The relationship between pulmonary arterial hypertension-specific drug therapy (PAH-SDT) and mortality in Eisenmenger syndrome (ES) is controversial. We aimed to investigate outcomes of patients with ES and their relationship with PAH-SDT.

Retrospective, observational, nationwide, multicenter, cohort study.

We included 340 patients with ES (genetic syndrome, n=119, 35.3%; pre-tricuspid defect, n=75, 22.1%). Overall, 276 patients (81.2%) received PAH-SDT (monotherapy: endothelin receptor antagonist (ERA) or phosphodiesterase 5 inhibitor (PDE5i), 46.7%; dual therapy: ERA+PDE5i, 40.9%; triple therapy: ERA+PDE5i+prostanoid, 9.1%). Median PAH-SDT duration was 5.5 years [3.0–9.1]. Events (death, lung or heart-lung transplantation) occurred in 95 (27.9%) patients at a median age of 40.5 years [29.4–47.6]. Cumulative occurrence of events was 16.7% [95% CI 12.8–21.6%] and 46.4% [95% CI 38.2–55.4%] at 40 and 60 years of age, respectively. With age at evaluation or time since PAH diagnosis as time scales, cumulative occurrence of events was lower in patients taking one or two PAH-SDTs (P=0.0001 and P=0.004, respectively), with the largest differences in the post-tricuspid defect subgroup (P<0.001 and P<0.02, respectively) versus patients without PAH-SDT. By multivariate Cox analysis with time since PAH diagnosis as the time scale, NYHA/WHO functional class III/IV, lower SaO₂, and pre-tricuspid defect were associated with a higher risk of events (P=0.002, P=0.01, and P=0.04, respectively) and one or two PAH-SDTs with a lower risk of events (P=0.009).

In ES, outcomes are poor but seem better with PAH-SDT. ES with pre-tricuspid defects has worse outcomes despite the delayed onset of the disease.