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

Abstract

Background Sodium-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). Methods In 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. Results At 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. Conclusions In 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.

Effect of sodium-glucose co-transporter-2 inhibitors on right ventricular function in patients with type 2 diabetes mellitus: A pilot study

“…In this pilot study, treatment with SGLT2i resulted in a significant improvement in TAPSE. In a former trial, em pagliflozin did not affect RV mass index (RVMi), RV enddi astolic and endsystolic volume index (RVEDVi, RVESVi), and RV ejection fraction (RVEF), while echocardiographic assessment documented a nonsignificant decrease in TAPSE [9]. In another trial, 3month treatment with empag liflozin resulted in a significant decrease in the pulmonary artery (PA) diastolic pressure in patients with HF regardless of left ventricular ejection fraction or presence of T2DM [10].…”

Empagliflozin and Left Ventricular Remodeling in People Without Diabetes: Primary Results of the EMPA-HEART 2 CardioLink-7 Randomized Clinical Trial

“…These clinical observations have driven a lot of interest to elucidate the mechanisms underlying how SGLT2 inhibitors retard the development and progression of heart failure. 17,57–81 Both direct and indirect cardiac pathways have been postulated to be modulated by SGLT2 inhibitors. For example, SGLT2 inhibitors have been suggested to directly affect cardiac ion channels and regulate pathways involved in cardiomyocyte autophagy, mitophagy, and inflammasome activation.…”

Benefits of Taking Sodium-Glucose Cotransporter 2 Inhibitors in Patients With Type 2 Diabetes Mellitus and Cardiovascular Disease: A Systematic Review

“…With their diuretic-like effect, SGLT2 inhibitors exhibit a similar response to thiazide and loop diuretics, which reduce blood pressure through natriuresis, leading to decreased plasma volume [19][20][21][22][23][24][25][28][29][30].…”

“…Sarak et al conducted a study to assess the effects of empagliflozin on right ventricular parameters and functions by using cardiac MRI (cMRI) among T2DM patients with previous myocardial infarction [ 23 ]. cMRI provides a standard assessment of right ventricular structure and function.…”