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Clinical manifestations and diagnosis of rheumatic heart disease

Authors: Liesl Zühlke, ChB DCH FCPaeds Cert Card MPH FESC FACC PhD, Ferande Peters, MBBCH FCP(SA)
FESC FACC FRCP (London)
Section Editor: Patricia A Pellikka, MD, FACC, FAHA, FASE
Deputy Editor: Susan B Yeon, MD, JD, FACC

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2018. | This topic last updated: Jan 23, 2018.

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].

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

A study of RHD cases estimated that in 2015, there were globally 33.4 million cases of RHD, 10.5 million
disability-adjusted life-years due to RHD, and 319,400 deaths due to RHD [4]. The global mortality burden of
RHD decreased by nearly 50 percent from 1990 to 2015, but the prevalence varied widely among countries
and was highest in Oceania, central sub-Saharan Africa, and South Asia. Estimated age-standardized
prevalence of RHD in 2015 was 3.4 cases per 100,000 population in nonendemic countries and 444 cases
per 100,000 population in endemic countries. Twenty countries with an endemic pattern of RHD had an age-
standardized prevalence exceeding 1 percent [4].

RHD is a disease affecting predominantly those living in poverty with inadequate access to health care and
unchecked exposure to group A streptococcus [5]. 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 slums but only 4 per 1000 among children attending the city schools [6]. 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 [7]. 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
developing communities of Australasia [4,8-12].

Echocardiographic studies have revealed high prevalence rates in developing countries. A robust systematic

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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 [13]. Based on these data, it is estimated that
the RHD burden could as much as double that in the Global Burden of Disease (GBD) study [4]. Based upon
the premise that children in sub-Saharan Africa represent 6 to 7 percent of total global RHD burden [4], there
may be an estimated 50 to 80 million persons currently affected with RHD worldwide [14].

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 [15]. These rates are in contrast to
the incidence of rheumatic fever in developed countries of <1/100,000 of the population per year [16].
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 26) with a mortality of 16.9 percent within the 24-month observation period [17,18].

Of note, the selected echocardiographic criteria for diagnosis of RHD affect the rate of detection of disease.
Echocardiographic criteria 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
criteria, as described below [19]. (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
1A-B). RHD is defined as permanent heart valve damage subsequent to ARF.

Rheumatic carditis — 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)
[20,21] and arthritis (35 to 66 percent) [20,21]. 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'.)

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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 [22]. 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 [23].

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 [24,25]. 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 [26]. 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 [27]. (See "Acute pericarditis: Clinical
presentation and diagnostic evaluation".)

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) [28,29]. 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 [28].

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 [30].

● 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)
[31]. 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.

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Chronic valve disease — While chronic RHD occurs only as a sequel of ARF, the majority of 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. 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 [17]. Patients with symptomatic chronic
RHD face high rates of mortality (16.9 percent in two years) and morbidity [18]. 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 1A) [15]. In the published literature of the current era, clinically detected RHD is
most commonly 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 developed countries, the progression of disease is more indolent and manifests
at older ages (above 50 years) [5].

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 [17]. 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 [17]. 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 commonly encountered single valve lesion after the age of 30. Rheumatic aortic
valve stenosis generally occurs in patients with concomitant or prior evidence of AR [32]. 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 [32], but early AS can
occur with a trileaflet valve [33].

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 [31]. 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

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of 591 Indigenous Australians aged 5 to 24 years diagnosed with RHD from 1999 to 2012 evaluated disease
course and outcomes [34]. 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 as long as 20 to 40 years
between the initial infection and the onset of clinical symptoms. In developing 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
[35].

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 "Clinical manifestations and diagnosis of
rheumatic mitral stenosis".)

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 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,

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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 in 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 [36].

● 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 [37]. 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 should
undergo echocardiography to determine if valve abnormalities are present. As noted in the 2014 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

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valvular regurgitation [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 [26,28].

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 [19].

Criteria for pathologic regurgitation — The following are Doppler echocardiography criteria for
pathologic regurgitation for acute rheumatic carditis (as well as for RHD) [19,21]. Regurgitant jet length is
measured from the vena contracta to the last pixel of regurgitant color [19].

● 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

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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 "Definition and diagnosis of mitral valve prolapse".)

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 past
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 or may conceive, 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, careful observation, and prompt treatment of complications should they arise. Mitral stenosis (MS)
is the most commonly 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 [19]. The morphologic features of RHD (for the mitral valve [MV]) differ from those for

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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 [19].

● 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 2) 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 2) [19]:

● 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.)

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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 [38], 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 [39]. 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 [4,12]. (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 [40-42] have raised the concern as outlined in the 2017 Cairo Accord [43] on RHD that
echocardiographic screening programs should be confined to research, as RHD meets some, but not all,
criteria for screening.

● 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

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remain stable after six months to over five years of follow-up [9,40,44-48].

● RHD has an initial latent stage that is detectable by simple testing and is amenable to treatment that
improves prognosis [8,9,49,50]. 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. It remains a concern
that some minor valvular abnormalities are termed "rheumatic" when these may be a variant of normal
[51].

● Secondary prophylaxis for clinical acute rheumatic fever (ARF) reduces recurrent rheumatic fever
episodes and frequency and duration of hospitalization (see "Acute rheumatic fever: Treatment and
prevention", section on 'Secondary prevention (antibiotic prophylaxis)'). However, the effect of secondary
prophylaxis on the course of subclinical RHD has not been established, although regression of lesions in
the context of ARF has been demonstrated [52].

● In addition, the cost-effectiveness of screening for RHD is uncertain. The majority of 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 [34,53]. 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.

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 3).

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 echocardiography for all,
followed by clinical examination of abnormal cases [13]. 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 [54]. Echocardiography offers greater sensitivity, thus screening using
echocardiography has become the norm, with new programs focusing on screening with focused shorter
protocols, utilizing handheld echocardiograms, and nonexpert sonographers [55-59].

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".)

SUMMARY AND RECOMMENDATIONS

● 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 developing countries. (See 'Epidemiology' above.)

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● 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 new Jones criteria incorporating epidemiology and Doppler echocardiography
should be applied. (See 'Rheumatic carditis' above.)

● 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.)

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

● 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 30 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.)

● 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.)

● 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 editorial staff at UpToDate would like to acknowledge Bongani Mayosi,
MBChB, PhD, FCP(SA), who contributed to an earlier version of this topic review.

Use of UpToDate is subject to the Subscription and License Agreement.

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GRAPHICS

Pathogenesis of rheumatic mitral valve disease

This figure depicts the theoretical pathway for the various phenotypic manifestations of rheumatic MV
disease. The initial inflammatory response following the first episode of ARC determines the degree and
extent of structural involvement of the MV apparatus. Severe inflammation of the chordal structures and
MV leaflets often lead to severe MR in the very young, whereas moderate inflammation followed by
repeated bouts of ARC is more likely to cause mixed MV disease (MR and MS) later in life. Isolated MS is
usually the consequence of milder or even subclinical forms of ARC followed by episodes of recurrent
carditis. In developing countries where the risk of recurrent ARC is high, MS presents at a younger age
and the valve leaflets are more likely to be pliable and not calcified. In Western societies where the risk
of recurrent ARC is low, MS presents later in life, and the MV leaflets are more likely to be rigid and
calcified.

ARC: acute rheumatic carditis; MS: mitral stenosis; MV: mitral valve; MR: mitral regurgitation.

Courtesy of Theo Meyer, MD, PhD.

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Hemodynamic alterations and structural sequelae of mitral stenosis

This figure illustrates the progressive hemodynamic alterations and structural sequelae of mitral
stenosis. Obstruction to flow through the stenotic valve leads to chronic LA pressure overload, which
over time results in PVH and LA enlargement. Remodeling of the LA is the substrate of atrial
fibrillation and in-situ thrombi. An enlarged LA may cause left recurrent laryngeal nerve compression.
PVH promotes broncho-pulmonary venous anastomoses and passively increases pulmonary arterial
pressures. In another group of patients with mitral stenosis, PAH bears little relationship to the LA
pressure. This type of reactive PAH is due to vasoconstriction and pathological remodeling of the
pulmonary vasculature (medial hypertrophy and intimal hyperplasia). The vascular remodeling and
in-situ arteriolar thrombosis promote progressive PAH, RV pressure overload, RV dilation, and TR.

RV: right ventricular; TR: tricuspid regurgitation; PAH: pulmonary arterial hypertension; PVH: pulmonary
venous hypertension; LA: left atrial.

Courtesy of Theo Meyer, MD, PhD.

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NYHA and other classifications of cardiovascular disability

New York Heart Canadian


Association Cardiovascular Specific activity
Class
functional Society functional scale [3]
classification [1] classification [2]

I Patients with cardiac Ordinary physical activity, Patients can perform to


disease but without such as walking and completion any activity
resulting limitations of climbing stairs, does not requiring ≥7 metabolic
physical activity. Ordinary cause angina. Angina equivalents, eg, can carry
physical activity does not with strenuous or rapid 24 lb up eight steps; do
cause undue fatigue, prolonged exertion at outdoor work (shovel
palpitation, dyspnea, or work or recreation. snow, spade soil); do
anginal pain. recreational activities
(skiing, basketball,
squash, handball,
jog/walk 5 mph).

II Patients with cardiac Slight limitation of Patients can perform to


disease resulting in slight ordinary activity. Walking completion any activity
limitation of physical or climbing stairs rapidly, requiring ≥5 metabolic
activity. They are walking uphill, walking or equivalents, eg, have
comfortable at rest. stair climbing after sexual intercourse
Ordinary physical activity meals, in cold, in wind, or without stopping, garden,
results in fatigue, when under emotional rake, weed, roller skate,
palpitation, dyspnea, or stress, or only during the dance fox trot, walk at 4
anginal pain. few hours after mph on level ground, but
awakening. Walking more cannot and do not
than two blocks on the perform to completion
level and climbing more activities requiring ≥7
than one flight of metabolic equivalents.
ordinary stairs at a
normal pace and in
normal conditions.

III Patients with cardiac Marked limitation of Patients can perform to


disease resulting in ordinary physical activity. completion any activity
marked limitation of Walking one to two requiring ≥2 metabolic
physical activity. They are blocks on the level and equivalents, eg, shower
comfortable at rest. Less climbing one flight in without stopping, strip
than ordinary physical normal conditions. and make bed, clean
activity causes fatigue, windows, walk 2.5 mph,
palpitation, dyspnea, or bowl, play golf, dress
anginal pain. without stopping, but
cannot and do not
perform to completion
any activities requiring
>5 metabolic
equivalents.

IV Patients with cardiac Inability to carry on any Patients cannot or do not


disease resulting in physical activity without perform to completion
inability to carry on any discomfort. Anginal activities requiring >2
physical activity without syndrome may be metabolic equivalents.
discomfort. Symptoms of present at rest. Cannot carry out
cardiac insufficiency or of activities listed above

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the anginal syndrome (specific activity scale


may be present even at III).
rest. If any physical
activity is undertaken,
discomfort is increased.

NYHA: New York Heart Association.

References:
1. The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of
Diseases of the Heart and Great Vessels, 9th ed, Little, Brown & Co, Boston, 1994. p.253.
2. Campeau L. Grading of angina pectoris. Circulation 1976; 54:522.
3. Goldman L, Hashimoto B, Cook EF, Loscalzo A. Comparative reproducibility and validity of systems for
assessing cardiovascular functional class: Advantages of a new specific activity scale. Circulation 1981;
64:1227.

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Morphological features of rheumatic heart disease

Features in the MV

AMVL thickening* ≥3 mm (age-specific) ¶

Chordal thickening

Restricted leaflet motion Δ

Excessive leaflet tip motion during systole ◊

Features in the AV

Irregular or focal thickening §

Coaptation defect

Restricted leaflet motion

Prolapse

MV: mitral valve; AMVL: anterior mitral valve leaflet; AV: aortic valve; RHD: rheumatic heart disease.
* AMVL thickness should be measured during diastole at full excursion. Measurement should be taken at the thickest
portion of the leaflet, including focal thickening, beading, and nodularity. Measurement should be performed on a
frame with maximal separation of chordae from the leaflet tissue. Valve thickness can only be assessed if the
images were acquired at optimal gain settings without harmonics and with a frequency ≥2.0 MHz.
¶ Abnormal thickening of the AMVL is age-specific and defined as follows: ≥3 mm for individuals aged ≤20 years;
≥4 mm for individuals aged 21 to 40 years; ≥5 mm for individuals aged >40 years. Valve thickness measurements
obtained using harmonic imaging should be cautiously interpreted and a thickness up to 4 mm should be considered
normal in those aged ≤20 years.
Δ Restricted leaflet motion of either the anterior or the posterior MV leaflet is usually the result of chordal shortening
or fusion, commissural fusion, or leaflet thickening.
◊ Excessive leaflet tip motion is the result of elongation of the primary chords, and is defined as displacement of the
tip or edge of an involved leaflet towards the left atrium resulting in abnormal coaptation and regurgitation.
Excessive leaflet tip motion does not need to meet the standard echocardiographic definition of MV prolapse disease,
as that refers to a different disease process. This feature applies to only those aged <35 years. In the presence of a
flail MV leaflet in the young (≤20 years), this single morphological feature is sufficient to meet the morphological
criteria for RHD (that is, where the criteria state "at least two morphological features of RHD of the MV," a flail
leaflet in a person aged ≤20 years is sufficient).
§ In the parasternal short axis view, the right and noncoronary aortic cusp closure line often appears echogenic
(thickened) in healthy individuals and this should be considered as normal.

Reprinted by permission from: Macmillan Publishers Ltd: Nature Reviews Cardiology. Reményi B, Wilson N, Steer A,
et al. World Heart Federation criteria for echocardiographic diagnosis of rheumatic heart disease--an evidence-based
guideline. Nat Rev Cardiol 2012; 9:297. Copyright © 2012. http://www.nature.com/nrcardio/.

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Diagnostic criteria for rheumatic heart disease based on history, cardiac


auscultation, and echocardiographic findings

Column A Column B Column C

Category of rheumatic Presence or history of Echocardiographic Echocardiographic


heart disease proven acute rheumatic valvular structural functional abnormality
fever abnormality (ie, typical (ie, presence of
rheumatic valve significant valve
AND/OR
morphology according to regurgitation according to
Finding on clinical cardiac the World Heart the World Heart
auscultation (ie, presence Federation criteria for Federation criteria for
of pathological murmur echocardiographic echocardiographic
of MR, MS, AR, and/or diagnosis of rheumatic diagnosis of rheumatic
AS) heart disease) heart disease)
AND/OR
Echocardiographic
structural and functional
changes of MS without
murmur (ie, silent MS)

Definite (presence of + + +
at least two of the
abnormalities
described in columns
A, B, and C)

Borderline (presence – + +
of abnormalities
described in either
column B or C)

Normal (none of the – – –


abnormalities
described in columns
A, B, and C)

MR: mitral regurgitation; MS: mitral stenosis; AR: aortic regurgitation; AS: aortic stenosis.

Data from:​
1. WHO Technical Report Series. Rheumatic fever and rheumatic heart disease: Report of a WHO expert panel,
Geneva 29 October - 1 November 2001. Geneva: WHO; 2004.
2. Remenyi B, Wilson N, Steer A, et al. World Heart Federation criteria for echocardiographic diagnosis of
rheumatic heart disease - an evidence-based guideline. Nat Rev Cardiol 2012; 9:297.

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