Ana Olga Mocumbi

Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study)

AIMS Rheumatic heart disease (RHD) accounts for over a million premature deaths annually; however, there is little contemporary information on presentation, complications, and treatment. METHODS AND RESULTS This prospective registry enrolled 3343 patients (median age 28 years, 66.2% female) presenting with RHD at 25 hospitals in 12 African countries, India, and Yemen between January 2010 and November 2012. The majority (63.9%) had moderate-to-severe multivalvular disease complicated by congestive heart failure (33.4%), pulmonary hypertension (28.8%), atrial fibrillation (AF) (21.8%), stroke (7.1%), infective endocarditis (4%), and major bleeding (2.7%). One-quarter of adults and 5.3% of children had decreased left ventricular (LV) systolic function; 23% of adults and 14.1% of children had dilated LVs. Fifty-five percent (n = 1761) of patients were on secondary antibiotic prophylaxis. Oral anti-coagulants were prescribed in 69.5% (n = 946) of patients with mechanical valves (n = 501), AF (n = 397), and high-risk mitral stenosis in sinus rhythm (n = 48). However, only 28.3% (n = 269) had a therapeutic international normalized ratio. Among 1825 women of childbearing age (12-51 years), only 3.6% (n = 65) were on contraception. The utilization of valvuloplasty and valve surgery was higher in upper-middle compared with lower-income countries. CONCLUSION Rheumatic heart disease patients were young, predominantly female, and had high prevalence of major cardiovascular complications. There is suboptimal utilization of secondary antibiotic prophylaxis, oral anti-coagulation, and contraception, and variations in the use of percutaneous and surgical interventions by country income level.

A Population Study of Endomyocardial Fibrosis in a Rural Area of Mozambique

BACKGROUND Endomyocardial fibrosis is the most common restrictive cardiomyopathy worldwide. It has no specific treatment and carries a poor prognosis, since most patients present with advanced heart failure. On the basis of clinical series, regional variations in distribution have been reported within several countries in Africa, Asia, and South America, but large-scale data are lacking on the epidemiologic features and early stages of the disease. METHODS We used transthoracic echocardiography to determine the prevalence of endomyocardial fibrosis in a rural area of Mozambique. We screened a random sample of 1063 subjects of all age groups selected by clustering. Major and minor diagnostic criteria were defined, and a severity score was developed and applied. Cases were classified according to the distribution and severity of the lesions in the heart. RESULTS The estimated overall prevalence of endomyocardial fibrosis was 19.8%, or 211 of 1063 subjects (95% confidence interval [CI], 17.4 to 22.2). The prevalence was highest among persons 10 to 19 years of age (28.1%, or 73 of 260 subjects [95% CI, 22.6 to 33.6]) and was higher among male than among female subjects (23.0% vs. 17.5%, P=0.03). The most common form was biventricular endomyocardial fibrosis (a prevalence of 55.5%, or 117 of 211 subjects [95% CI, 48.8 to 62.2]), followed by right-sided endomyocardial fibrosis (a prevalence of 28.0%, or 59 of 211 subjects [95% CI, 21.9 to 34.1]). Most affected subjects had mild-to-moderate structural and functional echocardiographic abnormalities. Only 48 persons with endomyocardial fibrosis (22.7%) were symptomatic. The frequency of familial occurrence was high. CONCLUSIONS Endomyocardial fibrosis is common in a rural area of Mozambique. By using echocardiography, we were able to detect early, asymptomatic stages of the disease. These findings may aid in the study of the pathogenesis of the disease and in the development of new management strategies.

The Drakensberg Declaration on the Control of Rheumatic Fever and Rheumatic Heart Disease in Africa

Bongani Mayosi, Kate Robertson, Jimmy Volmink, Wole Adebo, Kingsley Akinyore, Albert Amoah, Charles Bannerman, Shan Biesman-Simons, Jonathan Carapetis, Antoinette Cilliers, Patrick Commerford, Anne Croasdale, Albertino Damasceno, Jenny Dean, Michael Dean, Robert de Souza, Antonio Filipe, Chris Hugo-Hamman, Sally-Ann JurgensClur, Pierre Kombila-Koumba, Christelle Kotzenberg, John Lawrenson, Pravin Manga, Jonathan Matenga, Tshimbi Mathivha, Phindile Mntla, Ana Mocumbi, Tiny Mokone, Elijah Ogola, Samuel Omokhodion, Chapman Palweni, Adrian Pearce, Avril Salo, Baby Thomas, Kathie Walker, Charles Wiysonge, Salah Zaher

Neglected tropical cardiomyopathies: II. Endomyocardial fibrosis

Endomyocardial fibrosis (EMF) was described as a distinct clinicopathological entity in 1948 in Uganda.w1 Initially several terms were used to describe the disease. These included tropical endomyocardial disease, endocarditis parietalis fibroplastica, endocardial fibrosis, constrictive endocarditis and endocardial fibroelastose. EMF is thought to be the most common type of restrictive cardiomyopathy worldwide.1 Although most studies have been reported from Uganda, Ivory Coast, Nigeria, Brazil and India, the disease has been occasionally encountered outside the tropics.2 Geographic distribution of EMF is not uniform both in Africa and Asia.3 4 In the endemic areas of Africa, EMF is the second cause of admission for acquired cardiovascular disease in children and young adults, after rheumatic heart disease,5 w2 accounting for up to 20% of all causes of heart failure. To date our knowledge of the prevalence of the disease is derived from hospital based studies with absence of data from systematic studies in the community. EMF affects predominantly children and adolescents, usually from low socioeconomic background. More than half the cases are seen in the first decade of life. Male preponderance was found in Kerala and Nigeria, while female preponderance has been described in Brazil and Uganda. A bimodal age distribution has been reported in some studies.5 w3 The aetiology of EMF remains unknown. Several hypotheses have been proposed and explored including cardiotoxicity of the eosinophil, infectious agents, autoimmune processes, genetic predisposition, ethnicity, diet, climate and poverty. ### Hypereosinophilia EMF appears to share some pathogenic mechanisms with the hypereosinophilic syndromes, which comprise a heterogenous group of disorders characterised by peripheral eosinophilia for at least 6 months and end organ damage related to eosinophil infiltrations. These syndromes have been classified as idiopathic, clonal and reactive. The similarity of mechanisms responsible for EMF and the hypereosinophilic syndromes could have exciting therapeutic implications. …

Forgotten cardiovascular diseases in Africa

Much of the global burden of cardiovascular disease is now carried by low and middle income countries. Unfortunately, many of these regions are still grappling with poverty and infection-related cardiovascular diseases, such as endomyocardial fibrosis, tuberculous pericarditis and rheumatic heart disease. In addition, Africa has its unique diseases that occur more commonly in Africans as peripartum cardiomyopathy or, almost uniquely in Africa, as subvalvular aneurysm. We present our perspective on forgotten cardiovascular disease in Africa in the context of the epidemic of cardiovascular disease due to global changes in life style.

Clinical Outcomes in 3343 Children and Adults with Rheumatic Heart Disease from 14 Low and Middle Income Countries: 2-Year Follow-up of the Global Rheumatic Heart Disease Registry (the REMEDY study)

Background: There are few contemporary data on the mortality and morbidity associated with rheumatic heart disease or information on their predictors. We report the 2-year follow-up of individuals with rheumatic heart disease from 14 low- and middle-income countries in Africa and Asia. Methods: Between January 2010 and November 2012, we enrolled 3343 patients from 25 centers in 14 countries and followed them for 2 years to assess mortality, congestive heart failure, stroke or transient ischemic attack, recurrent acute rheumatic fever, and infective endocarditis. Results: Vital status at 24 months was known for 2960 (88.5%) patients. Two-thirds were female. Although patients were young (median age, 28 years; interquartile range, 18–40), the 2-year case fatality rate was high (500 deaths, 16.9%). Mortality rate was 116.3/1000 patient-years in the first year and 65.4/1000 patient-years in the second year. Median age at death was 28.7 years. Independent predictors of death were severe valve disease (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.80–3.11), congestive heart failure (HR, 2.16; 95% CI, 1.70–2.72), New York Heart Association functional class III/IV (HR, 1.67; 95% CI, 1.32–2.10), atrial fibrillation (HR, 1.40; 95% CI, 1.10–1.78), and older age (HR, 1.02; 95% CI, 1.01–1.02 per year increase) at enrollment. Postprimary education (HR, 0.67; 95% CI, 0.54–0.85) and female sex (HR, 0.65; 95% CI, 0.52–0.80) were associated with lower risk of death. Two hundred and four (6.9%) patients had new congestive heart failure (incidence, 38.42/1000 patient-years), 46 (1.6%) had a stroke or transient ischemic attack (8.45/1000 patient-years), 19 (0.6%) had recurrent acute rheumatic fever (3.49/1000 patient-years), and 20 (0.7%) had infective endocarditis (3.65/1000 patient-years). Previous stroke and older age were independent predictors of stroke/transient ischemic attack or systemic embolism. Patients from low- and lower-middle–income countries had significantly higher age- and sex-adjusted mortality than patients from upper-middle–income countries. Valve surgery was significantly more common in upper-middle–income than in lower-middle– or low-income countries. Conclusions: Patients with clinical rheumatic heart disease have high mortality and morbidity despite being young; those from low- and lower-middle–income countries had a poorer prognosis associated with advanced disease and low education. Programs focused on early detection and the treatment of clinical rheumatic heart disease are required to improve outcomes.

Echocardiographic screening for rheumatic heart disease

Rheumatic fever is a delayed sequel to throat infection by a group A streptococcus. More than one third of affected children develop carditis, followed many years later – especially in the case of recurrent rheumatic infections – by progressive and permanent valvular lesions, known as rheumatic heart disease. 2 Rheumatic heart disease is now largely restricted to developing countries and most of the reduction in its incidence in wealthy countries is attributable to better living conditions with consequent reductions in the transmission of group A streptococci. Nevertheless, with the decline in rheumatic fever in industrialized countries and the emphasis on diseases such as malaria and HIV in developing countries, there has been a parallel reduction in research into this still prevalent and important condition. 3 Rheumatic heart disease remains an obvious public health burden across the developing world causing more than 200 000 deaths a year. 4 An exaggerated immune response to specific bacterial epitopes in a susceptible host is thought to be the basis of the disease. 5 Rheumatic heart disease usually results from the cumulative damage from recurrent episodes of acute rheumatic fever. It has been reported that after a first episode of carditis, cardiac ausculta tion becomes unremarkable in one-third of children but even these children may progress to significant rheumatic valve disease in later life, as confirmed by echocardiography. 6 Thus early detection of “subclini cal” rheumatic valve disease is vital, as it presents an opportunity for case detection at a time when prophylactic penicillin – to prevent recurrent episodes – can prevent progression to important valve disease in young adult life. Early detection of rheumatic heart disease in school children is traditionally done by listening for murmurs by stethoscope, followed by echocardiographic confir mation only in suspected cases. Recently, we did systematic echocardiographic screening in schools in Cambodia and Mozambique, to assess whether early case detection could be improved by using portable ultrasound. 7 We achieved a case detection rate by echocardiography approximately 10-fold that achieved by clinical examination only. Such screening thus makes it possible to identify children at risk of developing severe rheumatic valve disease for whom secondary prevention with penicillin prophylaxis may be effective. Acute rheumatic fever episodes can be prevented by antibiotic treatment of group A streptococcal throat infections, a strategy known as primary prophy

Neglected tropical cardiomyopathies: I. Chagas disease

Cardiomyopathies, defined as diseases of the myocardium associated with cardiac dysfunction, are classified into dilated, hypertrophic, restrictive and arrhythmogenic right ventricular cardiomyopathy, as well as unclassified.1 More recently, molecular classification has been suggested.2 Cardiomyopathies continue to be a significant cause of morbidity and mortality in the developed world.w1 In developing countries, however, there appears to be an increased incidence of the “usual” forms of cardiomyopathy, with a modified clinical course possibly due to genetic differences or environmental factors such as malnutrition, infections and pollution.w2 In addition, there are specific cardiomyopathies endemic to the tropics such as Chagas and endomyocardial fibrosis, which cause a considerable amount of death and suffering and have been classified as neglected diseases. We here describe what is known about these two diseases, their aetiologies, pathogenesis and management and outline directions for further research. The present article will discuss Chagas disease, and a subsequent article will address endomyocardial fibrosis. Chagas disease is the leading cause of cardiac disease in many countries in Latin America, and the World Health Organization has estimated that 16–18 million people are currently infected and 90 million are at risk of infection.3 Chagas disease has been classified as one of the most neglected diseases in the world,w3 with no new drug development in the past 30 years.w4 Yet there are still 200 000 new cases of Chagas disease reported each year and some rural communities in Latin America have seroprevalence rates as high as 40%. Chagas disease is caused by the protozoan parasite Trypanosoma cruzi (fig 1), which is spread by triatomine bugs (fig 2). The disease is mainly constrained geographically to countries where its vector is endemic, ranging from South America to Mexico and southern USA. Transmission has also been shown to occur via blood transfusions, …

Seven key actions to eradicate rheumatic heart disease in Africa: the Addis Ababa communiqué.

Abstract Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) remain major causes of heart failure, stroke and death among African women and children, despite being preventable and imminently treatable. From 21 to 22 February 2015, the Social Cluster of the Africa Union Commission (AUC) hosted a consultation with RHD experts convened by the Pan-African Society of Cardiology (PASCAR) in Addis Ababa, Ethiopia, to develop a ‘roadmap’ of key actions that need to be taken by governments to eliminate ARF and eradicate RHD in Africa. Seven priority areas for action were adopted: (1) create prospective disease registers at sentinel sites in affected countries to measure disease burden and track progress towards the reduction of mortality by 25% by the year 2025, (2) ensure an adequate supply of high-quality benzathine penicillin for the primary and secondary prevention of ARF/RHD, (3) improve access to reproductive health services for women with RHD and other non-communicable diseases (NCD), (4) decentralise technical expertise and technology for diagnosing and managing ARF and RHD (including ultrasound of the heart), (5) establish national and regional centres of excellence for essential cardiac surgery for the treatment of affected patients and training of cardiovascular practitioners of the future, (6) initiate national multi-sectoral RHD programmes within NCD control programmes of affected countries, and (7) foster international partnerships with multinational organsations for resource mobilisation, monitoring and evaluation of the programme to end RHD in Africa. This Addis Ababa communiqué has since been endorsed by African Union heads of state, and plans are underway to implement the roadmap in order to end ARF and RHD in Africa in our lifetime.

Endemic Cardiovascular Diseases of the Poorest Billion.

The poorest billion people are distributed throughout the world, though most are concentrated in rural sub-Saharan Africa and South Asia. Cardiovascular disease (CVD) data can be sparse in low- and middle-income countries beyond urban centers. Despite this urban bias, CVD registries from the poorest countries have long revealed a predominance of nonatherosclerotic stroke, hypertensive heart disease, nonischemic and Chagas cardiomyopathies, rheumatic heart disease, and congenital heart anomalies, among others. Ischemic heart disease has been relatively uncommon. Here, we summarize what is known about the epidemiology of CVDs among the world’s poorest people and evaluate the relevance of global targets for CVD control in this population. We assessed both primary data sources, and the 2013 Global Burden of Disease Study modeled estimates in the world’s 16 poorest countries where 62% of the population are among the poorest billion. We found that ischemic heart disease accounted for only 12% of the combined CVD and congenital heart anomaly disability-adjusted life years (DALYs) in the poorest countries, compared with 51% of DALYs in high-income countries. We found that as little as 53% of the combined CVD and congenital heart anomaly burden (1629/3049 DALYs per 100 000) was attributed to behavioral or metabolic risk factors in the poorest countries (eg, in Niger, 82% of the population among the poorest billion) compared with 85% of the combined CVD and congenital heart anomaly burden (4439/5199 DALYs) in high-income countries. Further, of the combined CVD and congenital heart anomaly burden, 34% was accrued in people under age 30 years in the poorest countries, while only 3% is accrued under age 30 years in high-income countries. We conclude although the current global targets for noncommunicable disease and CVD control will help diminish premature CVD death in the poorest populations, they are not sufficient. Specifically, the current framework (1) excludes deaths of people <30 years of age and deaths attributable to congenital heart anomalies, and (2) emphasizes interventions to prevent and treat conditions attributed to behavioral and metabolic risks factors. We recommend a complementary strategy for the poorest populations that targets premature death at younger ages, addresses environmental and infectious risks, and introduces broader integrated health system interventions, including cardiac surgery for congenital and rheumatic heart disease.