AIMS: This study aimed to assess by a meta-analysis the clinical characteristics, all-cause and cardiovascular mortality, and hospitalization of patients with heart failure (HF) with mid-range ejection fraction (HFmrEF) compared with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF).

METHODS AND RESULTS: Data from 12 eligible observational studies including 109 257 patients were pooled. HFmrEF patients were significantly different and occupied a mid-position between HFrEF and HFpEF: mean age 73.6 ± 9.8 vs. 72.6 ± 9.8 and 77.6 ± 7.2 years, male gender 59% vs. 68.5% and 40%, ischaemic heart disease 49% vs. 52.6% and 39.4%, hypertension 67.3% vs. 61.5% and 76.5%, atrial fibrillation 45.2% vs. 39.6% and 46%, chronic obstructive pulmonary disease 26.4% vs. 24.9% and 30.5%, estimated glomerular filtration rate 62 ± 30 vs. 63.3 ± 23 and 59 ± 22.5, use of renin-angiotensin system inhibitors 79.6% vs. 90.1% and 68.7%, beta-blockers 82% vs. 89% and 73.5%, and aldosterone antagonists 20.3 vs. 31.5% and 26%, P-values < 0.05. After a mean follow-up of 31 ± 5 months, all-cause mortality was significantly lower in HFmrEF than in HFrEF and HFpEF (26.8% vs. 29.5% and 31%): risk ratio (RR) 0.95 [0.93-0.98; 95% confidence interval (CI)], P < 0.001, and 0.97 (0.94-0.99; 95% CI), P = 0.014, respectively. Cardiovascular mortality was lowest in HFmrEF (9.7% vs. 13% and 12.8%): RR = 0.81 (0.73-0.91), P < 0.001, and 1.10 (0.97-1.24; 95% CI), P = 0.13, respectively. HF hospitalization in HFmrEF compared to that in HFrEF and HFpEF was 23.9% vs. 27.6% and 23.3% with RR = 0.89 (0.85-0.93), P < 0.001, and RR = 1.12 (1.07-1.17), P < 0.001, respectively.

CONCLUSIONS: The results of this study support that HFmrEF is a distinct category characterized by a mid-position between HFrEF and HFpEF and with the lowest all-cause and cardiovascular mortality.