Impact of PAH-specific vasodilator therapy on long-term survival in eisenmenger syndrome: a prospective cohort study

Background Eisenmenger syndrome (ES) is a serious complication of unrepaired congenital systemic to pulmonary shunt lesions, associated with progressive pulmonary vascular disease and reduced life expectancy. Prospective real-world data from developing countries on the long-term survival impact of targeted pulmonary arterial hypertension (PAH) therapy in ES remain limited. Purpose To evaluate the impact of PAH-specific pulmonary vasodilator therapy on long-term survival in patients with Eisenmenger syndrome enrolled in a prospective registry. Methods The Eisenmenger Registry is an ongoing prospective registry enrolling consecutive adult patients with ES presenting to our institution since August 2018. For this analysis, patients enrolled until February 2026 were included. Baseline demographic, clinical, functional, and hemodynamic data were recorded. Patients received PAH-specific vasodilator therapy at enrollment or during follow-up, or remained on supportive therapy alone. Long term survival and clinical outcomes were compared between treatment groups. Results A total of 113 patients were included (median age 25 years [IQR 21–32]; 73% female). Lesion types comprised pre-tricuspid (22%), post-tricuspid (60%), and complex defects (18%). Median follow-up was 2.3 years (IQR 0.7–3.7). All-cause mortality occurred in 23.9% (n=27), with congestive cardiac failure as the leading cause of death (55.6%, 15/27), followed by cerebrovascular accidents (14.8%, 4/27), and pregnancy-related complications and infections (each 7.4%, 2/27). Overall, 67.2% (76/113) of patients experienced at least one complication, most commonly heart failure (31/113; 26.5%), followed by hyperviscosity and hemoptysis (27/113; 23.8%). Overall, 77 patients received PAH-specific vasodilator therapy, while 36 received supportive therapy alone. Table 1 compares baseline characteristics and outcomes between patients who received vasodilator therapy and those who did not. On Kaplan–Meier analysis (Figure 1), 2-year survival was significantly higher in the vasodilator group compared with supportive therapy (85.7% [95% CI 75.7–91.8] vs 54.3% [95% CI 36.7–69.0]; log-rank p=0.0002). After multivariable adjustment for age, sex, systolic blood pressure, baseline oxygen saturation, and right ventricular function, vasodilator therapy remained independently associated with lower mortality (adjusted HR 0.18, 95% CI 0.07–0.50; p<0.001). Conclusion In this prospective registry of patients with Eisenmenger syndrome, PAH-specific vasodilator therapy was independently associated with improved survival compared with supportive therapy alone. These real-world findings from a developing-country cohort suggest a meaningful survival benefit with targeted PAH therapy and support its early use in appropriately selected patients with ES.