Clinical characteristics and one-year all-cause mortality outcomes in Africans with dilated cardiomyopathy.

AIMS: Dilated cardiomyopathy (DCM) is a common cause of heart failure in sub-Saharan Africa (SSA). The affected individuals present with new-onset heart failure with reduced ejection fraction and no identifiable primary or secondary aetiology. We aim to describe the clinical characteristics of participants with heart failure of unknown origin. METHODS: We screened 161 participants with heart failure of unknown origin and prospectively excluded primary and secondary causes of DCM. All study participants were subjected to laboratory biochemical testing, echocardiography, cardiovascular magnetic resonance (CMR) imaging and invasive coronary angiography. RESULTS: The study comprised 93 participants with a mean age of 47.5 SD 13.1 years. Forty-six (56.1%) participants had evidence of late gadolinium enhancement (LGE) on imaging, and LGE was visualised in the mid wall in 28 (61.0%) of these participants. After a median duration of 13.4 months [interquartile range (IQR): 8.8-28.9 months], 18 (19%) participants died. Non-survivors had a higher median left atrial volume index (44.9 mL/m2 (IQR: 34.4-58.7) compared to survivors [32.9 mL/m2 (IQR: 24.5-47.0), p = 0.017)]. The rate of all-cause rehospitalisation was 29.3%, of which 17 of the 22 re-hospitalisations were heart failure related. CONCLUSION: Dilated cardiomyopathy in Africans primarily affects young males. In our cohort, this disease was associated with an all-cause mortality of 19% in one year. In SSA, large multicenter studies are required to investigate this disease's pathogenesis and outcomes.

The genetic basis for adult-onset idiopathic dilated cardiomyopathy in people of African descent.

Cardiomyopathies are a heterogeneous group of cardiac muscle disorders that result in dilated, hypertrophic, or restrictive pathophysiological entities. Dilated cardiomyopathy (DCM) is the most common form in sub-Saharan Africa (SSA). However, population-specific research studies reporting the actual burden of DCM in this region are still lacking. Also, little is known about the genetic basis of DCM in this population, and genetic testing is still not readily accessible. This review describes the common pathogenic genes implicated in DCM globally and discusses the evidence-based management of patients with DCM. We also present a summary of studies describing genes implicated or associated with DCM in patients residing in SSA.

Cardiovascular Magnetic Resonance Imaging Findings in Africans with Idiopathic Dilated Cardiomyopathy.

In sub-Saharan Africa, idiopathic dilated cardiomyopathy (IDCM) is a common yet poorly investigated cause of heart failure. Cardiovascular magnetic resonance (CMR) imaging is the gold standard for tissue characterisation and volumetric quantification. In this paper, we present CMR findings obtained from a cohort of patients with IDCM in Southern Africa suspected of having a genetic cause of cardiomyopathy. A total of 78 IDCM study participants were referred for CMR imaging. The participants had a median left ventricular ejection fraction of 24% [interquartile range, (IQR): 18-34]. Late gadolinium enhancement (LGE) was visualised in 43 (55.1%) participants and localised in the midwall in 28 (65.0%) participants. At the time of enrolment into the study, non-survivors had a higher median left ventricular end diastolic wall mass index of 89.4 g/m2 (IQR: 74.5-100.6) vs. 73.6 g/m2 (IQR: 51.9-84.7), p = 0.025 and a higher median right ventricular end-systolic volume index of 86 mL/m2 (IQR:74-105) vs. 41 mL/m2 (IQR: 30-71), p < 0.001. After one year, 14 participants (17.9%) died. The hazard ratio for the risk of death in patients with evidence of LGE from CMR imaging was 0.435 (95% CI: 0.259-0.731; p = 0.002). Midwall enhancement was the most common pattern, visualised in 65% of participants. Prospective, adequately powered, and multi-centre studies across sub-Saharan Africa are required to determine the prognostic significance of CMR imaging parameters such as late gadolinium enhancement, extracellular volume fraction, and strain patterns in an African IDCM cohort.

A comprehensive overview of pneumococcal vaccination recommendations for adults in South Africa, 2022.

Pneumococcal infections remain a common global cause of significant morbidity and mortality. The first recommendations for adult pneumococcal vaccination, published in South Africa in 1999, contained information only on the 23-valent polysaccharide vaccine (PPV23). With the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) for use in adults and the perceived uncertainty that most clinicians had regarding use of these vaccines in adults, these vaccine recommendations were updated in 2022. A Working Group, which consisted of individuals in various fields of medical practice in South Africa, who were from different areas of the country, and included clinicians from both the public and private sectors, was assembled to revise the recommendations. The expertise of the participants varied widely, dependent on their training and specialty, and encompassed different organ systems, disease conditions, and/or practice types. Each participant was allocated a different section, based on their expertise, for which they were required to do an extensive review of the current literature and write their section. The entire working group then reviewed the complete document several times, following additional comments and recommendations. This update contains recommendations for the use of both PPV23 and PCV13, either alone, or in sequence, both in vaccine naïve and in previously vaccinated individuals. It includes both age and risk categories, and encompasses the elderly (≥65 years), as well as younger adults (<65 years) with comorbid conditions or with high-risk conditions and/or immunocompromise. It is hoped that this review and its associated vaccine recommendations will clarify for clinicians, from all spheres of practice in South Africa, how, where, and when pneumococcal vaccines should be used in adults, with the ultimate goal of significantly increasing the appropriate use of these vaccines, in order to decrease the substantial morbidity and mortality associated with pneumococcal infections in adults in South Africa. Furthermore, it is hoped that this review of local epidemiological data and the manner in which this information was interpreted in the development of these local vaccine recommendations, could be used as an example for other regions of the world, to tailor their recommendations to locally available epidemiological data.

Emerging Role of Platelet-Endothelium Interactions in the Pathogenesis of Severe SARS-CoV-2 Infection-Associated Myocardial Injury.

Cardiovascular dysfunction and disease are common and frequently fatal complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Indeed, from early on during the SARS-CoV-2 virus pandemic it was recognized that cardiac complications may occur, even in patients with no underlying cardiac disorders, as part of the acute infection, and that these were associated with more severe disease and increased morbidity and mortality. The most common cardiac complication is acute cardiac injury, defined by significant elevation of cardiac troponins. The potential mechanisms of cardiovascular complications include direct viral myocardial injury, systemic inflammation induced by the virus, sepsis, arrhythmia, myocardial oxygen supply-demand mismatch, electrolyte abnormalities, and hypercoagulability. This review is focused on the prevalence, risk factors and clinical course of COVID-19-related myocardial injury, as well as on current data with regard to disease pathogenesis, specifically the interaction of platelets with the vascular endothelium. The latter section includes consideration of the role of SARS-CoV-2 proteins in triggering development of a generalized endotheliitis that, in turn, drives intense activation of platelets. Most prominently, SARS-CoV-2-induced endotheliitis involves interaction of the viral spike protein with endothelial angiotensin-converting enzyme 2 (ACE2) together with alternative mechanisms that involve the nucleocapsid and viroporin. In addition, the mechanisms by which activated platelets intensify endothelial activation and dysfunction, seemingly driven by release of the platelet-derived calcium-binding proteins, SA100A8 and SA100A9, are described. These events create a SARS-CoV-2-driven cycle of intravascular inflammation and coagulation, which contributes significantly to a poor clinical outcome in patients with severe disease.

Coronary revascularization in patients with HIV.

With combined antiretroviral therapy, people living with HIV (PLWH) survive longer and are now more likely to die from cardiovascular diseases. PLWH presenting with a ST-segment elevation myocardial infarction are likely to have a high thrombus burden and are at high risk for in-hospital and long-term adverse events. An increasing number of PLWH are presenting with stable coronary artery disease related to atherosclerosis. Revascularization in these patients is associated with higher in-hospital and long-term major adverse cardiovascular events, including stent thrombosis and in-stent restenosis. However, data in this expanding population concerning optimal revascularization strategy are still lacking. In particular, data comparing percutaneous versus surgical revascularization in PLWH are needed. In this review we highlight the currently available data related to coronary revascularization in PLWH.

The prevalence of depression, stress and anxiety symptoms in patients with chronic heart failure.

BACKGROUND: Mental health illnesses are associated with frequent hospitalisation and an increased risk of all-cause mortality. Despite the high prevalence of depression in patients with chronic heart failure (CHF), there is a paucity of data on this subject from low and middle-income countries (LMIC). The aim of this study was to determine the prevalence of depression, anxiety, and stress symptoms in patients attending a dedicated CHF clinic. METHODS: A prospective study was conducted at an outpatient heart failure clinic in a tertiary academic centre. The study participants completed a Depression, Anxiety and Stress (DASS-21) questionnaire to screen for the presence and severity of depression, anxiety and stress symptoms. Furthermore, the Minnesota Living with Heart Failure Questionnaire (MLHFQ) was completed and used to evaluate the impact of CHF on health-related quality of life (QoL). Descriptive statistics were used to describe patients' characteristics and logistic regression analysis to identify predictors of symptoms of depression. RESULTS: The study population comprised of 103 patients, predominantly female (62.1%) with a median age of 53 (interquartile range 38-61) years. Symptoms of depression were reported by 52.4%, with 11.6% reporting symptoms suggestive of extremely severe depression. Anxiety was diagnosed in 53.4% of patients and extremely severe anxiety was reported by 18.4% of patients. Fifty patients were classified as stressed, and only 7.7% had extremely severe stress. More than half of the patients (54.4%) were in New York Heart Association functional class I. The mean left ventricular ejection fraction in the entire cohort was 30% (SD = ± 11.1%). In the multivariable logistic regression model, the MLHFQ score [odds ratio (OR) 1.04, 95% CI:1.02-1.06, p = 0.001] and the six-minute walk test [OR 0.99, 95% CI: 0.98-0.99, p = 0.014] were identified as independent predictors of depression. CONCLUSION: Depression and anxiety symptoms were found in over half of patients attending the CHF clinic. We recommend that mental health screening should be routinely performed in patients with CHF. Prospective, adequately powered, multicentre studies from LMIC investigating the impact of depression, anxiety and stress on CHF outcomes such as health-related QoL, hospitalisation and mortality are required.

Pregnancy outcomes in women with aortic coarctation.

OBJECTIVE: Pregnancy in women with aortic coarctation (CoA) has an estimated moderately increased risk (mWHO II-III) of adverse cardiovascular, obstetric or fetal events, but prospective data to validate this risk classification are scarce. We examined pregnancy outcomes and identified associations with adverse outcomes. METHODS: Pregnancies in women with CoA were selected from the worldwide prospective Registry of Pregnancy and Cardiac Disease (ROPAC, n=303 out of 5739), part of the European Society of Cardiology EURObservational Research Programme. The frequency of and associations with major adverse cardiac events (MACE) and hypertensive disorders (pregnancy-induced hypertension, (pre-)eclampsia or haemolysis, elevated liver enzymes and low platelets syndrome) were analysed. RESULTS: Of 303 pregnancies (mean age 30 years, pregnancy duration 39 weeks), 9.6% involved unrepaired CoA and 27.1% were in women with pre-existing hypertension. No maternal deaths or aortic dissections occurred. MACE occurred in 13 pregnancies (4.3%), of which 10 cases were of heart failure (3.3%). Univariable associations with MACE included prepregnancy clinical signs of heart failure (OR 31.8, 95% CI 6.8 to 147.7), left ventricular ejection fraction <40% (OR 10.4, 95% CI 1.8 to 59.5), New York Heart Association class >1 (OR 11.4, 95% CI 3.6 to 36.3) and cardiac medication use (OR 4.9, 95% CI 1.3 to 18.3). Hypertensive disorders of pregnancy occurred in 16 (5.3%), cardiac medication use being their only predictor (OR 3.2, 95% CI 1.1 to 9.6). Premature births were 9.1%, caesarean section was performed in 49.7% of pregnancies. Of 4 neonatal deaths, 3 were after spontaneous extreme preterm birth. CONCLUSIONS: The ROPAC data show low MACE and hypertensive disorder rates during pregnancy in women with CoA, suggesting pregnancy to be more safe and better tolerated than previously appreciated.

Association of chronic inflammation and accelerated atherosclerosis among an indigenous black population with chronic kidney disease.

INTRODUCTION: Inflammation plays a major role in the development of atherosclerosis and cardiovascular morbidity and mortality in chronic kidney disease (CKD) patients. Toll-like receptor-4 (TLR4) is a major receptor for lipopolysaccharides (endotoxin) and other ligands involved in the pathogenesis of inflammation. We determined whether endotoxin levels and the presence of TLR4 polymorphisms are associated with markers of inflammation and atherosclerosis among South African CKD patients. MATERIALS AND METHODS: Endotoxin, lipopolysaccharide binding protein (LBP), serum CD14 (sCD14), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and carotid intima media thickness (CIMT) were measured in 160 participants (120 CKD patients and 40 controls). Associations between endotoxins and CIMT in the presence of sCD14, IL-8 and MCP-1, were assessed using odds ratios. Participants were screened for the presence of Asp299Gly and Thr399Ile TLR4 polymorphisms, and CIMT and inflammatory markers were compared between subjects with and without TLR4 polymorphisms. RESULTS: Endotoxin levels correlated with sCD14 (r = 0.441, p<0.001) and MCP-1 (r = 0.388, p<0.001) levels while increased CIMT was associated with MCP-1 (r = 0.448, p<0.001), sCD14 levels (r = 0.476, p<0.001), LBP (r = 0.340, p<0.001), and IL-8 (r = 0.395, p<0.001). Atherosclerosis was associated with endotoxin levels (odds ratio: 4.95; 95% confidence interval: 2.52-9.73; p<0.001), and was predicted by higher serum levels of inflammatory markers. Analysis of patients with TLR4 polymorphisms showed reduced serum levels of inflammatory markers and CIMT values compared with the patients carrying the wild type TLR4 alleles. CONCLUSION: The study demonstrated associations between circulating endotoxaemia, systemic inflammation and accelerated atherosclerosis among South African CKD patients, and showed that the atherogenic predictive power of endotoxaemia was significantly increased by the presence of elevated levels of inflammatory markers. Additional findings, which must be confirmed, suggest that TLR4 polymorphisms are associated with low levels of inflammatory markers and CIMT values.

APOL1 Genetic Variants Are Associated with Serum-Oxidized Low-Density Lipoprotein Levels and Subclinical Atherosclerosis in South African CKD Patients.

INTRODUCTION: Apolipoprotein L1 (APOL1) plays an important role in cholesterol metabolism and attenuation of low-density lipoprotein (LDL) oxidation. While protecting against Trypanosoma brucei rhodesiense infection, APOL1 risk alleles confer greater risk for CKD and cardiovascular disease among patients of African descent. OBJECTIVES: We investigated whether APOL1 risk variants are associated with atherosclerosis and oxidized LDL (OxLDL) levels among black South African CKD patients. METHODS: A cross-sectional study of 120 adult CKD patients and 40 controls was undertaken. DNA samples of participants were genotyped for APOL1 G1 and G2 variants. High-sensitivity C-reactive protein, serum lipids, and OxLDL levels were measured, and carotid doppler ultrasonography was performed on all participants. RESULTS: APOL1 alleles rs73885319, rs60910145, and rs71785313 had minor allele frequencies of 9.2, 8.8, and 17.5%, respectively, in the patients, and 8.8, 8.8, and 13.8%, respectively, in the controls. Of the 9 patients with 2 APOL1 risk alleles, 77.8% were compound G1/G2 heterozygotes and 22.2% were G2 homozygotes. Carriers of at least 1 APOL1 risk allele had a 3-fold increased risk of subclinical atherosclerosis (odds ratio 3.19; 95% confidence interval: 1.64-6.19; p = 0.01) compared to individuals with no risk alleles. Patients with 1 or 2 APOL1 risk alleles showed a significant increase in OxLDL levels when compared with those without the APOL1 risk allele. CONCLUSION: These findings suggest an increased risk for atherosclerosis in carriers of a single APOL1 risk variant, and the presence of APOL1 risk variants was associated with increased serum OxLDL levels in black South African CKD patients.

Biomarkers for Diagnosis and Prediction of Outcomes in Contrast-Induced Nephropathy.

BACKGROUND: Serum creatinine is suboptimal as a biomarker in the early diagnosis of contrast-induced nephropathy (CIN). In this study, we investigated a panel of novel biomarkers in the early diagnosis of CIN and in assessing patient outcomes. METHODS: This single-centre, nested, prospective case-controlled study included 30 patients with CIN and 60 matched controls. Serum and urine samples were collected before contrast administration and at 24 hours, 48 hours, and ≥5 days after contrast administration. Concentrations of NGAL, cystatin C, ß 2M, IL18, IL10, KIM1, and TNFα were determined using Luminex and ELISA assays. Outcomes were biomarker diagnostic discrimination performance for CIN and mortality after generation of area under receiver operating characteristic curves (AUROCs). RESULTS: Median serum levels for 24 h cystatin C (p < 0.01) and 48 h ß 2M levels (p < 0.001) and baseline urine NGAL (p=0.02) were higher in CIN patients compared to controls with AUROCs of 0.75, 0.78, and 0.74, respectively, for the early diagnosis of CIN. Serum ß 2M levels were higher in CIN patients at all time points. Elevated baseline serum concentrations of IL18 (p < 0.001), ß 2M (p=0.04), TNFα (p < 0.001), and baseline urine KIM (p=0.01) and 24 h urine NGAL (p=0.02) were significantly associated with mortality. Baseline serum concentrations of IL18, ß 2M, and TNFα showed the best discrimination performance for mortality with AUROCs, all >0.80. Baseline NGAL was superior for excluding patients at risk for CIN, with positive and negative predictive ranges of 0.50-0.55 and 0.81-0.88, respectively. Cystatin C (p=0.003) and ß 2M (p=0.03) at 24 h independently predicted CIN risk. ß 2M predicted increased mortality of 40% at baseline and 50% at 24 hours. CONCLUSION: Serum cystatin C at 24 h was the best biomarker for CIN diagnosis, while baseline levels of serum IL18, ß 2M, and TNFα were best for predicting prognosis.

Endothelial dysfunction in HIV-positive patients with acute coronary syndromes.

AIM: This study investigated endothelial function in HIV-positive patients with acute coronary syndrome (ACS). Flow-mediated dilatation, pulse-wave velocity, carotid intima-media thickness and endothelial biomarkers were used to non-invasively investigate endothelial dysfunction. METHODS: Twenty HIV-positive patients with ACS (HIV+/ACS) were compared to 20 HIV-negative patients with ACS (HIV-/ACS) and 20 HIV-positive patients without ACS (HIV+/no ACS). RESULTS: Endothelial function measured by flow-mediated dilatation (FMD) was similar in both the HIV+/ACS (5.2; IQR 1.4-13.4%) and HIV-/ACS groups (3.7; IQR 2.3-4.4%) (p = 0.78). Arterial stiffness, measured by pulse-wave velocity (PWV) was low in all three cohorts. Carotid intima-media thickness (CIMT) was also low in all three cohorts. The vascular cellular adhesion molecule-1 (VCAM-1) levels in HIV-positive patients with and without ACS were significantly higher than in the HIV-/ACS cohort (p = 0.033 and 0.024, respectively). CONCLUSIONS: Non-invasive investigations such as FMD, CIMT and PWV did not identify patients with HIV who were at high risk of ACS. Endothelial biomarkers may be more useful markers to identify HIV-positive patients who have endothelial dysfunction and increased risk of ACS.

Interleukin-6 gene polymorhisms and interleukin-6 levels are associated with atherosclerosis in CKD patients.

Inflammation is a major risk factor for atherosclerosis. Genetic polymorphisms in the inflammatory cytokine genes have been associated with atherosclerosis. Because levels of inflammatory cytokines are markedly elevated in patients with chronic kidney disease (CKD), we hypothesized that genotypic variations in the interleukin-6 (IL-6) gene are a cause of systemic inflammatory states and atherosclerosis in South African CKD patients. 120 CKD patients and 40 healthy controls were included. Serum IL-6 and high-sensitivity C-reactive protein (hs-CRP) levels were measured. Functional polymorphisms in the IL-6 genes were genotyped using polymerase chain reaction-sequence specific primer (PCR-SSP) methods. Carotid intima-media thickness (CIMT) and the presence of plaque were assessed by B-mode ultrasonography. Serum IL-6 and hs-CRP levels were increased in patients with CKD compared with healthy controls (p < 0.001). In CKD patients, serum IL-6 above the median value was associated with carotid plaque (OR: 2.11; 95% CI: 1.74 - 2.57, p = 0.004), with excess risk confined to the group with high IL-6 levels. Significant associations were found between the IL-6 gene and atherosclerosis in the CKD group (for G/G genotype: OR = 1.21, 95% CI = 1.05 - 1.39, p = 0.012; for GG+GC vs. CC: OR = 1.14, 95% CI = 1.02 - 1.28, p = 0.035). Patients with GG+GC genotype of the IL-6 gene polymorphism had higher levels of IL-6 than those with CC genotype (p = 0.029). In South African CKD patients, the IL-6 gene promoter polymorphism is associated with high serum IL-6 levels and atherosclerosis. The relationship between atherosclerosis and -174G/C polymorphism in the IL-6 gene suggests that IL-6 may be a potential pro-inflammatory mediator of atherosclerosis in CKD patients.

Dynamic Changes in the Molecular Signature of Adverse Left Ventricular Remodeling in Patients With Compensated and Decompensated Chronic Primary Mitral Regurgitation.

BACKGROUND: There is no proven medical therapy that attenuates adverse left ventricular remodeling in patients with chronic primary mitral regurgitation (CPMR). Identification of molecular pathways important in the progression of left ventricular remodeling in patients with CPMR may lead to development of new therapeutic strategies. METHODS AND RESULTS: We performed baseline echocardiographic, cardiac catheterization, and serum NT-pro-BNP analysis in patients with severe CPMR awaiting mitral valve surgery and stratified the study population into compensated or decompensated CPMR. We obtained left ventricular endomyocardial biopsies (n=12) for mRNA expression analysis, and compared baseline transcript levels of 109 genes important in volume-overload left ventricular remodeling with levels in normal hearts (n=5) and between patients with compensated (n=6) versus decompensated (n=6) CPMR. Patients were then randomized to treatment with and without carvedilol and followed until the time of surgery (mean follow-up 8.3 months) when repeat endomyocardial biopsies were obtained to correlate transcriptional dynamics with indices of adverse remodeling. CPMR was associated with increased NPPA expression levels (21.6-fold, P=0.004), decreased transcripts of genes important in cell survival, and enrichment of extracellular matrix genes. Decompensated CPMR was associated with downregulation of SERCA2 (0.77-fold, P=0.009) and mitochondrial gene expression levels and upregulation of genes related to inflammation, the extracellular matrix, and apoptosis, which were refractory to carvedilol therapy. CONCLUSIONS: Transition to decompensated CPMR is associated with calcium dysregulation, increased expression of inflammatory, extracellular matrix and apoptotic genes, and downregulation of genes important in bioenergetics. These changes are not attenuated by carvedilol therapy and highlight the need for development of specific combinatorial therapies, targeting myocardial inflammation and apoptosis, together with urgent surgical or percutaneous valve interventions.

Effects of Serelaxin in Patients with Acute Heart Failure.

BACKGROUND: Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. METHODS: In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 µg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. RESULTS: A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P = 0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P = 0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. CONCLUSIONS: In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778.).

Atherosclerotic plaque in HIV-positive patients presenting with acute coronary syndromes.

AIM: This study aimed to characterise the atherosclerotic plaque and plaque burden in HIV-positive patients presenting with acute coronary syndromes (ACS), using intravascular ultrasound (IVUS) and virtual histology (VH). METHODS: This was a prospective study of 20 HIV-positive patients who presented with ACS. IVUS and VH were used to assess plaque burden and plaque characteristics in the culprit and non-culprit coronary arteries. RESULTS: HIV-positive patients with ACS had a mean age of 51.1 ± 8.1 years. There were 13 (65%) male patients. ST-segment elevation myocardial infarction was the most common presentation of ACS (75%) with the left anterior descending artery being the most common culprit artery (60%). In 60% of patients, the total plaque burden was of moderate degree (40-70% stenosis) while it was of mild degree (< 40% stenosis) in 35%, and in 5% of patients it was severe (> 70% stenosis). A severe degree of total plaque burden was more commonly found in the culprit vessel (30%) than in the non-culprit vessels (5%). Furthermore, the plaque burden was found to be located predominantly in the proximal portion of the coronary arteries. The predominant plaque morphology consisted of fibrous plaque (55.4%) and fibro-fatty plaque (26.6%), while necrotic core was present in 13.3%. Dense calcium was present in only 4.7% of the cohort. CONCLUSIONS: IVUS and VH demonstrated a high burden of atherosclerosis in the left anterior descending artery and proximal vasculature of HIV-positive patients. The atherosclerotic plaque predominantly comprised non-calcified fibrous and fibro-fatty plaque.

Atherosclerotic vascular disease and its correlates in stable black South African kidney transplant recipients.

BACKGROUND: Despite remarkable improvement in renal function attributable to kidney transplantation, the burden of cardiovascular disease (CVD) among kidney transplant recipients (KTRs) remains high in the post-transplant period. Aggressive use of statins in KTRs may make lipoprotein ratios correlate better with atherosclerotic vascular disease (AsVD) when compared with traditional lipid profile parameters. We therefore evaluated the clinical and echocardiographic correlates of AsVD among non-diabetic, stable, black KTRs in South Africa. METHODS: This was a cross-sectional study of 41 adult (18-65 years), non-diabetic, stable KTRs and 41 age- and sex-matched healthy controls. An interviewer-administered questionnaire was used to obtain information on participants' sociodemographic and cardiovascular risk factors. Anthropometric parameters were measured. Urine and blood samples were obtained and analyzed. Echocardiography was performed and carotid intima media thickness (CIMT) was assessed in both right and left carotid arteries. Spearman's rank correlation and binary logistic regression were performed to determine the relationship between CVD risk factors and AsVD. RESULTS: AsVD was present in 46.3% of KTRs compared to 17.1% of healthy controls (p = 0.004). Left ventricular hypertrophy was present in 92.7% of the KTRs. There were statistically significant differences in waist-hip ratio, systolic blood pressure, mean arterial pressure, urine albumin-creatinine ratio, serum fibrinogen, serum creatinine, estimated glomerular filtration rate, left atrial diameter, left ventricular mass (LVM), and left ventricular mass index (LVMI) between KTRs and controls. A positive relationship was seen between CIMT and certain risk factors for CVD including LVM, LVMI, and mitral valve deceleration time, (p < 0.001). Castelli index 2 and lipoprotein combine index (LCI) showed positive correlation with CIMT. On multivariate analysis, increasing age and kidney transplant status were independent predictors of AsVD after controlling for other risk factors. CONCLUSION: AsVD was common among KTRs. Older age and kidney transplant status independently predicted AsVD. Castelli index 2 and LCI correlated with AsVD better than serum lipid parameters.

Transforming Growth Factor-ß Protects against Inflammation-Related Atherosclerosis in South African CKD Patients.

BACKGROUND: Transforming growth factor-ß (TGF-ß) may inhibit the development of atherosclerosis. We evaluated serum levels of TGF-ß isoforms concurrently with serum levels of endotoxin and various inflammatory markers. In addition, we determined if any association exists between polymorphisms in the TGF-ß1 gene and atherosclerosis in South African CKD patients. METHODS: We studied 120 CKD patients and 40 healthy controls. Serum TGF-ß1, TGF-ß2, TGF-ß3, endotoxin, and inflammatory markers were measured. Functional polymorphisms in the TGF-ß1 genes were genotyped using a polymerase chain reaction-sequence specific primer method and carotid intima media thickness (CIMT) was assessed by B-mode ultrasonography. RESULTS: TGF-ß isoforms levels were significantly lower in the patients with atherosclerosis compared to patients without atherosclerosis (p<0.001). Overall, TGF-ß isoforms had inverse relationships with CIMT. TGF-ß1 and TGF-ß2 levels were significantly lower in patients with carotid plaque compared to those without carotid plaque [TGF-ß1: 31.9 (17.2 - 42.2) versus 45.9 (35.4 - 58.1) ng/ml, p=0.016; and TGF-ß2: 1.46 (1.30 - 1.57) versus 1.70 (1.50 - 1.87) ng/ml, p=0.013]. In multiple logistic regression, age, TGF-ß2, and TGF-ß3 were the only independent predictors of subclinical atherosclerosis in CKD patients [age: odds ratio (OR), 1.054; 95% confidence interval (CI): 1.003 - 1.109, p=0.039; TGF-ß2: OR, 0.996; 95% CI: 0.994-0.999, p=0.018; TGF-ß3: OR, 0.992; 95% CI: 0.985-0.999, p=0.029). TGF-ß1 genotypes did not influence serum levels of TGF-ß1 and no association was found between the TGF-ß1 gene polymorphisms and atherosclerosis risk. CONCLUSION: TGF-ß isoforms seem to offer protection against the development of atherosclerosis among South African CKD patients.

Evaluation of coronary features of HIV patients presenting with ACS: The CUORE, a multicenter study.

BACKGROUND AND AIMS: The risk of recurrence of myocardial infarction (MI) in HIV patients presenting with acute coronary syndrome (ACS) is well known, but there is limited evidence about potential differences in coronary plaques compared to non-HIV patients. METHODS: In this multicenter case-control study, HIV patients presenting with ACS, with intravascular-ultrasound (IVUS) data, enrolled between February 2015 and June 2017, and undergoing highly active antiretroviral therapy (HAART), were retrospectively compared to non-HIV patients presenting with ACS, before and after propensity score with matching, randomly selected from included centers. Primary end-point was the prevalence of multivessel disease. Secondary end-points were the prevalence of abnormal features at IVUS, the incidence of major-acute-cardiovascular-events (MACE), a composite end point of cardiovascular death, MI, target lesion revascularization (TLR), stent thrombosis (ST), non-cardiac death and target vessel revascularization (TVR). For each end-point, a subgroup analysis was conducted in HIV patients with CD4 cell count <200/mm3. RESULTS: Before propensity score, 66 HIV patients and 120 non-HIV patients were selected, resulting in 20 and 40 after propensity score. Patients with multivessel disease were 11 and 17, respectively (p = 0.56). IVUS showed a lower plaque burden (71% vs. 75%, p < 0.001) and a higher prevalence of hyperechoic non-calcified plaques (100% vs. 35%, p < 0.05) in HIV patients; a higher prevalence of hypoechoic plaques (7% vs. 0%, p < 0.05), a higher incidence of MACE (17.4% vs. 9.1% vs. l'8.0%, p < 0.05), MI recurrence (17.2% vs. 0.0% vs. 2.3%, p < 0.05), and ST (6.7% vs. 0.3% vs. 03%, p < 0.05) in HIV patients with CD4 < 200/mm3. CONCLUSIONS: Our study may provide a part of the pathophysiological basis of the differences in coronary arteries between HIV-positive and HIV-negative patients, suggesting that the former present with peculiar morphological features at IVUS, even after adjustment for clinical variables. Furthermore, we confirmed that an advanced HIV infection is associated with a high risk of non-calcific plaques and with a worse prognosis, including cardiovascular events and ACS recurrence.