Hemodynamic and Thrombotic Vulnerability in Pulmonary Arterial Hypertension at High Altitude: Multivariable Predictors of Mortality

Background and Objectives: Pulmonary hypertension (PH) remains associated with substantial mortality despite advances in treatment. Although prognostic factors have been widely described at sea level, their behavior in populations living at high altitude remains insufficiently characterized. This study aimed to identify factors associated with mortality during follow-up in patients with Group 1 PH residing at high altitude. Materials and Methods: A retrospective cohort study was conducted including patients with confirmed Group I PH diagnosed by right heart catheterization and treated between 2017 and 2022. Clinical, functional, and hemodynamic variables were analyzed. A penalized logistic regression model using Elastic Net methodology was applied to identify variables associated with five-year mortality. Results: A total of 165 patients were included, with a mean age of 41 years (SD 13.93), and 84.2% were women. Among PH etiologies, congenital heart disease was the most frequent cause (50.3%), followed by idiopathic PH (33.3%) and connective tissue disease-associated PH (12.7%). Five-year mortality was 13.3% (22/165). Idiopathic pulmonary hypertension was significantly more frequent among deceased patients compared to survivors (13/22 [59.1%] vs. 42/143 [29.4%], p = 0.025). Mortality was associated with acute pulmonary embolism, greater smoking burden, worse functional class, and adverse hemodynamic parameters. In multivariable analysis, acute pulmonary embolism (coefficient 0.196; OR 1.216; 95% CI 1.16–1.27; p < 0.001), ESC/ERS risk stratification (coefficient 0.158; OR 1.171; 95% CI 1.08–1.26; p < 0.001), pulmonary vascular resistance > 25 wood units (coefficient 0.180; OR 1.198; 95% CI 1.13–1.26; p < 0.001), and age ≥ 65 years (coefficient 0.171; OR 1.187; 95% CI 1.10–1.27; p < 0.001) were identified as risk factors, while female sex showed a protective effect (coefficient −1.041; OR 0.353; 95% CI 0.33–0.37; p < 0.001). Conclusions: In patients with Group 1 PH living at high altitude, several clinical, functional, and hemodynamic variables were associated with increased mortality, including acute pulmonary embolism, elevated pulmonary vascular resistance, advanced age, and intermediate-high risk stratification. Female sex was associated with lower mortality.