Wh fecho criteriafordxrhdnrcardio.2012.7

NATURE REVIEWS | CARDIOLOGY VOLUME 9 | MAY 2012 | 297
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. 9, 297–309 (2012); published online 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 pathological
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, even 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.
REVIEWS
© 2012 Macmillan Publishers Limited. All rights reserved

298 | MAY 2012 | VOLUME 9 www.nature.com/nrcardio
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
epidemiologic 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
carditisinthesettingofARForforthediagnosisofRHDin
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 echocardiograms 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 echocardiography, at cardiac surgery,
and on postmortem examinations. The search terms “echo-
cardiography”, “surgery”, “pathology”, “mitral”, “aortic”,
“tricuspid”, “valve”, “normal”, “regurgitation”, “stenosis”,
“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,
REVIEWS

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 morphological
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
stenosis with a mean gradient ≥4 mmHg and at least two
morphological 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 individuals 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 pathological
aorticregurgitationandatleasttwomorphologicalfeatures
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.
REVIEWS

with RHD showed that isolated rheumatic AV disease
occurs in 4.5% of individuals aged ≤18 years and in 2.8%
of individuals 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 evidence), although studies have shown
conflicting associations between hypertension and trivial
or greater aortic regurgitation.70–73
Both aortic regurgita-
tion72–74
and valvular thickening70,75
are more common
with advancing age (level 2++ evidence). However, on the
basis of the CARDIA study71
—a population-based echo-
cardiographic study of individuals aged 20–35 years—
we can extrapolate that the criterion for RHD of the
AV remains highly specific for individuals aged up to
35 years. Of the 4,352 participants of the CARDIA study,71
only one had aortic regurgitation and a thickened AV, and
none would have met the diagnostic criteria for definite
RHD of the AV (level 2+ evidence).
Subcategory D—multivalvular RHD
Subcategory D of ‘definite RHD’ is ‘borderline’ disease of
both the AV and MV, as defined below. In individuals aged
≤20 years, this subcategory has a grade C recommendation
for its inclusion in the ‘definite RHD’ category.
Worldwide,RHDremainsthemost-commonetiologyof
combined AV and MV disease (level 2++ evidence).49,76,77
The morphological features that confirm rheumatic
etiology take time to develop (level 2+ evidence).35,40
Pathological aortic and mitral regurgitation, or patho-
logical aortic regurgitation in combination with morpho
logical changes of RHD, are extremely rare in children
with normal cardiac anatomy; data indicate a prevalence of
0% in New Zealand78
and in Israel,79
and similar data have
been found in the Australian gECHO study (J. Carapetis,
unpublished data) (level 2++ evidence). As a conse-
quence, in individuals aged ≤20 years who have a high
pretest probability of RHD, pathological aortic and mitral
regurgitation and pathological aortic regurgitation in
combination with two rheumatic morphological changes
of the MV, are considered to be rheumatic provided that
no alternative explanation for these signs exist. The latter
is also considered to be diagnostic for ‘definite RHD’
in individuals aged ≥20 years on the basis of consensus
opinion (level 4 evidence; see Box 1 for clarification).
Borderline RHD
The category of ‘borderline RHD’ only applies to indivi
duals aged ≤20 years; this age group is the least likely to
have manifested sufficient echocardiographic features to
meet the ‘definite RHD’ criteria because they can take time
to develop (level 2+ evidence).35,40
The ‘borderline RHD’
category was established to improve the sensitivity of the
echocardiographic criteria (at the expense of specificity)
in individuals aged ≤20 years, as this age group benefits
the most from early detection and secondary prevention
of RHD. Beyond the age of 20 years, mild valvular regurgi
tation is more common,71,72,74
and use of the ‘borderline
RHD’ category is not, therefore, recommended for this
age group (level 2+ evidence). Minor echocardiographic
Box 1 | 2012 WHF criteria for echocardiographic diagnosis of RHD
Echocardiographic criteria for individuals aged ≤20 years
Definite RHD (either A, B, C, or D):
■■ A) Pathological MR and at least two morphological features of RHD of the MV
■■ B) MS mean gradient ≥4 mmHg*
■■ C) Pathological AR and at least two morphological features of RHD of the AV‡
■■ D) Borderline disease of both the AV and MV§
Borderline RHD (either A, B, or C):
■■ A) At least two morphological features of RHD of the MV without pathological
MR or MS
■■ B) Pathological MR
■■ C) Pathological AR
Normal echocardiographic findings (all of A, B, C, and D):
■■ A) MR that does not meet all four Doppler echocardiographic criteria
(physiological MR)
■■ B) AR that does not meet all four Doppler echocardiographic criteria
(physiological AR)
■■ C) An isolated morphological feature of RHD of the MV (for example, valvular
thickening) without any associated pathological stenosis or regurgitation
■■ D) Morphological feature of RHD of the AV (for example, valvular thickening)
without any associated pathological stenosis or regurgitation
Echocardiographic criteria for individuals aged 20 years
Definite RHD (either A, B, C, or D):
■■ A) Pathological MR and at least two morphological features of RHD of the MV
■■ B) MS mean gradient ≥4 mmHg*
■■ C) Pathological AR and at least two morphological features of RHD of the AV,
only in individuals aged 35 years‡
■■ D) Pathological AR and at least two morphological features of RHD of the MV
*Congenital MV anomalies must be excluded. Furthermore, inflow obstruction due to
nonrheumatic mitral annular calcification must be excluded in adults. ‡
Bicuspid AV, dilated
aortic root, and hypertension must be excluded. §
Combined AR and MR in high prevalence
regions and in the absence of congenital heart disease is regarded as rheumatic.
Abbreviations: AR, aortic regurgitation; AV, aortic valve; MR, mitral regurgitation; MS, mitral
stenosis; MV, mitral valve; RHD, rheumatic heart disease; WHF, World Heart Federation.
Box 2 | Criteria for pathological regurgitation
Pathological mitral regurgitation
(All four Doppler echocardiographic criteria must be met)
■■ Seen in two views
■■ In at least one view, jet length ≥2 cm*
■■ Velocity ≥3 m/s for one complete envelope
■■ Pan-systolic jet in at least one envelope
Pathological aortic regurgitation
(All four Doppler echocardiographic criteria must be met)
■■ Seen in two views
■■ In at least one view, jet length ≥1 cm*
■■ Velocity ≥3 m/s in early diastole
■■ Pan-diastolic jet in at least one envelope
*A regurgitant jet length should be measured from the vena
contracta to the last pixel of regurgitant color (blue or red).
REVIEWS

changes that meet the criteria for ‘borderline RHD’ rep-
resent early RHD in some individuals,35
and normal
findings in others.78
Thus, when interpreting these echo-
cardiographic findings, the individual’s pretest probability
(or risk) of RHD must be considered. The subcategories
of ‘borderline RHD’ (A–C) are listed below.
Subcategory A—morphological features of the MV
Subcategory A of ‘borderline RHD’ is defined as at least
two morphological features of RHD of the MV without
pathological mitral regurgitation or mitral stenosis.
This subcategory has a grade C recommendation for its
inclusion in the ‘borderline RHD’ category.
Morphological features of RHD of the MV are likely
to be rheumatic in origin, regardless of whether they
are associated with hemodynamic effects, pathological
regurgitation, or stenosis (level 4 evidence). Among 396
low-risk children in New Zealand, none had two morpho-
logical features of RHD of the MV (level 2+ evidence).78
Among 2,170 high-risk children in Mozambique, 50
(2.3%) were identified as having two morphological
features of RHD of the MV without meeting the criteria
for pathological regurgitation or stenosis (level 2+ evi-
dence).16
These studies support the hypothesis that the
category ‘borderline A’ is part of the RHD spectrum.
Subcategory B—MV regurgitation
Subcategory B of ‘borderline RHD’ is defined as patho
logical mitral regurgitation. This subcategory has a
grade Brecommendationforitsinclusioninthe‘borderline
RHD’ category.
Isolated pathological mitral regurgitation is four times
as likely to occur in high-risk, compared with low-risk,
children in New Zealand, supporting the hypothesis that
it is part of the RHD spectrum (level 2++ evidence).78
Morphological features of RHD can take time to develop
and are more likely to be noted after a recurrence than
during the primary ARF episode (level 2+ evidence).35,40
Extrapolating evidence from surgical studies, approxi-
mately 5–7.5% of individuals with documented ARF and
severe valvular disease might not meet the ‘definite RHD’
echocardiographic criteria. Despite severe valvular insuf-
ficiency of a single valve, two morphological features might
not be present in individuals with acute carditis (level 2+
evidence).42,80
An echocardiographic study conducted in
Brazil has also highlighted the low sensitivity of the ‘defi-
nite RHD’ criteria in young people receiving secondary
prophylaxis. In this cohort of 27 patients with established
chronic isolated disease of the MV, only 70.4% met the
‘definite RHD’ criteria; the remaining 29.6% only had one
morphologicalfeatureofRHD(C.Mota,unpublisheddata;
level 2++ evidence). These studies highlight the impor-
tance of the ‘borderline RHD’ category to improve the
sensitivity of the echocardiographic criteria in the young.
Subcategory C—AV regurgitation
Subcategory C of ‘borderline RHD’ is defined as patho
logical aortic regurgitation. This subcategory has a grade B
recommendation for its inclusion in the ‘borderline
RHD’ category.
Pathological aortic regurgitation (Box 2) in the absence
of a well-defined valvular lesion (bicuspid valves or dilated
aortic root) is extremely rare in children who are at low
risk of ARF, RHD, or both.78,79
Among 1,360 children in
Israel79
and 396 children in New Zealand78
with structur-
ally normal hearts and low risk for RHD, none had patho-
logical aortic regurgitation (Level 2++ evidence). Among
1,142 high-risk children in New Zealand, the prevalence of
isolated pathological aortic regurgitation was 0.4%.19
This
increased prevalence of pathological aortic regurgitation
in high-risk school-aged children is, therefore, likely to
represent early RHD. Without associated morphological
features, the etiology cannot be confirmed; therefore, iso-
lated pathological aortic regurgitation is categorized as
‘borderline RHD’ in people aged ≤20 years.
Criteria for pathological mitral regurgitation
Wide experience differentiates physiological from patho
logical regurgitation.15,68,78,81–87
For a regurgitant jet to be
considered pathological, all four criteria must be met
(Box 2). The regurgitant MV jet must be pan-systolic,
Box 3 | Morphological features of RHD
Features in the MV
■■ AMVL thickening* ≥3 mm (age-specific)‡
■■ Chordal thickening
■■ Restricted leaflet motion§
■■ Excessive leaflet tip motion during systole||
Features in the AV
■■ Irregular or focal thickening¶
■■ Coaptation defect
■■ Restricted leaflet motion
■■ Prolapse
Important considerations
*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 21–40 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.
§
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.
Abbreviations: AMVL, anterior mitral valve leaflet; AV, aortic valve; MV, mitral valve;
RHD, rheumatic heart disease.
REVIEWS

high-velocity (≥3 m/s), visible from two views, and ≥2 cm
in length from at least one view. The 2 cm (rather than
the previously used 1 cm) jet length increases specific-
ity15
and decreases sensitivity, and will reduce over
diagnosis of pathological mitral regurgitation. This 2 cm
cut-off value is supported by data from healthy children
in populations with a low prevalence of RHD.78
The
requirements on Doppler echocardiography (high velo
city and pan-systolic) ensure that closing volumes and
trivial, but genuine, regurgitant jets81–83
are differentiated
from clinically relevant valve regurgitation. All substan-
tial regurgitant jets should produce a high velocity signal
with a complete envelope on continuous-wave Doppler
echocardiography. Data from New Zealand shows that,
after the exclusion of individuals with congenital defects,
0.5% of children who were at low risk for ARF, RHD,
or both had pathological MV regurgitation according
to the current criteria.78
The preliminary findings of the
Australian gECHO study also support the low preva-
lence of pathological mitral regurgitation among healthy
low-risk children (J. Carapetis, unpublished data).
By contrast, trivial MV regurgitation that does not meet
all four criteria (in Box 2) is very common, ranging from
3% to 45%,81–83
and should be considered to be physio
logical (level 2++ evidence) (grade B recommendation).
Criteria for pathological aortic regurgitation
Trivial aortic regurgitation that does not meet patho-
logical criteria (Box 2) occurs in up to 2% of children
(level 2++ evidence),78,81–83
and becomes more frequent
with advancing age (level 2++ evidence).71,72,74,82,84,85
For
aortic regurgitation to be considered pathological, it must
meet all four criteria (Box 2). The regurgitant jet must
be pan-diastolic, high velocity (≥3 m/s), visible from two
views, and ≥1 cm in length from at least one view. Such
pathological aortic regurgitation is extremely rare in chil-
dren with structurally normal hearts, with two studies
reporting 0% prevalence78,79
and similar data being found
in provisional analysis of the gECHO study (J. Carapetis,
unpublished data) (level 2++ evidence).
Trivial aortic regurgitation that does not meet all four
criteria for pathological aortic regurgitation should be
considered physiological (grade B recommendation).
Morphological features of RHD of the MV
The morphological features of RHD of the MV have
been examined in detail in echocardiographic, surgical,
and postmortem studies. The majority of these studies
involved individuals described as having severe or
advanced disease; however, standard definitions were
absent and inconsistencies were noted in the terminology
used. Morphological changes vary with the acuity of the
disease40
and with age,34
as regurgitant lesions dominate
in the young and mixed or stenotic lesions dominate with
advancing age.34
The morphological criteria of the MV (in
Box 2) is based on Carpentier’s functional classification of
valve disease,88
and are descriptive to avoid colloquialisms
(such as ‘dog-leg’ and ‘hockey-stick’ deformity).
Thickening of the MV leaflet
Valvular thickening has been demonstrated to be a
feature of RHD on echocardiography,35–40,52,86,87,89–95
at
surgery,41,43,96
and on postmortem examinations (level 2++
evidence).45,97,98
Valvular thickening is often most marked
at leaflet tips,45,92
where the chords thicken and can become
incorporated into the leaflet tissue (level 3 evidence).45
Thickening is present in 56–100% of patients with rheum
atic carditis (level 2+ evidence),38–40,43,87,89,92,95,99
and can also
be associated with nodularity (or beading),35,38,39
which is
often most pronounced during an episode of ARF and can
later regress (level 2+ evidence).35,39
Normal valve thickness was shown to be age-related
by Sahasakul et al. in a well-designed postmortem study
(level 2++ evidence),75
and correlation between surgical
and echocardiographic measurements seems to be good if
harmonic imaging is not used, as this modality increases
apparent tissue thickness (level 2+ evidence).39,100–103
On the basis of data from a study of 280 healthy children
in New Zealand,104
the normal echocardiographic thick-
ness of the anterior MV leaflet (AMVL) in school-aged
children is 1.12–2.92 mm (mean ± SD of 2.02 ± 2 mm)
(level 2++ evidence). Two smaller pediatric studies also
support the concept that normal valve thickness is 3 mm
(level 2+ evidence).38–86
Webb et al. demonstrated that measuring the AMVL
thickness during diastole in the parasternal long-axis
view, was associated with a good level of interobserver
agreement.104
To establish the normal range, they mea-
sured the thickest part of the leaflet on a frame with
maximal separation from chordal tissue. The investiga-
tors noted that the measurements of the posterior MV
leaflet were associated with a lower level of agreement.104
Studies of older age groups show increased mean
AMVL thickness. Weissman et al. reported on 100
healthy individuals with a mean age of 41 years and found
the mean AMVL thickness to be 2.38 mm (± 0.57 mm).105
The Framingham echocardiographic study106
assessed a
total of 217 individuals (mean age 57 years), whose mean
AMVL thickness was 3.2 mm (range and standard devia-
tions were not stated). This observed increase of echo-
cardiographic valve thickness relating to age is consistent
with Sahasakul’s postmortem anatomical study.75
The
age-related recommendations in these guidelines were
derived from the above-mentioned studies.38,75,86,104–106
Anterior MV thickness should only be objectively
assessed if images were acquired without harmonic
imaging and the gain settings were optimal for image
Box 4 | Echocardiography machine settings
■■ Nyquist limits for color-Doppler echocardiography should be set on maximum to
avoid overestimation of jet length
■■ Images for assessment of valvular and chordal thickness should be acquired
with harmonics turned off and probes with variable frequency set on ≥2.0 MHz;
low frequency settings and harmonics exaggerate valve and chordal thickness
■■ Gain settings should be adjusted to achieve optimal resolution; images
acquired with an excessive gain setting will not be suitable for objective valve
thickness measurements
■■ All other settings (including depth, sector size, and focus) should also be
optimized to achieve maximal frame rate (ideally 30–60 frames per second)
and resolution
REVIEWS

resolution (grade B recommendation). Cut-off values for
abnormally thickened valves are ≥3 mm for individuals
aged 0–19 years, ≥4 mm for individuals aged 20–39 years,
and ≥5 mm for individuals aged ≥40 years (grade B
recommendation). Valve thickness measurements
obtained using harmonic imaging should be cautiously
interpreted and we recommended that a thickness up to
4 mm be considered normal in individuals aged ≤20 years
(grade D recommendation). Objective assessment of
thickness of the posterior MV leaflet is less reproducible
and, at this stage, is not included in the echocardiographic
criteria (grade D recommendation).
Chordal thickening
Chordal thickening is a feature of RHD on echocardio-
graphic,35–40,52,86,87,89–95
surgical,41,43
and postmortem45,62,97,99
examinations (level 2+ evidence). Unlike valvular thick-
ness, no standardized objective way of assessing chordal
thickness on echocardiography exists, and its assessment
remains subjective.89
Chordal thickening can be identi-
fied in 100% of those with severe mitral stenosis requiring
balloon valvotomy,89
35–44% of those who require surgery
for predominant mitral regurgitation,43
and in 37% of
outpatients with RHD (C. Mota, unpublished data).
Chordal thickening must be subjectively assessed
without utilizing harmonic imaging and at optimal gain
settings (grade D recommendation).
Excessive leaflet tip motion
Excessive leaflet tip motion is defined as displacement
of the tip or edge of the involved leaflet towards the left
atrium, resulting in abnormal coaptation and regur-
gitation (Figure 1a,b). Excessive MV leaflet tip motion
of the AMVL or posterior MV leaflet is the result of
elongation or rupture of the primary chords (level 2++
evidence)41,42,44,80
and, together with annular dilatation,
is the predominant mechanism of mitral regurgitation
in the setting of acute rheumatic carditis (level 2+ evi-
dence).80
Excessive MV leaflet tip motion has been well
described in echocardiographic,34,35,37,38,41,80,87,95,107,108
surgi
cal,34,41–43,80,96,109–112
and anatomical44,98
studies (level 2+
evidence). Prevalence among patients with RHD ranges
from 11% to 97%,34,35,37,41–43,80,95,108,109,111
depending on
the population that is sampled. Excessive MV leaflet
tip motion is most common among young rheumatic
patients with pure mitral regurgitation,34,40
and is less
common beyond the third decade of life, when mitral
stenosis predominates (level 2+ evidence).34
Although the above definition of excessive leaflet tip
motion is the surgical definition of valvular prolapse, as
described by Barlow and Carpentier,80,88,113,114
the standard
echocardiographic definition of MV prolapse does not
need to be met in the setting of RHD, as that refers to
a different disease process. MV prolapse is a degenera-
tive condition that is common with advancing age, and
is defined as ≥2 mm billowing (or hooding) of the body
leaflet tissue into the left atrium during systole, which
must be visible from at least two echocardiographic views,
including the parasternal long-axis view (Figure 1c).115
The free edges of the leaflet generally remain in apposi-
tion below the plane of the MV annulus,88,113,114
and MV
prolapse might or might not lead to MV regurgitation.115
Billowing of the leaflet bodies is seldom the predominant
feature of rheumatic carditis.114
In the pediatric population, chordal rupture (an etiology
of excessive leaflet tip motion) predominantly occurs in
the setting of rheumatic carditis and is present in 7–17% of
patients undergoing rheumatic MV repair (level 2++ evi-
dence).40,41,43,80
Only a few case reports exist where chordal
rupture was attributed to other etiologies, such as severe
connective tissue disorders or myxomatous degeneration,
in children.116,117,11
In adults, the most-common etiology of
chordal rupture is myxomatous degeneration, followed by
endocarditis, and then RHD (level 1+ evidence).119
Excessive leaflet motion of the anterior or posterior MV
leaflet tips is a morphological feature of RHD (grade B
recommendation). This criterion applies to individuals
aged 35 years (grade C recommendation) as, beyond
the third decade of life, RHD is rarely characterized by
excessive leaflet motion and almost never without associ
ated restriction of other leaflet scallops and chordal or
valvular thickening. In the presence of a flail leaflet in
the young (≤20 years), only one morphological feature
is required to meet the morphological criteria for RHD,
if other causes have been excluded by clinical assessment
(grade C recommendation).
Figure 1 | Schematic images of the MV in systole. a | A normal MV. b | RHD with excessive leaflet tip motion, which results
in abnormal coaptation and regurgitation, but usually does not meet the echocardiographic definition of ‘MV prolapse’.
c | Echocardiographic MV prolapse, defined by 2 mm billowing of the leaflet tissue into the left atrium. In
echocardiographic MV prolapse (c), coaptation of leaflets often remains normal, as the free edges of the leaflet stay in
apposition below the plane of the MV annulus. Abbreviation: AMVL, anterior MV leaflet; MV, mitral valve; PMVL, posterior
MV leaflet; RHD, rheumatic heart disease.
AMVL
PMVL
2 mm
a b c
REVIEWS

Restricted MV leaflet motion
Restricted leaflet motion is the result of chordal shorten-
ing, chordal fusion, leaflet thickening, calcification, or
commissural fusion (level 2+ evidence).51,88
This condition
is one of the hallmarks of RHD and is observed in 100% of
patients with pure mitral stenosis or mixed lesion of the
MV (level 2++ evidence).34,35,92
In the setting of predomi-
nant mitral regurgitation, restricted MV leaflet motion is
present in 20–60% of patients.35,38–42,112
This phenomenon
is more common in individuals with chronic or estab-
lished RHD,34,35
and is more prevalent with advancing age
(level 2+ evidence).34,40
Generally absent during the first
episode of ARF,35
restricted MV leaflet motion develops
with time or recurrences.35
Restricted MV leaflet motion is diagnosed with real-
time diastolic imaging, and can affect either the anterior,
posterior, or both leaflets. When the anterior leaflet is
affected in association with valvular thickening, the terms
‘hockey stick’,47
‘dog-leg’, or ‘elbow’ deformity have been
used and reflect the combination of these two morpho
logical changes (Figure 2). Restricted motion of the pos-
terior MV leaflet is a hallmark of RHD and, when severe,
gives rise to the classic immobile appearance.
Restricted leaflet motion (the result of chordal shorten-
ing, chordal fusion, leaflet thickening, calcification, and
commissural fusion), is one of the morphological features
of RHD of the MV leaflet (grade B recommendation).
Morphological RHD features of the AV
Isolated disease of the AV is relatively rare and a paucity
of echocardiographic studies that systematically describe
morphological changes associated with rheumatic AV
disease exists in the English literature.36,95,120
The morpho-
logical changes associated with RHD of the AV have been
well described in surgical studies that have focused on AV
repair.121–126
As a result, the echocardiographic criteria for
morphological features of AV disease are extrapolated
from surgical and postmortem findings and are based on
Carpentier’s functional classification of AV disease.88
Irregular or focal thickening, coaptation defect,
restricted leaflet motion, and excessive leaflet motion are
echocardiographic features of RHD of the AV. However,
these characteristics are not unique to RHD and other
etiologies should be excluded by echocardiography and
clinical assessment (grade B recommendation).
AV thickening
The normal AV is a very thin structure 0.67 ± 0.21 mm
(mean ± SD), as established onpostmortem examinations.75
Because the valve is so thin, standardized, objective echo-
cardiographic measurements of its thickness have not
been established. One large, population-based echocardio-
graphic study of adults showed that subjective assessment
of AV thickness is acceptable and is associated with good
interobserver and intraobserver agreement (level 2+ evi-
dence).127
Surgical studies have demonstrated that aortic
leaflet thickening is present in 41–100% of individuals with
rheumatic aortic regurgitation (level 2++ evidence).121–126
Of these surgical studies, the one in which the oldest popu-
lation (mean age 51 years) was assessed had the highest
prevalence of AV thickening,126
and the study in which the
youngest cohort of rheumatic patients (mean age 12 years)
was observed demonstrated the lowest prevalence of surgi-
cally relevant valvular thickening.121
This thickening can be
nodular or irregular,64
commonly occurs at the free edge
of the AV, and can lead to abnormal coaptation and aortic
regurgitation. Surgically restoring normal valve thickness
alone can improve valvular coaptation.88,122,126
Coaptation defect
Surgical studies have described the most-common causes
of rheumatic aortic regurgitation as leaflet retraction and
rolling of the leaflet edges that result in a central (often
triangular shaped) coaptation defect that can be visualized
on 2D echocardiography (level 2+ evidence).121–125
Restricted leaflet motion
In an echocardiographic study, restricted aortic-leaflet
motion was found in 76% of 25 patients and was judged
to be the predominant mechanism of rheumatic aortic
regurgitation (level 2+evidence).120
In this echocardio-
graphic study, only one patient had excessive leaflet
motion and the remainder (20%) had normal leaflet
motion. In individuals with normal leaflet motion, aortic
regurgitation was probably the result of leaflet retrac-
tion and thickening. The echocardiographic finding
of restricted leaflet motion corresponds to the surgi-
cal description of ‘commissural fusion’ with or without
associated valvular thickening and calcification. In sur-
gical studies, a minor degree of commissural fusion is
surprisingly prevalent, even in predominantly regurgi-
tant valves, and ranges from 11% to 73.8% (level 2+evi-
dence).121–123
Similarly to AV thickening, commissural
fusion was less frequent in children.121
Prolapse or excessive leaflet motion
Excessive mobility or prolapse of the AV is present when
aortic cusp tissue extends below the level of the aortic
annulus, and has been demonstrated to be a feature of
RHD in echocardiographic,36,95,120
surgical,121–123
and
pathological44
studies (level 2++ evidence). AV prolapse
should only be diagnosed when associated with patho-
logical (commonly eccentric) regurgitation. Prolapse of
the aortic leaflet is not specific to RHD and care must be
exercised to exclude other etiologies by taking clinical
context into consideration.44,128
In a cohort of individuals
Figure 2 | Schematic images of the MV in diastole. a | A normal MV. b | A rheumatic
MV with thickened and restricted anterior and posterior leaflets. Abbreviations:
AMVL, anterior MV leaflet; MV, mitral valve; PMVL, posterior MV leaflet.
AMVL
PMVL
a b
REVIEWS

with acute rheumatic carditis, 11% of 66 patients (mean
age 12.5 years) had AV prolapse demonstrated on echo-
cardiography.95
Surgical studies that report on AV repair
techniques quote the prevalence of prolapse in rheumatic
aortic regurgitation to be 3.8–59%.121–123
Of the three sur-
gical studies, the highest prevalence was in the study with
the youngest population (mean age 12 years),121
and the
lowest prevalence was in the oldest population (mean age
40 years).122
Limitations of echocardiographic criteria
The 2012 WHF criteria for echocardiographic diagnosis
of RHD aim to differentiate mild RHD from normal
findings on echocardiography. They recognize that
more-sophisticated imaging modalities and quantita
tive techniques might not be possible using the portable
echocardiographic machines available in many resource-
poor settings. The criteria are, therefore, formulated on
the basis of 2D, color-Doppler, and continuous-wave-
Doppler echocardiography. The criteria to differenti-
ate physiological from pathological regurgitation are
derived from historical studies, some of which date back
a number of decades; however, they have been tested on
large cohorts of healthy children over the past 5 years.
Over the past 10 years, advances in the quantification of
valvular regurgitation and stenosis have occurred. The
vena contracta, the proximal isovelocity surface area,
and the effective regurgitant orifice area can now all be
measured to allow for grading of severity of valvular
regurgitation. These newer techniques allow for the dif-
ferentiation of mild from moderate and moderate from
severe disease. However, to date, little attention has been
focused on assessing their utility to differentiate physio
logical from pathological regurgitation. Importantly,
their use in the setting of RHD is limited, owing to the
eccentric nature of rheumatic regurgitant jets. Abnormal
loading conditions—such as fluid overload, hypertension,
and dehydration—can alter the severity of regurgitation
regardless of the method used (for example, might alter
regurgitant jet length). Fortunately, loading conditions
are generally normal in otherwise-healthy children who
undergo routine echocardiographic screening for RHD.
Structural or morphological changes are also recog-
nized to often only affect leaflet segments. As a result,
in children, pathology can be missed with 2D imaging
if only standard, adult-style echocardiographic views are
assessed. Technical pitfalls of image acquisition and echo-
cardiographic machine settings must always be addressed
at screening sites, as image qualityul is operator-
dependent and can substantially affect the interpreta-
tion of images. These 2012 WHF echocardiographic
criteria will likely require substantial modification as
technological advancements and increased affordabil-
ity of more-sophisticated portable machines allow for
better differentiation of physiological from pathological
echocardiographic findings in resource-poor countries.
Implications for RHD screening
Value of echocardiography screening programs
To date, perhaps the greatest impact of echocardiography
screening programs for RHD has been to stimulate inter-
est in, and advocacy for, RHD control. Echocardiography
has a role in defining RHD disease burden for various
regions, which assists health ministries to set priorities.
In addition, by identifying previously undiagnosed cases
of RHD, enabling these patients to commence second-
ary prophylaxis, echocardiography also has a substantial
impact on individual patients.
However, the expectation that echocardiographic
screening will directly lead to reductions in RHD disease
burden has yet to be proven. To date, investigators have
focused on defining disease prevalence through sentinel
studies, rather than evaluating the larger-scale impact
on disease control. Important gaps remain in our know
ledge that limit our ability to make definite recommenda-
tions about how, and in what settings, echocardiographic
screening for RHD should be undertaken, and how
abnormal findings should be managed.
Requirements for a population screening test
Echocardiographic screening for RHD meets many of the
requirements for disease screening. Firstly, an obvious
disease burden exists that is detectable in its preclinical
phase. Secondly, a suitable test is available; the echo
cardiographic standardization study provides the basis
for critically examining the question of whether echo
cardiography has appropriate sensitivity and specificity
as a screening tool. Thirdly, early treatment is likely to
lead to better outcomes.7–9,129
Arguably the most-important gap in our knowledge is
that the natural history of the condition is not fully under-
stood. Although the natural histories of ARF and clini-
cal RHD are known,3,6,7,23,130
whether disease progression
also occurs for those with subclinical disease detected
by echocardiography (without an accompanying clinical
pathological murmur) is unknown for both ‘definite’ and
‘borderline’ RHD.
Other requirements of an ideal screening test include
patient acceptability, defined intervals for repeating
the test, adequate health-service provision for the extra
clinical workload, and costs balanced against benefits.131
Regional and country-specific variations will affect how
well many of these criteria are met.
We emphasize the importance of having a well-run and
effective secondary prophylaxis program in place before
embarking on larger-scale screening, and the capacity
to upscale this program with newly detected patients.132
Countries with the highest disease burden might have the
fewest resources. In some regions, screening might be con-
sidered logistically unfeasible or secondary prophylaxis
insufficiently developed to recommend screening.
Who to screen and how to screen
Echocardiographic screening should only be considered in
settings where a high pretest probability of RHD exists;
in other words, in geographic locations with a high preva-
lence of RHD. The definition of ‘high prevalence’ is not
quantified here, as many countries or regions that are
planning RHD screening programs do not have reliable
epidemiological data to estimate background prevalence.
REVIEWS

In such regions, other data might be useful indicators of
a high disease burden (for example, hospitalizations for
ARF, RHD, or both). Alternatively, echocardiographic
screening could be considered as an epidemiological tool
to help establish disease burden.
The reader is referred to an overview of optimal active-
surveillance and passive-surveillance RHD programs.23
Resource-limited countries might still chose to preselect
patients with pathological murmurs for echocardio
graphy. This strategy allows a much larger population
to be screened for the same monetary value. However,
because auscultation is poorly sensitive at detecting
echocardiographically confirmed RHD lesions,14,17,19,22
this model will invariably underestimate the burden of
disease and leave many RHD cases undetected. Successful
screening programs can be conducted in schools17,19,21
or
be community-based.18,22
Use of handheld echo machines
AnimportantdebatearoundasymptomaticRHDconcerns
the most-appropriate model for undertaking screening in
resource-poor areas. Despite the increased affordability of
portable echocardiography machines over the past 5 years,
they remain exorbitantly priced for most low-income
countries. The ultraportable, handheld machines that
have been marketed for point-of-care echocardiography
in intensive care and trauma units might provide a cheaper
option.133
Although these pocket-sized imaging devices
are capable of producing 2D and color images, and are
simple to use by inexperienced staff, they currently cannot
perform either real-time measurements or continuous-
wave Doppler echocardiography. Ultraportability might
not necessarily confer a major additional advantage over
the existing portable machines and the smallness of the
screen could actually be a potential barrier to accurate
interpretation. Furthermore, these devices still require
extensive testing, careful validation, and further techno-
logical refinements before widespread independent use
can be recommended.134
On the basis of current informa-
tion, the diagnostic criteria presented in this article should
not be applied to screening using handheld machines.
Management of patients identified by screening
The uncertainty around the clinical relevance of subclini-
cal echocardiographic changes (see the following section
on future research priorities), and the absence of evidence-
based management protocols, mean that treatment deci-
sions, particularly thresholds for commencement of
secondary prophylaxis, will be influenced by local needs
and experience. A positive screening test should always be
followed by a full clinical assessment by an appropriately
qualified medical officer before initiating management,
which has been highlighted as another workforce issue.19
Management of definite RHD
After a screening test is performed, we recommend that
individuals with echocardiographic findings of ‘definite
RHD’ be considered to have RHD regardless of the pres-
ence or absence of a murmur (providing other etiologies
have been excluded by clinical context), and secondary
prophylaxis should be offered. Notably, no data are avail-
able to estimate the likelihood that an individual with
subclinical ‘definite RHD’ will subsequently develop an
episode of ARF. However, data to support that indivi
duals with mildly clinical ‘definite RHD’ will benefit the
most from secondary prophylaxis exists7–9
and, therefore,
withholding widely accepted treatment could be seen
as unethical.
Management of borderline RHD
The ‘borderline RHD’ echocardiographic category was
established to improve the sensitivity of the test at the
expense of specificity. These echocardiographic findings
are more common among children from regions where
RHD is highly prevalent than those from low-prevalence
regions.78
Changes consistent with ‘borderline RHD’
can, however, also occur in individuals considered to be
at low risk for ARF. Minor changes in ‘low-risk patients’
should be considered as normal variants. In regions of
high background prevalence of RHD, borderline echo-
cardiographic findings (with or without associated clini-
cal pathological murmur) are more likely to represent
rheumatic changes.19
In this population, the manage-
ment of ‘borderline RHD’ is not clear-cut. Some clinicians
might choose to offer secondary prophylaxis (accepting
that this strategy will inevitably lead to treatment of some
healthy children),129
and some might choose close clinical
follow-up and repeat echocardiography.
Future research priorities
Validation of the diagnostic criteria, including a blinded
review of large series of echocardiographic studies, is a
high priority. We are currently working towards a system
that will allow new investigators to test their accuracy
in applying the criteria using DVDs or online review
of echocardiograms.
An urgent need to evaluate the clinical relevance of
‘definite RHD’ in the absence of a pathological murmur
(that is, subclinical disease) and of ‘borderline RHD’
exists. A combination of studies will be needed. High-
quality, normal-range data are needed for children at
low risk of RHD, but living in high-prevalence regions.
Follow-up studies of children with abnormal and normal
echocardiograms, to compare the rate of progression of
echocardiographic changes as well as subsequent inci-
dence of ARF, should be achievable within the next
5 years. A randomized, controlled trial of secondary
prophylaxis versus no prophylaxis would provide high-
level evidence, but would necessitate an international,
multicenter study in regions with high-compliance to
secondary prophylaxis.
Large-scale screening programs aimed at disease
control, rather than just defining RHD epidemiology,
are required. Economic and cost-effectiveness evaluation
can then be calculated. In the meantime, mathematical
models using existing data could allow prediction of
effectiveness of large-scale screening programs.
Realistic estimates of disease burden should add
impetus to efforts to produce an effective group A
streptococcal vaccine.18
Moreover, echocardiography
REVIEWS

will have an important role in trials assessing the safety
and the efficacy of group A streptococcal vaccines, and in
RHD epidemiology for targeting vaccine delivery.
Conclusions
The purpose of these diagnostic guidelines is to define
the minimum echocardiographic criteria for RHD in
individuals without a clear history of ARF. The guide-
lines can be used in the setting of RHD screening pro-
grams or as a clinical tool when a diagnosis of RHD is
being considered. In all circumstances, these guidelines
should be used in conjunction with clinical findings
and evidence of risk factors for RHD. Decisions to com-
mence secondary prophylaxis, and about the duration
of such treatment, should be made on the basis of local
or regional guidelines wherever possible. The diagnostic
echocardiographic definitions of RHD in these guide-
lines have been made on the basis of the best evidence
available at this time and will need revision in future, as
more experience is gained and research is performed. In
the meantime, the investigators plan to work on a system
to ensure that the criteria can be made widely available,
and to support clinicians and public-health officials in all
regions of the world to be able to apply them accurately.
1. Carapetis, J. R., Steer, A. C., Mulholland, E. K.
Weber, M. The global burden of group A
streptococcal diseases. Lancet Infect. Dis.
5, 685–694 (2005).
2. Special Writing Group of the Committee on
Rheumatic Fever and Kawasaki Disease of the
Council on Cardiovascular Disease in the Young
of the American Heart Association. Guidelines for
the diagnosis of rheumatic fever. Jones Criteria,
1992 update. JAMA 268, 2069–2073 (1992).
3. World Health Organisation. Rheumatic Fever and
Rheumatic Heart Disease: Report of a WHO
Expert Consultation, Geneva, 29 October–1
November 2001. WHO [online] www.who.int/
entity/cardiovascular_diseases/resources/
trs923/en/ (2010).
4. National Heart Foundation of Australia and the
Cardiac Society of Australia and New Zealand.
Diagnosis and management of acute rheumatic
fever and rheumatic heart disease in Australia
—an evidence-based review. Heart Foundation
[online] http://www.heartfoundation.org.au/
Information-For-Professionals/
Clinical-Information/Pages/arf-rhd.aspx (2006).
5. Heart Foundation of New Zealand and Cardiac
Society of Australia and New Zealand. New
Zealand guidelines for rheumatic fever 1:
diagnosis, management and secondary
prevention. Heart Foundation [online]
http://www.heartfoundation.org.nz/uploads/
Rheumatic%20fever%20guideline%201(5).pdf
(2006).
6. Feinstein, A. R. et al. Rheumatic fever in children
and adolescents. A long-term epidemiologic
study of subsequent prophylaxis, streptococcal
infections, and clinical sequelae. vi. Clinical
features of streptococcal infections and
rheumatic recurrences. Ann. Intern. Med.
60 (Suppl. 5), 68–86 (1964).
7. Tompkins, D. G., Boxerbaum, B. Liebman, J.
Long-term prognosis of rheumatic fever patients
receiving regular intramuscular benzathine
penicillin. Circulation 45, 543–551 (1972).
8. Kassem, A. S., el-Walili, T. M., Zaher, S. R.
Ayman, M. Reversibility of mitral regurgitation
following rheumatic fever: Clinical profile and
echocardiographic evaluation. Indian J. Pediatr.
62, 717–723 (1995).
9. Milliken, A. The short term morbidity of acute
rheumatic fever in children and youth under the
age of 20 years at first diagnosis in Auckland,
1998–1999 (The University of Auckland,
Auckland, 2003).
10. Talbot, R. G. Rheumatic fever and rheumatic
heart disease in the Hamilton health district: II.
Long term follow-up and secondary prophylaxis.
N. Z. Med. J. 97, 634–637 (1984).
11. Abbasi, A. S., Hashmi, J. A., Robinson, R. D. Jr.,
Suraya, S. Syed, S. A. Prevalence of heart
disease in school children of Karachi. Am. J.
Cardiol. 18, 544–547 (1966).
12. Maharaj, B. et al. Screening for rheumatic heart
disease amongst black school children in
Inanda, South Africa. J.Trop. Pediatr. 33, 60–61
(1987).
13. Kumar, P., Garhwal, S. Chaudhary, V. Rheumatic
heart disease: a school survey in a rural area of
Rajasthan. Indian Heart J. 44, 245–246 (1992).
14. Steer, A. C., Adams, J., Carlin, J., Nolan, T.
Shann, F. Rheumatic heart disease in school
children in Samoa. Arch. Dis. Child. 81, 372
(1999).
15. Steer, A. C. et al. High prevalence of rheumatic
heart disease by clinical and echocardiographic
screening among children in Fiji. J. Heart Valve
Dis. 18, 327–335 (2009).
16. Marijon, E. et al. Rheumatic heart disease
screening by echocardiography: The inadequacy
of world health organization criteria for
optimizing the diagnosis of subclinical disease.
Circulation 120, 663–668 (2009).
17. Carapetis, J. R. et al. Evaluation of a screening
protocol using auscultation and portable
echocardiography to detect asymptomatic
rheumatic heart disease in Tongan
schoolchildren. Nat. Clin. Pract. Cardiovasc. Med.
5, 411–417 (2008).
18. Paar, J. A. et al. Prevalence of rheumatic heart
disease in children and young adults in
Nicaragua. Am. J. Cardiol. 105, 1809–1814
(2010).
19. Webb, R. H. et al. Optimising echocardiographic
screening for rheumatic heart disease in New
Zealand: not all valve disease is rheumatic.
Cardiol.Young 21, 436–443 (2011).
20. Reeves, B. M., Kado, J. Brook, M. High
prevalence of rheumatic heart disease in Fiji
detected by echocardiography screening.
J. Paediatr. Child Health 47, 473–478 (2011).
21. Bhaya, M., Panwar, S., Beniwal, R. Panwar, R. B.
High prevalence of rheumatic heart disease
detected by echocardiography in school children.
Echocardiography 27, 448–453 (2010).
22. Marijon, E. et al. Prevalence of rheumatic heart
disease detected by echocardiographic
screening. N. Engl. J. Med. 357, 470–476
(2007).
23. Carapetis, J., Parr, J. Cherian, T. Standardization
of epidemiologic protocols for surveillance of
post-streptococcal sequelae: acute rheumatic
fever, rheumatic heart disease and acute post-
streptococcal glomerulonephritis. Department of
Health and Human Services, National Institutes of
Health [online] http://www.niaid.nih.gov/topics/
strepThroat/Documents/groupasequelae.pdf
(2010).
24. Nair, R., Aggarwal, R. Khanna, D. Methods
of formal consensus in classification/diagnostic
criteria and guideline development. Semin.
Arthritis Rheum. 41, 95–105 (2011).
25. Scottish Intercollegiate Guidelines Network.
SIGN 50: a guideline developer’s handbook.
Scottish Intercollegiate Guidelines Network
[online] http://www.sign.ac.uk/guidelines/
fulltext/50/annexb.html (2011).
26. Jaine, R., Baker, M. Venugopal, K. Epidemiology
of acute rheumatic fever in New Zealand 1996–
2005. J. Paediatr. Child Health 44, 564–571
(2008).
27. Spinetto, H., Lennon, D. Horsburgh, M.
Rheumatic fever recurrence prevention: a nurse
led programme of 28 day penicillin in an area
of high endemnicity. J. Paediatr. Child Health 47,
228–234 (2011).
28. Jaine, R., Baker, M. Venugopal, K. Acute
rheumatic fever associated with household
crowding in a developed country. Pediatr. Infect.
Dis. J. 30, 315–319 (2011).
29. Longo-Mbenza, B. et al. Survey of rheumatic
heart disease in school children of Kinshasa
town. Int. J. Cardiol. 63, 287–294 (1998).
30. Sultan, F. A. et al. Rheumatic tricuspid valve
disease: an evidence-based systematic
overview. J. Heart Valve Dis. 19, 374–382
(2010).
31. Alkhalifa, M. S., Ibrahim, S. A. Osman, S. H.
Pattern and severity of rheumatic valvular
lesions in children in Khartoum, Sudan. East.
Mediterr. Health J. 14, 1015–1021 (2007).
32. Saleh, H. K. Pattern of rheumatic heart disease
in Southern Yemen. Saudi Med. J. 28, 108–113
(2007).
33. Aurakzai, H. A. et al. Echocardiographic profile
of rheumatic heart disease at a tertiary cardiac
centre. J.Ayub Med. Coll.Abbottabad. 21,
122–126 (2009).
34. Marcus, R. H., Sareli, P., Pocock, W. A.
Barlow, J. B. The spectrum of severe rheumatic
mitral valve disease in a developing country.
Correlations among clinical presentation,
surgical pathological findings, and hemodynamic
sequelae. Ann. Intern. Med. 120, 177–183
(1994).
35. Vasan, R. S. et al. Echocardiographic evaluation
of patients with acute rheumatic fever and
rheumatic carditis. Circulation 94, 73–82 (1996).
36. Yuko-Jowi, C. Bakari, M. Echocardiographic
patterns of juvenile rheumatic heart disease at
the Kenyatta National Hospital, Nairobi. East Afr.
Med. J. 82, 514–519 (2005).
37. Lembo, N. J. et al. Mitral valve prolapse in
patients with prior rheumatic fever. Circulation.
77, 830–836 (1988).
38. Atalay, S., Ucar, T., Ozcelik, N, , Ekici, F. Tutar, E.
Echocardiographic evaluation of mitral valve in
patients with pure rheumatic mitral regurgitation.
Turk. J. Pediatr. 49, 148–153 (2007).
REVIEWS

39. Vijayalakshmi, I. B., Vishnuprabhu, R. O.,
Chitra, N., Rajasri, R. Anuradha, T. V. The
efficacy of echocardiographic criterions for the
diagnosis of carditis in acute rheumatic fever.
Cardiol.Young 18, 586–592 (2008).
40. Camara, E. J., Neubauer, C., Camara, G. F.
Lopes, A. A. Mechanisms of mitral valvar
insufficiency in children and adolescents with
severe rheumatic heart disease: an
echocardiographic study with clinical and
epidemiological correlations. Cardiol.Young
14, 527–532 (2004).
41. Kalangos, A. et al. Anterior mitral leaflet prolapse
as a primary cause of pure rheumatic mitral
insufficiency. Ann.Thorac. Surg. 69, 755–761
(2000).
42. Chauvaud, S. et al. Long-term (29 years) results
of reconstructive surgery in rheumatic mitral
valve insufficiency. Circulation 104 (12 Suppl. 1),
I12–I15 (2001).
43. Skoularigis, J., Sinovich, V., Joubert, G. Sareli,
P. Evaluation of the long-term results of mitral
valve repair in 254 young patients with
rheumatic mitral regurgitation. Circulation
90 (5 Pt 2), II167–II174 (1994).
44. Tomaru, T. et al. Postinflammatory mitral and
aortic valve prolapse: a clinical and pathological
study. Circulation 76, 68–76 (1987).
45. Ungar, H. Ben-Ishay, Z. Rheumatic and age
changes of the heart in Israel: pathological and
statistical study. Isr. J. Med. Sci. 1, 50–61 (1965).
46. van der Bel-Kahn, J. Becker, A. E. The surgical
pathology of rheumatic and floppy mitral valves.
Distinctive morphologic features upon gross
examination. Am. J. Surg. Pathol. 10, 282–292
(1986).
47. Feigenbaum, H., Armstrong, W. F. Ryan, T. (Eds)
Feigenbaum’s Echocardiography, 6th edn Vol. 1
(Lippincott Williams Wilkins, Philadelphia,
2005).
48. Waller, B. F., Howard, J. Fess, S. Pathology of
mitral valve stenosis and pure mitral
regurgitation—Part I. Clin. Cardiol. 17, 330–336
(1994).
49. Iung, B. et al. Valvular heart disease in the
community: a European experience. Curr. Prob.
Cardiol. 32, 609–661 (2007).
50. Olson, L. J., Subramanian, R., Ackermann, D. M.,
Orszulak, T. A. Edwards, W. D. Surgical
pathology of the mitral valve: a study of 712
cases spanning 21 years. Mayo Clin. Proc.
62, 22–34 (1984).
51. Ratnakar, K. S., Rajagopal, P. Somaraju, B.
Surgical pathology of mitral valves—the Indian
scene. Int. J. Cardiol. 24, 124–126 (1989).
52. Wilkins, G. T., Weyman, A. E., Abascal, V. M.,
Block, P. C. Palacios, I. F. Percutaneous
balloon dilatation of the mitral valve: an analysis
of echocardiographic variables related to
outcome and the mechanism of dilatation.
Br. Heart J. 60, 299–308 (1988).
53. Moore, P. et al. Valvular heart disease: severe
congenital mitral stenosis in infants. Circulation
89, 2099–2106 (1994).
54. McElhinney, D. B. et al. Current management of
severe congenital mitral stenosis: outcomes of
transcatheter and surgical therapy in 108 infants
and children. Circulation 112, 707–714 (2005).
55. Serraf, A. et al. Congenital mitral stenosis with
or without associated defects: an evolving
surgical strategy. Circulation 102 (19 Suppl. 3),
III166–III171 (2000).
56. Selamet Tierney, E. S. et al. Echocardiographic
predictors of mitral stenosis-related death or
intervention in infants. Am. Heart J. 156,
384–390 (2008).
57. Akram, M. R., Chan, T., McAuliffe, S.
Chenzbraun, A. Non-rheumatic annular mitral
stenosis: prevalence and characteristics.
Eur. J. Echocardiogr. 10, 103–105 (2009).
58. Chockalingam, A., Gnanavelu, G., Elangovan, S.
Chockalingam, V. Clinical spectrum of chronic
rheumatic heart disease in India. J. Heart Valve
Dis. 12, 577–581 (2003).
59. Tantchou Tchoumi, J. C. Butera, G. Rheumatic
valvulopathies occurence, pattern and follow-up
in rural area: the experience of the Shisong
Hospital, Cameroon. Bull. Soc. Pathol. Exot.
102, 155–158 (2009).
60. Essien, I. O. et al. One year echocardiographic
study of rheumatic heart disease at Enugu,
Nigeria. Niger. Postgrad. Med. J. 15, 175–178
(2008).
61. Sani, M. U., Karaye, K. M. Borodo, M. M.
Prevalence and pattern of rheumatic heart
disease in the Nigerian savannah: an
echocardiographic study. Cardiovasc. J.Afr.
18, 295–299 (2007).
62. Deshpande, J., Vaideeswar, P., Amonkar, G.
Vasandani, S. Rheumatic heart disease in the
past decade: an autopsy analysis. Ind. Heart J.
54, 676–680 (2002).
63. Ozer, O., Davutoglu, V., Sari, I., Akkoyun, D. C.
Sucu, M. The spectrum of rheumatic heart
disease in the southeastern Anatolia endemic
region: results from 1900 patients. J. Heart Valve
Dis. 18, 68–72 (2009).
64. Clawson, B. J. Rheumatic heart disease. An
analysis of 796 cases. Am. Heart J. 20, 454–474
(1940).
65. Ba-Saddik, I. A. et al. Prevalence of rheumatic
heart disease among school-children in Aden,
Yemen. Ann.Trop. Paediatr. 31, 37–46 (2011).
66. Ravisha, M. S., Tullu, M. S. Kamat, J. R.
Rheumatic fever and rheumatic heart disease:
clinical profile of 550 cases in India. Arch. Med.
Res. 34, 382–387 (2003).
67. Dawber, T. R. Stokes, J. 3rd. Rheumatic heart
disease in the Framingham study. N. Engl. J. Med.
255, 1228–1233 (1956).
68. Veasy, L. G., Tani, L. Y. Hill, H. R. Persistence of
acute rheumatic fever in the intermountain area
of the United States. J. Pediatr. 124, 9–16
(1994).
69. Olson, L. J., Subramanian, R. Edwards, W. D.
Surgical pathology of pure aortic insufficiency:
a study of 225 cases. Mayo Clin. Proc. 59,
835–841 (1984).
70. Fox, E. R. et al. Epidemiology of pure valvular
regurgitation in the large middle-aged African
American cohort of the Atherosclerosis Risk
in Communities study. Am. Heart J. 154,
1229–1234 (2007).
71. Reid, C. L., Anton-Culver, H., Yunis, C.
Gardin, J. M. Prevalence and clinical correlates
of isolated mitral, isolated aortic regurgitation,
and both in adults aged 21 to 35 years (from the
CARDIA study). Am.J.Cardiol. 99, 830–834 (2007).
72. Singh, J. P. et al. Prevalence and clinical
determinants of mitral, tricuspid, and aortic
regurgitation (the Framingham Heart Study).
Am. J. Cardiol. 83, 897–902 (1999).
73. Palmieri, V. et al. Aortic root dilatation at sinuses
of valsalva and aortic regurgitation in
hypertensive and normotensive subjects: the
Hypertension Genetic Epidemiology Network
Study. Hypertension 37, 1229–1235 (2001).
74. Klein, A. L. et al. Age-related prevalence of
valvular regurgitation in normal subjects: a
comprehensive color flow examination of 118
volunteers. J.Am. Soc. Echocardiogr. 3, 54–63
(1990).
75. Sahasakul, Y., Edwards, W. D., Naessens, J. M.
Tajik, A. J. Age-related changes in aortic and
mitral valve thickness: implications for two-
dimensional echocardiography based on an
autopsy study of 200 normal human hearts.
Am. J. Cardiol. 62, 424–430 (1988).
76. Yaghoubi, A. R. Raeesi, K. Surgical pathology
of excised heart valves in a referral hospital in
Iran. RMJ 32, 70–72 (2007).
77. Yaghoubi, A. R. et al. A multi-center study
of the pathologies of valvular heart diseases:
5 year analysis of more than 3400 patients in
Iran. J. Cardiovasc. Thorac. Res. 2, 21–27
(2010).
78. Webb, R., Gentles, T., Stirling, J. Wilson, N.
Echocardiographic findings in a low risk
population for rheumatic heart disease (RHD):
implications for screening [Abstract; page 283].
XVIII Lancefield International Symposium [online],
http://www.lancefield2011.it/images/stories/
pdf/riassunti_definitivo_lancefield.pdf (2011).
79. Brand, A., Dollberg, S. Keren, A. The
prevalence of valvular regurgitation in children
with structurally normal hearts: a color Doppler
echocardiographic study. Am. Heart J. 123,
177–180 (1992).
80. Marcus, R. H. et al. Functional anatomy of severe
mitral regurgitation in active rheumatic carditis.
Am. J. Cardiol. 63, 577–584 (1989).
81. Wilson, N. J. Neutze, J. M. Echocardiographic
diagnosis of subclinical carditis in acute
rheumatic fever. Int. J. Cardiol. 50, 1–6 (1995).
82. Choong, C. Y. et al. Prevalence of valvular
regurgitation by Doppler echocardiography in
patients with structurally normal hearts by
two-dimensional echocardiography. Am. Heart J.
117, 636–642 (1989).
83. Yoshida, K. et al. Color Doppler evaluation
of valvular regurgitation in normal subjects.
Circulation 78, 840–847 (1988).
84. Akasaka TMD. et al. Age-related valvular
regurgitation: a study by pulsed Doppler
echocardiography. Circulation 76, 262–265
(1987).
85. Berger, M., Hecht, S. R., Van Tosh, A.
Lingam, U. Pulsed and continuous wave Doppler
echocardiographic assessment of valvular
regurgitation in normal subjects. J.Am. Coll.
Cardiol. 13, 1540–1545 (1989).
86. Caldas, A. M. et al. The case for utilizing more
strict quantitative Doppler echocardiographic
criterions for diagnosis of subclinical rheumatic
carditis. Cardiol.Young 17, 42–47 (2007).
87. Lanna, C. C. D., Tonelli, E., Barros, M. V. L.,
Goulart, E. M. A. Mota, C. C. C. Subclinical
rheumatic valvitis: a long-term follow-up. Cardiol.
Young. 13, 431–438 (2003).
88. Carpentier, A. Cardiac valve surgery—the
“French correction”. J.Thorac. Cardiovasc. Surg.
86, 323–337 (1983).
89. Anwar, A. M. et al. Validation of a new score for
the assessment of mitral stenosis using real-
time three-dimensional echocardiography.
J.Am. Soc. Echocardiogr. 23, 13–22 (2010).
90. Umeda, T., Kuwako, K. Machii, K. M‑mode
and cross-sectional echocardiographic
evaluation of rheumatic mitral valve disease.
Jpn. Circ. J. 43, 297–304 (1979).
91. Wann, L. S., Feigenbaum, H., Weyman, A. E.
Dillon, J. C. Cross-sectional echocardiographic
detection of rheumatic mitral regurgitation.
Am. J. Cardiol. 41, 1258–1263 (1978).
92. Naito, M., Morganroth, J., Mardelli, T. J.,
Chen, C. C. Dreifus, L. S. Rheumatic mitral
stenosis:cross-sectional echocardiographic
analysis. Am. Heart J. 100, 34–40 (1980).
93. Kabukcu, M., Arslantas, E., Ates, I.,
Demircioglu, F. Ersel, F. Clinical,
echocardiographic, and hemodynamic
characteristics of rheumatic mitral valve
stenosis and atrial fibrillation. Angiology 56,
159–163 (2005).
REVIEWS

94. Reid, C. L., McKay, C. R., Chandraratna, P. A.,
Kawanishi, D. T. Rahimtoola, S. H.
Mechanisms of increase in mitral valve area and
influence of anatomic features in double-balloon,
catheter balloon valvuloplasty in adults with
rheumatic mitral stenosis: a Doppler and two-
dimensional echocardiographic study. Circulation
76, 628–636 (1987).
95. Zhou, L. Y. Lu, K. Inflammatory valvular
prolapse produced by acute rheumatic carditis:
echocardiographic analysis of 66 cases of acute
rheumatic carditis. Int. J. Cardiol. 58, 175–178
(1997).
96. Murala, J. S. K. Kumar, A. S. Long-term results
of cusp-level chordal shortening for anterior
mitral leaflet prolapse. Tex. Heart Inst. J. 31,
246–250 (2004).
97. van der Bel-Kahn, J. M. D. Becker, A. E. M. D.
The surgical pathology of rheumatic and floppy
mitral valves: distinctive morphologic features
upon gross examination. Am. J. Surg. Pathol.
10, 282–292 (1986).
98. Nazarian, I. H. Aryanpur, I. Pathology of
chronic rheumatic mitral valvulitis in Iran and its
surgical implications. Jpn. Heart J. 19, 1–11
(1979).
99. Leong, S. W. et al. Morphological findings in 192
surgically excised native mitral valves. Can. J.
Cardiol. 22, 1055–1061 (2006).
100. Gorgulu, S. et al. Influence of different
echocardiographic imaging modes on the
assessment of anterior mitral leaflet thickness.
J. Heart Valve Dis. 14, 204–208 (2005).
101. Hirata, K. et al. Pitfalls of echocardiographic
measurement in tissue harmonic imaging:
in vitro and in vivo study. J.Am. Soc. Echocardiogr.
15, 1038–1044 (2002).
102. Prior, D. L. et al. Impact of tissue harmonic
imaging on the assessment of rheumatic mitral
stenosis. Am. J. Cardiol. 86, 573–576 (2000).
103. Hawkins, K., Henry, J. S. Krasuski, R. A. Tissue
harmonic imaging in echocardiography: better
valve imaging, but at what cost?
Echocardiography 25, 119–123 (2008).
104. Webb, R., Lean, F., Zeng, I. Wilson, N. Objective
measurement of mitral valve thickness with and
without rheumatic heart disease [Abstract]. 5th
World congress of paediatric cardiology and
cardiac surgery [online], http://www.pccs2009.
com/abstract/825.asp (2009).
105. Weissman, N. J. et al. In vivo mitral valve
morphology and motion in mitral valve prolapse.
Am. J. Cardiol. 73, 1080–1088 (1994).
106. Freed, L. A. et al. Mitral valve prolapse in the
general population: the benign nature of
echocardiographic features in the Framingham
Heart Study. J.Am. Coll. Cardiol. 40, 1298–1304
(2002).
107. Uysal, S., Baysal, K., Balat, A. Yukel, M. The
relationship between mitral valve prolapse and
acute rheumatic fever in pediatric patients. Jpn.
Heart J. 33, 585–590 (1992).
108. Wu, M. H., Lue, H. C., Wang, J. K. Wu, J. M.
Implications of mitral valve prolapse in children
with rheumatic mitral regurgitation. J.Am. Coll.
Cardiol. 23, 1199–1203 (1994).
109. Gometza, B., al-Halees, Z., Shahid, M.,
Hatle, L. K. Duran, C. M. Surgery for rheumatic
mitral regurgitation in patients below twenty
years of age. An analysis of failures. J. Heart
Valve Dis. 5, 294–301 (1996).
110. Perier, P. Surgical repair of the prolapsing
anterior leaflet with chordal shortening.
Sem. Thorac. Cardiovasc. Surg. 16, 174–181
(2004).
111. Kumar, A. S., Talwar, S., Saxena, A., Singh, R.
Velayoudam, D. Results of mitral valve repair in
rheumatic mitral regurgitation. Interact.
Cardiovasc.Thorac. Surg. 5, 356 (2006).
112. Bernal, J. M., Rabasa, J. M., Vilchez, F. G.,
Cagigas, J. C. Revuelta, J. M. Mitral valve
repair in rheumatic disease. The flexible
solution. Circulation 88, 1746–1753 (1993).
113. Stark, J., De Leval, M., Tsang, V. T. (Eds) Surgery
for Congenital Heart Defects 3rd
edn (John Wiley
Sons Ltd, London, 2006).
114. Barlow, J. B. Aspects of active rheumatic
carditis. Aust. N. Z. J. Med. 22 (5 Suppl.),
592–600 (1992).
115. American College of Cardiology/American Heart
Association Task Force on Practice Guidelines
et al. ACC/AHA 2006 guidelines for the
management of patients with valvular heart
disease: a report of the American College of
Cardiology/American Heart Association Task
Force on Practice Guidelines (writing committee
to revise the 1998 guidelines for the
management of patients with valvular heart
disease): developed in collaboration with the
Society of Cardiovascular Anesthesiologists:
endorsed by the Society for Cardiovascular
Angiography and Interventions and the Society of
Thoracic Surgeons. Circulation 114, e84–e231
(2006).
116. Baird, C. W., Constantinos, C., Lansford, E.
Pigula, F. A. Mitral valve chordal rupture
masquerades as endocarditis. Pediatr. Cardiol.
28, 297–299 (2007).
117. Jeresaty, R. M., Edwards, J. E. Chawla, S. K.
Mitral valve prolapse and ruptured chordae
tendineae. Am. J. Cardiol. 55, 138–142 (1985).
118. Weidenbach, M., Brenner, R., Rantamaki, T.
Redel, D. A. Acute mitral regurgitation due
to chordal rupture in a patient with neonatal
Marfan syndrome caused by a deletion in exon
29 of the FBN1 gene. Pediatr. Cardiol. 20,
382–385 (1999).
119. Gabbay, U. Yosefy, C. The underlying causes
of chordae tendinae rupture: a systematic
review. Int. J. Cardiol. 143, 113–118 (2010).
120. Cohen, G. I. et al. Color Doppler and two-
dimensional echocardiographic determination
of the mechanism of aortic regurgitation with
surgical correlation. J.Am. Soc. Echocardiogr.
9, 508–515 (1996).
121. Myers, P. O. et al. Aortic valve repair by cusp
extension for rheumatic aortic insufficiency in
children: long-term results and impact of
extension material. J.Thorac. Cardiovasc. Surg.
140, 836–844 (2010).
122. Bernal, J. M. et al. Repair of nonsevere
rheumatic aortic valve disease during other
valvular procedures: is it safe? J.Thorac.
Cardiovasc. Surg. 115, 1130–1135 (1998).
123. Talwar, S., Saikrishna, C., Saxena, A.
Kumar, A. S. Aortic valve repair for rheumatic
aortic valve disease. Ann.Thorac. Surg. 79,
1921–1925 (2005).
124. Bozbuga, N. et al. Midterm results of aortic valve
repair with the pericardial cusp extension
technique in rheumatic valve disease. Ann.
Thorac. Surg. 77, 1272–1276 (2004).
125. Grinda, J. M. et al. Aortic cusp extension
valvuloplasty for rheumatic aortic valve disease:
midterm results. Ann.Thorac. Surg. 74, 438–443
(2002).
126. Tekumit, H. et al. Cusp shaving for concomitant
mild to moderate rheumatic aortic insufficiency.
J. Cardiac Surg. 25, 16–22 (2010).
127. Sashida, Y. et al. Ethnic differences in aortic
valve thickness and related clinical factors.
Am. Heart J. 159, 698–704 (2010).
128. Shapiro, L. M., Thwaites, B., Westgate, C.
Donaldson, R. Prevalence and clinical
significance of aortic valve prolapse. Br. Heart J.
54, 179–183 (1985).
129. Bhaya, M., Beniwal, R., Panwar, S.
Panwar, R. B. Two years of follow-up validates
the echocardiographic criteria for the diagnosis
and screening of rheumatic heart disease in
asymptomatic populations. Echocardiography
28, 929–933 (2011).
130. Carapetis, J. R., Brown, A., Wilson, N. J.
Edwards, K. N. An Australian guideline for
rheumatic fever and rheumatic heart disease:
an abridged outline. Med. J.Aust. 186, 581–586
(2007).
131. Council of Europe Committee of Ministers.
Recommendation no. R(94)11 of the Committee
of Ministers to the Member Sates on screening
as a tool of preventative medicine. Council of
Europe [online] https://wcd.coe.int/wcd/
com.instranet.InstraServlet?command=com.
instranet.CmdBlobGetInstranetImage=534532
SecMode=1DocId=514336Usage=2 (1994).
132. McDonald, M., Brown, A., Noonan, S.
Carapetis, J. R. Preventing recurrent rheumatic
fever: the role of register based programmes.
Heart 91, 1131–1133 (2005).
133. Galderisi, M. et al. Improved cardiovascular
diagnostic accuracy by pocket size imaging
device in non-cardiologic outpatients: the
NaUSiCa (Naples Ultrasound Stethoscope in
Cardiology) study. Cardiovasc. Ultrasound 8, 51
(2010).
134. Sicari, R. et al. The use of pocket-size imaging
devices: a position statement of the European
Association of Echocardiography. Eur. J.
Echocardiogr. 12, 85–87 (2011).
Acknowledgments
We acknowledge the support of RHDAustralia and
Heart Association of Thailand in coordinating the
investigators’ meeting. B. Reményi’s research position
was funded by research scholarships from the National
Heart Foundation of New Zealand and the Lowitja
Institute of Australia. N. Wilson was funded part time
by the Green Lane Research and Education Fund in
2010. L. Zühlke is supported by the NIH through the
international clinical scholars and fellow program (R24
TW007988). Project grants were received from the
Medtronic Foundation for the investigators’ meeting
and from the Green Lane Research and Education
Fund for the website development.
Author contributions
B. Reményi wrote the article. All authors researched
data for the article, substantially contributed to
discussion of the content, and reviewed/edited the
manuscript before submission.
Supplementary information is linked to the online
version of the paper at www.nature.com/nrcardio.
REVIEWS

Wh fecho criteriafordxrhdnrcardio.2012.7

More Related Content

What's hot

Viewers also liked

Similar to Wh fecho criteriafordxrhdnrcardio.2012.7

Recently uploaded

Wh fecho criteriafordxrhdnrcardio.2012.7