Impact of empagliflozin on right ventricular parameters and function among patients with type 2 diabetes

Bradley Sarak,Hwee Teoh,Sumeet Gandhi,Richard E Gilbert,Vinay Garg,Djeven P Deva,Adrian Quan,Shaun G Goodman,Kim A Connelly,Karan Bami,Otávio R Coelho-Filho,Vineeta Ahooja,Subodh Verma,Andrew T Yan,C David Mazer

doi:10.1186/s12933-021-01390-8

Abstract

BackgroundSodium-glucose cotransporter 2 (SGLT2) inhibition reduces cardiovascular events in type 2 diabetes (T2DM) and is associated with a reduction in left ventricular (LV) mass index. However, the impact on right ventricular (RV) remodeling is unknown. Accordingly, the objective of this study was to assess the impact of SGLT2 inhibition on RV parameters and function in T2DM and coronary artery disease (CAD).MethodsIn EMPA-HEART CardioLink-6, 97 patients with T2DM and CAD were randomly assigned to empagliflozin 10 mg (n = 49) once daily or placebo (n = 48). Cardiac magnetic resonance imaging was performed at baseline and after 6 months. RV mass index (RVMi), RV end-diastolic and end-systolic volume index (RVEDVi, RVESVi) and RV ejection fraction (RVEF) were assessed in blinded fashion.ResultsAt baseline, mean RVMi (± SD) (11.8 ± 2.4 g/m2), RVEF (53.5 ± 4.8%), RVEDVi (64.3 ± 13.2 mL/m2) and RVESVi (29.9 ± 6.9 mL/m2) were within normal limits and were similar between the empagliflozin and placebo groups. Over 6 months, there were no significant differences in RVMi (− 0.11 g/m2, [95% CI − 0.81 to 0.60], p = 0.76), RVEF (0.54%, [95% CI − 1.4 to 2.4], p = 0.58), RVEDVi (− 1.2 mL/m2, [95% CI − 4.1 to 1.7], p = 0.41) and RVESVi (− 0.81 mL/m2, [95% CI − 2.5 to 0.90], p = 0.35) in the empaglifozin group as compared with the placebo group. In both groups, there was no significant correlation between RVMi and LVMi changes from baseline to 6 months.ConclusionsIn this post-hoc analysis, SGLT2 inhibition with empagliflozin had no impact on RVMi and RV volumes in patients with T2DM and CAD. The potentially differential effect of empagliflozin on the LV and RV warrants further investigation.Clinical Trial Registration: URL: https://www.clinicaltrials.gov/ct2/show/NCT02998970?cond=NCT02998970&draw=2&rank=1. Unique identifier: NCT02998970.

Highlights

The sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin reduces cardiovascular (CV) mortality, allcause mortality and heart failure (HF) hospitalization in patients with type 2 diabetes (T2DM) and established atherosclerotic CV disease (ASCVD) [1]
Two other patients were lost to followup. Both baseline and 6-month cardiac magnetic resonance imaging (cMRI) were available for 44 participants in the empagliflozin group and 46 in the placebo arm
The change in LVMi from baseline to 6 months was − 2.6 (7.8)g/m2 for the empagliflozin group and − 0.01 (5.7)g/m2 for the placebo group

Summary

Introduction

The sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin reduces cardiovascular (CV) mortality, allcause mortality and heart failure (HF) hospitalization in patients with type 2 diabetes (T2DM) and established atherosclerotic CV disease (ASCVD) [1]. The benefit of empagliflozin and dapagliflozin was confirmed in patients with HF with reduced ejection fraction with or without T2DM [6,7,8]. The mechanism of these benefits, on reducing HF hospitalizations and CV death, remains unclear. Sodium-glucose cotransporter 2 (SGLT2) inhibition reduces cardiovascular events in type 2 dia‐ betes (T2DM) and is associated with a reduction in left ventricular (LV) mass index. The objective of this study was to assess the impact of SGLT2 inhibition on RV parameters and function in T2DM and coronary artery disease (CAD)

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Conclusion