fever) consisting of granulomatous inflammation with Anitschkow cells (activated macrophages with central wavy ribbon of chromatin) and Aschoff giant cells; fibrinoid necrosis of valve connective tissue; chronic scarring, commissural fusion, fibrosis, and calcification
• Calcific aortic stenosis: calcium deposition within valve leaflets; osteoid and bone formation (heterotopic ossification); lipid accumulation; smooth muscle cells and myofibroblasts; neovascularization; minimal inflammatory infiltrate compared to rheumatic disease
• Myxomatous mitral valve disease (MVP): redundant leaflets with abnormal spongiosa; fibroxanthomatous replacement of the central fibrosa layer; elastic fiber fragmentation; excessive glycosaminoglycan deposition; increased cell density
• Endocarditis: vegetation composed of platelets, fibrin, bacteria, and inflammatory cells attached to valve leaflets; valve perforation or ulceration; abscess formation; acute inflammation
• Carcinoid heart disease: plaque-like deposits on valve surfaces and endocardium; smooth muscle proliferation; fibrosis without calcification; characteristic of right-sided valves (tricuspid > pulmonary)

Gross Pathology

• Stenotic lesions: leaflets appear thickened, white-tan, fibrotic, with restricted mobility; aortic stenosis shows central calcium nodules; mitral stenosis displays commissural fusion with a fish-mouth appearance of the orifice
• Regurgitant lesions: leaflets may show perforation, vegetation, or retraction; thickening and rolling of edges (chronic disease); dilated valve annulus
• Degenerative disease: granular, chalky appearance of valve surfaces; pebbled or bumpy texture from calcium deposition

Imaging

• Transthoracic echocardiography (TTE): two-dimensional and Doppler assessment of valve morphology, leaflet motion, chamber dimensions; trans-esophageal echocardiography (TEE) provides superior resolution, particularly for endocarditis, paravalvular defects, and surgical planning
• Cardiac catheterization: simultaneous recording of ventricular and atrial (or aortic and LV) pressures to calculate valve gradients and effective orifice area; measurement of cardiac output; coronary angiography to assess for CAD
• ECG: evidence of chamber hypertrophy, chamber enlargement, arrhythmias, ischemia
• Chest X-ray: cardiomegaly, chamber-specific enlargement, calcification (on fluoroscopy), pulmonary congestion

Diagnostic Criteria

• Aortic Stenosis Severity: mild (AVA >1.5 cm², mean gradient <25 mmHg), moderate (AVA 1.0-1.5 cm², mean gradient 25-40 mmHg), severe (AVA <1.0 cm², mean gradient >40 mmHg); low-gradient AS (<40 mmHg) with reduced EF represents severe disease with poor prognosis
• Aortic Regurgitation Severity: mild (small jet width <25% of aortic root), moderate (25-65% of aortic root), severe (>65% of aortic root, holodiastolic flow reversal in descending aorta, regurgitant volume >60 mL/beat)
• Mitral Stenosis Severity: mild (MVA >1.5 cm²), moderate (MVA 1.0-1.5 cm²), severe (MVA <1.0 cm²); mean transmitral gradient and pulmonary artery pressure assessed
• Mitral Regurgitation Severity: mild (small, central jet <20% of LA area), moderate (jet area 20-

Immediate stabilisation (acute, regurgitant lesions are the emergencies)

• Acute severe MR or AR (papillary muscle rupture, endocarditis, dissection): afterload reduction with an IV vasodilator (sodium nitroprusside) plus an inotrope (dobutamine) to unload the ventricle, with emergency surgery — per the ACC/AHA 2020 Valvular Heart Disease guideline the unadapted ventricle cannot compensate and medical therapy is only a bridge
• Contraindicated: intra-aortic balloon pump in significant AR (diastolic augmentation worsens regurgitation); beta blockade in acute AR (compensatory tachycardia shortens diastolic regurgitant time and is protective); aggressive preload/afterload reduction (nitrates, high-dose diuretics) in severe AS, where a fixed obstruction makes cardiac output preload-dependent and precipitates hypotension

Medical therapy — no drug reverses valve disease

• Rate control (beta blockers, e.g., metoprolol): lengthens diastolic filling time in mitral stenosis; AF onset often precipitates decompensation
• Anticoagulation (vitamin K antagonist, warfarin): ACC/AHA 2020 requires a VKA — not a DOAC — for AF with rheumatic mitral stenosis and for all mechanical valves
• Antihypertensives: ACE inhibitors/ARBs or dihydropyridine CCBs are safe and indicated for hypertension in chronic AR and AS; statins do not slow calcific AS
• Secondary rheumatic prophylaxis: intramuscular penicillin G benzathine per AHA recommendations after rheumatic fever
• Guideline-directed HF therapy (ARNI or ACEI/ARB, beta blocker, MRA, and SGLT2 inhibitor) is first-line for secondary MR before any valve intervention

Definitive management

• Severe symptomatic AS: aortic valve replacement (SAVR vs. TAVI) — ACC/AHA 2020 favors SAVR in younger patients with long life expectancy and TAVI in older/high-risk patients; also indicated when asymptomatic with reduced LVEF. Balloon valvuloplasty in adults is palliative only
• Severe primary MR: surgical repair preferred over replacement; transcatheter edge-to-edge repair for prohibitive surgical risk
• Severe rheumatic MS: percutaneous mitral balloon commissurotomy if morphology is favorable and there is no LA thrombus or more-than-mild MR

Disease-related

• Sudden cardiac death (emergency): in severe AS, fixed output plus subendocardial ischemia of the hypertrophied LV; heralded by exertional syncope — an indication for prompt valve replacement, not observation
• Atrial fibrillation with LA thrombus and systemic embolism (emergency): mitral stenosis raises LA pressure and causes LA dilatation/stasis; presents as acute stroke or limb ischemia
• Pulmonary hypertension and right heart failure: back-transmission of elevated LA pressure; signaled by RV heave, loud P2, elevated JVP with prominent CV wave, pulsatile liver
• Hemoptysis: rupture of dilated bronchial veins in mitral stenosis; Ortner syndrome is hoarseness from LA compression of the left recurrent laryngeal nerve
• Heyde syndrome: high shear across a stenotic aortic valve cleaves von Willebrand factor multimers (acquired type 2A vWD), causing GI bleeding from angiodysplasia; resolves after AVR
• Infective endocarditis: abnormal endothelium seeds bacteremia; new regurgitant murmur, fever, embolic phenomena
• Progressive heart failure: eccentric or concentric remodeling exhausts contractile reserve; falling LVEF in a regurgitant lesion is already late disease
• Conduction block: annular calcium extends into the septum near the AV node/His bundle

Treatment-related

• Complete heart block after TAVI (emergency): mechanical injury to the adjacent conduction system; new LBBB or high-grade block on telemetry → permanent pacemaker
• Prosthetic valve thrombosis (emergency): subtherapeutic INR; muffled mechanical click, new gradient on echo, embolism
• Prosthetic valve endocarditis: early cases favor coagulase-negative staphylococci; look for paravalvular abscess and new conduction delay
• Bioprosthetic structural deterioration and intravascular hemolysis (paravalvular leak): schistocytes, elevated LDH, low haptoglobin
• Warfarin-related hemorrhage; acute severe MR or tamponade after balloon commissurotomy

• Symptom onset in aortic stenosis is the pivot point: angina, syncope, or dyspnea in severe AS makes aortic valve replacement the single best next step (ACC/AHA 2020) — the distractor is "serial echocardiography" or "start a statin," neither of which alters calcific AS
• Rheumatic disease targets the mitral valve first (mitral > aortic > tricuspid); mitral stenosis is the lesion most specific for rheumatic heart disease. Mechanism is molecular mimicry between streptococcal M protein and cardiac myosin; look for Aschoff bodies with Anitschkow cells
• Heyde syndrome is the association examiners love: severe AS + GI bleeding from angiodysplasia via shear-mediated loss of high-molecular-weight vWF multimers
• Maneuvers: standing/Valsalva (↓preload) moves the MVP click earlier and lengthens its murmur and makes HCM louder; handgrip (↑afterload) augments MR, AR, and VSD but softens AS and HCM
• Libman–Sacks endocarditis — sterile, verrucous vegetations on both surfaces of the mitral valve in SLE/antiphospholipid syndrome. Distinguish from marantic (NBTE) vegetations, which are bland, on the line of closure, and associated with mucin-secreting adenocarcinoma
• Carcinoid heart disease is right-sided (TR ± pulmonic stenosis) because the lung inactivates serotonin; left-sided involvement implies a PFO or a bronchial primary. The plaques are fibrous and non-calcified
• Anticoagulation trap: DOACs are not acceptable for mechanical valves or for AF with rheumatic mitral stenosis — use warfarin
• Austin Flint murmur (AR jet on the anterior mitral leaflet) mimics mitral stenosis but has no opening snap and no loud S1
• Endocarditis prophylaxis (AHA) is reserved for the highest-risk patients — prosthetic valves/material, prior IE, certain congenital lesions, transplant valvulopathy — before dental procedures involving gingival or periapical manipulation; isolated MVP does not qualify