Effects of Dapagliflozin on myocardial performance in non-diabetic patients with Heart failure with reduced and mid-range ejection fraction (DAPA ECHO trial)

Abstract Background Sodium-glucose cotransporter type-2 inhibitors (SGLT2i) showed to reduced morbidity andmortality in HF patients. The aim of this study was to assess potential effects of dapagliflozin in non-diabetic patients with heart failure (HF) with reduced and mildly reduced ejection fraction (HFrEF and HFmrEF) on cardiac function assessed by speckle tracking echocardiography (STE). Methods This randomized, prospective, single-center, open-label trial compared consecutive non-diabetic outpatients with HFrEF or HFmrEF receiving dapagliflozin with patients treated with optimal medical therapy (OMT) except SGLT2i (Fig.1). Primary endpoint was the modification of left ventricular (LV) global longitudinal strain (GLS), diastolic function (as peak atrial longitudinal strain, PALS) and right ventricular (RV) function by STE from baseline to 6 months. Cardiovascular events and parameters of congestion were assessed as safety-exploratory endpoints. Results Overall, 88 patients (38% HFmrEF) were enrolled and randomized to start dapagliflozin on top of OMT (n=44) or to continue with OMT (n=44). All STE values improved in dapagliflozin group after 6 months, while there was a non-significant improvement in OMT group (Fig.1). Moreover, when comparing the modification of STE parameters at follow up in HFrEF and HFmrEF patients, only the main treatment effect resulted statistically significant in both groups (p<0.0001), indicating a significant difference between dapagliflozin and OMT. Conclusions This study provided randomized data on the beneficial effect of dapagliflozin in non-diabetic patients with HFrEF and HFmrEF in terms of myocardial performance measured by the most sensitive echocardiographic technique i.e. STE. This suggests its usefulness for LV reverse remodeling and better quality of life in patients with HFrEF and HFmrEF.