Rheumatic Heart Disease: Pathogenesis, Symptoms, Diagnosis, Management and Prevention

Rheumatic Heart Disease: Pathogenesis, Clinical Features and Management

~Introduction

Rheumatic Heart Disease (RHD) is a chronic valvular condition resulting from damage to the heart valves caused by rheumatic fever, a sequela of untreated or inadequately treated Group A β-hemolytic streptococcal (GAS) pharyngitis. Although largely preventable, RHD remains a major cause of cardiovascular morbidity and mortality in low- and middle-income countries, particularly affecting children and young adults. The disease is a tragic reminder of the link between infection, immunity, and poverty in global health.

RHD is characterized by permanent deformity of the cardiac valves—most commonly the mitral valve, followed by the aortic, tricuspid, and rarely, the pulmonary valve. Chronic inflammation leads to fibrosis, commissural fusion, and calcification, causing stenosis, regurgitation, or a combination of both. The natural history of RHD spans decades, beginning with acute rheumatic fever (ARF) and progressing to chronic valvular dysfunction if not managed appropriately.

~Epidemiology

Rheumatic heart disease disproportionately affects socio-economically disadvantaged populations.

• Global burden: Over 40 million people worldwide live with RHD, leading to over 300,000 deaths annually.

• Geographic distribution: High prevalence persists in South Asia, Sub-Saharan Africa, the Pacific Islands, and certain Indigenous communities in Australia and New Zealand.

• Age group: RHD primarily affects children aged 5–15 years, but its complications manifest in adulthood.

• Gender differences: Females are more commonly affected than males, possibly due to hormonal and social factors.

In high-income countries, the incidence of rheumatic fever has sharply declined due to improved living conditions, early antibiotic therapy, and public health initiatives.

~Etiology and Pathogenesis

1. Causative Agent

RHD results from an autoimmune response to infection with Group A β-hemolytic Streptococcus (Streptococcus pyogenes), which typically causes pharyngitis or tonsillitis. Not all individuals with streptococcal infections develop rheumatic fever—genetic and immune factors play critical roles.

2. Pathogenesis of Acute Rheumatic Fever

The disease develops 2–3 weeks after untreated or inadequately treated streptococcal throat infection. It is not the bacteria itself but the immune reaction that causes tissue injury.

• Molecular Mimicry: The streptococcal M protein shares structural similarities with human cardiac myosin, laminin, and other connective tissue proteins. The immune system, in attacking the bacteria, also targets host tissues.

• Autoimmune Inflammation: Cross-reactive antibodies and T-cells infiltrate the heart, joints, skin, and central nervous system, producing a multisystem inflammatory disease—acute rheumatic fever.

3. Cardiac Involvement

All three layers of the heart—endocardium, myocardium, and pericardium—can be inflamed, leading to pancarditis.

• Endocarditis: The most significant manifestation, leading to valvulitis and long-term scarring.

• Myocarditis: Causes cardiac dilation and heart failure during the acute phase.

• Pericarditis: Leads to friction rub and pericardial effusion, which usually resolves without sequelae.

Repeated attacks of rheumatic fever result in cumulative damage to the valves, leading to chronic rheumatic heart disease.

~Pathology

Acute Phase

• Aschoff bodies: Pathognomonic lesions consisting of foci of swollen eosinophilic collagen surrounded by T-cells, plasma cells, and Anitschkow cells (activated macrophages with “caterpillar” nuclei).

• Valvulitis: Small vegetations (verrucae) form along the lines of valve closure, especially on the mitral valve.

Chronic Phase

• Fibrosis and Calcification: Repeated inflammation leads to thickened leaflets and fused commissures.

• Chordae Tendineae Shortening: Causes leaflet retraction and restricted motion.

• Valve Deformities:

  • Mitral stenosis (most common)

  • Mitral regurgitation

  • Aortic regurgitation or mixed lesions

These changes impair forward flow, increase cardiac workload, and eventually cause heart failure, arrhythmias, and thromboembolic events.

~Clinical Features

A. Acute Rheumatic Fever (ARF)

1. Major Criteria (Jones Criteria)

• Carditis: May involve pericardium, myocardium, or endocardium. Presents with tachycardia, murmurs, cardiomegaly, or heart failure.

• Polyarthritis: Migratory, affecting large joints.

• Sydenham’s chorea: Involuntary movements due to basal ganglia involvement.

• Erythema marginatum: Non-pruritic rash with serpiginous margins, typically on the trunk.

• Subcutaneous nodules: Firm, painless nodules over extensor surfaces.

2. Minor Criteria

• Fever

• Arthralgia

• Elevated ESR or CRP

• Prolonged PR interval on ECG

3. Supporting Evidence of Streptococcal Infection

• Positive throat culture for GAS

• Elevated antistreptolysin-O (ASO) titers

• Recent scarlet fever

Diagnosis requires two major or one major and two minor criteria plus evidence of streptococcal infection.

B. Chronic Rheumatic Heart Disease

Symptoms

• Dyspnea on exertion or at rest

• Fatigue and reduced exercise tolerance

• Palpitations due to atrial fibrillation

• Hemoptysis (in mitral stenosis)

• Orthopnea and paroxysmal nocturnal dyspnea

Signs

• Cardiac murmurs:

  • Mitral stenosis: Low-pitched diastolic rumble with an opening snap.

  • Mitral regurgitation: Holosystolic murmur at apex radiating to axilla.

  • Aortic regurgitation: Early diastolic decrescendo murmur at left sternal border.

• Other findings:

  • Elevated jugular venous pressure, hepatomegaly, ascites, and pedal edema in right heart failure.

  • Tapping apex beat in mitral stenosis.

~Complications

• Heart Failure: Due to chronic pressure and volume overload.

• Atrial Fibrillation: Especially in mitral stenosis.

• Thromboembolism: Formation of left atrial thrombi leading to stroke or systemic emboli.

• Infective Endocarditis: Damaged valves are prone to bacterial colonization.

• Pulmonary Hypertension: Secondary to mitral stenosis and left atrial hypertension.

• Death: Often due to refractory heart failure or embolic complications.

~Diagnosis

1. Laboratory Investigations

• Evidence of recent streptococcal infection:

  • Elevated ASO titers (>200 units)

  • Anti-DNase B antibodies

  • Positive throat culture for GAS

• Inflammatory markers: Elevated ESR and CRP during acute phase.

• Complete blood count: Mild leukocytosis and anemia in chronic disease.

2. Electrocardiography (ECG)

• Prolonged PR interval in acute carditis.

• Atrial fibrillation or right ventricular hypertrophy in chronic cases.

3. Chest X-Ray

• Cardiomegaly, straightening of left heart border (mitral configuration).

• Pulmonary congestion and left atrial enlargement.

4. Echocardiography

The most useful diagnostic tool:

• Demonstrates valvular thickening, restricted motion, fused commissures, and calcification.

• Assesses severity of stenosis or regurgitation and ventricular function.

• Doppler echocardiography helps in measuring gradients and valve areas.

5. Cardiac Catheterization

Used when non-invasive tests are inconclusive or before surgical intervention to measure pressures and assess coronary anatomy.

~Management

A. Acute Rheumatic Fever

1. Eradication of Streptococcal Infection

• Benzathine Penicillin G: Single intramuscular dose (1.2 million units for adults; 600,000 units for children <27 kg).

• For penicillin-allergic patients: Erythromycin or Azithromycin.

2. Anti-inflammatory Therapy

• Aspirin: 80–100 mg/kg/day in divided doses for arthritis.

• Corticosteroids: Prednisolone (1–2 mg/kg/day) for severe carditis.

3. Supportive Treatment

• Bed rest during active inflammation.

• Diuretics and digitalis for heart failure.

• Management of chorea with haloperidol or valproic acid if needed.

B. Chronic Rheumatic Heart Disease

1. Medical Management

• Penicillin prophylaxis to prevent recurrent attacks (secondary prevention).

  • Benzathine Penicillin G every 3–4 weeks intramuscularly.

  • Lifelong or at least until age 40 in those with residual valvular disease.

• Diuretics for volume overload and heart failure.

• Beta-blockers or Digoxin for rate control in atrial fibrillation.

• Anticoagulation (Warfarin) for patients with atrial fibrillation or large left atria to prevent thromboembolism.

• Endocarditis prophylaxis during dental or surgical procedures.

2. Surgical and Interventional Therapy

Indicated when symptoms persist despite medical treatment or when hemodynamic compromise is significant.

• Percutaneous Mitral Balloon Valvotomy (PMBV):
  Preferred for pliable, non-calcified valves with commissural fusion and minimal regurgitation.

• Valve Repair:
  Preserves native valve function when feasible.

• Valve Replacement:
  Required for severely damaged or calcified valves. Mechanical valves require lifelong anticoagulation, while bioprosthetic valves may need re-replacement after 10–15 years.

3. Follow-Up

Regular echocardiographic surveillance is essential to assess valve function, detect restenosis, and monitor heart size and function. Lifelong follow-up improves long-term survival and quality of life.

~Prevention

1. Primary Prevention

• Early diagnosis and antibiotic treatment of streptococcal pharyngitis.

  • Benzathine penicillin G (IM single dose) or oral penicillin V for 10 days.

• Public health measures:

  • Improved hygiene, reduced overcrowding, and access to primary healthcare.

• School health programs for early recognition of sore throat and fever in children.

2. Secondary Prevention

• Long-term penicillin prophylaxis in patients with previous ARF or RHD.

• Adherence to scheduled intramuscular injections every 3–4 weeks is crucial to prevent recurrences.

3. Tertiary Prevention

• Prevention of complications in established RHD through regular monitoring, endocarditis prophylaxis, and timely surgical interventions.

~Prognosis

The prognosis of RHD varies widely depending on the severity of valve damage, access to medical care, and adherence to secondary prophylaxis.

• With early diagnosis and good follow-up, patients can live for decades without severe disability.

• Untreated or recurrent disease often leads to chronic heart failure, stroke, or death by early adulthood.

• Surgical or interventional correction markedly improves survival and quality of life.

Despite being preventable, RHD continues to exact a heavy toll in resource-poor regions due to limited healthcare infrastructure and socioeconomic barriers.

~Recent Advances and Research

• Echocardiographic screening programs in endemic areas have improved early detection among school-aged children.

• Vaccine development targeting Group A Streptococcus is under research to provide primary prevention at the community level.

• Telemedicine initiatives are being deployed for remote monitoring of patients receiving long-term prophylaxis.

• Global RHD control programs, such as the World Heart Federation’s Roadmap for RHD, aim to eradicate the disease through integrated healthcare strategies.

~Public Health Perspective

RHD is often referred to as a “disease of poverty” because it thrives in settings of overcrowding, poor sanitation, and inadequate healthcare access. Effective control requires a multi-sectoral approach combining medical, social, and educational measures. Community awareness, school health initiatives, training of healthcare workers, and ensuring availability of antibiotics at the primary level are essential.

~Conclusion

Rheumatic Heart Disease remains a significant but preventable cause of cardiovascular morbidity and mortality worldwide. It arises from an autoimmune response to Group A Streptococcal infection and progresses from acute rheumatic fever to chronic valvular deformities, predominantly affecting the mitral valve. Early recognition, appropriate antibiotic therapy, and sustained secondary prevention are critical to halting disease progression. In advanced cases, surgical or percutaneous valve interventions can restore function and improve prognosis. Ultimately, the eradication of RHD depends not only on medical advances but also on socio-economic improvements, universal healthcare access, and global commitment to disease prevention.