Emmy Okello

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.

The utility of handheld echocardiography for early rheumatic heart disease diagnosis: A field study

AIMS The World Heart Federation (WHF) guidelines for rheumatic heart disease (RHD) are designed for a standard portable echocardiography (STAND) machine. A recent study in a tertiary care centre demonstrated that they also had good sensitivity and specificity when modified for use with handheld echocardiography (HAND). Our study aimed to evaluate the performance of HAND for early RHD diagnosis in the setting of a large-scale field screening. METHODS AND RESULTS STAND was performed in 4773 children in Gulu, Uganda, with 10% randomly assigned to also undergo HAND. Additionally, any child with mitral or aortic regurgitation also underwent HAND. Studies were performed by experienced echocardiographers and blindly reviewed by cardiologists using 2012 WHF criteria, which were modified slightly for HAND--due to the lack of spectral Doppler capability. Paired echocardiograms were performed in 1420 children (mean age 10.8 and 53% female), resulting in 1234 children who were normal, 133 who met criteria for borderline RHD, 47 who met criteria for definite RHD, and 6 who had other diagnoses. HAND had good sensitivity and specificity for RHD detection (78.9 and 87.2%, respectively), but was most sensitive for definite RHD (97.9%). Inter- and intra-reviewer agreement ranged between 66-83 and 71.4-94.1%, respectively. CONCLUSIONS HAND has good sensitivity and specificity for diagnosis of early RHD, performing best for definite RHD. Protocols for RHD detection utilizing HAND will need to include confirmation by STAND to avoid over-diagnosis. Strategies that evaluate simplified screening protocols and training of non-physicians hold promise for more wide spread deployment of HAND-based protocols.

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.

Cardiovascular complications in newly diagnosed rheumatic heart disease patients at Mulago Hospital, Uganda.

Background Complications of rheumatic heart disease are associated with severe morbidity and mortality in developing countries where the disease prevalence remains high. Due to lack of screening services, many patients present late, with severe valve disease. In Uganda, the disease and its complications are still not well studied. Objective To profile and describe cardiovascular complications in newly diagnosed rheumatic heart disease patients attending the Mulago National Referral Hospital in Uganda. Methods This was a cross-sectional study where consecutive, newly diagnosed rheumatic heart disease patients were assessed and followed up for complications, such as heart failure, pulmonary hypertension, atrial fibrillation, recurrence of acute rheumatic fever, and stroke. Results A total of 309 (115 males and 196 females) definite rheumatic heart disease patients aged 15–60 years were enrolled in the study and analysed. Complications occurred in 49% (152/309) of the newly diagnosed rheumatic heart disease cases, with heart failure (46.9%) the most common complication, followed by pulmonary arterial hypertension (32.7%), atrial fibrillation (13.9%), recurrence of acute rheumatic fever (11.4%), infective endocarditis (4.5%) and stroke (1.3%). Atrial fibrillation and acute rheumatic fever were the most common complications associated with heart failure. Conclusion In this study we found that about 50% of newly diagnosed rheumatic heart disease patients in Uganda presented with complications. Heart failure and pulmonary arterial hypertension were the most commonly observed complications.

Presenting features of newly diagnosed rheumatic heart disease patients in Mulago Hospital: a pilot study

INTRODUCTION Rheumatic heart disease (RHD) continues to cause gross distortions of the heart and the associated complications of heart failure and thromboembolic phenomena in this age of numerous high-efficacy drugs and therapeutic interventions. Due to the lack of contemporary local data, there is no national strategy for the control and eradication of the disease in Uganda. This study aimed to describe the presenting clinical features of newly diagnosed patients with RHD, with particular reference to the frequency of serious complications (atrial fibrillation, systemic embolism, heart failure and pulmonary hypertension) in the study group. METHODS One hundred and thirty consecutive patients who satisfied the inclusion criteria were recruited over a period of eight months from June 2011 to January 2012 at the Mulago Hospital, Uganda. Data on demographic characteristics, disease severity and presence of complications were collected by means of a standardised questionnaire. RESULTS Seventy-one per cent of the patients were female with a median age of 33 years. The peak age of the study group was 20 to 39 years, with the commonest presenting symptoms being palpitations, fatigue, chest pain and dyspnoea. The majority of the patients presented with moderate-to-severe valvular disease. Pure mitral regurgitation was the commonest valvular disease (40.2%), followed by mitral regurgitation plus aortic regurgitation (29%). Mitral regurgitation plus aortic regurgitation plus mitral stenosis was found in 11% of patients. There was only one case involving the tricuspid valve. The pulmonary valves were not affected in all patients; 45.9% of patients presented in severe heart failure in NYHA class III/IV, 53.3% had pulmonary hypertension, 13.9% had atrial fibrillation and 8.2% had infective endocarditis. All patients presented with dilated atria (> 49 mm). CONCLUSION A significant proportion of RHD patients present to hospital with severe disease associated with severe complications of advanced heart failure, pulmonary hypertension, infective endocarditis and atrial fibrillation. There is a need to improve awareness of the disease among the population, and clinical suspicion in primary health workers, so that early referral to specialist management can be done before severe damage to the heart ensues.

Benzathine penicillin adherence for secondary prophylaxis among patients affected with rheumatic heart disease attending Mulago Hospital.

Introduction Rheumatic heart disease (RHD) frequently occurs following recurrent episodes of acute rheumatic fever (ARF). Benzathine penicillin (benzapen) is the most effective method for secondary prophylaxis against ARF whose efficacy largely depends on adherence to treatment. Various factors determine adherence to therapy but there are no data regarding current use of benzapen in patients with RHD attending Mulago Hospital. The study aims were (1) to determine the levels of adherence with benzapen prophylaxis among rheumatic heart disease patients in Mulago Hospital, and (2) establish the patient factors associated with adherence and, (3) establish the reasons for missing monthly benzathine penicillin injections. Methods This was a longitudinal observational study carried out in Mulago Hospital cardiac clinics over a period of 10 months; 95 consecutive patients who satisfied the inclusion criteria were recruited over a period of four months and followed up for six months. Data on demographic characteristics and disease status were collected by means of a standardised questionnaire and a card to document the injections of benzapen received. Results Most participants were female 75 (78.9%). The age range was five to 55 years, with a mean of 28.1 years (SD 12.2) and median of 28 years. The highest education level was primary school for most patients (44, 46.3%) with eight (8.4%) of the patients being illiterate. Most were either NYHA stage II (39, 41.1%) or III (32, 33.7%). Benzathine penicillin adherence: 44 (54%) adhered to the monthly benzapen prophylaxis, with adherence rates ≥ 80%; 38 (46%) patients were classified as non-adherent to the monthly benzapen, with rates less than 80%. The mean adherence level was 70.12% (SD 29.25) and the median level was 83.30%, with a range of 0–100%; 27 (33%) patients had extremely poor adherence levels of ≤ 60%. Factors associated with adherence: higher education status, residing near health facility favoured high adherence, while painful injection was a major reason among poor performers. Conclusion The level of non-adherence was significantly high (46%). Residence in a town/city and having at least a secondary level of education was associated with better adherence, while the painful nature of the benzapen injections and lack of transport money to travel to the health centre were the main reasons for non-adherence among RHD patients in Mulago.

Socioeconomic and environmental risk factors among rheumatic heart disease patients in Uganda.

Background Although low socioeconomic status, and environmental factors are known risk factors for rheumatic heart disease in other societies, risk factors for rheumatic heart disease remain less well described in Uganda. Aims and Objective The objective of this study was to investigate the role of socio-economic and environmental factors in the pathogenesis of rheumatic heart disease in Ugandan patients. Methods This was a case control study in which rheumatic heart disease cases and normal controls aged 5–60 years were recruited and investigated for socioeconomic and environmental risk factors such as income status, employment status, distance from the nearest health centre, number of people per house and space area per person. Results 486 participants (243 cases and 243 controls) took part in the study. Average age was 32.37+/−14.6 years for cases and 35.75+/−12.6 years for controls. At univariate level, Cases tended to be more overcrowded than controls; 8.0+/−3.0 versus 6.0+/−3.0 persons per house. Controls were better spaced at 25.2 square feet versus 16.9 for cases. More controls than cases were employed; 45.3% versus 21.1%. Controls lived closer to health centers than the cases; 4.8+/−3.8 versus 3.3+/−12.9 kilometers. At multivariate level, the odds of rheumatic heart disease was 1.7 times higher for unemployment status (OR = 1.7, 95% CI = 1.05–8.19) and 1.3 times higher for overcrowding (OR = 1.35, 95% CI = 1.1–1.56). There was interaction between overcrowding and longer distance from the nearest health centre (OR = 1.20, 95% CI = 1.05–1.42). Conclusion The major findings of this study were that there was a trend towards increased risk of rheumatic heart disease in association with overcrowding and unemployment. There was interaction between overcrowding and distance from the nearest health center, suggesting that the effect of overcrowding on the risk of acquiring rheumatic heart disease increases with every kilometer increase from the nearest health center.

Management of rheumatic heart disease in uganda: the emerging epidemic of non-AIDS comorbidity in resource-limited settings.

The expansion of antiretroviral therapy (ART) in resource-limited settings (RLS) has dramatically changed the face of the AIDS epidemic in Sub-Saharan Africa over the past decade 1. The progress in HIV/AIDS care is in large part due to successful bilateral and multilateral collaborations of governments and non-governmental AIDS organizations. In Uganda, for example, with funding support from the National Institutes of Health (NIH) and the Presidents Emergency Plan for AIDS Relief, Case Western Reserve University (CWRU) and others have partnered with Ugandan institutions to develop a comprehensive HIV/AIDS infrastructure. Because of this concerted effort, the country has seen a fall in HIV prevalence from a peak of 25-30% in major urban areas to now less than 7% nationally, and nearly half of those who qualify for treatment are currently receiving it 2. These successes, however, bring new challenges. As HIV has now become a manageable chronic disease, the infected population has aged, and the higher prevalence of co-morbidities such as cardiovascular disease is increasingly recognized. The specter of a dual epidemic of HIV/AIDS and non-communicable disease threatens to place significant demands on these fragile healthcare systems 3. In addition to the higher risk of ischemic heart disease observed in the developed and developing world, the burden of endemic cardiovascular disease such as tuberculous pericarditis and rheumatic heart disease among persons living with HIV in RLS is unknown. Recognizing this emerging need, Makerere University School of Medicine, Mulago Hospital, and the Uganda Heart Institute have partnered with CWRU to extend collaboration beyond HIV/AIDS to cardiovascular disease (CVD), neurology, and oncology. Funded in part by the NIH/Fogarty International Medical Education Partnership Initiative (MEPI), the cardiology collaboration aims to provide contextually appropriate training of cardiovascular specialists and conduct research on CVD risk factors, including the impact of HIV/AIDS. As part of the MEPI collaboration, a team of cardiologists from CWRU traveled to Kampala, Uganda in August 2012 to perform procedures in the newly opened cardiac catheterization laboratory at the Uganda Heart Institute (UHI), Mulago Hospital, including the countrys first percutaneous mitral balloon valvuloplasties (PMBV) for rheumatic mitral stenosis (Figure 1A and B). Although rarely seen in the developed world, rheumatic heart disease (RHD) remains a leading cause of cardiovascular morbidity and mortality in RLS, affecting over 1 million children in Sub-Saharan Africa alone 4. RHD is a chronic complication of rheumatic fever, an auto-immune reaction to antecedent Group A streptococcus pharyngitis that causes varying degrees of carditis 5. Significant valvular regurgitation or stenosis may occur during the initial insult or after repeated damage to the valve from recurrent bouts of acute rheumatic fever 5. Congestive heart failure then develops insidiously and may lead to death in the 2nd to 5th decades of life if the valve is not repaired. The current treatment of choice in developed countries for rheumatic mitral valve stenosis without significant regurgitation is percutaneous balloon valvuloplasty6. Figure 1 A) Members of the Case Western Reserve University team with the Uganda Heart Institute physicians and cardiac catheterization lab staff. The new facility at the Uganda Heart Institute was completed in February of 2012. B) Dr. Marco Costa and Dr. Dan Simon ... The first patient to benefit from this minimally-invasive procedure in Uganda was HIV-infected. In a country with a high prevalence of HIV/AIDS, it may be coincidence that this patient happened to be HIV-infected. Nonetheless, several questions arise regarding the impact of HIV on RHD (and other endemic non-communicable disease) in the country. Are perinatally HIV-infected children more or less likely than their uninfected peers to acquire acute rheumatic fever? What is the role of chronic inflammation and immune activation associated with HIV on outcomes among children with RHD? In patients with AIDS, does the CD4+ lymphopenia associated with acute rheumatic fever lead to further immunosuppression and increased susceptibility to opportunistic infections? Is someone with subclinical RHD acquired in childhood more or less likely to develop progressive disease if they become HIV-infected as an adult? Among patients colonized with Group A streptococci who are started on ART therapy, can subclinical rheumatic carditis develop within the spectrum of immune reconstitution inflammatory syndromes (IRIS)? Although RHD is rare in the developed world, other rheumatic/immunologic complications of HIV/AIDS are not uncommon. The spectrum of disease has changed since the introduction of combination ART in the mid-1990s 8,9. Autoimmunity appears to be increased in chronic HIV-infection, and molecular mimicry may be an important mechanism 10. For example, in a recent study from South Africa, anti-cyclic citrullinated peptide (anti-CCP) antibody titers were increased in advanced HIV-infection compared to controls and decreased after initiation of antiretroviral therapy 11. In this context, the anti-CCP antibodies lacked the typically high specificity for rheumatoid arthritis. In some cases, inflammatory arthritis such as psoriatic arthritis 12 or rheumatoid arthritis 13 may be the initial presentation of HIV/AIDS. On the other hand, advanced immunosuppression may suppress the clinical manifestations of pre-existing auto-immune conditions such as inflammatory bowel disease, systemic lupus erythematosis and rheumatoid arthritis 14. Despite this literature, little is known about the interaction of HIV with rheumatic fever and RHD. Some studies have demonstrated an increased risk for group A streptococcal infection with underlying HIV infection15; however, to our knowledge, only one case of acute rheumatic fever in an AIDS patient has been reported previously 16. The CWRU team continues to return quarterly to Uganda as part of a comprehensive skills transfer program that also includes training for Ugandan physicians in Cleveland, Ohio. In addition, CWRU has partnered with the UHI and the Joint Clinical Research Centre (a center in existence in Uganda for care and research in HIV/AIDS) to focus specifically on RHD through an innovative foundation-funded project. This program will utilize an existing network of HIV/AIDS infrastructure to create community-based RHD treatment centers of excellence. If successful, this program may serve as a model for leveraging HIV/AIDS resources for the treatment of non-communicable diseases among both HIV-infected and uninfected patients in RLS. We are now at a crossroads. An opportunity exists to build upon the dramatic improvements in healthcare infrastructure that HIV/AIDS investment has brought over the past decade. To extend the benefits of the ART rollout to the treatment of non-AIDS co-morbidities such as RHD will require a coordinated research effort and capital investment in health systems, particularly in human resources. Multilateral collaborations in medical specialties beyond infectious diseases that share the tripartite mission of research, education, and clinical care such as the one described in this report will be needed to move to the next level of HIV/AIDS treatment in Sub-Saharan Africa and other RLS.

Brief Report: Prevalence of Latent Rheumatic Heart Disease Among HIV-Infected Children in Kampala, Uganda.

Abstract:Rheumatic heart disease (RHD) remains highly prevalent in resource-constrained settings around the world, including countries with high rates of HIV/AIDS. Although both are immune-mediated diseases, it is unknown whether HIV modifies the risk or progression of RHD. We performed screening echocardiography to determine the prevalence of latent RHD in 488 HIV-infected children aged 5–18 in Kampala, Uganda. The overall prevalence of borderline/definite RHD was 0.82% (95% confidence interval: 0.26% to 2.23%), which is lower than the published prevalence rates of 1.5%–4% among Ugandan children. There may be protective factors that decrease the risk of RHD in HIV-infected children.

Statistics on the use of cardiac electronic devices and interventional electrophysiological procedures in Africa from 2011 to 2016: report of the Pan African Society of Cardiology (PASCAR) Cardiac Arrhythmias and Pacing Task Forces

Abstract Aims To provide comprehensive information on the access and use of cardiac implantable electronic devices (CIED) and catheter ablation procedures in Africa. Methods and results The Pan-African Society of Cardiology (PASCAR) collected data on invasive management of cardiac arrhythmias from 2011 to 2016 from 31 African countries. A specific template was completed by physicians, and additional information obtained from industry. Information on health care systems, demographics, economics, procedure rates, and specific training programs was collected. Considerable heterogeneity in the access to arrhythmia care was observed across Africa. Eight of the 31 countries surveyed (26%) did not perform pacemaker implantations. The median pacemaker implantation rate was 2.66 per million population per country (range: 0.14–233 per million population). Implantable cardioverter-defibrillator and cardiac resynchronization therapy were performed in 12/31 (39%) and 15/31 (48%) countries respectively, mostly by visiting teams. Electrophysiological studies, including complex catheter ablations were performed in all countries from Maghreb, but only one sub-Saharan African country (South Africa). Marked variation in cost (up to 1000-fold) was observed across countries with an inverse correlation between implant rates and the procedure fees standardized to the gross domestic product per capita. Lack of economic resources and facilities, high cost of procedures, deficiency of trained physicians, and non-existent fellowship programs were the main drivers of under-utilization of interventional cardiac arrhythmia care. Conclusion There is limited access to CIED and ablation procedures in Africa. A quarter of countries did not have pacemaker implantation services, and catheter ablations were only available in one country in sub-Saharan Africa.