Controversies, uncertainties and future research on the treatment of chronic thromboembolic pulmonary hypertension

Abstract

A number of controversies exist regarding the pathophysiology, natural history, diagnosis, and treatment of chronic thromboembolic pulmonary hypertension (CTEPH). Although CTEPH is regarded by many to be a complication of pulmonary embolism (PE) arising subsequent to venous thromboembolism (VTE)-the embolic hypothesis-it has been suggested that PE is rarely the sole cause of CTEPH and that primary arteriopathy with secondary in situ thrombosis may be relevant in the pathogenesis and progression of the disease-the thrombotic hypothesis. A number of lines of evidence support this. Only about half of patients referred with suspected CTEPH have a history of VTE. In addition, data suggest that acute PE is often diagnosed, and possibly misdiagnosed, in patients with preexisting pulmonary artery pathology. There has been much research and debate on the importance of distal arteriopathy in both the initiation and progression of CTEPH. Histopathologic studies have indicated distinct overlap in the microvascular pathology of CTEPH and idiopathic pulmonary arterial hypertension (IPAH), and it has been queried whether class IV CTEPH (increased pulmonary vascular resistance due to distal arteriopathy in the absence of central organized thrombi) and IPAH represent extremes of a disease continuum. Together, these issues may impact on effective diagnosis, preoperative screening criteria for pulmonary endarterectomy surgery, and the likelihood of persistent pulmonary hypertension or even mortality after surgery. They are particularly relevant when considering the possible future use of medical therapies in long-term disease management.