The genetics of chronic thromboembolic pulmonary hypertension: no longer a stab in the dark

Extract Chronic thromboembolic pulmonary hypertension (CTEPH) is technically a rare form of pulmonary hypertension, with an incidence of 5–13 cases per million inhabitants per year, most often developing as a complication of acute pulmonary embolism (PE) [1]. Therapeutic advances over recent decades have dramatically transformed its prognosis, and now allow for a more personalised medicine approach. These include multimodal treatment options such as pulmonary endarterectomy, balloon pulmonary angioplasty and pharmacological therapies targeting endothelial dysfunction. Yet, the underlying pathophysiology of CTEPH remains incompletely understood and no work to date has been able to address secondary prevention in the well-defined at-risk populations. Mechanisms such as predisposition to thrombus formation, aberrant fibrinogen structure and thrombus resolution, inflammatory thrombosis, dysregulated intrathrombus angiogenesis, and possible in situ thrombosis have been proposed [1]. Only a minority of patients who experience an acute PE eventually develop CTEPH, suggesting a role for individual susceptibility, possibly of genetic origin.