Dapagliflozin effects on right ventricular function, pulmonary pressure and coupling: a propensity score analysis from the RIVED-HF

BACKGROUND: Right ventricular (RV) dysfunction (RVD) represents a power independent prognostic factor in patients with chronic heart failure (CHF); poor evidence exists about the effect of current guideline directed medical therapy on RVD.We investigated whether dapagliflozin improves right ventricular function, right ventricular-pulmonary arterial coupling and pulmonary artery systolic pressure compared with standard therapy in CHF. METHODS: This is a prospective observational registry with propensity score analysis investigating RV function and right heart failure(RIVED), focused on the effects of Dapagliflozin.Efficacy measures were intra and inter-groups changes from baseline to 6 months in RV end diastolic diameter(RVEDD), tricuspid annular peak systolic excursion(TAPSE), RV global longitudinal strain(RVGLS), fractional area changes(FAC), RV systolic tissue doppler wave(S'), PASP values,TAPSE/PASP,and tricuspid regurgitation(TR).Secondary endpoints were N-terminal pro B-type natriuretic peptide(NTproBNP) levels changes and combined adverse events rate of mortality and hospitalization at 180 days. RESULTS: The final population analysed was of 142 patients,in a balanced dataset consisting of 71 treated with standard HF therapy plus dapagliflozin(Dapa group) and 71 treated with standard therapy without dapagliflozin(control group).Median age was 78 [75-84] years old and 62% of patients were men. Patients in dapa group were younger(76[66-82] vs 82[74-88] years old;p<0.001) and more frequently affected by diabetes mellitus(44% vs 22%; p=0.002) compared to control group. No significant differences were observed between the two groups in terms of gender, renal function, NTproBNP and NYHA class.Over the 6 months follow-up,the Dapa group showed a significant improvement of RV function compared with controls(TAPSE +1.03 mm,p < 0.001 and S' +0.48 cm/s,p = 0.006); whereas no significant differences between-groups were observed for FAC(p = 0.16).RV GLS at follow-up was significantly improved in the Dapagliflozin group compared with controls(adjusted mean difference -1.54%, p < 0.001). as well as of the pulmonary-arterial coupling (TAPSE/PASP adjusted differences ranging from +0.07 to +0.17,p = 0.025).In patients with PH, a significant decrease in PASP(30[25-34] vs 37[31-45] mmHg,p<0.001) associated with a RVGLS significant improvement (-20 [-22 - -19] vs -19 [-20 - -17] p<0.001) in the Dapagliflozin group were observed.TAPSE/PASP ratio was significantly improved in Dapagliflozin group with respect to the control group(0.67[052-0.78] vs 0.51[0.42-0.61], p<0.001).Secondary endpoints analysis revealed that NT-proBNP levels were significantly improved from baseline to follow-up only in dapaglifozin group(from 938 to 726 pg/ml p = 0.013).The rate of 180-days adverse events was significantly higher in control group with respect to Dapaglifozin group(21% vs 8%, p<0.01). CONCLUSIONS: In a real-world HF cohort,dapagliflozin was associated with improved RV morphology and function, lower PASP,and better RV-PA coupling,suggesting a direct haemodynamic and RV-targeted benefit beyond LV remodelling.Trial Registration: (ClinicalTrials.gov Identifier: NCT06002321).