Current concepts in the pathogenesis of chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by fibrotic obstruction of the proximal pulmonary arteries, and it is believed to result from incomplete thrombus resolution after acute pulmonary embolism. While treatment for this condition with surgery and medical therapy has improved outcomes, our understanding of the molecular mechanisms underlying CTEPH is incomplete. Numerous risk factors have been associated with the development of CTEPH, including but not limited to acquired thrombophilias and chronic inflammatory states. A minority of patients with CTEPH have an abnormal fibrin structure that may delay thrombus resolution. Recently, examination of resected scar material in patients with CTEPH has suggested that deficient angiogenesis may play a role in thrombus nonresolution, and there is increasing interest in factors that drive intravascular scar formation. An additional challenge in CTEPH research is understanding the etiology and implications of the small-vessel disease present in many patients. Future work will likely be directed at understanding the pathways important to disease pathogenesis through further examinations of resected tissue material, continued work on animal models, and genomic approaches to identify alterations in gene expression or gene variants that may distinguish CTEPH from other forms of pulmonary hypertension.