Heart Failure With Mid-range or Recovered Ejection Fraction: Differential Determinants of Transition

The recent definition of an intermediate clinical phenotype of heart failure (HF) based on an ejection fraction (EF) of between 40% and 49%, namely HF with mid-range EF (HFmrEF), has fuelled investigations into the clinical profile and prognosis of this patient group. HFmrEF shares common clinical features with other HF phenotypes, such as a high prevalence of ischaemic aetiology, as in HF with reduced EF (HFrEF), or hypertension and diabetes, as in HF with preserved EF (HFpEF), and benefits from the cornerstone drugs indicated for HFrEF. Among the HF phenotypes, HFmrEF is characterised by the highest rate of transition to either recovery or worsening of the severe systolic dysfunction profile that is the target of disease-modifying therapies, with opposite prognostic implications. This article focuses on the epidemiology, clinical characteristics and therapeutic approaches for HFmrEF, and discusses the major determinants of transition to HFpEF or HFrEF.