Abstract Body (Do not enter title and authors here): Background: Right ventricle (RV) function is an independent predictor of major adverse cardiac events in patients with known or suspected cardiovascular disease. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) significantly reduce adverse cardiovascular outcomes in HF patients across the complete spectrum of left ventricular ejection fraction (LVEF). The effect of SGLT2i on RV function remains unknown. We hypothesized that SGLT2i reduces severity of RV dysfunction.

Method: We searched Embase, PubMed, and Web of Science from January 2015 to December 2023 for eligible studies. A random-effects model was used to estimate weighted mean differences with 95% CIs of the collected variables. The studies were divided into two subgroups: diabetic patients without diagnosis of HF (preHF), and heart failure patients (HF subgroup). To test whether SGLT2i changes RV function depending on its effect on LV function, correlations between tricuspid annular plane systolic excursion (TAPSE), and LVEF, pulmonary artery systolic pressure (PASP), and left ventricular global longitudinal strain (LVGLS) were performed. We computed Pearson’s correlation coefficient to investigate the association between the standardized mean difference (SMD) of different parameters.

Results: We identified 12 studies where the subjects were treated with SGLT2 inhibitors for 3-6 months. The preHF subgroup showed no statically significant difference in changes of echocardiographic parameters. In the HF subgroup, TAPSE significantly increased (mean=2.34; 95%CI 1.24 to 3.43). There is also statistically significant increase in fractional area change (FAC) (mean=4.16, 95%CI 2.47 to 5.84), and improvement in RV’s longitudinal contraction (RVS) (mean=2.56, 95%CI 1.60 to 3.51) and longitudinal strain of free wall of right ventricle (RVFWS) (mean=-2.81, 95%CI -4.91 to -0.72). TAPSE was positively associated with LVEF and negatively associated with LVGLS. However, these associations were not statistically significant (p > 0.05). The TAPSE changes were not associated with the PASP changes (r = 0.11).

Conclusion: This updated meta-analysis showed that SGLT2 inhibitors improves right ventricular function in heart failure patients. However, it is unclear whether the effect of SGLT2 inhibitors on the RV function is a secondary outcome from their effect on LV or a primary direct effect on RV or a combined effect.