Frequency and predictors for chronic thromboembolic pulmonary hypertension after a first unprovoked pulmonary embolism: Results from PADIS studies

Abstract

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening complication of a pulmonary embolism (PE) whose incidence and predictors are not precisely determined. Objective: To determine the frequency and predictors for CTEPH after a first unprovoked PE. Patients/Methods: In a randomized trial comparing an additional 18-month warfarin versus placebo in patients after a first unprovoked PE initially treated with vitamin K antagonist for 6 months, we applied recommended CTEPH screening strategies through an 8-year follow-up to determine cumulative incidence of CTEPH. CTEPH predictors were estimated using Cox models. Pulmonary vascular obstruction (PVO) and systolic pulmonary arterial pressure (sPAP) at PE diagnosis and 6 months were studied by receiver operating curves analysis. All CTEPH cases and whether they were incident or prevalent were adjudicated. Results: During a median follow-up of 8.7 years, nine CTEPH cases were diagnosed among 371 patients, with a cumulative incidence of 2.8% (95% confidence interval [CI] 0.95–4.64), and of 1.31% (95% CI 0.01–2.60) after exclusion of five cases adjudicated as prevalent. At PE diagnosis, PVO > 45% and sPAP > 56 mmHg were associated with CTEPH with a hazard ratio (HR) of 33.00 (95% CI 1.64–667.00, p =.02) and 12.50 (95% CI 2.10–74.80, p 65 years, lupus anticoagulant antibodies and non-O blood groups were also predictive of CTEPH. PVO > 14% and sPAP > 34 mmHg at 6 months were associated with CTEPH (HR 63.90 [95% CI 3.11–1310.00, p