P1500Effects of empagliflozin on cardiac function in patients with type 2 diabetes mellitus: echocardiographic substudy of the EMPA-HEART cardiolink-6 trial

Abstract Background The EMPA-HEART trial showed a reduction in left ventricular (LV) mass index by cardiac MRI at 6 months in patients treated with Empagliflozin vs placebo. A secondary analysis of key echocardiographic parameters was performed to provide further insight into the mechanism of LV remodeling. Methods All patients enrolled prospectively underwent transthoracic echocardiography (TTE) at baseline and at 6 months. Measurements were performed according to the American Society of Echocardiography guidelines. Key outcomes of interest included changes in diastolic function and right ventricle parameters at 6 months in patients treated with Empagliflozin vs placebo. Results A total of 97 patients were enrolled (49 treated with Empagliflozin and 48 in the placebo group). There was no significant difference in the change in average E/E' at 6-months in the Empagliflozin group vs placebo (−0.4 vs +0.2, adjusted difference −0.2, 95% CI [−1.3 to 0.82], p=0.7) Similarly, there was no difference between the groups in secondary TTE parameters (Table 1). Subgroup analyses showed no benefit among patients with baseline LVEF >50% vs. ≤50%, and baseline LV mass index ≥60 g/m2 vs <60 g/m2. Echocardiographic Parameter Placebo (n=48) Empagliflozin (n=49) Adjusted Difference Between Groups 95% CI P-Value Baseline 6 months Change Baseline 6 months Change LVEF (%)* 55.5 (8.7) 54.3 (8.9) −1.0 (6.5) 58.0 (7.5) 59.1 (8.57) 0.72 (5.1) 2.2 (−0.2, 4.7) 0.1 Diastolic Parameters: Average E/e' 10.1 (3.1) 10.3 (2.5) 0.2 (3.0) 10.6 (3.0) 10.5 (3.6) −0.4 (2.5) −0.2 (−1.3, 0.8) 0.7 Medial E/e' 12.3 (3.9) 12.5 (3.6) 0.1 (3.7) 12.6 (4.2) 12.6 (5.2) −0.3 (3.3) −0.3 (−1.7, 1.1) 0.7 Lateral E/e' 8.0 (2.8) 8.2 (2.2) 0.2 (2.7) 8.7 (2.6) 8.4 (2.5) −0.4 (2.7) −0.1 (−1.0, 0.8) 0.8 E velocity (cm/sec) 68.6 (15.2) 70.6 (14.7) 1.8 (15.4) 74.4 (18.2) 71.2 (16.8) −3.2 (15.1) −2.3 (−7.9, 3.3) 0.4 A velocity (cm/sec) 74.7 (17.9) 77.9 (18.8) 2.9 (15.9) 76.2 (16.5) 75.8 (14.5) −1.4 (11.7) −3.5 (−8.9, 1.6) 0.2 LA volume index (mL/m2) 32.7 (7.9) 30.8 (8.1) −2.0 (6.7) 30.2 (6.7) 28.7 (5.5) −1.6 (6.5) −0.9 (−3.4, 1.6) 0.5 RV Parameters: TAPSE (cm) 1.8 (0.5) 1.8 (0.4) 0.1 (0.4) 2.0 (1.2) 1.8 (0.4) −0.3 (1.4) −0.1 (−0.3, 0.1) 0.3 RV S' TDI (cm/sec) 10.9 (2.9) 10.6 (2.5) −0.1 (2.2) 10.4 (2.7) 10.2 (2.6) −0.4 (2.0) −0.3 (−1.2, 0.5) 0.4 *Measured by cardiac MRI. LA, left atrium; LVEF, left ventricular ejection fraction; RV, right ventricle; TAPSE, tricuspid annular plane systolic excursion; TDI, tissue Doppler imaging. Data expressed as mean (standard deviation). Conclusion This study showed no significant change in key echocardiographic parameters in patients treated with Empagliflozin, suggesting that changes in loading conditions induced by empagliflozin (i.e. preload) do not mediate the reduction in LV mass.