Background—: Although balloon pulmonary angioplasty (BPA) for inoperable patients with chronic thromboembolic pulmonary hypertension was first reported over a decade ago, its clinical application has been restricted because of limited efficacy and complications. We have refined the procedure of BPA to maximize its clinical efficacy. Methods and Results—: Sixty-eight consecutive patients with inoperable chronic thromboembolic pulmonary hypertension underwent BPA. We evaluated pulmonary artery diameters and determined the appropriate balloon size by using intravascular ultrasound. We performed BPA in a staged fashion over multiple, separate procedures to maximize efficacy and reduce the risk of reperfusion pulmonary injury. A total of 4 (2–8) sessions were performed in each patient, and the number of vessels dilated per session was 3 (1–14). The World Health Organization functional class improved from 3 to 2 ( P <0.01), and mean pulmonary arterial pressure was decreased from 45.4±9.6 to 24.0±6.4 mm Hg ( P <0.01). One patient died because of right heart failure 28 days after BPA. During follow-up for 2.2±1.4 years after the final BPA, another patient died of pneumonia, and the remaining 66 patients are alive. In 57 patients who underwent right heart catheterization at follow-up, improvement of mean pulmonary arterial pressure was maintained (24.0±5.8 mm Hg at 1.0±0.9 years). Forty-one patients (60%) developed reperfusion pulmonary injury after BPA, but mechanical ventilation was required in only 4 patients. Conclusions—: Our refined BPA procedure improves clinical status and hemodynamics of inoperable patients with chronic thromboembolic pulmonary hypertension, with a low mortality. A refined BPA procedure could be considered as a therapeutic approach for patients with inoperable chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism, either symptomatic or not. The occlusion of proximal pulmonary arteries by fibrotic intravascular material, in combination with a secondary microvasculopathy of vessels <500 µm, leads to increased pulmonary vascular resistance and progressive right heart failure. The mechanism responsible for the transformation of red clots into fibrotic material remnants has not yet been elucidated. In patients with pulmonary hypertension, the diagnosis is suspected when a ventilation/perfusion lung scan shows mismatched perfusion defects, and confirmed by right heart catheterisation and vascular imaging. Today, in addition to lifelong anticoagulation, treatment modalities include surgery, angioplasty and medical treatment according to the localisation and characteristics of the lesions. This statement outlines a review of the literature and current practice concerning diagnosis and management of CTEPH. It covers the definitions, diagnosis, epidemiology, follow-up after acute pulmonary embolism, pathophysiology, treatment by pulmonary endarterectomy, balloon pulmonary angioplasty, drugs and their combination, rehabilitation and new lines of research in CTEPH. It represents the first collaboration of the European Respiratory Society, the International CTEPH Association and the European Reference Network-Lung in the pulmonary hypertension domain. The statement summarises current knowledge, but does not make formal recommendations for clinical practice.

Background—Balloon pulmonary angioplasty (BPA) is an alternative therapy for patients with chronic thromboembolic pulmonary hypertension who are ineligible for pulmonary endarterectomy—the standard therapy. Currently, most reported results of BPA are from relatively small cohorts treated at single centers. The present study evaluated the safety and efficacy of BPA for chronic thromboembolic pulmonary hypertension based on a multicenter registry. Methods and Results—A total of 308 patients (62 men and 246 women; mean age, 61 years) underwent 1408 procedures at 7 institutions in Japan. Data were retrospectively reviewed to evaluate clinical outcome and complications. Hemodynamics were significantly improved in 249 patients in whom BPA was terminated, most often because of improvement in mean pulmonary arterial pressure or symptomatic improvement after 1154 procedures. In 196 patients who underwent follow-up right heart catheterization, improvement of hemodynamic parameters was maintained. Mean pulmonary arterial pressure decreased from 43.2±11.0 to 24.3±6.4 mm Hg after final BPA and 22.5±5.4 mm Hg at follow-up, with significant reduction of concomitant use of pulmonary hypertension-targeted therapy and oxygen supplementation. Complications occurred in 511 (36.3%), including pulmonary injury (17.8%), hemoptysis (14.0%), and pulmonary artery perforation (2.9%). Twelve patients (3.9%) died during follow-up, including 8 patients who died within 30 days after BPA. The leading causes of death were right heart failure, multiorgan failure, and sepsis. Overall survival was 96.8% (95% confidence interval, 93.7%–98.4%) at 1 and 2 years and 94.5% (95% confidence interval, 89.3%–97.3%) at 3 years, respectively, after the initial BPA procedure for all 308 patients. Conclusions—This multicenter registry suggested improved hemodynamic results after BPA. Complication rates were high, but overall survival was comparable with pulmonary endarterectomy. BPA may be an important therapeutic option in patients with chronic thromboembolic pulmonary hypertension.

Background—: Balloon pulmonary angioplasty (BPA) is an alternative therapy for patients with chronic thromboembolic pulmonary hypertension who are ineligible for standard therapy, pulmonary endarterectomy. Although there are several classifications of vascular lesions, these classifications are based on the features of the specimen removed during pulmonary endarterectomy. Because organized thrombi are not removed during balloon pulmonary angioplasty, we attempted to establish a new classification of vascular lesions based on pulmonary angiographic images. We evaluated the success and complication rate of BPA in accordance with the location and morphology of thromboembolic lesions. Methods and Results—: We reviewed 500 consecutive procedures (1936 lesions) of BPA in 97 patients with chronic thromboembolic pulmonary hypertension and investigated the outcomes of BPA based on the lesion distribution and the angiographic characteristics of the thromboembolic lesions, as follows: type A, ring-like stenosis lesion; type B, web lesion; type C, subtotal lesion; type D, total occlusion lesion, and type E, tortuous lesion. The success rate was higher, and the complication rate was lower in ring-like stenosis and web lesions. The total occlusion lesions had the lowest success rate. Tortuous lesions were associated with a high complication rate and should be treated only by operators with extensive experience with BPA. Conclusions—: We modified the previous angiographic classification and established a new classification for each vascular lesion. We clarified that the outcome and complication rate of the BPA are highly dependent on the lesion characteristics.

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%.

Background: Pulmonary endarterectomy (PEA), pulmonary arterial hypertension (PAH) therapy and balloon pulmonary angioplasty (BPA) are currently accepted therapies for chronic thromboembolic pulmonary hypertension (CTEPH). This international CTEPH Registry identifies clinical characteristics of patients, diagnostic algorithms and treatment decisions in a global context.Methods: 1010 newly diagnosed consecutive patients were included in the registry between February 2015 and September 2016. Diagnosis was confirmed by right heart catheterisation, ventilation–perfusion lung scan, computerised pulmonary angiography and/or invasive pulmonary angiography after at least 3 months on anticoagulation.Results: Overall, 649 patients (64.3%) were considered for PEA, 193 (19.1%) for BPA, 20 (2.0%) for both PEA and BPA, and 148 (14.7%) for PAH therapy only. Reasons for PEA inoperability were technical inaccessibility (n=235), comorbidities (n=63) and patient refusal (n=44). In Europe and America and other countries (AAO), 72% of patients were deemed suitable for PEA, whereas in Japan, 70% of patients were offered BPA as first choice. Sex was evenly balanced, except in Japan where 75% of patients were female. A history of acute pulmonary embolism was reported for 65.6% of patients. At least one PAH therapy was initiated in 35.8% of patients (26.2% of PEA candidates, 54.5% of BPA candidates and 54.1% of those not eligible for either PEA or BPA). At the time of analysis, 39 patients (3.9%) had died of pulmonary hypertension-related causes (3.5% after PEA and 1.8% after BPA).Conclusions: The registry revealed noticeable differences in patient characteristics (rates of pulmonary embolism and sex) and therapeutic approaches in Japan compared with Europe and AAO.