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REVIEW
CORRESPONDING AUTHOR:
Samuel Seitler, MBChB
MRCP(UK)
Royal Free Hampstead NHS
Trust, Royal Free London NHS
Foundation Trust, Pond St,
London NW3 2QG, UK
sam.seitler92@gmail.com
KEYWORDS:
ultrasound; pregnancy;
rheumatic heart disease;
rheumatic fever; cardiac disease
TO CITE THIS ARTICLE:
Seitler S, Ahmad M, Ahuja
SAC, Ahmed MT, Stevenson A,
Schreiber TR, Sodhi PS, Diyasena
HK, Ogbeide O, Arularooran
S, Shokraneh F, Cassandra M,
Marijon E, Celermajer DS, Khanji
MY, Providencia R. Routine
Antenatal Echocardiography
in High-Prevalence Areas of
Rheumatic Heart Disease: A
WHO-Guideline Systematic
Review. Global Heart. 2024;
19(1): 39. DOI: https://doi.
org/10.5334/gh.1318
Routine Antenatal
Echocardiography in
High-Prevalence Areas of
Rheumatic Heart Disease: A
WHO-Guideline Systematic
Review
SAMUEL SEITLER
MAHMOOD AHMAD
SANJALI ANIL CHU AHUJA
MALIK TAKREEM AHMED
ALEXANDER STEVENSON
TAMAR RACHEL SCHREIBER
PREM SINGH SODHI
HIRUNA KOJITHA DIYASENA
OSARUMWENSE OGBEIDE
SANKAVI ARULAROORAN
FARHAD SHOKRANEH
MIRYAN CASSANDRA
ELOI MARIJON
DAVID S. CELERMAJER
MOHAMMED Y. KHANJI
RUI PROVIDENCIA
*Author affiliations can be found in the back matter of this article
ABSTRACT
Background: Rheumatic Heart Disease (RHD) is the most common cause of valvular
heart disease worldwide. Undiagnosed or untreated RHD can complicate pregnancy
and lead to poor maternal and fetal outcomes and is a significant factor in non-
obstetric morbidity. Echocardiography has an emerging role in screening for RHD. We
aimed to critically analyse the evidence on the use of echocardiography for screening
pregnant women for RHD in high-prevalence areas.
Methods: We searched MEDLINE and Embase to identify the relevant reports. Two
independent reviewers assessed the reports against the eligibility criteria in a double-
blind process.
Results: The searches (date: 4 April 2023) identified 432 records for screening. Ten
non-controlled observational studies were identified, five using portable or handheld
echocardiography, comprising data from 23,166 women. Prevalence of RHD varied
across the studies, ranging from 0.4 to 6.6% (I2, heterogeneity >90%). Other cardiac
abnormalities (e.g., congenital heart disease and left ventricular systolic dysfunction)
were also detected <1% to 2% of cases. Certainty of evidence was very low.
Conclusion: Echocardiography as part of antenatal care in high-prevalence areas
may detect RHD or other cardiac abnormalities in asymptomatic pregnant women,
potentially reducing the rates of disease progression and adverse labor-associated
outcomes. However, this evidence is affected by the low certainty of evidence, and
lack of studies comparing echocardiography versus standard antenatal care.
Prospective Registration: PROSPERO 2022 July 4; CRD42022344081 Available from:
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=344081.
Research question: ‘In areas with a high prevalence of rheumatic heart disease,
should handheld echocardiography be added to routine antenatal care?’
2Seitler et al.
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DOI: 10.5334/gh.1318
INTRODUCTION
Rheumatic heart disease (RHD) is the most common cause of valvular heart disease worldwide,
impacting millions, especially in low- and middle-income countries [1]. RHD is a long-term
consequence of untreated and recurrent acute rheumatic fever (ARF), an autoimmune
response to infection with Group A Streptococcus (Strep A), with ARF-associated carditis leading
to lasting damage to heart valves which can eventually lead to heart failure and death [2].
Pregnancy results in major changes in the cardiovascular system including increases in blood
volume, heart rate, and stroke volume, such that cardiac output increases up to 50% when
compared to non-pregnant levels [3]. These changes can often unmask previously unrecognized
cardiac disease or exacerbate clinical symptoms in women with known disease. It has been
reported that pulmonary edema occurs in approximately 60% of women with significant mitral
stenosis when the vascular volume is near its peak, at 30 weeks [4].
Data from 5,739 pregnancies on the Registry of Pregnancy and Cardiac disease (ROPAC), which
included data from 138 centres in 53 countries (low-, mid-, and high-income) over a 12-year
period showed that congenital heart disease and valvular heart disease were the two most
prevalent diagnoses, accounting for 57% and 29% of the total, respectively. RHD accounted
for 56% of cases of valvular heart disease [5]. A higher proportion of RHD was observed in two
single tertiary-centre studies from South Africa, a high-prevalence country, with RHD present in
up to 80% of pregnant women with heart disease [6–7].
Undiagnosed or untreated RHD can complicate pregnancy and is a significant factor for non-
obstetric morbidity and an important cause of maternal death [8]. Preterm birth has been
reported in 23% of cases, intrauterine growth restriction in 21%, low birthweight (below the 10th
percentile) in 28%, and unfavorable fetal outcome (i.e., spontaneous or therapeutic abortion, or
stillbirth) observed in 11% of pregnancies from a tertiary centre high-risk obstetrics/cardiology
clinic [8]. Involvement of the mitral valve has an important prognostic impact, with a subgroup
analysis of women with mitral valve disease in the ROPAC registry (mitral stenosis in two thirds
and isolated mitral regurgitation in the remaining) revealing that heart failure occurred in one
fourth of all mitral valve disease women [9]. This rate increased to one third and nearly one half,
in cases of moderate and severe mitral stenosis, respectively. An intervention during pregnancy
was required in 4.1%, either percutaneous balloon mitral commissurotomy (n = 14) or mitral
valve replacement (n = 2). Complications, mainly pulmonary oedema, and occurring in the third
trimester, were observed in >50% in a series of 138 consecutive pregnant women with mitral
stenosis [10], and 14.5% (n = 20) required balloon valvulotomy. Four women (1.0%) died within
the first six months in the ROPAC registry [9], and seven (3.3%) died in a South African cohort [6].
The heightened risks faced by pregnant women with RHD demand greater emphasis on timely
detection and prompt management to prevent complications to mother and child. Early
diagnosis is of importance to prevent disease progression, with a systematic review of nine
randomized and quasi-randomized studies showing reduction of ARF recurrence with secondary
prevention with penicillin [11]. A recent trial including 818 cases of subclinical mild RHD showed
that secondary antibiotic prophylaxis reduced the risk of progression at two years [12].
Two-dimensional (2D) echocardiography is established as the mainstay imaging modality
for the diagnosis and monitoring of RHD [13] and ARF [14]. Echocardiography can be
performed using handheld, portable, or stationary devices. Handheld echocardiography has
advantages for screening, due to simplicity and being lightweight, but does not possess the
advanced high-tech imaging features of heavier portable and stationary devices. Handheld
2D echocardiography has an emerging role in screening for RHD [15]. Mirabel and colleagues
have shown that focused echocardiogram can be performed with reliable accuracy and
reproducibility following relatively simple training of non-experts (i.e., two nurses) [16]. This
approach is followed by a confirmatory echocardiographic study if the screening results are
suggestive of RHD. Advantages and issues with each of the different echocardiography options
for screening RHD are discussed in detail in Appendix 1 (Supplementary Material).
Clinical diagnosis of ARF and RHD may miss a significant percentage of cases, with auscultation
only detecting murmurs in 6 out of 27 cases with subclinical RHD in Zühlke et al. [17], and missing
RHD and ARF in 16% and 24%, respectively, in 281 children with febrile illness but not presenting
with clinical criteria for ARF [18]. The role of echocardiography for screening pregnant women
3Seitler et al.
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DOI: 10.5334/gh.1318
in high RHD prevalence areas is still uncertain. This systematic review will critically analyse the
available evidence on the use of transthoracic echocardiography (handheld, portable, and non-
portable) for screening pregnant women for RHD in high-prevalence areas.
METHODS
This systematic review was performed to address one of the questions (Question 11) of the
World Health Organization Update of Guidelines on Prevention and Management of ARF and
RHD: ‘In areas with a high prevalence of RHD: should handheld echocardiography be added to
routine antenatal care?’
ORIGINAL PROTOCOL
The detailed protocol was pre-published on PROSPERO – 2022/CRD42022344081 [19], and
available as supplementary material (Annex 1). We did not identify any studies comparing
routine antenatal screening with echocardiography versus standard antenatal care.
Consequently, we were not able to assess the diagnostic test accuracy of echocardiography vs
standard antenatal care for detecting RHD in pregnancy in high prevalence areas or assess the
impact of this approach on pregnancy-related outcomes.
MODIFIED PROTOCOL
After discussion with the Guideline Committee in March 2023, it was accepted that the inclusion
criteria and study design would have to be broadened so observational studies using handheld
echocardiography, or any other form of echocardiography (i.e., standard echocardiography), in
the absence of a control group would also be considered eligible. This change aimed to gain
further knowledge on the rate of important cardiac findings obtained through echocardiographic
screening in pregnancy in high-prevalence populations.
The population of interest for this review was: pregnant women in areas with high prevalence of
RHD; we used the data from Watkins et al. 2017 [20] to define high-prevalence areas. The Index
Test was echocardiography during routine antenatal care. No comparator or reference test was
required. The outcomes of interest were:
• Carditis in ARF, based on revised Jones Criteria by American Heart Association [13], or
other criteria locally in use at the time of the study
• RHD, based on the 2012 World Heart Federation (WHF) criteria for echocardiographic
diagnosis [14], or other criteria locally in use at the time of the study
• Adverse events (deaths, obstetrics complications, other)
• Time to diagnosis
• Acceptability to provider and patient
Studies were eligible for the purpose of this systematic review when describing findings
of echocardiographic screening in pregnant women in areas of high prevalence of RHD. No
age restrictions were applied. Studies not reporting on echocardiographic findings were not
considered eligible.
Searches were run, documented, and reported by a senior information specialist (FS) on
Embase via Ovid SP (1974–present) and MEDLINE via Ovid SP (1946–present). The original
search strategy for diagnostic test accuracy studies is described in detail in Appendix 1 and 2
(Supplementary Material). This was subsequently revised and rerun on 4 April 2023, using the
search terms ‘Pregnan*’ and ‘Echocardiogr*’ and ‘Rheumatic’, also targeting non-controlled,
prevalence studies.
The search results were imported into EndNote 20. After removal of duplicates, the remaining
records were then imported into Rayyan, for double-blind screening by two reviewers (SS &
SACA). The blinding was inactivated when the screening was finished to resolve the conflicts by
a third reviewer (MA).
The following data were extracted from all studies (MA) and double-checked by an independent
reviewer (RP).
4Seitler et al.
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• Study characteristics: authors, year of publication, country, study design, sample size,
study period, setting, patient selection (random/consecutive), follow-up period.
• Patient characteristics: patient type, age, sex, highest level of education, presence of
cardiovascular risk factors (hypertension, diabetes mellitus), HIV status, known cardiac
disease, gestational age, gestation number, primigravida, presence of symptoms, or New
York Heart Association functional status.
• Index test details: Handheld echography device used (type – handheld, portable,
stationary device; model), level of experience of the sonographer, screening protocol, and
diagnostic criteria.
• Outcomes: Carditis-ARF, RHD, any adverse event (deaths, complication), time to diagnosis,
and acceptability to provider and patient
• Other echocardiographic findings, n and%: left ventricular (LV) systolic dysfunction
(reported as LV ejection fraction value, class, or other utilized measure), LV hypertrophy,
right ventricular dilation, and presence and severity of mitral regurgitation, mitral
stenosis, aortic regurgitation, aortic stenosis, and pulmonary hypertension. Data on
detection and type of congenital heart disease were also extracted.
We contacted the authors of the studies on an as-required basis to obtain the data or
information.
Quality assessment of studies was done by two researchers (SS & MA) using the Newcastle
Ottawa scale, which comprises three domains: selection, comparability, and outcome/exposure
[21]. Studies were classified as low, moderate, or high quality according to the following criteria:
studies scoring a total of 7 to 8 were considered low risk of bias; studies with a score of 6 were
considered to have a medium risk of bias; studies scoring 5 points or less were considered
to have a high risk of bias. With respect to selection, studies were considered to have a low,
medium, or high risk of bias if they scored 3, 1 to 2, or 0 points, respectively [22]. With respect
to comparability, studies were considered to have a low, medium, or high risk of bias if they
scored 2, 1 or 0 point, respectively. Finally, with respect to outcome, studies scoring 3, 2, or 1
point, were, respectively, considered to have a low, medium, or high risk of bias. Disagreements
between the two researchers were resolved by consensus or via a third party (RP).
Statistical heterogeneity was quantified using the I2 statistic, which describes the percentage
of total variation across studies due to heterogeneity rather than chance. Values of <25%,
25% to 50%, and >50% are by convention classified as low, moderate, and high degrees of
heterogeneity, respectively.
We summarised % rates with 95% confidence intervals across studies in a forest plot. Meta-
analysis using a random-effects model was planned if heterogeneity as per I2 was not
considered high (i.e., if I2 < 50%) [23]. Funnel plots were used for evaluating the presence of
publication bias and traced for outcomes of interest including ≥10 studies [24].
RESULTS
The searches identified 4,565 records, but we were unable to find any controlled studies looking
at handheld echocardiography versus standard transthoracic echo or standard clinical care to
diagnose RHD in pregnant women (Figure S-1; Supplementary Material). Following the revision
of the inclusion criteria in the abovementioned WHO Guideline Committee meeting (March
2023), a new search on 4 of April 2023 yielded additional 432 records for screening. Ten non-
controlled observational studies were identified using echocardiography for screening of cardiac
disease in pregnant women from high prevalence areas of RHD [25–34], five using portable or
handheld echocardiography [25–29] (Figure 1). One study [30] was published as abstract, and
the remaining as full text. Four studies were conducted in sub-Saharan Africa [25–26, 28, 31],
four studies were conducted in India [29–30, 32, 34], one in Brazil [27] and one in Turkey [33].
The sample sizes were highly variable, ranging from 300 [32] to 14,275 [34], with a combined
total of 23,166 women across studies.
In one study all approached women accepted to participate [25]. In Nascimento et al. nearly
50% of women with positive findings on the screening echo failed to attend the recommended
follow-up echocardiogram despite the multiple contact attempts [27]. In Snelgrove et al., of
5Seitler et al.
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DOI: 10.5334/gh.1318
810 potentially eligible women, only 601 consented and accepted to undergo echocardiography
[28]. No other studies provided information on acceptability to patent of provider.
Demographic information for the included women is shown in Table 1. Maternal age was
consistent throughout the studies, as were pre-existing medical co-morbidities. Maternal HIV
status was recorded in two of the studies. Mean gestational age was similar in four of the studies,
with most women being scanned in the second or third trimester. Four studies were single-
centre studies conducted in a tertiary maternity care setting [28, 30, 33–35]. The remainder
were multi-centre studies, coordinated across several clinics in a single city [26] or several
states [27, 29]. Two studies had no participants with known cardiac disease at baseline [25,
33], two studies had less than 1% [26–27], and two [29, 30] had up to 5% of pregnant women
with known disease at baseline. Bozkaya et al. only recruited women in the first trimester [33].
In three studies most women had an echocardiogram between the 22nd and 25th week of
gestation [26–28]. In Otto et al. most echocardiograms were performed at 30 weeks or later
[25]. Alshaqri et al. was the only study to also include post-partum women in the analysis [29].
Echocardiography was conducted as part of antenatal care in all studies. The images were
acquired by operators and interpreted with a variety of experience. Otto et al. [25] and Beaton
et al. [26] used specially trained medical students and nurses, respectively, while Snelgrove
et al. [28] used an accredited sonographer. The acquired images were then locally reviewed
by cardiologists or trained sonographers [25–26, 28]. Alsharqi et al. [29] employed trained
obstetricians and Nascimento et al. [27] used healthcare workers to acquire the images. These
two studies exported DICOMs internationally for remote analysis by experts. Echocardiography
was performed by a cardiologist in Bozkaya et al. [33].
Scanning protocols differed among the studies, with Nascimento et al. adapting a simplified
seven- view echocardiographic protocol for handheld devices, and Alsharqi et al. using the
MaatHRI focused image acquisition protocol (Table 2). The criteria used for diagnosis of RHD were
not uniform. Four studies [26, 28, 31, 33] used the 2012 WHF criteria for the echocardiographic
diagnosis of RHD [14] (Table 3). Otto et al. [25] conducted their study prior to the development
of these criteria but used similar morphological abnormalities for diagnosing RHD. Two studies
[27, 29] used criteria from the American Society of Echocardiography. The remaining studies
did not define the echocardiographic criteria for RHD diagnosis.
Figure 1 PRISMA flow diagram.
STUDY ID COUNTRY DESIGN SETTING SAMPLE
SIZE
AGE (YEARS)
(MEAN ± SD)
HIGHEST LEVEL
OF EDUCATION
HYPERTENSION,
n (%)
DIABETES,
n (%)
HIV n
(%)
KNOWN
CARDIAC
DISEASE
n (%)
GESTATIONAL
AGE AT FIRST
VISIT, WEEKS
(MEAN SD)
PRIMIGRAVIDA,
n (%)
Studies using Handheld or Portable Echocardiography
Otto 2011 Eritrea Prospective
cross sectional
4 clinics in single city 348 26.9 (±6) NA 0 NA NA 0 30.9 ± 6.7 NA
Beaton 2019 Uganda 24-month
prospective
longitudinal
investigation
2 health centres,
1 regional referral
hospital
3506 24.09 (N/A) University Degree:
87 (2.5%)
6 (1.7%) NA 141
(4.0%)
2 (0.06%) 24 (median) 359 (10.2%)
Nascimento
2021
Brazil 13-month
prospective
longitudinal
investigation
22 primary care
centres
1112 27 ± 8 years NA 50 (4.5%) 27 (2.4%) NA 9 (0.8%) 22 ± 9 NA
Snelgrove
2021
Kenya Cross sectional
study
Antenatal clinic at
tertiary maternity
centre
601 26.6 years (SD
5.7)
University degree:
82 (13.6%)
1 (0.2%) 1 (0.2%) 45
(7.5%)
27 (4.5%) 25.3 ± 9.5 NA
AlSharqi 2022 India cross sectional
study
10 hospitals across
three states-India
301 25.4 (18–42) University degree:
31 (10.6%)
NA NA NA 17 (5.6%) NA 183 (60.8%)
Screening using Standard Echocardiography or unspecified echocardiographer
Selvarani
2014
India 6 months Cross
sectional study
Antenatal clinic at
a tertiary maternity
centre
1125 23.41 NA NA NA NA NA NA. 55.73%
Bacha 2019 Ethopia Cross Sectional
Study
Antenatal clinic at
tertiary maternity
centre
398 27.0 (±4.6) College/University
49 (12.31%)
8 (2%) 7 (1.8%) NA NA NA NA
Gomathi 2019 India 4-month cross-
sectional study
Cardiology
department at
tertiary center
300 NA NA NA NA NA 0 NA 186 (62%)
Bozkaya 2020 Turkey 12-month cross-
sectional study
Tertiary delivery
center
900 27.4 (±5.8) NA 0 0 0 0 NA/first
trimester
NA
Patel 2021 India 36 month long
cross sectional
study
Antenatal care at
two large hospitals
14275 NA NA NA NA NA NA NA NA
Table 1 Demographic and obstetric data.
PROTOCOL OPERATORS LVSD, n (%) LV
HYPER-
TROPHY,
n (%)
PULMONARY
HYPER
TENSION, n
(%)
RV
DILATATION,
n (%)
SYMPTOMS/
NYHA
FUNCTIONAL
CLASS AT ENTRY
CONGENITAL
HEART
DISEASE
(ANY) n
Studies using Portable or Handheld Echocardiography
Otto 2011 Full TTE with
Doppler; Vivid-I GE
Healthcare
Trained
Medical
students
Moderate LVSD:
1 (0.29%)
0 0 0 Asymptomatic Any: 1 (0.3%)
ASD
Beaton
2019
Focussed Echo;
Vivid-Q GE
Healthcare or
Philips ClearVue
350
Nurses DCM, Mild LVSD:
1 (0.03%)
0 Any: 1
(0.03%)
0 Cases with echo
findings:
I–7 (13.4%)
II–41 (78.8%)
III–4 (7.7%)
IV–0 (0%)
Any: 1 (0.03%)
Large
secundum
ASD: 1
Nasci-
mento
2021
Focussed 7-view
protocol; Vscan
GE Healthcare
and Vivid-Q & IQ
GE Healthcare, if
positive scan
Healthcare
workers
Mild/moderate
LVSD: 1 (0.1%)
2 (0.2%) 0 3 (0.3%) 37.7% (419) had
dyspnoea
0
Snelgrove
2021
Focussed Echo;
Vivid-Q GE
Healthcare
Cardiac
sonographer
0 0 Any: 1 (0) 0 10.3% (62)
had unspecific
symptoms
Any: 2 (0.3%)
Unroofed CS:
1; PDA: 1
AlSharqi
2022
Focussed protocol;
Lumify Philips
Healthcare
Obstetricians LVEF 45–54%
8.4% (25)
LVEF 30–44%
8.8% (26)
LVEF <30%
4.7% (14)
0 0 19/285
(6.7%)
Cases with echo
findings (n = 172):
I–13 (7.8%)
II–37 (22.2%)
III–19 (11.4%)
IV–98 (58.6%)
0
Screening using Standard Echocardiography or unspecified echocardiographer
Selvarani
2014
Full TTE with
Doppler;
Echocardiographer
not specified
NA Any: 1 (0.1%)
DCM: 1
0 0 0 All asymptomatic
“except for a few
in NYHA class II”
Any: 24 (2.1%)
ASD: 7; VSD:
2; MVP: 3;
Bicuspid Ao: 3;
Corrected: 9
Bacha
2019
Full TTE with
Doppler; Vivid-E9
GE Healthcare
NA Any: 1 (0.3%)
Peri-natal CM: 1
5 (1.3%) Any: 15
(3.8%)
Mild: 11
Moderate: 2
Severe: 2
NA NA 0
Gomathi
2019
Full TTE with
Doppler;
Echocardiographer
not specified
NA NA NA NA NA Asymptomatic Any: 7 (2.3%)
ASD: 2; MVP: 3;
Pulm Stenosis:
1; Aortic
Coarct: 1
Bozkaya
2020
Full TTE with
Doppler; – Vivid
S5 System, GE
Healthcare
Cardiologist 0 NA NA 0 Asymptomatic Any: 9 (1.0%)
ASD: 8; PDA
(1)
Patel
2021
“Screening
echocardiogram”;
Echocardiographer
not specified
NA Cardiomyopathy:
66 (0.5%)
DCM: 30 (0.2%)
LVEF < 55% 36
(0.3)
27(0.18%) NA NA NA Any: 63 (0.4%)
ASD or PFO:
43; VSD:
4; PDA (7),
Bicuspid Aortic
valve (9)
Table 2 Echo protocols and findings.
Legend: LVSD – left ventricular systolic dysfunction; ASD – atrial septal defect; CS – coronary sinus; PDA – patent ductus arteriosus; CM –
cardiomyopathy, MVP – mitral valve prolapse; Pulm – pulmonary; Coartct – coarctation. Other findings: Alsharqi et al. reported 4 thrombi;
Bozkaya et al. also reported significant cases of non-rheumatic valve disease: moderate pulmonary stenosis (1), moderate AR (1), moderate
MR (5), and severe MR (1).
RHEUMATIC HEART DISEASE
Due to high heterogeneity (I2 > 90%) across the observational studies, data were not pooled,
and a narrative description is presented below.
Studies from different global regions were identified, with RHD prevalence ranging from 0.5%
in Kenya [28], 1.1% in Brazil [27], 1.5% in Uganda [26], 2.3% in Ethiopia [31], 2.9% in Turkey
[33], 4.6% in Eritrea [25] to 6.6% in India [29]. Prevalence of RHD in studies conducted in India
varied: Patel et al 0.4% [34], Selvarani et al 1.5% [30], Gomathi et al 2.6% [32] (Figures 2 and
3, and Tables 2 and 3).
CRITERIA USED RHD ANY
n, %
MITRAL
REGURGITATION,
n (%)
MITRAL STENOSIS
(ANY), n (%)
AORTIC
REGURGITATION
(ANY), n (%)
AORTIC
STENOSIS
(ANY), n (%)
Studies using Portable or Handlehd Echocardiography
Otto 2011 WHO consensus
statement 2001
Any: 16 (4.6%)
Definite: 8
Nondefinite: 8
Any: 12 (3.6%)
Mild: 7
Mid/Moderate: 2
Moderate: 2
Moderate/Severe: 1
0 Any: 6 (1.7%)
Mild: 6
0
Beaton 2019 WHF Any: 51 (1.5%)
Mild: 31
Moderate: 14
Severe: 6
Any: 45 (1.3%)
Mild: 28
Moderate: 15
Severe: 2
Any: 3 (0.1%)
Mild: 2
Moderate: 1
Any: 7 (0.2%)
Mild: 5
Moderate: 1
Severe: 1
0
Nascimento
2021
Adapted ASE
criteria for major
heart disease
Any: 12
(1.1%)*
Any: 12 (1.1%)
Mild to moderate: 11
Moderate: 1
Any: 1 (0.1%)
Mild: 1
Any: 3 (0.3%)
Mild: 3
Any: 1 (0.1%)
Mild: 1
Snelgrove
2021
WHF Any: 3 (0.5%) Any: 1 (0.2%)
Moderate: 1
Any: 2 (0.33%)
Severe: 2
Any: 1 (0.2%)
Moderate: 1
0
AlSharqi 2022 ASE/EACVI
recommendations
Any: 20 (6.6%) ‘mitral valve involvement’:
20 (6.6%)
Significant: 17
(5.6%)
‘aortic valve
involvement’ 3 (1%)
Significant: 1
(0.3%)
Screening using standard echocardiography or nonspecified echocardiographer
Selvarani 2014 NA Any: 17 (1.5%) Any: 1 (0.1%) Any: 14 (1.2%) Any: 3 (0.03%) NA
Bacha 2019 WHF Significant:
9 (2.3%)
Any: 4 (1%)
Moderate to Severe: 2
NS: 2
Moderate to Severe:
3 (0.8%)
Moderate to Severe:
2 (0.5%)
Moderate
to Severe:
2(0.5%)
Gomathi 2019 NA Any: 12 (4.0%) Any: 4 (1.3%) Any: 4 (1.3%)
Moderate: 3
Not specified: 1
Any: 1 (0.3%)
Not specified: 1
Any: 1 (0.3%)
Not specified:
1
Bozkaya 2020 WHF Any: 26 (2.9%) Any 24 (2.7%)
Mild: 20
Moderate: 4
Mild: 2 (0.2%) 0 0
Patel 2021 NA 61 (0.4%) Any: not specified; ‘mitral
valve involvement’: 61
Number not
specified, but
‘90% were mild to
moderate, and 67%
had Wilkins score <8’
NA NA
Table 3 Rheumatic heart
disease findings on screening
echo.
*RHD on screening was
suspected in 36 women
(3.2%), but only 56 of the
100 women who screened
positive had a confirmatory
echocardiogram.
Figure 2 Prevalence of RHD
in studies using portable or
handheld echocardiography.
9Seitler et al.
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DOI: 10.5334/gh.1318
Otto et al. classified their results into three groups, based on pre-defined criteria that predated
the 2012 WHF classification (supplementary material – Table S-1) into: definite RHD (n = 8,
2.3%); non-definite RHD (n = 8, 2.3%); and no structural abnormalities. Across the definite and
non-definite groups, the mitral valve was the most frequently affected (in 12 of 16 cases). All
participants in the study were asymptomatic and none reported known previous RF [25].
Nascimento et al. demonstrated the benefits of portable echo as a screening tool for RHD.
Suspected RHD was observed in 36 (3.2%) of 1,112 pregnant women scanned with handheld
devices, utilizing a simplified echo protocol [27], and confirmed using more sophisticated
portable machines in a smaller subset of women, all with mitral valve involvement and two with
additional aortic valve compromise. Prevalence of positive screening findings was comparable
in the first (8.9%), second (9.7%) and third (7.2%) trimester [27].
Beaton et al. identified heart disease in 58 women, corresponding to a community prevalence
of 1.5% (95% CI 1.3% to 2.1%), with 51 out of 58 cases (87.9%) attributed to RHD [26]. Alsharqi
et al., using handheld echocardiography, reported RHD in 20 women (6.6%), all of whom had
mitral valve involvement, but no further information was provided regarding the severity of the
valvulopathy [29]. Snelgrove et al. identified only 3 cases of RHD (0.5%) [27].
Severe RHD was a rare finding across all studies. Beaton et al. identified 31 women (60.8%)
with mild, 14 (24.1%) with moderate, and 6 (11.8%) with severe valvular involvement. Nearly
97% of cases (i.e., all but two) of RHD were new diagnoses. This was the only study providing
prospective follow-up of the women diagnosed with RHD during screening, with cardiovascular
complications occurred in 51.8% (95% CI 39.0 to 64.3) of these women (heart failure in one
third, pulmonary hypertension in one tenth and 5% with arrhythmia), and cardiovascular
medication was required in over half [26]. One quarter of the identified women with heart
disease were considered either high risk or moderate risk by the combined cardiology/obstetric
team. Caesarean delivery was recommended for one woman at the national referral centre,
delivery at the regional centre was recommended for seven and six additional women were
referred for delivering in hospital [26]. Snelgrove et al. found that none of the three women
identified with RHD had a prior formal diagnosis or knowledge of existing CVD disease, despite
mitral stenosis being classified as severe in two of the cases [28]. Bozkaya et al. identified mild-
to-moderate valve disease in 92.3% of the RHD cases [33]. Patel et al. described the highest
number of women with RHD but did not stratify the distribution in any way [34].
Figure 3 Prevalence of
RHD in studies using
stationary or non-specified
echocardiography.
Figure 4 Funnel-plots for
assessment of publication bias.
10Seitler et al.
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DOI: 10.5334/gh.1318
OTHER FINDINGS
Among studies using handheld echocardiography, left ventricular systolic dysfunction (LVSD)
was an uncommon finding in most of the studies. Two studies reported no cases of LVSD [28,
33] and three reported less than 0.5% prevalence of mild or moderate LVSD [25–27]. The
exception was Alsharqi et al., who identified 51 (16.9%) cases of mild/moderate LVSD and 16
(4.7%) cases of severe LVSD from the 301 women imaged [29]. These results were skewed by
the inclusion criteria, which comprised a large cohort of women with suspected heart failure
(over 50% were NYHA IV at recruitment).
Several studies identified undiagnosed congenital heart diseases in their participants, most
commonly intracardiac shunts. Otto et al. and Beaton et al. identified one case each of atrial
septal defect [25–26]. Gomathi et al. identified two cases of ASD [32]. Snelgrove et al. detected
one case of patent ductus arteriosus, and one case of unroofed coronary sinus [28]. Prevalence
in other studies ranged from 1.0% (33), to 2.1% (30) or 2.3% (32) (details in Table 3).
No studies reported on detecting carditis in pregnant participants with clinical presentation
compatible with ARF, or time to diagnosis.
QUALITY ASSESSMENT
Study quality varied across studies, with those using portable or handheld echocardiography
scoring higher: four out of five studies were judged as low risk and one study [25] was considered
medium risk (Table 4). The remaining studies were of lower quality: two were considered low
[33] and medium risk [31], all remaining papers were considered high risk [30, 32, 34].
Assessing the three Newcastle-Ottawa scale domains in isolation, all studies but one [32],
which was considered high risk, were classified as medium risk for selection bias. Regarding
comparability, seven studies were considered low risk [25–29, 31, 33], and 3 were considered
high risk [30, 32, 34]. Finally, with respect to outcome, five studies were considered low risk
[26–29, 33], and the remaining were medium risk.
Certainty of evidence was considered very low. All studies were observational, and certainty
was downgraded on the basis of concerns with risk of bias, inconsistency, imprecision, and
publication bias (Figure 4). Justification for the decisions is provided in Table 5.
STUDY ID SELECTION COMPAR-
ABILITY
OUTCOME TOTAL RESULT
REPRESENTAT-
IVENESS OF THE
SAMPLE
SAMPLE
SIZE
NON-
RESPONDENTS
ΨASSESSMENT
OF OUTCOME
STATISTICAL
TEST
Studies using Portable or Handheld Echocardiography
Otto 2011 * - * ** ** - 6 Medium Risk
Beaton 2019 * * - ** ** * 7 Low Risk
Nascimento
2021
* * - ** ** * 7 Low Risk
Snelgrove
2021
* * - ** ** * 8 Low Risk
AlSharqi 2022 * - * ** ** * 7 Low Risk
Screening using Standard Echocardiography or nonspecified echocardiographer
Selvarani
2014
- * - * ** - 4 High Risk
Bacha 2019 * * - ** ** - 6 Medium Risk
Gomathi 2019 - - - - ** - 2 High Risk
Bozkaya 2020 * * - ** ** * 7 Low Risk
Patel 2021 * * - - ** - 4 High Risk
Table 4 Newcastle Ottawa
scale for quality assessment of
cross-sectional studies.
Ψ Comparability of subjects
across studies with enough
information provided on
study design, analysis, and
confounding factors (**);
information provided on 2 of
the 3 previously mentioned
factors (*).
DISCUSSION
Our review shows that screening the antenatal population using handheld or portable
echocardiography can identify an important proportion of women with previously undiagnosed
RHD living in high-prevalence areas. The observed prevalence varied across the included studies
and different global regions. This is not unexpected and may be due to wide variation of RHD
prevalence in some geographical areas, as well as the different criteria for diagnosing and
reporting RHD across studies. These findings are in-keeping with recent data estimating that
the prevalence in countries where RHD remains endemic is >1%, and greatest in women of
childbearing ages [7, 34].
A large proportion of the RHD detected was mild in severity, which is generally well tolerated
in pregnancy [9]. Although RHD was the most common finding, other clinically relevant
conditions, such as congenital heart disease were detected. Some women had LVSD, pulmonary
hypertension and high-risk left-sided valve lesions (e.g., aortic valve area <1.5 cm2, mitral valve
area <2 cm2, or moderate to severe mitral regurgitation), which are included as part of widely
accepted risk stratification schemes for women and cardiovascular disease such as CARPREG-II
(Table S-2) [35], and the modified WHO classification of maternal cardiovascular risk (Table S-3)
[36]. This is of relevance has it shows that besides being important for identifying women in
need for secondary antibiotic prophylaxis, echocardiography as part of antenatal screening may
be of importance for early detection and planning of pregnancy care in a significant number
of women with undetected high-risk cardiovascular conditions living in high-prevalence areas.
The WHO has defined 13 recommendations for maternal and fetal assessment as part of their
recommendations for antenatal care (Table S-4 – Supplementary Material) [37]. These include
testing for HIV in high prevalence areas, screening for tuberculosis in areas with a prevalence >
1/1000 and an early ultrasound, before 24 weeks of gestation. According to the latest UNAIDS
report, prevalence of HIV among adults aged 16 to 45 in Eastern and Southern Africa, and
Western and central Africa, was 5.9 and 1.1%, respectively [38]. The early ultrasound may
detect fetal anomalies in 1.2% [39], and multiple pregnancies in 1.7% of gestations [40]. These
rates are comparable to the prevalence figures we described for RHD screening in our review.
Portable and handheld echocardiography screening may provide a more accessible strategy
in these low-income settings where standard stationary transthoracic echocardiography
is not easily accessible. There were variations in the strategy used for implementing
echocardiography screening the studies we identified. Three studies trained nurses and/or
obstetricians for obtaining an echocardiogram, and having the images interpreted remotely
by trained cardiologists [26–27, 29]. This strategy seems feasible and therefore might be easier
to implement where antenatal care is largely led by community-based clinics, such as in Brazil
[27]. Obstetricians, alongside nurses and midwives, perform WHO’s recommended antenatal
ultrasound in high-prevalence areas for RHD [41] and may constitute potential alternatives
upon receival of appropriate training in regions where cardiologists are sparse or lacking.
Timing for echocardiographic screening in pregnancy is still a matter of debate, and further
research is needed to address this matter. Earlier screening has the potential advantage of
improved acoustic window and adjusting pregnancy management planning in case changes
are detected. Data from Beaton et al. provides evidence that antenatal screening with portable
echocardiography at median of 24 weeks gestation can impact upon antenatal care and delivery
planning [26]. However, we did not identify any studies comparing routine echocardiographic
antenatal screening versus standard antenatal care that could provide direct evidence on the
impact such an intervention might have upon maternal, fetal, and neonatal outcomes. This is
an important knowledge gap that requiring further investigation.
NO OF
STUDIES
RISK OF BIAS INCONSIS-
TENCY
INDIRECTNESS IMPRECI SION PUBLICATION BIAS CERTAI NTY
10 Serious Serious Low risk Serious Serious ⨁◯◯◯
Very low
5 of 10 studies had
medium to high risk
of bias as per the
Newcastle Ottawa scale
Inconsistency
was very high:
I2 = 95%
Study population of
pregnant women
in high prevalence
countries in all studies
The detection
rate of RHD was
<1% in 2 studies
Asymmetric funnel
plot, with Four
studies are outside
the 95%CI limits
Table 5 Assessment of
Certainty of Evidence using
the GRADE approach.
12Seitler et al.
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DOI: 10.5334/gh.1318
Dealing with screening findings implies additional resource availability and utilization, as
follow-up and need for further assessment and imaging of incidental findings may be required.
Also, the findings may cause anxiety for the patient and relatives. Cost-effectiveness data were
absent in the included studies. False positives and false negatives may be important points to
factor, as these can potentially add to health system’s costs, but may be less of a problem with
echocardiography than with cardiac auscultation.
By targeting pregnant women with suspected heart failure, Alsharqi et al. detected the
highest rate of RHD, 6.6% [29], suggesting that, in regions where lack of resources could be
a barrier for global screening, screening of higher risk groups with higher chances of findings
could constitute an alternative. However, the best way to detect high-risk women remains to
be clarified as studies in our review detected an important rate of RHD, ranging from 0.4 to
4.0% [25, 32], in asymptomatic women. Not only could some of these women be high-risk
and become symptomatic only later in pregnancy, as reported in the ROPAC registry [9], but
also, missing these cases could deny them the chance of being offered secondary antibiotic
prophylaxis to prevent progression of disease [12]. Studies focusing on patient selection vs
global screening, applied to the local reality of the area where screening programs are being
considered, are of importance to address this uncertainty.
The quality of most studies was low overall, and that was the main limitation of this systematic
review. Most of the studies included in our review did not report the severity or type of valvular
involvement. Data from the ROPAC registry shows that severe mitral stenosis is an independent
risk factor for adverse fetal outcomes [9]. Interestingly, even in the ROPAC registry, severity of
mitral of mitral stenosis was not classified in 20% of participants. Future studies and registries
should provide more detailed information on degree of valvular involvement, and on RHD
stage as per the 2023 World Heart Federation echocardiographic diagnosis guidelines [42].
Several factors could have contributed to the heterogeneity in the observed prevalence of
RHD across studies: differences in the selected populations (e.g., some studies included only
asymptomatic women or women without history of diagnosed cardiac disorders, whilst others
included patients with suspected heart failure, or even with surgically corrected heart disease),
utilized echocardiographer model, utilized criteria (WHF 2012 or other), and level of reporting
(e.g., some studies only reported the more advanced cases of RHD). Most importantly, operator
experience, which is key for an operator-dependent procedure like echocardiography, and
background (cardiologists, obstetricians, sonographers, or other health professionals) varied
across studies. Only two studies utilized handheld echocardiography, but with accessibility and
ease of use, evidence for this technology is likely to grow.
CONCLUSION
The observational studies identified in our review show that using echocardiography as part
of routine antenatal care may detect between 0.4 to 6.6% of undiagnosed of RHD among
pregnant women in high-prevalence areas. Reasons for the observed differences across studies
need to be further clarified. Only two studies utilized handheld echocardiography in this setting,
highlighting the need for more research in the field.
Evidence in this review is affected by the very low certainty of evidence, heterogeneity,
lack of controlled trials (of handheld or portable echocardiography vs. standard stationary
echocardiography), or cost-effectiveness studies.
ADDITIONAL FILE
The additional file for this article can be found as follows:
• Supplementary Material. Figure S1, Tables S1 to S4 and Appendices 1 to 3. DOI: https://
doi.org/10.5334/gh.1318.s1
FUNDING INFORMATION
The World Health Organization (WHO) commissioned this review to support the development
of WHO’s clinical practice guidelines on the prevention and management of Acute Rheumatic
Fever and Rheumatic Heart Disease.
13Seitler et al.
Global Heart
DOI: 10.5334/gh.1318
The funder supplied the research questions, defined the PICO (Population, Index test,
Comparators, Outcomes) and had no role in study design, collection, analysis, and interpretation
of data, or writing of the report. The funder commissioned independent reviewers who
commented on the review’s protocol and final report several times.
COMPETING INTERESTS
The authors have no competing interests to declare.
AUTHOR AFFILIATIONS
Samuel Seitler, MBChB MRCP(UK) orcid.org/0000-0003-0228-5698
Royal Free Hampstead NHS Trust, Royal Free London NHS Foundation Trust, Pond St, London NW3 2QG, UK
Mahmood Ahmad
Royal Free Hampstead NHS Trust, Royal Free London NHS Foundation Trust, Pond St, London NW3 2QG, UK
Sanjali Anil Chu Ahuja
Barts and The London School of Medicine and Dentistry Turner St, London E1 2AD, UK
Malik Takreem Ahmed
GKT School of Medical Education, King’s College London, UK
Alexander Stevenson
Department of Cardiology, High Wycombe Hospital, Queen Alexandra Rd, High Wycombe HP11 2TT, UK
Tamar Rachel Schreiber
Royal Free Hampstead NHS Trust, Royal Free London NHS Foundation Trust, Pond St, London NW3 2QG, UK
Prem Singh Sodhi
Royal Free Hampstead NHS Trust, Royal Free London NHS Foundation Trust, Pond St, London NW3 2QG, UK
Hiruna Kojitha Diyasena
Royal Free Hampstead NHS Trust, Royal Free London NHS Foundation Trust, Pond St, London NW3 2QG, UK
Osarumwense Ogbeide
Royal Free Hampstead NHS Trust, Royal Free London NHS Foundation Trust, Pond St, London NW3 2QG, UK
Sankavi Arularooran
Royal Free Hampstead NHS Trust, Royal Free London NHS Foundation Trust, Pond St, London NW3 2QG, UK
Farhad Shokraneh orcid.org/0000-0001-9687-8560
GENEs health and social care evidence SYnthesiS unit, Institute of Health Informatics, University College
London, UK; Evidence Synthesis, Systematic Review Consultants LTD, Nottingham, UK
Miryan Cassandra
Hospital Ayres de Menezes, São Tomé, ST
Eloi Marijon orcid.org/0000-0001-7227-3428
Paris Cardiovascular Research Centre, INSERM U970, European Georges Pompidou Hospital, Paris, FR;
Department of Cardiology, European Georges Pompidou Hospital, Paris, FR
David S. Celermajer orcid.org/0000-0001-7640-0439
The University of Sydney, Sydney, AU; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, AU
Mohammed Y. Khanji orcid.org/0000-0002-5903-4454
Cardiology Department, Barts Heart Centre, Barts Health NHS Trust, London, UK; Newham University
Hospital, Barts Health NHS Trust, Glen Road, Plaistow, London E13 8SL, UK; NIHR Barts Biomedical
Research Centre, William Harvey Research Institute, Queen Mary University, London EC1A 7BE, UK
Rui Providencia orcid.org/0000-0001-9141-9883
GENEs health and social care evidence SYnthesiS unit, Institute of Health Informatics, University College
London, UK; Cardiology Department, Barts Heart Centre, Barts Health NHS Trust, London, UK; Newham
University Hospital, Barts Health NHS Trust, Glen Road, Plaistow, London E13 8SL, UK
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TO CITE THIS ARTICLE:
Seitler S, Ahmad M, Ahuja
SAC, Ahmed MT, Stevenson A,
Schreiber TR, Sodhi PS, Diyasena
HK, Ogbeide O, Arularooran
S, Shokraneh F, Cassandra M,
Marijon E, Celermajer DS, Khanji
MY, Providencia R. Routine
Antenatal Echocardiography
in High-Prevalence Areas of
Rheumatic Heart Disease: A
WHO-Guideline Systematic
Review. Global Heart. 2024;
19(1): 39. DOI: https://doi.
org/10.5334/gh.1318
Submitted: 06 October 2023
Accepted: 20 March 2024
Published: 25 April 2024
COPYRIGHT:
© 2024 The Author(s). This is an
open-access article distributed
under the terms of the Creative
Commons Attribution 4.0
International License (CC-BY
4.0), which permits unrestricted
use, distribution, and
reproduction in any medium,
provided the original author
and source are credited. See
http://creativecommons.org/
licenses/by/4.0/.
Global Heart is a peer-reviewed
open access journal published
by Ubiquity Press.
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