Rheumatic Heart Disease (RHD)

Definition

RHD is chronic valvular damage resulting from one or more episodes of acute rheumatic fever (ARF), which is itself a delayed, non-suppurative sequela of Group A beta-hemolytic streptococcal (GAS) pharyngitis. It is the most common acquired heart disease in young people globally.

Epidemiology

Worldwide: over 15 million cases of RHD with ~282,000 new cases annually; approximately 220,000 deaths per year (about 0.4% of total global deaths)
Highest burden in developing countries - India, Sub-Saharan Africa, South Asia, Pacific islands
India: prevalence 5-7 per 1,000 in the 5-15 age group; ~1 million cases; constitutes 20-30% of hospital admissions due to cardiovascular disease
Peak age: 5-15 years (school-age children); adults account for ~20% of cases
Prognosis is worse in females than males
Declining in affluent countries (North America, Western Europe, Japan) due to improved living standards, though disease persists in poverty pockets
- Park's Textbook of Preventive and Social Medicine

Etiology and Pathogenesis

Trigger

GAS (Group A beta-hemolytic Streptococcus) pharyngeal infection (NOT skin infection)
M protein serotype 5 is particularly associated with rheumatogenicity
RF occurs in 1-3% of GAS throat infections; not all strains are "rheumatogenic"

Molecular Mimicry (the core mechanism)

The immune response to streptococci cross-reacts with host cardiac tissue:

Antibodies against N-acetyl-glucosamine (streptococcal carbohydrate) cross-react with:
- Cardiac myosin (N-terminal M5/M6 protein epitope: Gln-Lys-Ser-Lys-Gln)
- Laminin in valvular basement membrane
- Tropomyosin in myocardium
Adhesion molecules upregulated: VCAM-1, ICAM, P-selectin, VLA-4 - facilitating CD4+ T lymphocyte extravasation into valve tissue
Chemokines driving inflammation:
- CCL3/MIP-1α - upregulated in myocardium
- CCL1/I-309 and CXCL9/Mig - highly expressed in valvular tissue
- T cells in valvular lesions migrate toward CXCL9/Mig gradient
T cell reactivity: 63.2% of intralesional T cell clones recognize light meromyosin (LMM) peptides; 34% show cross-reactivity patterns against myosin, valve proteins, and M5 peptides
Matrix disruption: TNF (pro-inflammatory), TGF-beta (anti-inflammatory), and MMP-25 (matrix degradation) mediate valve damage. Protein imbalance found: elevated vimentin, lumican, apolipoprotein-A1; reduced collagen-VI, biglycan, cartilage oligomeric matrix protein.

Firestein & Kelley's Textbook of Rheumatology

Valvular Pathology

Valve	Involvement	Lesion
Mitral	~100%	Regurgitation (most common acute), then Stenosis (chronic scarring) - most common cause of MS worldwide
Aortic	20-30%	Regurgitation > Stenosis
Tricuspid	15-40% (histologic)	Rarely clinically relevant
Pulmonic	Rare	-

Mitral regurgitation is the most common acute valvular pathology
Mitral stenosis develops after progressive fibrosis and scarring; RHD is the leading cause of MS globally
Severe valvular disease typically manifests in the 3rd-4th decade of life
"Juvenile mitral stenosis" - unique to India; earlier onset, faster progression, associated with pulmonary arterial hypertension
- Goldman-Cecil Medicine

Clinical Features of Acute Rheumatic Fever (ARF)

Feature	Details
Fever	Onset with acute illness, can last ~12 weeks, tends to recur
Polyarthritis	90% of cases; large joints (ankles, knees, elbows, wrists); migratory; resolves without residual damage
Carditis	60-70% clinically; 18% subclinical on echo; tachycardia, murmurs, cardiomegaly, pericarditis, HF; first-degree AV block on ECG
Subcutaneous nodules	Appear 4 weeks after onset; small, painless; self-resolving
Sydenham's chorea	Jerky, purposeless movements; self-resolving
Erythema marginatum	Skin rash; self-resolving

Key point: Only carditis causes permanent damage - all other manifestations resolve without sequelae.

Diagnosis - WHO/Jones Criteria (2002-2003 Revision)

For a PRIMARY episode of RF: 2 major OR 1 major + 2 minor manifestations + evidence of preceding GAS infection

Major Manifestations	Minor Manifestations
Carditis	Fever
Polyarthritis	Polyarthralgia
Chorea	Elevated ESR or leukocyte count
Erythema marginatum	Prolonged PR interval on ECG
Subcutaneous nodules

Evidence of preceding GAS infection (within 45 days):

Elevated/rising ASLO (antistreptolysin-O) or other streptococcal antibodies
Positive throat culture
Rapid antigen test for Group A streptococci
Recent scarlet fever

Special diagnostic categories:

Recurrent RF in a patient without established RHD: 2 major OR 1 major + 2 minor + GAS evidence
Recurrent RF in a patient with established RHD: only 2 minor + GAS evidence
Rheumatic chorea or insidious onset carditis: no other criteria required
Chronic valve lesions (pure MS or mixed MV disease): no additional criteria needed - diagnosed as RHD on clinical presentation alone
Park's Textbook of Preventive and Social Medicine

Prevention

Primary Prevention

Prevent the first ARF attack by treating all GAS pharyngitis with penicillin:

Single IM injection: Benzathine benzyl penicillin 1.2 million units (adults) or 600,000 units (children)
OR Oral Penicillin V/G for 10 days
Practical challenge: many GAS infections are inapparent; lab facilities often unavailable in endemic areas
Focus on high-risk groups: school-age children 5-15 years

Secondary Prevention (most important in practice)

Prevent recurrent ARF attacks in patients with established RF/RHD:

Benzathine benzyl penicillin G IM every 3 weeks (preferred) - 1.2 million units (adults), 600,000 units (children)
Duration guidelines:
- No carditis: at least 5 years or until age 18, whichever is later
- Mild mitral regurgitation or healed carditis: 10 years after last attack OR until age 25, whichever is longer
- Moderate-severe carditis with persistent valvular disease: 10 years after last attack OR until age 40, sometimes lifelong
Penicillin allergy: use sulfadiazine or erythromycin

A 2024 Cochrane systematic review (PMID 39312290) confirms long-term benzathine penicillin prophylaxis reduces recurrence and progression to RHD. A 2024 meta-analysis (PMID 39542478) highlights that adherence to secondary prophylaxis remains a major challenge in endemic regions.

Management of Established RHD

Medical

Secondary prophylaxis (as above) - critical to slow progression
Anticoagulation for atrial fibrillation (very common complication due to LA enlargement from MS)
Diuretics, beta-blockers for heart failure/rate control
Infective endocarditis prophylaxis during bacteremia-causing procedures

Interventional / Surgical

Percutaneous Mitral Balloon Valvuloplasty (PMBV): treatment of choice for suitable mitral stenosis (pliable, non-calcified, no significant MR, no LA thrombus)
- A 2026 systematic review (PMID 41862112) evaluates outcomes of PMBV even in patients with LA appendage thrombus
Mitral valve repair or replacement: for severe MR or unsuitable MS anatomy
Aortic valve repair/replacement: for significant aortic involvement
Surgery typically needed in the 3rd-4th decade in untreated or inadequately prophylaxed patients

Complications

Mitral stenosis - most characteristic long-term lesion
Atrial fibrillation - from LA dilatation
Pulmonary hypertension
Heart failure
Infective endocarditis - RHD is a leading predisposing cause in developing countries
Stroke/systemic embolism - from LA thrombus in AF
Premature death - usually by age 35 in untreated severe disease

Key Risk Factors for Severity

Number of previous ARF attacks
Time between disease onset and start of therapy
Female sex
Poor adherence to secondary prophylaxis
Socioeconomic deprivation, overcrowding, poor housing

Summary: RHD is a preventable disease. The key principle is that primary prevention (treating GAS pharyngitis) prevents the first attack, and secondary prevention (long-term benzathine penicillin) prevents recurrence and progressive valvular damage. Echocardiographic screening in endemic regions detects latent disease and guides prophylaxis to reduce prevalence of progressive RHD.

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