The Causes of HIV-Associated Cardiomyopathy: A Tale of Two Worlds

Antiretroviral therapy (ART) has transformed the clinical profile of human immunodeficiency virus (HIV) from an acute infection with a high mortality into a treatable, chronic disease. As a result, the clinical sequelae of HIV infection are changing as patients live longer. HIV-associated cardiomyopathy (HIVAC) is a stage IV, HIV-defining illness and remains a significant cause of morbidity and mortality among HIV-infected individuals despite ART. Causes and clinical manifestations of HIVAC depend on the degree of host immunosuppression. Myocarditis from direct HIV toxicity, opportunistic infections, and nutritional deficiencies are implicated in causing HIVAC when HIV viral replication is unchecked, whereas cardiac autoimmunity, chronic inflammation, and ART cardiotoxicity contribute to HIVAC in individuals with suppressed viral loads. The initiation of ART has dramatically changed the clinical manifestation of HIVAC in high income countries from one of severe, left ventricular systolic dysfunction to a pattern of subclinical cardiac dysfunction characterized by abnormal diastolic function and strain. In low and middle income countries, however, HIVAC is the most common HIV-associated cardiovascular disease. Clear diagnostic and treatment guidelines for HIVAC are currently lacking but should be prioritized given the global burden of HIVAC

Footprint and imprint: an ecologic time-trend analysis of cardiovascular publications in general and specialty journals.

Studies have demonstrated strong associations between publication source and citations, as well as investigatory analysis of collaboration effects, in general and medical literature, but are limited to specific journals or short duration of time. This study sought to analyze time trends in cardiovascular research publications in leading general and specialty journals and to determine the association between collaboration and citation index. Cardiovascular publications were retrieved from Web of Knowledge by a cardiovascular bibliometric filter, and annual publication volumes in 8 general and specialty journals were compared. Univariable linear regression models were used to determine global and journal-specific trends for overall publication, cardiovascular publication, proportion of cardiovascular publication, collaboration, and citations. Cardiovascular publications increased (1999 to 2008) by 36% and number of sources by 74%. Volume increased in European Heart Journal (beta: 18.4, 95% confidence interval [CI]: 10.6 to 26.3) and decreased in Circulation (beta: -42.9, 95% CI: -79.3 to -6.5), Annals of Internal Medicine (beta: -1.9, 95% CI: -3.5 to -0.3), and Lancet (beta: -11.2, 95% CI: -14.7 to -7.8). Number of contributing countries increased in 3 journals: BMJ (beta: 0.8, 95% CI: 0.2 to 1.5), European Heart Journal (beta: -1.2, 95% CI: 0.8 to 1.7), and New England Journal of Medicine (beta: 1.6, 95% CI: 0.6 to 2.7). Fraction of collaborative publications increased (beta: 1.1 to 2.9) in all but Annals of Internal Medicine. Collaboration was associated with a higher median actual citation index (p < 0.0001). We found increasing trends in collaboration and citation in both general and specialty journals. Contribution by country in selected journals was disproportionate and under-represents total cardiovascular research in low- and middle-income countries

Building focused cardiac ultrasound capacity in a lower middle-income country: A single centre study to assess training impact

Background: In low- and middle-income countries (LMICs) where echocardiography experts are in short supply, training non-cardiologists to perform Focused Cardiac Ultrasound (FoCUS) could minimise diagnostic delays in time-critical emergencies. Despite advocacy for FoCUS training however, opportunities in LMICs are limited, and the impact of existing curricula uncertain. The aim of this study was to assess the impact of FoCUS training based on the Focus Assessed Transthoracic Echocardiography (FATE) curriculum. Our primary objective was to assess knowledge gain. Secondary objectives were to evaluate novice FoCUS image quality, assess inter-rater agreement between expert and novice FoCUS and identify barriers to the establishment of a FoCUS training programme locally. Methods: This was a pre-post quasi-experimental study at a tertiary hospital in Nairobi, Kenya. Twelve novices without prior echocardiography training underwent FATE training, and their knowledge and skills were assessed. Pre- and post-test scores were compared using the Wilcoxon signed-rank test to establish whether the median of the difference was different than zero. Inter-rater agreement between expert and novice scans was assessed, with a Cohen\u27s kappa \u3e0.6 indicative of good inter-rater agreement. Results: Knowledge gain was 37.7%, with a statistically significant difference between pre-and post-test scores (z = 2.934, p = 0.001). Specificity of novice FoCUS was higher than sensitivity, with substantial agreement between novice and expert scans for most FoCUS target conditions. Overall, 65.4% of novice images were of poor quality. Post-workshop supervised practice was limited due to scheduling difficulties. Conclusions: Although knowledge gain is high following a brief training in FoCUS, image quality is poor and sensitivity low without adequate supervised practice. Substantial agreement between novice and expert scans occurs even with insufficient practice when the prevalence of pathology is low. Supervised FoCUS practice is challenging to achieve in a real-world setting in LMICs, undermining the effectiveness of training initiatives

Screening for Diabetes and Hypertension in a Rural Low Income Setting in Western Kenya Utilizing Home-Based and Community-Based Strategies

BACKGROUND: The burdens of hypertension and diabetes are increasing in low- and middle-income countries (LMICs). It is important to identify patients with these conditions early in the disease process. The goal of this study, therefore, is to compare community- versus home-based screening for hypertension and diabetes in Kenya. METHODS: This was a feasibility study conducted by the Academic Model Providing Access to Healthcare (AMPATH) program in Webuye, a town in western Kenya. Home-based (door-to-door) screening occurred in March 2010 and community-based screening in November 2011. HIV counselors were trained to screen for diabetes and hypertension in the home-based screening with local district hospital based staff conducting the community-based screening. Participants \u3e18 years old qualified for screening in both groups. Counselors referred all participants with a systolic blood pressure (SBP) ≥ 160 mmHg and/or a random blood glucose ≥ 7 mmol/L (126 mg/dL) to a local clinic for follow-up. Differences in likelihood of screening positive between the two strategies were compared using Fischer\u27s Exact Test. Logistic regression models were used to identify factors associated with the likelihood of following-up after a positive screening. RESULTS: There were 236 participants in home-based screening: 13 (6%) had a SBP ≥ 160 mmHg, and 54 (23%) had a random glucose ≥ 7 mmol/L. There were 346 participants in community-based screening: 35 (10%) had a SBP ≥ 160 mmHg, and 27 (8%) had a random glucose ≥ 7 mmol/L. Participants in community-based screening were twice as likely to screen positive for hypertension compared to home-based screening (OR=1.93, P=0.06). In contrast, participants were 3.5 times more likely to screen positive for a random blood glucose ≥ 7 mmol/L with home-based screening (OR=3.51, P CONCLUSION: Community- or home-based screening for diabetes and hypertension in LMICs is feasible. Due to low rates of follow-up, screening efforts in rural settings should focus on linking cases to care

Global burden of atherosclerotic cardiovascular disease in people with hepatitis C virus infection: a systematic review, meta-analysis, and modelling study

Background: More than 70 million people worldwide are estimated to have hepatitis C virus (HCV) infection. Emerging evidence indicates an association between HCV and atherosclerotic cardiovascular disease. We aimed to determine the association between HCV and cardiovascular disease, and estimate the national, regional, and global burden of cardiovascular disease attributable to HCV. Methods: For this systematic review and meta-analysis, we searched MEDLINE, Embase, Ovid Global Health, and Web of Science databases from inception to May 9, 2018, without language restrictions, for longitudinal studies that evaluated the risk ratio (RR) of cardiovascular disease in people with HCV compared with those without HCV. Two investigators independently reviewed and extracted data from published reports. The main outcome was cardiovascular disease, defined as hospital admission with, or mortality from, acute myocardial infarction or stroke. We calculated the pooled RR of cardiovascular disease associated with HCV using a random-effects model. Additionally, we calculated the population attributable fraction and disability-adjusted life-years (DALYs) from HCV-associated cardiovascular disease at the national, regional, and global level. We also used age-stratified and sex-stratified HCV prevalence estimates and cardiovascular DALYs for 100 countries to estimate country-level burden associated with HCV. This study is registered with PROSPERO, number CRD42018091857. Findings: Our search identified 16 639 records, of which 36 studies were included for analysis, including 341 739 people with HCV. The pooled RR for cardiovascular disease was 1·28 (95% CI 1·18-1·39). Globally, 1·5 million (95% CI 0·9-2·1) DALYs per year were lost due to HCV-associated cardiovascular disease. Low-income and middle-income countries had the highest disease burden with south Asian, eastern European, north African, and Middle Eastern regions accounting for two-thirds of all HCV-associated cardiovascular DALYs. Interpretation: HCV infection is associated with an increased risk of cardiovascular disease. The global burden of cardiovascular disease associated with HCV infection was responsible for 1·5 million DALYs, with the highest burden in low-income and middle-income countries

Disparities in cardiovascular research output and disease outcomes among high-, middle- and low-income countries - An analysis of global cardiovascular publications over the last decade (2008-2017)

Background: Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. Health research is crucial to managing disease burden. Previous work has highlighted marked discrepancies in research output and disease burden between high-income countries (HICs) and low- and lower-middle-income countries (LI-LMICs) and there is little data to understand whether this gap has bridged in recent years. We conducted a global, country level bibliometric analysis of CVD publications with respect to trends in disease burden and county development indicators.Methods: A search filter with a precision and recall of 0.92 and 0.91 respectively was developed to extract cardiovascular publications from the Web of Science (WOS) for the years 2008-2017. Data for disease burden and country development indicators were extracted from the Global Burden of Disease and the World Bank database respectively.Results: Our search revealed 847,708 CVD publications for the period 2008-17, with a 43.4% increase over the decade. HICs contributed 81.1% of the global CVD research output and accounted for 8.1% and 8.5% of global CVD DALY losses deaths respectively. LI-LMICs contributed 2.8% of the total output and accounted for 59.5% and 57.1% global CVD DALY losses and death rates.Conclusions: A glaring disparity in research output and disease burden persists. While LI-LMICs contribute to the majority of DALYs and mortality from CVD globally, their contribution to research output remains the lowest. These data call on national health budgets and international funding support to allocate funds to strengthen research capacity and translational research to impact CVD burden in LI-LMICs

Strengthening Referral Networks for Management of Hypertension Across the Health System (STRENGTHS) in western Kenya: a study protocol of a cluster randomized trial

BACKGROUND: Hypertension is a major risk factor for cardiovascular disease (CVD), yet treatment and control rates for hypertension are very low in low- and middle-income countries (LMICs). Lack of effective referral networks between different levels of the health system is one factor that threatens the ability to achieve adequate blood pressure control and prevent CVD-related morbidity. Health information technology and peer support are two strategies that have improved care coordination and clinical outcomes for other disease entities in other settings; however, their effectiveness and cost-effectiveness in strengthening referral networks to improve blood pressure control and reduce CVD risk in low-resource settings are unknown. METHODS/DESIGN: We will use the PRECEDE-PROCEED framework to conduct transdisciplinary implementation research, focused on strengthening referral networks for hypertension in western Kenya. We will conduct a baseline needs and contextual assessment using a mixed-methods approach, in order to inform a participatory, community-based design process to fully develop a contextually and culturally appropriate intervention model that combines health information technology and peer support. Subsequently, we will conduct a two-arm cluster randomized trial comparing 1) usual care for referrals vs 2) referral networks strengthened with our intervention. The primary outcome will be one-year change in systolic blood pressure. The key secondary clinical outcome will be CVD risk reduction, and the key secondary implementation outcomes will include referral process metrics such as referral appropriateness and completion rates. We will conduct a mediation analysis to evaluate the influence of changes in referral network characteristics on intervention outcomes, a moderation analysis to evaluate the influence of baseline referral network characteristics on the effectiveness of the intervention, as well as a process evaluation using the Saunders framework. Finally, we will analyze the incremental cost-effectiveness of the intervention relative to usual care, in terms of costs per unit decrease in systolic blood pressure, per percentage change in CVD risk score, and per disability-adjusted life year saved. DISCUSSION: This study will provide evidence for the implementation of innovative strategies for strengthening referral networks to improve hypertension control in LMICs. If effective, it has the potential to be a scalable model for health systems strengthening in other low-resource settings worldwide

Genetic mutations in African patients with atrial fibrillation: Rationale and design of the Study of Genetics of Atrial Fibrillation in an African Population (SIGNAL)

BACKGROUND: There is an urgent need to understand genetic associations with atrial fibrillation in ethnically diverse populations. There are no such data from sub-Saharan Africa, despite the fact that atrial fibrillation is one of the fastest growing diseases. Moreover, patients with valvular heart disease are underrepresented in studies of the genetics of atrial fibrillation. METHODS: We designed a case-control study of patients with and without a history of atrial fibrillation in Kenya. Cases with atrial fibrillation included those with and without valvular heart disease. Patients underwent clinical phenotyping and will have laboratory analysis and genetic testing of >240 candidate genes associated with cardiovascular diseases. A 12-month follow-up assessment will determine the groups' morbidity and mortality. The primary analyses will describe genetic and phenotypic associations with atrial fibrillation. RESULTS: We recruited 298 participants: 72 (24%) with nonvalvular atrial fibrillation, 78 (26%) with valvular atrial fibrillation, and 148 (50%) controls without atrial fibrillation. The mean age of cases and controls were 53 and 48 years, respectively. Most (69%) participants were female. Controls more often had hypertension (45%) than did those with valvular atrial fibrillation (27%). Diabetes and current tobacco smoking were uncommon. A history of stroke was present in 25% of cases and in 5% of controls. CONCLUSION: This is the first study determining genetic associations in valvular and nonvalvular atrial fibrillation in sub-Saharan Africa with a control population. The results advance knowledge about atrial fibrillation and will enhance international efforts to decrease atrial fibrillation-related morbidity

Optimizing linkage and retention to hypertension care in rural Kenya (LARK hypertension study): study protocol for a randomized controlled trial

BACKGROUND: Hypertension is the leading global risk factor for mortality. Hypertension treatment and control rates are low worldwide, and delays in seeking care are associated with increased mortality. Thus, a critical component of hypertension management is to optimize linkage and retention to care. METHODS/DESIGN: This study investigates whether community health workers, equipped with a tailored behavioral communication strategy and smartphone technology, can increase linkage and retention of hypertensive individuals to a hypertension care program and significantly reduce blood pressure among them. The study will be conducted in the Kosirai and Turbo Divisions of western Kenya. An initial phase of qualitative inquiry will assess facilitators and barriers of linkage and retention to care using a modified Health Belief Model as a conceptual framework. Subsequently, we will conduct a cluster randomized controlled trial with three arms: 1) usual care (community health workers with the standard level of hypertension care training); 2) community health workers with an additional tailored behavioral communication strategy; and 3) community health workers with a tailored behavioral communication strategy who are also equipped with smartphone technology. The co-primary outcome measures are: 1) linkage to hypertension care, and 2) one-year change in systolic blood pressure among hypertensive individuals. Cost-effectiveness analysis will be conducted in terms of costs per unit decrease in blood pressure and costs per disability-adjusted life year gained. DISCUSSION: This study will provide evidence regarding the effectiveness and cost-effectiveness of strategies to optimize linkage and retention to hypertension care that can be applicable to non-communicable disease management in low- and middle-income countries. TRIAL REGISTRATION: This trial is registered with (NCT01844596) on 30 April 2013