Empagliflozin in heart failure with preserved ejection fraction: first success in mission impossible

Heart failure and preserved ejection fraction (EF) is a common disease with a poor prognosis and increasing prevalence in the community. The current treatment paradigm includes symptomatic therapy, such as diuretics, risk factor control, and treatment of comorbidities. According to the most recent European guidelines, there is no effective therapy in patients with heart failure and left ventricular EF >= 50%, while the pharmacological compounds normally used in heart failure with reduced EF could also be implemented in patients with EF slightly reduced (between 40 and 50%), with a recommendation class IIB. The recently published Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction (EMPEROR-Preserved) study challenged current guidelines, showing for the first time in patients with heart failure and EF >40% better outcomes with the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin than with placebo. This result was consistent in patients with and without diabetes, as well as in those with EF below and above 50%. The purpose of the review is to describe the rationale for this important finding and the main results of the EMPEROR-Preserved study and to provide some suggestions for the daily clinical management of SGLT2 inhibitors.