Oxylipins and the Surgical Classification of Chronic Thromboembolic Pulmonary Hypertension

Surgically accessible lesions of chronic thromboembolic pulmonary hypertension (CTEPH) are classified as proximal or distal based on the distribution of thrombus burden in the pulmonary vasculature post operatively. Surgically accessible distal CTEPH lesions typically has a higher risk profile and worse clinical outcomes in less experienced centers, but the underlying molecular differences between proximal and distal CTEPH lesions remain unknown. Oxylipins, a diverse group of bioactive lipid mediators, have previously been implicated in a range of disorders including pulmonary hypertension. Therefore, we sought to characterize oxylipin profiles among patients with proximal and distal operable CTEPH lesions, as well as those with idiopathic pulmonary arterial hypertension (IPAH). We studied 271 patients with proximal operable CTEPH (n=123), distal operable CTEPH (n=74), or IPAH (n=74). Liquid chromatography-mass spectrometry was used to analyze oxylipin profiles in each patient. We found that patients with distal operable CTEPH had elevated levels of proinflammatory oxylipins while those with proximal CTEPH had an increase in procoagulant oxylipins. Notably, the proinflammatory oxylipins elevated in distal operable CTEPH were similarly elevated in IPAH. These findings suggest that distal operable and proximal CTEPH represent heterogenous disease processes. Furthermore, oxylipin profiles may be useful for potential risk stratification and therapeutic targeting in CTEPH.