Related Experiment Video
Updated: Sep 2, 2025
Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction
Published on: February 13, 2021
SGLT2-Inhibitors on HFpEF Patients. Role of Ejection Fraction
Juan Antonio Requena-Ibanez1, Carlos G Santos-Gallego1, M Urooj Zafar1
1Atherothrombosis Research Unit, Icahn School of Medicine at Mount Sinai, Mount Sinai Heart, New York, NY, 10029, USA.
Insights
Sodium-glucose cotransporter 2 (SGLT2) inhibitors show promise for heart failure with preserved ejection fraction (HFpEF). Further research is needed to understand their effectiveness across the spectrum of ejection fraction and in specific HFpEF phenotypes.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Sodium-glucose cotransporter 2 (SGLT2) inhibitors represent a significant advancement in treating heart failure with preserved ejection fraction (HFpEF).
- DELIVER and EMPEROR-Preserved trials demonstrated efficacy in patients with ejection fraction (EF) > 40%.
Purpose of the Study:
- To analyze the detailed effects of SGLT2 inhibitors, specifically empagliflozin, across the spectrum of EF in HFpEF.
- To address doubts regarding empagliflozin's efficacy at higher EF levels and within diverse HFpEF phenotypes.
Main Methods:
- Review of results from the DELIVER and EMPEROR-Preserved clinical trials.
- Detailed analysis of SGLT2 inhibitor effects, focusing on varying ejection fraction ranges.
- Consideration of HFpEF heterogeneity and comorbid conditions.
Main Results:
- SGLT2 inhibitors show efficacy in HFpEF patients with EF > 40%.
- Concerns exist regarding the attenuation of effect at higher EF levels.
- HFpEF is increasingly recognized as a heterogeneous condition with multiple phenotypes.
Conclusions:
- HFpEF should not be treated as a single entity due to its heterogeneity.
- Future research should focus on unequivocally preserved EF (>50%), dynamic EF changes, and advanced imaging (e.g., CMR).
- Pathophysiology-based classifications and HF phenotypes are crucial for designing future personalized treatment trials.
Abstract:
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.
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