Heart failure with preserved (HFpEF) and mildly reduced ejection fraction (HFmrEF) account for more than half of all heart failure decompensations [1]. Patients are exposed to a high risk of subsequent cardiac decompensations and mortality [2,3]. In HFmrEF, and more so in HFpEF, prognosis is strongly determined by the number of comorbidities, and non-cardiovascular mortality is proportionally higher than in patients with heart failure with reduced ejection fraction (HFrEF) [4]. Phase III pivotal outcome trials targeting HFpEF/HFmrEF investigated inhibition of angiotensin II receptor (CHARM-Preserved, I-PRESERVE), mineralocorticoid receptor (MRA; TOPCAT), angiotensin receptor-neprilysin (ARNI; PARAGON-HF), and the sodium–glucose co-transporter 2 (SGLT2i; EMPEROR-Preserved, DELIVER) [5–10].
