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Clinical manifestations and diagnosis of rheumatic heart disease

Clinical manifestations and diagnosis of rheumatic heart disease

INTRODUCTION — Rheumatic heart disease (RHD) remains a major cause of cardiovascular disease in resource-limited nations, although the prevalence of RHD has declined sharply in industrialized countries during the last century [1].

This topic will review the clinical manifestations and diagnosis of RHD. The management of RHD and the pathogenesis, epidemiology, diagnosis, treatment, and prevention of acute rheumatic fever are discussed separately. (See "Management and prevention 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".)

EPIDEMIOLOGY — RHD is by far the most important form of acquired heart disease in children and young adults living in resource-limited countries (which are inhabited by 80 percent of the world’s population); RHD accounts for approximately 15 percent of all patients with heart failure (HF) in endemic countries [2,3]. The epidemiology of acute rheumatic fever is discussed separately. (See "Acute rheumatic fever: Epidemiology and pathogenesis", section on 'Epidemiology'.)

The prevalence of RHD has been rising steadily since 1990, reaching 40.5 million (95 percent uncertainty interval [UI] 32.0 to 50.0 million) currently affected in 2019 [4]. The global mortality burden of RHD decreased by nearly 50 percent from 1990 to 2015 [5], and in an estimate from the Global Burden of Disease study, disability-adjusted life-years (DALY) due to RHD, deaths, and years of life lost have all steadily decreased (10.7 million [95 percent UI 9.2 to 12.1 million], 305,000 [95 percent UI 259,000 to 340,000], and 8.7 million [95 percent UI 7.4 to 9.8 million] respectively in 2019), while years lived with disability have increased to 2.0 million (95 percent UI 1.2 to 3.0 million). In addition, RHD continues to show substantial global heterogeneity. The lowest age-standardized DALY rates are seen in the highest income regions (eg, high-income Asia-Pacific, North America, and Western Europe all <25 per 100,000), reflecting the combined benefit of lower prevalence and higher access to diagnosis and treatment, including cardiac surgery; however, high numbers of age-standardized DALYs occur in Oceania (627 per 100,000), which, along with central sub-Saharan Africa, are two regions that have not experienced a significant decrease in DALYs since 1990. Age-standardized DALY rates in sub-Saharan Africa also remain among the highest in the world (>100 per 100,000 in all four subregions) [4].

RHD is a disease affecting predominantly those living in poverty with inadequate access to health care and unchecked exposure to group A streptococcus [6]. The impact of socioeconomic status is illustrated by a study from Kinshasa where the prevalence based on clinical examination was 22.2 per 1000 among children who lived in a dense poor urban environment but only 4 per 1000 among children attending the city schools [7]. A later report outlined the increased risk of RHD in association with overcrowding and unemployment as well as overcrowding and distance from the nearest health center [8]. The importance of socioeconomic factors is further underscored by the virtual disappearance of RHD in industrialized countries since the mid-20th century, which started well before the introduction of penicillin. By contrast, RHD is still endemic in Africa, Asia, South America, and resource-limited communities of Australasia [5,9-13].

Echocardiographic studies have revealed high prevalence rates in resource-limited countries. A robust systematic review and meta-analysis calculated the prevalence of clinically silent RHD (21.1 per 1000 people, 95% CI 14.1-31.4) to be approximately seven to eight times higher than that of clinically manifest disease (2.7 per 1000 people, 95% CI 1.6-4.4), with prevalence increasing with age, from 4.7 per 1000 children (95% CI 0.0-11.2) 5 years of age to 21.0 per 1000 children (95% CI 6.8-35.1) 16 years of age; prevalence is positively associated with increasing Gini coefficient for social inequality [14]. Based on these data, it is estimated that the RHD burden could be as much as double that in the Global Burden of Disease (GBD) study [5]. Based upon the premise that children in sub-Saharan Africa represent 6 to 7 percent of total global RHD burden [5], there may be an estimated 50 to 80 million persons currently affected with RHD worldwide [15].

RHD causes symptomatic valvular heart disease in children who are younger than five years of age in Africa and Asia, and the burden of disease rises with age. In South Africa, the incidence of HF due to RHD increases from 30 per 100,000 per year in the 14- to 19-year age group to over 53 per 100,000 per year in older adults, resulting in an average incidence of 23 per 100,000 per year [16]. These rates contrast with the reported incidence of rheumatic fever in resource-abundant countries of <1/100,000 of the population per year [17].

Longitudinal registries have shown that in low- and middle-income countries, patients present young with complications at diagnosis, advanced disease, and suffer significant morbidity and mortality. The multinational REMEDY study demonstrated clear gaps in evidence-based interventions in a young population (median age of 28) with a mortality of 16.9 percent within the 24-month observation period [18,19].

Of note, the echocardiographic criteria selected for diagnosis of RHD affect the rate of detection of disease. Echocardiographic criteria for subclinical disease have evolved from World Health Organization criteria [1] to definitions of definite and probable RHD identified by an expert consensus statement endorsed by the World Heart Federation, as described below [20]. While clinical disease is not defined by the World Heart Federation guidelines, these guidelines have impacted the Jones criteria for diagnosis of acute rheumatic fever with echocardiographic proven carditis replacing cardiac auscultation in the 2015 revision [21]. (See 'Diagnosis of rheumatic heart disease' below.)

CLINICAL MANIFESTATIONS — Rheumatic carditis includes a spectrum of lesions ranging from pericarditis, myocarditis, and valvulitis during acute rheumatic fever (ARF); there is a transition from rheumatic carditis to RHD with chronic valvular lesions that evolve over years following one or more episodes of ARF (algorithm 1 and figure 1). RHD is defined as permanent heart valve damage subsequent to ARF.

Rheumatic carditis — Typically, the clinical features of ARF occur two to three weeks following a streptococcal throat infection, and the most common clinical manifestations are rheumatic carditis (30 to 80 percent of cases) [21,22] and arthritis (35 to 66 percent) [21,22]. There is increasing evidence that in some countries, skin infections have played an important pathogenetic role [23].

ARF causes pancarditis, affecting the pericardium (pericarditis), epicardium, myocardium (myocarditis, sometimes manifest as conduction system disease), and endocardium (valvulitis). Since valvulitis is generally a prominent manifestation of rheumatic carditis, a diagnosis of rheumatic carditis should be reevaluated if pericarditis, myocarditis, or conduction abnormality occurs in the absence of valvulitis.

Noncardiac clinical manifestations of ARF are discussed separately. (See "Acute rheumatic fever: Clinical manifestations and diagnosis".)

The predominant manifestation of rheumatic carditis is endocardial involvement presenting clinically as valvulitis, particularly affecting the mitral and aortic valves [1]. The clinical correlate of valvulitis is pathologic valvular regurgitation, which may be detected clinically (as regurgitant murmurs) or only on echocardiography. Mitral regurgitation (MR) may be detected as an apical holosystolic murmur and may or may not be accompanied by an apical mid-diastolic murmur (Carey-Coombs murmur) and/or aortic regurgitation (AR; which may be detected as a basal early diastolic murmur). (See "Auscultation of cardiac murmurs in adults", section on 'Carey-Coombs murmur'.)

Approximately 10 percent of patients with ARF develop severe acute valvulitis with mitral and/or aortic insufficiency after the first episode of ARF, with consequent symptoms including dyspnea and exercise intolerance. A proportion of these will need medical management and early intervention [24]. Rheumatic carditis detected only by echocardiography (as valve disease with valvular regurgitation) is termed subclinical carditis, which may constitute up to 53 percent of rheumatic carditis cases [25].

MR is the most common early valvular manifestation and may be accompanied by AR and/or uncommonly by tricuspid regurgitation (TR); isolated AR is less common [26,27]. The mechanism of MR during ARF has been postulated to relate to a combination of annulitis with annular dilatation, chorditis with chordal elongation, and valvulitis resulting in typically anterior mitral leaflet prolapse and pathologic MR [28]. Chordal rupture is a rare complication of rheumatic carditis, which in some cases may require emergency mitral valve (MV) repair. (See "Acute mitral regurgitation in adults".)

Pericarditis occurs in approximately 15 percent of cases of ARF and may present with precordial chest pain and a pericardial friction rub [1]. The pericarditis may be transient and generally resolves without sequelae. Cardiac tamponade has been reported only rarely in this setting [29]. (See "Acute pericarditis: Clinical presentation and diagnosis".)

Heart failure (HF) and left ventricular (LV) dilation in patients with ARF are caused chiefly by severe valve disease (mainly MR with or without AR) [30,31]. Although myocarditis is common in autopsy cases, the main cause of LV dilation and HF appears to be severe MR with or without AR, as suggested by prompt reduction in LV dimensions and preserved systolic function following valve surgery [30].

The electrocardiogram may demonstrate any degree of atrioventricular block, including third-degree block. Chest radiography may demonstrate cardiomegaly. (See 'Diagnosis of rheumatic carditis' below.)

Transition from acute to chronic disease — Progressive valvular disease commonly develops in the years following one or more episodes of ARF, as illustrated by the following examples:

A prospective study of children with ARF followed for 2 to 15 years during the modern era in Brazil found that 72 percent of the 258 subjects developed chronic valvular disease, and 16 percent progressed to severe aortic and/or mitral disease [32].

Frequent development of chronic valvular disease was also observed in the largest prospective study of the natural history of ARF in the pre-antibiotic era (also prior to the development of echocardiography) [33]. Twenty-year follow-up by clinical examination of this North American series of 1000 children and adolescents yielded the following observations:

Sixty-five percent of patients had clinical evidence of valvular heart disease after recovery from the initial episode of rheumatic fever. By the end of 20 years of follow-up, clinical signs of rheumatic valvular disease had disappeared in 17 percent of these patients.

The remaining 35 percent of patients recovered from their initial attack without detectable valvular heart disease. However, by the end of 20 years of follow-up, 44 percent of these patients had overt signs of valvular heart disease. Pure mitral stenosis (MS) developed in 12 percent of patients.

In this pre-antibiotic series, the mortality rate following ARF was 1.5 percent per year, with recurrent rheumatic fever and HF together accounting for 80 percent of fatalities and bacterial endocarditis for an additional 10 percent.

Chronic valve disease — While chronic 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, with the initial or recurrent insults being subclinical or not detected [34]. RHD generally presents as valve disease, which may or may not be detected by a murmur. Some cases of RHD are detected as part of research screening programs. (See 'Screening in endemic settings' below.)

The frequency of symptoms and signs of HF (eg, dyspnea and evidence of pulmonary edema) and of embolic events (eg, stroke) among patients with RHD varies depending upon the stage of valve disease at diagnosis. Contemporary data suggest that in endemic areas presentation with advanced disease is common, and thus complications such as HF (33 percent), atrial fibrillation (22 percent), pulmonary hypertension (29 percent), and less commonly cardio-embolic stroke (7 percent) are detected [18]. Patients with symptomatic chronic RHD face high rates of mortality (16.9 percent in two years) and morbidity [19]. Morbidity relates to the development of complications such as new-onset HF, atrial fibrillation, stroke, recurrent carditis, and infective endocarditis and is exacerbated by limited resource allocation to operate on such patients.

The MV is involved in nearly all cases of RHD, including those with other affected valves. The aortic valve is involved in approximately 20 to 30 percent of cases. The tricuspid valve is commonly affected, but tricuspid valve disease is frequently subclinical until surgery is required. Pulmonic valve involvement is rare.

Disease course and relationship to age — The incidence and pattern of MV pathology in RHD varies according to age (algorithm 1) [16]. In the published literature of the current era, clinically detected RHD is most diagnosed in individuals aged 20 to 50 years with nearly two-thirds of cases occurring in females. In endemic areas, the disease may progress more rapidly with children presenting with severe valvular lesions, whereas in resource-abundant countries, the progression of disease is more indolent and manifests at older ages (above 50 years) [6].

The multicenter REMEDY study provided insight into contemporary patterns and presentations of RHD, which differs in comparison with disease presentation in prior decades, such as the pre-antibiotic era during which isolated lesions were most common [18]. In the current era, isolated MR is the predominant lesion encountered in those under 20 years of age, MS develops from the third decade, and multivalvular disease (varying combinations of stenotic or regurgitant lesions involving the mitral and aortic valves) is the predominant abnormality in older adults [18]. The clinical presentation, hemodynamic consequences, and complications of these mixed valvular and multivalvular lesions require insightful clinical, echocardiographic, and occasionally invasive assessment.

Isolated MS is the most encountered single valve lesion after the age of 30. Rheumatic aortic valve stenosis generally occurs in patients with concomitant or prior evidence of AR [35]. Rheumatic aortic stenosis (AS) generally develops over a period of decades, and pure rheumatic AS is rare under the age of 30. Concomitant bicuspid aortic valve has been suspected in some cases of early AS [35], but early AS can occur with a trileaflet valve [36].

In the above cited pre-antibiotic era series, a characteristic blowing diastolic murmur of AR was observed in 19 percent of children with a first episode of rheumatic fever, and subsequently developed in a similar proportion of untreated patients followed over time, such that a total of 38 percent developed AR over the course of 20 years [33]. Isolated AR was observed in only 3 percent of cases of rheumatic valve disease, with the remainder having coexistent MV disease.

Contemporary data on disease course in patients with RHD illustrate the risk of progression. A registry study of 591 Aboriginal Australians aged 5 to 24 years diagnosed with RHD from 1999 to 2012 evaluated disease course and outcomes [37]. Among the 96 patients with severe RHD, 50 percent underwent valve surgery by two years, and 10 percent were dead within six years. Among the patients with moderate RHD, at 10 years, one-third had progressed to severe, one-third stayed the same, and one-third regressed to mild. Among patients with mild RHD, 64 percent remained mild after 10 years, but 11.4 percent progressed to severe RHD.

Disease course for specific valve lesions

Mitral stenosis — The natural history of MS varies across geographic areas [1]. In North America, for example, it is most commonly a slowly progressive disease, with a latency period of 20 to 40 years between the initial infection and the onset of clinical symptoms. In resource-limited countries, on the other hand, MS progresses much more rapidly and may lead to symptoms in patients who are less than five years of age [38].

Survival is greater than 80 percent at 10 years for patients who are asymptomatic or minimally symptomatic (New York Heart Association [NYHA] functional class I or II) (table 1) at time of diagnosis; 60 percent of such patients may not experience any progression of symptoms over this timeframe [1]. Once limiting symptoms (NYHA functional class III or IV) develop, however, survival without intervention predictably worsens and has been estimated at 0 to 15 percent over the ensuing 10 years. Mean survival time falls to less than three years if severe pulmonary hypertension has intervened. (See "Pathophysiology and natural history of mitral stenosis".)

The clinical manifestations of MS (which is caused chiefly by RHD) are discussed further separately. Of note, among the acquired heart valve lesions, MS is associated with the highest risk of systemic thromboembolism. The risk increases markedly following the onset of atrial fibrillation and is considerably higher for patients with MS compared with those with isolated MR. Patients who suffer a first embolus are at increased risk for repeat embolization, particularly over the ensuing six months. (See "Rheumatic mitral stenosis: Clinical manifestations and diagnosis".)

Mitral regurgitation — For patients with chronic MR, there is frequently a prolonged asymptomatic phase as the volume load of chronic MR may be well-tolerated for several years. Indeed, the low total impedance associated with MR may obscure recognition of LV contractile dysfunction until relatively late in the natural history [1]. (See "Pathophysiology and natural history of chronic mitral regurgitation".)

The clinical manifestations of chronic MR are discussed further separately. (See "Clinical manifestations and diagnosis of chronic mitral regurgitation".)

Mixed mitral stenosis/regurgitation — Many patients with rheumatic MV disease have important stenotic and regurgitant components owing to commissural fusion and the "fish mouth" deformity imparted by the pathologic process. Pathologically, the valves are more deformed than with pure regurgitant or pure stenotic lesions. One lesion may predominate, or the components may be more closely balanced, creating a hybrid natural history [1].

Aortic regurgitation — Patients with chronic, severe AR usually have a long, yet variable, compensated phase, characterized by an increase in LV end-diastolic volume and a combination of both eccentric and concentric hypertrophy associated with increased chamber compliance. Asymptomatic patients with LV dysfunction, however, develop symptoms (angina, HF) at a rate of greater than 25 percent per year, and symptomatic patients with severe AR have an expected mortality that exceeds 10 percent per year [1]. (See "Natural history and management of chronic aortic regurgitation in adults".)

The clinical manifestations of chronic AR are discussed further separately. (See "Clinical manifestations and diagnosis of chronic aortic regurgitation in adults".)

Aortic stenosis — Isolated rheumatic AS is very rarely seen. AS generally progresses gradually over years with a prolonged asymptomatic phase, although the clinical course is variable. Mortality dramatically increases after the development of symptoms. Average survival without valve replacement after the onset of angina, syncope, or HF is only two to three years. (See "Indications for valve replacement for high gradient aortic stenosis in adults" and "Natural history, epidemiology, and prognosis of aortic stenosis".)

The clinical manifestations of AS are discussed further separately. (See "Clinical manifestations and diagnosis of aortic stenosis in adults".)

Tricuspid valve disease — RHD can cause organic TR and/or tricuspid stenosis. Rheumatic tricuspid valve disease is almost invariably associated with MV disease [39].

RHD is a cause of primary TR with shortened and thickened tricuspid leaflets that are imperfectly sealed during ventricular systole. Clinical manifestations are discussed separately. (See "Etiology, clinical features, and evaluation of tricuspid regurgitation".)

In addition, RHD is often associated with secondary (functional) TR occurring with right HF because dilatation of the right ventricle stretches the tricuspid valve ring.

Tricuspid stenosis without regurgitation is a relatively uncommon condition, and since the diagnosis is difficult to make on physical examination, it is often missed [40]. The normal tricuspid valve area is greater than 7.0 cm2, and reduction of this orifice size to less than 1.5 cm2 results in hemodynamically significant stenosis. Clinical manifestations are discussed separately. (See "Tricuspid stenosis".)

DIAGNOSIS OF RHEUMATIC CARDITIS

When to suspect rheumatic carditis — Rheumatic carditis should be suspected in all patients with suspected acute rheumatic fever (ARF). Rheumatic carditis is one of the five major manifestations of ARF but the only one associated with mortality and permanent damage. Carditis is a major diagnostic criterion in both low- and moderate/high-risk populations. The diagnosis of ARF requires evidence of preceding streptococcal infection and other criteria based on the 2015 revised Jones criteria, as discussed separately [21]. (See "Acute rheumatic fever: Clinical manifestations and diagnosis", section on 'Diagnostic criteria'.)

In addition, rheumatic carditis can develop as an indolent carditis (with limited or no noncardiac manifestations of ARF) in a patient presenting months after acute group A streptococcal infection. Thus, rheumatic carditis should also be suspected in patients without history of ARF with new or worsened mitral regurgitation (MR).

Diagnosis of rheumatic carditis — Patients with suspected or confirmed ARF or a new murmur must undergo echocardiography to determine if valve abnormalities are present. As noted in the 2015 revised Jones criteria, the diagnosis of rheumatic carditis may or may not be suspected clinically but in all cases must be confirmed with an echocardiogram showing both morphologic valvular involvement of mitral and/or aortic valves (except for very early cases with normal valve morphology) and Doppler evidence of pathologic valvular regurgitation (table 2) [21]. (See 'Morphologic criteria' below and 'Criteria for pathologic regurgitation' below.)

Morphologic criteria — The following are echocardiographic morphologic findings of rheumatic valvulitis [21]. However, very early on in the disease course, the aortic or mitral valve (MV) morphology may appear normal and may manifest with only pathologic regurgitation. (See "Approach to the infant or child with a cardiac murmur" and "Auscultation of cardiac murmurs in adults".)

MV changes (acute) – The following morphologic features are suggestive of MV involvement in ARF: annular dilatation, MV prolapse typical of rheumatic carditis involving the anterior (or less commonly posterior) mitral leaflet, beading and focal thickening of the leaflet (verrucous vegetations), elongated chordae, and chordal rupture (which may result in flail leaflet with severe MR) [21]. In ARF, MR may be caused by MV prolapse, which appears to be due to annular dilation, chordal elongation, or in severe cases, chordal rupture. MV prolapse in ARF involves predominantly the anterior leaflet with minimal leaflet redundancy [28,30].

In addition, there should be no features suggestive of chronic RHD such as leaflet thickening, chordal thickening and fusion, calcification, and restricted leaflet motion.

Aortic valve changes (acute or chronic) – The morphologic features of aortic valve involvement are less specific (irregular or focal leaflet thickening, coaptation defect, restricted leaflet motion, leaflet prolapse) and may share similar features to that of chronic RHD [20].

Criteria for pathologic regurgitation — The following are Doppler echocardiography criteria for pathologic regurgitation for acute rheumatic carditis (as well as for RHD) [20,21]. Regurgitant jet length is measured from the vena contracta to the last pixel of regurgitant color [20].

Pathologic MR (diagnosis requires all four criteria):

Seen in at least two views

Jet length ≥2 cm in at least one view

Peak velocity ≥3 m/s for one complete envelope

Pansystolic jet in at least one envelope

Pathologic aortic regurgitation (AR; diagnosis requires all four criteria):

Seen in at least two views

Jet length ≥1 cm in at least one view

Peak velocity ≥3 m/s in early diastole

Pandiastolic jet in at least one envelope

Other echocardiographic findings — Echocardiography also enables serial assessment of valve lesions, ventricular and atrial dilatation, and ventricular function. A pericardial effusion may be identified but is not diagnostic of rheumatic carditis in the absence of evidence of valve disease.

Aortic or mitral stenosis is unusual at presentation of rheumatic carditis; these are typically late manifestations of RHD due to scarring and calcification of damaged valves. (See 'Mitral stenosis' above and 'Aortic stenosis' above.)

Differential diagnosis of rheumatic carditis — In patients with suspected ARF, identification of MR and/or AR is not sufficient to diagnose rheumatic valvulitis. Echocardiography is helpful in distinguishing rheumatic carditis from other conditions:

Pathologic regurgitation should be distinguished from physiologic valve regurgitation (trace to mild MR or trace AR), which is common in normal individuals [21]. (See "Echocardiographic evaluation of the mitral valve".)

Functional MR may be observed with other febrile illnesses such as viral myocarditis. (See "Clinical manifestations and diagnosis of myocarditis in children" and "Clinical manifestations and diagnosis of myocarditis in adults".)

MV prolapse caused by ARF should be distinguished from MV prolapse due to degenerative myxomatous disease, which more commonly involves the posterior leaflet and is associated with prominent leaflet redundancy [21]. (See "Mitral valve prolapse: Clinical manifestations and diagnosis".)

These echocardiographic features are intended to aid in excluding physiologic regurgitation especially within the context of hyperdynamic states, congenital heart disease, functional MR secondary to cardiomyopathy/myocarditis, and MV prolapse, which may manifest clinically with murmurs of MR, AR, and tricuspid regurgitation. Hence, the absence of echocardiographic correlates of valvulitis implies that an alternate diagnosis to ARF should be explored. The findings of echocardiographic features of chronic RHD accompanied by a clinical scenario suggestive of ARF are suggestive of recurrent carditis.

DIAGNOSIS OF RHEUMATIC HEART DISEASE

When to suspect rheumatic heart disease — Chronic RHD should be suspected in patients with a history of acute rheumatic fever (ARF) and/or suspected pathologic cardiac murmur [21]. The index of suspicion for RHD is highest in patients from regions in which ARF/RHD is endemic.

It is particularly important to identify RHD in females who are pregnant, may conceive, or are making decisions regarding future pregnancies, as RHD poses a significant risk during pregnancy, particularly when the predominant hemodynamic valve lesion is stenotic, as pregnancy frequently precipitates worsening symptoms. This clinical setting requires precise hemodynamic diagnosis, early discussion of risks and their management, careful observation, and prompt treatment of complications should they arise. Mitral stenosis (MS) is the most encountered clinically significant RHD lesion in pregnant women. The diagnosis and management of RHD during pregnancy is discussed separately. (See "Pregnancy and valve disease" and "Pregnancy in women with mitral stenosis".)

Diagnosis of rheumatic heart disease — The diagnosis of RHD is generally confirmed by transthoracic echocardiography, which enables assessment of valve morphology and severity of valve dysfunction (regurgitation and/or stenosis). Echocardiography is also used to assess left and right ventricular size and function and may enable estimation of pulmonary artery systolic pressure. (See "Echocardiographic assessment of the right heart", section on 'Pulmonary artery pressure' and "Echocardiographic evaluation of the mitral valve" and "Echocardiographic evaluation of the aortic valve".)

We use the World Heart Federation criteria for the echocardiographic diagnosis of RHD in patients with or without history of ARF [20]. The morphologic features of RHD (for the mitral valve [MV]) differ from those for acute rheumatic carditis. By contrast, the criteria for pathologic regurgitation for RHD are the same as those for acute rheumatic carditis. (See 'Criteria for pathologic regurgitation' above.)

For patients with no history of ARF — We use the following criteria for patients with no prior history of ARF [20].

Definite RHD is diagnosed if one or more of the following criteria are present:

Pathologic mitral regurgitation (MR) and at least two morphologic MV features of RHD.

MS mean gradient ≥4 mmHg (congenital MV anomalies and nonrheumatic mitral annular calcification must be excluded).

Pathologic aortic regurgitation (AR) and at least two morphologic features of RHD of the MV. For individuals ≤20 years old, bicuspid aortic valve, dilated root, and hypertension must be excluded.

For individuals ≤20 years old, borderline disease of both the aortic valve and MV. (Combined AR and MR, particularly in high-prevalence regions and in the absence of congenital heart disease, is regarded as rheumatic.)

For individuals <35 years old, pathologic AR, and at least two morphologic features of RHD of the aortic valve. Bicuspid aortic valve, dilated aortic root, and hypertension must be excluded.

Borderline RHD only applies to individuals ≤20 years old and is present if one of the following criteria is present:

At least two morphologic features of RHD of the MV without pathologic MR or MS

Pathologic MR (see 'Criteria for pathologic regurgitation' above)

Pathologic AR (see 'Criteria for pathologic regurgitation' above)

For patients with history of ARF — For patients with history of ARF, we consider the diagnosis of RHD definite if there is a typical valvular abnormality (as defined by one or more morphologic World Heart Federation criteria of RHD (table 3) or evidence of World Heart Federation criteria for pathologic regurgitation). (See 'Criteria for pathologic regurgitation' above.)

Morphologic criteria for RHD — The following are morphologic features of RHD (further details are provided in the table) (table 3) [20]:

MV changes – The following morphologic features are suggestive of MV involvement in RHD: anterior MV leaflet thickening (age-specific), chordal thickening, restricted leaflet motion, excessive leaflet tip motion during systole.

Aortic valve changes (acute or chronic) – The morphologic features of aortic valve involvement are less specific (irregular or focal leaflet thickening, coaptation defect, restricted leaflet motion, leaflet prolapse) and may share similar features to that of acute rheumatic carditis.

Pathologic regurgitation in RHD — The criteria for pathologic regurgitation in RHD are the same as those described above for acute rheumatic carditis. (See 'Criteria for pathologic regurgitation' above.)

Differential diagnosis of RHD — Similar to rheumatic carditis, RHD should be distinguished from other causes of valve regurgitation and stenosis including the following conditions:

Pathologic regurgitation should be distinguished from physiologic valve regurgitation (trace to mild MR or trace AR), which is common in normal individuals [21]. (See "Echocardiographic evaluation of the mitral valve".)

RHD should be distinguished from other causes of valve regurgitation including functional (secondary) MR, which may be caused by a variety of conditions such as cardiomyopathy. (See "Clinical manifestations and diagnosis of chronic mitral regurgitation" and "Clinical manifestations and diagnosis of chronic mitral regurgitation", section on 'Identifying the cause of MR'.)

RHD should be distinguished from other causes of valve stenosis such as congenital MS or mitral annular calcification causing MS (see "Clinical manifestations and diagnosis of mitral annular calcification") and bicuspid aortic valve or calcific disease causing aortic stenosis. (See "Clinical manifestations and diagnosis of aortic stenosis in adults".)

SCREENING IN ENDEMIC SETTINGS

Role of screening — Echocardiographic screening programs for RHD should be confined to research, as RHD meets some, but not all, criteria for screening. The improved diagnostic accuracy of echocardiography compared with auscultation has motivated the use of screening echocardiography to diagnose subclinical disease and attempt to avert the progression to overt RHD and its complications. Despite a plethora of screening programs in virtually every endemic region of the world [41], some critical concerns remain regarding the positioning of screening within the RHD landscape.

As outlined by Wilson and Jungner in their classic treatise "Principles and practice of screening for disease," the key goal of screening is to identify disease in asymptomatic individuals to provide more timely treatment and thus improve outcomes and reduce individual and society disease burden [42]. Thus, a disease suitable for screening must meet all four of the following criteria:

The disease must be a significant burden. RHD screening has been advocated given the significant disease burden in schoolchildren and young adults in endemic settings [5,13]. (See 'Epidemiology' above.)

The natural course of the disease should be well established, and the disease should include an initial latent stage that can be detected by a highly sensitive and specific test that is acceptable to the screened population.

Effective treatment or intervention must be available and acceptable.

Screening followed by diagnosis and intervention in an early stage of disease should improve prognosis compared with intervention for symptomatic, self-referred cases.

Several reports [43-45] have raised the concern as outlined in the 2017 Cairo Accord [46] on RHD that echocardiographic screening programs should be confined to research, as RHD meets some, but not all, criteria for screening. In the discussion below, "screening" refers to echocardiographic screening of asymptomatic populations. Sufficient evidence exists to confirm that screening in these populations using Doppler echocardiography (either with portable or, increasingly, hand-held echocardiography [47]) is far more sensitive than traditional auscultation.

The natural history of subclinical RHD is not well understood. Several observational studies suggest that subclinical valve lesions can progress to clinically evident disease, resolve with and without therapy, and remain stable after six months to over five years of follow-up [10,43,48-52].

RHD has an initial asymptomatic latent stage (latent RHD) that is detectable by echocardiography [9,10,14,48,53,54]. There are large numbers of presymptomatic cases with typical auscultatory and echocardiographic abnormalities, and portable echocardiography is a sensitive tool for screening, though the specificity of minor echocardiographic findings is uncertain [55,56]. It remains a concern that some minor valvular abnormalities are termed "rheumatic" when these may be a variant of normal [57].

The course of latent RHD is highly variable, as illustrated by echocardiographic regression (improvement in valve lesion) in nearly half of all patients with latent RHD with or without secondary antibiotic prophylaxis in the GOAL trial [58]. (See "Acute rheumatic fever: Treatment and prevention" and "Acute rheumatic fever: Treatment and prevention", section on 'Secondary prevention (antibiotic prophylaxis)'.)

Secondary prophylaxis for clinical acute rheumatic fever (ARF) reduces recurrent rheumatic fever episodes and frequency and duration of hospitalization. Prophylaxis in individuals with latent rheumatic heart disease reduces the risk of echocardiographic progression, as discussed separately. (See "Acute rheumatic fever: Treatment and prevention" and "Acute rheumatic fever: Treatment and prevention", section on 'Secondary prevention (antibiotic prophylaxis)'.)

The cost-effectiveness of screening for RHD is uncertain. Most reports looking at the cost-effectiveness have modeled virtual costs, although a later publication used multistate models and local data to review costs and concluded that screening could be cost-effective if RHD was diagnosed at least two years earlier [37,59]. However, the areas in which RHD is endemic are highly variable, and thus it is difficult to weigh the costs and potential benefits of screening with other demands on health care resources in endemic areas [60].

In summary, echocardiographic screening for RHD shows improved sensitivity over screening using auscultation to detect subclinical or missed disease in asymptomatic populations. However, the use of screening as a public health tool within a prevention and control program needs further exploration regarding real-time cost-effectiveness, effect on long-term prognosis, and implementation of an effective program in resource-limited endemic RHD settings [61].

Types of screening — Screening for RHD involves eliciting a history of ARF, clinical cardiac auscultation, and echocardiography in an asymptomatic individual with active surveillance (not an individual seeking care). Largely, screening programs have occurred at schools, although home-based, antenatal clinic and community-based screening programs have developed. An individual with a typical cardiac valvular abnormality with a history of ARF, regardless of severity, represents a definite case of RHD that requires antibiotics for secondary prevention of ARF (this should be defined as a missed case if detected during a screening program). A useful classification system for cases without a history of ARF that are identified by combined echocardiographic and clinical screening is shown in the following table (table 4).

There are two screening approaches that have been applied to rheumatic valve disease in high-risk communities in individuals with or without a history of rheumatic fever: clinical cardiac auscultation followed by echocardiographic confirmation in patients with a significant murmur; or portable screening echocardiography for all, followed by clinical examination of abnormal cases [14]. However, cardiac auscultation has been shown to lack sensitivity and specificity for detection of valve pathology by echocardiography, leaving many subclinical cases of RHD undiagnosed [62]. Since echocardiography offers greater sensitivity, screening using echocardiography has become the norm, with programs involving shorter focused screening protocols, handheld echocardiography, and performance of studies by sonographers from diverse fields, such as community health, students, or nurses [47,63-67].

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

Epidemiology – Rheumatic heart disease (RHD) is the leading cause of heart disease in children and young adults under the age of 40 years who live in resource-limited countries. (See 'Epidemiology' above.)

Rheumatic carditis

ARF – Acute rheumatic fever (ARF) causes a pancarditis, affecting the valve leaflets, pericardium, epicardium, myocardium, and endocardium. Mitral regurgitation (MR; with or without aortic regurgitation) is the most common valve lesion. The revised Jones criteria incorporating epidemiology and Doppler echocardiography should be applied (table 2). (See 'Rheumatic carditis' above.)

Diagnosis of rheumatic carditis – Patients with suspected or confirmed ARF or a new murmur should undergo echocardiography to determine if valve abnormalities are present. The diagnosis of rheumatic carditis is confirmed by echocardiography showing both morphologic valvular involvement of mitral and/or aortic valves (except for very early cases with normal valve morphology) and Doppler evidence of pathologic valvular regurgitation. (See 'Diagnosis of rheumatic carditis' above.)

Rheumatic heart disease

History of ARF – While RHD occurs only as a sequela of ARF, most patients with RHD lack a history of past ARF, suggesting that the diagnosis of ARF is frequently missed. (See 'Chronic valve disease' above.)

Age and pattern of disease – The incidence and pattern of mitral valve (MV) pathology in RHD varies according to age and geography. In general, younger patients under the age of 20 present predominantly with isolated MR, whereas middle-aged adult patients develop mitral stenosis from the third decade, with mixed MV disease becoming more dominant in older patients. (See 'Disease course and relationship to age' above.)

Diagnosis – RHD should be suspected in patients with past history of ARF and/or suspected pathologic cardiac murmur. The diagnosis is confirmed by the presence of echocardiographic morphologic and Doppler criteria. (See 'Diagnosis of rheumatic heart disease' above.)

Role of screening – Widespread echocardiographic screening programs for RHD should be confined to research, as RHD meets some, but not all, criteria for screening. (See 'Role of screening' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Bongani Mayosi, MBChB, PhD, FCP(SA) (deceased), who contributed to earlier versions of this topic review.

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Topic 13612 Version 25.0

References

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