NATURE REVIEWS | CARDIOLOGY ADVANCE ONLINE PUBLICATION | 1
Green Lane Pediatric
and Congenital Cardiac
Service, Starship
Children’s Hospital,
Auckland, New Zealand
(B. Reményi, N. Wilson,
J. Stirling). Royal
Children’s Hospital,
Australia (A. Steer).
Maputo Heart Institute,
Mozambique
(B. Ferreira). Fiji
Ministry of Health, Fiji
Islands (J. Kado).
Amrita Institute of
Medical Sciences, India
(K. Kumar).
Stellenbosch University,
South Africa
(J. Lawrenson). James
Cook University,
Australia (G. Maguire).
Hôpital Européen
Georges Pompidou,
France (E. Marijon,
M. Mirabel). University
Eduardo Mondlane,
Mozambique
(A. O. Mocumbi).
Federal University of
Minas Gerais, Brazil
(C. Mota). WakeMed
Hospital, USA (J. Paar).
All India Institute of
Medical Sciences, India
(A. Saxena). Johns
Hopkins Hospital, USA
(J. Scheel). Medical
Specialist Clinic,
Samoa (S. Viali).
Sri Jayadeva Institute
of Cardiovascular
Sciences and
Research, India
(V. I. Balekundri).
Women’s and Children’s
Hospital, Australia
(G. Wheaton).
University of Cape
Town, South Africa
(L. Zühlke). Menzies
School of Health
Research, Australia
(J. Carapetis).
Correspondence to:
B. Reményi
bo.remenyi@
menzies.edu.au
World Heart Federation criteria for
echocardiographic diagnosis of rheumatic heart
disease—an evidence-based guideline
Bo Reményi, Nigel Wilson, Andrew Steer, Beatriz Ferreira, Joseph Kado, Krishna Kumar,
John Lawrenson, Graeme Maguire, Eloi Marijon, Mariana Mirabel, Ana Olga Mocumbi, Cleonice Mota,
John Paar, Anita Saxena, Janet Scheel, John Stirling, Satupaitea Viali, Vijayalakshmi I. Balekundri,
Gavin Wheaton, Liesl Zühlke and Jonathan Carapetis
Abstract | Over the past 5 years, the advent of echocardiographic screening for rheumatic heart disease
(RHD) has revealed a higher RHD burden than previously thought. In light of this global experience, the
development of new international echocardiographic guidelines that address the full spectrum of the
rheumatic disease process is opportune. Systematic differences in the reporting of and diagnostic approach
to RHD exist, reflecting differences in local experience and disease patterns. The World Heart Federation
echocardiographic criteria for RHD have, therefore, been developed and are formulated on the basis of the
best available evidence. Three categories are defined on the basis of assessment by 2D, continuous-wave,
and color-Doppler echocardiography: ‘definite RHD’, ‘borderline RHD’, and ‘normal’. Four subcategories of
‘definite RHD’ and three subcategories of ‘borderline RHD’ exist, to reflect the various disease patterns.
The morphological features of RHD and the criteria for pathological mitral and aortic regurgitation are also
defined. The criteria are modified for those aged over 20 years on the basis of the available evidence. The
standardized criteria aim to permit rapid and consistent identification of individuals with RHD without a clear
history of acute rheumatic fever and hence allow enrollment into secondary prophylaxis programs. However,
important unanswered questions remain about the importance of subclinical disease (borderline or definite
RHD on echocardiography without a clinical pathological murmur), and about the practicalities of implementing
screening programs. These standardized criteria will help enable new studies to be designed to evaluate the
role of echocardiographic screening in RHD control.
Reményi, B. et al. Nat. Rev. Cardiol. advance online publication 28 February 2012; doi:10.1038/nrcardio.2012.7
Introduction
Rheumatic heart disease (RHD), the only long-term
consequence of acute rheumatic fever (ARF), continues
unabated among middle-income and low-income coun-
tries and in some indigenous communities of the indus-
trialized world. At least 15 million people are estimated
to be affected by RHD worldwide.1 The American Heart
Association (AHA) has well-established clinical diag-
nostic criteria for ARF—the Jones criteria2—and, with
some modifications and revisions, these guidelines have
been accepted and utilized worldwide.3–5 No such widely
accepted criteria exist for RHD.
The only cost-effective approach to controlling RHD is
secondary prophylaxis in the form of penicillin injections
every 3–4 weeks to prevent recurrent attacks of group A
streptococcal infection that cause ARF and, thus, the wors-
ening of RHD.6 However, the majority of patients who
enroll into register-based programs are symptomatic with
advanced disease, indicating that they have had a number
of silent or undetected attacks of ARF. Patients with mild,
asymptomatic RHD have the most to gain from second-
ary prophylaxis because, in the absence of ARF recur-
rence, the majority will have no detectable disease within
5–10 years.7–9 Screening to detect asymptomatic cases is,
therefore, an attractive strategy.
Traditionally, RHD was diagnosed by auscultating for
a heart murmur in those with a history of ARF. Until the
past decade, the stethoscope was the only noninvasive
diagnostic tool available to physicians in low-income
countries and in remote settings where ARF and RHD
are most prevalent. However, detection rates were usually
low.10–15 Echocardiography has proven to be more sensitive
and specific than auscultation.16–22 RHD detected on echo-
cardiography without an associated clinically patho logical
cardiac murmur is referred to as ‘subclinical RHD’.16 With
the advent of portable technology, echocardiography can
now be performed at a relatively low cost, eve n in remote
settings.20 This development raises the possibility that
people with previously undiagnosed RHD, including
those without a known history of ARF, can be diagnosed
Competing interests
The authors declare no competing interests.
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and secondary prophylaxis started at an earlier stage of the
illness than previously possible, thus potentially reducing
morbidity and mortality.
Since 2004, the World Health Organization (WHO)
has recommended echocardiographic screening for
RHD in high-prevalence regions.23 In 2005, a joint WHO
and National Institutes of Health (NIH) working party
established consensus case definitions for RHD, which
were published 5 years later, in 2010.24 The definitions
were based on expert consensus, but have their limi-
tations because they were not evidence-based, the full
spectrum of morphological features of RHD were not
considered, and in 2005 there was insufficient experience
with normal echocardiographic findings in children.16
Since 2005, a number of countries—including Australia,
Cambodia, Fiji, India, Laos, Mali, Mozambique, New
Caledonia, New Zealand, Nicaragua, Pakistan, Samoa,
South Africa, Tonga, and Yemen—have embarked on
large-scale echocardiography-based RHD screening
programs.16–19,21,22 Some of these screening programs
used the 2005 WHO and NIH consensus definitions,
but others used different criteria to define abnormal-
ity of both cardiac valve structure (morphology) and
function (regurgitation or stenosis), often on the basis
of local experience with RHD. This global experience,
and the concern that echocardiography might be overly
sensitive in some children with normal variation in
valvular structure and function, has given impetus to
develop an internationally endorsed evidence-based
echocardiographic diagnostic guideline for RHD. In
this article, we present the 2012 World Heart Federation
(WHF) criteria for echocardiographic diagnosis of
RHD. For ease of use in the clinical environment, a
concise summary of these guidelines—containing the
four key Boxes in this article—is available online as
Supplementary Information.
Intent of these guidelines
Our primary aim in developing these guidelines was to
define the minimum echocardiographic criteria for the
diagnosis of RHD and to highlight the evidence on which
these criteria are based. Use of these guidelines should
enable rapid identification of RHD in patients who do not
have a history of ARF. Importantly, the guidelines should
allow for consistent and reproducible echocardiographic
reporting of RHD worldwide and, therefore, facilitate
epidemio logic studies and evaluation of interventions,
such as group A streptococcal vaccine trials, aimed at
reducing the worldwide burden of RHD. The guidelines
are also intended to aid the long-term evaluation of minor
echocardiographic lesions that do not meet the current
echocardiographic criteria for definite RHD.
These guidelines are not intended for the diagnosis of
carditis in the setting of ARF or for the diagnosis of RHD in
patients with a history of ARF. In addition, this document
does not contain recommendations on the management
of ARF or RHD; for information on treatment, the reader
is directed to local guidelines, or to the websites of the
AHA,2 WHO,3 Heart Foundation of Australia,4 and Heart
Foundation of New Zealand.5
Development of these guidelines
An international advisory group of experts in RHD
screening and echocardiographic manifestations of RHD
was formed in 2009 (see the author list for this article).
Under the auspices of the WHF, this group of 21 investi-
gators from six continents developed evidence-based
echocardiographic diagnostic guidelines for RHD. Expert
panel members reported on echo cardiograms online and
systematic differences in reporting and diagnostic styles
were identified. Via a series of web-based seminars, these
differences were resolved and provisional echocardio-
graphic criteria for RHD were agreed. A systematic lit-
erature review was performed using the Medline, Embase,
and Cochrane databases to identify diagnostic features of
established RHD by echocardio graphy, at cardiac surgery,
and on post mortem examinations. The search terms “echo-
cardiography”, “surgery”, “pathology”, “mitral”, “aortic”,
“tricuspid”, “valve”, “normal”, “regurgitation”, “sten osis”,
“prolapse”, “RHD” and “rheumatic” were optimally com-
bined. The search was limited to papers published in the
English language and was supplemented by careful review
of the reference list of the relevant articles. A total of 3,218
abstracts and 170 full-text articles were reviewed; 108 were
found to be directly relevant and are included in the refer-
ence list. All relevant articles were reviewed by at least two
members of the panel. Evidence-based guidelines were
finalized at a workshop in Thailand in 2011, where the
expert panel members reviewed the 108 papers identi-
fied as directly relating to RHD and echocardiography.
Results of completed, but not yet published, studies (by
investigators who were part of the expert panel) were also
critically reviewed. Whenever evidence for or against the
provisional criteria was insufficient, a formal consensus
method24 was used to reach agreement.
Grading evidence
The level of evidence was established and each recom-
mendation was graded using the guidelines of the
Scottish Intercollegiate Guidelines Network25 (Tables 1
and 2), as they seemed to be the most applicable to this
diagnostic setting.
Diagnostic criteria
Echocardiographic findings should always be inter-
preted in conjunction with the patient’s clinical findings
and with consideration of the individual’s pretest prob-
ability of RHD, which varies with geographical location
(level 1+ evidence),1 ethnicity (level 2+ evidence),26,27 and
living conditions (level 2+ evidence) (grade B recom-
mendation).28,29 An individual’s clinical history, including
possible or probable ARF, should also be considered. In
those with a history of definite ARF, any structural and
functional abnormality of the valves must be considered
to represent RHD until proven otherwise.
The concise echocardiographic criteria for ‘definite
RHD’ and ‘borderline RHD’ are detailed in Boxes 1–3.
The optimal settings for the echocardiography machine,
which allow objective measurement, are summarized
in Box 4. The echocardiographic features listed in
Boxes 1–3 are not unique to RHD. Congenital, acquired,
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NATURE REVIEWS | CARDIOLOGY ADVANCE ONLINE PUBLICATION | 3
and degenerative heart disease should always be excluded
as the etiology of mitral valve (MV) and aortic valve
(AV) abnormalities before presuming rheumatic origin
(grade D recommendation). Congenital cardiac defects
are easily differentiated from RHD, as they have unique
identifying features (for example, bicuspid AV or MV
cleft). Degenerative conditions are rare in the young, and
other acquired conditions (for example, infective endo-
carditis) can be differentiated from RHD on the basis of
clinical findings (level 4 evidence).
RHD predominantly affects the left-sided cardiac valves,
causing regurgitation, stenosis, or mixed hemodynamic
effects. The tricuspid valve and (seldomly) the pulmonary
valve can also be affected, but rarely (if ever) without MV
involvement (99.3% on echocardiography and 100% on
postmortem examination have coexisting disease of the
MV;30 level 1+ evidence). Similarly, AV stenosis is rare in
isolation (0–0.5%;31–33 level 2+ evidence). Hence, neither
right-sided valve lesions nor aortic stenosis are included in
the diagnostic criteria (grade B recommendation).
Rationale and evidence for criteria
Definite RHD
Echocardiographic changes that meet the criteria for
‘definite RHD’ are considered to be rheumatic in origin,
provided that other etiologies have been excluded by echo-
cardiography and clinical context. In interpreting echo-
cardiograms, the individual’s pretest probability of RHD
must be considered. The subcategories of ‘definite RHD’
(A–D) are listed below.
Subcategory A—RHD of the MV with regurgitation
Subcategory A of ‘definite RHD’ is defined as pathologi-
cal mitral regurgitation and at least two morpho logical
features of RHD of the MV. This subcategory has a
grade B recommendation for its inclusion in the ‘definite
RHD’ category.
MV disease in the form of regurgitation is the most-
common manifestation of RHD in the young (level 2++
evidence).31–36 Echocardiographic,35–40 surgical,41–43
and postmortem anatomical44–46 studies have demon-
strated that a combination of the morphological features
(Box 3) is present in advanced disease (level 2+ evidence).
Colloquial descriptions of the MVs—such as ‘dog-leg’,
‘elbow’, or ‘hockey stick’ deformities47—also portray a
combination of morphological changes (thickening and
restricted motion of the anterior MV leaflet; Figures 1
and 2).
Subcategory B—RHD of the MV with stenosis
Subcategory B of ‘definite RHD’ is defined as mitral
steno sis with a mean gradient ≥4 mmHg and at least two
morpho logical changes of RHD of the MV. This sub-
category has a grade B recommendation for its inclusion
in the ‘definite RHD’ category.
Worldwide, the most-common cause of MV stenosis is
RHD,48–51 and the condition is associated with at least two
morphological changes of RHD (level 2+ evidence).51,52
Typically, leaflets are thickened and the posterior leaflet
is relatively immobile and moves parallel during diastole
with the anterior MV leaflet. The second-most-common
etiology of mitral stenosis is congenital MV steno-
sis,48,50 which is readily differentiated from RHD as it is
frequently associated with abnormal papillary muscle
arrangements and (in 84–97% cases) with other congeni-
tal cardiac defects (level 2++ evidence).53–56 Worldwide,
RHD is still responsible for 95–99.3% of all MV stenoses
in indivi duals aged <50 years (level 2++ evidence).48,49 In
those aged >50 years, nonrheumatic mitral annular cal-
cification is a differential diagnosis of mitral stenosis that
should be considered (level 2+ evidence).49,57
Subcategory C—RHD of the AV
Subcategory C of ‘definite RHD’ is defined as patho logical
aortic regurgitation and at least two morphological features
of RHD of the AV. This subcategory only applies to indivi-
duals aged <35 years and has a grade B recommendation
for its inclusion in the ‘definite RHD’ category.
Although less common than isolated MV involvement,
isolated disease of the AV is a recognized manifestation
of RHD. A large study of 10,000 consecutive patients
Table 1 | Levels of evidence, as defined in the guidelines of the SIGN25
Level of
evidence
Study description
1++ High quality meta-analyses, systematic reviews of RCTs, or RCTs with
a very low risk of bias
1+ Well-conducted meta-analyses, systematic reviews, or RCTs with a low risk
of bias
1– Meta-analyses, systematic reviews, or RCTs with a high risk of bias
2++ High-quality systematic reviews of case–control or cohort studies,
or high-quality case–control or cohort studies with a very low risk of
confounding or bias, and a high probability that the relationship is causal
2+ Well-conducted case–control or cohort studies with a low risk of confounding
or bias, and a moderate probability that the relationship is causal
2– Case–control or cohort studies with a high risk of confounding or bias,
and a significant risk that the relationship is not causal
3 Nonanalytic studies (for example, case reports or case series)
4 Expert opinion
Abbreviations: RCT, randomized, controlled trial; SIGN, Scottish Intercollegiate Guidelines Network.
Permission obtained from SIGN © 2001–2011.
Table 2 | Grade of recommendation, as defined in the guidelines of the SIGN25
Grade* Strength of evidence
A At least one meta-analysis, systematic review, or RCT rated as 1++
(see Table 1 for information about various levels of evidence) and directly
applicable to the target population; or a body of evidence consisting
primarily of studies rated as 1+, directly applicable to the target population,
and demonstrating overall consistency of results
B A body of evidence including studies rated as 2++, directly applicable
to the target population, and demonstrating overall consistency of results;
or extrapolated evidence from studies rated as 1++ or 1+
C A body of evidence including studies rated as 2+, directly applicable
to the target population and demonstrating overall consistency of results;
or extrapolated evidence from studies rated as 2++
D Evidence level 3 or 4; or extrapolated evidence from studies rated as 2+
*The grade of recommendation relates to the strength of the evidence on which the recommendation is
based; it does not reflect the clinical importance of the recommendation. Abbreviations: RCT, randomized,
controlled trial; SIGN, Scottish Intercollegiate Guidelines Network. Permission obtained from SIGN ©
2001–2011.
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with RHD showed that isolated rheumatic AV disease
occurs in 4.5% of individuals aged ≤18 years and in 2.8%
of indivi duals aged >18 years (level 2+ evidence).58 In
smaller series, the prevalence has been reported to be
0–21.4%.31–33,36,59–68 In AV disease, the presence of mul-
tiple morphological features (Box 3) enables confirmation
of rheumatic etiology on gross inspection (level 2+ evi-
dence).69 For consistency with the criteria for MV disease,
and to increase specificity, the definite criteria for RHD of
the AV require the presence of two rheumatic morpho-
logical features of the AV in addition to pathological
aortic regurgitation. The two most-common differential
diagnoses are bicuspid AV and aortic root dilatation,69
and both are easily differentiated on echocardiography.
Other causes, such as endocarditis and other inflamma-
tory carditis (systemic lupus erythematosus and ankylos-
ing spondylitis), can be excluded by clinical context.
Hypertension should also be excluded as an underlying
etiology (level 4 evidenc