Rheumatic Aortic Regurgitation

Diastolic leak of blood from the aorta into the left ventricle through a valve scarred by rheumatic fever: thickened, retracted and shortened leaflets with commissural fusion that leaves a central gap. Scarring often narrows the valve too, giving mixed aortic disease.

• Rheumatic heart disease affects about 40 million people, mostly in sub-Saharan Africa, South Asia and the Pacific. The aortic valve is involved in about a quarter to a third of rheumatic valve disease, almost always with mitral disease. Isolated rheumatic aortic regurgitation is uncommon.
• Mechanism: group A streptococcal pharyngitis triggers an immune response that cross reacts with valve tissue, and repeated attacks add fibrosis. Chronic regurgitation causes volume overload, eccentric hypertrophy, a wide pulse pressure from diastolic run off, and low diastolic aortic pressure that reduces coronary perfusion (angina can occur with normal coronary arteries).
• Natural history: years without symptoms. Asymptomatic severe regurgitation with normal left ventricular function progresses to symptoms or dysfunction at about 4 to 6% per year. Once symptoms appear, mortality without surgery is about 10 to 20% per year. Acute severe regurgitation is poorly tolerated because the ventricle cannot dilate.

• Chronic disease: exertional dyspnoea, fatigue, forceful palpitations, angina (including at night with sweating), orthopnoea and oedema late.
• Signs:
  • Collapsing (water hammer) pulse, pulse pressure greater than 80 mmHg with diastolic pressure often less than 50 mmHg, head nodding (de Musset sign), capillary pulsation (Quincke sign), femoral to-and-fro murmur (Duroziez sign), popliteal systolic pressure exceeding brachial by more than 60 mmHg (Hill sign).
  • Displaced, hyperdynamic apex. Early diastolic decrescendo murmur at the left sternal edge, best heard sitting forward in held expiration. Austin Flint mid-diastolic apical murmur. Ejection systolic flow murmur. S3 in decompensation.
• Acute severe regurgitation (endocarditis, dissection, trauma): sudden pulmonary oedema, tachycardia, shock, a short soft diastolic murmur, a soft first heart sound and a normal or narrow pulse pressure.
• Differential diagnosis: pulmonary regurgitation, aortic root dilatation (Marfan syndrome, hypertension, syphilis, bicuspid valve), endocarditis, aortic dissection, ventricular septal defect with cusp prolapse, and high output states with a wide pulse pressure but no regurgitation (thyrotoxicosis, severe anaemia, arteriovenous fistula, Paget disease, pregnancy).
• Complications: heart failure, left ventricular dysfunction, angina, ventricular arrhythmia and sudden death, atrial fibrillation (with mitral disease), infective endocarditis, and recurrent rheumatic fever with further valve damage.

• ECG: left ventricular hypertrophy with strain, a prolonged PR interval in active carditis. Chest X-ray: cardiomegaly, dilated aortic root, pulmonary congestion.
• Echocardiography: thickened or retracted leaflets, fused commissures, and jet direction. Severe regurgitation: vena contracta greater than 0.6 cm, jet width greater than 65% of the outflow tract, pressure half time less than 200 ms, holodiastolic flow reversal in the descending aorta, regurgitant volume 60 mL or more, regurgitant fraction 50% or more, effective regurgitant orifice area 0.3 cm2 or more.
• Left ventricular decompensation: end systolic diameter greater than 50 mm (or greater than 25 mm/m2), end diastolic diameter greater than 65 to 70 mm, ejection fraction 55% or less.
• Cardiac MRI: regurgitant fraction greater than 48% is severe; use when echocardiography is discordant. CT for the aortic root and ascending aorta. Transoesophageal echocardiography if endocarditis or dissection is suspected.
• Coronary angiography before surgery in men over 40, women over 50, and anyone with coronary risk factors.
• Blood tests: full blood count, CRP, ESR, antistreptolysin O titre and anti-DNase B if recent infection, blood cultures if febrile, HIV test.

• Explain the course and that surgery is planned by symptoms and ventricular size. Avoid heavy isometric exertion once the ventricle is dilated.
• Medical therapy (relieves symptoms and treats hypertension; it does not repair the valve):
  • Amlodipine 5 to 10 mg daily or nifedipine retard 30 to 60 mg daily.
  • Ramipril 2.5 to 10 mg daily, titrated to blood pressure and renal function (check creatinine and potassium at 1 to 2 weeks).
  • Target systolic pressure less than 140 mmHg (lower if tolerated), with diastolic pressure kept at 50 mmHg or more to protect coronary flow.
  • Furosemide 20 to 80 mg daily and spironolactone 12.5 to 50 mg daily for congestion.
  • Beta blockers lengthen diastole and increase regurgitant volume, so avoid high doses and avoid them in acute regurgitation. Use bisoprolol 1.25 to 5 mg daily only for rate control of atrial fibrillation or after surgery.
  • Atrial fibrillation with rheumatic mitral involvement: warfarin to INR 2.0 to 3.0; direct oral anticoagulants are not advised.
• Secondary prophylaxis against further rheumatic attacks:
  • Benzathine benzylpenicillin 1.2 million units IM every 3 to 4 weeks (600,000 units if under 30 kg), or penicillin V 250 mg orally twice daily. For penicillin allergy: sulfadiazine 1 g daily (500 mg if under 30 kg) or erythromycin 250 mg twice daily.
  • Duration: 10 years after the last attack or to age 40, whichever is longer; lifelong with severe disease or after valve surgery.
• Active acute rheumatic fever: benzathine benzylpenicillin 1.2 million units IM once (600,000 units if under 30 kg) or penicillin V 500 mg orally twice daily for 10 days; aspirin 75 to 100 mg/kg/day in 4 divided doses for arthritis (monitor for salicylate toxicity); prednisolone 1 to 2 mg/kg/day (maximum 80 mg) for carditis with heart failure.
• Surgery:
  • Indications: symptomatic severe regurgitation; asymptomatic severe regurgitation with ejection fraction 55% or less, end systolic diameter greater than 50 mm (or greater than 25 mm/m2), or end diastolic diameter greater than 70 mm; severe regurgitation when other cardiac surgery is planned.
  • Repair is rarely possible in rheumatic valves, so replacement is the usual operation. Mechanical valve for patients under 50 who can take warfarin (INR 2.5, range 2.0 to 3.0; INR 3.0, range 2.5 to 3.5 with atrial fibrillation, previous embolism, ejection fraction less than 35% or a hypercoagulable state). Bioprosthesis for patients over 65 or those unable to take warfarin (aspirin 75 to 100 mg daily, or warfarin to INR 2.5 for 3 months). Direct oral anticoagulants must not be used with mechanical valves.
  • Avoid the Ross operation because the pulmonary valve may be rheumatic. Transcatheter valve implantation has limited evidence in pure regurgitation.
  • Operative mortality about 2 to 5% for isolated replacement, higher with combined mitral surgery or reduced ejection fraction.
• Acute severe regurgitation: urgent surgery. While waiting: furosemide 40 to 80 mg IV, sodium nitroprusside 0.3 to 10 micrograms/kg/min if blood pressure allows, dobutamine 2.5 to 10 micrograms/kg/min or noradrenaline if hypotensive. Avoid beta blockers and intra aortic balloon pump. If endocarditis is the cause, start antibiotics after blood cultures.
• Endocarditis prophylaxis only after valve replacement or previous endocarditis: amoxicillin 2 g orally (50 mg/kg in children) 30 to 60 minutes before dental procedures; azithromycin or clarithromycin 500 mg (15 mg/kg in children) if allergic to penicillin (clindamycin is no longer recommended).
• Special groups:
  • Pregnancy: asymptomatic patients with normal ventricular function usually tolerate it; furosemide for congestion; nifedipine retard 10 to 20 mg twice daily or hydralazine for hypertension; avoid ACE inhibitors and ARBs; continue penicillin prophylaxis. Mechanical valves need specialist anticoagulation planning (enoxaparin 1 mg/kg twice daily with anti-Xa monitoring, or warfarin at 5 mg/day or less).
  • Children: repair is occasionally possible; strict prophylaxis and echocardiography every 6 to 12 months.
  • Renal impairment: reduce ramipril and spironolactone doses.
• Red flags: pulmonary oedema, angina at rest, syncope, fever with a new murmur, rapid ventricular dilatation, missed penicillin injections.
• Follow up: severe asymptomatic disease every 6 months with echocardiography; moderate every year; mild every 1 to 2 years.