Project description:Balloon pulmonary angioplasty (BPA) is an emerging treatment option for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who have inoperable, segmental/subsegmental disease, or residual disease after pulmonary endarterectomy. In the past decade, advances in the techniques for BPA have led to better clinical outcomes with improvements in hemodynamics, pulmonary perfusion, exercise tolerance, functional capacity, and quality of life. We present the experience with BPA at our university, the largest CTEPH center in the world, followed by reviewing the published data regarding the efficacy and safety of BPA in patients with CTEPH. There is increasing evidence to support that the initial hemodynamic improvement is sustained for ≥3 years after the procedure. Although infrequent, complications observed with BPA are associated with pulmonary vascular injury or rarely reperfusion pulmonary edema. As the technique for percutaneous pulmonary artery revascularization has improved, the procedural risk and complications have continued to decrease. This promising technique continues to develop, and future research is required to demonstrate the long-term benefits of BPA, standardize the technique, and define a uniform institutional infrastructure for providing BPA as a part of the treatment of CTEPH.
Project description:Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare major vessel pulmonary vascular disease that is characterised by fibrotic obstructions deriving from an organised clot. Recent advances in treatments for CTEPH have significantly improved outcomes. Apart from classical surgical pulmonary endarterectomy, balloon pulmonary angioplasty (BPA) and vasodilator drugs that were tested in randomised controlled trials of non-operable patients are now available. In Europe, CTEPH affects males and females equally. In the first European CTEPH Registry, women with CTEPH underwent pulmonary endarterectomy less frequently than men, especially at low-volume centres. In Japan, CTEPH is more common in females and is predominantly treated by BPA. More data on gender-specific outcomes are expected from the results of the International BPA Registry (NCT03245268).
Project description:Balloon pulmonary angioplasty (BPA) is beneficial for patients with chronic thromboembolic pulmonary disease (CTEPD) with pulmonary hypertension (PH). However, the clinical benefit of BPA for the patients with CTEPD without PH remains unknown. In this study, we aimed to evaluate the efficacy, safety, and long-term outcomes of BPA in patients with CTEPD without PH. We retrospectively analyzed the data from 84 CTEPD patients with mean pulmonary artery pressure (mPAP) < 25 mmHg and 39 CTEPD patients with mPAP ≤ 20 mmHg (without PH). Among the 39 patients with CTEPD without PH, 14 underwent BPA (BPA-treated group), and the remaining 25 received no treatment (untreated group). In the patients with CTEPD without PH, BPA led to improvements in symptoms, pulmonary vascular resistance (3.6 ± 1.6 to 2.6 ± 1.1 Wood units, p < 0.001), peak oxygen consumption (16.1 ± 4.0 to 18.8 ± 4.3 mL/kg/min, p = 0.033), minute ventilation versus carbon dioxide production slope (41.4 ± 12.2 to 35.1 ± 6.7, p = 0.026), and mPAP/cardiac output slope (7.0 ± 2.6 to 4.4 ± 2.0 mmHg/L/min, p = 0.004) and facilitated the discontinuation of home oxygenation therapy, with no serious complications. Kaplan-Meier analysis showed no significant difference in all-cause mortality between the untreated and BPA-treated groups. BPA may be a safe treatment option for the patients with CTEPD without PH that can alleviate symptoms, improve exercise capacity, and facilitate weaning from home oxygen therapy. Further prospective randomized trials are needed to confirm these findings.
Project description:Objective:Inoperable chronic thromboembolic pulmonary hypertension (CTEPH) managed medically has a poor prognosis. Balloon pulmonary angioplasty (BPA) offers a new treatment for inoperable patients. The national BPA service for the UK opened in October 2015 and we now describe the treatment of our initial patient cohort. Methods:Thirty consecutive, inoperable, anatomically suitable, symptomatic patients on stable medical therapy for CTEPH were identified and offered BPA. They initially underwent baseline investigations including Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) quality of life (QoL) questionnaire, cardiopulmonary exercise test, 6 min walk distance (6MWD), transthoracic echocardiography, N-terminal probrain natriuretic peptide (NT pro-BNP) and right heart catheterisation. Serial BPA sessions were then performed and after completion, the treatment effect was gauged by comparing the same investigations at 3 months follow-up. Results:A median of 3 (IQR 1-6) BPA sessions per patient resulted in a significant improvement in functional status (WHO functional class ≥3: 24 vs 4, p<0.0001) and QoL (CAMPHOR symptom score: 8.7±5.4 vs 5.6±6.1, p=0.0005) with reductions in pulmonary pressures (mean pulmonary artery pressure: 44.7±11.0 vs 34.4±8.3 mm Hg, p<0.0001) and resistance (pulmonary vascular resistance: 663±281 vs 436±196 dyn.s.cm-5, p<0.0001). Exercise capacity improved (minute ventilation/carbon dioxide production: 55.3±12.2 vs 45.0±7.8, p=0.03 and 6MWD: 366±107 vs 440±94 m, p<0.0001) and there was reduction in right ventricular (RV) stretch (NT pro-BNP: 442 (IQR 168-1607) vs 202 (IQR 105-447) pg/mL, p<0.0001) and dimensions (mid RV diameter: 4.4±1.0 vs 3.8±0.7 cm, p=0.002). There were no deaths or life-threatening complications and the mild-moderate per-procedure complication rate was 10.5%. Conclusions:BPA is safe and improves the functional status, QoL, pulmonary haemodynamics and RV dimensions of patients with inoperable CTEPH.
Project description:Chronic thromboembolic pulmonary hypertension (CTEPH) is a complex chronic disease in which pulmonary artery stenosis or obstruction caused by organized thrombus can lead to increased pulmonary artery pressure and pulmonary vascular resistance, ultimately triggering progressive right heart failure and death. Currently, its exact mechanism is not fully understood. Pulmonary endarterectomy (PEA) has immediate effects with low perioperative mortality and satisfactory prognosis in experienced expert centers for CTEPH patients with proximal lesions. Nevertheless, 37% of patients are deemed unsuitable for PEA surgery due to comorbidities and other factors, and nearly half of the operated patients have residual or recurrent pulmonary hypertension. Riociguat is the only approved drug for CTEPH, although its effect is limited. Balloon pulmonary angioplasty (BPA) is a promising alternative treatment for patients with CTEPH. After more than 30 years of development and refinements, emerging evidence has confirmed its role in patients with inoperable CTEPH or residual/recurrent pulmonary hypertension, with acceptable complications and comparable long-term prognosis to PEA. This review summarizes the pathophysiology of CTEPH, BPA history and development, therapeutic principles, indications and contraindications, interventional procedures, imaging modalities, efficacy and prognosis, complications and management, bridging and hybrid therapies, ongoing clinical trials and future prospects.
Project description:In this study, we aimed to assess the efficacy and safety of balloon pulmonary angioplasty (BPA) in patients with technically inoperable distal-type chronic thromboembolic pulmonary hypertension (d-CTEPH) and technically operable proximal-type disease (p-CTEPH) by analyzing the results of BPA treatment in two collaborating CTEPH referral centers. We assessed hemodynamic results, functional efficacy, complication and survival rate after BPA treatment in 70 CTEPH patients (median age 64 years; (interquartile range (IQR): 52-73 years)), of whom 16 (median age 73 years; (QR 62-82 years)) were in the p-CTEPH subgroup. Altogether, 377 BPA procedures were performed, resulting in significant (p < 0.001) improvement in mean pulmonary artery pressure (mPAP 48.6 ± 10 vs. 31.3 ± 8.6 mmHg), pulmonary vascular resistance (694 ± 296 vs. 333 ± 162 dynes*s*cm-5), six-minute walk test (365 ± 142 vs. 433 ± 120 metres) and N-terminal pro B-type natriuretic peptide (1307 (510-3294) vs. 206 (83-531) pg/mL). The rate of improvement did not differ between the sub-groups. Lung injury episodes and severe hemoptysis were similarly infrequent in d-CTEPH and p-CTEPH (6.4% vs. 5%; p = 0.55 and 1.0% vs. 2.5; p = 0.24, respectively). There was no significant difference between the sub-groups regarding survival (p = 0.53 by log-rank test). BPA may be beneficial in patients with p-CTEPH who cannot undergo pulmonary endarterectomy (PEA). Larger long-term studies are needed to better define the efficacy, safety, and optimal BPA procedural standards in this population.
Project description:Background Balloon pulmonary angioplasty (BPA) improves exercise tolerance and hemodynamic parameters in patients with chronic thromboembolic pulmonary hypertension. However, it is still unclear which patient characteristics contribute to the improvement in exercise tolerance after BPA in chronic thromboembolic pulmonary hypertension. Methods and Results We retrospectively analyzed 126 patients with chronic thromboembolic pulmonary hypertension (aged 63±14 years; female, 65%) who underwent BPA without concomitant programmed exercise rehabilitation at Keio University between November 2012 and April 2018. Hemodynamic data and 6-minute walk distance (6MWD), as a measure of exercise tolerance, were evaluated before and 1 year after BPA. The clinical characteristics that contributed to improvement in exercise tolerance were elucidated. The 6MWD significantly increased from 372.0 m (256.5-431.3) to 462.0 m (378.8-537.0) 1 year after BPA (P<0.001). The improvement rate in the 6MWD after BPA exhibited a good correlation with age, height, mean pulmonary artery pressure, and 6MWD at baseline (Spearman rank correlation coefficients=-0.28, 0.24, -0.40, and 0.44, respectively). Additional multivariable linear regression analysis revealed that young age, tall height, high mean pulmonary artery pressure, short 6MWD at baseline, and high lung capacity at baseline were significant predictors of the improvement in 6MWD by BPA (standardized partial regression coefficient -0.39, 0.22, 0.19, -0.62, and 0.25, P<0.001, 0.007, 0.011, <0.001, and <0.001, respectively). Conclusions BPA without concomitant programmed exercise rehabilitation significantly improves exercise tolerance. This was particularly true in young patients with high stature, high mean pulmonary artery pressure, short 6MWD, and lung capacity at the time of diagnosis.
Project description:BackgroundInflammatory response and endothelial dysfunction contribute to the progression of chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to assess changes in biomarkers involved in those processes in inoperable CTEPH patients treated with balloon pulmonary angioplasty (BPA).MethodsWe enrolled 20 patients with inoperable CTEPH qualified for BPA and a control group. Interleukin 6, 8, 10 (IL-6, IL-8, IL-10), monocyte chemoattractant protein-1 (MCP-1), and C-reactive protein (hsCRP) constituted the markers of systemic inflammation. Endothelin 1 (ET-1) served as a marker of endothelial dysfunction. Selected markers were assessed before the BPA treatment, 24 h after the first BPA, and six months after completion of the BPA treatment.ResultsAt baseline, the CTEPH patients had increased serum concentrations of IL-6, IL-8 and ET-1. Twenty-four hours after a BPA session, we observed an increase in concentrations of IL-6 (∆ = 3.67 (1.41; 7.16); p < 0.001), of IL-10 (∆ = 0.25 (0; 0.47); p = 0.003), of MCP-1 (∆ = 111 (60.1; 202.8); p = 0.002), and of hsCRP (∆ = 4.81 (3.46; 8.47); p < 0.001). Six months after completion of the BPA treatment, there was a decrease in concentrations of IL-6 (∆ = -1.61 (-3.11; -0.20); p = 0.03), of IL8 (∆ = -3.24 (-7.72; 0.82); p = 0.01), and of ET-1 (∆ = -0.47 (-0.96; 0.05); p = 0.005).ConclusionsPatients with inoperable CTEPH exhibit increased systemic inflammation and endothelial dysfunction, which improves after completion of the BPA treatment. A single BPA session evokes an acute inflammatory response.
Project description:BackgroundCurrent guidelines give balloon pulmonary angioplasty (BPA) a Class IIb recommendation for use in inoperable chronic thromboembolic pulmonary hypertension (CTEPH), as its safety and efficacy remain poorly defined. We conducted a systematic review and meta-analysis to evaluate BPA effectiveness.MethodsMedline, Cochrane Library and Scopus were searched for original studies from database inception dates until 24th May 2018. Prospective studies reporting outcomes before and after BPA in inoperable CTEPH patients were included. Studies with <20 patients were excluded. Data were pooled using a random effects model represented as weighted mean differences with 95% confidence intervals (CIs).ResultsSeventeen noncomparative studies comprising 670 CTEPH patients (mean age 62 years; 68% women) were included. Meta-analysis showed significantly decreased mean pulmonary artery pressure (-14.2 mm Hg [95% CI -18.9, -9.5]), pulmonary vascular resistance (-303.5 dyn·s/cm5 [95% CI -377.6, -229.4]) and mean right atrial pressure (-2.7 mm Hg [95% CI -4.1, -1.3]) after BPA. Six-minute walk distance (67.3 m [95% CI 53.8, 80.8]) and cardiac output (0.2 l/min [95% CI 0.0, 0.3]) were significantly increased following BPA. From 12 studies reporting mortality with median follow-up of 9 months after BPA (range, 1-51 months), pooled incidence of short (≤1 month) and long-term mortality (>1 month) was 1.9% and 5.7%, respectively.ConclusionThis systematic review and meta-analysis suggests mildly improved hemodynamics and overall low mortality rates following BPA in inoperable CTEPH patients. This non-comparative evidence can be used to facilitate decision making until the results of larger, controlled studies become available.