Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism and a major cause of chronic PH leading to right heart failure and death. Lung ventilation/perfusion scintigraphy is the screening test of choice; a normal scan rules out CTEPH. In the case of an abnormal perfusion scan, a high-quality pulmonary angiogram is necessary to confirm and define the pulmonary vascular involvement and prior to making a treatment decision. PH is confirmed with right heart catheterisation, which is also necessary for treatment determination. In addition to chronic anticoagulation therapy, each patient with CTEPH should receive treatment assessment starting with evaluation for pulmonary endarterectomy, which is the guideline recommended treatment. For technically inoperable cases, PH-targeted medical therapy is recommended (currently riociguat based on the CHEST studies), and balloon pulmonary angioplasty should be considered at a centre experienced with this challenging but potentially effective and complementary intervention.

Chronic thromboembolic pulmonary hypertension is a complication of pulmonary embolism and a treatable cause of pulmonary hypertension. The pathology is a unique combination of mechanical obstruction due to failure of clot resolution, and a variable degree of microvascular disease, that both contribute to pulmonary vascular resistance. Accordingly, multiple treatments have been developed to target the disease components. However, accurate diagnosis is often delayed. Evaluation includes high-quality imaging modalities, necessary for disease confirmation and for appropriate treatment planning. All patients with chronic thromboembolic pulmonary disease, and especially those with pulmonary hypertension, should be referred to expert centres for multidisciplinary team decision on treatment. The first decision remains assessment of operability, and the best improvement in symptoms and survival is achieved by the mechanical therapies, pulmonary endarterectomy and balloon pulmonary angioplasty. With the advances in multimodal therapies, excellent outcomes can be achieved with 3-year survival of >90%.

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.

BACKGROUND: The European Chronic Thromboembolic Pulmonary Hypertension (CTEPH) registry, conducted between 2007 and 2012, reported the major impact of pulmonary endarterectomy (PEA) on the long-term survival of patients with CTEPH. Since then, 2 additional treatments for inoperable CTEPH have become available: balloon pulmonary angioplasty (BPA), and an approved oral drug therapy with the guanylate cyclase stimulator riociguat. The current registry aimed to evaluate the effect of these new therapeutic approaches in a worldwide context. METHODS: Participation in this international global registry included 34 centers in 20 countries. Between February 2015 and September 2016, 1009 newly diagnosed, consecutive patients were included and followed until September 2019. RESULTS: Overall, 605 patients (60%) underwent PEA and 185 (18%) underwent BPA; 76% of the 219 remaining patients not receiving mechanical intervention (ie, neither PEA nor BPA) were treated with pulmonary hypertension drugs. Of patients undergoing PEA and BPA, 38% and 78% also received drugs for pulmonary hypertension, respectively. Median age at diagnosis was higher in the BPA and No PEA/BPA groups than in the PEA group: 66 and 69, respectively, versus 60 years. Pulmonary vascular resistance (PVR) was similar in all groups, with an average of 643 dynes.s.cm ⁻⁵ . During the observation period (>3 years; ≤5.6 years), death was reported in 7%, 11%, and 27% of patients treated by PEA and BPA, and those receiving no mechanical intervention ( P <0.001). In Kaplan-Meier analysis, 3-year survival was 94%, 92%, and 71% in the 3 groups, respectively. PEA 3-year survival improved by 5% from that observed between 2007 and 2012. There was no survival difference in patients receiving vitamin K antagonists and non–vitamin K oral anticoagulants ( P =0.756). In Cox regression, reduced mortality was associated with: PEA and BPA in the global cohort; history of venous thromboembolism and lower PVR in the PEA group; lower right atrial pressure in the BPA group; and use of pulmonary hypertension drugs, oxygen therapy, and lower right atrial pressure, as well as functional class in the group receiving no mechanical intervention. CONCLUSIONS: This second international CTEPH registry reveals important improvement in patient survival since the introduction of BPA and an approved drug for pulmonary hypertension. The type of anticoagulation regimen did not influence survival. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02656238.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension caused by obstruction and vascular remodelling of pulmonary arteries following pulmonary embolism. Risk factors that predispose patients to CTEPH include the size of the initial thrombus and numerous associated host or medical conditions. Haemostatic risk factors include elevated levels of factor VIII and phospholipid antibodies or intrinsic abnormalities in fibrinogen. Medical conditions that are associated with an increased risk of CTEPH include a history of splenectomy, cancer, ventriculoatrial shunt, chronic inflammatory disease, antiphospholipid antibodies and hypothyroidism. Although CTEPH is potentially curable by pulmonary endarterectomy (PEA), up to 40% of patients evaluated for PEA may be denied surgery depending on the level of surgical experience and disease accessibility after pre-operative assessment. Furthermore, an estimated 10–15% of patients are at risk for residual pulmonary hypertension following PEA surgery, due to significant concomitant small-vessel disease. However, pre-operative identification of small-vessel involvement remains a challenge.The current medications effective in the treatment of pulmonary arterial hypertension have not demonstrated efficacy in CTEPH. Accordingly, identification of CTEPH, followed by early referral for evaluation and treatment by an experienced PEA centre, is recommended.