Valve Disease

Aortic Stenosis & Regurgitation

Aortic Stenosis

Aortic stenosis (AS) is obstruction to left ventricular (LV) outflow across the aortic valve during systole. Normal aortic valve area is approximately 3–4 cm²; symptoms usually develop when area falls below about 1.0 cm². The LV must generate markedly increased systolic pressure, producing pressure overload and concentric hypertrophy by adding sarcomeres in parallel. This initially preserves ejection fraction but decreases compliance, raising LV end-diastolic pressure and causing diastolic dysfunction.

Major causes are age-dependent. In older adults, the most common cause is degenerative calcific stenosis. In patients younger than approximately 70 years, suspect a bicuspid aortic valve, which undergoes premature calcification due to abnormal shear stress. Rheumatic heart disease may cause AS but more classically affects the mitral valve and often produces combined valve disease.

Severity of Aortic Stenosis	Aortic Valve Area	Peak Velocity	Mean Gradient
Mild	>1.5 cm2	2.0–2.9 m/s	<20 mm Hg
Moderate	1.0–1.5 cm2	3.0–3.9 m/s	20–39 mm Hg
Severe	≤1.0 cm2	≥4.0 m/s	≥40 mm Hg

The pressure gradient is related to velocity by the simplified Bernoulli equation: ΔP = 4v². Thus, a peak velocity of 4 m/s corresponds to a gradient of about 64 mm Hg. Classic symptoms are angina, syncope, and heart failure. Angina occurs because hypertrophied myocardium has increased oxygen demand while coronary perfusion is impaired by elevated LV diastolic pressure. Syncope classically occurs with exertion because fixed outflow obstruction prevents adequate rise in cardiac output.

Physical examination shows a harsh crescendo-decrescendo systolic ejection murmur at the right upper sternal border radiating to the carotids, often with a delayed and diminished carotid upstroke called pulsus parvus et tardus. Severe AS may have a soft or absent A2 component of S2. Squatting increases venous return and generally increases AS murmur intensity; Valsalva decreases it. This helps distinguish AS from hypertrophic obstructive cardiomyopathy, whose murmur increases with Valsalva.

High-yield complications include Heyde syndrome, in which severe AS causes shear-mediated degradation of von Willebrand factor multimers, leading to acquired von Willebrand disease and bleeding from gastrointestinal angiodysplasia. Once symptoms occur, prognosis worsens without valve replacement: approximate average survival is 5 years after angina, 3 years after syncope, and 2 years after heart failure.

Guideline-based intervention is generally indicated for symptomatic severe AS, severe AS with LVEF <50%, or very severe AS with high-risk features such as Vmax ≥5.0 m/s. Transcatheter aortic valve replacement was validated in major trials such as PARTNER, but Step 1 emphasis is on recognizing the lesion and its physiology.

Aortic Regurgitation

Aortic regurgitation (AR) is diastolic backflow from the aorta into the LV due to incompetent valve closure. Causes involve either the valve leaflets or the aortic root. Leaflet causes include bicuspid aortic valve, infective endocarditis, rheumatic disease, and trauma. Aortic root causes include chronic hypertension, Marfan syndrome due to fibrillin-1 defects, syphilitic aortitis with vasa vasorum obliteration and “tree-bark” aorta, ankylosing spondylitis, and aortic dissection.

Chronic AR produces volume overload. The LV adapts by eccentric hypertrophy, adding sarcomeres in series, allowing dilation and increased stroke volume. This creates wide pulse pressure: elevated systolic pressure from high stroke volume and low diastolic pressure from diastolic runoff into the LV. Acute AR, such as from infective endocarditis or dissection, is poorly tolerated because the LV has not dilated; LV diastolic pressure rises abruptly, causing pulmonary edema and cardiogenic shock.

Feature	Chronic Aortic Regurgitation	Acute Aortic Regurgitation
LV adaptation	Eccentric hypertrophy and dilation	No time for compensation
Pulse pressure	Wide	May be narrow or normal
Murmur	High-pitched early diastolic decrescendo	Often shorter and softer
Clinical course	Years of compensation, then LV failure	Rapid pulmonary edema/shock

The classic murmur is a high-pitched, blowing, early diastolic decrescendo murmur best heard along the left sternal border with the patient leaning forward in held expiration. A severe regurgitant jet may strike the anterior mitral leaflet, causing functional mitral stenosis and an apical mid-diastolic rumble called an Austin Flint murmur.

Peripheral signs reflect widened pulse pressure: Corrigan pulse is bounding “water-hammer” carotid pulsation; de Musset sign is head bobbing; Quincke sign is capillary nail-bed pulsation; and Duroziez sign is a femoral bruit with compression.

Echocardiographic markers of severe AR include regurgitant volume ≥60 mL/beat, regurgitant fraction ≥50%, effective regurgitant orifice area ≥0.30 cm², and pressure half-time <200 ms. Surgical consideration is classically triggered by symptoms, LV systolic dysfunction, or LV dilation; current guideline cutoffs include LVEF ≤55% or LV end-systolic dimension >50 mm.

Medical therapy targets afterload reduction in selected chronic AR, especially with hypertension. Examples include dihydropyridine calcium-channel blockers such as nifedipine extended release 30–90 mg orally daily, ACE inhibitors, or hydralazine. In acute severe AR, vasodilators such as nitroprusside 0.3–10 mcg/kg/min IV may be used as temporary stabilization, but definitive correction is mechanical. Beta-blockers can be harmful in severe AR because slowing heart rate prolongs diastole and may increase regurgitant volume.

Mitral Stenosis & Regurgitation

Mitral Stenosis

Mitral stenosis (MS) is obstruction to blood flow from the left atrium (LA) to the left ventricle (LV) during diastole. The normal mitral valve area is approximately 4–6 cm²; symptoms typically develop when the area falls below 2.0 cm², and severe MS is usually defined as valve area ≤1.5 cm². The most classic cause worldwide is chronic rheumatic heart disease, producing commissural fusion, leaflet thickening, and chordal shortening, often decades after group A streptococcal pharyngitis.

The key physiologic abnormality is an elevated LA pressure needed to drive blood across a narrowed valve. This causes LA dilation, predisposing to atrial fibrillation and mural thrombus. Increased LA pressure transmits backward to pulmonary veins, causing exertional dyspnea, orthopnea, pulmonary edema, and eventually pulmonary hypertension with right ventricular hypertrophy/failure. Because LV filling is restricted, LV size and systolic function are often normal or reduced in preload rather than primarily damaged.

Feature	High-yield findings in mitral stenosis
Murmur	Low-pitched mid-diastolic rumble best heard at the apex with the bell in the left lateral decubitus position
Opening snap	Occurs shortly after S2 due to abrupt tensing of stenotic leaflets; shorter A2–opening snap interval = more severe MS because LA pressure is higher
Severity clue	Longer duration of diastolic rumble correlates with more severe stenosis
Associated findings	Loud S1 early in disease; irregularly irregular rhythm if atrial fibrillation; signs of pulmonary hypertension such as loud P2

On echocardiography, MS severity is assessed by valve area, mean transmitral gradient, and pulmonary pressures. Gradients are flow-dependent: tachycardia worsens MS by shortening diastole, raising LA pressure, and increasing pulmonary congestion. A commonly tested formula is mitral valve area = 220 / pressure half-time, where pressure half-time is the time in milliseconds for the transmitral pressure gradient to fall by half.

Mitral stenosis severity	Mitral valve area	Mean gradient	Pulmonary artery systolic pressure
Mild	>1.5 cm2	<5 mm Hg	<30 mm Hg
Moderate	1.0–1.5 cm2	5–10 mm Hg	30–50 mm Hg
Severe	<1.0 cm2	>10 mm Hg	>50 mm Hg

Medical therapy is aimed at physiology, not anatomic cure. Beta-blockers or nondihydropyridine calcium channel blockers slow heart rate, lengthening diastole and improving LV filling. Example doses commonly used clinically include metoprolol tartrate 25–50 mg orally twice daily or diltiazem extended-release 120–360 mg orally daily. If atrial fibrillation occurs with moderate-to-severe rheumatic MS, anticoagulation is classically with warfarin targeting INR 2.0–3.0; direct oral anticoagulants are generally avoided in this setting, supported by the INVICTUS trial, in which rivaroxaban was inferior to vitamin K antagonist therapy for rheumatic heart disease–associated atrial fibrillation. Percutaneous balloon mitral valvotomy is favored when valve morphology is suitable; the Wilkins score grades leaflet mobility, thickening, calcification, and subvalvular disease from 1–4 each, with total score ≤8 predicting better outcomes.

Mitral Regurgitation

Mitral regurgitation (MR) is systolic backflow of blood from LV to LA due to failure of leaflet coaptation. It may be primary, caused by intrinsic valve apparatus disease, or secondary/functional, caused by LV dilation or papillary muscle displacement with structurally normal leaflets.

Cause	Mechanism	Step 1 association
Mitral valve prolapse	Myxomatous degeneration; leaflet billowing	Mid-systolic click with late systolic murmur
Rheumatic disease	Leaflet scarring and chordal fusion	Often mixed MS/MR
Infective endocarditis	Leaflet perforation or chordal rupture	Acute severe MR with fever and emboli
Papillary muscle rupture	Post-myocardial infarction mechanical complication	Posteromedial papillary muscle is vulnerable because it usually has single PDA blood supply
Dilated cardiomyopathy	Annular dilation and tethering	Functional MR with LV systolic dysfunction

In chronic MR, LV ejects into both the high-pressure aorta and low-pressure LA, decreasing effective forward stroke volume while increasing total stroke volume. Volume overload causes eccentric LV hypertrophy and LA dilation. The dilated LA accommodates regurgitant volume at lower pressure, so pulmonary symptoms may be delayed. Eventually LV contractility fails; importantly, the ejection fraction can appear “normal” despite early systolic dysfunction because the LV ejects into a low-resistance chamber. In severe primary MR, an LVEF ≤60% or LV end-systolic diameter ≥40 mm indicates LV decompensation risk.

In acute MR, the LA has not adapted and is noncompliant, so a sudden regurgitant volume produces marked LA and pulmonary venous hypertension, causing flash pulmonary edema and cardiogenic shock. The murmur may be short or soft because LV and LA pressures rapidly equalize.

Finding	Mitral regurgitation
Murmur	Holosystolic, blowing murmur best heard at apex, classically radiating to the axilla
Extra sounds	S3 due to increased LV volume; displaced hyperdynamic apical impulse in chronic severe MR
Dynamic maneuvers	Handgrip increases afterload and generally increases MR intensity; standing/Valsalva decrease venous return and usually decrease intensity
Severe echo criteria	Effective regurgitant orifice area ≥0.40 cm2, regurgitant volume ≥60 mL/beat, regurgitant fraction ≥50%, vena contracta width ≥0.7 cm

Pharmacologically, acute afterload reduction can increase forward output in severe MR; nitroprusside 0.3–10 mcg/kg/min IV is a classic vasodilator example because it reduces systemic vascular resistance and regurgitant fraction. Diuretics such as furosemide 20–40 mg IV may reduce pulmonary congestion. For Step 1, the key principle is that MR is worsened by increased afterload, whereas MS is worsened by tachycardia.

Mitral Valve Prolapse

Definition and Core Pathophysiology

Mitral valve prolapse (MVP) is systolic displacement of one or both mitral valve leaflets into the left atrium during ventricular contraction. On transthoracic echocardiography, the standard diagnostic criterion is >2 mm superior displacement of the mitral leaflet beyond the mitral annular plane in the parasternal long-axis view. MVP is common, with a population prevalence of approximately 2–3%, and is the most frequent cause of isolated chronic primary mitral regurgitation in developed countries.

The key histopathologic mechanism is myxomatous degeneration: accumulation of proteoglycan-rich extracellular matrix within the valve, fragmentation of collagen and elastin, and expansion of the spongiosa layer. This weakens leaflet structure, causing redundant “billowing” leaflets and elongation or rupture of chordae tendineae. During systole, left ventricular pressure forces the abnormal leaflet backward into the left atrium. If leaflet coaptation is impaired, mitral regurgitation (MR) occurs.

Associations and Etiology

MVP may be sporadic or associated with connective tissue disorders. Step 1 commonly tests the link between abnormal connective tissue and valve redundancy.

Association	Mechanistic Link	High-Yield Clue
Marfan syndrome	Fibrillin-1 mutation causing abnormal elastic tissue architecture	Tall habitus, lens subluxation, aortic root dilation
Ehlers-Danlos syndrome	Defective collagen synthesis/structure	Hyperextensible skin, joint hypermobility
Osteogenesis imperfecta	Type I collagen abnormality	Blue sclerae, fractures, hearing loss
Autosomal dominant polycystic kidney disease	Extrarenal connective tissue abnormalities	Bilateral renal cysts, berry aneurysms

Auscultation and Bedside Physiology

The classic auscultatory finding is a mid-systolic click followed by a late systolic murmur best heard at the cardiac apex. The click represents sudden tensing of elongated chordae tendineae as the prolapsing leaflet reaches maximal excursion. The murmur occurs if prolapse causes MR, producing turbulent flow from the left ventricle to the left atrium during systole.

MVP is highly sensitive to maneuvers that alter left ventricular volume. A smaller left ventricle allows the mitral leaflets to prolapse earlier in systole; a larger left ventricle delays prolapse.

Maneuver	Effect on LV Volume	Effect on MVP Click/Murmur
Standing	Decreases venous return and LV end-diastolic volume	Click occurs earlier; murmur becomes longer
Valsalva strain	Decreases venous return	Click earlier; murmur longer
Squatting	Increases venous return and afterload	Click occurs later; murmur becomes shorter
Passive leg raise	Increases venous return	Click later; murmur shorter
Handgrip	Increases systemic vascular resistance/afterload	May increase MR murmur intensity; prolapse tends to occur later

Clinical Features and Complications

Most patients are asymptomatic. Some report palpitations, atypical chest pain, dyspnea, anxiety-like symptoms, or presyncope. These symptoms are nonspecific and often reflect heightened adrenergic tone or associated arrhythmias rather than severe valve dysfunction.

Important complications include progressive mitral regurgitation, infective endocarditis on abnormal valve tissue, atrial fibrillation due to left atrial enlargement, and rarely sudden cardiac death from ventricular arrhythmias. Sudden death is uncommon, generally estimated at <1% per year, but risk is higher with severe MR, reduced left ventricular function, bileaflet prolapse, marked leaflet thickening, or complex ventricular ectopy.

Diagnosis and Classification

Echocardiography is the diagnostic test of choice. Classic MVP involves leaflet displacement >2 mm; “classic” myxomatous MVP often also has leaflet thickness ≥5 mm, whereas “nonclassic” MVP has less leaflet thickening. Doppler echocardiography assesses associated MR by evaluating regurgitant jet area, vena contracta, pulmonary vein flow, and chamber remodeling.

Feature	MVP without Significant MR	MVP with Significant MR
Primary abnormality	Leaflet billowing/prolapse	Prolapse plus failure of leaflet coaptation
Auscultation	Mid-systolic click may predominate	Click plus late or holosystolic apical murmur
Hemodynamic consequence	Usually minimal	Left atrial and left ventricular volume overload
Long-term risk	Often benign	Heart failure, atrial fibrillation, pulmonary hypertension

Management Principles Relevant to Step 1

Asymptomatic MVP without significant MR generally requires reassurance and periodic follow-up rather than drug therapy. For symptomatic palpitations without dangerous arrhythmia, beta-blockers may reduce adrenergic symptoms; examples include metoprolol tartrate 25–50 mg orally twice daily or propranolol 10–40 mg orally 2–4 times daily. The pharmacologic mechanism is β₁-receptor blockade, decreasing heart rate, AV nodal conduction, and myocardial oxygen demand.

Routine antibiotic prophylaxis for dental procedures is not recommended for isolated MVP, even with a murmur. Current American Heart Association guidance limits infective endocarditis prophylaxis to highest-risk groups such as prior infective endocarditis, prosthetic valves, selected congenital heart disease, and cardiac transplant recipients with valvulopathy.

If MVP causes severe chronic primary MR, management follows MR severity and ventricular response. A key guideline threshold from ACC/AHA valvular disease recommendations is intervention for asymptomatic severe primary MR when LVEF ≤60% or LV end-systolic diameter ≥40 mm, reflecting that EF may appear “normal” despite early systolic dysfunction because the ventricle ejects into both the aorta and the low-pressure left atrium.

Tricuspid & Pulmonic Disease

Tricuspid Valve Disease

The tricuspid valve separates the right atrium from the right ventricle. Because right-sided pressures are normally low, tricuspid lesions are often clinically quieter than left-sided lesions but produce prominent systemic venous findings. Normal right atrial pressure is approximately 0–8 mm Hg, and normal right ventricular systolic pressure is approximately 15–30 mm Hg. Bedside auscultation is strongly affected by respiration: right-sided murmurs classically increase with inspiration due to increased venous return to the right heart, a finding called Carvallo sign.

Lesion	Major Causes	Murmur	Key Findings
Tricuspid regurgitation	Functional RV dilation from pulmonary hypertension; infective endocarditis in IV drug use; carcinoid syndrome; Ebstein anomaly; rheumatic disease	Holosystolic murmur at left lower sternal border, louder with inspiration	Prominent v waves in JVP, pulsatile liver, peripheral edema, ascites
Tricuspid stenosis	Rheumatic heart disease, carcinoid syndrome, congenital disease	Diastolic rumble at left lower sternal border, louder with inspiration	Prominent a waves, hepatomegaly, systemic venous congestion

Tricuspid regurgitation (TR) occurs when the valve fails to coapt during systole, allowing blood to flow backward from the right ventricle into the right atrium. The most common mechanism is functional TR: pulmonary hypertension or left-sided heart disease increases RV afterload, causing RV dilation and annular dilation. The valve leaflets may be structurally normal. In contrast, primary TR involves leaflet pathology, such as infective endocarditis, carcinoid plaques, or congenital malformation.

On venous pulse tracing, systolic backflow into the right atrium creates large v waves. Severe TR may cause systolic hepatic pulsations because the regurgitant pressure wave is transmitted through the inferior vena cava into hepatic veins. Echocardiographic markers of severe TR include vena contracta width ≥0.7 cm, effective regurgitant orifice area ≥40 mm², regurgitant volume ≥45 mL/beat, and systolic flow reversal in hepatic veins. Doppler pressure gradients use the simplified Bernoulli equation: ΔP = 4v², where velocity is measured in m/s.

Tricuspid stenosis (TS) obstructs right atrial emptying during diastole. It is rare and most often rheumatic, usually accompanying mitral valve disease. It produces elevated right atrial pressure without primary pulmonary congestion. Severe TS is suggested by mean diastolic gradient ≥5 mm Hg and tricuspid valve area approximately ≤1.0 cm². The murmur is a low-pitched diastolic rumble best heard at the left lower sternal border and intensified by inspiration. Because atrial contraction must force blood across a narrowed valve, prominent a waves occur unless atrial fibrillation is present.

High-Yield Etiologic Associations

• IV drug use: classically causes right-sided infective endocarditis, most often due to Staphylococcus aureus, producing TR with fever, bacteremia, and septic pulmonary emboli.
• Carcinoid heart disease: serotonin and other vasoactive substances cause fibrous endocardial plaques, classically affecting the tricuspid and pulmonic valves. Left-sided valves are usually spared because pulmonary monoamine oxidase metabolizes serotonin, unless there is a right-to-left shunt or primary bronchial carcinoid.
• Ebstein anomaly: apical displacement of the tricuspid valve into the right ventricle, “atrialization” of part of the RV, severe TR, and association with maternal lithium exposure.

Pulmonic Valve Disease

The pulmonic valve separates the right ventricle from the pulmonary artery. Pulmonic lesions are often congenital and may be isolated or part of syndromic congenital heart disease. Right ventricular outflow obstruction increases RV systolic pressure and can cause RV hypertrophy; regurgitation causes RV volume overload.

Lesion	Typical Causes	Murmur	Step 1 Clues
Pulmonic stenosis	Congenital; Noonan syndrome; tetralogy of Fallot	Systolic ejection murmur at left upper sternal border, louder with inspiration; ejection click may decrease with inspiration	RV hypertrophy, delayed/soft P2, post-stenotic pulmonary artery dilation
Pulmonic regurgitation	Pulmonary hypertension; repaired congenital heart disease; carcinoid syndrome	Early diastolic decrescendo murmur at left upper sternal border	RV volume overload; Graham Steell murmur when due to pulmonary hypertension

Pulmonic stenosis (PS) is usually congenital and involves commissural fusion or a dysplastic valve. It is associated with Noonan syndrome, an autosomal dominant RAS/MAPK pathway disorder with short stature, webbed neck, pectus deformity, and normal karyotype. PS also contributes to the right ventricular outflow obstruction in tetralogy of Fallot. Severity is commonly estimated by Doppler peak gradient: mild <36 mm Hg, moderate 36–64 mm Hg, and severe >64 mm Hg, corresponding roughly to peak jet velocity >4 m/s for severe disease.

The murmur of PS is a crescendo-decrescendo systolic ejection murmur at the left upper sternal border. It increases with inspiration. Severe PS may cause a right ventricular heave and widened splitting of S2 because RV ejection is prolonged, delaying pulmonic valve closure. Unlike aortic stenosis, PS does not classically radiate to the carotids.

Pulmonic regurgitation (PR) is diastolic flow from the pulmonary artery back into the right ventricle. The most common high-yield cause is pulmonary hypertension, which dilates the pulmonary artery and annulus; the resulting high-pitched early diastolic murmur is called the Graham Steell murmur. PR may also follow surgical repair of congenital heart disease or occur in carcinoid syndrome. Chronic PR produces RV dilation and volume overload; acute severe PR is poorly tolerated because the thin-walled RV cannot rapidly accommodate increased diastolic volume.

For pharmacology correlation, carcinoid syndrome symptoms are reduced by somatostatin analogs such as octreotide, commonly 50–100 micrograms subcutaneously every 8 hours acutely or long-acting release 20–30 mg intramuscularly every 4 weeks; its short-acting half-life is approximately 1.5–2 hours. This controls hormone-mediated flushing and diarrhea but established fibrotic valvular plaques generally do not regress.

Prosthetic Valve Complications

Prosthetic valves replace severely stenotic or regurgitant native valves. On Step 1, the key distinction is between mechanical valves, which are highly durable but thrombogenic, and bioprosthetic valves, which are less thrombogenic but prone to structural degeneration. Complications arise from altered blood-flow physics, foreign material exposure, impaired endothelialization, and chronic mechanical stress.

Valve Type	Examples	Major Advantage	Major Complication	Typical Durability
Mechanical	Bileaflet tilting-disc, older caged-ball	Long-lasting	Thrombosis and thromboembolism	>20–30 years
Bioprosthetic	Porcine valve, bovine pericardial valve, homograft	Lower thrombogenicity	Calcific degeneration, tearing, stenosis/regurgitation	Usually 10–15 years; shorter in younger patients

Thrombosis and Thromboembolism

Mechanical valves create nonphysiologic flow with high shear stress, turbulence, and blood contact with artificial surfaces. This activates platelets and the coagulation cascade, predisposing to valve thrombosis and systemic embolization. The risk is greatest in the mitral position because left atrial flow is lower than aortic outflow; stasis promotes clot formation. Additional risks include atrial fibrillation, prior embolism, left ventricular dysfunction, hypercoagulable states, and older-generation caged-ball valves.

Thrombus can obstruct leaflet motion, causing acute prosthetic stenosis or regurgitation. Clinically, this may produce dyspnea, pulmonary edema, syncope, or a change in the expected prosthetic click. Embolization from a left-sided valve can cause ischemic stroke, limb ischemia, renal infarction, or splenic infarction.

Situation	Typical Anticoagulation Target
Bileaflet mechanical aortic valve, no risk factors	Warfarin, target INR 2.5; acceptable range 2.0–3.0
Mechanical mitral valve	Warfarin, target INR 3.0; acceptable range 2.5–3.5
Mechanical aortic valve with risk factors or older-generation valve	Warfarin, target INR 3.0; acceptable range 2.5–3.5
Adjunct in selected mechanical valves	Aspirin 75–100 mg/day if bleeding risk is acceptable

Warfarin inhibits vitamin K epoxide reductase, decreasing gamma-carboxylation of factors II, VII, IX, X and proteins C and S. Its half-life is approximately 36–42 hours, but the antithrombotic effect depends heavily on factor II depletion, whose half-life is about 60–72 hours. Direct oral anticoagulants are contraindicated in mechanical valves; the RE-ALIGN trial of dabigatran in mechanical valves was stopped early because of excess thromboembolic and bleeding events.

Bleeding from Anticoagulation

The major tradeoff for preventing thrombosis is hemorrhage. Warfarin-associated bleeding risk rises with supratherapeutic INR, advanced age, liver disease, interacting drugs, and poor dietary consistency. Important drug interactions include amiodarone, trimethoprim-sulfamethoxazole, metronidazole, azole antifungals, and many macrolides, which can raise INR. Rifampin and carbamazepine induce hepatic metabolism and can lower INR. Step 1 commonly tests the principle that mechanical valves require lifelong anticoagulation, whereas many bioprosthetic valves do not require lifelong warfarin unless another indication exists, such as atrial fibrillation.

Prosthetic Valve Endocarditis

Prosthetic material provides an adhesive surface for bacteria and is relatively resistant to immune clearance. Prosthetic valve endocarditis is classically divided into early and late forms. Early infection, often defined as within 60 days of surgery, is frequently due to perioperative contamination and is associated with Staphylococcus aureus, coagulase-negative staphylococci such as Staphylococcus epidermidis, and gram-negative bacilli. Late infection more closely resembles native valve endocarditis and may involve viridans streptococci, enterococci, or S. aureus.

Complications include annular abscess, conduction abnormalities due to extension near the AV node, paravalvular dehiscence, septic emboli, and heart failure. Prosthetic valves are a high-risk group for infective endocarditis prophylaxis before certain dental procedures involving gingival manipulation. A standard adult regimen is amoxicillin 2 g orally 30–60 minutes before the procedure; alternatives are used for severe beta-lactam allergy.

Structural Valve Deterioration and Pannus

Bioprosthetic valves fail mainly through progressive leaflet calcification, collagen degeneration, cusp tearing, and stiffening. Calcium deposition is accelerated in younger patients because of more active calcium metabolism and stronger hemodynamic stress. Failure produces recurrent stenosis, regurgitation, or mixed disease. In contrast, mechanical valves rarely undergo intrinsic structural failure but can be obstructed by pannus, a slowly growing fibrovascular tissue ingrowth from the sewing ring. Pannus develops gradually and is less responsive to anticoagulation than thrombus.

Paravalvular Leak, Dehiscence, and Hemolysis

A paravalvular leak occurs when blood flows around rather than through the prosthetic valve, usually because of suture disruption, annular calcification, infection, or tissue fragility. Severe dehiscence may cause acute regurgitation and heart failure. High-velocity jets through small gaps can mechanically fragment red blood cells, causing microangiopathic hemolytic anemia. Laboratory findings include elevated lactate dehydrogenase, increased indirect bilirubin, low haptoglobin, reticulocytosis, and schistocytes on peripheral smear.

Patient-Prosthesis Mismatch

Patient-prosthesis mismatch occurs when the effective orifice area of the prosthetic valve is too small for the patient’s body size, producing persistently elevated transvalvular gradients despite a normally functioning valve. This is a hemodynamic rather than structural problem. It is most relevant after aortic valve replacement and can mimic residual aortic stenosis, with exertional dyspnea and incomplete regression of left ventricular hypertrophy.

Rheumatic Heart Disease

Rheumatic heart disease (RHD) is chronic valvular damage caused by acute rheumatic fever (ARF), an immune-mediated, nonsuppurative complication of untreated group A β-hemolytic Streptococcus pyogenes pharyngitis. ARF typically occurs 2–4 weeks after pharyngitis, not after streptococcal skin infection. The key Step 1 concept is molecular mimicry: antibodies and T cells directed against streptococcal M protein cross-react with host tissues, especially cardiac myosin, laminin, and valvular endothelium.

Pathogenesis and Cardiac Pathology

ARF causes a pancarditis, meaning inflammation of all three cardiac layers: endocardium, myocardium, and pericardium. The endocardial component is most clinically important because repeated or severe inflammation leads to chronic valve scarring.

• Endocarditis/valvulitis: classically affects the mitral valve most often, followed by the aortic valve. Tricuspid and pulmonic involvement is uncommon.
• Myocarditis: characterized by Aschoff bodies, granuloma-like lesions containing T cells, plasma cells, macrophages, and activated macrophages called Anitschkow cells with “caterpillar” nuclei.
• Pericarditis: may produce a fibrinous “bread-and-butter” pericarditis, usually without chronic constrictive disease.

In acute rheumatic carditis, inflamed valves may cause regurgitant murmurs, especially mitral regurgitation. Over years to decades, healing by fibrosis produces commissural fusion, leaflet thickening, and shortened, thickened chordae tendineae. The classic chronic lesion is mitral stenosis with a “fish-mouth” or “buttonhole” valve. Chronic RHD is the most common cause of mitral stenosis worldwide.

Diagnosis of Acute Rheumatic Fever: Jones Criteria

ARF is diagnosed clinically using the revised Jones criteria, requiring evidence of recent group A streptococcal infection plus either 2 major criteria or 1 major and 2 minor criteria. Evidence of recent infection includes positive throat culture or rapid antigen test, elevated or rising antistreptolysin O (ASO) or anti-DNase B titers, or recent scarlet fever. ASO titers begin rising at about 1 week, peak at 3–5 weeks, and may remain elevated for months.

Jones Criteria Component	High-Yield Features
Major: migratory polyarthritis	Large joints; painful; “flits” from joint to joint; improves dramatically with NSAIDs.
Major: carditis	Pancarditis; new murmur, cardiomegaly, heart failure, pericardial rub; may be subclinical on echocardiography.
Major: Sydenham chorea	Involuntary, purposeless movements; emotional lability; may occur months after infection.
Major: erythema marginatum	Serpiginous, nonpruritic rash with central clearing, classically on trunk/proximal limbs.
Major: subcutaneous nodules	Firm, painless nodules over extensor surfaces; associated with severe carditis.
Minor criteria	Fever, arthralgia, elevated ESR/CRP, prolonged PR interval on ECG.

Classic Step 1 mnemonic: JONES = Joints, O heart, Nodules, Erythema marginatum, Sydenham chorea. The “O” is often remembered as “carditis” because the heart is the central organ of long-term morbidity.

Chronic Rheumatic Valvular Disease

Chronic RHD usually manifests years later as left-sided valve disease. The mitral valve is affected in approximately 65%–70% of cases, combined mitral and aortic disease in about 25%, and isolated aortic disease less commonly. Mitral stenosis increases left atrial pressure, causing left atrial dilation, atrial fibrillation, pulmonary venous congestion, pulmonary hypertension, and eventually right-sided heart failure. Clinically, mitral stenosis produces an opening snap followed by a low-pitched diastolic rumble best heard at the apex; a shorter interval between S2 and the opening snap suggests more severe stenosis because higher left atrial pressure opens the valve earlier.

Treatment and Prophylaxis Principles

Initial therapy eradicates residual group A streptococci and reduces inflammation. Importantly, antibiotics prevent ARF after streptococcal pharyngitis but do not directly reverse established autoimmune inflammation once ARF has developed.

Intervention	Typical Regimen / High-Yield Detail
Primary treatment of streptococcal pharyngitis	Penicillin V orally for 10 days or single-dose intramuscular benzathine penicillin G; prevents ARF if given within about 9 days of symptom onset.
ARF eradication therapy	Benzathine penicillin G 1.2 million units IM once if ≥27 kg; 600,000 units IM once if <27 kg.
Anti-inflammatory therapy	Aspirin or NSAIDs for arthritis/carditis symptoms; corticosteroids may be used for severe carditis, but this is less Step 1–central.
Secondary prophylaxis	Benzathine penicillin G 1.2 million units IM every 4 weeks; every 3 weeks in high-risk settings.

Secondary prophylaxis prevents recurrent ARF, which markedly increases the risk of progressive RHD. Guideline durations depend on carditis and residual valve disease: 5 years or until age 21 for ARF without carditis; 10 years or until age 21 for carditis without residual valvular disease; and 10 years or until age 40, sometimes lifelong, for carditis with persistent valvular disease.

High-Yield Differentiation

RHD should be distinguished from infective endocarditis. ARF is sterile, autoimmune, and follows pharyngitis; infective endocarditis is microbial infection of valves with vegetations and persistent bacteremia. Rheumatic vegetations are small, sterile verrucae along lines of valve closure during acute disease, whereas chronic RHD is dominated by fibrosis, commissural fusion, and stenosis. For Step 1, the most testable chain is: S. pyogenes pharyngitis → anti-M protein immune cross-reactivity → Aschoff bodies and Anitschkow cells → chronic mitral stenosis.