Cardiovascular death risk in mid-range ejection fraction heart failure: insights from cardiopulmonary exercise test

Background: Heart failure with midrange ejection fraction (HFmrEF) represents a heterogeneous cate- gory where phenotype, as well as prognostic assessment, remains debated. The present study explores a specific HFmrEF subset, namely those who recovered from a reduced EF (rec-HFmrEF) and, particularly, it focuses on the possible additive prognostic role of cardiopulmonary exercise testing. Methods and Results: We analyzed data from 4535 patients with HFrEF and 1176 patients with rec- HFmrEF from the Metabolic Exercise combined with Cardiac and Kidney Indexes database. The end point was cardiovascular death at 5 years. The median follow-up was 1343 days (25th 75th range 627 2403 days). Cardiovascular death occurred in 552 HFrEF and 61 rec-HFmrEF patients. The multivariate analysis confirmed an independent role of the MECKI score’s variables in HFrEF (C-index = 0.744) whereas, in the rec-HFmrEF group, only age and peak oxygen uptake (pVO2) remained associated to the end point (C- index = 0.745). A peak oxygen uptake of 55% of predicted and a ventilatory efficiency of 31 resulted as the most accurate cut-off values in the outcome prediction.