SGLT2-Inhibitors on HFpEF Patients. Role of Ejection Fraction

Results from DELIVER trial and publication of EMPEROR-Preserved with sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with heart failure (HF) with ejection fraction (EF) > 40% represent a significant step forward in the treatment of HF with preserved EF (HFpEF). However, detailed analysis and attenuation of effect at higher EF levels have sparked some doubts about whether empagliflozin is effective across the entire spectrum of EF. HFpEF is no longer considered as one disease entity, but has been reconceptualized as a heterogenous group of phenotypes with derangements in multiple organ systems, driven by comorbidities. This heterogeneity suggests that it should not be considered as a single group in terms of treatment goals or clinical approach. Future research at the higher range of EF should ideally tailor investigations for unequivocally preserved EF (> 50%), consider the dynamic nature of EF over time, and use low-variability imaging techniques such as CMR. Furthermore, classifications based on pathophysiology and HF phenotypes beyond the EF construct will shape the design of future trials and help narrow down groups of patients who may respond to personalized treatment.