Clinical Correlates of a Nonplexiform Vasculopathy in Patients With a Diagnosis of Idiopathic Pulmonary Arterial Hypertension

BACKGROUND: The clinical phenotype of idiopathic pulmonary arterial hypertension (IPAH) patients has changed. Whether subgroups of patients with IPAH have different vascular phenotypes is a subject of debate.

RESEARCH QUESTION: What are the histologic patterns and their clinical correlates in patients with a diagnosis of IPAH or hereditary pulmonary arterial hypertension (PAH)?

STUDY DESIGN AND METHODS: In this this cross-sectional registry study, lung histologic examination of 50 patients with IPAH was assessed qualitatively by two experienced pathologists. In addition, quantitative analysis by means of histopathologic morphometry using immunohistochemistry was performed. Histopathologic characteristics were correlated with clinical and hemodynamic parameters.

RESULTS: In this cohort of 50 patients with IPAH, a plexiform vasculopathy was observed in 26 of 50 patients (52%), whereas 24 of 50 patients (48%) showed a nonplexiform vasculopathy. The nonplexiform vasculopathy was characterized by prominent pulmonary microvascular (arterioles and venules) remodeling and vascular rarefaction. Although hemodynamic parameters were comparable in plexiform vs nonplexiform vasculopathy, patients with nonplexiform vasculopathy were older, more often were male, had a stronger history of cigarette smoking, and lower diffusing capacity of the lungs for carbon monoxide (Dlco) at diagnosis. No mutations in established PAH genes were found in the nonplexiform group.

INTERPRETATION: This study revealed different vascular phenotypes within the current spectrum of patients with a diagnosis of IPAH, separated by clinical characteristics (age, sex, history of cigarette smoking, and Dlco at diagnosis). Potential differences in underlying pathobiological mechanisms between patients with plexiform and nonplexiform microvascular disease should be taken into account in future research strategies unravelling the pathophysiologic features of pulmonary hypertension and developing biology-targeted treatment approaches.