Effect of phosphodiesterase-5 inhibition on SystEmic Right VEntricular size and function - a multi-center, double-blind, randomized, placebo-controlled trial - SERVE

BACKGROUND AND AIMS In adults with congenital heart disease and systemic right ventricles, progressive right ventricular systolic dysfunction is common and is associated with adverse outcomes. Our aim was to assess the impact of the phosphodiesterase-5-inhibitor tadalafil on right ventricular systolic function. METHODS AND RESULTS This was a double-blind, randomized, placebo-controlled, multi-center superiority trial (NCT03049540) involving 100 adults with systemic right ventricles (33 women, mean age: 40.7 years, SD 10.7), comparing tadalafil 20mg once daily versus placebo (1:1-ratio). Primary endpoint was the change in right ventricular endsystolic volume after three years of therapy. Secondary endpoints were changes in right ventricular ejection fraction, exercise capacity and NT-proBNP-concentration. Primary endpoint assessment by intention to treat analysis at three years of follow up was possible in 83 patients (42 patients in the tadalafil group and 41 patients in the placebo group). No significant changes over time in right ventricular endsystolic volumes were observed in the tadalafil and the placebo-group, and no significant differences between treatment groups (3.4ml, 95% CI, -4.3 to 11.0, p=0.39). No significant changes over time were observed for the pre-specified secondary endpoints for the entire study population, without differences between the tadalafil and the placebo-group. CONLCUSIONS In this trial in adults with systemic right ventricles, right ventricular systolic function, exercise capacity and neuro-hormonal activation remained stable over a three-year follow-up period. No significant treatment effect of tadalafil was observed. Further research is needed to find effective treatment for improvement of ventricular function in adults with systemic right ventricles. This article is protected by copyright. All rights reserved.