Unveiling the true burden of hospitalizations in pulmonary arterial hypertension: a comprehensive follow-up analysis

Background Hospitalizations are frequent in pulmonary arterial hypertension (PAH) and carry major prognostic implications. Yet, most studies focus only on the first admission, potentially underestimating the cumulative clinical burden and its long-term impact. Purpose To comprehensively characterize all hospitalizations during long-term follow-up in a real-world PAH cohort, differentiating PAH-related from unrelated causes and assessing their prognostic significance. Methods We retrospectively analysed all consecutive patients with confirmed PAH followed at a tertiary Pulmonary Hypertension Unit. All hospital admissions during follow-up were systematically reviewed and classified as PAH-related or unrelated. Hospitalizations for maternal delivery were excluded. Baseline characteristics, aetiology, and survival data were collected. Mean follow-up was 8.2 ± 5.9 years. Results Eighty-two patients were included, most were female (69.5%). The predominant aetiologies were congenital heart disease (32.9%), idiopathic PAH (20.7%), connective tissue disease (17,1%), and HIV-associated PAH (14.6%). During follow-up, 85.4% of patients were hospitalized at least once and 80% had ≥2 admissions. PAH-related hospitalizations occurred in 70.7% of patients, mainly for acute right heart failure (63.8%), therapy escalation (11.8%), right heart catheterization (9.9%), initiation of intravenous therapy (8.7%), or central line procedures (5.8%). PAH-unrelated hospitalizations affected 45.1% of patients, driven by respiratory failure (30.4%), non–line-related infections (19.1%), pneumonia (17.1%), surgical procedures (12.3%), and gastrointestinal disorders (12.3%). Overall mortality reached 40.2%. The coexistence of an acute heart failure admission and any PAH-unrelated hospitalization independently predicted reduced 5-year survival (HR 1.6; 95% CI 1.2–2.9; p = 0.01). Conclusions Recurrent hospitalizations are almost universal in PAH, encompassing both cardiac and non-cardiac causes. PAH-unrelated admissions represent a major and often overlooked component of disease burden. Their occurrence, particularly when combined with cardiac decompensation, is associated with worse long-term survival. These findings highlight the need for an integrated, multidisciplinary strategy aimed at preventing both PAH-related and unrelated hospitalizations to improve prognosis and quality of life in this vulnerable population.