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 < .01), respectively. Age > 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 < .01]and HR 17.2 [95% CI 2.75–108, p < .01]). Conclusion After a first unprovoked PE, CTEPH cumulative incidence was 2.8% during an 8‐year follow‐up. PVO and sPAP at PE diagnosis and at 6 months were the main predictors for CTEPH diagnosis.

Keep minds opening for chronic thromboembolic pulmonary hypertension: More data, less clarity

“…Considering near 4‐fold higher incidence in the unprovoked PE cohort, the incidence of 2.8% after unprovoked PE was consistent compared to the incidence of 0.56% after overall PE cohort pooled in meta‐analysis 4 . Notably, within PADIS‐PE, a programmed screening strategy was predesigned for all patients, consisting of transthoracic echocardiography; ventilation‐perfusion lung scanning at PE diagnosis, 6 months after PE, and 5 years after index PE; and whether patients were symptomatic or not 6 . This strategy helped screen out those CTEPH patients that presented with preserved cardiac function and exercise capacity, which enhanced the evidence of the results.…”

“…4 Notably, within PADIS-PE, a programmed screening strategy was predesigned for all patients, consisting of transthoracic echocardiography; ventilation-perfusion lung scanning at PE diagnosis, 6 months after PE, and 5 years after index PE; and whether patients were symptomatic or not. 6 This strategy helped screen out those CTEPH patients that presented with preserved cardiac function and exercise capacity, which enhanced the evidence of the results.…”

“…On this controversial academic topic, Fauché et al 6 recently reported their new findings that published in this issue of J Thromb Haemost . In this study, they assessed patients enrolled in the randomized, double‐blind, multicenter Prolonged Anticoagulation During 18 months versus Placebo after Initial Six‐month Treatment for a First Episode of Idiopathic Pulmonary Embolism (PADIS‐PE) trial 7 and applied programmed strategies to screen for CTEPH cases.…”

Oxygenation index and NT-proBNP as predictors of pulmonary hypertension and ventilation/perfusion mismatch in acute pulmonary embolism

“…V/Q scanning is the standard for assessing PVO ( 18 ) that can evaluate the extent and degree of embolism. During an 8-year follow-up study, PVO at the initial PE diagnosis (HR: 33.00, 95% CI: 1.64–667.00, P = 0.02) was the main predictor for CTEPH ( 6 ). A V/Q scan appointment always involves long wait times, is not as fast as the computed tomography pulmonary angiogram (CTPA) test, and is not available at all hospitals.…”

“…The extent of V/Q mismatch at diagnosis is the main predictor of poor APE prognosis ( 6 ). In addition to pulmonary circulation function, risk stratification and adverse outcomes in APE have also been increasingly studied in relation to respiratory perfusion functions such as partial pressure of oxygen (PO 2 ) and oxygenation index (OI) ( 7 , 8 ).…”