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Item Characteristics and clinical outcomes of patients with acute heart failure with a supranormal left ventricular ejection fraction(Wiley, 2023) van Essen, Bart J.; Tromp, Jasper; Ter Maaten, Jozine M.; Greenberg, Barry H.; Gimpelewicz, Claudio; Felker, G. Michael; Davison, Beth A.; Severin, Thomas; Pang, Peter S.; Cotter, Gad; Teerlink, John R.; Metra, Marco; Voors, Adriaan A.; Emergency Medicine, School of MedicineAim: Recent data suggest that guideline-directed medical therapy of patients with heart failure (HF) with reduced ejection fraction (HFrEF) might improve clinical outcomes in patients with 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 multicentre, 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. Echocardiograms were performed at hospital admission in 6128 patients: 155 (2.5%) patients were classified as HF with supranormal ejection fraction (HFsnEF; LVEF >65%), 1440 (23.5%) as HF with preserved ejection fraction (HFpEF; LVEF 50-65%), 1353 (22.1%) as HF with mildly reduced ejection fraction (HFmrEF; LVEF 41-49%) and 3180 (51.9%) as HFrEF (LVEF <40%). Patients with HFsnEF compared to HFpEF were more often women, had higher prevalence of non-ischaemic HF, had lower levels of natriuretic peptides, were less likely to be treated with beta-blockers and had higher blood urea nitrogen plasma levels. All-cause mortality was not statistically different between groups, although patients with HFsnEF had the highest numerical rate. A declining trend was seen in the proportion of 180-day deaths due to CV causes from HFrEF (290/359, 80.8%) to HFsnEF (14/24, 58.3%). The reverse was observed with death from non-CV causes. No treatment effect of serelaxin was observed in any of the subgroups. Conclusions: In this study, only 2.5% of patients were classified as HFsnEF. HFsnEF was primarily characterized by female sex, lower natriuretic peptides and a higher risk of non-CV death.Item Effects of Serelaxin in Patients with Acute Heart Failure(Massachusetts Medical Society, 2019-08) Metra, M.; Teerlink, J. R.; Cotter, G.; Davison, B. A.; Felker, G. M.; Filippatos, G.; Greenberg, B. H.; Pang, P. S.; Ponikowski, P.; Voors, A.A.; Adams, K. F.; Anker, S. D.; Arias‑Mendoza, A.; Avendaño, P.; Bacal, F.; Böhm, M.; Bortman, G.; Cleland, J. G. F.; Cohen-Solal, A.; Crespo-Leiro, M. G.; Dorobantu, M.; Echeverría, L. E.; Ferrari, R.; Goland, S.; Goncalvesová, E.; Goudev, A.; Køber, L.; Lema‑Osores, J.; Levy, P. D.; McDonald, K.; Manga, P.; Merkely, B.; Mueller, C.; Pieske, B.; Silva-Cardoso, J.; Špinar, J.; Squire, I.; Stępińska, J.; Van Mieghem, W.; von Lewinski, D.; Wikström, G.; Yilmaz, M. B.; Hagner, N.; Holbro, T.; Hua, T. A.; Sabarwal, S. V.; Severin, T.; Szecsödy, P.; Gimpelewicz, C.; Emergency Medicine, School of MedicineBACKGROUND 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. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. RESULTS A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P=0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P=0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. CONCLUSIONS In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo.