Relax-ahf

AIMS: Acute heart failure (AHF) can result in worsening of heart failure (WHF), cardiogenic shock (CS), or death. Risk factors for these adverse outcomes are not well characterized. This study aimed to identify predictors for WHF or new-onset CS in patients hospitalized for AHF. METHODS AND RESULTS: Prospective cohort study enrolling consecutive patients with AHF admitted to a large tertiary care centre with follow-up until death or discharge. WHF was defined by the RELAX-AHF-2 criteria...

AIMS: The impact of mitral regurgitation (MR) in patients hospitalized for acute heart failure (AHF) is not well established. We assessed the role of MR in patients enrolled in the Relaxin in Acute Heart Failure 2 (RELAX-AHF-2) trial. METHODS AND RESULTS: Patients enrolled in RELAX-AHF-2 with available data regarding MR status were included in this analysis. Baseline characteristics, in-hospital data, and clinical outcomes through 180-day follow-up were evaluated...

BACKGROUND: Recent data suggest that guideline directed medical treatment of patients with heart failure with reduced ejection fraction (HFrEF) might improve clinical outcomes in patients with heart failure (HF) up to a left ventricular ejection fraction (LVEF) of 55-65%, whereas patients with higher LVEF do not seem to benefit. Recent data have shown that LVEF may have a U-shaped relation with outcome, with poorer outcome also in patients with supranormal values. This suggests that patients with supranormal LVEF may be a distinctive group of patients METHODS AND RESULTS: RELAX AHF-2 was a multicenter, placebo-controlled trial on the effects of serelaxin on 180-day cardiovascular (CV) mortality and worsening HF at day 5 in patients with acute HF...

Previous studies have suggested that the neutrophil-to-lymphocyte ratio (NLR) is a novel yet readily evaluable inflammatory biomarker that may be useful for determining cardiovascular prognosis during acute episodes. The study investigated the role of NLR in predicting cardiovascular (CV) outcomes in patients with acute heart failure (HF). Individual patient data from the BLAST-AHF (phase 2b study of the biased ligand of the angiotensin 2 type 1 receptor, TRV027), Pre-RELAX-AHF (phase 2b study of recombinant human relaxin-2, serelaxin), and RELAX-AHF (phase 3 study of serelaxin) randomized, placebo-controlled studies for patients with acute HF were pooled for analysis...

BACKGROUND: For patients with acute heart failure (AHF), substantial diuresis after administration of loop diuretics is generally associated with better clinical outcomes but may cause creatinine to rise, suggesting renal function decline. We investigated the interaction between diuretic response and worsening renal function (WRF) on clinical outcomes in patients with AHF. METHODS AND RESULTS: In two AHF cohorts (PROTECT, n = 1698 and RELAX-AHF-2, n = 5586 in current analysis), the prognostic impact of WRF (creatinine ≥0...

OBJECTIVES: The aim of this study was to investigate the association between systolic blood pressure (SBP) drop, worsening renal function (WRF), and prognosis in patients with acute heart failure (AHF). BACKGROUND: A large drop in SBP early after hospital admission for AHF might be associated with increased risk for WRF and prognosis. However, there is a paucity of data regarding the interaction between WRF and a drop in SBP on clinical outcomes. METHODS: A post hoc analysis among 6,544 patients with AHF enrolled in the RELAX-AHF-2 (Relaxin in Acute Heart Failure-2) trial was performed...

OBJECTIVES: This study sought to better understand the discrepant results of 2 trials of serelaxin on acute heart failure (AHF) and short-term mortality after AHF by analyzing causes of death of patients in the RELAX-AHF-2 (Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF-2) trial. BACKGROUND: Patients with AHF continue to suffer significant short-term mortality, but limited systematic analyses of causes of death in this patient population are available...

BACKGROUND: Whether risk of worsening renal function (WRF) during acute heart failure (AHF) hospitalization or the association between in-hospital WRF and post-discharge outcomes vary according to left ventricular ejection fraction (LVEF) are uncertain. We assessed incidence of WRF, factors related to its development and impact of WRF on post-discharge outcomes across the spectrum of LVEF in patients enrolled in RELAX-AHF-2. METHODS AND RESULTS: 6112 patients who had LVEF measured on admission and renal function determined prospectively during hospitalization were included...

AIMS: Although left ventricular ejection fraction (LVEF) is routinely used to categorize patients with heart failure (HF), whether it predicts outcomes after hospitalization for acute heart failure (AHF) is uncertain. Consequently, we assessed the relationship between LVEF and cardiovascular (CV) outcomes in a large, well characterized cohort of patients hospitalized for AHF. METHODS AND RESULTS: The 6128 patients from the RELAX-AHF-2 trial who had LVEF measured during AHF hospitalization were separated into LVEF quartiles and the relationship between LVEF and a composite of CV mortality and rehospitalization for HF or renal failure through 180 days was assessed...

No abstract text is available yet for this article.

The peptide hormone relaxin was originally linked to reproductive physiology, where it is believed to mediate systemic and renal hemodynamic adjustments to pregnancy. Recently, its broad range of effects in the cardiovascular system has been the focus of intensive research regarding its implications under pathological conditions and potential therapeutic potential. An understanding of the multitude of cardioprotective actions prompted the study of serelaxin, recombinant human relaxin-2, for the treatment of acute heart failure...

AIMS: Episodes of acute heart failure (AHF) may lead to end-organ dysfunction. In this post hoc analysis of the Relaxin in Acute Heart Failure trial, we used the MELD-XI (Model of End-Stage Liver Dysfunction) score to examine hepatorenal dysfunction in patients with AHF. METHODS AND RESULTS: On admission, the MELD-XI score was elevated (abnormal) in 918 (82%) patients, with 638 (57%) having isolated renal dysfunction (creatinine > 1 mg/dL), 73 (6.5%) isolated liver dysfunction (bilirubin > 1 mg/dL), and 207 (18...

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...

AIM: Serelaxin is a recombinant human relaxin-2 hormone, which confers receptor-mediated vasodilatation in a tissue-specific fashion. The RELAX-AHF-EU study assessed the effect of serelaxin when added to standard-of-care (SoC) therapy on worsening heart failure (WHF)/all-cause death through Day 5 in patients hospitalised for acute heart failure (AHF) in Europe. METHODS AND RESULTS: This multicentre, prospective, randomised, open-label, blinded-endpoint validation study enrolled hospitalised AHF patients and randomised (2:1) eligible patients (mild-to-moderate renal impairment and systolic blood pressure ≥ 125 mmHg) within 16 h of presentation with signs/symptoms of AHF, to receive 48 h intravenous infusion of 30 μg/kg/day serelaxin + SoC or SoC alone...

Peptide hormone relaxin-2, a member of the insulin family of peptides, plays a key role in hemodynamics and renal function and has shown preclinical efficacy in multiple disease models, including acute heart failure, fibrosis, preeclampsia, and corneal wound healing. Recently, serelaxin, a recombinant version of relaxin-2, has been studied in a large phase 3 clinical trial (RELAX-AHF-2) for acute decompensated heart failure patients with disappointing outcome. The poor in vivo half-life of relaxin-2 may have limited its therapeutic efficacy and long-term cardiovascular benefit...

Since its discovery in the 1920's the relaxin peptide hormone family has not only grown in number to now seven members (relaxin-1, relaxin-2, relaxin-3, insulin-like peptide (INSL) 3, INSL4, INSL5 and INSL6), but ever more effects, suchs as vasodilatory, angiogenic, anti-apoptopic, anti-fibriotic and anti-inflammatory, have been linked to them. While relaxin-2 has mainly been investigated in the context of cardiac protection, most comprehensively in the RELAX-AHF and RELAX AHF2 studies, a small number of studies have furthermore assessed the potential neuroprotective effects of especially relaxin-2 and other members of the relaxin family...

BACKGROUND: Site selection is critical in acute heart failure trials. We assessed whether the enrollment rate per site affects patients' characteristics, outcomes and treatment response. METHODS AND RESULTS: A total of 1161 patients enrolled at 96 sites in the RELAX-AHF trial (serelaxin vs placebo) were included. Annualized enrollment rate was calculated as the total number of patients enrolled at each site divided by time that the site was open (patients per year)...

Despite recent advances in the management of heart failure with reduced ejection fraction (HFrEF), the burden of acute heart failure (AHF) remains significant with a high morbidity and mortality that has not been improved by any treatment modality. A meta-analysis summarized the study results on the effects of tolvaptan on AHF, which failed to demonstrate an improvement in short-term and long-term mortality, length of hospital stay and reduced frequency of worsening heart failure (WHF). Similar trial results were also reported in other AHF studies, such as the ASCEND-HF and the RELAX-AHF-2 trials...

No abstract text is available yet for this article.

BACKGROUND: Acute heart failure (AHF) is a heterogeneous disorder, with most of the patients presenting with breathlessness along with varying degrees of peripheral edema. The presence of peripheral edema suggests that volume overload is the cause of decompensation leading to AHF, whereas breathlessness in the absence of edema may reflect a "vascular phenotype." This analysis investigated the characteristics, therapeutic response, and outcome of patients with AHF, with and without overt peripheral edema in the RELAX-AHF trial...