Heart failure with mid-range ejection fraction: Current evidence and uncertainties

Heart failure (HF) with mid-range ejection fraction (HFmrEF) has been conceptualized by the European Society of Cardiology guidelines with the aim of stimulating research to fill a gap in knowledge: whether such a condition exists as a distinct pathophysiological and clinical entity, or it is just a residual category of ejection fraction indeed is still a matter of debate. Current evidence suggests that HFmrEF represents up to one fifth of patients with HF, who may ultimately result in an intermediate clinical phenotype, as for age and gender, with an intermediate prevalence of comorbidities. Nevertheless, a strong connection exists with HF with reduced ejection fraction, since ischemic aetiology is common in both categories, conveying relevant implications for prognosis and therapeutic response. Little is known about its pathophysiology: mild systolic impairment may be not enough and advocating diastolic dysfunction may be an oversimplification. An increasing amount of data is clarifying how many of HFmrEF patients are the results of deteriorating or recovering hearts, thus underscoring that aetiology may be, more than EF, the key to understand this new category. Sparse evidence points toward a potential benefit of common HF therapies in those patients, but further research is still needed.