Risk Of Rheumatic Heart Disease Research Articles

Associations of <i>TLR</i> gene polymorphism with the risk of rheumatic heart disease

Aim of the study was to investigate the associations between TLR gene polymorphism and the risk of rheumatic heart disease (RHD).Material and methods. 251 RHD patients (190 females and 61 males) and 300 healthy donors (190 females and 110 males), whose age was 57 [29; 77] and 53 [21; 80] years (median [lower quartile; upper quartile]), respectively, were recruited in the presented study. Eight polymorphic variants in the TLR gene were genotyped by realtime PCR.Results. We found no statistically significant differences in the frequency of eight polymorphic variants in the TLR1, TLR2, TLR4 and TLR6 genes in the general group of patients. Stratification by gender and age showed that the frequency of the C/C genotype of the TLR1 gene (rs5743551) was increased in females with RHD (11.6 %) compared to the control group (5.3 %); a risk effect was determined for recessive inheritance patterns (odds ratio 2.43, 95 % confidence interval 1.07–5.52, p = 0.029). Moreover, the combination of polymorphic variants TLR2 (rs5743708) – TLR4 (rs4689791) – TLR1 (rs5743551) – TLR2 (rs3804099) showed the greatest significance in RHD risk.Conclusions. Future research on the different populations will allow to discover the general patterns of RHD pathogenesis, which will finally lead to the establishment of therapeutic targets for treatment of streptococcal infection and RHD prevention.

Development and validation of a predictive model for the diagnosis of rheumatic heart disease in low-income countries based on two cross-sectional studies

ObjectivesWe developed a questionnaire-based risk-scoring system to identify children at risk for rheumatic heart disease (RHD) in rural India. The resulting predictive model was validated in Nepal, in a population with a similar demographic profile to rural India. MethodsThe study involved 8646 students (mean age 13.0 years, 46% boys) from 20 middle and high schools in the West Midnapore district of India. The survey asked questions about the presence of different signs and symptoms of RHD. Students with possible RHD who experienced sore throat and joint pain were offered an echocardiogram to screen for RHD. Their findings were compared with randomly selected students without these symptoms. The data were analyzed to develop a predictive model for identifying RHD. ResultsBased on our univariate analyses, seven variables were used for building a predictive model. A four-variable model (joint pain plus sore throat, female sex, shortness of breath, and palpitations) best predicted the risk of RHD with a C-statistic of 0.854. A six-point scoring system developed from the model was validated among similarly aged children in Nepal. ConclusionsA simple questionnaire-based predictive instrument could identify children at higher risk for this disease in low-income countries where RHD remains prevalent. Echocardiography could then be used in these high-risk children to detect RHD in its early stages. This may support a strategy for more effective secondary prophylaxis of RHD.

Rationale, Design, and the Baseline Characteristics of the RHDGen (The Genetics of Rheumatic Heart Disease) Network Study†.

The genetics of rheumatic heart disease (RHDGen) Network was developed to assist the discovery and validation of genetic variations and biomarkers of risk for rheumatic heart disease (RHD) in continental Africans, as a part of the global fight to control and eradicate rheumatic fever/RHD. Thus, we describe the rationale and design of the RHDGen study, comprising participants from 8 African countries. RHDGen screened potential participants using echocardiography, thereafter enrolling RHD cases and ethnically-matched controls for whom case characteristics were documented. Biological samples were collected for conducting genetic analyses, including a discovery case-control genome-wide association study (GWAS) and a replication trio family study. Additional biological samples were also collected, and processed, for the measurement of biomarker analytes and the biomarker analyses are underway. Participants were enrolled into RHDGen between December 2012 and March 2018. For GWAS, 2548 RHD cases and 2261 controls (3301 women [69%]; mean age [SD], 37 [16.3] years) were available. RHD cases were predominantly Black (66%), Admixed (24%), and other ethnicities (10%). Among RHD cases, 34% were asymptomatic, 26% had prior valve surgery, and 23% had atrial fibrillation. The trio family replication arm included 116 RHD trio probands and 232 parents. RHDGen presents a rare opportunity to identify relevant patterns of genetic factors and biomarkers in Africans that may be associated with differential RHD risk. Furthermore, the RHDGen Network provides a platform for further work on fully elucidating the causes and mechanisms associated with RHD susceptibility and development.

Abstract 15393: Low Risk of Rheumatic Heart Disease Among Children Found to Have an Alternate Diagnosis to Acute Rheumatic Fever in a High Risk Setting

Introduction: In 2015, the American Heart Association revised the Jones Criteria, the gold standard for diagnosis of acute rheumatic fever (ARF). This revision included changes to increase the sensitivity for ARF in high-risk settings. The objective of this study was to determine if there were children who were found to be ARF-negative by strict application of these criteria in a high risk setting but found to have rheumatic heart disease (RHD) on follow-up evaluation. Methods: Between 2017 and 2020, we conducted an epidemiological study to determine the incidence of ARF in Uganda. Children and adolescents, 3-17 years, presenting with clinical concern for ARF (fever and joint pain, suspicion of carditis, or suspicion of chorea) were enrolled and evaluated using the Jones Criteria. Children ultimately found to have a laboratory-confirmed alternate diagnosis and those who did not meet ARF criteria but had an unknown final diagnosis, were asked to participate in a longitudinal echocardiographic follow-up study to monitor for development of RHD. Presence of RHD was considered a false negative test and used to calculate the false negative error of not receiving a diagnosis of ARF. Results: There were 351 children determined to have an alternate diagnosis during the study period; 180 with a laboratory confirmed final diagnosis (127 malaria, 20 non-rheumatic cardiac disease, 15 influenza, 18 other) and 171 with an unknown final diagnosis. Of these, 220 (62.7%) had at least one follow-up visit (median 366 days, range 10-1054). One child (1/220, <1%) developed echocardiographic evidence of borderline RHD during the follow-up period. Diagnostic overlap (met Jones Criteria but found to have a laboratory confirmed alternate diagnosis) was seen in 18% (33/180) of those with laboratory confirmed alternate diagnosis. Of these, 21 of 33 attended at least one follow-up (median 340 days, range 10-1054), and none showed echocardiographic evidence of RHD. Conclusions: Application of the 2015 Jones Criteria showed an exceptionally low rate of subsequent RHD, even in cases of diagnostic overlap. Clinicians working in ARF-endemic settings can have high confidence that children who do not meet criteria for ARF have a low risk of false negative diagnosis and short-term risk of RHD.

Investigation of the Familial Risk of Rheumatic Heart Disease with Systematic Echocardiographic Screening: Data from the PROVAR+ Family Study.

We aimed to use echocardiographic (echo) screening to evaluate the risk of Rheumatic Heart Disease (RHD) among the relatives of patients with advanced RHD, who were enrolled in the University Hospital’s outpatient clinics from February 2020 to September 2021. Consenting first-degree relatives were invited for echo screening using handheld devices (GE VSCAN) by non-physicians, with remote interpretation. Matched controls (spouses, neighbors) living in the same household were enrolled in a 1:5 fashion. A standard echo (GE Vivid-IQ) was scheduled if abnormalities were observed. In 16 months, 226 relatives and 47 controls of 121 patients were screened, including 129 children, 77 siblings and 20 parents. The mean age was 40 ± 17 years, 67% of the patients were women, and 239 (88%) lived with the index case for >10 years. Echo findings suggestive of RHD were confirmed in zero controls and 14 (7.5%) relatives (p = 0.05): 11 patients had mild/moderate mitral regurgitation, and four were associated with mitral stenosis and abnormal morphology. Two patients had mild aortic regurgitation and abnormal morphology, which were associated with mild aortic and mitral stenosis, and two patients with advanced RHD had bioprostheses in the mitral (2) and aortic (1) positions. In conclusion, first-degree relatives of individuals with clinical RHD are at greater risk of having RHD, on top of socioeconomic conditions.

Relationship between Environmental Factors and Rheumatic Heart Disease

Background. Rheumatic fever (RF) and rheumatic heart disease (RHD) are the most common acquired heart diseases in children. Environmental factors have been reported to play an important role in RHD’s prevalence
 Aim. The main purpose of this study is to assess the associations between environmental factors and RHD in children.
 Methods. A case control study was conducted in the Department of Child Health, Haji Adam Malik Hospital from April to June 2017. The case group consisted of children aged 5-18 years with RHD while control group consisted of healthy children. Demographic, anthropometric, and laboratory data were collected along with environmental factors. Statistical analysis was done using Statistical Product and Service Solution (SPSS). A P value of <0,05 with 95% confidence interval was considered significant.
 Results. A total of 39 children were enrolled in each group. Subjects’ father who only went to elementary and junior high school had a higher risk of having children with RHD (OR 28; p = 0.032 and OR 15.75; p = 0.011, respectively). Subjects’ mother who only went to junior high school had 7 times higher risk of having children with RHD (p = 0.026). Low monthly income increased the risk of RHD (OR 3,68; p = 0,009). Tap water usage, meat consumption more than once per week, and feasibility to buy clothes >1 pair per year decreased the risk of RHD at 0,31 (p = 0,013), 0,3 (p = 0,016), and 0,04 times (p <0,001) respectively.
 Conclusion. Parent’s education, monthly family income, water source, frequency of meat consumption, and feasibility to buy clothes are related to RHD in children.

M12. Network Meta-Analysis about Cytokine Gene Functional Polymorphisms Towards the Susceptibility and Severity of Acute Rheumatic Fever and Rheumatic Heart Disease among Asian and Non-Asian People

Abstract Background Great diversity among public hereditary variants may play a role in the susceptibility and severity of acute rheumatic fever (ARF)/rheumatic heart disease (RHD). Cytokine gene polymorphisms may contribute to the disease-associated cytokine imbalance. However, to the best of our knowledge, there is no existing meta-analysis concerning an association of the cytokine gene functional polymorphisms with the susceptibility / severity of ARF/RHD. Aims To investigate the potential association between cytokine gene functional polymorphisms of TNF-α, TGF-β, IL-10, IL-6 and IL-1β and the susceptibility and severity of ARF/RHD. Methods Comprehensive and structured search on Pubmed/Medline, Embase, EBSCO, and Cochrane Central Register of Controlled Trials was performed. Statistical analyses were performed using STATA. First, we performed direct pairwise meta-analysis. Then, a network meta-analysis was performed with the consistency model to compare the genetic models of different cytokine gene polymorphisms. Results Evidence derived from the meta-analysis of 24 retrospective cohort and case-control studies identified that elevated serum levels of TNF-α have been observed in ARF cases, occurring as a result of a SNP (-308G>A) in the promoter site of the TNF-α gene. Our results also suggest that IL-1β (-511) C/T polymorphism, TGF-β1 [rs1800469], and IL-1β [rs2853550] single nucleotide polymorphisms (SNPs) contributed to the susceptibility of ARF/RHD. Egger’s test did not demonstrate significant asymmetry in the dominant. Conclusion In summary, the polymorphism model increased the risk of RHD in the dominant genetic model, recessive genetic model, homozygote model and allelic genetic model among non-Asians while, recessive genetic model and homozygote model among Asians.

Abstract 11802: Evaluation of Family Risk of Rheumatic Heart Disease With Systematic Echocardiographic Screening: Data From the Provar+ Study

Introduction: Rheumatic Heart Disease (RHD) is determined by a complex interaction between socioeconomic environment and host susceptibility. Relatives of patients with advanced RHD share both, and may be at high-risk. We aimed to use echocardiographic (echo) family screening to evaluate the risk of RHD among 1 st degree relatives of patients with advanced RHD. Methods: From Feb 2020 - Jun 2021 patients with advanced RHD were consecutively enrolled in the University Hospital’s outpatient clinics. Consented 1 st degree relatives were invited for echo screening (2012 World Heart Federation Criteria) utilizing handheld devices (GE VSCAN) by non-physicians, with telemedicine interpretation by 2 experts. Matched controls (spouses, neighbors) living in the same household were also enrolled in a 1:5 fashion. A confirmatory full echo (GE Vivid IQ) was scheduled if abnormalities were observed, and all positive RHD cases were referred for follow-up. Results: In 16 months, 202 relatives and 42 controls of 117 patients were screened, including 114 children, 68 siblings and 20 parents. Mean age was 41±18 years, 62% were women and 214 (88%) lived with the index case for >10 years. At total 51 (21%) individuals had hypertension, 17 (7%) diabetes, 5 reported a previous stroke and only 5 (all relatives) had personal history of RHD. Among index cases, 73% reported current or past prescription of Penicillin. Echo findings suggestive of RHD were observed in 0 controls and 14 (7%) relatives (p=0.08), being 11 with mitral valve (MV) disease and 3 with mixed (mitral and aortic valve (AV)) disease. Eleven patients had mild/moderate MV regurgitation, 4 with associated MV stenosis and abnormal morphology. Two patients had mild AV regurgitation and abnormal AV morphology, associated with mild AV and MV stenosis, and 1 patient had bioprostheses in the MV and AV. One case of mild left ventricular dysfunction was observed, and 1 patient had indication of commissurotomy for MV stenosis at the time of diagnosis. Conclusions: First-degree relatives of individuals with clinical RHD are at greater risk of having RHD and family screening should be considered. Genotyping studies are warranted to better understand individual and family susceptibility to RHD, in addition to socioeconomic conditions.

Community-based prevalence of rheumatic heart disease in rural Ethiopia: Five-year follow-up

As little is known about the prevalence and clinical progression of subclinical (latent) rheumatic heart disease (RHD) in sub-Saharan Africa, we report the results of a 5 year follow-up of a community based, echocardiographic study of the disease, originally carried out in a rural area around Jimma, Ethiopia. Individuals with evidence of RHD detected during the baseline study as well as controls and their family members were screened with a short questionnaire together with transthoracic echocardiography. Of 56 individuals with RHD (37 definite and 19 borderline) in the original study, 36 (26 definite and 10 borderline) were successfully located 57.3 (range 44.9-70.7) months later. At follow-up two thirds of the definite cases still had definite disease; while a third had regressed. Approximately equal numbers of the borderline cases had progressed and regressed. Features of RHD had appeared in 5 of the 60 controls. There was an increased risk of RHD in the family relatives of borderline and definite cases (3.8 and 4.0 times respectively), notably among siblings. Compliance with penicillin prophylaxis was very poor. We show the persistence of echocardiographically demonstrable RHD in a rural sub-Saharan population. Both progression and regression of the disease were found; however, the majority of the individuals who had definite features of RHD had evidence of continuing RHD lesions five years later. There was an increased risk of RHD in the family relatives of borderline and definite cases, notably among siblings. The findings highlight the problems faced in addressing the problem of RHD in the rural areas of sub-Saharan Africa. They add to the evidence that community-based interventions for RHD will be required, together with appropriate ways of identifying active disease, achieving adequate penicillin prophylaxis and developing vaccines for primary prevention.

Association of Novel Locus With Rheumatic Heart Disease in Black African Individuals

Rheumatic heart disease (RHD), a sequela of rheumatic fever characterized by permanent heart valve damage, is the leading cause of cardiac surgery in Africa. However, its pathophysiologic characteristics and genetics are poorly understood. Understanding genetic susceptibility may aid in prevention, control, and interventions to eliminate RHD. To identify common genetic loci associated with RHD susceptibility in Black African individuals. This multicenter case-control genome-wide association study (GWAS), the Genetics of Rheumatic Heart Disease, examined more than 7 million genotyped and imputed single-nucleotide variations. The 4809 GWAS participants and 116 independent trio families were enrolled from 8 African countries between December 31, 2012, and March 31, 2018. All GWAS participants and trio probands were screened by use of echocardiography. Data analyses took place from May 15, 2017, until March 14, 2021. Genetic associations with RHD. This study included 4809 African participants (2548 RHD cases and 2261 controls; 3301 women [69%]; mean [SD] age, 36.5 [16.3] years). The GWAS identified a single RHD risk locus, 11q24.1 (rs1219406 [odds ratio, 1.65; 95% CI, 1.48-1.82; P = 4.36 × 10-8]), which reached genome-wide significance in Black African individuals. Our meta-analysis of Black (n = 3179) and admixed (n = 1055) African individuals revealed several suggestive loci. The study also replicated a previously reported association in Pacific Islander individuals (rs11846409) at the immunoglobulin heavy chain locus, in the meta-analysis of Black and admixed African individuals (odds ratio, 1.16; 95% CI, 1.06-1.27; P = 1.19 × 10-3). The HLA (rs9272622) associations reported in Aboriginal Australian individuals could not be replicated. In support of the known polygenic architecture for RHD, overtransmission of a polygenic risk score from unaffected parents to affected probands was observed (polygenic transmission disequilibrium testing mean [SE], 0.27 [0.16] SDs; P = .04996), and the chip-based heritability was estimated to be high at 0.49 (SE = 0.12; P = 3.28 × 10-5) in Black African individuals. This study revealed a novel candidate susceptibility locus exclusive to Black African individuals and an important heritable component to RHD susceptibility in African individuals.

The variable spectrum of anterior mitral valve leaflet restriction in rheumatic heart disease screening.

The World Heart Federation (WHF) screening criteria do not incorporate a strict, reproducible definition of anterior mitral valve leaflet (AMVL) restriction. Using a novel definition, we have identified two distinct AMVL restriction configurations. The first, called "distal tip" AMVL restriction is associated with additional morphological features of rheumatic heart disease (RHD), while the second, "gradual bowing" AMVL restriction is not. This "arch-like" leaflet configuration involves the base to tip of the medial MV in isolation. We hypothesize that this configuration is a normal variant. The prevalence and associated leaflet configurations of AMVL restriction were assessed in schoolchildren with an established "very low" (VLP), "high" (HP), and "very high" prevalence (VHP) of RHD. 936 studies were evaluated (HP 577 cases; VLP 359 cases). Sixty-five cases of "gradual bowing" AMVL restriction were identified in the HP cohort (11.3%, 95% CI 8.9-14.1) and 35 cases (9.7%, 95% CI 7-13.2) in the VLP cohort (P=.47). In the second analyses, an enriched cohort of 43 studies with proven definite RHD were evaluated. "Distal tip" AMVL restriction was identified in all 43 VHP cases (100%) and affected the central portion of the AMVL in all cases. "Gradual bowing" AMVL restriction appears to be a normal, benign variant of the MV, not associated with RHD risk nor with any other morphological features of RHD. Conversely, "Distal tip" AMVL restriction was present in all cases in the VHP cohort with no cases exhibiting a straight, nonrestricted central portion of the AMVL. This novel finding requires further investigation as a potential RHD rule-out test of the MV.

Determining the Risk of Developing Rheumatic Heart Disease Following a Negative Screening Echocardiogram.

Background: Screening echocardiograms can detect early-stage rheumatic heart disease (RHD), offering a chance to limit progression. Implementation of screening programs is challenging and requires further research. This is the first large-scale study assessing the risk of RHD among previous screen-negative children.Methods: This retrospective cohort study, conducted in Gulu, Uganda, performed school-based echo screening on children ages 5–18 years. Surveys were used to determine which children underwent initial screening 3–5 years prior. Age, gender, and disease severity were compared between cohorts. Relative risk (RR) of RHD was calculated for those with a prior screen-negative echo (exposed cohort) compared to those undergoing first screening (unexposed cohort).Results: Echo screening was completed in 75,708 children; 226 were excluded, leaving 1,582 in the exposed cohort and 73,900 in the unexposed cohort. Prevalence of new RHD was 0.6% (10/1,582) and 1% (737/73,900), in the exposed and unexposed cohorts, respectively. The RR of RHD was 0.64 (95% CI 0.3–1.2, p = 0.15), a nearly 40% reduced risk of RHD in those with a prior negative echo. There was no difference in age or gender between RHD cohorts. All cases in the exposed cohort were borderline/mild; 2.6% of cases in the unexposed cohort had moderate/severe disease.Conclusion: There was no statistical difference in RHD prevalence between previous screen-negative children and children with no prior echocardiogram, however, there was a trend toward decreased risk and severity. This information has important implications for the design of screening programs and the use of screening echocardiograms in endemic RHD regions.

Abstract 14693: Rheumatic Heart Disease and Deprivation in the United States: A Retrospective Review

Introduction: Rheumatic heart disease (RHD) tracks with other cardiovascular health inequities in the US; however, RHD mortality captures a fraction of those affected and lags behind diagnosis by decades. There is little contemporary data on children living with acute rheumatic fever (ARF) and RHD within the US. This study describes recent pediatric ARF/RHD in the US and examines the association with community deprivation. Methods: Sixty US institutions were invited to participate in a 10-year review (2008-2018). Geocoding was used to determine a census tract-based socioeconomic deprivation index (DI) ranging from 0-1 (1 being most deprived). Independent sample t-test was used to compare DI means. Odds ratios (OR) with 95% confidence intervals were obtained from multivariable logistic regression. The DI was scaled to provide ORs for a one standard deviation increase. Results: Data for 947 cases from 22 institutions showed median age at diagnosis of 9 years, with half identifying as male (51%) and non-white (52%), and three-quarters (74%) identifying as non-Hispanic. Most identified English as their primary language, had health insurance, and were first diagnosed in the US (84%, 89%, and 82%, respectively). Of the 157 (17%) with travel exposure, Pacific Islands (38%) and Africa (21%) were most commonly identified. Nearly three-quarters (73%) were diagnosed with ARF and most (98%) had an echocardiogram at diagnosis. While 96% of patients were prescribed secondary prophylaxis, only half (58%) were prescribed intramuscular Benzathine penicillin (BPG), the gold standard. The mean DI was 0.39±0.15. Higher deprivation was associated with RHD as opposed to ARF at diagnosis (DI 0.42 vs. 0.38, p<0.001). Additionally, higher deprivation was associated with increased risk of severe RHD (OR 1.34; 95% CI 1.11-1.62) and increased use of BPG vs enteral penicillin for secondary prevention (OR 0.67; 95% CI 0.56-0.8). Conclusions: Recent pediatric cases of ARF and RHD in the US are endemic, rather than from foreign exposure and children who live in more deprived communities are at risk for more severe disease. Additional research is needed into why intramuscular penicillin, which has superior efficacy compared to oral penicillin, is prescribed in only half of cases.

Epidemiologic profiles of subclinical rheumatic heart disease in children

Background Rheumatic heart disease (RHD) causes premature deaths every year worldwide. Low socioeconomic level is considered to be a risk factor facilitating the transmission of airway infections due to Streptococcus pyogenes. Subclinical RHD is a stage of RHD in which heart valve abnormalities have occurred according to the WHO or WHF classification but without any complaints to the subject. Echocardiography is used to screen subclinical RHD in several countries.
 Objective To estimate the prevalence, risk factors, and echocardiographic features of subclinical RHD in children.
 Methods This cross-sectional study was conducted on 250 elementary school children in Palembang, South Sumatera. We interviewed subject's parents about family characteristics, environment, and history of recurrent sore throat. Subjects underwent anthropometric examination, auscultation, and echocardiography. Diagnosis of RHD was based on World Health Organization (WHO) and World Heart Federation (WHF) criteria.
 Results Of 250 subjects, 132 (53.8%) were girls. Subjects’ age range was 5-14 years. The prevalence of subclinical RHD was 8% (95%CI 4.8 to 11.6). Of the 20 subclinical RHD subjects, 15 (75%) met the possible RHD criteria, 5 (25%) met the probable RHD criteria, and none met the definite RHD criteria. Multivariate analysis showed that household crowding (OR 8.135; 95%CI 1.048 TO 63.143; P=0.045), history of recurrent sore throat within the previous 6 months (OR 6,476; 95%CI 1.79 to 23.427; P=0.004) and age > 10 years (OR 3.167, 95%CI 1.184 to 8.471; P=0.022) significantly increased the risk of subclinical RHD.
 Conclusion The prevalence of subclinical RHD in elementary school children in Palembang was 8%. For echocardiographic features, most cases met the WHO/WHF possible RHD criteria. Factors significantly associated with the incidence of subclinical RHD are age > 10 years, household crowding, and history of recurrent sore throat in the previous 6 months.

Integrating the Prevention and Control of Rheumatic Heart Disease into Country Health Systems: A Systematic Review and Meta-Analysis.

Background:National and international political commitments have been made recently on rheumatic heart disease (RHD), a preventable heart condition that is endemic in low-resource countries. To inform best practice and identify evidence gaps, we assessed the effectiveness of RHD prevention and control programmes and the extent and nature of their integration into local health systems.Methods:We conducted a systematic review and meta-analysis using a previously published protocol that included electronic and manual searches for studies published between January 1990 and July 2019 reporting on prevention and control programmes for populations at risk for streptococcal pharyngitis, rheumatic fever, and/or RHD. We analysed programme integration according to a previously published framework and programme effectiveness using a results-chain framework. We meta-analysed secondary prophylaxis adherence using random-effects models. Study quality was assessed using peer-reviewed checklists (CASP and PRISM). PROSPERO registration: CRD42017076307.Findings:Five observational studies met with the inclusion criteria. Studies were similar in extent and nature of integration into health systems; no programme was completely integrated or non-integrated. A single study reported on programme impact. Secondary prophylaxis adherence improved among partially integrated RHD programmes (RR, 1.18 [95% CI, 1.03 to 1.36], 3 studies, n = 618). Risk of bias was low in two studies, and indeterminable in the remaining three studies.Interpretation:There is evidence that partially integrated RHD programmes are beneficial for a range of intermediate health outcomes. This review provides a starting point for the design and implementation of future RHD programmes by outlining current best practice for integration and identifying key gaps in knowledge.Funding:National Research Foundation of South Africa.

Echocardiographic screening to determine progression of latent rheumatic heart disease in endemic areas: A systematic review and meta-analysis.

BackgroundThe World Health Organisation previously recommended routine screening in school-aged children in countries with a high prevalence of rheumatic heart disease (RHD); however, it is unclear if screening-detected (latent) valve disease will inevitably evolve to a pathological lesion. Understanding the natural history of latent RHD is essential prior to recommendation of screening in endemic areas. Studies documenting the progression of latent RHD have had contrasting conclusions about the pathogenicity of latent valvular lesions. This review provides estimates of rates of progression of latent RHD.Methods and findingsIn this systematic review and meta-analysis, we searched EMBASE, MEDLINE, Global Index Medicus, Africa Wide, Cochrane Database of Systematic Reviews and Global Health Database for studies published before April 30, 2019. Study data were extracted from all studies which reported follow-up data on progression of latent valve lesions. Studies with control cohorts were used to calculate comparative prevalence ratios. This study is registered with PROSPERO, number CRD42019119427. We identified 12 studies reporting follow-up data on latent RHD for 950 people in 9 countries. The estimated pooled prevalence rate for progression per year of latent RHD was 5%/year (95% CI 2–8). Eight studies reported on the progression of borderline latent RHD with an estimated pooled prevalence of 2%/year (95% CI 0–4). Three studies included control groups. There was a significant increase in the risk of progression of valvular disease in the latent group compared with controls (RR = 3.57 (95%CI = 1.65–7.70, P = 0.001). The overall risk of bias was low. Given most studies included penicillin administration we were unable to document the natural history of latent RHD. Furthermore, we were unable to perform a sensitivity analysis to determine the effect of administering penicillin prophylaxis on progression of valve disease given prescription of penicillin was not standardised.ConclusionLatent RHD has a slow rate of progression but it is significantly higher compared to controls, with definite latent RHD having a higher rate of progression compared with borderline latent disease. There are a massive number of individuals at risk for RHD in the developing world as well as logistical challenges of screening and delivering penicillin prophylaxis. The low rate of progression from untargeted screening may be an important consideration in resource-constrained environments.

747 Poor Domestic Smoke Ventilation is associated With an Increased Risk of Rheumatic Heart Disease in Sri Lankan Children

747 Poor Domestic Smoke Ventilation is associated With an Increased Risk of Rheumatic Heart Disease in Sri Lankan Children

A Validation Study: How Predictive Is a Diagnostic Coding Algorithm at Identifying Rheumatic Heart Disease in Western Australian Hospital Data?

International Classification of Diseases codes for rheumatic heart disease (RHD) (ICD-10 I05-I08) include valvular heart disease of unspecified origin, limiting their usefulness for estimating RHD burden. An expert opinion-based algorithm was developed to increase their accuracy for epidemiological case ascertainment. The algorithm included codes not defaulting to RHD ('probable') plus selected codes pertaining to mitral valve involvement in patients <60 years ('possible'). We aimed to determine the positive predictive value (PPV) for RHD of algorithm-selected hospital admissions. Chart reviews of RHD-coded admissions (n=368) to Western Australian tertiary hospitals (2009-2016) authenticated RHD diagnosis. We selected all cases with algorithm-positive codes from populations at high-risk of RHD and an age-stratified random sample from low-risk groups. RHD status was determined from echocardiographic reports or clinical diagnosis in charts. PPVs were compared by population risk status (high-risk/low-risk), age group, gender, principal/secondary diagnosis and probable/possible codes. High-risk patients had higher PPVs than low-risk patients (83.8% vs 54.9%, p<0.0001). PPVs were 91.5% and 51.5% respectively for algorithm-defined 'probable RHD' and 'possible' codes (p<0.0001). The PPVs in low-risk patients were higher for principal diagnoses than secondary diagnoses (84.5% vs 44.8%, weighted p<0.0001) but were similar in high-risk patients (92.5% vs 81.7%, p=0.096). The algorithm performs well for RHD coded as a principal diagnosis, 'probable' codes or in populations at high risk of RHD. Refinement is needed for identifying true RHD in low-risk groups.

Echocardiographic screening for rheumatic heart disease in Turkish schoolchildren.

The aim of this study is to investigate the prevalence of subclinical rheumatic heart disease in schoolchildren aged 5-18 by using portable echocardiography in Ankara, Turkey. The portable echocardiography screening was performed by a paediatric cardiologist for all of the cases. The mean age of 2550 healthy students was 11.09 ± 2.91 years (1339 females, 1211 males) in three private and three public schools. Echocardiographic studies were assessed according to 2012 World Heart Federation criteria for rheumatic heart disease. After reviewing the echocardiographic images, 73 students were reevaluated by an advanced echocardiography device in the university hospital. Evidence of definite subclinical rheumatic heart disease was found in 39 students (15/1000) and borderline rheumatic heart disease in 20 students (8/1000). No children had any clinical symptoms. The mean age of children diagnosed with rheumatic heart disease and borderline rheumatic heart disease is 12.4 and 11.4 years, respectively. The risk of rheumatic heart disease was found to be increased sevenfold in girls between 14 and 18 years. We surprisingly observed that the prevalence of definite rheumatic heart disease in private schools located in high-income areas of Ankara was higher than that in public schools. This is the first and largest single-centred echocardiographic screening study for subclinical rheumatic heart disease in Turkish schoolchildren. The frequency of rheumatic heart disease has been found to be 15/1000. This finding is similar to those of recent echocardiographic screening studies performed in middle and high-risk populations. We conclude that to decrease the burden of rheumatic heart disease, echocardiographic screening studies are necessary, and long-term follow-up of children with echocardiographically diagnosed subclinical rheumatic heart disease is needed.

Public health and economic perspectives on acute rheumatic fever and rheumatic heart disease.

Public health and economic perspectives on acute rheumatic fever and rheumatic heart disease.