PurposePatients with pulmonary arterial hypertension (PAH) and additional cardiac or pulmonary comorbidities have a poor prognosis and are frequently excluded from clinical trials. The purpose of this study was to evaluate outcomes of patients with PH secondary to a range of World Symposium on PH (WSPH) groups treated with inhaled treprostinil (iTRE) in a real-world setting. MethodsPatients with PH who were started on treatment with iTRE at Duke University were classified by WSPH Group, and included patients with Group 1, Group 2, Group 3, combined Group 2 & 3 (PH in the setting of left heart failure and chronic lung disease), Group 4, and Group 5 PH. Time to disease worsening, a composite of death, lung transplantation or transition to intravenous prostacyclin, was compared by WSPH Group, and iTRE treatment status using a multivariable Cox proportional hazards model adjusted for age, sex, and REVEAL Lite 2 risk score. Treatment with iTRE was defined as a time-varying covariate. ResultsThe cohort included 270 patients with PH: 30.6% Group 1; 10% Group 2; 32.2% Group 3; 11.1% combined Group 2 & 3; and 15.9% with either Group 4 or 5 PH. At 3-months and 6-months of follow-up, 24.8% and 38.9% of patients respectively were no longer treated with iTRE. Patients who discontinued treatment with iTRE had a significantly higher risk of disease worsening (adjusted HR: 5.02, 95% CI: 3.44 – 7.31). There was no significant difference in disease worsening among WSPH Groups. ConclusionIn a real-world setting, many patients with PH secondary to a range of WSPH Groups tolerated treatment with iTRE. Future studies should phenotype patients with PH based on both comorbidities and therapeutic responsiveness.