Association of early dapagliflozin initiation with subclinical changes in cardiac function during anticancer therapy
Subclinical cardiac dysfunction involving myocardial deformation, diastolic mechanics, left atrial (LA) remodeling may develop during cardiotoxic anticancer therapy, while the impact of early cardioprotective intervention in routine practice remains unclear. To evaluate the association between early dapagliflozin initiation and 12-month subclinical changes in left ventricular (LV) mechanics and LA structure and function during anticancer therapy. This multicenter retrospective study included 149 patients with HER2-positive breast cancer treated with anthracycline-based chemotherapy followed by trastuzumab across four centers. Dapagliflozin 10 mg once daily was prescribed at the treating physician’s discretion. Patients were classified as early dapagliflozin (≤3 months; n=67) versus no dapagliflozin use (n=82). Transthoracic echocardiography was performed at baseline, 6, 12 months. LV global longitudinal strain (GLS), tissue Doppler e′ velocities, average E/e′, LV ejection fraction (LVEF), indexed LA volumes (LAVmax, LAVmin) with total LA emptying function (LAEF) were assessed. Longitudinal changes were analyzed using linear mixed-effects models adjusted for baseline variables. Baseline clinical and echocardiographic characteristics were comparable between groups. Over 12 months, GLS deteriorated from −20.3 ± 1.9% to −17.9 ± 2.1% in the early dapagliflozin group, compared with −19.6 ± 2.1% to −15.8 ± 2.5% in patients without dapagliflozin (p<0.001). Average E/e′ increased from 9.8 ± 2.0 to 12.5 ± 2.4 versus 10.6 ± 2.3 to 15.3 ± 2.9, respectively (p<0.001). LAEF declined from 62.1 ± 7.8% to 56.2 ± 7.9% with early dapagliflozin and to 47.1 ± 9.8% without dapagliflozin (p<0.001). Indexed LAVmin increased from 9.5 ± 3.8 to 13.0 ± 4.5 ml/m² versus 10.8 ± 4.1 to 18.1 ± 5.8 ml/m², respectively (p<0.001). LVEF remained within the normal range in both groups throughout follow-up. Early dapagliflozin initiation during anthracycline–trastuzumab therapy was associated with better preservation of LV mechanics and LA remodeling over 12 months.