Characteristics and long‐term prognosis of patients with heart failure and mid‐range ejection fraction compared with reduced and preserved ejection fraction: a systematic review and meta‐analysis

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.