Incidence of Chronic Thromboembolic Pulmonary Hypertension After Pulmonary Embolism in the Era of Direct Oral Anticoagulants: From the COMMAND VTE Registry-2

Abstract

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening complication post-acute pulmonary embolism (PE). The assessment of CTEPH incidence and risk factors post-acute PE in the era of direct oral anticoagulants remains insufficient.

Methods and results: The COMMAND VTE Registry-2 (contemporary management and outcomes in patients with venous thromboembolism registry-2) is a multicenter registry that recruited consecutive patients with acute symptomatic venous thromboembolism from 31 centers across Japan. The primary outcome was to demonstrate the detection rate of CTEPH after acute PE in routine clinical practice. Out of the 5197 patients with venous thromboembolism included in the COMMAND VTE Registry-2, 2787 were diagnosed with acute PE. Following a median follow-up duration of 747 days, 48 cases of CTEPH were detected, and the cumulative diagnosis of CTEPH in routine clinical practice was 2.3% at 3 years. Independent risk factors for the detection of CTEPH by multivariable Cox regression analysis included women (hazard ratio [HR] 2.09 [95% CI, 1.05-4.14]), longer interval from symptom onset to diagnosis of PE (each 1 day, HR 1.04 [95% CI, 1.01-1.07]), hypoxemia at diagnosis (HR 2.52 [95% CI, 1.26-5.04]), right heart load (HR 9.28 [95% CI, 3.19-27.00]), lower D-dimer value (each 1 μg/mL, HR 0.96 [95% CI, 0.92-0.99]), and unprovoked PE (HR 2.77 [95% CI, 1.22-6.30]).

Conclusions: In the direct oral anticoagulant era, the cumulative diagnosis of CTEPH after acute PE was 2.3% at 3 years, and several independent risk factors for CTEPH were identified, which could be useful for screening a high-risk population after acute PE.

Keywords: acute pulmonary embolism; chronic thromboembolic pulmonary hypertension; direct oral anticoagulants.

Figure 1. Study flow chart.

CTEPH indicates chronic thromboembolic pulmonary hypertension; PE, pulmonary embolism; and VTE, venous thromboembolism.

Figure 2. Kaplan–Meier curve for the diagnosis of CTEPH.

CTEPH indicates chronic thromboembolic pulmonary hypertension; and PE, pulmonary embolism.

Figure 3. A representative case of CTEPH.

After acute PE, exertional dyspnea persisted. Right heart catheterization 6 months later showed mPAP 34 mm Hg and PVR 6.4 Wood unit, leading to a diagnosis of CTEPH. A and B, CT scan at diagnosis of acute PE. A thrombus was identified in the right pulmonary artery (white arrow), and the RV/LV ratio was 1.15. C and D, CT scan 6 months after onset of acute PE. No thrombus was detectable by CT scan, but the RV/LV ratio remained at 0.92, still high. E, Multiple perfusion defects were identified in the pulmonary perfusion scintigraphy (black arrows). F, Selective pulmonary artery angiography revealed multiple pulmonary artery stenoses and occlusions (white arrowheads). CT indicates computed tomography; CTEPH, chronic thromboembolic pulmonary hypertension; mPAP, mean pulmonary arterial pressure; PE, pulmonary embolism; PVR, pulmonary vascular resistance; and RV/LV ratio, right ventricular diameter/left ventricular diameter ratio.