van Essen, Bart J.Tromp, JasperTer Maaten, Jozine M.Greenberg, Barry H.Gimpelewicz, ClaudioFelker, G. MichaelDavison, Beth A.Severin, ThomasPang, Peter S.Cotter, GadTeerlink, John R.Metra, MarcoVoors, Adriaan A.2023-12-192023-12-192023van Essen BJ, Tromp J, Ter Maaten JM, et al. Characteristics and clinical outcomes of patients with acute heart failure with a supranormal left ventricular ejection fraction. Eur J Heart Fail. 2023;25(1):35-42. doi:10.1002/ejhf.2695https://hdl.handle.net/1805/37422Aim: 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.en-USAttribution-NonCommercial 4.0 InternationalAcute heart failureHeart failure with supranormal ejection fractionClinical outcomeSerelaxinArticle