Aims
Inflammation is a central process in the pathophysiology of heart failure (HF), but trials targeting tumour necrosis factor (TNF)‐α were largely unsuccessful. Interleukin (IL)‐6 is an important ...inflammatory mediator and might constitute a potential pharmacologic target in HF. However, little is known regarding the association between IL‐6 and clinical characteristics, outcomes and other inflammatory biomarkers in HF. We thus aimed to identify and characterize these associations.
Methods and results
Interleukin‐6 was measured in 2329 patients 89.4% with a left ventricular ejection fraction (LVEF) ≤ 40% of the BIOSTAT‐CHF cohort. The primary outcome was all‐cause mortality and HF hospitalization during 2 years, with all‐cause, cardiovascular (CV), and non‐CV death as secondary outcomes. Approximately half (56%) of all included patients had plasma IL‐6 values greater than the previously determined 95th percentile of normal values at baseline. Elevated N‐terminal pro‐brain natriuretic peptide, procalcitonin and hepcidin, younger age, TNF‐α/IL‐1‐related biomarkers, or having iron deficiency, atrial fibrillation and LVEF > 40% independently predicted elevated IL‐6 levels. IL‐6 independently predicted the primary outcome HR (95% confidence interval) per doubling: 1.16 (1.11–1.21), P < 0.001, all‐cause mortality 1.22 (1.16–1.29), P < 0.001 and CV as well as non‐CV mortality 1.16 (1.09–1.24), P < 0.001; 1.31 (1.18–1.45), P < 0.001, but did not improve discrimination in previously published risk models.
Conclusions
In a large, heterogeneous cohort of HF patients, elevated IL‐6 levels were found in more than 50% of patients and were associated with iron deficiency, reduced LVEF, atrial fibrillation and poorer clinical outcomes. These findings warrant further investigation of IL‐6 as a potential therapeutic target in specific HF subpopulations.
The practical management of heart failure remains a challenge. Not only are heart failure patients expected to adhere to a complicated pharmacological regimen, they are also asked to follow salt and ...fluid restriction, and to cope with various procedures and devices. Furthermore, physical training, whose benefits have been demonstrated, is highly recommended by the recent guidelines issued by the European Society of Cardiology, but it is still severely underutilized in this particular patient population. This position paper addresses the problem of non‐adherence, currently recognized as a main obstacle to a wide implementation of physical training. Since the management of chronic heart failure and, even more, of training programmes is a multidisciplinary effort, the current manuscript intends to reach cardiologists, nurses, physiotherapists, as well as psychologists working in the field.
The European Society of Cardiology heart failure guidelines firmly recommend regular physical activity and structured exercise training (ET), but this recommendation is still poorly implemented in ...daily clinical practice outside specialized centres and in the real world of heart failure clinics. In reality, exercise intolerance can be successfully tackled by applying ET. We need to encourage the mindset that breathlessness may be evidence of signalling between the periphery and central haemodynamic performance and regular physical activity may ultimately bring about favourable changes in myocardial function, symptoms, functional capacity, and increased hospitalization‐free life span and probably survival. In this position paper, we provide practical advice for the application of exercise in heart failure and how to overcome traditional barriers, based on the current scientific and clinical knowledge supporting the beneficial effect of this intervention.
Guidelines on heart failure (HF) stress the importance of lifestyle advice, although there is little evidence that such recommendations improve symptoms or prognosis. Patients experience symptoms of ...different intensities which impair their daily activities and reduce the quality‐of‐life. To cope with their clinical condition, many patients seek advice about lifestyle and self‐management strategies when in contact with medical care providers, particularly specialized HF services. Self‐care management is an important part of HF treatment, thus health professionals working with patients with HF have recognized the need for more specific recommendations on lifestyle advice. The present paper summarizes the available evidence, promotes self‐care management, and aims to provide practical advice for health professionals delivering care to HF patients. It also defines avenues of research to optimize self‐care strategies in a number of key areas to derive further benefits.
Aims
A higher body mass index (BMI) is associated with better survival in heart failure (HF) patients, also known as the obesity paradox. However, BMI does not account for body composition. We ...therefore analysed the association between abdominal fat, measured via waist‐to‐hip ratio (WHR), BMI and all‐cause mortality in patients with HF.
Methods and results
For this analysis, 1738 patients from the Scottish BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT‐CHF) validation study were included. Patients without waist and hip measurements were excluded. WHR was defined as waist circumference/hip circumference, divided into tertiles and split for sex. A linear regression of principal components from an extensive panel of biomarkers was performed to provide insight in the pathophysiology behind a higher WHR. In total, 1479 patients were included, of which 33% were female and mean age was 75 ±11 years. A higher WHR was independently associated with a higher BMI, a higher prevalence of diabetes and higher New York Heart Association functional class. There was a significant interaction between sex and WHR on its association with mortality (P <0.001). In women, a higher WHR was associated with a higher mortality risk hazard ratio (HR) 2.23, 95% confidence interval (CI) 1.37–3.63; P =0.001, whereas no significant association was found in men (HR 0.87, 95% CI 0.63–1.20; P = 0.409). We found a strong association between a higher WHR and elevated markers of inflammation and MAPK cascade in women, while these associations were less profound in men.
Conclusions
A higher WHR was associated with a higher risk of death in female but not in male HF patients. These findings challenge the obesity paradox, and suggest that fat deposition is pathophysiologically harmful and may be a target for therapy in female patients with HF.
Summary Background Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are known to reduce proteinuria. Their combination might be more effective than either ...treatment alone, but long-term data for comparative changes in renal function are not available. We investigated the renal effects of ramipril (an ACE inhibitor), telmisartan (an ARB), and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage. Methods The trial ran from 2001 to 2007. After a 3-week run-in period, 25 620 participants were randomly assigned to ramipril 10 mg a day (n=8576), telmisartan 80 mg a day (n=8542), or to a combination of both drugs (n=8502; median follow-up was 56 months), and renal function and proteinuria were measured. The primary renal outcome was a composite of dialysis, doubling of serum creatinine, and death. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00153101. Findings 784 patients permanently discontinued randomised therapy during the trial because of hypotensive symptoms (406 on combination therapy, 149 on ramipril, and 229 on telmisartan). The number of events for the composite primary outcome was similar for telmisartan (n=1147 13·4%) and ramipril (1150 13·5%; hazard ratio HR 1·00, 95% CI 0·92–1·09), but was increased with combination therapy (1233 14.5%; HR 1·09, 1·01–1·18, p=0·037). The secondary renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 2·21%) and ramipril (174 2·03%; HR 1·09, 0·89–1·34) and more frequent with combination therapy (212 2·49%: HR 1·24, 1·01–1·51, p=0·038). Estimated glomerular filtration rate (eGFR) declined least with ramipril compared with telmisartan (−2·82 SD 17·2 mL/min/1·73 m2 vs −4·12 17·4, p<0·0001) or combination therapy (−6·11 17·9, p<0·0001). The increase in urinary albumin excretion was less with telmisartan (p=0·004) or with combination therapy (p=0·001) than with ramipril. Interpretation In people at high vascular risk, telmisartan's effects on major renal outcomes are similar to ramipril. Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes. Funding Boehringer-Ingelheim.
Heart failure is a global public health problem, affecting a large number of individuals from low-income and middle-income countries. REPORT-HF is, to our knowledge, the first prospective global ...registry collecting information on patient characteristics, management, and prognosis of acute heart failure using a single protocol. The aim of this study was to investigate differences in 1-year post-discharge mortality according to region, country income, and income inequality.
Patients were enrolled during hospitalisation for acute heart failure from 358 centres in 44 countries on six continents. We stratified countries according to a modified WHO regional classification (Latin America, North America, western Europe, eastern Europe, eastern Mediterranean and Africa, southeast Asia, and western Pacific), country income (low, middle, high) and income inequality (according to tertiles of Gini index). Risk factors were identified on the basis of expert opinion and knowledge of the literature.
Of 18 102 patients discharged, 3461 (20%) died within 1 year. Important predictors of 1-year mortality were old age, anaemia, chronic kidney disease, presence of valvular heart disease, left ventricular ejection fraction phenotype (heart failure with reduced ejection fraction HFrEF vs preserved ejection fraction HFpEF), and being on guideline-directed medical treatment (GDMT) at discharge (p<0·0001 for all). Patients from eastern Europe had the lowest 1-year mortality (16%) and patients from eastern Mediterranean and Africa (22%) and Latin America (22%) the highest. Patients from lower-income countries (ie, ≤US$3955 per capita; hazard ratio 1·58, 95% CI 1·41–1·77), or with greater income inequality (ie, from the highest Gini tertile; 1·25, 1·13–1·38) had a higher 1-year mortality compared with patients from regions with higher income (ie, >$12 235 per capita) or lower income inequality (ie, from the lowest Gini tertile). Compared with patients with HFrEF, patients with HFpEF had a lower 1-year mortality with little variation by income level (pinteraction for HFrEF vs HFpEF <0·0001).
Acute heart failure is associated with a high post-discharge mortality, particularly in patients with HFrEF from low-income regions with high income inequality. Regional differences exist in the proportion of eligible patients discharged on GDMT, which was strongly associated with mortality and might reflect lack of access to post-discharge care and prescribing of GDMT.
Novartis Pharma.
Endpoint selection is a critically important step in clinical trial design. It poses major challenges for investigators, regulators, and study sponsors, and it also has important clinical and ...practical implications for physicians and patients. Clinical outcomes of interest in heart failure trials include all‐cause mortality, cause‐specific mortality, relevant non‐fatal morbidity (e.g. all‐cause and cause‐specific hospitalization), composites capturing both morbidity and mortality, safety, symptoms, functional capacity, and patient‐reported outcomes. Each of these endpoints has strengths and weaknesses that create controversies regarding which is most appropriate in terms of clinical importance, sensitivity, reliability, and consistency. Not surprisingly, a lack of consensus exists within the scientific community regarding the optimal endpoint(s) for both acute and chronic heart failure trials. In an effort to address these issues, the Heart Failure Association of the European Society of Cardiology (HFA‐ESC) convened a group of expert heart failure clinical investigators, biostatisticians, regulators, and pharmaceutical industry scientists (Nice, France, 12–13 February 2012) to evaluate the challenges of defining heart failure endpoints in clinical trials and to develop a consensus framework. This report summarizes the group's recommendations for achieving common views on heart failure endpoints in clinical trials.
Heart failure is a serious condition and equivalent to malignant disease in terms of symptom burden and mortality. At this moment only a comparatively small number of heart failure patients receive ...specialist palliative care. Heart failure patients may have generic palliative care needs, such as refractory multifaceted symptoms, communication and decision making issues and the requirement for family support. The Advanced Heart Failure Study Group of the Heart Failure Association of the European Society of Cardiology organized a workshop to address the issue of palliative care in heart failure to increase awareness of the need for palliative care. Additional objectives included improving the accessibility and quality of palliative care for heart failure patients and promoting the development of heart failure-orientated palliative care services across Europe. This document represents a synthesis of the presentations and discussion during the workshop and describes recommendations in the area of delivery of quality care to patients and families, education, treatment coordination, research and policy.
The presence of coexisting conditions has a substantial effect on the outcome of acute myocardial infarction. Renal failure is associated with one of the highest risks, but the influence of milder ...degrees of renal impairment is less well defined.
As part of the Valsartan in Acute Myocardial Infarction Trial (VALIANT), we identified 14,527 patients with acute myocardial infarction complicated by clinical or radiologic signs of heart failure, left ventricular dysfunction, or both, and a documented serum creatinine measurement. Patients were randomly assigned to receive captopril, valsartan, or both. The glomerular filtration rate (GFR) was estimated by means of the four-component Modification of Diet in Renal Disease equation, and the patients were grouped according to their estimated GFR. We used a 70-candidate variable model to adjust and compare overall mortality and composite cardiovascular events among four GFR groups.
The distribution of estimated GFR was wide and normally shaped, with a mean (+/-SD) value of 70+/-21 ml per minute per 1.73 m2 of body-surface area. The prevalence of coexisting risk factors, prior cardiovascular disease, and a Killip class of more than I was greatest among patients with a reduced estimated GFR (less than 45.0 ml per minute per 1.73 m2), and the use of aspirin, beta-blockers, statins, or coronary-revascularization procedures was lowest in this group. The risk of death or the composite end point of death from cardiovascular causes, reinfarction, congestive heart failure, stroke, or resuscitation after cardiac arrest increased with declining estimated GFRs. Although the rate of renal events increased with declining estimated GFRs, the adverse outcomes were predominantly cardiovascular. Below 81.0 ml per minute per 1.73 m2, each reduction of the estimated GFR by 10 units was associated with a hazard ratio for death and nonfatal cardiovascular outcomes of 1.10 (95 percent confidence interval, 1.08 to 1.12), which was independent of the treatment assignment.
Even mild renal disease, as assessed by the estimated GFR, should be considered a major risk factor for cardiovascular complications after a myocardial infarction.
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