Chronic thromboembolic disease is associated with exercise-induced pulmonary hypertension and functional right ventricle deterioration

Abstract

Abstract Background and Aim Chronic thromboembolic pulmonary disease (CTED) is a progressive disease caused by a wall-adherent, fibrotic thrombus in the pulmonary circulation persisting despite oral anticoagulation and despite vascular remodeling of the small arteries. Despite normal pulmonary hemodynamics at rest, exercise intolerance and dyspnea have been reported. Drivers and risk factors, as well as the clinical impact of CTED, are not yet adequately characterized. We evaluated clinical factors predictive of the development of postthrombotic pulmonary disease in a cohort of patients with a history of acute pulmonary embolism on oral anticoagulant therapy. We also evaluated its impact on functional capacity, pulmonary haemodinamics at rest and after exercise and right ventricle morphology and function. Methods We compared 33 consecutive patients with a history of acute pulmonary embolism and normal pulmonary vascular imaging (group 1, n=16) or persistent defects on perfusion scan (positive P scan) despite therapeutic anticoagulation for 4 months (group 2, n=17), for the following parameters: 1. Thrombotic load (extension of pulmonary thromboembolism on CT angiography) and Pulmonary Embolism Severity Index (PESI) score at the time of admission to the Intensive Care Unit (ICU); 2. Presence of thrombophilia (factor V Leiden, prothrombin variant, lupus anticoagulant); 3. Cardiovascular risk factors; 4. Anthropometric and demographic parameters; 5. Anticoagulation treatment in ICU and at discharge. The two groups of patients were also compared for the World Health Organization functional class (WHO-FC), NT-proBNP, cardiopulmonary exercise test (CPET) and echocardiographic parameters at rest and after exercise (ESE), at 4 and after 24 months. Results Compared with group 1, patients with persisting perfusion defects (group 2) featured higher thrombotic load (p=0.004) and PESI score (p=0.02) at the time of ICU admission. At 4 months, group 2 developed exercise-induced pulmonary hypertension (Ex-PH) at CPET (p<0.001) and ESE (p<0.001). At the 24 months follow-up group 2 showed higher NT-proBNP (p<0.001) and WHO-FC (p<0.001), systolic (p<0.001) and diastolic (p=0.037) right ventricular (RV) dysfunction and worse echo indices of RV-Arterial Coupling (TAPSE/PAPs (p<0.001)), despite maintaining a low or intermediate echocardiographic probability of PH (Table 1). Conclusions Despite the low and intermediate echocardiographic probability of PH, patients with persistent positive P scan had reduced functional capacity, and developed ExPH and RV functional deterioration.