Evaluation and Management of Chronic Thromboembolic Pulmonary Hypertension

Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) is a treatable form of pulmonary hypertension and right heart failure. CTEPH (group 4 pulmonary hypertension) is caused by persistent organized thromboembolic obstruction of the pulmonary arteries from incompletely resolved acute pulmonary embolism. CTEPH also may present without prior VTE history, which can contribute to its underrecognition. The true incidence of CTEPH is unclear, but is estimated to be approximately 3% after acute pulmonary embolism. V˙/Q˙ scintigraphy is the best screening test for CTEPH, with CT scan imaging and other advanced imaging methods now playing a larger role in disease detection and confirmation. Perfusion defects on V˙/Q˙ scintigraphy in the setting of pulmonary hypertension are suggestive of CTEPH, but pulmonary angiography and right heart catheterization are required for confirmation and treatment planning. CTEPH potentially is curative with pulmonary thromboendarterectomy surgery, with mortality rates of approximately 2% at expert centers. Advances in operative techniques are allowing more distal endarterectomies to be performed successfully with favorable outcomes. However, more than one-third of patients may be considered inoperable. Although these patients previously had minimal therapeutic options, effective treatments now are available with pharmacotherapy and balloon pulmonary angioplasty. Diagnosis of CTEPH should be considered in all patients with suspicion of pulmonary hypertension. Treatments for CTEPH have advanced with improvements in outcomes for both operable and inoperable patients. Therapy should be tailored based on multidisciplinary team evaluation to ensure optimal treatment response.

Keywords: Riociguat; balloon pulmonary angioplasty; chronic thromboembolic pulmonary hypertension; pulmonary endarterectomy; pulmonary hypertension.

Figure 1

Flowchart showing diagnostic and treatment process for CTEPH. Symptoms and signs often are nonspecific and can include dyspnea on exertion, lightheadedness, palpitations, and lower extremity edema. Echocardiography, $\dot{\mathit{V}}/\dot{\mathit{Q}}$ scintigraphy, CTPA of the chest, and CPET may demonstrate abnormal findings suggestive of CTEPH. Right heart catheterization is required to confirm and determine severity of pulmonary hypertension (PH), and pulmonary angiography can confirm the pulmonary vasculature features of chronic thromboembolic disease. After CTEPH is confirmed, treatment decisions are individualized and require a multidisciplinary team consisting of a PTE surgeon, BPA specialist, PH provider, and chest radiologist with expertise in CTEPH. BPA = balloon pulmonary angioplasty; CTA = CT angiography; CTEPH = chronic thromboembolic pulmonary hypertension; CTPA = CT pulmonary angiography; mPAP = mean pulmonary artery pressure; PAWP = pulmonary artery wedge pressure; PTE = pulmonary thromboendarterectomy; PVR = pulmonary vascular resistance; RV = right ventricle; RVSP = right ventricular systolic pressure; Vd/Vt = ventilatory dead space; VE/VCO₂ = ratio of minute ventilation to carbon dioxide; WU = Wood unit.

Figure 2

A-L, $\dot{\mathit{V}}/\dot{\mathit{Q}}$ scans showing mismatched $\dot{\mathit{V}}/\dot{\mathit{Q}}$ defects in patient with pulmonary hypertension, consistent with chronic thromboembolic disease. Top row displays ¹³³Xe ventilation images. Bottom two rows display ^99mTc macroaggregated albumin planar perfusion images.

Figure 3

A-D, Photographs showing pulmonary thromboendarterectomy specimens and University of California, San Diego, level classification based on level of disease: level I disease indicates obstructive material in the main pulmonary arteries (A), level II disease starts at the lobar branches (B), level III disease starts at the segmental branches (C), and level IV disease is in the subsegmental branches primarily (D). Level 0 means no disease.

Figure 4

A-G, Selective pulmonary angiograms obtained from two different patients (A-D and E-G) during balloon pulmonary angioplasty. A, E, Selective pulmonary angiograms showing occlusion of the posterior left lower lobe pulmonary artery before balloon angioplasty. B, C, F, Wire passed through the occlusion and vessels treated with balloon inflation. D, G, Selective angiograms obtained after balloon angioplasty showing improved blood flow in the left lower lobe.