WITHDRAWN: Diuretics for heart failure.

This protocol was withdrawn in April 2016 as the author team was unable to progress to the final review stage. An editorial decision was taken not to pursue this title. The editorial group responsible for this previously published document have withdrawn it from publication.

Central and peripheral quadriceps fatigue in congestive heart failure.

Aims: The clinical syndrome of heart failure includes exercise limitation that is not directly linked to measures of cardiac function. Quadriceps fatigability may be an important component of this and this may arise from peripheral or central factors.

Methods And Results: We studied 10 men with CHF and 10 healthy age-matched controls.

Diuretics for heart failure.

Background: Chronic heart failure is a major cause of morbidity and mortality worldwide. Diuretics are regarded as the first-line treatment for patients with congestive heart failure since they provide symptomatic relief. The effects of diuretics on disease progression and survival remain unclear.

Ursodeoxycholic acid in patients with chronic heart failure: a double-blind, randomized, placebo-controlled, crossover trial.

Objectives: This study sought to assess the effects of ursodeoxycholic acid (UDCA) on endothelial function and inflammatory markers in patients with chronic heart failure (CHF).

Background: Endothelial dysfunction is commonly observed in patients with CHF, and it contributes to the limitation in exercise capacity that accompanies this condition. Bacterial lipopolysaccharide may trigger proinflammatory cytokine release and promote further endothelial dysfunction.

Suppression of erythropoiesis in patients with chronic heart failure and anaemia of unknown origin: evidence of an immune basis.

Aims: Anaemia is a prevalent and adverse comorbidity in chronic heart failure (CHF) but its origins are frequently elusive. Diffuse inflammation is also prominent in CHF and a potent inhibitor of erythrocyte production. We tested the hypothesis that unexplained anaemia in CHF might be subsequent to diminished erythropoiesis as a result of an immune-mediated suppression of erythroid colony formation.

Cardiothoracic ratio from postero-anterior chest radiographs: a simple, reproducible and independent marker of disease severity and outcome in adults with congenital heart disease.

Objective: The wide spectrum of intracardiac anatomy and reparative surgery available for adults with congenital heart disease (ACHD) makes uniform measurement of cardiac size and disease severity challenging. The aim of this study was to assess the prognostic potential of cardiothoracic ratio, a simple marker of cardiomegaly, in a large cohort of ACHD.

Patients And Setting: Chest radiographs from 3033 ACHD patients attending our institution between 1998 and 2007 and 113 normal controls of similar age were analyzed blindly.

Prevalence and outcome of subclinical rheumatic heart disease in India: the RHEUMATIC (Rheumatic Heart Echo Utilisation and Monitoring Actuarial Trends in Indian Children) study.

Objective: To study the prevalence and medium term outcome of subclinical rheumatic heart disease (RHD) in India.

Design: Cross sectional echocardiographic screening study.

Setting: School children aged 5-15 years living in rural areas of north India.

Disordered iron homeostasis in chronic heart failure: prevalence, predictors, and relation to anemia, exercise capacity, and survival.

Objectives: The aim of this study was to comprehensively delineate iron metabolism and its implications in patients with chronic heart failure (CHF).

Background: Iron deficiency is an emerging therapeutic target in CHF.

Methods: Iron and clinical indexes were quantified in 157 patients with CHF.

Role of cardiovascular magnetic resonance as a gatekeeper to invasive coronary angiography in patients presenting with heart failure of unknown etiology.

Background: In patients presenting with new-onset heart failure of uncertain etiology, the role of coronary angiography (CA) is unclear. Although conventionally performed to differentiate underlying coronary artery disease from dilated cardiomyopathy, CA is associated with a risk of complications and may not detect an ischemic cause resulting from arterial recanalization or an embolic episode. In this study, we assessed the diagnostic accuracy of a cardiovascular magnetic resonance (CMR) protocol incorporating late gadolinium enhancement (LGE) and magnetic resonance CA as a noninvasive gatekeeper to CA in determining the etiology of heart failure in this subset of patients.

Erythropoietin resistance contributes to anaemia in chronic heart failure and relates to aberrant JAK-STAT signal transduction.

Background: Chronic heart failure (CHF) patients are frequently anaemic despite elevated endogenous erythropoietin (Epo) levels. We tested the hypothesis that this might be due to Epo resistance and investigated whether any defects apparent were due to Epo receptor (EpoR) downregulation and/or impaired Epo-induced signal transduction.

Methods: We studied 28 CHF patients (age 64 ± 10 yrs, LVEF 29 ± 9%, 89% male) and 12 healthy controls (65 ± 11 yrs, 75% male).

Predictors of clinical outcomes in elderly patients with heart failure.

Aims: Heart failure (HF) in the elderly carries a poor prognosis. We used the SENIORS dataset of elderly HF patients aged ≥70 years in order to develop a risk model for this population.

Methods And Results: The SENIORS trial evaluated the effects of nebivolol and enrolled 2128 patients ≥70 years with HF (ejection fraction ≤35%, or recent HF admission).

SERCA2a gene transfer decreases sarcoplasmic reticulum calcium leak and reduces ventricular arrhythmias in a model of chronic heart failure.

Background: Sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) gene therapy improves mechanical function in heart failure and is under evaluation in a clinical trial. A critical question is whether SERCA2a gene therapy predisposes to increased sarcoplasmic reticulum calcium (SR Ca(2+)) leak, cellular triggered activity, and ventricular arrhythmias in the failing heart.

Methods And Results: We studied the influence of SERCA2a gene therapy on ventricular arrhythmogenesis in a rat chronic heart failure model.

Deficiencies in circulating testosterone and dehydroepiandrosterone sulphate, and depression in men with systolic chronic heart failure.

Aims: Elderly men with androgen deficiencies are prone to develop late-onset depression. We investigated links between circulating androgens and depression, and their combined impact on outcome in men with chronic heart failure (CHF).

Methods And Results: Serum total testosterone (TT) and dehydroepiandrosterone sulphate (DHEAS) were measured using immunoassays in 163 men with stable systolic CHF [age: 60 +/- 10 years, NYHA class (I/II/III/IV): 27/84/46/6] and 316 healthy men.

Impairment of autonomic reactivity is a feature of heart failure whether or not the left ventricular ejection fraction is normal.

Background: Autonomic dysfunction (AD) is associated with morbidity and mortality in patients with systolic heart failure (SHF). The extent of AD when LV ejection fraction is preserved (HF-NEF), is unclear. Our objectives were: 1) quantitative assessment of autonomic function in SHF and HF-NEF; and 2) exploration of relationships among AD, symptoms and cardiac function.

Gender differences in cardiac remodeling and clinical outcomes in chronic stable angina pectoris (from the ACTION Trial).

Our objective was to determine the gender differences in the relation between the echocardiographic parameters of cardiac remodeling and clinical outcomes in patients with chronic stable angina. The baseline ejection fraction (EF), end-diastolic volume, and end-systolic volume were assessed in 7,016 patients in the study "A Coronary disease Trial Investigating Outcomes with Nifedipine gastrointestinal therapeutic system" (ACTION). All-cause and cardiac mortality and incident heart failure were determined after a median of 5.

Hyponatraemia: A strong predictor of mortality in adults with congenital heart disease.

Aims: We studied the prevalence of hyponatraemia and its prognostic implications in a large population of adult patients with congenital heart disease (ACHD).

Methods And Results: A total of 1004 ACHD patients were retrospectively entered in this study (mean age 36.2 +/- 14.

Anemia in adults with congenital heart disease relates to adverse outcome.

Objectives: To assess the relation of anemia in noncyanotic adults with congenital heart disease (ACHD) to functional capacity and mortality.

Background: Anemia is common in acquired heart failure and affects prognosis. The presence of anemia and its relation to outcome in ACHD remain unknown.

Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial.

Background: Angiotensin-receptor blockers (ARBs) are effective treatments for patients with heart failure, but the relation between dose and clinical outcomes has not been explored. We compared the effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure.

Methods: This double-blind trial was undertaken in 255 sites in 30 countries.

Ferric carboxymaltose in patients with heart failure and iron deficiency.

Background: Iron deficiency may impair aerobic performance. This study aimed to determine whether treatment with intravenous iron (ferric carboxymaltose) would improve symptoms in patients who had heart failure, reduced left ventricular ejection fraction, and iron deficiency, either with or without anemia.

Methods: We enrolled 459 patients with chronic heart failure of New York Heart Association (NYHA) functional class II or III, a left ventricular ejection fraction of 40% or less (for patients with NYHA class II) or 45% or less (for NYHA class III), iron deficiency (ferritin level <100 microg per liter or between 100 and 299 microg per liter, if the transferrin saturation was <20%), and a hemoglobin level of 95 to 135 g per liter.

Rationale and design of Ferinject assessment in patients with IRon deficiency and chronic Heart Failure (FAIR-HF) study: a randomized, placebo-controlled study of intravenous iron supplementation in patients with and without anaemia.

Aims: Iron deficiency (ID) and anaemia are common in patients with chronic heart failure (CHF). The presence of anaemia is associated with increased morbidity and mortality in CHF, and ID is a major reason for the development of anaemia. Preliminary studies using intravenous (i.

Effects of carvedilol or metoprolol on PAI-1, tPA-mass concentration or Von Willebrand factor in chronic heart failure--a COMET substudy.

Introduction: In COMET (Carvedilol or Metoprolol European Trial), carvedilol reduced mortality compared with metoprolol in patients with chronic heart failure. We hypothesized that carvedilol might have greater effects on endothelial derived haemostatic factors than metoprolol. We aimed to study the effects of carvedilol or metoprolol on tissue plasminogen activator (tPA), its inhibitor PAI-1 and Von Willebrand factor (VWF) in patients with heart failure.

Maximizing survival benefit with primary prevention implantable cardioverter-defibrillator therapy in a heart failure population.

Background: Although implantable cardioverter-defibrillator (ICD) therapy reduces mortality in moderately symptomatic heart failure patients with an ejection fraction
Methods And Results: Using a modification of a previously validated risk prediction model based on routine clinical variables, we examined the relationship between baseline predicted mortality risk and the relative and absolute survival benefits of ICD treatment in the primary prevention Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). In the placebo arm, predicted 4-year mortality grouped into 5 equal-sized risk groups varied from 12% to 50% (c statistic=0.

Effects of low-dose oral enoximone administration on mortality, morbidity, and exercise capacity in patients with advanced heart failure: the randomized, double-blind, placebo-controlled, parallel group ESSENTIAL trials.

Aims: Use of inotropic agents in patients with heart failure (HF) has been limited by adverse effects on outcomes. However, administration of positive inotropes at lower doses and concomitant treatment with beta-blockers might increase benefit-risk ratio. We investigated the effects of low doses of the positive inotrope enoximone on symptoms, exercise capacity, and major clinical outcomes in patients with advanced HF who were also treated with beta-blockers and other guideline-recommended background therapy.

Efficacy and safety of nebivolol in elderly heart failure patients with impaired renal function: insights from the SENIORS trial.

Aim: To determine the safety and efficacy of nebivolol in elderly heart failure (HF) patients with renal dysfunction.

Methods And Results: SENIORS recruited patients aged 70 years or older with symptomatic HF, irrespective of ejection fraction, and randomized them to nebivolol or placebo. Patients (n = 2112) were divided by tertile of estimated glomerular filtration rate (eGFR).