Outcome and prognostic factors in patients with adult congenital heart disease and pulmonary vascular disease: insights from a nationwide cohort of 1,067 patients

Background Pulmonary vascular disease (PVD) and pulmonary hypertension (PH) are associated with considerable morbidity and mortality in adults with congenital heart disease (ACHD). In PVD especially patients in univentricular circulation represent a complex and expanding high-risk population. Contemporary real-world data defining phenotype and survival determinants remain scarce. Purpose To characterise baseline clinical features of ACHD-associated PH/PVD in a nationwide cohort and to identify independent predictors of all-cause mortality. Methods This retrospective cohort study analysed data of a national register for congenital heart defects. Patients enrolled until November 2025 were screened for CHD-associated PH (CHD-PH) and univentricular PVD (UNIV-PVD) using large language models applied to the entire register structure. Clinical, laboratory and echocardiographic data were extracted from pseudonymised records via structured and AI-assisted review. The primary endpoint was all-cause mortality. Univariable Cox regression identified candidate predictors, followed by multivariable modelling. Kaplan–Meier analysis compared survival between CHD-PH and UNIV-PVD. Results A total of 1,067 patients (54.0% female, 972 CHD-PH and 95 UNIV-PVD (predominantly Fontan physiology)) were included. Patients with UNIV-PVD were younger, more frequently cyanotic, had lower resting oxygen saturation and a higher prevalence of liver cirrhosis (all p≤0.035, Table 1). During follow-up 304 deaths occurred. Survival was significantly impaired in UNIV-PVD compared with CHD-PH (log-rank p=0.006, Figure 1). In univariable analysis, strong predictors of mortality were NYHA class IV (hazard ratio (HR) 9.40), dyspnoea at rest (HR 6.41), ascites (HR 8.30), chronic kidney disease (HR 4.34), liver cirrhosis (HR 4.52), syncope and lower oxygen saturation (all p≤0.004). Echocardiographic markers associated with mortality included aortic valve stenosis (HR 6.59), increased septal thickness (HR 1.10/mm), larger left atrial area (HR 1.02/cm²), increased LV systolic diameter (HR 1.04/mm), reduced LV ejection fraction (HR 0.98/%), reduced fractional shortening (HR 0.96/%), pleural effusion (HR 3.20), right atrial dilation (HR 1.44), elevated RV systolic pressure (HR 1.01/mmHg) and moderate tricuspid regurgitation (all p≤0.03). In multivariable analysis, independent predictors were lower oxygen saturation (HR 0.95 per 1% increase), older age (HR 1.03/year), NYHA IV (HR 4.50), syncope (HR 3.14; all p<0.001), chronic kidney disease (HR 2.37; p=0.001), ascites (HR 2.52; p=0.046) and univentricular PVD phenotype (HR 2.41; p=0.012). Conclusions Univentricular PVD constitutes a distinct, high-risk phenotype with markedly impaired survival. Mortality is driven by hypoxaemia, advanced functional limitation, organ dysfunction and univentricular physiology, underscoring the need for phenotype-specific risk stratification in CHD-associated pulmonary vascular disease.