Rheumatic Heart Diseases

Epidemiology & Disease Burden

Most common cause of acquired, nonatherosclerotic heart disease worldwide.
Global prevalence estimated at 33.4 million in 2015, rising to 40.5 million in 2019.
Approximately 300,000 deaths annually worldwide.
Predominantly afflicts disadvantaged, marginalized populations in low- and middle-income (LMI) countries (Sub-Saharan Africa, South Asia, Oceania).
Acute Rheumatic Fever (ARF) peaks between 5-14 years of age.
RHD prevalence peaks in adulthood between 20-44 years.
Female predominance, especially after age 15.

Etiopathogenesis

Immunological disorder initiated by Group A beta-hemolytic streptococci (GAS) pharyngitis.
Latent period of 10 days to several weeks between pharyngitis and ARF onset.

Molecular Mimicry Mechanism

Feature	Description
Concept	Host and micro-organism share T-cell epitopes.
Antigens	GAS M protein and carbohydrate antigen ( $N$ -acetyl- $β$ -D-glucosamine).
Host Targets	Human cardiac myosin and laminin on heart valves.
Immune Response	T-cell activation (CD4+). B-cell antibody production (IgM, IgG).
Endocardial Injury	Humoral immune response damages endothelium. Expression of vascular cell adhesion molecule 1 (VCAM-1). CD4+, CD8+, and macrophages infiltrate connective tissue core. Neovascularization occurs.

Genetic Predisposition

Monozygotic twin susceptibility significantly higher than dizygotic twins.
Polymorphisms in candidate genes controlling inflammatory mediators (TGFB1, IL1B, IL10, TNF, CTLA4) associated with RHD susceptibility.

Diagnostic Criteria: Revised Jones Criteria (2015)

Requires evidence of preceding GAS infection + 2 Major criteria OR 1 Major + 2 Minor criteria.
For ARF recurrences: 3 Minor criteria sufficient.

Population Definition

Low-Risk Populations

Acute rheumatic fever incidence <2 per 100,000 school-going children.
Rheumatic heart disease (RHD) prevalence <1 per 1,000 population.

Moderate and High-Risk Populations

Rheumatic heart disease (RHD) prevalence ≥ 1 per 1,000 population.
Applies to populations not strictly meeting low-risk epidemiological thresholds.

Essential Criteria

Positive throat culture or rapid streptococcal antigen test.
Elevated or rising anti-streptococcal antibody titer (e.g., ASO titer >250 units, Anti-DNase B).
Recent scarlet fever.

Major and Minor Criteria (Stratified by Risk)

Criteria Category	Low-Risk Populations	Moderate/High-Risk Populations
Major	- Carditis (clinical/subclinical) - Polyarthritis - Chorea - Erythema marginatum - Subcutaneous nodules	- Carditis (clinical/subclinical) - Monoarthritis, Polyarthritis, Polyarthralgia - Chorea - Erythema marginatum - Subcutaneous nodules
Minor	- Polyarthralgia or Monoarthritis - Fever ( $\geq$ 38.5°C) - ESR $\geq$ 60 mm/hr OR CRP $\geq$ 3.0 mg/dL - Prolonged PR interval	- Monoarthralgia - Fever ( $\geq$ 38.0°C) - ESR $\geq$ 30 mm/hr OR CRP $\geq$ 3.0 mg/dL - Prolonged PR interval

Clinical Manifestations

Non-Cardiac Manifestations

Arthritis: Earliest manifestation (60-80% cases). Migratory polyarthritis involving large joints (knees, ankles, elbows). Swelling, warmth, redness, severe pain. Leaves no residual damage.
Sydenham's Chorea: Late manifestation (1-6 months post-infection). Semi-purposeful, jerky, involuntary movements. Emotional lability. Self-limiting course of 2-6 weeks.
Subcutaneous Nodules: Late manifestation. Painless, firm nodules over bony prominences (elbows, shins, occiput). Highly associated with severe carditis.
Erythema Marginatum: Early, rare. Faintly reddish, non-itching, serpiginous rash with pale centers. Predominantly on trunk.

Cardiac Manifestations (Carditis & Chronic RHD)

Pancarditis involving pericardium, myocardium, and endocardium. Valvular damage permanent.
Subclinical Carditis: Silent clinically. Identified exclusively via echocardiography demonstrating pathological regurgitation.

Mitral Regurgitation (MR)

Commonest manifestation of acute and chronic rheumatic carditis.
Pathophysiology: Annular dilatation, chordal elongation/rupture causing anterior leaflet prolapse, focal nodular leaflet thickening. Left atrial and ventricular volume overload.
Hemodynamics: Systolic leak into left atrium. Rapid filling in early diastole causes third heart sound (S3). Increased left atrial pressure leads to pulmonary congestion.
Clinical Signs: Displaced, hyperkinetic apex. Pansystolic murmur best heard at apex, radiating to axilla. Wide split S2. Carey Coombs murmur (soft delayed diastolic murmur) in acute phase.

Mitral Stenosis (MS)

Chronic process requiring $\geq$ 10 years to establish. Result of fibrosis, commissural adhesions, and contracture of leaflets/chordae.
Pathophysiology: Restricted leaflet motion. Impaired left ventricular filling. Left atrial hypertrophy, pulmonary venous hypertension, elevated pulmonary vascular resistance, right ventricular failure.
Clinical Signs: Dyspnea, cough, hemoptysis, paroxysmal nocturnal dyspnea. Tapping apex. Loud S1. Opening snap. Mid-diastolic rumbling murmur with presystolic accentuation.

Aortic Regurgitation (AR)

Isolated pure rheumatic AR extremely rare; almost always accompanies mitral disease.
Pathophysiology: Sclerosis, distortion, and retraction of cusps. Left ventricular volume overload, dilatation, and hypertrophy.
Clinical Signs: Wide pulse pressure. Early diastolic decrescendo murmur at left sternal border.

Tricuspid Regurgitation (TR)

Primary involvement rare. Usually functional secondary to left-sided valvular disease, right ventricular dilatation, and pulmonary hypertension.
Clinical Signs: Prominent jugular V waves. Systolic hepatic pulsations. Holosystolic murmur at lower left sternal border, increasing with inspiration.

Investigations

Echocardiography (Gold Standard)

Excludes subclinical carditis. Mandated in modern Jones Criteria.
Acute Changes: Annular dilation, chordal elongation, flail leaflet, anterior leaflet tip prolapse, beading/nodularity of leaflet tips.
Chronic Changes: Leaflet thickening, chordal thickening/fusion, restricted leaflet motion, calcification.
MS Specifics: "Hockey-stick" appearance of anterior mitral leaflet in diastole.
Color Doppler: Quantifies severity of regurgitant jets (jet length, peak velocity, pan-systolic/pan-diastolic nature).

Electrocardiography (ECG)

Prolonged PR interval (non-specific, does not alone indicate carditis).
Advanced AV block (rare).
P-mitrale (broad, bifid P waves) indicating left atrial enlargement.
RV/LV hypertrophy signs depending on specific valvular lesion.
Atrial fibrillation common in advanced chronic MS.

Radiography (CXR)

Cardiomegaly (left atrial/ventricular enlargement).
Pulmonary venous congestion, prominent hilar vessels.
Kerley B lines in advanced MS.
Double atrial shadow, elevation of left bronchus in massive LA enlargement.

Laboratory Evaluation

Acute Phase Reactants: Elevated ESR and CRP. Normalize with steroid therapy or resolution of active inflammation.
Streptococcal Antibodies: ASO titer (>250 units suggestive of recent infection). Anti-DNase B.

Management Strategies

Medical Management of Acute Rheumatic Fever

Eradication of GAS: Single intramuscular injection of Benzathine Penicillin G. Alternatives: Oral Penicillin V for 10 days, or Azithromycin (if penicillin allergic).
Anti-inflammatory Therapy:
- Arthritis/Mild Carditis: High-dose Aspirin or NSAIDs (Naproxen).
- Severe Carditis (with CHF): Corticosteroids (Prednisone/Methylprednisolone) indicated to rapidly suppress inflammation, resolve friction rubs, and manage severe hemodynamic compromise.
Heart Failure Management:
- Diuretics (Furosemide) for volume overload.
- ACE inhibitors or Angiotensin Receptor Blockers (ARBs) for afterload reduction in severe regurgitation.
- Beta-blockers (Carvedilol). Digoxin in select cases. Caution with vasodilators to avoid hypotension.

Secondary Prophylaxis

Crucial to prevent recurrent ARF and progressive valvular damage.
Regimen: Intramuscular Benzathine Penicillin G every 3 to 4 weeks. (Every 2 weeks in highly endemic regions for patients <30 kg).
Duration (AHA Guidelines):

Patient Category	Recommended Duration
ARF without carditis	5 years after last ARF episode OR until age 21 (whichever is longer).
ARF with carditis, NO residual RHD	10 years after last ARF episode OR until age 21 (whichever is longer).
ARF with carditis AND residual RHD	10 years after last ARF episode OR until age 40 (whichever is longer). Lifelong prophylaxis often required.

Surgical & Interventional Management

Indicated for refractory heart failure, severe symptoms despite medical therapy, or progressive cardiomegaly.
Mitral Valve Repair: Preferred over replacement in children/adolescents. Involves annuloplasty, chordal reconstruction. Avoids need for lifelong anticoagulation.
Mitral Valve Replacement: Indicated when repair unfeasible. Requires lifelong anticoagulation (Warfarin) with strict INR monitoring. High risk of mechanical valve thrombosis or structural failure of bioprosthetic valves in young patients.
Percutaneous Balloon Mitral Valvotomy: Treatment of choice for rheumatic MS without severe calcification, marked subvalvular fusion, or significant concomitant MR.
Aortic Valve Surgery: Repair rarely feasible. Replacement via mechanical prosthesis or homograft.

Complications & Prognosis

Short-Term & Long-Term Complications

Congestive Heart Failure: Primary cause of morbidity and mortality.
Arrhythmias: Atrial fibrillation (AF) strongly associated with left atrial dilation in MS. High risk of thromboembolism.
Thromboembolism: Systemic embolization leading to stroke. Incidence elevated in AF and massive left atrial enlargement.
Infective Endocarditis: Damaged endothelium serves as nidus. Risk mandates rigorous dental hygiene. Antibiotic prophylaxis indicated prior to bacteremia-inducing procedures in patients with established RHD or prosthetic valves.
Pulmonary Hypertension: Irreversible pulmonary vascular disease consequence of untreated, long-standing left-sided valvular lesions.

Prognosis

Determined by severity of initial carditis and frequency of recurrent ARF episodes.
Post-ARF progression to RHD occurs in ~60-65% of patients.
Timely secondary prophylaxis drastically reduces morbidity. Non-compliance results in progressive valvular destruction, heart failure, and premature mortality often in the 3rd or 4th decade of life.