Imaging-based Pulmonary Hypertension Phenotypes in Connective Tissue Disease-related Interstitial Lung Disease

BACKGROUND: Patients with interstitial lung disease related to connective tissue disease (CTD-ILD) may develop pulmonary hypertension (PH) through pulmonary parenchymal destruction and chronic hypoxia or via endovascular changes driven by their underlying autoimmunity. Distinguishing which process - parenchymal or vascular - is the primary cause has important therapeutic and prognostic implications. RESEARCH QUESTION: Can chest imaging be used to systematically classify patients with CTD-ILD and PH as having a parenchymal or vascular PH phenotype? STUDY DESIGN AND METHODS: Chest computed tomography (CT) was used to classify 275 adult patients with CTD-ILD and PH in the Johns Hopkins ILD and PH registries as having a parenchymal or vascular PH phenotype. CT-based PH phenotypes were determined using a validated ILD severity staging tool which involves visual inspection of the percentage of lung affected by CTD-ILD. The primary outcome was time to clinical worsening (defined as a composite of physiologic worsening, hospital admission for a pulmonary or cardiac diagnosis, lung transplantation, or death) which was compared between the two phenotypes. Secondary outcomes included comparisons of baseline cardiopulmonary testing, time to physiologic worsening, time to hospital admission, and time to lung transplantation or death. Clinical outcomes were also compared between the CT-based PH phenotypes and the conventional World Symposium on PH (WSPH) group classifications. RESULTS: Patients with CTD-ILD and the parenchymal PH phenotype were 1.76 times more likely to experience clinical worsening than those with the vascular phenotype. They were also more likely to experience physiologic worsening, hospitalization, and lung transplantation or death. CT-based PH phenotypes were more closely associated with clinical outcomes than the WSPH group classifications. INTERPRETATION: Patients with CTD-ILD and the parenchymal PH phenotype have worse clinical outcomes than those with the vascular PH phenotype. CT-based PH phenotypes may characterize patients' risk for clinical worsening more reliably than the WSPH groups.