Pulmonary arterial hypertension with signs of venous/capillary involvement in connective tissue diseases: paradigms and paradoxes.

Abstract

Pulmonary arterial hypertension (PAH) with features of venous and/or capillary involvement, formerly pulmonary veno-occlusive disease (PVOD), represents a rare and severe subset of pulmonary hypertension. While PVOD is typically idiopathic, heritable or drug/toxin-induced, "PVOD-like" features have long been recognised in PAH associated with connective tissue diseases (CTDs), especially systemic sclerosis (SSc). This review synthesises the available evidence on this phenotype, integrating published data with an unreported cohort of 25 patients. Venular remodelling is a frequent histological finding in SSc-PAH lung explants, but high-resolution computed tomography (HRCT) signs of PVOD are inconsistently observed at PAH presentation, reflecting a progression of the lung vasculopathy and/or an unmasking effect of pulmonary vasodilators. Patients often exhibit major functional limitation, profound impairment in gas transfer and severe haemodynamic compromise. Assessing venular involvement in SSc-PAH poses unique challenges, due to possible lung fibrosis on HRCT and differential diagnosis with an occult post-capillary component. Despite the lack of robust evidence, PAH-approved therapies are commonly used, although with caution due to a high risk of pulmonary oedema with pulmonary vasodilators. As these patients also display significant arteriolar involvement, which can benefit from these drugs, dedicated treatment strategies warrant further investigation. Prognosis remains dismal, with a 5-year survival around 45-50%. Similar PVOD-like patterns have also anecdotally been reported in systemic lupus erythematosus, rheumatoid arthritis, mixed connective tissue disease, Sjögren syndrome and inflammatory myopathies, with comparable features. Overall, PVOD-like disease in CTD-PAH constitutes a high-risk phenotype with unresolved pathogenic and management challenges, requiring refined patient stratification and improved therapeutic strategies.