Are HFpEF and HFmrEF So Different? The Need to Understand Distinct Phenotypes

Traditionally, patients with heart failure (HF) are divided according to ejection fraction (EF) threshold more or <50%. In 2016, the ESC guidelines introduced a new subgroup of HF patients including those subjects with EF ranging between 40 and 49% called heart failure with midrange EF (HFmrEF). This group is poorly represented in clinical trials, and it includes both patients with previous HFrEF having a good response to therapy and subjects with initial preserved EF appearance in which systolic function has been impaired. The categorization according to EF has recently been questioned because this variable is not really a representative of the myocardial contractile function and it could vary in relation to different hemodynamic conditions. Therefore, EF could significantly change over a short-term period and its measurement depends on the scan time course. Finally, although EF is widely recognized and measured worldwide, it has significant interobserver variability even in the most accredited echo laboratories. These assumptions imply that the same patient evaluated in different periods or by different physicians could be classified as HFmrEF or HFpEF. Thus, the two HF subtypes probably subtend different responses to the underlying pathophysiological mechanisms. Similarly, the adaptation to hemodynamic stimuli and to metabolic alterations could be different for different HF stages and periods. In this review, we analyze similarities and dissimilarities and we hypothesize that clinical and morphological characteristics of the two syndromes are not so discordant.