The Prospective Risk Factor Evaluation and Discovery In Chronic Thromboembolic Pulmonary Hypertension Study

Chronic thromboembolic pulmonary hypertension (CTEPH) is due to non-resolution of pulmonary embolism (PE), and is the most serious long-term sequela of PE. Without treatment, CTEPH leads to progressive right heart failure and death. Fortunately, most cases of CTEPH are potentially curable by a surgical procedure in which the chronic thromboembolic material is removed from the pulmonary arterial tree, and for those who are not surgical candidates a novel medical therapy is now available. Multiple studies have shown, however, that the majority of CTEPH cases go undiagnosed, and thus many symptomatic patients are never offered these potentially beneficial treatments. Because persistent dyspnea affects up to 50% of patients who survive an acute PE, selecting which patients should undergo further invasive testing for CTEPH is a difficult clinical problem. In this study, the investigators propose to prospectively follow a cohort of high-risk patients after acute PE until CTEPH is either diagnosed or excluded, and perform serial collection and banking of biospecimens that will allow for prospective and longitudinal screening of biomarkers that might predict future risk of CTEPH. Biomarker screening will initially be focused on a panel of 20 pre-specified plasma proteins with roles in coagulation/fibrinolysis or inflammation, as well as assays of fibrinolysis, as these are processes that existing literature suggests are linked to the pathophysiology of CTEPH. The biorepository created for this study could also be used in the future to perform unbiased screening with proteomic techniques or RNAseq in the hopes of identifying novel biomarkers and novel biological processes that are relevant to the development of CTEPH. As there is no current consensus as to whether structured follow-up after PE to detect signs and symptoms of CTEPH is beneficial, this study also includes an analysis of whether a novel structured follow-up program improves identification of incident CTEPH cases. This study has the potential to dramatically improve post-PE care by facilitating stratification of patients by future risk of CTEPH at the time of acute PE, thus allowing for expert follow-up to be tailored to those patients at highest risk for CTEPH. The investigators hope that these efforts will improve the rate at which CTEPH cases are identified, so that more patients can benefit from existing treatments.