Heart Failure with Mid-range Ejection Fraction - What is it, if Anything?

Abstract The patient cohort with left ventricular ejection fraction (LVEF) of 41-49% represents a significant proportion of the heart failure (HF) population which has been defined as heart failure with mid-range ejection fraction (HFmrEF). Despite the clear cut-offs established by the different society guidelines, confusion remains regarding the exact significance of mid-range LVEF within the HF syndrome. Patients with an LVEF between 41-49% represent a heterogenous group of patients sharing pathophysiological mechanisms, biomarker profiles, comorbidities, and clinical characteristics with patients with preserved and reduced LVEF. In this clinical review, we will discuss the underlying pathophysiological mechanisms that culminate in the clinical syndrome of HF and contribute to the disparities observed between HFpEF, HFrEF, and HFmrEF. We will highlight differences and similarities in clinical characteristics and imaging features between HFpEF and HFrEF, in an effort to disentangle the heterogenous group of patients with mid-range LVEF, but, ultimately conclude that the LVEF should be seen as simply one important element of a continuum throughout the HF syndrome, and that although useful is an oversimplification, as HF syndrome is more of a continuum. The underlying pathophysiology, etiology and co-morbidities of patients presenting with HF is becoming more and more important as the limitations of a classification solely based on LVEF are being better recognized, and as patient-specific personalization of care is becoming more and more important.