Review
Chronic thromboembolic pulmonary hypertension

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Summary

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but debilitating and life-threatening complication of acute pulmonary embolism. CTEPH results from persistent obstruction of pulmonary arteries and progressive vascular remodelling. Not all patients presenting with CTEPH have a history of clinically overt pulmonary embolism. The diagnostic work-up to detect or rule out CTEPH should include ventilation-perfusion scintigraphy, which has high sensitivity and a negative predictive value of nearly 100%. CT angiography usually reveals typical features of CTEPH, including mosaic perfusion, part or complete occlusion of pulmonary arteries, and intraluminal bands and webs. Patients with suspected CTEPH should be referred to a specialist centre for right-heart catheterisation and pulmonary angiography. Surgical pulmonary endarterectomy remains the treatment of choice for CTEPH and is associated with excellent long-term results and a high probability of cure. For patients with inoperable CTEPH, various medical and interventional therapies are being developed.

Introduction

Chronic thromboembolic pulmonary hypertension (CTEPH) is defined as raised mean pulmonary artery pressure (of at least 25 mm Hg at rest) caused by persistent obstruction of pulmonary arteries after pulmonary embolism that has not resolved despite at least 3 months of therapeutic anticoagulation.1 Occasionally patients present with clinical and diagnostic features of CTEPH, including widespread obstruction of pulmonary arteries, but have no pulmonary hypertension. Formally, this presentation should not be classified as CTEPH and instead may be termed chronic thromboembolic disease, although the management of these patients is usually similar to that of patients with classic CTEPH.

Non-resolving acute pulmonary embolism is the most common cause of CTEPH, and can occur after one or multiple episodes. CTEPH might occasionally develop owing to in-situ pulmonary artery thrombosis, which could be associated with inflammation of the vessel walls.2 CTEPH is underdiagnosed, which is problematic because many affected patients can be effectively treated by surgical pulmonary endarterectomy (PEA). For patients who are not surgical candidates, medical and interventional treatments have been developed and specialist centres can now offer tailored therapies for almost all affected patients. In this Review we summarise the available information on the diagnosis and treatment of CTEPH.

Section snippets

Epidemiology, natural history, and pathogenesis

Incomplete resolution of pulmonary embolism is not uncommon. In fact, despite effective therapeutic anticoagulation, more than 50% of patients have residual perfusion defects 6 months after diagnosis of pulmonary embolism.3 Most of these patients, however, do not develop manifest chronic pulmonary hypertension. Even patients who present with signs of pulmonary hypertension during an episode of acute pulmonary embolism are unlikely to develop CTEPH, and in most of these patients,

Symptoms and diagnosis

As in other forms of pulmonary hypertension, progressive dyspnoea on exertion is the predominant symptom of CTEPH. Additionally, patients might present with fatigue, syncope, haemoptysis, and signs of right-heart failure. CTEPH should be considered in all patients who have a history of clinically overt acute pulmonary embolism, although around 25% of patients diagnosed as having CTEPH have no documented acute pulmonary embolism events.31 Thus, CTEPH should be considered in any patient with

Treatment

Although never assessed in clinical trials, the need for lifelong anticoagulation for patients with CTEPH is undisputed, even in patients who underwent successful PEA. The target international normalised ratio is 2·0–3·0. Vitamin K antagonists remain the most widely used drugs to treat CTEPH. Subcutaneous low-molecular-weight heparins or fondaparinux and novel anticoagulants are suitable alternative drugs, especially in patients in whom a stable international normalised ratio is difficult to

Economic considerations

The costs of PEA and balloon pulmonary angioplasty vary widely between centres and are difficult to assess as few data have been published. Comparison of the costs at two centres that perform PEA and balloon pulmonary angioplasty, in Osaka, Japan, and Hannover, Germany, provides the following estimates: in Osaka, the average full costs for PEA are around ¥5 800 000 (US$50 000) and for four balloon pulmonary angioplasty procedures (the median number of interventions required per patient) are

Conclusions

CTEPH is a life-threatening complication of pulmonary embolism. Treatment differs substantially from that of other forms of pulmonary hypertension. A robust diagnostic workup in patients with unexplained pulmonary hypertension, therefore, should include appropriate imaging, including ventilation-perfusion scintigraphy. The final diagnosis of CTEPH requires right-heart catheterisation and pulmonary angiography, which should be done in expert centres, where the best therapeutic approach for

Search strategy and selection criteria

References for this Review were identified through searches of PubMed for articles published from January, 1970, to January, 2014, with the search terms “chronic thromboembolic pulmonary hypertension”, “pulmonary endarterectomy”, “pulmonary thrombendarterectomy”, “balloon pulmonary angioplasty”, and “pulmonary embolism and pulmonary hypertension”. Articles of interest were selected on the basis of review by MMH and LJR. Relevant references cited in retrieved articles were also reviewed.

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