Recent Advances in Chronic Thromboembolic Pulmonary Hypertension: Expanding the Disease Concept and Treatment Options

Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive form of pulmonary hypertension characterized by unresolved thromboembolic occlusion of pulmonary arteries, leading to increased pulmonary arterial pressure and right heart failure. This review examines recent advances in the pathophysiology, diagnosis, and management of CTEPH, focusing on expanding disease concepts and evolving therapeutic approaches. The incidence of CTEPH has been revised upward with improved diagnostic techniques revealing a higher prevalence than previously recognized. Advances in surgical and interventional therapies, particularly pulmonary endarterectomy and balloon pulmonary angioplasty, have significantly improved outcomes. Emerging medical therapies, including pulmonary vasodilators like riociguat, have offered new hope for inoperable cases. The understanding of CTEPH has broadened, leading to better diagnostic strategies and more comprehensive treatment options that significantly enhance patient outcomes. Multidisciplinary team approaches are crucial in managing the disease effectively.

Keywords: Balloon pulmonary angioplasty; Chronic thromboembolic pulmonary disease; Chronic thromboembolic pulmonary hypertension; Pulmonary endarterectomy.

Figure 1. Lung perfusion scan comparison of operable vs. inoperable CTEPH. The right panel initially identified as idiopathic pulmonary arterial hypertension, was ultimately diagnosed as inoperable CTEPH with primarily distal subsegmental lesions.

ANT = anterior; CTEPH = chronic thromboembolic pulmonary hypertension; LAO = left anterior oblique; LLAT = left lateral; LPO = left posterior oblique; POST = posterior; RAO = right anterior oblique; RLAT = right lateral; RPO = right posterior oblique.

Figure 2. Lung perfusion SPECT provides enhanced anatomical information, demonstrating its utility in detailed vascular imaging. (A) Lung perfusion scan; (B) Surgical specimen; (C) Lung SPECT.

ANT = anterior; LAO = left anterior oblique; LPO = left posterior oblique; LTLAT = left lateral; POST = posterior; RAO = right anterior oblique; RPO = right posterior oblique; RTLAT = right lateral; SPECT = single-photon emission computed tomography.

Figure 3. Not all obstructive lesions in pulmonary arteries are due to chronic thromboembolic pulmonary hypertension. Differentiation from acute pulmonary thromboembolism or tumors is essential before surgery. (A) Acute pulmonary embolism; (B) Chronic thromboembolic disease; (C) Acute on chronic thromboembolism; (D) Pulmonary artery sarcoma.

Figure 4. Typical computed tomography angiography features in chronic thromboembolic pulmonary hypertension patients. (A) Mosaic pattern of lung parenchyma; (B) Reduced visibility of distal vessels, calcified thrombi, and chronic thrombi; (C) Lung infarction; (D) Enlargement of the right atrium and ventricle, deviation of left ventricular septum.

Figure 5. CTEPH treatment algorithm as suggested by the 7th World Symposium on Pulmonary Hypertension CTEPH working group.

BPA = balloon pulmonary angioplasty; CTEPH = chronic thromboembolic pulmonary hypertension; MDT = multidisciplinary team; mPAP = mean pulmonary arterial pressure; PEA = pulmonary endarterectomy; PH = pulmonary hypertension; PVR = pulmonary vascular resistance. ^*CTEPH MDT requires pulmonary endarterectomy surgeon, PH expert, BPA specialist and chest radiologist. ^†Treatment of choice for technically operable disease. ^‡Riociguat therapy prior to BPA: mean pulmonary arterial pressure ≥40 mmHg or pulmonary vascular resistance >4 Wood units. ^§Other PH medications approved in select regions. ^∥Structured follow-up; may include imaging and hemodynamic assessment.

Figure 6. Case of rescue BPA following PEA. A 51-year-old woman with breast cancer and antithrombin III deficiency was admitted with acute pulmonary thromboembolism on a background of chronic thromboembolic pulmonary hypertension. Lack of response to anticoagulation and progressive disease necessitated emergency PEA. Post-PEA, high pulmonary arterial pressure persisted and cardiogenic shock progressed, requiring immediate ECMO support. After 2 sessions of BPA, she was successfully weaned from ECMO and discharged. (A) CT scan before surgery; (B) Surgical specimen from PEA; (C) Pulmonary angiography a week after PEA. Vascular obstruction is noted; (D) BPA was done for a targeted vessel; (E) Vascular beds are improved.

BPA = balloon pulmonary angioplasty; ECMO = extracorporeal membrane oxygenation; PEA = pulmonary endarterectomy.