Latent tuberculosis is associated with heightened levels of pro-and anti-inflammatory cytokines among Kenyan men and women living with HIV on long-term antiretroviral therapy.

BACKGROUND: Persons with HIV (PWH) on antiretroviral therapy (ART) have persistent immune activation associated with increased risk for non-AIDS related diseases. Latent tuberculosis infection (LTBI), endemic in Africa, may contribute to this immune dysregulation. We evaluated the impact of HIV and TB co-infection on plasma pro- and anti-inflammatory cytokines among Kenyan adults. METHODS: We compared data from 221 PWH on long-term ART and 177 HIV-negative adults examining biomarkers of pro-[sCD14, interleukin (IL)-2, IL-6, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-12p70, IL-17A] and anti(IL-4, IL-5, IL-13) inflammatory cytokines, by HIV/LTBI status (HIV+LTBI+, HIV+LTBI-, HIV-LTBI+, HIV-LTBI-). LTBI was diagnosed based on a positive QuantiFERON TB Gold-Plus test in the absence of active TB symptoms. Linear regression was used to evaluate the associations of HIV, LTBI, and HIV/LTBI status with biomarkers adjusting for clinical factors including HIV-specific factors. RESULTS: Half of the participants were women and 52% had LTBI. HIV was independently associated with higher sCD14, IL-15, IL-6, IL-4, IL-5. LTBI was independently associated with higher TNF-α, IL-12p70, IL-17A, IL-4, IL-13 in adjusted models ( P  < 0.05). LTBI status was associated with higher IL-4 and IL-12p70 only among PWH, but not HIV-negative participants ( P  < 0.05 for interactions). In multivariate analysis, only HIV+LTBI+ demonstrated elevated levels of TNF-α, IL-6, IL-12p70, IL-15, IL-17A, IL4, IL-5, IL-13 in comparison to the HIV-LTBI- ( P  < 0.05 for all). The effect of LTBI on cytokines among PWH was independent of CD4 + T-cell count and ART duration. CONCLUSIONS: Despite viral suppression, persons with HIV and LTBI exhibit abnormal cytokine production accompanied by high concentrations of pro- and anti-inflammatory cytokines.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Rivaroxaban in Rheumatic Heart Disease-Associated Atrial Fibrillation.

BACKGROUND: Testing of factor Xa inhibitors for the prevention of cardiovascular events in patients with rheumatic heart disease-associated atrial fibrillation has been limited. METHODS: We enrolled patients with atrial fibrillation and echocardiographically documented rheumatic heart disease who had any of the following: a CHA2DS2VASc score of at least 2 (on a scale from 0 to 9, with higher scores indicating a higher risk of stroke), a mitral-valve area of no more than 2 cm2, left atrial spontaneous echo contrast, or left atrial thrombus. Patients were randomly assigned to receive standard doses of rivaroxaban or dose-adjusted vitamin K antagonist. The primary efficacy outcome was a composite of stroke, systemic embolism, myocardial infarction, or death from vascular (cardiac or noncardiac) or unknown causes. We hypothesized that rivaroxaban therapy would be noninferior to vitamin K antagonist therapy. The primary safety outcome was major bleeding according to the International Society of Thrombosis and Hemostasis. RESULTS: Of 4565 enrolled patients, 4531 were included in the final analysis. The mean age of the patients was 50.5 years, and 72.3% were women. Permanent discontinuation of trial medication was more common with rivaroxaban than with vitamin K antagonist therapy at all visits. In the intention-to-treat analysis, 560 patients in the rivaroxaban group and 446 in the vitamin K antagonist group had a primary-outcome event. Survival curves were nonproportional. The restricted mean survival time was 1599 days in the rivaroxaban group and 1675 days in the vitamin K antagonist group (difference, -76 days; 95% confidence interval [CI], -121 to -31; P<0.001). A higher incidence of death occurred in the rivaroxaban group than in the vitamin K antagonist group (restricted mean survival time, 1608 days vs. 1680 days; difference, -72 days; 95% CI, -117 to -28). No significant between-group difference in the rate of major bleeding was noted. CONCLUSIONS: Among patients with rheumatic heart disease-associated atrial fibrillation, vitamin K antagonist therapy led to a lower rate of a composite of cardiovascular events or death than rivaroxaban therapy, without a higher rate of bleeding. (Funded by Bayer; INVICTUS ClinicalTrials.gov number, NCT02832544.).

The joint 15th Pan-African Society of Cardiology and Kenya Cardiac Society congress proceedings, 2021.

The 15th biennial Pan-African Society of Cardiology (PASCAR) congress held in Mombasa, Kenya, in November 2021, convened in its legacy of being the largest Pan-African conference on cardiovascular diseases (CVDs). The congress brough together members of cardiovascular societies from across the continent in the shared mission of advancing cardiovascular health in Africa. In partnership with the Kenyan Cardiac Society (KCS), the specific aims of the PASCAR conference were to (1) advance knowledge on CVDs in the region; (2) share local data, clinical cases, challenges and solutions and reinforce collaborative capacity initiatives in research and workforce training; (3) engage with policy makers to address health-system issues affecting access to CVD care in Africa; and (4) bring together local and international thought leaders in cardiovascular medicine to strengthen the partnerships between PASCAR, KCS, other African cardiac societies and key global stakeholders. Due to the COVID-19 pandemic, this congress demonstrated great success in providing both an in-person and a virtual platform of attendance, therefore making this an inaugural hybrid PASCAR congress, with inclusive and widespread participation from across the globe. We highlight the key areas of focus, various educational programmes and innovative initiatives that shaped the 15th PASCAR congress, including expert consensus on the future directions for advancing CVD care in Africa.

Data-independent acquisition mass spectrometry in severe rheumatic heart disease (RHD) identifies a proteomic signature showing ongoing inflammation and effectively classifying RHD cases.

BACKGROUND: Rheumatic heart disease (RHD) remains a major source of morbidity and mortality in developing countries. A deeper insight into the pathogenetic mechanisms underlying RHD could provide opportunities for drug repurposing, guide recommendations for secondary penicillin prophylaxis, and/or inform development of near-patient diagnostics. METHODS: We performed quantitative proteomics using Sequential Windowed Acquisition of All Theoretical Fragment Ion Mass Spectrometry (SWATH-MS) to screen protein expression in 215 African patients with severe RHD, and 230 controls. We applied a machine learning (ML) approach to feature selection among the 366 proteins quantifiable in at least 40% of samples, using the Boruta wrapper algorithm. The case-control differences and contribution to Area Under the Receiver Operating Curve (AUC) for each of the 56 proteins identified by the Boruta algorithm were calculated by Logistic Regression adjusted for age, sex and BMI. Biological pathways and functions enriched for proteins were identified using ClueGo pathway analyses. RESULTS: Adiponectin, complement component C7 and fibulin-1, a component of heart valve matrix, were significantly higher in cases when compared with controls. Ficolin-3, a protein with calcium-independent lectin activity that activates the complement pathway, was lower in cases than controls. The top six biomarkers from the Boruta analyses conferred an AUC of 0.90 indicating excellent discriminatory capacity between RHD cases and controls. CONCLUSIONS: These results support the presence of an ongoing inflammatory response in RHD, at a time when severe valve disease has developed, and distant from previous episodes of acute rheumatic fever. This biomarker signature could have potential utility in recognizing different degrees of ongoing inflammation in RHD patients, which may, in turn, be related to prognostic severity.

Association of Novel Locus With Rheumatic Heart Disease in Black African Individuals: Findings From the RHDGen Study.

Importance: 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. Objective: To identify common genetic loci associated with RHD susceptibility in Black African individuals. Design, Setting, and Participants: 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. Main Outcomes and Measures: Genetic associations with RHD. Results: 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. Conclusions and Relevance: This study revealed a novel candidate susceptibility locus exclusive to Black African individuals and an important heritable component to RHD susceptibility in African individuals.

May Measurement Month 2019: an analysis of blood pressure screening results from Kenya.

Elevated blood pressure (BP) is the leading cause of global mortality, but control rates remain poor because most patients, especially in Africa, are unaware. May Measurement Month (MMM) is an annual global BP screening campaign that was initiated by the International Society of Hypertension (ISH) in 2017 to raise awareness of raised BP. Following participation in 2017 and 2018, Kenya participated again in 2019 and the results are reported here. Screening was carried out in 30 sites by volunteers coordinated by the Kenya Cardiac Society. Participants had three BP readings by standard methods with the last two being averaged and recorded. Heart rate, weight, height, socio-demographic parameters, and co-morbidities were documented. Hypertension was defined as a systolic BP (SBP) ≥140 mmHg and/or a diastolic BP (DBP) ≥90 mmHg or being on treatment with at least one antihypertensive medication. A total of 33 992 participants were screened, mean age was 42.5 (SD 16.8) years and 58.7% of participants were female. Only 27.3% had their BPs checked within the preceding 12 months. After multiple imputation, 26.1% were hypertensive, of whom 34.5% were aware of their hypertension and 31.5% were on treatment. Of those on treatment, 59.7% were controlled translating to 18.8% of all hypertensives. Being on treatment for hypertension, overweight, obese or having had hypertension in previous pregnancy were associated with increased SBP and DBP, while diabetes was associated with raised SBP. Two-thirds of hypertensives were unaware. Only a third of those aware were on treatment, with about 60% of these controlled. Lack of awareness remains a significant barrier to BP control. Programmes to raise awareness such as MMM are significant in raising population awareness.

May Measurement Month 2018: an analysis of blood pressure screening from Kenya.

Hypertension (HTN) is highly prevalent and the leading cardiovascular risk factor for death globally. A large proportion of individuals with high blood pressure (BP) are unaware leading to under treatment and poor control. To address this, the International Society of Hypertension (ISH) initiated a global mass screening campaign, the May Measurement Month 2017 (MMM17), in which Kenya participated. Following the success of the campaign, its successor MMM18 was launched. Here, we present the Kenyan results for MMM18. Opportunistic screening of consenting adults was done in various sites across Kenya in May 2018, by volunteers trained using ISH material, under the co-ordination of the Kenya Cardiac Society. Blood pressure, pulse rate, weight, and height were measured by standard methods. Definitions of HTN and statistical methods all adhered to the standard MMM protocol. We screened 49 548 subjects, mean age 39.95 (15.3) years. In total, 49.4% had never had a BP measurement taken. After multiple imputation, 17.1% were hypertensive and of those who were hypertensive, 30.7% were aware, 26.6% were on antihypertensive treatment, and 13.0% had controlled BP. Alcohol use, excess weight, and treatment for HTN were associated with higher BP. The Kenyan MMM18 sites successfully screened more than three times the number screened in 2017, hence improving public awareness. Less than half the population had ever had a BP check. Less than a third of the hypertensives were aware with correspondingly poor treatment and control rates. Opportunistic mass screening is useful in raising public awareness.

The INVICTUS rheumatic heart disease research program: Rationale, design and baseline characteristics of a randomized trial of rivaroxaban compared to vitamin K antagonists in rheumatic valvular disease and atrial fibrillation.

BACKGROUND: Rheumatic heart disease (RHD) is a neglected disease affecting 33 million people, mainly in low and middle income countries. Yet very few large trials or registries have been conducted in this population. The INVICTUS program of research in RHD consists of a randomized-controlled trial (RCT) of 4500 patients comparing rivaroxaban with vitamin K antagonists (VKA) in patients with RHD and atrial fibrillation (AF), a registry of 17,000 patients to document the contemporary clinical course of patients with RHD, including a focused sub-study on pregnant women with RHD within the registry. This paper describes the rationale, design, organization and baseline characteristics of the RCT and a summary of the design of the registry and its sub-study. Patients with RHD and AF are considered to be at high risk of embolic strokes, and oral anticoagulation with VKAs is recommended for stroke prevention. But the quality of anticoagulation with VKA is poor in developing countries. A drug which does not require monitoring, and which is safe and effective for preventing stroke in patients with valvular AF, would fulfill a major unmet need. METHODS: The INVestIgation of rheumatiC AF Treatment Using VKAs, rivaroxaban or aspirin Studies (INVICTUS-VKA) trial is an international, multicentre, randomized, open-label, parallel group trial, testing whether rivaroxaban 20 mg given once daily is non-inferior (or superior) to VKA in patients with RHD, AF, and an elevated risk of stroke (mitral stenosis with valve area ≤2 cm2, left atrial spontaneous echo-contrast or thrombus, or a CHA2DS2VASc score ≥2). The primary efficacy outcome is a composite of stroke or systemic embolism and the primary safety outcome is the occurrence of major bleeding. The trial has enrolled 4565 patients from 138 sites in 23 countries from Africa, Asia and South America. The Registry plans to enroll an additional 17,000 patients with RHD and document their treatments, and their clinical course for at least 2 years. The pregnancy sub-study will document the clinical course of pregnant women with RHD. CONCLUSION: INVICTUS is the largest program of clinical research focused on a neglected cardiovascular disease and will provide new information on the clinical course of patients with RHD, and approaches to anticoagulation in those with concomitant AF.

Evaluation of a portable assembly catheter simulator using a 3D-printed heart model for percutaneous transvenous mitral commissurotomy in developing countries: Catheter simulator for PTMC.

AIMS: We developed a catheter simulator for percutaneous transvenous mitral commissurotomy (PTMC) based on the data from a patient with mitral valve stenosis. The simulator has the following characteristics: 1) the simulator is portable and easy to assemble and disassemble, 2) the cardiac portion is created using a 3D-printer, based on patient computed tomography data, 3) the simulator uses a foot-operated water pump to create pulsatile flow, and 4) the fossa ovalis in the atrial septum of the heart model is made of a thin polyurethane membrane and is interchangeable. We aimed to assess the effectiveness of this novel simulator for training in PTMC using the Inoue balloon in developing countries. METHODS AND RESULTS: We used this simulator for training in the National Institute of Cardiovascular Diseases in Bangladesh (13 physicians), and in Kenyatta National Hospital in Kenya (11 physicians). The effectiveness of training was evaluated by questionnaire and the procedure time in simulation. The questionnaire obtained from the trainees showed that the model scored 4.7±0.5 for realism, utility of pulsatile flow scored 4.7±0.5, simulator utility scored 4.9±0.3, and the effect of training on PTMC performance scored 4.9±0.5. The procedure time in simulation was shortened from 30.0±12.6 min (first time), to 23.4±11.9 min (second time) and to 20.4 ± 11.1 min (third time) (p<0.01). CONCLUSIONS: The novel portable assembly catheter simulator using a 3D-printed heart model for PTMC received positive comments and improved the skills of trainees.

May Measurement Month 2017: the results of blood pressure screening of 14 845 individuals in Kenya-Sub-Saharan Africa.

Elevated blood pressure (BP) is a growing burden worldwide leading to over 10 million deaths each year. Sub-Saharan Africa has the highest age-adjusted prevalence of hypertension. In Kenya, 24.5% of adults have elevated BP with lack of awareness being the main barrier to achieving satisfactory control rates. May Measurement Month (MMM17) is a global initiative aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programmes worldwide. An opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2017. Screening was coordinated by the Kenya Cardiac Society in 17 sites across the country. Blood pressure measurements, the definition of hypertension and statistical analysis followed the standard MMM protocol. A total of 14 847 individuals were screened. After multiple imputation, 3647 (24.6%) had hypertension. Of individuals not receiving any antihypertensive medication, 2019 (15.3%) were hypertensive. Of individuals receiving antihypertensive medication, 740 (45.5%) had uncontrolled BP. Being diabetic and having a body mass index (BMI) ≥25 kg/m2 were associated with higher BP. Lack of awareness and poor control in those identified is a major challenge in Kenya. The MMM project demonstrated that mass screening for elevated BP is feasible, even in settings with limited resources. The presence of hypertension in a quarter of Kenyan adults with poor awareness and control rates demonstrates the need for programmes to raise awareness in the community.

Development of the certificate course in the management of hypertension in Africa (CCMH-Africa): proceedings of the first continental faculty meeting, Nairobi, Kenya, 25-26 February 2018.

BACKGROUND: In response to the call by the World Health Organisation to reduce premature deaths from non-communicable diseases by 25% by the year 2025 (25×25), the Pan-African Society of Cardiology (PASCAR), in partnership with several organisations, including the World Heart Federation, have developed an urgent 10-point action plan to improve detection, treatment and control of hypertension in Africa. Priority six of this action plan is to promote a task-shifting/task-sharing approach in the management of hypertension. AIM: This capacity-building initiative aims to enhance the knowledge, skills and core competences of primary healthcare physicians in the management of hypertension and related complications. METHODS: In a collaborative approach with the International Society of Hypertension, the British and Irish Hypertension Society, the Public Health Foundation of India and the Centre for Chronic Disease Control, the PASCAR hypertension taskforce held a continental faculty meeting in Kenya on 25 and 26 February 2018 to review and discuss a process of effective contextualisation and implementation of the Indian hypertension management course on the African continent. RESULTS: A tailored African course in terms of evidence-based learning, up-to-date curriculum and on-the-job training was developed with a robust monitoring and evaluation strategy. The course will be offered on a modular basis with a judicious mix of case studies, group discussions and contact sessions, with great flexibility to accommodate participants' queries. CONCLUSIONS: Hypertension affects millions of people in Africa and if left untreated is a major cause of heart disease, kidney disease and stroke. CCMH-Africa will train in the next 10 years, 25 000 certified general physicians and 50 000 nurses, capable of adequately managing uncomplicated hypertension, thereby freeing the few available specialists to focus on severe or complicated cases.

Presentation, management and outcomes of acute coronary syndrome: a registry study from Kenyatta National Hospital in Nairobi, Kenya.

BACKGROUND: Acute coronary syndrome (ACS) is understudied in sub-Saharan Africa despite its increasing disease burden. We sought to create an ACS registry at Kenyatta National Hospital to evaluate the presentation, management and outcomes of ACS patients. METHODS: From November 2016 to April 2017, we conducted a retrospective review of ACS cases managed at Kenyatta National Hospital between 2013 and 2016, with a primary discharge diagnosis of ACS, based on International Classification of Diseases (ICD) 10 coding (I20-I24). We compared the presentation, management and outcomes by ACS subtype using analysis of variance testing. We created multivariable logistic regression models using the Global Registry of Acute Coronary Events (GRACE) risk score to evaluate the association between clinical variables, including guideline-directed medical therapy and in-hospital outcomes. RESULTS: Among 196 ACS admissions, the majority (65%) was male, and the median age was 58 years. Most (57%) ACS admissions were for ST-segment-elevation myocardial infarction (STEMI). In-hospital dual antiplatelet (> 85%), beta-blockade (72%) and anticoagulant (72%) therapy was common. A minority (33%) of patients with STEMI was eligible for reperfusion therapy but only 5% received reperfusion. In-hospital mortality rate was 17%, and highest among individuals presenting with STEMI (21%). After multivariable adjustment, higher serum creatinine level was associated with higher odds of in-hospital death (OR = 1.84, 95% CI: 1.21 - 2.78), and STEMI and Killip class > 1 were associated with in-hospital composite of death, re-infarction, stroke, major bleeding or cardiac arrest (STEMI: OR = 8.70, 95% CI: 2.52 - 29.93; Killip > 1: OR = 10.7, 95% CI: 3.34-34.6). CONCLUSIONS: We describe the largest ACS registry at Kenyatta National Hospital to date and identify potential areas for improved ACS care related to diagnostics and management to optimise in-hospital outcomes.

Facilitators, context of and barriers to acute coronary syndrome care at Kenyatta National Hospital, Nairobi, Kenya: a qualitative analysis.

BACKGROUND: The prevalence of ischaemic heart disease and its acute manifestation, acute coronary syndrome (ACS), is growing throughout sub-Saharan Africa, including Kenya. To address this increasing problem, we sought to understand the facilitators, context of and barriers to ACS care at Kenyatta National Hospital, with the aim of improving the quality of care of ACS. METHODS: We conducted in-depth interviews with healthcare providers involved in the management of ACS patients from January to February 2017 at Kenyatta National Hospital in Nairobi, Kenya. We selected an initial sample of key participants for interviewing and used a snowballing technique to identify additional participants until we achieved saturation. After transcription of audio recordings of the interviews, two authors conducted data coding and analysis using a framework approach. RESULTS: We conducted 16 interviews with healthcare providers. Major themes included the need to improve the diagnostic and therapeutic capabilities of the hospital, including increasing the number of ECG machines and access to thrombolytics. Participants highlighted an overall wide availability of other guideline-directed medical therapies, including antiplatelets, beta-blockers, statins, anticoagulants and ACE inhibitors. All participants also stated the need for and openness to accepting future interventions for improvement of quality of care, including checklists and audits to improve ACS care at Kenyatta National Hospital. CONCLUSION: Major barriers to ACS care at Kenyatta National Hospital include inadequate diagnostic and therapeutic capabilities, lack of hospital-wide ACS guidelines, undertraining of healthcare providers and delayed presentation of patients seeking care. We also identified potential targets, including checklists and audits for future improvements in quality of care from the perspective of healthcare providers.

Clinical Outcomes in 3343 Children and Adults With Rheumatic Heart Disease From 14 Low- and Middle-Income Countries: Two-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.

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

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 organisations 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.

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.