Long-term outcome of patients with Eisenmenger syndrome receiving pulmonary arterial hypertension-targeted therapy.

BACKGROUND: Eisenmenger syndrome (ES) is a severe and fatal complication of uncorrected congenital heart disease characterised by the development of pulmonary arterial hypertension (PAH) due to chronic left-to-right shunting. Despite the increasing use of PAH-targeted therapies, evidence of their long-term effects on the survival of patients with ES remains limited. METHODS: We reviewed 101 consecutive adult patients with ES (69% female; mean age, 34±18 years) who were referred to our centre between December 1972 and December 2023. We investigated the clinical, haemodynamic and treatment data from medical records. The primary outcome measure was transplantation-free survival. The effect of PAH-targeted therapy on transplantation-free survival was analysed using a time-dependent Cox proportional hazards model. RESULTS: Among the 101 patients, 57 (56%) received PAH-targeted therapy (PAH therapy group), while 44 (44%) did not (treatment-naïve group). In the PAH therapy group, 75% received combination therapy (25%, monotherapy; 56%, dual-combination therapy; and 19%, triple-combination therapy). The median follow-up time since diagnosis of ES was 8.8 (IQR: 4.1-22.3) years. The median follow-up transplantation-free survival rates were significantly higher in the PAH therapy group than in the treatment-naïve group (100%, 100% and 89% vs 95%, 66% and 53% at 1, 5 and 10 years, respectively; p<0.001). In the multivariate analysis adjusting for age, sex, WHO functional class (III/IV vs I/II) and PAH-targeted therapy, PAH-targeted therapy was independently associated with improved transplantation-free survival (adjusted HR=0.275, 95% CI 0.132 to 0.572). CONCLUSIONS: The long-term survival of patients with ES who received PAH-targeted therapy was better than that of those who did not. These results support the benefits of PAH-targeted therapies in this population while underscoring the need for large-scale studies to better define optimal treatment strategies.