Outcome of adults with Eisenmenger syndrome treated with drugs specific to pulmonary arterial hypertension: A French multicentre study

Abstract

Background The relationship between pulmonary arterial hypertension-specific drug therapy (PAH-SDT) and mortality in Eisenmenger syndrome (ES) is controversial. Aims To investigate outcomes in patients with ES, and their relationship with PAH-SDT. Methods Retrospective, observational, nationwide, multicentre cohort study. Results We included 340 patients with ES: genetic syndrome (n = 119; 35.3%); pretricuspid defect (n = 75; 22.1%). Overall, 276 (81.2%) patients 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 years]. 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]. The cumulative occurrence of events was 16.7% [95% confidence interval 12.8–21.6%] and 46.4% [95% confidence interval 38.2–55.4%] at age 40 and 60 years, 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 multivariable Cox analysis, with time since PAH diagnosis as time scale, New York Heart Association/World Health Organization functional class III/IV, lower peripheral arterial oxygen saturation and pretricuspid 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). Conclusions Outcomes are poor in ES, but seem better with PAH-SDT. ES with pretricuspid defects has worse outcomes despite the delayed disease onset.