Dapaglifozin in adults with a systemic right ventricle:initial results from the DAPA-SERVE trial

Abstract Background Sodium-glucose Cotransporter-2(SGLT2) inhibitors are currently recommended as first line therapy for all patients with heart failure with reduced ejection fraction (HFrEF).Adults with a systemic right ventricle (sRV) may develop progressive systolic dysfunction during follow-up. Optimal medical therapy for HFrEF remains still to be determined in this complex population. Purpose We aimed to assess safety and evaluate potential clinical benefit of dapagliflozin in patients with a sRV compared to standard medical treatment for HF. Methods Inclusion criteria were:age ≥ 18 years; transposition of the great arteries (TGA) following Senning/Mustard repair or congenitally corrected TGA, sRV EF ≤ 40%, already on optimized medical therapy including sacubitril/valsartan for at least 3 months. Exclusion criteria were: systolic blood pressure (SBP) <90 mmHg, glomerular filtration rate (GFR)<30ml/min and univentricular physiology. All eligible patients attending our tertiary center for adult congenital heart disease were randomly assigned to the treatment or control group. Patients in the treatment arm were prescribed 10 mg dapagliflozin o.d. on top of their medical therapy, while control group continued standard therapy. Patients were scheduled for a structured follow-up including clinical evaluation, blood test, echocardiography, and 6 minute-walking at 6 months from study inclusion for both groups. Results Fifty patients (41±11 years, 54% male, 64% TGA) met the inclusion criteria: 25(50%) were started on 10 mg dapagliflozin. There was no significant difference in terms of age (p=0.4), sex(p=0.1), anatomy(p=0.2) and baseline sRV EF (p=0.2). Up to February 2023, 14 patients in the treatment group and 13 controls completed the 6-month follow-up. Clinical and echocardiographic findings at baseline and at 6-month in the treatment group are summarized in Table1: dapagliflozin was well tolerated and no major adverse events were reported. Treatment did not impact on the systolic blood pressure and renal function. However a significant improvement in the sRV freewall global longitudinal strain(GLS) was found (-15.8±3 Vs -18.3±3; p=0.03). Differences in main echocardiographic indices of sRV systolic function between baseline and follow-up in the two arms are shown in Table2: treatment resulted in significant positive changes of sRV FAC, GLS, and free wall GLS compared to the group on standard therapy. Conclusions Initial results from the ongoing single-centre DAPA-SERVE trial provided reassuring data on the safety profile of dapagliflozin in patients with a sRV. Furthermore, significant improvement of echocardiographic indices of sRV function in patients on dapagliflozin compared to those on standard medical therapy was demonstrated at 6-month. Longer follow-up is warranted to determine the clinical impact of those positive changes and to shed light on the potential benefit of SGLT2 inhibitors use on top of standard therapy in this complex population.