Fibroblast growth factor 23 correlates with volume status in haemodialysis patients and is not reduced by haemodialysis.

Background: Recent data suggest a role for fibroblast growth factor 23 (FGF-23) in volume regulation. In haemodialysis patients, a large ultrafiltration volume (UFV) reflects poor volume control, and both FGF-23 and a large UFV are risk factors for mortality in this population. We studied the association between FGF-23 and markers of volume status including UFV, as well as the intradialytic course of FGF-23, in a cohort of haemodialysis patients.

Aortic valve prosthesis-patient mismatch and exercise capacity in adult patients with congenital heart disease.

Objectives: To report the prevalence of aortic valve prosthesis-patient mismatch (PPM) in an adult population with congenital heart disease (CHD) and its impact on exercise capacity. Adults with congenital heart disease (ACHD) with a history of aortic valve replacement may outgrow their prosthesis later in life. However, the prevalence and clinical consequences of aortic PPM in ACHD are presently unknown.

Omecamtiv mecarbil: a new cardiac myosin activator for the treatment of heart failure.

Introduction: Current available inotropic agents increase cardiac contractility, but are associated with myocardial ischemia, arrhythmias, and mortality. A novel selective cardiac myosin activator, omecamtiv mecarbil (CK-1827452/ AMG-423) is a small molecule that activates the sarcomere proteins directly, resulting in prolonged systolic ejection time and increased cardiac contractility.

Areas Covered: This paper discusses the chemistry, pharmacokinetics, clinical efficacy and safety of omecamtiv mecarbil.

MicroRNAs relate to early worsening of renal function in patients with acute heart failure.

Background: Deregulation of microRNAs (miRNAs) may be involved in the pathogenesis of heart failure (HF) and renal disease. Our aim is to describe miRNA levels related to early worsening renal function in acute HF patients.

Method And Results: We studied the association between 12 circulating miRNAs and Worsening Renal Function (WRF; defined as an increase in the serum creatinine level of 0.

Plasma kidney injury molecule-1 in heart failure: renal mechanisms and clinical outcome.

Aims: Urinary kidney injury molecule-1 (KIM-1) is a marker of tubular damage and associated with worse outcome in heart failure (HF). Plasma KIM-1 has not been described in HF.

Methods And Results: In a renal mechanistic cohort of 120 chronic HF patients, we established the association between plasma KIM-1, renal invasive haemodynamic parameters {renal blood flow ([(131) I]hippuran clearance) and measured glomerular filtration rate (GFR; [(125) I]iothalamate)} and urinary tubular damage markers.

The clinical course of health status and association with outcomes in patients hospitalized for heart failure: insights from ASCEND-HF.

Aims: A longitudinal and comprehensive analysis of health-related quality of life (HRQOL) was performed during hospitalization for heart failure (HF) or soon after discharge.

Methods And Results: A post-hoc analysis was performed of the ASCEND-HF trial. The EuroQOL five dimensions questionnaire (EQ-5D) was administered to study participants at baseline, 24 h, discharge/day 10, and day 30.

Biomarkers and low risk in heart failure. Data from COACH and TRIUMPH.

Aim: Traditionally, risk stratification in heart failure (HF) emphasizes assessment of high risk. We aimed to determine if biomarkers could identify patients with HF at low risk for death or HF rehospitalization.

Methods And Results: This analysis was a substudy of The Coordinating Study Evaluating Outcomes of Advising and Counselling in Heart Failure (COACH) trial.

Circulating Kidney Injury Molecule-1 Levels in Acute Heart Failure: Insights From the ASCEND-HF Trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure).

Objectives: This study sought to determine the relationship of KIM-1 levels with adverse clinical outcomes in acute decompensated heart failure (ADHF).

Background: Kidney injury molecule (KIM)-1 is a biomarker expressed by the nephron in acute tubular injury, and is a sensitive and specific marker for early acute kidney injury. Although commonly measured in urine, KIM-1 levels are also detectable in plasma, but its clinical and prognostic utility in ADHF is unknown.

Comparative effectiveness of torsemide versus furosemide in heart failure patients: insights from the PROTECT trial.

Aim: The authors assessed the comparative effectiveness of torsemide versus furosemide in the PROTECT trial.

Methods: The authors assessed the relationship between loop diuretic at discharge and death or cardiovascular/renal hospitalization within 30 days, and death through 150 days postdischarge using inverse probability weighting.

Results: Out of 1004 patients, 83.

Unsolved challenges in diuretic therapy for acute heart failure: a focus on diuretic response.

Loop diuretics represent the mainstay of management of patients hospitalized for heart failure (HF). Diuretic resistance is commonly encountered in clinical practice, but limited evidence-based approaches are available to address it. Recent clinical investigations have proposed common definitions of diuretic response: a change in body weight, net fluid loss or total urinary output to 40 mg of furosemide dose equivalents.

Signature of circulating microRNAs in patients with acute heart failure.

Aims: Our aim was to identify circulating microRNAs (miRNAs) associated with acute heart failure (AHF).

Methods And Results: Plasma miRNA profiling included 137 patients with AHF from 3 different cohorts, 20 with chronic heart failure (CHF), 8 with acute exacerbation of COPD, and 41 healthy controls. Levels of circulating miRNAs were measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR).

Serial high sensitivity cardiac troponin T measurement in acute heart failure: insights from the RELAX-AHF study.

Aims: Troponin elevation is common in acute heart failure (AHF) and may be useful for prognostication; however, available data are mixed and many previous studies used older, less sensitive assays. We examined the association between serial measurements of high-sensitivity cardiac troponin T (hs-cTnT) and outcomes in RELAX-AHF.

Methods And Results: Hs-cTnT was measured at baseline and days 2, 5, and 14.

Growth differentiation factor 15 (GDF-15) in patients admitted for acute heart failure: results from the RELAX-AHF study.

Background: Growth differentiation factor 15 (GDF-15) was found to be upregulated in patients with chronic heart failure (HF) and associated with disease severity, however, data on patients with acute heart failure (AHF) is lacking.

Methods And Results: Levels of GDF-15 were measured at pre-specified time-points (baseline and at days 2, 5, 14, and 60) in patients enrolled in the placebo-controlled RELAXin in Acute Heart Failure (RELAX-AHF) study, which examined the effect of serelaxin in 1161 patients with AHF, systolic blood pressure >125 mmHg, and mild to moderate renal impairment. Neither baseline nor changes in GDF-15 were associated with the degree of dyspnoea or dyspnoea relief.

Identification of novel biomarkers in plasma for prediction of treatment response in patients with heart failure.

Background: Heart failure is a complex clinical syndrome that occurs at the end stage of heart disease. Despite advances in therapy for heart failure, improvement of clinical outcomes remains a challenge for physicians. The identification of treatment response early in the course of disease would be useful to improve management of these patients.

Diuretic response in acute heart failure-an analysis from ASCEND-HF.

Background: Diuretic unresponsiveness often occurs during hospital admission for acute heart failure (AHF) and is associated with adverse outcome. This study aims to investigate determinants, clinical outcome, and the effects of nesiritide on diuretic response early after admission for AHF.

Methods: Diuretic response, defined as weight loss per 40 mg of furosemide or equivalent, was examined from hospital admission to 48 hours in 4,379 patients from the ASCEND-HF trial.

Predictors of clinical outcomes in acute decompensated heart failure: Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure outcome models.

Background: Patients hospitalized for acute decompensated heart failure (ADHF) are at high risk for early mortality and rehospitalization. Risk stratification of ADHF using clinically available data on admission is increasingly important to integrate with clinical pathways. Our goal was to create a simple method of screening patients upon admission to identify those with increased risk of future adverse events.

A combined clinical and biomarker approach to predict diuretic response in acute heart failure.

Background: Poor diuretic response in acute heart failure is related to poor clinical outcome. The underlying mechanisms and pathophysiology behind diuretic resistance are incompletely understood. We evaluated a combined approach using clinical characteristics and biomarkers to predict diuretic response in acute heart failure (AHF).

Effects of sildenafil on invasive haemodynamics and exercise capacity in heart failure patients with preserved ejection fraction and pulmonary hypertension: a randomized controlled trial.

Background: Heart failure with preserved ejection fraction (HFpEF), with associated pulmonary hypertension is an increasingly large medical problem. Phosphodiesterase (PDE)-5 inhibition may be of value in this population, but data are scarce and inconclusive.

Methods And Results: In this single centre, randomized double-blind, placebo-controlled trial, we included 52 patients with pulmonary hypertension [mean pulmonary artery pressure (PAP) >25 mmHg; pulmonary artery wedge pressure (PAWP) >15 mmHg] due to HFpEF [left ventricular ejection fraction (LVEF) ≥45%].

Long-term changes in renal function and perfusion in heart failure patients with reduced ejection fraction.

Introduction: Little is known about the natural course of renal function and renal hemodynamics in heart failure patients with reduced ejection fraction (HFREF).

Methods And Results: We prospectively studied effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) in 73 HFREF patients with (125)I-iothalamate/(131)I-hippuran clearances with a mean follow-up of 34.6 ± 4.

Finerenone : third-generation mineralocorticoid receptor antagonist for the treatment of heart failure and diabetic kidney disease.

Introduction: The mineralocorticoid receptor antagonists (MRAs) spironolactone and eplerenone reduce the risk of hospitalizations and mortality in patients with heart failure (HF) with reduced ejection fraction (HFrEF), and attenuate progression of diabetic kidney disease. However, their use is limited by the fear of inducing hyperkalemia, especially in patients with renal dysfunction. Finerenone is a novel nonsteroidal MRA, with higher selectivity toward the mineralocorticoid receptor (MR) compared to spironolactone and stronger MR-binding affinity than eplerenone.

Early vs. late worsening heart failure during acute heart failure hospitalization: insights from the PROTECT trial.

Background: Worsening heart failure (WHF) symptoms despite initial therapy during admission for acute heart failure (AHF) is associated with worse outcomes. The association between the time of the WHF event and the intensity of WHF therapy with outcomes is unknown.

Methods And Results: In the PROTECT trial of 2033 AHF patients, we investigated the association between time of occurrence of WHF and intensity of therapy, with subsequent outcomes.

Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction).

Aims: We examined the effect of the renin inhibitor, aliskiren, on renal blood flow (RBF) in patients with heart failure with reduced ejection fraction (HFREF) and decreased glomerular filtration rate (GFR). Renal blood flow is the main determinant of GFR in HFREF patients. Both reduced GFR and RBF are associated with increased mortality.

Worsening Heart Failure Following Admission for Acute Heart Failure: A Pooled Analysis of the PROTECT and RELAX-AHF Studies.

Objectives: These studies conducted analyses to examine patient characteristics and outcomes associated with worsening heart failure (WHF).

Background: WHF during an admission for acute heart failure (AHF) represents treatment failure and is a potential therapeutic target for clinical trials of AHF.

Methods: Individual patient data from the PROTECT (Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function) and RELAX-AHF (Relaxin in Acute Heart Failure) phase II and III studies were pooled for analysis.

Erythropoietin in the general population: reference ranges and clinical, biochemical and genetic correlates.

Background: Although erythropoietin has been used for decades in the treatment of anemia, data regarding endogenous levels in the general population are scarce. Therefore, we determined erythropoietin reference ranges and its clinical, biochemical and genetic associations in the general population.

Methods: We used data from 6,777 subjects enrolled in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study.