Molecular Pathophysiology of Chronic Thromboembolic Pulmonary Hypertension: A Clinical Update from a Basic Research Perspective.

Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but severe condition characterized by persistent obstruction and vascular remodeling in the pulmonary arteries following an acute pulmonary embolism (APE). Although APE is a significant risk factor, up to 25% of CTEPH cases occur without a history of APE or deep vein thrombosis, complicating the understanding of its pathogenesis. Herein, we carried out a narrative review discussing the mechanisms involved in CTEPH development, including fibrotic thrombus formation, pulmonary vascular remodeling, and abnormal angiogenesis, leading to elevated pulmonary vascular resistance and right heart failure. We also outlined how the disease's pathophysiology reveals both proximal and distal pulmonary artery obstruction, contributing to the development of pulmonary hypertension. We depicted the risk factors predicting CTEPH, including thrombotic history, hemostatic disorders, and certain medical conditions. We finally looked at the molecular mechanisms behind the role of endothelial dysfunction, gene expression alterations, and inflammatory processes in CTEPH progression and detection. Despite these insights, there is still a need for improved diagnostic tools, biomarkers, and therapeutic strategies to enhance early detection and management of CTEPH, ultimately aiming to reduce diagnostic delay and improve patient outcomes.