From Pulmonary Embolism to Chronic Thromboembolic Pulmonary Hypertension: A Pathophysiological Approach

Venous thromboembolism presenting as deep vein thrombosis or pulmonary embolism (PE) remains to be an important cause of mortality and morbidity worldwide. Despite its significance and incidence, compared to many other cardiovascular conditions there are significant gaps in knowledge in many aspects of it, including its pathophysiology. A rare sequela of PE is chronic thromboembolic pulmonary hypertension (CTEPH). This complication has a poor outcome and data is scarce in this field. Many therapeutic approaches are based solely on clinical expertise, which can be explained by the complex and not fully understood pathobiology of this disease. Over the years, many theories have been proposed regarding its genesis. Although generally acute PE is accepted as a trigger for CTEPH, this condition is multifactorial and cannot be explained by recurring PEs only. By reviewing the current evidence, we have demonstrated that thrombus non-resolution in CTEPH is due to multiple mechanisms and predisposing factors including: inflammation, small-vessel disease, impaired angiogenesis, platelet dysfunction, coagulopathies, malignancy, impaired fibrinolysis, genetics and many other components. Based on the current evidence, we aimed to explain the pathophysiology CTEPH, PE and the connection between these two important diseases. Furthermore, we highlight the negative hemodynamic effects of CTEPH and PE on the right ventricle and its role in further exacerbation of these patients.