Identification of pulmonary arterial hypertension patients with venous or capillary involvement

While therapeutic advances have improved survival for patients with Group 1 pulmonary arterial hypertension (PAH), patients with Group 1.5 "PAH with features of venous/capillary involvement" (formerly pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis, now collectively termed PVOD/PCH) remain underrecognized, develop serious complications from usual PAH therapy titrations, and suffer high mortality awaiting necessary lung transplant. Identifying PVOD/PCH early before therapy initiation could aid management and expedite transplant referral.

We aimed to develop a likelihood score distinguishing PVOD/PCH from other forms of PAH using clinical variables.

Due to low PVOD/PCH prevalence and no dedicated registries, we leveraged published case-control/case-series studies to assess the ability of several clinical variables to discriminate PVOD/PCH from PAH. From pooled literature-derived data, we performed sensitivity/specificity and simulation-based receiver operating characteristic (ROC) analyses to estimate variable performance. Top-performing variables formed a PVOD/PCH likelihood score, which had its accuracy tested for distinguishing histopathology-confirmed PVOD/PCH cases (n = 37) from PAH controls (n = 60) in 3 cohorts of transplant-eligible patients from the United States, Spain, and the Netherlands.

DLCO, 6-minute walk desaturation, PaO2, sex, smoking history, computed tomography (CT) septal line thickening, and CT lymphadenopathy had the highest sensitivity and specificity performance and were incorporated into the PVOD score. Across test cohorts, the score achieved a ROC area under the curve of 0.97 (95% CI, 0.93-1.00) for discriminating PVOD/PCH and it retained accuracy when data were missing.

This score could facilitate early PVOD/PCH identification in incident PAH, potentially helping expedite transplant referral and informing therapy initiation/titration decisions.