Liesl Zühlke

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.

Congenital heart disease and rheumatic heart disease in Africa: recent advances and current priorities

Africa has one of the highest prevalence of heart diseases in children and young adults, including congenital heart disease (CHD) and rheumatic heart disease (RHD). We present here an extensive review of recent data from the African continent highlighting key studies and information regarding progress in CHD and RHD since 2005. Main findings include evidence that the CHD burden is underestimated mainly due to the poor outcome of African children with CHD. The interest in primary prevention for RHD has been recently re-emphasised, and new data are available regarding echocardiographic screening for subclinical RHD and initiation of secondary prevention. There is an urgent need for comprehensive service frameworks to improve access and level of care and services for patients, educational programmes to reinforce the importance of prevention and early diagnosis and a relevant research agenda focusing on the African context.

Global research priorities in rheumatic fever and rheumatic heart disease

We now stand at a critical juncture for rheumatic fever (RF) and rheumatic heart disease (RHD) control. In recent years, we have seen a surge of interest in these diseases in regions of the world where RF/RHD mostly occur. This brings real opportunities to make dramatic progress in the next few years, but also real risks if we miss these opportunities. Most public health and clinical approaches in RF/RHD arose directly from programmes of research. Many unanswered questions remain, including those around how to implement what we know will work, so research will continue to be essential in our efforts to bring a global solution to this disease. Here we outline our proposed research priorities in RF/RHD for the coming decade, grouped under the following four challenges: Translating what we know already into practical RHD control; How to identify people with RHD earlier, so that preventive measures have a higher chance of success; Better understanding of disease pathogenesis, with a view to improved diagnosis and treatment of ARF and RHD; and Finding an effective approach to primary prevention. We propose a mixture of basic, applied, and implementation science. With concerted efforts, strong links to clinical and public health infrastructure, and advocacy and funding support from the international community, there are good prospects for controlling these RF and RHD over the next decade.

Acute rheumatic fever and rheumatic heart disease.

Acute rheumatic fever (ARF) is the result of an autoimmune response to pharyngitis caused by infection with group A Streptococcus. The long-term damage to cardiac valves caused by ARF, which can result from a single severe episode or from multiple recurrent episodes of the illness, is known as rheumatic heart disease (RHD) and is a notable cause of morbidity and mortality in resource-poor settings around the world. Although our understanding of disease pathogenesis has advanced in recent years, this has not led to dramatic improvements in diagnostic approaches, which are still reliant on clinical features using the Jones Criteria, or treatment practices. Indeed, penicillin has been the mainstay of treatment for decades and there is no other treatment that has been proven to alter the likelihood or the severity of RHD after an episode of ARF. Recent advances — including the use of echocardiographic diagnosis in those with ARF and in screening for early detection of RHD, progress in developing group A streptococcal vaccines and an increased focus on the lived experience of those with RHD and the need to improve quality of life — give cause for optimism that progress will be made in coming years against this neglected disease that affects populations around the world, but is a particular issue for those living in poverty.

Echocardiographic Screening for Subclinical Rheumatic Heart Disease Remains a Research Tool Pending Studies of Impact on Prognosis

The application of portable echocardiography to the screening of asymptomatic children and young adults for rheumatic heart disease (RHD) in developing countries indicates that the disease may affect 62 million to 78 million individuals worldwide, which could potentially result in 1.4 million deaths per year from RHD and its complications. The World Heart Federation has developed a guideline for the echocardiographic diagnosis of RHD in asymptomatic individuals without a history of acute rheumatic fever (ARF) in order to ensure the reliability, comparability, and reproducibility of findings of the echocardiographic screening studies. Early studies suggest that a third of individuals with asymptomatic subclinical RHD revert to normal echocardiographic findings on repeat testing after 6–12 months, suggesting that repeat echocardiography may be necessary to confirm the findings prior to consideration of interventions such as antibiotic prophylaxis. It is not known, however, whether echocardiographic screening for asymptomatic subclinical RHD or the introduction of antibiotic prophylaxis for affected individuals improves the prognosis of RHD. Furthermore, the cost-effectiveness of this screening method has not been established in the vast majority of affected countries. Therefore, echocardiographic screening for asymptomatic subclinical RHD remains a research tool until studies of impact on prognosis and cost-effectiveness are conducted.

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.

Rationale and design of a Global Rheumatic Heart Disease Registry: The REMEDY study

BACKGROUND Rheumatic heart disease (RHD) is the principal cause of valvular heart disease-related mortality and morbidity in low- and middle-income countries. The disease predominantly affects children and young adults. It is estimated that RHD may potentially be responsible for 1.4 million deaths annually worldwide and 7.5% of all strokes occurring in developing countries. Despite the staggering global burden, there are no contemporary data documenting the presentation, clinical course, complications, and treatment practices among patients with RHD. METHODS The REMEDY study is a prospective, international, multicenter, hospital-based registry planned in 2 phases: the vanguard phase involving centers in Africa and India will enroll 3,000 participants with RHD over a 1-year period. We will document clinical and echocardiographic characteristics of patients at presentation. Over a 2-year follow-up, we will document disease progression and treatment practices with particular reference to adherence to secondary prophylaxis and oral anticoagulation regimens. With 3,000 patients, we will be able to reliably determine the incidence of all-cause mortality, worsening heart failure requiring hospitalization, systemic embolism (including stroke), and major bleeding individually among all participants. We will identify barriers to care in a subgroup of 500 patients. CONCLUSION The REMEDY study will provide comprehensive, contemporary data on patients with RHD and will help in the development of strategies to prevent and manage RHD and its complications.

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.

Prevalence of rheumatic heart disease in 4720 asymptomatic scholars from South Africa and Ethiopia

Background In Africa, screening for asymptomatic rheumatic heart disease (RHD) has been conducted in single communities using non-standardised echocardiographic criteria. The use of different diagnostic criteria has led to widely variable estimates of the prevalence of RHD in the same communities. Methods Randomly selected school pupils, from 4 to 24 years of age in Bonteheuwel and Langa communities of Cape Town, South Africa, and Jimma, Ethiopia, respectively, were screened for RHD according to standardised evidence-based echocardiographic diagnostic criteria of the World Heart Federation (WHF). Results We screened 4720 scholars. In South Africa (n=2720), 1604 (58.9%) were female and the mean age was 12.2±4.2 years. In Ethiopia (n=2000), 1012 (50.6%) were female and the mean age was 10.7±2.5 years. Echocardiographic screening revealed 55 cases of definite and borderline RHD by WHF criteria in South Africa and 61 cases in Ethiopia, corresponding to a prevalence of 20.2 cases per 1000 (95% CI 15.3 to 26.2) and 31 cases per 1000 (95% CI 23.4 to 39.0), respectively. The odds of detecting a scholar with RHD in Ethiopia were 1.5 times higher than in South Africa (OR 1.5; 95% CI 1.04 to 2.2, p=0.02). The prevalence of RHD was 27 cases per 1000 (95% CI 19.3 to 36.8) in Langa, and 12.5 cases per 1000 (95% CI 7.1 to 20.2) in Bonteheuwel. The odds of detecting a schoolchild with RHD in Langa compared with Bonteheuwel were 2.2 (OR 2.2; 95% CI 1.2 to 4.2, p=0.0071). Interpretation There were significant differences in detecting asymptomatic RHD in school pupils of different countries and in different communities within a country in sub-Saharan Africa. The variation in the prevalence of RHD between countries and communities has important implications for the modelling of the global burden of RHD.

Rheumatic Fever: Neglected Again

We appreciate M. Enserinks News of the Week story (“Some neglected diseases are more neglected than others,” 6 February, p. [700][1]) on the Moran et al. study analyzing the current state of research into so-called “neglected diseases” ([1][2]). We would like to highlight one neglected