Effect of dapagliflozin on left ventricular longitudinal strain and atrioventricular coupling in heart failure with preserved ejection fraction and chronic kidney disease

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), including dapagliflozin, were initially developed for type 2 diabetes mellitus. Despite the established benefits of SGLT2i in heart failure (HF) with preserved ejection fraction (HFpEF), their effects on myocardial deformation (assessed by global longitudinal strain, GLS) and left atrioventricular coupling (quantified by the left atrioventricular coupling index, LACI) in HFpEF patients with concomitant chronic kidney disease (CKD)—hereafter referred to as HFpEF-CKD—remain unclear. This study aimed to evaluate the effects of dapagliflozin on GLS and LACI in this high-risk comorbid population. This prospective cohort study enrolled 259 patients with HFpEF-CKD from September 2023 to October 2024. Participants were assigned to two groups: the dapagliflozin group (dapagliflozin 10 mg/day added to conventional HF and CKD therapy without SGLT2i, n = 138) and the control group (conventional HF and CKD therapy without SGLT2i, n = 121). Conventional and speckle-tracking echocardiography were performed at baseline and 6-month follow-up to assess GLS, LACI, left ventricular ejection fraction (LVEF) and left atrial volume (LAV) parameters, including minimal LAV (LAVmin) and LAV index (LAVI). Compared with controls, dapagliflozin decreased GLS (between-group Δ: -1.34%, 95% CI: -1.72 to -0.97; Cohen’s d = 0.875) and reduced LACI (Δ: -0.07, 95% CI: -0.09 to -0.05; Cohen’s d = 0.855), both p < 0.001. The dapagliflozin group showed greater reductions in LAV parameters (ΔLAVmin: -6.38 ± 9.06 mL vs. -1.25 ± 3.78 mL, p < 0.001; ΔLAVI: -0.82 ± 1.79 mL/m² vs. -0.43 ± 1.57 mL/m², p = 0.075). LVEF remained stable in both groups ( p = 0.264). Multivariable regression analysis confirmed dapagliflozin as an independent predictor for both GLS reduction ( B = -1.335, 95% CI: -1.686 to -1.006, p < 0.001) and LACI reduction ( B = -0.057, 95% CI: -0.074 to -0.040, p < 0.001). In patients with HFpEF-CKD, dapagliflozin improves left ventricular longitudinal function and atrioventricular coupling. The superior sensitivity of novel echocardiographic parameters—GLS, LACI, and LAVmin—supports their clinical utility for monitoring early cardiac functional recovery during treatment.