Pilot Study on Prevalence of Rheumatic Heart Disease in Urban and Rural Angola by Echocardiography-Juniper Publishers
Juniper Publishers-Journal of Cardiology
Abstract
Rheumatic
heart disease is an important cause of death and disability in young
people in sub-Saharan Africa. Prevalence of rheumatic heart disease has
been studied in many African countries, but no such report for Angola.
The objective of this pilot study is to address rheumatic heart disease
prevalence in Angola. Echocardiography has been shown to be much more
sensitive than clinical detection of rheumatic heart disease. Portable
and handheld echo devices were used to screen for prevalence in urban
and rural areas. Five sites with no previous rheumatic heart disease
screening were chosen and classified according to levels of healthcare
access (Table 1). At each site children between ages 4-20 who consented
were screened. Two cardiologists performed onsite echo and diagnosed
rheumatic heart disease based on 2012 World Heart Federation criteria.
Abnormal studies were externally reviewed to confirm the diagnosis.
Positive cases were referred to local clinics for follow-up. 574 cases
were screened, with 17 positive. Overall prevalence was 29.6 cases per
1000, with a 95% confidence interval between 17.3-47.0. External review
concordance rate was 94%. Level 3 areas (lowest healthcare access) had
highest prevalence of rheumatic heart disease. (Level 1= 0, Level 2 =
23.0, Level 3 = 71.4, per 1000, p = 0.04). Mitral valve was
predominately affected (MV=17, AV=3). Posterior mitral regurgitation was
the dominant lesion in early disease (MR = 17, MS =3). Average age of
positive cases was 10. Rheumatic heart disease is highly prevalent in
Angola, and areas with lower access to healthcare had a higher disease
rate. Early disease is mainly manifested through posterior mitral
regurgitation. This study demonstrates an urgent need for a bigger study
involving broader regions to define true disease burden, as well as
public health intervention including early detection and secondary
prophylaxis in reducing rheumatic heart disease in resource-limited
areas.
Keywords: Sudden death; Hemopericardium; Medicolegal autopsy
Introduction
Rheumatic
Heart Disease (RHD) is an important cause of death in young people
living in developing countries, particularly in sub-Saharan Africa.
Rheumatic Heart Disease results from repeated exposure to Group A
streptococcus (GAS) infections, which over time causes valve scarring
and dysfunction [1]. Data from previous studies has shown that most
patients present as young adults when symptoms are severe enough to
cause functional limitations [2,3]. Rheumatic heart disease places a
massive healthcare burden on healthcare systems that have severely
limited budgets and human resources.
Worldwide,
the prevalence is estimated to be at least 15.6 million cases, with an
annual incidence of 282,000 cases and 233,000 deaths per year [4].
Sub-Saharan Africa is the most affected region; with an estimated
prevalence of 1-14 per 1000 children aged 5-14, affecting more than 1
million children [4]. However this figure may be a gross underestimation
as no prospective population-based study of acute rheumatic fever in
Africa is available [5]. Many of the prevalence studies did not use
echocardiography as screening tool and may underestimate true disease
burden. In addition, these data were based on studies over 10 years ago
and may not reflect current situation.
Many
patients who present to RHD programs already have existing symptoms and
advanced disease, overlooking milder or silent cases of RHD that occur.
Symptomatic rheumatic heart disease in adult carries high mortality and
morbidity, and is often complicated by congestive heart failure,
pulmonary hypertension, atrial fibrillation and stroke [6]. A large
multinational study determined RHD to be the most frequent cause of
heart failure amongst children and young adults, giving a 180-day
mortality as high as 17.8% [7]. Treatment of these patients are very
challenging, especially in resource limited areas [6]. Early detection
including asymptomatic cases with secondary prophylaxis may prevent
progression of valve damage and is a much more cost-effective public
health measure.
Echocardiography has become the
method of choice for screening rheumatic heart disease. It has been
shown to be ten times more sensitive than clinical auscultation of
murmurs [8]. The prevalence detected by echocardiography in children
with clinically silent RHD in sub-Saharan Africa is estimated to
7.5-51.6 per 1000 children [9]. In the past there were no standardized
echo criteria for diagnosing RHD, so different studies used different
criteria, making the comparison of prevalence data challenging. In 2012
the World Heart Federation (WHF) defined specific criteria for the
echocardiographic diagnosis of RHD for both symptomatic and silent RHD (Appendix). This allows for comparison of prevalence data between studies.
To
date, most prevalence studies have been based on schools, clinics or
hospital. With portable technology becoming increasingly available
worldwide, echocardiography can easily be used in rural and remote
settings to diagnose RHD [10]. There is a need to study both school and
non-school children to obtain real world data.
Although
there have been estimates done for sub-Saharan Africa as a whole and in
specific countries in sub-Saharan Africa such as Senegal, Uganda,
Mozambique, Cameroon, and Democratic Republic of Congo [8,11-14] no
known such study has been performed in Angola. Rheumatic heart disease
prevalence shows a high regional variation between countries. There is
also regional variation within a country. Therefore each country needs
to establish its own data. Such data need to be established before
effective prevention measures can be planned. We performed an initial
screening study in Angola to determine the prevalence of RHD using
portable echocardiography.
Materials and Methods
Materials and Methods
We
conducted our screening in five sites in Angola) over two weeks in
August 2013. Four of these sites were located in the province of Huila
(Humpata, Kahima, Tchitunda, Tchincombe) and one was in the neighbouring
province of Huambo (Cavango.) Sites were chosen based on the
availability of local contacts through a local hospital (Centro
Evangélico de Medicina do Lubango) and its rural outreach (Rio da Huila
Hospital), and the ability of local healthcare services to follow up on
positive findings. None of the sites had undergone previous screening
for RHD.
Categorization of sites
We
categorized our five sites into three levels of healthcare access.
Level 1 was a urban/suburban area with easy access to city hospital;
Level 2 was rural with onsite basic primary care level healthcare
facility/clinic, and Level 3 was rural with no onsite healthcare
facility and difficult access to health facility.
Diagnostic Criteria
Prior to the study the investigating cardiologists agreed upon using the 2012 WHF diagnostic criteria for RHD (Appendix).
Echocardiographic protocol and study population
This
study involved patients aged 4-20. Two cardiologists with experience in
rural echocardiography (KK and MBT) performed all on-site
echocardiographic examinations. At each site, local clinical contacts
promoted free heart screening for children who had previously never been
examined for heart disease. Children whose parents consented verbally
were included for screening. 80-120 children from each site were
screened. Equipment used for screening involved handheld V-Scan (GE
Medical Systems, Milwaukee, WI) with a 4V2-A phased array transducer or
SonoSiteMicromaxx (Providian Medical Equipment, Willowick, OH) with a
5-1 MHz 17mm broadband phased array transducer. A paediatric probe
(Sonosite) was also used. Cases found positive by screening were given a
more detailed focused echocardiographic study using the
SonoSiteMicromaxx. Another expert in echocardiography (CMC) blindly
reviewed the echo images independently to confirm or refute the
diagnosis. Patients found positive were referred back to local clinics
for follow-up and secondary prophylaxis. Research Ethics Board approval
for the project was obtained from North York General Hospital (Figure
1).
Statistical Analysis
The
study had 73% power to detect a difference in prevalence among levels
of access to healthcare at the 0.05 significance level. The data were
analysed using contingency tables to compare the prevalence of rheumatic
heart disease between areas of varying access to healthcare, and also
by age and sex. A two-sided fisher’s exact test was used due to small
cell counts, and Holm’s method was used to control the family-wise error
rate for pair wise comparisons.
Results
The
study examined 574 children over 5 sites, which were grouped into the 3
previously discussed levels of access to healthcare. The mean age of
the children was 10.14 years, and 56% of them were female.
Echocardiographic screening detected evidence of rheumatic heart disease
in 17 of the children, with 10 definite and 7 borderline according to
the 2012 WHF criteria, resulting in an overall prevalence of 29.6 per
thousand (95% Confidence Interval, 17.3 – 47.0). Table 2 One 4-year old
patient met the revised Jones Criteria for acute rheumatic fever and was
referred to a local physician for treatment and follow-up (Figure 2
& Table 2).
The prevalence of rheumatic heart
disease varied dramatically by access to healthcare ranging from
0.0(95% CI, 0 – 36.2) per thousand in the area where healthcare was most
readily available, to 70.9(95% CI, 33.2 – 131.3) per thousand in the
Level 3 areas (p=0.004) (Table 2). While controlling for the family-wise
error rate, significant differences in the prevalence of rheumatic
heart disease were detected between the highest level of healthcare
access and the lowest level (p=0.015), and between highest level of
healthcare access and the middle level (p=0.043) (Table 3).
Rheumatic
heart disease was also more prevalent in older children, with the
prevalence ranging from 7.1 per thousand among children less 10 years
old, to 51.7 per thousand in children over 10 years and older (p=.002)
(Table 3). No significant difference was observed based on sex. A
multivariate analysis undertaken with firth logistic regression suggests
that the minor differences in age distributions between the accesses to
healthcare groups did not significantly confound the healthcare access
effect (Tables 4 & 5).
Morphology of valve lesions
The
mitral valve was the most commonly affected valve (17/17 cases, 100%).
Aortic valve involvement was found in only 3 cases (17.6%) and was
always concomitant with mitral valve involvement. All cases with aortic
valve involvement were patients older than 10 years of age.
Mitral
stenosis was uncommon in early disease (3/7 cases), with mitral
regurgitation being the most common functional abnormality (16/17
cases). The mitral regurgitation was mostly posteriorly directed,
suggesting an anterior leaflet problem.
All
definite cases had both WHF defined morphologic features of rheumatic
mitral valve and pathologic MR. Three definite cases also met the WHF
2012 mitral stenosis criteria. The borderline cases were mainly
qualified by presence of pathologic MR based on WHF criteria.
Discussion
We
found the overall prevalence of RHD to be 29.6 per 1000 children aged
4-20 in our selected sites in Huila and Humpata provinces. This high
prevalence is consistent with similar echocardiographic studies
conducted in sub-Saharan Africa and other developing countries such as
Cambodia, Fiji, India, Laos, Mozambique, New Caledonia, Nicaragua,
Pakistan, Samoa, South Africa, Tonga, and Yemen [10].
By
applying our findings to the urban/rural demographics of Huila
province, we can estimate that there are 28,600 cases of RHD in the
province in children aged 4-20 (Appendix). Our confidence is this
estimate however is limited by our method of site selection. The
non-randomized nature of the selection raises concerns about the
generalizability of the results. However it does give a snapshot of
disease prevalence and its regional variation in the areas screened.
There is a need for urgent action including bigger scale study and
health policy change.
The association between RHD
with environmental factors is well known, however there are few
good-quality prevalence surveys of rheumatic heart disease in developing
countries. Previous studies are also inconsistent in the timing and
quality of their surveys making comparisons difficult. Known factors
associated with RHD include overcrowding, urbanization, and poor early
childhood nutrition. The best-studied factor is low Socio-economic
status [14-19]. While it has been suggested that access to medical
services and prophylaxis programs can also explain the difference in RHD
between developed and developing countries, this factor has not been
well studied [15,20].
Our study is unique in
that is it the one of the first studies to examine the link between
access to healthcare services and rheumatic heart disease. We were
surprised by the high burden of disease in the site with the lowest
access to healthcare. Cavango had by far the highest prevalence of RHD,
and also had the highest level of definite disease. Not only the remote
access site has the highest prevalence, it also has the most severe
cases. Three cases of severe rheumatic disease, characterized by
moderate to severe mitral regurgitation and severe pulmonary
hypertension (RVSP 66-90mmHg) were identified in the study, and all of
them were in Cavango. This kind of regional variation has important
resource planning implication. The difficult to reach areas tend to be
underserved. Our study suggests that areas with poor access to health
facility can benefit the most from rheumatic disease screening and
improved access to health services.
Most
prevalence studies of RHD to date have either been based in clinics or
schools. However, the usage of mobile echocardiography also allowed us
to be the one of first studies we are aware of that did not screen
schoolchildren in clinics, but rather gathered a broader sample of
children by visiting communities directly. This avoids a potential bias
in that school attendance is likely to be negatively associated with
major risk factors of rheumatic heart disease [1]. The children with
symptomatic disease are also less likely to be able to attend school.
Echocardiography
has been proven to be more sensitive and specific than auscultation,
identifying roughly ten times more cases with RHD [8,10]. Although
echocardiography machines are costly, especially for low-income
countries, the increased availability of handheld ultrasound machines
has allowed RHD to be screened systematically at lower cost. Handheld
echocardiography has shown to be highly sensitive (90.2%) and specific
(92.9%) at distinguishing between normal and definite RHD patients. It
is best used as a screening tool in early detection of RHD, with
positive results to be confirmed by fully functioning echocardiography
machines [16].
In our study we employed the 2012
World Heart Foundation guidelines for the diagnosis of RHD. Previous
criteria include the 2005 joint WHO and National Institute of Health
expert definitions, which were limited due to insufficient experience
with echocardiographic findings in children and not considering the full
morphological spectrum of RHD. Studies done prior to the WHF criteria
employed different criteria to define disease morphology and function,
often based on local experience with RHD. Hence, prevalence reporting
has varied widely, making comparison difficult [10]. Our application of
the WHF guidelines allows us to report disease prevalence based on an
internationally endorsed evidence-based echocardiographic diagnostic
guideline for asymptomatic patients.
In contrast
to mature disease which is usually characterized by mitral stenosis
and/or multiple valve involvement, early rheumatic disease predominately
showed single valve involvement, and mainly mitral regurgitation.
Interestingly the MR jet is mainly posterior directed suggesting
anterior leaflet lesion. Another interesting observation was that mitral
valve is affected much more commonly and earlier that aortic valve.
This is consistent with a recent study [6]. The reason for mitral more
than aortic valve involvement is partly secondary to different
hemodynamic stress on the valves. Current research also links genetic
predisposition and immunologic factors in pathogenesis of valvular
damage [22].
Conclusion
While
our study suffered from limitations of non-randomized site selection
and small sample sizes, this is the first study that has attempted to
assess the prevalence of RHD in Angola. The disease started at early
age, and has high regional variation. Our results have important
implications for forming national and regional control strategies to
reduce the burden of disease. Bigger scale study involving randomized
sites and broader regions to attain better estimates of the prevalence
of RHD in Angola, with particular emphasis on prospective cohort studies
to chart the progression of disease for children with subclinical
disease. Such children will receive the highest benefit from early
detection and subsequent secondary prophylaxis. On a public health
scale, the impact of RHD on disability and mortality and health
economics can also be studied. Above all, urgent action including public
health interventions are needed to reduce the burden of disease
[16,21].
Acknowledgement
We
would like to thank the staff at Rio da Huila Hospitaland Centro
Evangélico de Medicina do Lubango who wereinstrumental in organizing the
outreaches at the various sites.We would also like to thank Austin
Yuen, Christine Poon, TiffanyNg, Conor Sheridan, Dr. Robert Ting, Grace
Ting, Julie Ting, andRyan Ting for assisting with data collection
on-site and for data analysis.
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