Trajectory of Congestion Metrics by Ejection Fraction in Patients With Acute Heart Failure (from the Heart Failure Network).

Differences in the clinical course of congestion by underlying ejection fraction (EF) have not been well-characterized in acute heart failure (AHF). A post hoc analysis was performed using pooled data from the Diuretic Optimization Strategies Evaluation in Acute Heart Failure, Cardiorenal Rescue Study in Acute Decompensated Heart Failure, and Renal Optimization Strategies Evaluation in Acute Heart Failure trials. All patients were admitted for a primary diagnosis of AHF.

Biased ligand of the angiotensin II type 1 receptor in patients with acute heart failure: a randomized, double-blind, placebo-controlled, phase IIB, dose ranging trial (BLAST-AHF).

Aims: Currently, no acute heart failure (AHF) therapy definitively improves outcomes. Reducing morbidity and mortality from acute heart failure (AHF) remains an unmet need. TRV027 is a novel 'biased' ligand of the angiotensin II type 1 receptor (AT1R), selectively antagonizing the negative effects of angiotensin II, while preserving the potential pro-contractility effects of AT1R stimulation.

Day vs night: Does time of presentation matter in acute heart failure? A secondary analysis from the RELAX-AHF trial.

Background: Signs and symptoms of heart failure can occur at any time. Differences between acute heart failure (AHF) patients who present at nighttime vs daytime and their outcomes have not been well studied. Our objective was to determine if there are differences in baseline characteristics and clinical outcomes between AHF patients presenting during daytime vs nighttime hours within an international, clinical trial.

Serelaxin in addition to standard therapy in acute heart failure: rationale and design of the RELAX-AHF-2 study.

Patients admitted for acute heart failure (AHF) experience high rates of in-hospital and post-discharge morbidity and mortality despite current therapies. Serelaxin is recombinant human relaxin-2, a hormone with vasodilatory and end-organ protective effects believed to play a central role in the cardiovascular and renal adaptations of human pregnancy. In the phase 3 RELAX-AHF trial, serelaxin met its primary endpoint of improving dyspnoea through day 5 in patients admitted for AHF.

Role of Biomarkers for the Prevention, Assessment, and Management of Heart Failure: A Scientific Statement From the American Heart Association.

Background And Purpose: Natriuretic peptides have led the way as a diagnostic and prognostic tool for the diagnosis and management of heart failure (HF). More recent evidence suggests that natriuretic peptides along with the next generation of biomarkers may provide added value to medical management, which could potentially lower risk of mortality and readmissions. The purpose of this scientific statement is to summarize the existing literature and to provide guidance for the utility of currently available biomarkers.

Implications of Alternative Hepatorenal Prognostic Scoring Systems in Acute Heart Failure (from DOSE-AHF and ROSE-AHF).

Because hepatic dysfunction is common in patients with heart failure (HF), the Model for End-Stage Liver Disease (MELD) may be attractive for risk stratification. Although alternative scores such as the MELD-XI or MELD-Na may be more appropriate in HF populations, the short-term clinical implications of these in patients with acute heart failure (AHF) are unknown. The MELD-XI and MELD-Na were calculated at baseline in 453 patients with AHF in the DOSE-AHF and ROSE-AHF trials.

Comparison of Clinical Characteristics and Outcomes of Patients With Versus Without Diabetes Mellitus and With Versus Without Angina Pectoris (from the Duke Databank for Cardiovascular Disease).

Angina pectoris (AP) has different prognostic implications in various populations. Patients with diabetes mellitus (DM) may experience neuropathy such that AP may not be perceived in the setting of coronary artery disease (CAD). The prognostic utility of AP in DM patients with CAD is not well known.

Myocardial Damage Detected by Late Gadolinium Enhancement Cardiac Magnetic Resonance Is Uncommon in Peripartum Cardiomyopathy.

Background: In peripartum cardiomyopathy, the prevalence of focal myocardial damage detected by late gadolinium enhancement (LGE) cardiovascular magnetic resonance is important to elucidate mechanisms of myocardial injury and cardiac dysfunction. LGE equates irreversible myocardial injury, but LGE prevalence in peripartum cardiomyopathy is uncertain.

Methods And Results: Among 100 women enrolled within the Investigations of Pregnancy Associated Cardiomyopathy cohort, we recruited 40 women at 13 centers to undergo LGE cardiovascular magnetic resonance, enrolled within the first 13 weeks postpartum.

Plasma Levels of MicroRNA-155 Are Upregulated with Long-Term Left Ventricular Assist Device Support.

Left ventricular assist device (LVAD) therapy unloads the failing heart but exposes the human body to unique pathophysiologic demands such as continuous blood flow and complete univentricular support, which are associated with increased risk of adverse clinical outcomes. MicroRNAs (miRNAs) are 22-23 nucleotide RNAs involved in regulation of multiple biologic processes including the pathogenesis of heart failure (HF). Thus, measurement of miRNAs may have potential in both diagnostics as circulating biomarkers and in therapeutics for targeted interventions.

Suppression of Tumorigenicity 2 in Heart Failure With Preserved Ejection Fraction.

Background: Soluble suppression of tumorigenicity 2 (sST2) receptor is a biomarker that is elevated in certain systemic inflammatory diseases. Comorbidity-driven microvascular inflammation is postulated to play a key role in heart failure with preserved ejection fraction (HFpEF) pathophysiology, but data on how sST2 relates to clinical characteristics or inflammatory conditions or biomarkers in HFpEF are limited. We sought to determine circulating levels and clinical correlates of sST2 in HFpEF.

Serelaxin in acute heart failure patients with and without atrial fibrillation: a secondary analysis of the RELAX-AHF trial.

Background: Atrial fibrillation (AFib) is a common comorbidity in HF and affects patients' outcome. We sought to assess the effects of serelaxin in patients with and without AFib.

Methods: In a post hoc analysis of the RELAX-AHF trial, we compared the effects of serelaxin on efficacy end points, safety end points and biomarkers in 1161 patients with and without AFib on admission electrocardiogram.

A multimarker multi-time point-based risk stratification strategy in acute heart failure: results from the RELAX-AHF trial.

Aims: We evaluated the added prognostic value of a multi-time point-based multimarker panel of biomarkers in patients with acute heart failure (AHF).

Methods And Results: Seven circulating biomarkers [NT-proBNP, high sensitivity cardiac troponin T (hs-cTnT), soluble ST2 (sST2), growth differentiation factor 15 (GDF-15), cystatin-C, galectin-3, and high sensitivity C-reactive protein (hs-CRP)] were measured at baseline and on days 2, 5, 14, and 60 in 1161 patients enrolled in the RELAX-AHF trial. Patients with BNP ≥350 ng/L or NT-proBNP ≥1400 ng/L, mild to moderate renal impairment, and systolic blood pressure >125 mmHg were included in the trial.

Body Weight Change During and After Hospitalization for Acute Heart Failure: Patient Characteristics, Markers of Congestion, and Outcomes: Findings From the ASCEND-HF Trial.

Objectives: This study sought to examine the relationships between in-hospital and post-discharge body weight changes and outcomes among patients hospitalized for acute heart failure (AHF).

Background: Body weight changes during and after hospitalization for AHF and the relationships with outcomes have not been well characterized.

Methods: A post hoc analysis was performed of the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide and Decompensated Heart Failure) trial, which enrolled patients admitted for AHF regardless of ejection fraction.

Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure (COSMIC-HF): a phase 2, pharmacokinetic, randomised, placebo-controlled trial.

Background: Impaired contractility is a feature of heart failure with reduced ejection fraction. We assessed the pharmacokinetics and effects on cardiac function and structure of the cardiac myosin activator, omecamtiv mecarbil.

Methods: In this randomised, double-blind study, done at 87 sites in 13 countries, we recruited patients with stable, symptomatic chronic heart failure and left ventricular ejection fraction 40% or lower.

Sex differences in early dyspnea relief between men and women hospitalized for acute heart failure: insights from the RELAX-AHF study.

Aims: Women with heart failure are typically older, and more often have hypertension and a preserved left ventricular ejection fraction as compared with men. We sought to analyze if these sex differences influence the course and outcome of acute heart failure.

Methods And Results: We analyzed sex differences in acute heart failure in 1161 patients enrolled in the RELAX-AHF study.

Composite End Points in Acute Heart Failure Research: Data Simulations Illustrate the Limitations.

Composite end points are frequently used in clinical trials of investigational treatments for acute heart failure, eg, to boost statistical power and reduce the overall sample size. By incorporating multiple and varying types of clinical outcomes they provide a test for the overall efficacy of the treatment. Our objective is to compare the performance of popular composite end points in terms of statistical power and describe the uncertainty in these power estimates and issues concerning implementation.

Efficacy and Safety of Tolvaptan in Patients Hospitalized With Acute Heart Failure.

Background: The oral vasopressin-2 receptor antagonist tolvaptan causes aquaresis in patients with volume overload, potentially facilitating decongestion and improving the clinical course of patients with acute heart failure (AHF).

Objectives: The TACTICS-HF (Targeting Acute Congestion with Tolvaptan in Congestive Heart Failure) study was conducted to address the acute use of tolvaptan to improve congestion in AHF.

Methods: The TACTICS-HF study randomized patients (n = 257) within 24 h of AHF presentation in a prospective, double blind, placebo-controlled trial.

Rationale and Design of the ATHENA-HF Trial: Aldosterone Targeted Neurohormonal Combined With Natriuresis Therapy in Heart Failure.

Although therapy with mineralocorticoid receptor antagonists (MRAs) is recommended for patients with chronic heart failure (HF) with reduced ejection fraction and in post-infarction HF, it has not been studied well in acute HF (AHF) despite being commonly used in this setting. At high doses, MRA therapy in AHF may relieve congestion through its natriuretic properties and mitigate the effects of adverse neurohormonal activation associated with intravenous loop diuretics. The ATHENA-HF (Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure) trial is a randomized, double-blind, placebo-controlled study of the safety and efficacy of 100 mg/day spironolactone versus placebo (or continued low-dose spironolactone use in participants who are already receiving spironolactone at baseline) in 360 patients hospitalized for AHF.

Implications of Using Different Definitions on Outcomes in Worsening Heart Failure.

Background: In-hospital worsening heart failure (WHF) is an important event that has inconsistent definitions used across trials. We used data from 2 acute heart failure (HF) trials from the National Institutes of Health HF Network, DOSE (Diuretic Optimization Strategies Evaluation) and ROSE (Renal Optimization Strategies), to understand event rates associated with different WHF definitions.

Methods And Results: We pooled data from 668 patients in DOSE and ROSE and assessed the relationship between WHF and the composite end point of rehospitalization, emergency room visits for HF, and mortality through 60 days.

Differential Response to Low-Dose Dopamine or Low-Dose Nesiritide in Acute Heart Failure With Reduced or Preserved Ejection Fraction: Results From the ROSE AHF Trial (Renal Optimization Strategies Evaluation in Acute Heart Failure).

Background: The ROSE AHF trial (Renal Optimization Strategies Evaluation in Acute Heart Failure) found that when compared with placebo, neither low-dose dopamine (2 µg/kg per minute) nor low-dose nesiritide (0.005 μg/kg per minute without bolus) enhanced decongestion or preserved renal function in AHF patients with renal dysfunction. However, there may be differential responses to vasoactive agents in AHF patients with reduced versus preserved ejection fraction (EF).

Effects of Liraglutide on Clinical Stability Among Patients With Advanced Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.

Importance: Abnormal cardiac metabolism contributes to the pathophysiology of advanced heart failure with reduced left ventricular ejection fraction (LVEF). Glucagon-like peptide 1 (GLP-1) agonists have shown cardioprotective effects in early clinical studies of patients with advanced heart failure, irrespective of type 2 diabetes status.

Objective: To test whether therapy with a GLP-1 agonist improves clinical stability following hospitalization for acute heart failure.