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Rheumatic heart disease (RHD) is prevalent in sub-Saharan Africa, where the capacity for diagnosis and evaluation of disease severity and complications is not always optimal. While the medical history and physical examination are important in the assessment of patients suspected to have RHD, cardiovascular imaging techniques are useful for confirmation of the diagnosis. Echocardiography is the workhorse modality for initial evaluation and diagnosis of RHD. Cardiovascular magnetic resonance is complementary and may provide additive information, including tissue characteristics, where echocardiography is inadequate or non-diagnostic. There is emerging evidence on the role of computed tomography, particularly following valve replacement surgery, in the monitoring and management of RHD. This article summarises the techniques used in imaging RHD patients, considers the evidence base for their utility, discusses their limitations and recognises the clinical contexts in which indications and imaging with various modalities are expanding.

Background Quantitative cardiovascular magnetic resonance T1-mapping is increasingly used for myocardial tissue characterization. However, the lack of standardization limits direct comparability between centers and wider roll-out for clinical use or trials. Purpose To develop a quality assurance (QA) program assuring standardized T1 measurements for clinical use. Methods MR phantoms manufactured in 2013 were distributed, including ShMOLLI T1-mapping and reference T1 and T2 protocols. We first studied the T1 and T2 dependency on temperature and phantom aging using phantom datasets from a single site over 4 years. Based on this, we developed a multiparametric QA model, which was then applied to 78 scans from 28 other multi-national sites. Results T1 temperature sensitivity followed a second-order polynomial to baseline T1 values (R2 > 0.996). Some phantoms showed aging effects, where T1 drifted up to 49% over 40 months. The correlation model based on reference T1 and T2, developed on 1004 dedicated phantom scans, predicted ShMOLLI-T1 with high consistency (coefficient of variation 1.54%), and was robust to temperature variations and phantom aging. Using the 95% confidence interval of the correlation model residuals as the tolerance range, we analyzed 390 ShMOLLI T1-maps and confirmed accurate sequence deployment in 90%(70/78) of QA scans across 28 multiple centers, and categorized the rest with specific remedial actions. Conclusions The proposed phantom QA for T1-mapping can assure correct method implementation and protocol adherence, and is robust to temperature variation and phantom aging. This QA program circumvents the need of frequent phantom replacements, and can be readily deployed in multicenter trials., Highlights • CMR T1 correlated with reference T1 and T2; this derives the QA model for T1-map. • The proposed QA model is robust to temperature variations and phantom aging. • This QA method requires no frequent phantom replacements. • The T1-map QA program can be readily deployed in multicenter trials.

The COVID-19 pandemic, which started around December 2019 has, at present, resulted in over 450,000 deaths globally, and approximately 1% of these deaths have been reported in Africa. Despite the high prevalence of COVID-19 risk factors, namely: hypertension, diabetes, chronic pulmonary disease, cardiovascular diseases (CVDs) such as rheumatic heart disease, compromised immunity and obesity, low case fatality rates have been recorded in many parts of Africa so far. COVID-19 severity has previously been shown to be worse in patients with CVD and hypertension. We observed the severity of COVID-19 and mortality rates in Africa, and compared outcomes with prevalence of established risk factors (hypertension and CVD). We stratified data as per the United Nations’ 5 African subregions. North African countries show a positive association between the risk factors and the mortality rates from COVID-19. However, we observed discordant patterns in the relationship between COVID-19, and either CVD or hypertension, in sub-Saharan African countries. In this paper, we also review the pathogenesis of SARS-CoV-2 infection and how it worsens CVD and postulate that the differences in modulation of the renin–angiotensin–aldosterone system (RAAS) axis which controls angiotensin-converting enzyme (ACE)/ACE2 balance may be an important determinant of COVID-19 outcomes in Africa. Electronic supplementary material The online version of this article (10.1007/s00392-020-01720-y) contains supplementary material, which is available to authorized users.

Rheumatic heart disease (RHD) is a major cause of cardiovascular morbidity and mortality in low- and middle-income countries, where living conditions promote spread of group A β-haemolytic streptococcus. Autoimmune reactions due to molecular mimicry of bacterial epitopes by host proteins cause acute rheumatic fever (ARF) and subsequent disease progression to RHD. Despite knowledge of the factors that predispose to ARF and RHD, determinants of the progression to valvular damage and the molecular events involved remain incompletely characterised. This review focuses on altered protein expression in heart valves, myocardial tissue and plasma of patients with RHD and pathogenic consequences on RHD. Proteins mainly involved in structural organization of the valve matrix, blood homeostasis and immune response were altered due to RHD pathogenesis. Study of secreted forms of these proteins may aid the development of non-invasive biomarkers for early diagnosis and monitoring outcomes in RHD. Valve replacement surgery, the single evidence-based strategy to improve outcomes in severe RHD, is costly, largely unavailable in low- and middle-income countries (LMIC) and requires specialised facilities. When diagnosed early, penicillin prophylaxis may be used to delay progression to severe valvular damage. Echocardiography and cardiovascular magnetic resonance and the standard imaging tools recommended to confirm early diagnosis remain largely unavailable and inaccessible in most LMIC and both require expensive equipment and highly skilled persons for manipulation as well as interpretation of results. Changes in protein expression in heart valves and myocardium are associated with progressive valvular deformation in RHD. Understanding these protein changes should shed more light on the mechanisms of pathogenicity, while secreted forms of these proteins may provide leads towards a biomarker for non-invasive early detection of RHD.

Background People with human immunodeficiency virus (PWH) face increased risks for heart failure and adverse heart failure outcomes. Myocardial steatosis predisposes to diastolic dysfunction, a heart failure precursor. We aimed to characterize myocardial steatosis and associated potential risk factors among a subset of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) participants. Methods Eighty-two PWH without known heart failure successfully underwent cardiovascular magnetic resonance spectroscopy, yielding data on intramyocardial triglyceride (IMTG) content (a continuous marker for myocardial steatosis extent). Logistic regression models were applied to investigate associations between select clinical characteristics and odds of increased or markedly increased IMTG content. Results Median (Q1, Q3) IMTG content was 0.59% (0.28%, 1.15%). IMTG content was increased (> 0.5%) among 52% and markedly increased (> 1.5%) among 22% of participants. Parameters associated with increased IMTG content included age (P = .013), body mass index (BMI) ≥ 25 kg/m2 (P = .055), history of intravenous drug use (IVDU) (P = .033), and nadir CD4 count Conclusions A substantial proportion of antiretroviral therapy–treated PWH exhibited myocardial steatosis. Age, BMI ≥ 25 kg/m2, low nadir CD4 count, and history of IVDU emerged as possible risk factors for myocardial steatosis in this group. Clinical Trials Registration NCT02344290; NCT03238755.

Aims Efforts to improve access to antiretroviral therapy (ART) have shifted morbidity and mortality among persons living with HIV (PLWH) from AIDS to non‐communicable diseases, such as cardiovascular disease (CVD). However, contemporary data on CVD among PLWH in sub‐Saharan Africa in the current ART era are lacking. The aim of this study was to assess the burden of cardiac stress among PLWH in South Africa via measurement of N‐terminal prohormone of brain natriuretic peptide (NT‐proBNP). Methods and results NT‐proBNP was measured at baseline in 224 PLWH enrolled in a sub‐study of a tuberculosis vaccine trial in Khayelitsha township near Cape Town, South Africa. Thresholds were applied at the assay's limit of detection (≥137 pg/mL) and a level indicative of symptomatic heart failure in the acute setting (>300 pg/mL). Mean (SD) age of participants was 39 (6) years, 86% were female, and 19% were hypertensive. Mean (SD) duration of HIV diagnosis was 8.3 (3.9) years and CD4 + count was 673 (267) with 79% prescribed ART for a duration of 5.6 (2.7) years. Thirty‐one percent of participants had NT‐proBNP > 300 pg/mL. Elevated vs. undetectable NT‐proBNP level was associated with older age (P = 0.04), no ART (P = 0.03), and higher plasma tumour necrosis factor‐α (P = 0.01). Conclusions Among South African PLWH largely free of known CVD and on ART with high CD4 + counts and few comorbidities, we observed a high proportion with elevated NT‐proBNP levels, suggesting the burden of cardiac stress in this population may be high. This observation underscores the need for more in‐depth research, including the current effect of HIV on heart failure risk among a growing ART‐treated population in sub‐Saharan Africa.

Background Human immunodeficiency virus (HIV) and antiretroviral therapy (ART) confer cardiovascular disease (CVD) risk in adults with HIV. Few studies have assessed endothelial dysfunction (ED), an early marker of subclinical CVD risk, in youth living with perinatally acquired HIV (YLPHIV). Methods Using peripheral arterial tonometry, we compared ED in YLPHIV and age-matched youth without HIV. A reactive hyperemic index ≤1.35 was defined as ED. Eligible participants included those aged 9–14 years and on ART ≥6 months at enrollment. Results Overall, 431 YLPHIV and 93 youth without HIV with a median age of 14.1 versus 13.9 years, respectively, were included. YLPHIV had a lower BMI z score (BMIZ; −0.2 vs 0.4; P 500 cell/mm3 (RR, 1.04; P = .76), VL (RR, 1.01; P = .78), and current ART class (protease inhibitor based vs nonnucleoside inhibitor based: relative risk, 0.90; P = .186) were not associated with ED after adjustment. Conclusions Even after adjusting for physiologic differences, YLPHIV appear to be at increased risk of ED compared with age-matched youth without HIV. These findings have important implications for the life course of YLPHIV who may be at increased risk of premature CVD and complications.

In sub-Saharan Africa (SSA), the burden of noncommunicable diseases (NCDs) is rising disproportionately in comparison to the rest of the world, affecting urban, semi-urban and rural dwellers alike. NCDs are predicted to surpass infections like human immunodeficiency virus, tuberculosis and malaria as the leading cause of mortality in SSA over the next decade. Heart failure (HF) is the dominant form of cardiovascular disease (CVD), and a leading cause of NCD in SSA. The main causes of HF in SSA are hypertension, cardiomyopathies, rheumatic heart disease, pericardial disease, and to a lesser extent, coronary heart disease. Of these, the cardiomyopathies deserve greater attention because of the relatively poor understanding of mechanisms of disease, poor outcomes and the disproportionate impact they have on young, economically active individuals. Morphofunctionally, cardiomyopathies are classified as dilated, hypertrophic, restrictive and arrhythmogenic; regardless of classification, at least half of these are inherited forms of CVD. In this review, we summarise all studies that have investigated the incidence of cardiomyopathy across Africa, with a focus on the inherited cardiomyopathies. We also review data on the molecular genetic underpinnings of cardiomyopathy in Africa, where there is a striking lack of studies reporting on the genetics of cardiomyopathy. We highlight the impact that genetic testing, through candidate gene screening, association studies and next generation sequencing technologies such as whole exome sequencing and targeted resequencing has had on the understanding of cardiomyopathy in Africa. Finally, we emphasise the need for future studies to fill large gaps in our knowledge in relation to the genetics of inherited cardiomyopathies in Africa.

New and changing patterns of multimorbidity (MM), i.e., multiple concurrent acute or chronic diseases in a person, are emerging in low- and middle-income countries (LMICs). The interplay of underlying population-specific factors and lifestyle habits combined with the colliding epidemics of communicable and non-communicable diseases presents new disease combinations, complexities and risks that are not common in high-income countries (HICs). The complexities and risks include those arising from potentially harmful drug-drug and drug-disease interactions (DDIs), the management of which may be considered as MM in the true sense. A major concern in LMICs is the increasing burden of leading cardiovascular diseases, prevalence of associated risk factors and co-occurrence with other morbidities. New models of MM management and integrated care can respond to the needs of specific multimorbid populations, with some LMICs making substantial progress (e.g., integration of tuberculosis and HIV services in South Africa). But there is a dearth of relevant data on the changing patterns and underlying factors and determinants of MM, the associated complexities and risks of DDIs in MM management, and the barriers to integrated care in LMICs. This requires careful attention.

Heart failure (HF) is a global public health concern with disproportionate socioeconomic, morbidity and mortality burden on low- and middle-income countries (LMICs). This review summarises contemporary data on the demographic and clinical characteristics, aetiologies, treatment, economic burden and outcomes of HF in LMICs. Patients with HF in LMICs are younger than those from high-income countries (HICs) and present at advanced stages of the disease. Hypertension, ischaemic heart disease (IHD), cardiomyopathy (CMO), and rheumatic heart disease (RHD) are the leading causes of HF in LMICs. The contribution of infectious diseases to HF remains prominent in many LMICs. Most health facilities in LMICs lack adequate diagnostic tools for HF, and the use of evidence-based medical and device therapies is suboptimal. Further, HF in LMICs is associated with prolonged hospital stay and high in-hospital and one-year mortality. Finally, HF has profound economic impact on individual patients who, mostly, have no health insurance, and on societies where patients are young, comprising those who have the greatest potential to contribute to economic productivity.

The burden of cardiovascular disease in people living with HIV (PLWH) has tripled over the last 20 years, with cardiac manifestations of disease ranging from coronary disease to heart failure (1). The pathophysiological mechanisms involved in the development of HIV cardiomyopathy remain elusive. Subclinical structural and functional changes have been demonstrated in PLWH, but studies that used advanced imaging techniques focused on patients already treated with antiretroviral therapy (ART), potentially limiting the understanding of cardiac manifestations of HIV...

Background: A routine diagnostic work-up does not identify structural abnormalities in a substantial proportion of patients with idiopathic ventricular arrhythmias (VAs). We investigated the added value of cardiac magnetic resonance (CMR) imaging in this group of patients. Methods: A single-centre prospective study was undertaken of 72 patients (mean age 46 ± 16 years; 53% females) with frequent premature ventricular contractions (PVCs ≥ 500/24 h) and/or non-sustained ventricular tachycardia (NSVT), an otherwise normal electrocardiogram, normal echocardiography and no coronary artery disease. Results: CMR provided an additional diagnostic yield in 54.2% of patients. The most prevalent diagnosis was previous myocarditis (23.6%) followed by possible PVC-related cardiomyopathy (20.8%), non-ischaemic cardiomyopathy (8.3%) and ischaemic heart disease (1.4%). The predictors of abnormal CMR findings were male gender, age and PVCs/NSVT non-outflow tract-related or with multiple morphologies. Patients with VAs had an impaired peak left ventricular (LV) global radial strain (GRS) compared with the controls (28.88% (IQR: 25.87% to 33.97%) vs. 36.65% (IQR: 33.19% to 40.2%), p < 0.001) and a global circumferential strain (GCS) (−17.66% (IQR: −19.62% to −16.23%) vs. −20.66% (IQR: −21.72% to −19.6%), p < 0.001). Conclusion: CMR reveals abnormalities in a significant proportion of patients with frequent idiopathic VAs. Male gender, age and non-outflow tract PVC origin can be clinical indicators for CMR referral.

Peripartum cardiomyopathy (PPCM) is a potentially life-threatening condition in which heart failure and systolic dysfunction occur late in pregnancy or within months following delivery. To date, no reliable biomarkers or therapeutic interventions for the condition exist, thus necessitating an urgent need for identification of novel PPCM drug targets and candidate biomarkers. Leads for novel treatments and biomarkers are therefore being investigated worldwide. Pregnancy is generally accompanied by dramatic hemodynamic changes, including a reduced afterload and a 50% increase in cardiac output. These increased cardiac stresses during pregnancy potentially impair protein folding processes within the cardiac tissue. The accumulation of misfolded proteins results in increased toxicity and cardiac insults that trigger heart failure. Under stress conditions, molecular chaperones such as heat shock proteins (Hsps) play crucial roles in maintaining cellular proteostasis. Here, we critically assess the potential role of Hsps in PPCM. We further predict specific associations between the Hsp types Hsp70, Hsp90 and small Hsps with several proteins implicated in PPCM pathophysiology. Furthermore, we explore the possibility of select Hsps as novel candidate PPCM biomarkers and drug targets. A better understanding of how these Hsps modulate PPCM pathogenesis holds promise in improving treatment, prognosis and management of the condition, and possibly other forms of acute heart failure.

Neutralization escape by SARS-CoV-2 variants, as has been observed in the 501Y.V2 (B.1.351) variant, has impacted the efficacy of first generation COVID-19 vaccines. Here, the antibody response to the 501Y.V2 variant was examined in a cohort of patients hospitalized with COVID-19 in early 2021 - when over 90% of infections in South Africa were attributed to 501Y.V2. Robust binding and neutralizing antibody titers to the 501Y.V2 variant were detected and these binding antibodies showed high levels of cross-reactivity for the original variant, from the first wave. In contrast to an earlier study where sera from individuals infected with the original variant showed dramatically reduced potency against 501Y.V2, sera from 501Y.V2-infected patients maintained good cross-reactivity against viruses from the first wave. Furthermore, sera from 501Y.V2-infected patients also neutralized the 501Y.V3 (P.1) variant first described in Brazil, and now circulating globally. Collectively these data suggest that the antibody response in patients infected with 501Y.V2 has a broad specificity and that vaccines designed with the 501Y.V2 sequence may elicit more cross-reactive responses.

BackgroundWhilst global health research often involves international collaborations, achieving or promoting equity within collaborations remains a key challenge, despite established conceptual approaches and the development of frameworks and guidelines to promote equity. There have also been several empirical studies documenting researchers’ experiences of inequity and views on what is required to advance equity in global health collaborations. While these empirical studies provide critical insights, there has been no attempt to systematically synthetize what constitutes equity and how it can be achieved. To address this gap, we conducted a scoping review of qualitative studies, opinion and editorial pieces about what equity is and how it can be promoted in international collaborations.MethodsWe conducted a scoping review to explore domains of equity in international health collaborations. This review included qualitative studies and opinion pieces or editorial pieces on equity in international health collaborations. We mapped the data and identified common themes using a thematic analysis approach.ResultsThis initial search retrieved a total of 7611 papers after removing duplicates. A total of 11 papers were included in this review, 10 empirical studies and 1 editorial piece. We conducted our search between October – November 2019. We identified 10 key domains which are important for promoting equity in international collaborations: funding; capacity building; authorship; sample ownership and export; trust; research agreement; acknowledging inequality; recognition and communication.DiscussionOur findings suggest that for international collaborations to be considered more equitable, it must at least consider the 10 domains we highlighted. The 10 domains map onto five key aspects of social justice theory, namely avoiding unequal power relations like subordination, group recognition and affirmation, promoting the well-being of all, inclusion in decision-making and ensuring self-development.

Background Heart failure is a prominent cardiovascular disease (CVD) manifestation in sub-Sarahan Africa. Myocardial fibrosis is a central feature of heart failure that we aimed to characterize among persons with human immunodeficiency virus (PWH) in South Africa. Methods Cardiovascular magnetic resonance (CMR) imaging was performed among PWH with viral suppression and uninfected controls, both free of known CVD. Plasma levels of N-terminal pro B-type natriuretic peptide (NT-proBNP) were measured. Comparisons by human immunodeficiency virus (HIV) status were made using linear and logistic regression, adjusted for age, sex, and hypertension. Results One hundred thirty-four PWH and 95 uninfected persons completed CMR imaging; age was 50 and 49 years, with 63% and 67% female, respectively. Compared with controls, PWH had greater myocardial fibrosis by extracellular volume fraction ([ECV] absolute difference, 1.2%; 95% confidence interval [CI], 0.1–2.3). In subgroup analyses, the effect of HIV status on ECV was more prominent among women. Women (vs controls) were also more likely to have elevated NT-proBNP levels (>125 pg/mL; odds ratio, 2.4; 95% CI, 1.0–6.0). Among all PWH, an elevated NT-proBNP level was associated with higher ECV (3.4% higher; 95% CI, 1.3–5.5). Conclusions Human immunodeficiency virus disease may contribute to myocardial fibrosis, with an effect more prominent among women. Research is needed to understand heart failure risk among PWH within sub-Saharan Africa.

Introduction Peripartum cardiomyopathy (PPCM) is an important cause of pregnancy-associated heart failure worldwide. Although a significant number of women recover their left ventricular (LV) function within 12 months, some remain with persistently reduced systolic function. Methods Knowledge gaps exist on predictors of myocardial recovery in PPCM. N-terminal pro-brain natriuretic peptide (NT-proBNP) is the only clinically established biomarker with diagnostic value in PPCM. We aimed to establish whether NT-proBNP could serve as a predictor of LV recovery in PPCM, as measured by LV end-diastolic volume (LVEDD) and LV ejection fraction (LVEF). Results This study of 35 women with PPCM (mean age 30.0 ± 5.9 years) had a median NT-proBNP of 834.7 pg/ml (IQR 571.2–1840.5) at baseline. Within the first year of follow-up, 51.4% of the cohort recovered their LV dimensions (LVEDD 50%). Women without LV recovery presented with higher NT-proBNP at baseline. Multivariable regression analyses demonstrated that NT-proBNP of ≥ 900 pg/ml at the time of diagnosis was predictive of failure to recover LVEDD (OR 0.22, 95% CI 0.05–0.95, P = 0.043) or LVEF (OR 0.20 [95% CI 0.04–0.89], p = 0.035) at follow-up. Conclusions We have demonstrated that NT-proBNP has a prognostic value in predicting LV recovery of patients with PPCM. Patients with NT-proBNP of ≥ 900 pg/ml were less likely to show any improvement in LVEF or LVEDD. Our findings have implications for clinical practice as patients with higher NT-proBNP might require more aggressive therapy and more intensive follow-up. Point-of-care NT-proBNP for diagnosis and risk stratification warrants further investigation.

The presentation and identification of cardiovascular disease in women pose unique diagnostic challenges compared to men, and underrecognized conditions in this patient population may lead to clinical mismanagement.This article reviews the sex differences in cardiovascular disease, explores the diagnostic and prognostic role of cardiovascular magnetic resonance (CMR) in the spectrum of cardiovascular disorders in women, and proposes the added value of CMR compared to other imaging modalities. In addition, this article specifically reviews the role of CMR in cardiovascular diseases occurring more frequently or exclusively in female patients, including Takotsubo cardiomyopathy, connective tissue disorders, primary pulmonary arterial hypertension and peripartum cardiomyopathy. Gaps in knowledge and opportunities for further investigation of sex-specific cardiovascular differences by CMR are also highlighted.

In this review, the role of cardiovascular magnetic resonance (CMR), magnetic resonance angiography (MRA) and magnetic resonance spectroscopy (MRS) in the diagnosis, risk stratification, management and prognostication of inflammatory arthropathies and systemic rheumatic diseases (IASRD) is discussed. There have been several recent publications and it is timely to place into perspective the rapidly evolving concepts of advanced imaging in IASRDs through review and critical appraisal of the literature. IASRD are multisystemic autoimmune disorders with predilection for cardiovascular involvement and complications. Persons with IASRD have increased risk of coronary artery disease, stroke, peripheral vascular disease, myocarditis, cardiomyopathy and heart failure that may not be fully explained by traditional CVD risk factors, and inflammation is presumed to be an important determinant of CVD. There is increasing evidence that lowering systemic inflammation reduces prevalence of CVD in IASRD patients. CMR is an advanced imaging modality, free of ionising radiation, with high spatial and temporal resolution, performed via excitation of atomic nuclei with uneven spin and capable of providing detailed anatomical, functional and haemodynamic information on the heart and vasculature. CMR is the single imaging modality capable of assessing noninvasively global and regional cardiac function, fibrosis, perfusion, flow, vascular function and oedema. The unique strengths of CMR are its ability to noninvasively image the entire cardiovascular tree (myocardium and vessels) with high resolution and to reveal tissue characteristics for the study of inflammation, infarction, fibrosis and infiltration. CMR combined with MRA is capable of visualising vascular complications of IASRD as well as to track disease progression or regression following therapy. MRS reported no abnormalities in IASRD on proton MRS, but impaired myocardial energetics on phosphorous MRS. CMR, MRA and MRS have significantly improved our understanding of disease mechanisms, diagnosis, risk stratification, management and prognostication of IASRD. Further CMR can be used for the study of inflammation and fibrosis and to track disease progression and regression following therapeutic interventions.

This article provides a review of how rapid Cardiac Magnetic Resonance (CMR) has been used successfully in different clinical settings, outlining the current role of CMR and the unique, incremental information provided in the care of the patient. The article will provide a review of the abbreviated protocols used, future developments and ways to optimize these protocols. A major emphasis of the application of this technology is in Low and Middle-Income Countries (LMICs) where Cardiovascular disease (CVD) is the major cause of morbidity and mortality, however the principles and protocols can be applied across a broad array of clinical platforms. By using a truncated protocol for CMR, most scans can be performed in under 30 minutes, with an average time of 18 minutes for scans which evaluates function and fibrosis (contrast study). A study can be performed within 8 minutes for the assessment of cardiac iron overload (non-contrast study). Rapid CMR can alter clinical management in up to 56% of patients. Rapid CMR protocols do not need state-of-the-art equipment or software. These protocols can be implemented in many centers around the world with appropriate exposure and training. CMR can be performed rapidly without compromising the diagnostic yield of the technique. Rapid CMR can reduce the costs of performing CMR, increase throughput through the scanner and potentially increase the use of the modality in centers worldwide. This could lead to the improvement of clinical care through superior diagnostics and better targeting of therapy.

Aims Cardiovascular disease is the leading cause of maternal morbidity and mortality, frequently requiring cardiac imaging for diagnosis, and follow-up. This need does not change pregnancy; however, many centres do not offer cardiovascular magnetic resonance (CMR) to pregnant patients. This paper explores current practice of CMR in pregnancy in four large volume centres, its safety and its impact on patient management. Methods and results Between 2008 and 2017, we collected consecutive pregnant patients between four centres. Guidelines and local standard operating procedures were followed and outcomes recorded modelled on the EuroCMR registry. Eighty-three women had diagnostic CMR without immediate complications. The commonest indication was vascular or congenital disease (48%), followed by cardiomyopathy/myocarditis (43%). Nineteen percent received contrast, and CMR changed management in 35% and in 50% of patients who received contrast. Conclusion In this largest cohort to date describing CMR in pregnancy, we found that results frequently change management, thus adding valuable guidance for patient care. We conclude that CMR should be offered to pregnant women when indicated, including the administration of contrast as per current guidelines.

In Sub-Saharan Africa (SSA), chronic non-communicable diseases and cardiovascular diseases in particular, are progressively taking over infectious diseases as the leading cause of morbidity and mortality. Heart failure is a major public health problem in the region. We summarize here available data on the prevalence, aetiologies, treatment, rates and predictors of mortality due to heart failure in SSA. Keywords: Heart failure, Prevalence, Aetiologies, Treatment, Mortality, Sub-Saharan Africa

Objective To summarise available data on the prevalence, aetiology, treatment and prognosis of heart failure (HF) in sub-Saharan Africa (SSA). Setting This systematic review and meta-analysis included data from individuals recruited in primary to tertiary health facilities in SSA. Participants All published and unpublished literatures between January 1, 1996 and June 23, 2017, of individuals aged 12years and older and residing in sub-Saharan Africa. They must be of African descent. Outcome Number of heart failure admissions into general wards or HF clinics; number of cases of the different aetiologies of HF; number of participants on the different medications for HF; number of cases of all-cause mortality in participants with HF, and the predictors of all-cause mortality. Due to a limited word count, only results on the aetiologies of HF will be presented in the abstract. Results Thirty five full text articles were selected after screening of an initial 3785 titles and abstract. Hypertensive heart disease (HHD) (39.2% [95% CI=32.6–45.9]) was the commonest cause of HF in SSA, followed by cardiomyopathies (CMO) (21.4% [95% CI=16.0–27.2]) and rheumatic heart disease (RHD) (14.1% [95% CI=10.0–18.8]). Ischaemic heart disease (7.2% [95% CI=4.1–11.0]) was rare. Conclusion HHD, CMO and RHD are the most common causes of HF in SSA, with HHD and CMO responsible for over 50% of the cases. Also, the last two decades have witnessed a relative reduction in the prevalence of RHD below 15.0%.

Africa is witnessing an epidemic of cardiovascular disease (CVD), with staggering morbidity and mortality. The spectrum of CVD includes hypertension, rheumatic heart disease, cardiomyopathy, atherosclerotic disease, congenital heart disease and tuberculous pericarditis. Opportunities exist to alter the trajectory of CVD epidemiology but require committed policy makers, functional health systems and an engaged citizenry.

RATIONALE: The utility of heated and humidified high-flow nasal oxygen (HFNO) for severe COVID-19-related hypoxaemic respiratory failure (HRF), particularly in settings with limited access to intensive care unit (ICU) resources, remains unclear, and predictors of outcome have been poorly studied. METHODS: We included consecutive patients with COVID-19-related HRF treated with HFNO and awake proning at two tertiary hospitals in Cape Town, South Africa. The primary outcome was the proportion of patients who were successfully weaned from HFNO, whilst failure comprised intubation or death on HFNO. FINDINGS: The median (IQR) arterial oxygen partial pressure to fraction inspired oxygen ratio (PaO2/FiO2) was 68 (54-92) in 293 enrolled patients. 137/293 (47%) of patients [PaO2/FiO2 76 (63-93)] were successfully treated with HFNO. The median duration of HFNO was 6 (3-9) in those successfully treated versus 2 (1-5) days in those who failed (p

Background: Most biomedical research has focused on sampling COVID-19 patients presenting to hospital with advanced disease, with less focus on the asymptomatic or paucisymptomatic. We established a bioresource with serial sampling of health care workers (HCWs) designed to obtain samples before and during mainly mild disease, with follow-up sampling to evaluate the quality and duration of immune memory. Methods: We conducted a prospective observational study on HCWs from three hospital sites in London, initially at a single centre (recruited just prior to first peak community transmission in London), but then extended to multiple sites 3 weeks later (recruitment still ongoing, target n=1,000). Asymptomatic participants attending work complete a health questionnaire, and provide a nasal swab (for SARS-CoV-2 RNA by RT-PCR tests) and blood samples (mononuclear cells, serum, plasma, RNA and DNA are biobanked) at 16 weekly study visits, and at 6 and 12 months. Results: Preliminary baseline results for the first 731 HCWs (400 single-centre, 331 multicentre extension) are presented. Mean age was 38±11 years; 67% are female, 31% nurses, 20% doctors, and 19% work in intensive care units. COVID-19-associated risk factors were: 37% black, Asian or minority ethnicities; 18% smokers; 13% obesity; 11% asthma; 7% hypertension and 2% diabetes mellitus. At baseline, 41% reported symptoms in the preceding 2 weeks. Preliminary test results from the initial cohort (n=400) are available: PCR at baseline for SARS-CoV-2 was positive in 28 of 396 (7.1%, 95% CI 4.9-10.0%) and 15 of 385 (3.9%, 2.4-6.3%) had circulating IgG antibodies. Conclusions: This COVID-19 bioresource established just before the peak of infections in the UK will provide longitudinal assessments of incident infection and immune responses in HCWs through the natural time course of disease and convalescence. The samples and data from this bioresource are available to academic collaborators by application https://covid-consortium.com/application-for-samples/.

IntroductionIn Sub-Saharan Africa, the rising rates of cerebrovascular and cardiovascular diseases (CBD/CVD) are intersecting with an ageing HIV-infected population. The widespread use of antiretroviral therapy (ART) may confer an additive risk and may not completely suppress the risk associated with HIV infection. High-quality prospective studies are needed to determine if HIV-infected patients in Africa are at increased risk of CBD/CVD and to identify factors associated with this risk. This study will test the hypothesis that immune activation and dysfunction, driven by HIV and reactivation of latent herpesvirus infections, lead to increased CBD/CVD risk in Malawian adults aged ≥35 years.Methods and analysisWe will conduct a single-centre, 36-month, prospective cohort study in 800 HIV-infected patients initiating ART and 190 HIV-uninfected controls in Blantyre, Malawi. Patients and controls will be recruited from government ART clinics and the community, respectively, and will be frequency-matched by 5-year age band and sex. At baseline and follow-up visits, we will measure carotid intima-media thickness and pulse wave velocity as surrogate markers of vasculopathy, and will be used to estimate CBD/CVD risk. Our primary exposures of interest are cytomegalovirus and varicella zoster reactivation, changes in HIV plasma viral load, and markers of systemic inflammation and endothelial function. Multivariable regression models will be developed to assess the study’s primary hypothesis. The occurrence of clinical CBD/CVD will be assessed as secondary study endpoints.Ethics and disseminationThe University of Malawi College of Medicine and Liverpool School of Tropical Medicine research ethics committees approved this work. Our goal is to understand the pathogenesis of CBD/CVD among HIV cohorts on ART, in Sub-Saharan Africa, and provide data to inform future interventional clinical trials. This study runs between May 2017 and August 2020. Results of the main trial will be submitted for publication in a peer-reviewed journal.Trial registration numberISRCTN42862937.

Patients with cardiomyopathy are at risk of developing atrial fibrillation (AF) which is a strong risk factor for thromboembolic events, progression to heart failure, and mortality or heart transplantation. This systematic review and meta-analysis sought to estimate the prevalence of AF in a global population with cardiomyopathy. PubMed and EMBASE were searched from inception until June 30, 2017 for published articles on AF and major cardiomyopathies without language restrictions. Eligible papers were independently assessed for methodological qualities. The prevalence of AF in patients with cardiomyopathy was estimated using a random-effect model. The chi-square test on Cochrane's Q statistics was used to evaluate heterogeneity across studies. In total 220 full texts representing a population of 118,668 participants were included in the meta-analysis. The ages of the participants ranged from a median of 31 to 72 years. The proportion of males ranged from 3% to 97%. Considering only cardiomyopathies with more than one contributing study, the prevalence of AF was highest in participants with dilated (24% [95% confidence interval: 21 to 28]), ischemic (20% [8 to 35]), and hypertrophic (19% [17 to 21]) cardiomyopathies, and lowest in patients with peripartum cardiomyopathies (5% [1 to 11]). In conclusion, with the exception of peripartum cardiomyopathy, an average of 1 to 2 in every 10 patients with a cardiomyopathy had AF, with no gender difference. Future guidelines need to take into consideration the management of AF in all the forms of cardiomyopathy.

Mobile phones, due to their audio processing capabilities, have the potential to facilitate the diagnosis of heart disease through automated auscultation. However, such a platform is likely to be used by non-experts, and hence, it is essential that such a device is able to automatically differentiate poor quality from diagnostically useful recordings since non-experts are more likely to make poor-quality recordings. This paper investigates the automated signal quality assessment of heart sound recordings performed using both mobile phone-based and commercial medical-grade electronic stethoscopes. The recordings, each 60 s long, were taken from 151 random adult individuals with varying diagnoses referred to a cardiac clinic and were professionally annotated by five experts. A mean voting procedure was used to compute a final quality label for each recording. Nine signal quality indices were defined and calculated for each recording. A logistic regression model for classifying binary quality was then trained and tested. The inter-rater agreement level for the stethoscope and mobile phone recordings was measured using Conger's kappa for multiclass sets and found to be 0.24 and 0.54, respectively. One-third of all the mobile phone-recorded phonocardiogram (PCG) signals were found to be of sufficient quality for analysis. The classifier was able to distinguish good- and poor-quality mobile phone recordings with 82.2% accuracy, and those made with the electronic stethoscope with an accuracy of 86.5%. We conclude that our classification approach provides a mechanism for substantially improving auscultation recordings by non-experts. This work is the first systematic evaluation of a PCG signal quality classification algorithm (using a separate test dataset) and assessment of the quality of PCG recordings captured by non-experts, using both a medical-grade digital stethoscope and a mobile phone.

Summary Background Little is known about the clinical characteristics, spectrum of causal genetic mutations and outcome of hypertrophic cardiomyopathy (HCM) in Africans. The objective of this study was to delineate the clinical and genetic features and outcome of HCM in African patients. Methods Information on clinical presentation, electrocardiographic and echocardiographic findings, and outcome of cases with HCM was collected from the Cardiac Clinic at Groote Schuur Hospital over a mean duration of follow up of 9.1 ± 3.4 years. Genomic DNA was screened for mutations in 15 genes that cause HCM, i.e. cardiac myosinbinding protein C (MYBPC3), cardiac β-myosin heavy chain (MYH7), cardiac troponin T2 (TNNT2), cardiac troponin I (TNNI3), regulatory light chain of myosin (MYL2), essential light chain of myosin (MYL3), tropomyosin 1 (TPM1), phospholamban (PLN), α-actin (ACTC1), cysteine and glycine-rich protein 3 (CSRP3), AMP-activated protein kinase (PRKAG2), α-galactosidase (GLA), four-and-a-half LIM domains 1 (FHL1), lamin A/C (LMNA) and lysosomeassociated membrane protein 2 (LAMP2). Survival and its predictors were analysed using the Kaplan–Meier and Cox proportional hazards regression methods, respectively. Results Forty-three consecutive patients [mean age 38.5 ± 14.3 years; 25 (58.1%) male; and 13 (30.2%) black African] were prospectively enrolled in the study from January 1996 to December 2012. Clinical presentation was similar to that reported in other studies. The South African founder mutations that cause HCM were not found in the 42 probands. Ten of 35 index cases (28.6%) tested for mutations in 15 genes had disease-causing mutations in MYH7 (six cases or 60%) and MYBPC3 (four cases or 40%). No disease-causing mutation was found in the other 13 genes screened. The annual mortality rate was 2.9% per annum and overall survival was 74% at 10 years, which was similar to the general South African population. Cox’s proportional hazards regression showed that survival was predicted by New York Heart Association (NYHA) functional class at last visit (p = 0.026), but not by the presence of a disease-causing mutation (p = 0.474). Conclusions Comprehensive genetic screening was associated with a 29% yield of causal genetic mutations in South African HCM cases, all in MYH7 and MBPC3 genes. A quarter of the patients had died after a decade of follow up, with NYHA functional class serving as a predictor of survival.

The survival of patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) who have access to highly active antiretroviral therapy (ART) has dramatically increased in recent times. This review focuses on HIV‐associated heart failure in sub‐Saharan Africa (SSA). In HIV infected persons, heart failure may be related to pathology of the pericardium, the myocardium, the valves, the conduction system, or the coronary and pulmonary vasculature. HIV‐associated heart failure can be because of direct consequences of HIV infection, autoimmune reactions, pro‐inflammatory cytokines, opportunistic infections (OIs) or neoplasms, use of ART or therapy for OIs and presence of traditional cardiovascular risk factors. Myocardial involvement includes diastolic dysfunction, asymptomatic left ventricular dysfunction, cardiomyopathy, myocarditis, fibrosis, and steatosis. Pericardial diseases include pericarditis, pericardial effusions (rarely causing tamponade), pericardial constriction, and effusive‐constrictive syndromes. Coronary artery disease is commonly reported in industrial nations, although its prevalence is thought to be low in HIV‐infected persons from SSA.

Peripartum cardiomyopathy (PPCM) is a condition in which heart failure and systolic dysfunction occur late in pregnancy or within months following delivery. Over the last decade, genetic advances in heritable cardiomyopathy have provided new insights into the role of genetics in PPCM. In this review, we summarise current knowledge of the genetics of PPCM and potential avenues for further research, including the role of molecular chaperone mutations in PPCM. Evidence supporting a genetic basis for PPCM has emanated from observations of familial disease, overlap with familial dilated cardiomyopathy, and sequencing studies of PPCM cohorts. Approximately 20% of PPCM patients screened for cardiomyopathy genes have an identified pathogenic mutation, with TTN truncations most commonly implicated. As a stress-associated condition, PPCM may be modulated by molecular chaperones such as heat shock proteins (Hsps). Recent studies have led to the identification of Hsp mutations in a PPCM model, suggesting that variation in these stress-response genes may contribute to PPCM pathogenesis. Although some Hsp genes have been implicated in dilated cardiomyopathy, their roles in PPCM remain to be determined. Additional areas of future investigation may include the delineation of genotype-phenotype correlations and the screening of newly-identified cardiomyopathy genes for their roles in PPCM. Nevertheless, these findings suggest that the construction of a family history may be advised in the management of PPCM and that genetic testing should be considered. A better understanding of the genetics of PPCM holds the potential to improve treatment, prognosis, and family management.

Pregnant women with known or suspected cardiovascular disease (CVD) often require cardiovascular imaging during pregnancy. The accepted maximum limit of ionising radiation exposure to the foetus during pregnancy is a cumulative dose of 5 rad. Concerns related to imaging modalities that involve ionising radiation include teratogenesis, mutagenesis and childhood malignancy. Importantly, no single imaging study approaches this cautionary dose of 5 rad (50 mSv or 50 mGy). Diagnostic imaging procedures that may be used in pregnancy include chest radiography, fluoroscopy, echocardiography, invasive angiography, cardiovascular computed tomography, computed tomographic pulmonary angiography, cardiovascular magnetic resonance (CMR) and nuclear techniques. Echocardiography and CMR appear to be completely safe in pregnancy and are not associated with any adverse foetal effects, provided there are no general contra-indications to MR imaging. Concerns related to safety of imaging tests must be balanced against the importance of accurate diagnosis and thorough assessment of the pathological condition. Decisions about imaging in pregnancy are premised on understanding the physiology of pregnancy, understanding basic concepts of ionising radiation, the clinical manifestations of existent CVD in pregnancy and features of new CVD. The cardiologist/physician must understand the indications for and limitations of, and the potential harmful effects of each test during pregnancy. Current evidence suggests that a single cardiovascular radiological study during pregnancy is safe and should be undertaken at all times when clinically justified. In this article, the different imaging modalities are reviewed in terms of how they work, how safe they are and what their clinical utility in pregnancy is. Furthermore, the safety of contrast agents in pregnancy is also reviewed.

Background: Rheumatoid arthritis (RA) is a multisystem, autoimmune disorder and confers one of the strongest risks for cardiovascular disease (CVD) morbidity and mortality. Objective: To assess myocardial function and vascular stiffness in RA patients with and without cardiovascular risk factors (CVRFs) using cardiovascular magnetic resonance (CMR). Methods: Twenty-three RA patients with no CVRFs (17 female, mean age 52 ± 13 years), 46 RA patients with CVRFs (32 female, mean age 53 ± 12), 50 normal controls (32 female, mean age 50 ± 11 years), and 13 controls with CVRFs (7 female, mean age 55 ± 7 years), underwent CMR at 1.5 Tesla, including evaluation of left ventricular (LV) ejection fraction, strain, and vascular elasticity (aortic distensibility [AD] and pulse wave velocity [PWV]). Disease activity and duration were recorded for each patient. Subjects with known symptomatic CVD were excluded. Results: LV volumes, mass, and ejection fraction were similar in the four groups. RA patients with CVRFs showed the greatest abnormality in mid short-axis circumferential systolic strain, peak diastolic strain rate, and vascular indices. RA patients without CVRFs showed a similar degree of vascular dysfunction and deformational abnormality as controls with CVRFs. AD and total PWV correlated with myocardial strain and RA disease activity. On multivariate regression analysis, strain was related to age, RA disease activity, AD, and PWV. Conclusion: CMR demonstrates impaired myocardial deformation and vascular function in asymptomatic RA patients, worse in those with CVRFs. Subclinical cardiovascular abnormalities are frequent and appear to be incremental to those due to traditional CVRFs and likely contribute to the excess CVD in RA. Keywords: Rheumatoid arthritis, left ventricular function, myocardial strain, vascular function, cardiovascular magnetic resonance

Aims. Cardiovascular magnetic resonance (CMR) permits a comprehensive evaluation of stable coronary artery disease (CAD). We sought to assess whether, in a large contemporaneous population receiving optimal medical therapy, CMR independently predicts prognosis beyond conventional cardiovascular risk factors (RF). Methods. We performed a single centre, observational prospective study that enrolled 465 CAD patients (80% males; 63±11 years), optimally treated with ACE-inhibitors/ARB, aspirin, and statins (76-85%). Assessments included conventional evaluation (clinical history, atherosclerosis RF, electrocardiography, and echocardiography) and a comprehensive CMR with LV dimensions/function, late gadolinium enhancement (LGE), and stress perfusion CMR (SPCMR). Results. During a median follow-up of 62 months (IQR 23-74) there were 50 deaths and 92 major adverse cardiovascular events (MACE). CMR variables improved multivariate model prediction power of mortality and MACE over traditional RF alone (F-test p[95% CI]: 3.4 [1.3−8.8]); moreover, LGE (3.3 [1.7−6.3]) and SPCMR (2.1 [1.4−3.2]) were the best predictors of MACE. Conclusion. LGE is an independent noninvasive marker of mortality in the long term in patients with stable CAD and optimized medical therapy. Furthermore, LGE and SPCMR independently predict MACE beyond conventional risk stratification.

The purpose of this article is to review the literature on HIV and myocarditis and HIV-associated heart failure.Currently, 17 million people are receiving antiretroviral therapy (ART) globally. There is a decrease in mortality from HIV in the last decade with increased survival in those receiving ART. HIV-associated cardiac failure is on the increase, with more cases of diastolic dysfunction reported in the ART era. The pathophysiology of HIV-associated myocarditis is multifactorial. Cardiovascular magnetic resonance (CMR), through tissue characterization, demonstrates increased native T1 values which reflect both increased myocardial inflammation and fibrosis in HIV infection.HIV-associated myocarditis is common and may be an important cause of HIV-associated cardiac failure. CMR is an important imaging modality for the study of myocardial inflammation.

Despite ongoing advances in the treatment of patients with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), they remain a major global public health concern conferring an increased risk of morbidity and mortality in affected individuals. This is, in part, because of the widespread dysfunction imposed by HIV and its treatment on the cardiovascular system, including the myocardium, valvular apparatus, pericardium and coronary, pulmonary and peripheral vasculature. In recent times, cardiovascular magnetic resonance (CMR) imaging has emerged as the gold standard tool for assessment of a variety of indications, allowing comprehensive characterisation of functional, morphological, metabolic and haemodynamic sequelae of several cardiovascular pathologies. Furthermore, continued advancement in imaging techniques has yielded novel insights into the underlying pathophysiology and guides future therapeutic strategies. In this article, we review the various clinical phenotypes of HIV-associated cardiovascular disease and highlight the utility of CMR in their assessment.

Cardiovascular magnetic resonance imaging plays a central role in the assessment and monitoring of patients with cardiomyopathy. It offers a comprehensive assessment during a single scan setting, with information on ventricular volumes, function and mass as well as tissue characterisation, fibrosis, flow, viability and perfusion. Acute tissue injury (oedema and necrosis) can be distinguished from fibrosis, infiltration and iron overload. It provides information on the cause and prognosis of the cardiomyopathy, and its high measurement accuracy makes it ideal for monitoring disease progression and effects of therapy. The present review highlights the main features of commonly encountered cardiomyopathies in imaging practice.