Rheumatic Heart Disease

Acute Rheumatic Fever → Chronic RHD Progression

Molecular mimicry and cross-reactive immunity

• GAS pharyngeal infection triggers antibody responses against streptococcal M protein and N-acetyl-β-D-glucosamine
• These epitopes share homology with cardiac myosin, tropomyosin, and other sarcolemmal proteins
• Cross-reactive T cells and B cells perpetuate autoimmune responses against myocardial and valvular tissue
• HLA associations (HLA-DR2, HLA-DR3, HLA-DR7) predispose to exaggerated immune responses

Acute carditis mechanisms

• Pancarditis develops: myocarditis (reversible inflammation), endocarditis (valvular inflammation), pericarditis (fibrinous serositis)
• Aschoff bodies (pathognomonic lesions) consist of central fibrinoid necrosis surrounded by inflammatory cells
• Valvular edema and inflammation cause acute regurgitation; valve commissures may temporarily fuse

Chronic valvular remodeling

• Repeated episodes of acute carditis lead to fibrosis and collagen deposition
• Mitral valve most commonly affected (75-80% of cases):
• Commissural fusion causes stenosis
• Chordal shortening and thickening produce regurgitation
• Combined lesions frequent
• Aortic valve (30% of cases): primarily regurgitation initially, then stenosis
• Tricuspid and pulmonary valves rarely affected
• Endothelial injury promotes thrombus formation on valvular surfaces

Hemodynamic consequences

• Stenotic lesions increase pressure gradients; regurgitant lesions cause volume overload
• Left atrial enlargement predisposes to atrial fibrillation (AF), which further promotes thrombus formation in the left atrial appendage
• Progressive left ventricular dysfunction from chronic pressure/volume overload

Primary cause

• Group A Streptococcus pharyngitis (untreated or inadequately treated)
• Risk increases with repeated or delayed treatment
• Not associated with streptococcal skin infections (pyoderma)
• Peak incidence 5-15 years after initial ARF

Risk factors for ARF/RHD development

• Genetic predisposition: HLA gene polymorphisms, familial clustering (10-30% recurrence in siblings)
• Socioeconomic factors: Overcrowding, poor hygiene, malnutrition, limited healthcare access
• Immunologic factors: Young age at initial ARF (higher risk), female predominance
• Geographic location: Highest burden in Sub-Saharan Africa, South Asia, Pacific Islands, Central America
• Streptococcal factors: Highly virulent M serotypes (M1, M5, M6, M19)
• Recurrent GAS infections: Each subsequent infection increases cumulative RHD risk

Acute Rheumatic Fever (preceding event)

• Migratory polyarthritis (knees, ankles, shoulders, elbows) - more severe in adults
• Carditis: dyspnea, chest pain, palpitations, syncope
• Chorea (Sydenham's chorea): involuntary movements, emotional lability, weakness
• Erythema marginatum: transient pink rash with pale centers on trunk
• Subcutaneous nodules: painless firm nodules over bony prominences
• Fever, malaise, elevated inflammatory markers

Chronic Rheumatic Heart Disease

Cardiac symptoms

• Dyspnea (exertional initially, progressing to orthopnea/paroxysmal nocturnal dyspnea as disease advances)
• Palpitations (irregular rhythm from atrial fibrillation)
• Fatigue and reduced exercise tolerance
• Chest discomfort (anginal or pleuritic)
• Syncope (particularly with mitral stenosis and decreased cardiac output)
• Hemoptysis (from pulmonary edema or pulmonary hypertension)

Mitral stenosis-specific features

• Low-pitched diastolic murmur at apex with opening snap
• Atrial fibrillation (very common, often first presentation)
• Signs of right heart failure: peripheral edema, hepatomegaly, ascites
• Malar flush (from reduced cardiac output and cutaneous vasoconstriction)

Mitral regurgitation-specific features

• High-pitched holosystolic murmur at apex radiating to axilla
• Wide pulse pressure, hyperdynamic precordium
• Left ventricular heave (lateral and sustained)

Aortic valve involvement

• Aortic regurgitation: early diastolic decrescendo murmur, wide pulse pressure
• Aortic stenosis: systolic ejection murmur, delayed carotid upstroke
• Austin Flint murmur (mid-diastolic rumble from AR-induced mitral inflow obstruction)

Physical exam findings across RHD

• Irregular pulse (atrial fibrillation)
• Loud S1 (mitral stenosis - valve closes abruptly at high LA pressure)
• Opening snap (snapping sound 40-100 ms after A2 from abrupt halt of stenotic mitral valve)
• Rumbling diastolic murmur (mitral stenosis, best heard with patient in left lateral decubitus position with bell of stethoscope)
• Carey Coombs murmur (mid-diastolic or presystolic murmur in acute carditis from mitral regurgitation jet striking endocardium)

Clinical criteria for Acute Rheumatic Fever (revised Jones criteria, 2015)

• Initial ARF episode: 2 major criteria OR 1 major + 2 minor criteria
• Recurrent ARF (in patient with prior ARF/RHD): 2 major OR 1 major + 2 minor OR 3 minor criteria
• Plus evidence of preceding GAS infection (elevated/rising ASO titer, positive throat culture, positive rapid GAS test)

Major criteria JONES

• Joint involvement (monoarthritis/polyarthritis in low-risk populations; polyarthralgia in high-risk)
• Organs (carditis)
• Nodules (subcutaneous)
• Erythema marginatum
• Sydenham's chorea

Minor criteria (low-risk)

• Polyarthralgia
• Fever ≥38.5°C
• ESR ≥60 mm/hr AND/OR CRP ≥3 mg/dL
• Leukocytosis ≥11,000/μL

Minor criteria (high-risk populations)

• Monoarthritis
• Fever ≥38°C
• ESR ≥30 mm/hr AND/OR CRP ≥3 mg/dL

Laboratory findings

• Elevated acute phase reactants: ESR (>60 mm/hr), CRP (>3 mg/dL)
• ASO titer: ≥1:200 (or fourfold rise in serial titers) confirms recent GAS infection
• Anti-DNase B antibodies: alternative marker of recent streptococcal infection
• Normocytic anemia, thrombocytosis
• No specific lab defines RHD itself; diagnosis is clinical and echocardiographic

Electrocardiography

• Atrial fibrillation (common with chronic disease)
• First-degree AV block (in acute carditis)
• Left atrial enlargement (P-mitrale: biphasic P waves in precordial leads)
• Left ventricular hypertrophy (chronic mitral stenosis increases afterload)
• Right ventricular hypertrophy (from pulmonary hypertension)

Echocardiography (diagnostic gold standard for RHD)

• Transthoracic echocardiography (TTE):
• Visualizes valve morphology: leaflet thickening, restricted motion, commissural fusion, chordal shortening
• Mitral stenosis: Doppler mean gradient ≥5 mmHg, mitral valve area (MVA) <2 cm² (severe <1 cm²)
• Mitral regurgitation: Color Doppler jet width, regurgitant volume, regurgitant fraction
• Aortic stenosis/regurgitation: Peak gradient, aortic valve area, regurgitant jet dimensions
• Left atrial size: dilated in chronic mitral stenosis/regurgitation
• Left ventricular function: global ejection fraction, regional wall motion
• Pulmonary artery pressure estimation: from tricuspid regurgitation jet velocity
• Thrombus detection: particularly in left atrial appendage

• Transesophageal echocardiography (TEE):
• Superior resolution for left atrial/left atrial appendage thrombus detection
• Better evaluation of commissural anatomy in mitral stenosis
• Guides percutaneous mitral balloon valvotomy (PMBV)

World Heart Federation (2012) echocardiographic criteria for RHD diagnosis

• Pathological mitral regurgitation and ≥2 morphological features of RHD on TTE (anterior leaflet thickening ≥3 mm, posterior leaflet restriction, excessive leaflet tip motion during systole)
• Mitral stenosis (mean gradient ≥4 mmHg on Doppler)
• Borderline disease (1-2 morphological features without pathological MR/MS)

Chest X-ray

• Left atrial enlargement: straightening of left heart border, double density at right heart border
• Pulmonary edema: Kerley B lines, bat-wing infiltrates (in acute decompensation)
• Pulmonary hypertension: enlarged pulmonary arteries
• Left ventricular enlargement: increased cardiothoracic ratio

World Heart Federation 2012 RHD Screening Criteria (for echocardiographic detection)

• Definite RHD: pathological MR + ≥2 morphological features OR MS (mean gradient ≥4 mmHg)
• Borderline RHD: 1-2 morphological features in absence of pathological MR/MS (requires follow-up)

Primary Prevention (Prevention of ARF)

• Penicillin V 250 mg PO QID × 10 days (oral) OR benzathine penicillin G 1.2 million units IM × 1 (parenteral preferred for compliance) for acute GAS pharyngitis
• Mechanism: Eliminates streptococci, prevents ARF if given within 9 days of symptom onset
• For penicillin-allergy: amoxicillin (preferred), first-generation cephalosporin, macrolide (azithromycin), or clindamycin

Secondary Prevention (RHD established, prevent recurrent ARF)

Indicated in all patients with documented RHD to prevent disease progression

• Benzathine penicillin G 1.2 million units IM every 4 weeks (or 600,000 units if <27 kg)
• Preferred agent; most reliable compliance
• Continue for minimum 5 years after last ARF episode if no carditis
• Continue to age 21-25 years if carditis without RHD
• Continue for life if RHD with carditis or significant valve disease
• Alternative dosing: every 3 weeks acceptable if high risk

• Oral alternatives (if patient refuses IM):
• Penicillin V 250 mg BID or TID
• Amoxicillin 500 mg daily
• Macrolide (erythromycin 500 mg BID) - less preferred

• Penicillin-allergic patients:
• Sulfonamides: sulfadiazine 0.5-1 g QID
• Macrolides: erythromycin 250 mg QID
• Clindamycin 150-300 mg QID (less data)
• DO NOT use cephalosporins in patients with anaphylaxis to penicillin

Tertiary Prevention (complications of established RHD)

Heart failure management

• ACE inhibitors/ARBs: first-line for reduced ejection fraction; renal protection
• Beta-blockers: control heart rate in atrial fibrillation, reduce afterload in regurgitant lesions
• Diuretics: furosemide, thiazides for volume overload, pulmonary edema
• Aldosterone antagonists: spironolactone for systolic dysfunction
• Ivabradine: if beta-blockers contraindicated and high resting heart rate (reduces myocardial oxygen demand)

Anticoagulation

• Warfarin (target INR 2-3) absolutely indicated:
• All RHD patients with atrial fibrillation
• Left atrial thrombus on imaging
• Mechanical prosthetic valves (target INR 2.5-3.5)
• Consider in severe mitral stenosis even in sinus rhythm (high thromboembolism risk)
• Direct oral anticoagulants (DOACs): increasingly used in AF; rivaroxaban, dabigatran, apixaban acceptable (apixaban preferred per some guidelines)
• Aspirin 75-100 mg daily: if no anticoagulation indication and sinus rhythm

Arrhythmia management

• Rate control in atrial fibrillation:
• Beta-blockers (metoprolol, carvedilol)
• Non-dihydropyridine calcium channel blockers (diltiazem, verapamil)
• Digoxin (particularly if concurrent heart failure)
• Rhythm control: amiodarone (often required given structural heart disease); sotalol, flecainide less preferred

Valve-specific medical management

• Diuretics for congestion; restrict sodium/fluid
• Rate control to allow adequate diastolic filling time
• Anticoagulation (as above)
• Avoid positive inotropes (worsen obstruction) and vasodilators (may worsen symptoms)

• ACE inhibitors/ARBs to reduce afterload and regurgitant volume
• Beta-blockers for rate control and afterload reduction
• Diuretics for pulmonary edema
• Avoid negative inotropes if ejection fraction reduced

• Similar approach to non-RHD aortic disease
• ACE inhibitors/ARBs for aortic regurgitation
• Avoid afterload reduction in stenosis

Invasive/Surgical Interventions

Mitral stenosis

• Percutaneous mitral balloon valvotomy (PMBV):
• First-line intervention for symptomatic mitral stenosis (NYHA ≥II)
• Requires suitable anatomy: non-calcified, pliable leaflets; no thrombus in LAA
• Success rate 80-90%; excellent hemodynamic results
• Risks: stroke, tamponade, severe mitral regurgitation (5-10%)
• Echocardiographic score (Wilkins score) predicts success

• Surgical commissurotomy:
• Open approach if PMBV failed or anatomy unsuitable
• Outcomes inferior to PMBV; primarily historical

Thromboembolic (highest-yield)

• Atrial fibrillation: chronic left atrial stretch and fibrosis create reentrant substrate; signaled by an irregularly irregular pulse and loss of presystolic accentuation of the diastolic rumble (no atrial kick).
• Cardioembolic stroke — emergency: stasis in the left atrial appendage forms thrombus; sudden focal deficit mandates immediate noncontrast head CT and stroke-team activation. Rheumatic mitral stenosis carries embolic risk even in sinus rhythm, which is why CHA₂DS₂-VASc does not govern the anticoagulation decision here.
• Ball-valve LA thrombus: intermittent obstruction of the mitral orifice → positional syncope.

Hemodynamic

• Acute pulmonary edema — emergency: anything that shortens diastole (fever, exercise, pregnancy, new AF with rapid ventricular response) abruptly raises left atrial pressure; treat the rate, not the "pump," and cardiovert if unstable.
• Pulmonary hypertension with right heart failure: passive congestion plus reactive arteriolar remodeling; loud P2, right ventricular heave, TR murmur, JVD, ascites, edema.
• Hemoptysis: rupture of dilated bronchial venous collaterals; massive hemoptysis is an airway emergency.

Structural and infectious

• Infective endocarditis: damaged, regurgitant valves are the nidus; fever plus a changing murmur or embolic phenomena → three sets of blood cultures before antibiotics and echocardiography.
• Ortner (cardiovocal) syndrome: giant left atrium compresses the left recurrent laryngeal nerve → hoarseness; esophageal compression → dysphagia.
• Recurrent acute rheumatic fever: nonadherence to secondary prophylaxis; each recurrence deepens valve injury.

Treatment-related

• Percutaneous mitral balloon valvotomy: acute severe mitral regurgitation from leaflet tear (emergent surgery), tamponade from transseptal puncture, procedural stroke, residual atrial septal defect.
• Anticoagulation: intracranial hemorrhage is an emergency — reverse warfarin with 4-factor PCC plus IV vitamin K.
• Prosthetic valve thrombosis — emergency: muffled mechanical closing click, new gradient or dyspnea; obtain TEE/fluoroscopy urgently.
• Benzathine penicillin anaphylaxis: epinephrine 0.3 mg IM; observe after each injection.

• The buzzword cluster for rheumatic mitral stenosis: loud S1, opening snap, low-pitched apical diastolic rumble in the left lateral decubitus with the bell, plus malar flush and hemoptysis in an immigrant or young adult from an endemic region.
• Severity is timed, not loud: a shorter A2–opening snap interval means higher left atrial pressure and more severe stenosis. The murmur's intensity does not track severity — a common distractor.
• Single best next step for any suspected RHD murmur is transthoracic echocardiography, not cardiac catheterization or CT. Echo defines valve morphology, gradient, and valve area and is the diagnostic standard endorsed by the ACC/AHA 2020 valvular heart disease guideline.
• The association examiners test: prior GAS pharyngitis, not skin infection. Impetigo can cause poststreptococcal glomerulonephritis but does not cause acute rheumatic fever. Confirm prior infection with ASO or anti-DNase B titers.
• Anticoagulation choice: the ACC/AHA 2020 guideline recommends a vitamin K antagonist (warfarin), not a DOAC, for atrial fibrillation with rheumatic mitral stenosis and for mechanical prosthetic valves. Choosing apixaban in a stem describing rheumatic MS with AF is the classic trap.
• Secondary prophylaxis is the answer far more often than antibiotic prophylaxis before dental work: AHA does not recommend infective endocarditis prophylaxis for native-valve rheumatic disease — only for prosthetic valves/material, prior IE, certain congenital lesions, and cardiac transplant valvulopathy. Monthly IM benzathine penicillin G remains lifelong in significant RHD.
• Histology stem: Aschoff bodies with plump Anitschkow cells ("caterpillar cells") and fibrinoid necrosis are pathognomonic of rheumatic carditis; chronic valves show commissural fusion and "fish-mouth" or "buttonhole" mitral orifice with thickened, shortened chordae.
• Pregnancy decompensates mitral stenosis in the second and third trimesters as volume and heart rate rise; rate control with a beta blocker plus diuresis is the move, and ACE inhibitors — including captopril — are contraindicated throughout pregnancy.