Heart Failure With Mid-range Ejection Fraction: A Distinctive Subtype or a Transitional Stage?

Heart failure with mid-range ejection fraction (HFmrEF) was first proposed by Lam and Solomon in 2014, and was listed as a new subtype of heart failure (HF) in 2016 European Society of Cardiology guidelines. Since then, HFmrEF has attracted an increasing amount of attention, and the number of related studies on this topic has grown rapidly. The diagnostic criteria on the basis of left ventricular ejection fraction (LVEF) are straightforward; however, LVEF is not a static parameter, and it changes dynamically during the course of HF. Thus, HFmrEF may not be an independent disease with a uniform pathophysiological process, but rather a collection of patients with different characteristics. HFmrEF is often associated with various cardiovascular and non-cardiovascular diseases. Thus, the pathophysiological mechanisms of HFmrEF are particularly complex, and its clinical phenotypes are diverse. The complexity and heterogeneity of HFmrEF may be one reason for inconsistent results between clinical studies. In fact, whether HFmrEF is a distinctive subtype or a transitional stage between HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) is controversial. In this review, we discuss the clinical characteristics, treatment and prognosis of patients with HFmrEF, as well as the differences among HFmrEF, HFrEF, and HFpEF.