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

Background: Heart failure with midrange ejection fraction (HFmrEF) represents a heterogeneous category where phenotype, as well as prognostic assessment, remains still 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 (CPET). Methods and results: We analyzed data of 4,535 HF with reduced EF (HFrEF) and 1,176 rec-HFmrEF outpatients from the Metabolic Exercise combined with Cardiac and Kidney Indexes (MECKI) database. The end-point was cardiovascular death at 5 years. The median follow-up was 1,343 days (25th-75th range, 627-2,403 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 pVO2 ≤55% of predicted and a ventilatory efficiency ≥31 resulted as the most accurate cut-off values in the outcome prediction. Conclusions: Present data support the CPET and, particularly, the pVO2, as a useful tool in the rec-HFmrEF prognostic assessment. Peak VO2≤55% predicted and ventilatory efficiency ≥31 might help to identify a high risk rec-HFmrEF subgroup.