How should rheumatic valvular disease be managed, including secondary prophylaxis, medical therapy for complications, and indications for valve intervention?

Management of Rheumatic Valvular Disease

All patients with rheumatic valvular disease require long-term secondary antibiotic prophylaxis with benzathine penicillin G 1.2 million units intramuscularly every 4 weeks, and this must continue even after valve replacement surgery. 1, 2

Secondary Prophylaxis: The Cornerstone of Management

First-Line Antibiotic Regimen

• Benzathine penicillin G 1.2 million units intramuscularly every 4 weeks is the gold standard, with approximately 10 times greater efficacy than oral antibiotics in preventing recurrent rheumatic fever 1, 2, 3
• For high-risk patients or those with recurrence despite adherence, administer benzathine penicillin G every 3 weeks instead of every 4 weeks to maintain more consistent protective levels 1, 2, 3

Alternative Regimens for Penicillin Allergy

• Penicillin V 250 mg orally twice daily as second-line option 1, 2, 3
• Sulfadiazine 1 gram orally once daily (0.5 gram for patients ≤27 kg) for penicillin-allergic patients 1, 2, 3
• Macrolide or azalide antibiotics only for patients allergic to both penicillin and sulfadiazine, but avoid in patients taking cytochrome P450 3A inhibitors (azole antifungals, HIV protease inhibitors, some SSRIs) 1, 3

Duration of Secondary Prophylaxis

The duration is stratified by disease severity and must be calculated as the longer of two time periods 1, 4:

For severe RHD with persistent valvular disease:

• Minimum 10 years after most recent acute rheumatic fever episode OR until age 40 years, whichever is longer 1, 4
• Consider lifelong prophylaxis in high-risk patients with severe valvular disease and high exposure to group A streptococcus 1, 3

For moderate RHD:

• Minimum 10 years after most recent acute rheumatic fever OR until age 35 years, whichever is longer 1

For mild RHD:

• Minimum 10 years after most recent acute rheumatic fever OR until age 21 years, whichever is longer 1
• If no documented acute rheumatic fever episode, minimum 5 years following diagnosis OR until age 21 years, whichever is longer 1

For rheumatic fever without carditis:

• 5 years after last attack OR until age 21 years, whichever is longer 1, 4, 3

Critical Pitfall: Post-Surgical Prophylaxis

• Secondary prophylaxis must continue after valve surgery because valve replacement does not eliminate the risk of recurrent acute rheumatic fever from group A streptococcus infection 1, 4
• This represents a critical departure from the common misconception that valve replacement eliminates the need for prophylaxis 4
• Before initiating long-term prophylaxis, administer a full therapeutic course of penicillin to eradicate any residual group A streptococcus, even if throat culture is negative 2, 3

Medical Management of Cardiac Complications

Heart Failure and Left Ventricular Dysfunction

• Apply guideline-directed medical therapy including diuretics, ACE inhibitors or ARBs, beta-blockers, and aldosterone antagonists for left ventricular systolic dysfunction 2, 3
• Consider sacubitril/valsartan as part of contemporary heart failure management 3

Rate Control in Atrial Fibrillation

• Beta-blockers are the first-line agents for heart rate control, lengthening diastole to improve left ventricular filling 1
• Digoxin may be added for additional rate control if beta-blockers alone are insufficient 1

Anticoagulation Indications

• Chronic or paroxysmal atrial fibrillation requires anticoagulation with vitamin K antagonists targeting INR 2.0-3.0 1, 5
• Consider anticoagulation for patients in sinus rhythm with very severe left atrial dilatation, spontaneous echo contrast, or heart failure 1
• History of previous thromboembolism is an absolute indication for anticoagulation 5

Critical Pitfall: Blood Pressure Management

• Avoid abrupt lowering of blood pressure in patients with stenotic valve lesions (particularly mitral stenosis) to prevent hemodynamic collapse 2, 3

Infective Endocarditis Prophylaxis: Clarifying the Misconception

Current guidelines do NOT recommend routine endocarditis prophylaxis for rheumatic heart disease alone 2, 3

When Endocarditis Prophylaxis IS Indicated

Prophylaxis is reasonable only for patients with rheumatic heart disease who have 1:

• Prosthetic cardiac valves or prosthetic material used for valve repair
• Previous infective endocarditis

Procedures Requiring Prophylaxis (in high-risk patients only)

• Dental procedures involving manipulation of gingival tissue, periapical region, or perforation of oral mucosa 1
• Dermatological and musculoskeletal procedures involving infected skin, skin structures, or tissues 1
• Tonsillectomy, adenoidectomy, or invasive respiratory tract procedures to treat infection 1
• Genitourinary and gastrointestinal procedures only if established infection is present 1

Important Consideration

• For patients receiving penicillin prophylaxis for rheumatic fever who require endocarditis prophylaxis for dental procedures, use an agent other than penicillin because oral α-hemolytic streptococci likely have developed penicillin resistance 4, 3
• Maintaining optimal oral health remains the most important component of preventing infective endocarditis 1, 2

Indications for Valve Intervention

Mitral Stenosis: Percutaneous Mitral Balloon Commissurotomy (PMBC)

PMBC is the first-line intervention for severe rheumatic mitral stenosis and should be performed at comprehensive valve centers by experienced operators 1

Indications for PMBC:

• Symptomatic patients (NYHA class III-IV) with moderate-severe mitral stenosis (MVA <1.5 cm²) despite medical therapy 1
• Asymptomatic patients with severe rheumatic mitral stenosis (MVA ≤1.5 cm²) who have favorable valve morphology 1
• Before pregnancy in women with moderate-severe mitral stenosis who are considering pregnancy 1
• During pregnancy (after 20th week only) in experienced centers for patients with severe symptoms despite medical therapy, with exact timing requiring multidisciplinary team consultation 1

When to Consider Surgical Valve Replacement

• Patients with degenerative mitral valve disease (not suitable for PMBC) 1
• Concurrent significant mitral regurgitation 1
• Unfavorable valve morphology for PMBC (heavy calcification, severe subvalvular disease) 1
• Failed previous PMBC with restenosis, though repeat PMBC may be considered if surgical risk is high 1

Timing of Intervention

• Evaluate all patients with symptomatic severe rheumatic mitral stenosis for intervention within 3 months of diagnosis 3
• Asymptomatic patients with severe mitral stenosis should undergo exercise testing to confirm absence of symptoms and assess hemodynamic response (particularly pulmonary artery systolic pressure >50 mmHg during exercise) 1

Additional Preventive Measures

• Influenza and pneumococcal vaccinations should be administered following standard recommendations 1, 2, 3
• Regular aerobic exercise is encouraged to improve cardiovascular fitness in patients with asymptomatic valvular heart disease 2, 3

Evidence Supporting Prolonged Prophylaxis

A large Brazilian cohort study demonstrated that patients with rheumatic heart disease undergoing regular secondary prophylaxis showed regression of mitral valve lesions in 69.9% and aortic valve lesions in 48.7%, with no disease progression in compliant patients 6. However, a retrospective study of adult patients post-valve replacement found no significant difference in mortality, valve-related hospitalization, or reoperation rates between those receiving versus not receiving secondary antibiotic prophylaxis 7. Despite this, guidelines uniformly recommend continuing prophylaxis post-surgery based on the rationale of preventing recurrent acute rheumatic fever rather than improving post-surgical outcomes 1, 4.