DAPAgliflozin‐Related Cardiac REverse Remodeling by 2D and 3D Echocardiography in OptiMally Treated HFrEF Patients: The DAPA‐REM Study

Purpose: Sodium-glucose cotransporter-2 inhibitors promote cardiac reverse remodeling in heart failure (HF), yet data integrating two-dimensional and three-dimensional echocardiography (2DE and 3DE, respectively) in optimally treated HFrEF populations are limited. This study aimed to evaluate heart chambers size and function by 2D/3DE after dapagliflozin initiation, and to explore whether baseline estimated glomerular filtration rate (eGFR) or myocardial fibrosis on cardiac magnetic resonance (CMR) influence reverse remodeling. Methods: Seventy-five patients with LVEF ≤ 40% on guideline-directed therapy were prospectively enrolled. Echocardiographic and clinical data were collected at baseline and 6-month follow-up (6MFU) after introduction of dapagliflozin 10 mg daily. Sub- analyses were performed according to eGFR ( < 45 vs. ≥ 45 mL/min/1.73 m2 ) and extent of late gadolinium enhancement (LGE) on CMR. Results: After 6MFU, left ventricular (LV) end-diastolic and end-systolic volumes reduced, and LVEF increased as assessed by both 2DE (respectively: 88[72–122] vs. 92[79–122]mL/m2 , 58[42–80] vs. 57[48–88]mL/m2 , 36.6 ± 8.8 vs. 34.5 ± 7.7%; p < 0.001) and 3DE (respectively: 100[79–140] vs. 108[90–136]mL/m2 , 64[46–82] vs. 69[55–93]mL/m2 , 37.4 ± 8.7 vs. 34.4 ± 7.9%; p < 0.001). No significant association between eGFR and the magnitude of LV reverse remodeling was detected, while CMR analyses suggested a possible inverse correlation between LGE burden and improvement in 2D LVEF. LV diastolic function improved (grade ≥ 2 diastolic dysfunction: 4.7% vs. 18.7%; p = 0.015), along with systolic pulmonary artery pressure (25[23–29] vs. 27[24–29]mmHg; p = 0.037). Conclusion: In optimally treated HFrEF patients, LV size and systolic and diastolic function significantly improved during the 6MFU following dapagliflozin initiation. No significant differences in the magnitude of LV reverse remodeling were detected according to eGFR or LGE burden.