Browsing by Subject "Rheumatic Heart Disease"

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    A cost-effective strategy for primary prevention of acute rheumatic fever and rheumatic heart disease in children with pharyngitis
    (2013) Irlam, James H; Mayosi, Bongani M; Engel, Mark E; Gaziano, Thomas A
    Primary prevention of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) in children depends on prompt and effective diagnosis and treatment of pharyngitis at the primary level of care. Cost-effectiveness modeling shows that the most cost-effective strategy for primary prevention in South Africa (SA) is to use a simple symptomatic clinical decision rule (CDR) to diagnose pharyngitis in children presenting at the primary level of care and then to treat them with a single dose of intramuscular penicillin. Treat All and CDR2+ strategies are affordable and simple and miss few cases of streptococcal pharyngitis at the primary level of care. The CDR2+ strategy is the most cost-effective for primary prevention of ARF and RHD in urban SA and should complement primordial and secondary prevention efforts.
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    A novel trans-catheter heart valve system for low- to middle-income countries: need assessment, surgical feasibility and preclinical translation
    (2024) Scherman, Jacques; Zilla, Peter
    My thesis covers the clinical translation of a unique initiative at a South African tertiary institution towards a comprehensive, tailor-made African answer to a global health problem affecting millions of indigent patients outside the industrialized world. Rheumatic Heart Disease is typically a disease of poverty, leading to different levels of destruction of patients' heart valves in an estimated 33 million patients of low- to middle income countries globally. Heart valve surgery is often the only life-saving remedy but seriously underprovided in developing countries. Moreover, replacement heart valve prostheses were developed for degenerative pathologies prevailing in high-income countries and poorly suited for the majority of patients suffering from rheumatic heart disease. As a clinician at the interface of the developing and developed world, I dedicated the first part of my thesis establishing the shortcomings of contemporary replacement heart valves in rheumatic patients. This included one of the rare follow-up studies in indigent patients confirming the need for a radically different concept. Providing the clinical end-goals to an engineering endeavor at the University of Cape Town to develop a replacement heart valve for rheumatic patients, the second part of my PhD focused on the in-vivo translation of this concept. In the absence of an established animal model for such a trans-catheter solution, the extensive implant series I performed achieved two goals: optimization of the devices in close interaction with the engineers and establishment of anatomical inclusion/exclusion criteria in both the sheep and pig model. Based on these accomplishments, I worked out an optimal implantation technique and demonstrated short and long-term performance of the developed heart valve devices in the animal models I established. Having successfully provided all the regulatory preclinical data required for ‘first-in-human' implants, I used a statistical analysis approach to extrapolate clinical and pre-clinical data towards size predictions for the replacement valves expected to be needed in an upcoming clinical trial while also defining anatomical exclusion criteria. I trust that this comprehensive clinical and laboratory-based PhD thesis that systematically progressed through the clinical translation process of a novel university-based development complies with the high standards defining the highest of postgraduate degrees.
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    Clinical characteristics and outcomes of children with rheumatic heart disease: a global rheumatic heart disease registry (REMEDY) sub-analysis
    (2021) Makate, Sindiswa A; Zühlke, Lisel Joanna
    Background: Despite Rheumatic Heart Disease (RHD) contributing to an estimated disease burden in 2019 of 40 million people and 285 500 deaths, few studies document the characteristics and outcomes in children. We undertook a sub-analysis of children from the multi-centre prospective two-year global Rheumatic Heart Disease Registry (REMEDY) to document their presentation, clinical characteristics and outcomes. Methods: Nine-hundred and twenty-one children were enrolled into the REMEDY registry among the 3,343 symptomatic RHD patients from 25 hospitals in 12 African countries, India and Yemen and followed up over 24 months to assess characteristics, complications and outcome. Results: More than half of the children enrolled in the REMEDY study presented with severe valvular heart disease; 60% had more than one valve involved, 30% were classified as NYHA class III/IV and 17.7% died within 24 months. Just over 20% of children were not on penicillin prophylaxis. Although 20% met criteria for surgery, only less than 9% (n=78, 8.5%) had had percutaneous or surgical intervention with half from upper-middle-income countries. The major risk factors associated with mortality included older age (Hazard Ratio (HR): 1.01, p=0.001) and atrial fibrillation or flutter (HR: 2.3, p=0.028). Female gender(HR: 0.68, p=0.062) and education level above primary school (HR: 0.88, p=0.68) did not confer significant protection. However, a past medical history of ARF conferred some protection against mortality (HR: 0.61, p=0.031). In follow-up, 30% (n=238, 29.6%) of children experienced an adverse cardiovascular event, nearly 15% (n=114, 14.1%) were hospitalised and six young women became pregnant during the study period. Conclusion: Children with RHD in low- and middle-income countries are severely affected, with significant mortality and morbidity. The use of penicillin was suboptimal and the substantial need for surgery is evident. Our findings support the recommendations of the World Health Assembly (WHA) Resolution 71.14 passed in May 2018 for consistent provision of penicillin, integrated collaborative efforts focused on children and adolescent health as well as access to specialised services including cardiac surgery.
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    Outcomes of asymptomatic and symptomatic rheumatic heart disease
    (2015) Zühlke, Liesl Joanna; Mayosi, Bongani M; Engel, Mark E
    Rheumatic Heart Disease (RHD) is a leading cause of heart disease in children and young adults in the developing world, with significant associated morbidity and mortality. Early secondary prophylaxis may retard the deleterious progression from its antecedent, acute rheumatic fever to permanent heart valve damage, and thus several echocardiographic screening programmes to detect asymptomatic RHD and institute early prophylaxis have been conducted. While effective interventions are available for ameliorating the effects of RHD, research on their use in different settings is scant. Key questions remain regarding the natural history of asymptomatic RHD and the optimal method for early detection. In addition, there is a lack of contemporary estimates of mortality and morbidity among the symptomatic population in the developing world. The primary purpose of the thesis was to determine the outcomes of asymptomatic and symptomatic RHD. More specifically, I sought to quantify the incidence, prevalence and outcomes of RHD in South Africa over the past two decades, determine the natural history of asymptomatic RHD and validate a focused protocol for screening in schoolchildren from Cape Town. In addition, I determined the baseline characteristics, prevalent sequelae and gaps in evidence-based implementation in children and adults from14 developing countries. Finally, I investigated the independent predictors for mortality and morbidity of RHD over a two-year period in patients from Cape Town, South Africa. My thesis has five key findings. Firstly, a systematic review of the literature showed that the incidence and prevalence of RHD over the past two decades in South Africa remains high, although there is evidence of falling cause-specific mortality at a population level. Secondly, asymptomatic RHD has a variable natural history that ranges from regression to a normal state, to persistence of disease, and progression to symptomatic RHD. Thirdly, a focused hand-held echocardiography protocol shows promising levels of sensitivity and specificity for detecting subclinical RHD. Fourthly, the baseline data from the global rheumatic heart disease registry demonstrates significant gaps in the implementation of medical and surgical interventions of proven effectiveness in low- and middle-income countries. Finally, the annual mortality rate for children and adults with RHD in Cape Town over a two-year period is 4.1%with cardiovascular events occurring at a rate of 0.18 events per patient per year. The findings encapsulated in this thesis have important implications for policy, practice and research related to the management of asymptomatic and symptomatic RHD in the world.
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    The natural history of latent rheumatic heart disease in a 5 year follow-up study: a prospective observational study
    (2016) ZYhlke, Liesl; Engel, Mark E; Lemmer, Carolina E; van de Wall, Marnie; Nkepu, Simpiwe; Meiring, Alet; Bestawros, Michael; Mayosi, Bongani M
    BackgroundLatent rheumatic heart disease (RHD) occurs in asymptomatic individuals with echocardiographic evidence of RHD and no history of acute rheumatic fever. The natural history of latent RHD is unclear but has important clinical and economic implications about whether these children should receive penicillin prophylaxis or not. We performed a 5-year prospective study of this question.MethodsIn August 2013 through September 2014, we conducted a follow-up study of latent RHD among school pupils using the World Heart Federation (WHF) echocardiographic criteria. Contingency tables were used to assess progression, persistence or regression of latent RHD.ResultsForty two borderline and 13 definite cases of RHD (n 55) were identified, 44 (80%; mean age 13.8 ± 4.0years; 29 (65.9%) female) of whom were available for echocardiographic examination at a median follow-up of 60.8months (interquartile range 51.3-63.5). Over the follow-up period, half the participants (n = 23; 52.3%) improved to normal or better WHF category (regressors), a third (n = 14, 31.8%) remained in the same category (persistors), while seven others (15.9%) progressed from borderline to definite RHD (progressors). In total, 21 subjects (47.7%) reverted to a normal status, nine (20.4%) either improved from definite to borderline or remained in the borderline category, and 14 (31.8%) either remained definite or progressed from borderline to a definite status. Two cases (20%) progressed to symptomatic disease.ConclusionsLatent RHD has a variable natural history that ranges from regression to normal in nearly half of cases, to persistence, progression or development of symptoms in the remainder of subjects.