Effect of phosphodiesterase-5 inhibition on SystEmic Right VEntricular size and function. A multicentre, double-blind, randomized, placebo-controlled trial: SERVE

Eur J Heart Fail. 2023 Jul;25(7):1105-1114. doi: 10.1002/ejhf.2924. Epub 2023 Jun 13.

Abstract

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, multicentre superiority trial (NCT03049540) involving 100 adults with systemic right ventricles (33 women, mean age: 40.7 ± 10.7 years), comparing tadalafil 20 mg once daily versus placebo (1:1 ratio). The primary endpoint was the change in right ventricular end-systolic volume after 3 years of therapy. Secondary endpoints were changes in right ventricular ejection fraction, exercise capacity and N-terminal pro-B-type natriuretic peptide concentration. Primary endpoint assessment by intention to treat analysis at 3 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 end-systolic volumes were observed in the tadalafil and the placebo group, and no significant differences between treatment groups (3.4 ml, 95% confidence interval -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.

Conclusions: In this trial in adults with systemic right ventricles, right ventricular systolic function, exercise capacity and neuro-hormonal activation remained stable over a 3-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.

Keywords: Atrial switch operation; Congenitally corrected transposition of the great arteries; Phosphodiesterase-5 inhibitor; Systemic right ventricle; d-Transposition of the great arteries.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cyclic Nucleotide Phosphodiesterases, Type 5 / pharmacology
  • Cyclic Nucleotide Phosphodiesterases, Type 5 / therapeutic use
  • Double-Blind Method
  • Female
  • Heart Failure*
  • Heart Ventricles / diagnostic imaging
  • Humans
  • Middle Aged
  • Stroke Volume
  • Tadalafil / pharmacology
  • Tadalafil / therapeutic use
  • Transposition of Great Vessels* / complications
  • Transposition of Great Vessels* / drug therapy
  • Ventricular Function, Right / physiology

Substances

  • Tadalafil
  • Cyclic Nucleotide Phosphodiesterases, Type 5

Associated data

  • ClinicalTrials.gov/NCT03049540