INTRODUCTION — Rheumatic heart disease (RHD) remains a major cause of cardiovascular disease in developing nations, although the prevalence of RHD has declined sharply in industrialized countries during the last century [1]. Global Burden of Disease estimates show a steady increase in prevalence in low- and middle-income countries, with an estimated 40 million people affected by RHD globally in 2019 [2].
This topic will review the management and prevention of RHD. The clinical manifestations and diagnosis of RHD and the epidemiology, pathogenesis, diagnosis, treatment, and prevention of acute rheumatic fever (ARF) are discussed separately. (See "Clinical manifestations and diagnosis of rheumatic heart disease" and "Acute rheumatic fever: Epidemiology and pathogenesis" and "Acute rheumatic fever: Clinical manifestations and diagnosis" and "Acute rheumatic fever: Treatment and prevention".)
PREVENTION
Primary prevention — Prevention of the initial development of acute rheumatic fever (ARF) involves prompt diagnosis and antibiotic treatment of group A streptococcal (GAS) infection predominantly due to tonsillopharyngitis, as discussed separately [3]. In tropical countries, a link between GAS pyoderma and subsequent ARF/RHD is highly likely and is under investigation [4,5]. (See "Acute rheumatic fever: Treatment and prevention", section on 'Primary prevention'.)
Secondary prevention
Secondary prevention of recurrent ARF with continuous antibiotic prophylaxis is recommended for patients with definite history of ARF (table 1) (see "Acute rheumatic fever: Clinical manifestations and diagnosis", section on 'Diagnosis') or diagnosis of definite RHD (table 2) (see "Clinical manifestations and diagnosis of rheumatic heart disease", section on 'Diagnosis of rheumatic heart disease'). Continuous antimicrobial prophylaxis is recommended because recurrent ARF can be triggered by GAS infection even if asymptomatic. Patients should be registered in regional ARF prevention programs, where available [6]. Antibiotic selection, duration of therapy, supporting evidence, and patient education are described separately. (See "Acute rheumatic fever: Treatment and prevention", section on 'Secondary prevention (antibiotic prophylaxis)'.)
Based on limited evidence, we agree with guidelines that adjust the duration of prophylactic antibiotic administration depending upon the severity of heart disease, as outlined in the table (table 2) [7-9]. For individuals with RHD with previous valvulitis but not residual valvular disease (with additional criteria to confirm a definitive diagnosis of RHD), secondary prophylaxis is suggested for 10 years after the last attack or at least until 40 years of age (whichever is longer) [8]. For patients with more severe valvular damage (eg, causing heart failure [HF]) or after valve surgery, lifelong secondary prophylaxis is suggested. The appropriate duration of prophylaxis for those diagnosed with latent RHD within screening and research studies is uncertain pending completion of long-term longitudinal studies.
As discussed separately, there is evidence that secondary prophylaxis with penicillin reduces streptococcal infections, recurrent attacks of ARF, and frequency and duration of hospitalization in patients with ARF and RHD [10,11] and that secondary prophylaxis in individuals with latent rheumatic heart disease reduces the risk of echocardiographic progression [12]. (See "Acute rheumatic fever: Treatment and prevention" and "Acute rheumatic fever: Treatment and prevention", section on 'Secondary prevention (antibiotic prophylaxis)'.)
The available evidence is inconclusive, but clinical experience suggests that prophylaxis against ARF is unlikely to alter the natural history of RHD once symptomatic valve dysfunction is present, particularly if there is associated HF [13]. (See "Acute rheumatic fever: Treatment and prevention", section on 'Secondary prevention (antibiotic prophylaxis)'.)
MANAGEMENT OF CARDITIS IN ACUTE RHEUMATIC FEVER
General management of carditis — The mainstays of management of carditis (which is chiefly manifest as valvulitis) in acute rheumatic fever (ARF) are early diagnosis and assessment of severity using echocardiography, management of HF and other complications when present, and commencement of secondary prophylaxis [14]. (See "Clinical manifestations and diagnosis of rheumatic heart disease" and 'Severe carditis' below and 'Secondary prevention' above.)
We suggest not treating carditis with glucocorticoids and intravenous immune globulin (IVIG). A systematic review of eight randomized controlled trials (most published prior to 1966) involved 996 patients treated with antiinflammatory treatment (such as glucocorticoids, aspirin, and IVIG) [15-19]. There was no significant difference in risk of cardiac disease at one year between glucocorticoid- and aspirin-treated groups (six studies, 907 participants, risk ratio [RR] 0.87, 95% CI 0.66-1.15) [17]. There was no significant effect on presence of carditis at one year in a single study comparing IVIG with placebo (RR 0.87, 95% CI 0.55-1.39) [17]. However, as noted below, some experts use glucocorticoid therapy in some cases of severe carditis (see 'Severe carditis' below).
The general management of ARF is discussed separately. (See "Acute rheumatic fever: Treatment and prevention".)
Severe carditis — Patients with severe carditis (HF that is generally caused by severe regurgitation with or without variable degrees of atrioventricular [AV] block) should be treated with standard medical therapy for these conditions. (See "Heart failure in children: Management".)
The cause of HF in ARF is generally severe mitral regurgitation (MR; eg, associated with a ruptured chord). The patient should be stabilized and treated with optimal medical management and referred to a Heart Valve Team to assess the need for optimum timing and type of surgery [20]. Valve surgery is rarely necessary during an acute episode of ARF, usually only in patients with chordae tendineae rupture (flail segment) with acute severe MR, for whom surgery can be lifesaving. If the patient can be stabilized medically, surgery should be deferred since surgical outcomes are generally better if valve surgery is performed when carditis is quiescent [21]. (See "Acute mitral regurgitation in adults" and 'Management of mitral regurgitation' below.)
Third-degree AV block in patients with rheumatic carditis is typically transient, but persistent third-degree AV block requiring permanent pacemaker implantation has been reported [22,23]. (See "Bradycardia in children", section on 'Congenital heart disease' and "Third-degree (complete) atrioventricular block".)
As noted above, we suggest not treating patients with RHD with antiinflammatory agents given the lack of evidence of benefit. However, some experts use glucocorticoids (eg, prednisone 1 to 2 mg/kg/day, maximum daily dose 80 mg) in patients with severe carditis with acute cardiac failure, particularly in the presence of persisting high inflammatory markers or in patients facing imminent surgery, despite the lack of evidence supporting such therapy. However, the side effects of glucocorticoids include gastrointestinal bleeding and fluid retention, both of which can worsen HF. If glucocorticoids are used, aspirin or nonsteroidal antiinflammatory agents are stopped but are restarted once glucocorticoid treatment is discontinued. Glucocorticoids are stopped when HF is controlled and inflammatory markers have improved. If a course longer than one week is needed, then it is prudent to taper the dose by approximately 25 percent per week.
A case series of 120 patients with severe rheumatic carditis suggested a role for pulsed steroids in select cases [24], but the evidence remains insufficient to support routine use of glucocorticoids.
The role of antiinflammatory agents in treatment of ARF-associated arthritis is discussed separately. (See "Acute rheumatic fever: Treatment and prevention", section on 'Arthritis management'.)
Risk of progression to RHD — While RHD occurs only as a sequel of ARF, most patients with RHD lack a history of past ARF, suggesting that the diagnosis of ARF is frequently missed. (See "Acute rheumatic fever: Epidemiology and pathogenesis" and "Acute rheumatic fever: Clinical manifestations and diagnosis".)
The pathway from ARF to RHD is complex and not well defined. Risk factors for progression include the presence of carditis during the initial ARF episode or any subsequent ARF recurrences [13]. Of the 16.2 percent of patients with severe RHD at diagnosis, derived from modelling the Australia registry data, 50 percent had proceeded to valve surgery by two years, and 10 percent were dead within six years. Although patients with mild RHD at diagnosis were the most stable, with 64 percent continuing to have mild RHD after 10 years, 11.4 percent progressed to severe RHD, and half of these required surgery [25].
MANAGEMENT OF RHEUMATIC HEART DISEASE
General management of rheumatic heart disease — Patients with rheumatic valve disease should undergo periodic clinical and echocardiographic evaluation with frequency based upon the severity of disease, as described for individual valve lesions below. Standard indications for valve intervention apply. The choice of procedure (eg, mitral valve [MV] repair or replacement) is based upon patient characteristics and available treatment options.
As noted above, secondary prevention of rheumatic fever is recommended in patients with history of acute rheumatic fever and/or RHD. (See 'Secondary prevention' above.)
Annual influenza vaccination and meticulous dental hygiene with annual check-ups are recommended for patients with RHD [6].
Prophylaxis against infective endocarditis (IE) is recommended for patients with prosthetic heart valves or a previous history of IE who undergo invasive dental procedures. Endocarditis prophylaxis guidelines are discussed in detail separately. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)
Pregnancy — Pregnancy presents a unique set of problems for women with valve disease, especially those with prosthetic heart valves. These issues are discussed in detail separately. (See "Pregnancy and valve disease" and "Pregnancy in women with mitral stenosis" and "Management of antithrombotic therapy for a prosthetic heart valve during pregnancy".)
Management of mitral regurgitation — Mild rheumatic mitral regurgitation (MR) is usually well tolerated, and the patient often remains asymptomatic for years, so these patients can be seen annually. Patients with moderate MR should be seen and undergo echocardiography yearly or sooner if symptoms occur. Patients with severe MR should be seen at least every 6 to 12 months to monitor for the development of symptoms by clinical examination and left ventricular (LV) systolic dysfunction by echocardiography.
Symptoms and/or signs of LV systolic dysfunction (defined by an LV ejection fraction [LVEF] <60 percent and/or an end-systolic dimension ≥4 cm) are indications for surgery. Symptomatic status, ventricular functional status, and the likelihood of valve repair versus replacement all affect the timing of valve surgery, as discussed in detail separately. (See "Management of chronic primary mitral regurgitation" and "Indications for intervention for chronic severe primary mitral regurgitation".)
For patients with rheumatic MR with an indication for MV surgery, valve repair, if feasible, is preferred over valve replacement since repair avoids the risk of complications of prosthetic valves, such as thromboembolism, bleeding, and the limited durability of bioprosthetic valves in younger patients [1,26-31]. Avoidance of a need for anticoagulation in patients in sinus rhythm is particularly important for patients with significant barriers to compliance and limited access to monitoring as well as for patients undergoing valve surgery prior to possible pregnancy, given the risk of maternal and fetal complications including fetal adverse effects of vitamin K antagonist (VKA; eg, warfarin) therapy. (See "Management of chronic primary mitral regurgitation" and "Management of chronic primary mitral regurgitation", section on 'Surgical mitral valve repair versus replacement'.)
Rheumatic disease causes progressive fibrotic thickening of the mitral leaflets and scarring of chordal structures, which limits the durability of MV repair, but repair produces reasonable outcomes in selected patients with rheumatic MR. In young populations with rheumatic MR, the possibility of repair may be high, but the long-term durability of repair is lower than for repair of degenerative mitral disease because of progressive rheumatic fibrosis [32-34]. Data on comparative outcomes for MV repair versus replacement are limited to observational series which suggest that outcomes following repair are at least as good as those following replacement, as illustrated by the following studies:
A systematic review included 16 observational studies in which 2467 patients underwent surgical MV repair and 6192 underwent MV replacement (mechanical or bioprosthetic) from 1976 to 2017 [35].
●The MV repair group experienced lower early and long-term mortality rates and fewer valve-related events and major adverse events compared with those undergoing MV replacement, but required more reoperations.
●In patients undergoing concomitant aortic valve replacement surgery, MV repair was associated with increased risk of mitral reoperation and early and long-term mortality compared with MV replacement.
In individual studies, mortality rates with surgical MV repair were generally similar to or lower than those with MV replacement, but reoperation was more common after MV repair:
●A study using the Australian Cardiac Surgery Database analyzed outcomes of 119 surgical MV repairs and 1078 MV replacements for RHD [36]. Mortality rates were similar with MV repair and replacement, but reoperation was more frequent after MV repair. In survival analysis to five years, outcomes for RHD MV repair and replacement were similar (adjusted hazard ratio [HR] 0.7, 95% CI 0.4-1.6).
●A study using Taiwan's National Health Insurance Research Database identified 467 propensity-score matched pairs of patients with RHD who underwent MV repair or MV replacement [37]. In-hospital mortality rates were similar, and mortality rates at a mean follow-up of six years were also similar (33.4 versus 32.5 percent; HR 1.01, 95% CI 0.81-1.25). However, higher risk of MV reoperation was observed in the MV repair group (subdistribution HR 4.32, 95% CI 2.02-9.23), and prior percutaneous mitral balloon commissurotomy was identified as a risk factor of MV reoperation in the repair group [37].
●A series from South Africa and Portugal included 241 patients with RHD undergoing MV repair (most for predominant MR) from 1980 to 1984, 386 undergoing mechanical MV replacement from 1980 to 1984, and 289 undergoing bioprosthetic MV replacement from 1976 to 1980 [38]. Although actuarial survival at five years was higher for MV repair than for mechanical or bioprosthetic valve replacement (90 versus 76 and 62 percent, respectively), reoperation was more frequent after mitral repair (4.3 percent per year) than after mechanical replacement (1.5 percent per year).
●A series from South Korea compared 122 patients with RHD undergoing MV repair with 418 patients with RHD undergoing valve replacement from 1997 to 2007 [39]. There were similar 10-year survival rates in the repair and replacement groups (86 and 85 percent, respectively). Similar 10-year freedom from reoperation rates were observed (97 and 94 percent, respectively). The repair group was younger, more likely to have predominant MR, and less likely to have mitral stenosis (MS), atrial fibrillation (AF), significant tricuspid regurgitation (TR), or pulmonary hypertension.
●An study reported long-term outcomes (mean follow-up 5.6 years, range 0 to 22.3 years) of an MV repair approach in 419 children in Malaysia [40]. Survival of patients who underwent MV repair was 93.9 percent at both 10 and 20 years, which was higher than for those undergoing mechanical MV replacement (80.1 and 66.8 percent, respectively) or bioprosthetic valve replacement (59 percent at 10 years). Freedom from thrombotic, embolic, and hemorrhagic events at 10 years was 98.2 percent for patients with MV repair compared with 88.5 percent in patients with mechanical valve replacement and 100 percent for patients with bioprosthetic replacement.
Management of mitral stenosis — Clinical manifestations, diagnosis (including the key role of transthoracic echocardiography), staging, monitoring, and management of rheumatic MS are discussed separately. (See "Rheumatic mitral stenosis: Clinical manifestations and diagnosis" and "Rheumatic mitral stenosis: Overview of management".)
Since MS is a mechanical disorder, the patient with severe MS should be referred for evaluation for percutaneous valvotomy or surgery as soon as symptoms develop. Patients with severe MS who present with pulmonary edema without another precipitating cause should be stabilized medically and referred immediately for evaluation for percutaneous valvotomy or surgery. For patients with moderate MS but exertional symptoms, Doppler hemodynamic exercise echocardiography can be useful in identifying those who would benefit from valvotomy or surgery. Since evidence suggests that the presence of pulmonary hypertension (PH) substantially increases operative risk, intervention should be contemplated in patients who develop asymptomatic PH (pulmonary artery systolic pressure >50 mmHg at rest). (See "Percutaneous mitral balloon commissurotomy in adults" and "Surgical and investigational approaches to management of mitral stenosis" and "Rheumatic mitral stenosis: Overview of management", section on 'Indications for intervention'.)
Symptoms may be precipitated by any intercurrent illness resulting in a tachycardia, including the following factors:
●Intercurrent infection
●Onset of AF
●Pregnancy
●Thyrotoxicosis
●Pulmonary embolism
●Anemia
It is important to rule out these factors, as successful treatment may relieve the symptoms of effort intolerance.
The late stages of uncorrected, severe MS may be complicated by the development of PH and by failure of the right side of the heart, with edema and ascites. TR commonly coexists and is more often secondary to right ventricular dilatation than to primary rheumatic involvement. (See 'Management of tricuspid valve disease' below.)
Atrial fibrillation — Patients with MS are particularly susceptible to the development of AF. Although episodic and paroxysmal at first, AF tends to become persistent over time. With the onset of AF, there is as much as a 30 percent reduction in cardiac output, largely due to rapid ventricular rates with shortened diastolic filling times. These changes may cause an abrupt increase in left atrial pressure, and prompt therapy is often required. In addition, there is a substantial risk of thromboembolism. Management of these issues is discussed in detail separately. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation" and "Rheumatic mitral stenosis: Overview of management", section on 'Management of atrial fibrillation'.)
Thromboembolism prevention — Patients with MS at highest risk for embolic events are those with paroxysmal or persistent AF, left atrial thrombus, or a history of prior embolus. Treatment to reduce the risk of thromboembolism is discussed separately. In up to 20 percent of patients with RHD, thromboembolism may be the first clinical manifestation. MS should therefore be considered in the differential for thromboembolic disease, particularly when other cardiovascular risk factors are absent. (See "Rheumatic mitral stenosis: Overview of management", section on 'Prevention of thromboembolism'.)
Management of mixed mitral disease — The natural history of concomitant MS and MR is worse than for isolated regurgitation. Only two-thirds of untreated patients with mixed mitral disease are expected to be alive at five years and only one-third at 10 years [7]. An echocardiographic study found that, in patients with mixed MV disease, transmitral mean pressure gradient ≥6 mmHg is associated with adverse clinical outcomes (mortality, MV replacement, HF admission, and stroke) independent of the presence of symptoms (HR 3.69, 95% CI 1.31–10.44) [41].
Prosthetic valve replacement is required when symptoms are present and there is mixed moderate stenosis and moderate regurgitation, as the combined moderate lesions have effects on outcomes like severe valve disease. Decision-making for patients with mixed valvular heart disease, particularly RHD, is complex and requires context-specific decision-making by the heart valve team.
Management of aortic regurgitation — Since the rate of progression to symptoms and/or systolic dysfunction due to chronic aortic regurgitation (AR) is slow, these patients should be expectantly followed. Recommended frequency of monitoring varies with severity of AR and LV chamber dimensions. (See "Natural history and management of chronic aortic regurgitation in adults", section on 'General approach'.)
Patients with mild to moderate AR have excellent survival rates and require no intervention. Surgery is indicated in patients with severe AR at the onset of symptoms or decreasing LV function (ie, LVEF ≤50 percent) and/or increasing LV size (ie, LV end-diastolic dimension ≥75 mm, LV end-systolic dimension ≥55 mm, and/or indexed LV end-systolic dimension >25 mm/m2) assessed by echocardiography. Limited evidence suggests that aortic valve repair has good early and midterm results and is, therefore, a viable alternative to replacement with a bioprosthesis, especially for young patients who choose to avoid VKA therapy [42]. (See "Natural history and management of chronic aortic regurgitation in adults", section on 'Aortic valve surgery'.)
The role of vasodilator therapy in patients with AR is discussed separately. (See "Natural history and management of chronic aortic regurgitation in adults", section on 'Pharmacologic therapy'.)
Management of aortic stenosis — Medical management of asymptomatic aortic stenosis includes serial evaluation, treatment of associated cardiovascular disease, and limitation of physical activity, as appropriate. No medical therapies have been proven to delay progression of leaflet disease. Patients should receive education about the expected disease course and symptoms that should be reported, such as dyspnea, reduced exercise tolerance, exertional chest pain, lightheadedness, and syncope. Serial evaluation is recommended to monitor for development of symptoms and increasing severity of aortic stenosis by clinical examination and echocardiography. These issues are discussed in detail separately. (See "Medical management of asymptomatic aortic stenosis in adults", section on 'Serial evaluation' and "Natural history, epidemiology, and prognosis of aortic stenosis".)
Symptomatic severe aortic stenosis is an indication for aortic valve replacement. Surgery remains the mainstay of therapy in such patients, as most patients have concomitant MV disease requiring surgery. Surgery for symptomatic aortic stenosis is associated with marked reduction in symptoms and mortality. For patients with symptomatic rheumatic aortic stenosis who do not have a concomitant indication for mitral (or other) valve surgery, transcatheter aortic valve implantation is an option, although experience is limited [43-45]. With certain exceptions, valve replacement should not be performed for isolated, severe aortic stenosis in asymptomatic patients, as discussed separately. (See "Indications for valve replacement for high gradient aortic stenosis in adults" and "Choice of intervention for severe calcific aortic stenosis".)
Palliative care is recommended for patients with severe symptomatic aortic stenosis who are not candidates for valve replacement. (See "Medical management of symptomatic aortic stenosis".)
Management of mixed aortic valve disease — Combined AR and stenosis produces a variable clinical picture dependent on whether regurgitation or stenosis is the dominant lesion or whether both lesions are equally significant. Therapy is dictated by close supervision (ie, visits every 6 to 12 months) by clinical examination for development of symptoms and echocardiography for progression of valve disease and evidence of LV dysfunction. Aortic valve replacement is indicated if symptoms develop and/or LV function deteriorates.
Management of tricuspid valve disease — Although data are limited, severe tricuspid stenosis may be amenable to percutaneous balloon valvotomy. Surgical correction of the stenotic lesion is indicated in patients whose valve is not suitable for balloon techniques. (See "Tricuspid stenosis".)
Management of TR, including indications for surgery, is discussed in detail separately (see "Management and prognosis of tricuspid regurgitation", section on 'Approach to management'). TR often accompanies rheumatic MV disease and often progresses after MV surgery. For patients with TR and MR undergoing surgery for correction of MV disease, concurrent tricuspid valve annuloplasty is indicated if TR is severe, or if moderate TR is accompanied by a dilated tricuspid annulus. The rationale and indications for concurrent tricuspid valvuloplasty at the time of MV surgery are discussed separately. (See "Indications for intervention for chronic severe primary mitral regurgitation".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiac valve disease" and "Society guideline links: Acute rheumatic fever and rheumatic heart disease".)
SUMMARY AND RECOMMENDATIONS
●The mainstays of management of carditis (which is chiefly manifest as valvulitis) in acute rheumatic fever (ARF) are early diagnosis and assessment of severity using echocardiography, management of heart failure (HF) and other complications when present, and commencement of secondary prophylaxis. (See 'General management of rheumatic heart disease' above.)
●The duration of prophylactic antibiotic administration for secondary prevention of ARF is adjusted depending upon the severity of rheumatic heart disease (RHD) as outlined in the table (table 2). (See 'Secondary prevention' above and "Acute rheumatic fever: Treatment and prevention", section on 'Secondary prevention (antibiotic prophylaxis)'.)
●We suggest not treating carditis with glucocorticoids or intravenous immune globulin (Grade 2C). The available limited-quality evidence has not demonstrated an improvement in cardiac outcomes with these agents. However, some experts use glucocorticoids in patients with severe carditis with acute cardiac failure. (See 'General management of carditis' above and 'Severe carditis' above.)
●The cause of HF in ARF is generally severe mitral regurgitation (MR; eg, associated with a ruptured chord). The patient should be stabilized medically and referred to a Heart Valve Team to assess the need for optimum timing and type of surgery. (See 'Severe carditis' above and 'Management of mitral regurgitation' above and "Acute mitral regurgitation in adults", section on 'Treatment'.)
●Patients with rheumatic valve disease should undergo periodic clinical and echocardiographic evaluation with frequency based upon the severity of disease, as described for individual valve lesions above. Standard indications for valve intervention apply with choice of procedure (eg, mitral valve [MV] repair or replacement) based upon patient characteristics and available treatment options. (See 'General management of rheumatic heart disease' above.)
●For patients with rheumatic MR with an indication for MV surgery, valve repair, if feasible, is preferred over valve replacement since repair avoids the need for long-term anticoagulation associated with mechanical valves and the long-term risk of deterioration of a bioprosthesis. (See 'Management of mitral regurgitation' above and "Management of chronic primary mitral regurgitation", section on 'Surgical mitral valve repair versus replacement'.)
●Since mitral stenosis (MS) is a mechanical disorder, the patient with progressive or severe MS should be referred for evaluation for percutaneous valvotomy or surgery as soon as symptoms develop. (See 'Management of mitral stenosis' above and "Rheumatic mitral stenosis: Overview of management".)
●The natural history of concomitant MS and MR is worse than for isolated regurgitation. Prosthetic valve replacement is required when symptoms are present and there is mixed moderate stenosis and moderate regurgitation, even though either lesion in isolation might not be considered "severe." (See 'Management of mixed mitral disease' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Bongani Mayosi, MBChB, PhD, FCP(SA) (deceased), who contributed to an earlier version of this topic review.