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

backgroundRight 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.

methodsThis 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.

resultsThe 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 < .001] and more frequently affected by diabetes mellitus (44% vs 22%; P = .002) compared with 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 < .001 and S' +0.48 cm/s, P = .006); whereas no significant differences between-groups were observed for FAC (P = .16). RV GLS at follow-up was significantly improved in the Dapagliflozin group compared with controls (adjusted mean difference -1.54%, P < .001) as well as of the pulmonary-arterial coupling (TAPSE/PASP adjusted differences ranging from +0.07 to +0.17, P = .025). In patients with PH, a significant decrease in PASP [30 (25-34) vs 37 (31-45) mmHg, P < .001] associated with a RVGLS significant improvement [-20 (-22 to -19) vs -19 (-20 to -17) P < .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 < .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 = .013). The rate of 180-days adverse events was significantly higher in control group with respect to Dapaglifozin group (21% vs 8%, P < .01).

conclusionsIn 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).