Chronic thromboembolic pulmonary hypertension results from mechanical obstruction of major pulmonary artery lumina with fibrotic tissue. Main treatment has been pulmonary endarterectomy, a complex surgical procedure removing vascular obstruction. However, at least 40% of patients are not candidates for pulmonary endarterectomy because of technical inoperability, comorbidities, or limited access to surgery. Balloon pulmonary angioplasty (BPA) has emerged as an interventional treatment for these patients.

The International BPA Registry (NCT03245268) was designed to investigate BPA practice across 18 established centers in the United States, Europe, and Japan.

A total of 500 patients were prospectively and consecutively enrolled between March 2018 and March 2020, with follow-up until March 2022. Of these, 484 patients were included in the analysis set.

Regional differences were seen in patient characteristics (fewer patients with prior pulmonary endarterectomy and more elderly women in Japan) and procedural details (less medical pretreatment, more jugular access, more segments and more occlusive lesions treated per session and patient, less conscious sedation, less contrast and less radiation, shorter intervals between BPA sessions in Japan). Female sex, procedure in Europe/United States, pulmonary hypertension medications at any time, and higher baseline pulmonary vascular resistance (PVR), calculated as transpulmonary pressure gradient divided by cardiac output, emerged as independent predictors of complications during BPA. After a median of 5 (Q1-Q3: 3-6) BPA sessions per patient within a median time of 4.9 months (Q1-Q3: 1.7-11.0 months), a 15-mm Hg (38%) decrease in mPAP, a 332 dynes/s/cm-5 (57%) decrease in PVR, and a 3.2% increase in arterial saturation (medians; P < 0.001) were observed, and there were significant improvements in functional class, 6-minute walk distance, serum levels of N-terminal probrain natriuretic peptide, and Borg dyspnea index. BPA complications occurred in 11.3% of sessions and 33.9% of patients and were mostly hemoptyses. No patient died within 30 days of BPA.

Our data are in line with previous reports on changes of clinical and hemodynamic parameters and complication rates of BPA. Centers with more experience providing BPAs were more likely to achieve a higher percentage decrease in PVR.

Balloon pulmonary angioplasty (BPA) is frequently used in chronic thromboembolic pulmonary hypertension (CTEPH)/chronic thromboembolic pulmonary disease (CTED). Nevertheless, noninvasive pulmonary perfusion imaging after BPA is scarce. In this study, change in perfusion on ventilation/perfusion (V/Q) scan after BPA was assessed and correlated with clinical outcomes.

Retrospectively, all consecutive patients with CTEPH/CTED patients who completed BPA and received planar V/Q scans baseline and 6 months follow-up were included. Perfusion was evaluated using gestalt interpretation and semiquantitative calculation of the pulmonary vascular obstruction (PVO) index, with obligatory use of the lung segment reference chart. Interobserver variability was assessed for both methods, and the correlation between PVO index and clinical parameters was tested.

Thirty-three patients with CTEPH/CTED (mean age: 60.4 ± 14.7 years, 70% female) underwent 127 BPA procedures. Gestalt interpretation showed improved perfusion in 79% of all patients, and PVO index decreased significantly compared with baseline (45 ± 15-35 ± 15%; P < 0.001). The gestalt method showed a weak level of agreement (k = 0.32; P = 0.06), and the PVO method showed a moderate to strong reliability (R2 : 0.71, P < 0.001). The PVO index showed a significant (P < 0.001) but weak correlation with log N-terminal probrain natriuretic peptide, mean pulmonary artery pressure, and pulmonary vascular resistance (R2 : 0.26, 0.24, and 0.18, respectively).

Perfusion on V/Q scan significantly improved after BPA in patients with CTEPH/CTED. Semiquantitative calculation of PVO was more reliable in comparison to gestalt interpretation, however, clinical parameters showed only a weak correlation with the PVO index.

Nocturnal desaturation is occasionally observed in patients with chronic thromboembolic pulmonary hypertension (CTEPH) despite the absence of parenchymal lung disease; however, the underlying mechanism remains unclear. This study aimed to clarify the clinical features of nocturnal desaturation in patients with CTEPH.

Data of 163 patients with CTEPH who underwent balloon pulmonary angioplasty (BPA) between March 2011 and December 2022 were retrospectively analyzed. We evaluated their hemodynamics using right heart catheterization, arterial blood gas examination, respiratory function tests, nocturnal oximetry, and cardiopulmonary exercise testing, which were routinely performed at baseline and after BPA.

A higher ratio of dead space to tidal volume (VD/VT) (p < 0.001) and higher alveolar-arterial oxygen difference (A-aDO2) (p = 0.026) at baseline were associated with greater nocturnal desaturation in the multivariable linear analysis. After BPA, nearly normal hemodynamics was achieved (mean pulmonary arterial pressure: 37.5 ± 10.0 to 20.2 ± 4.9 mmHg, p < 0.01). Nocturnal desaturation also improved from - 13.3 ± 5.8% at baseline to -10.3 ± 5.4% after BPA (p < 0.01). Improvement in VD/VT correlated well with improvement in nocturnal desaturation after BPA (p < 0.001, R2 linear = 0.18).

Nocturnal desaturation often coexists with CTEPH. VD/VT, a marker of physiologic dead-space fraction, A-aDO2, a marker of ventilation-perfusion mismatch, and lung diffusing capacity were strongly associated. Nocturnal desaturation improved slightly after BPA, which was associated with a decrease in the physiological dead- space fraction. Our study emphasizes the importance of including nocturnal oximetry in routine evaluations and continuation of nocturnal oxygen therapy, if necessary, in patients with CTEPH.

The heterozygous ring finger protein 213 (RNF213) p.Arg4810Lys variant has been identified in patients with chronic thromboembolic pulmonary hypertension (CTEPH). This study aimed to clarify the influence of the RNF213 p.Arg4810Lys variant on the response to balloon pulmonary angioplasty (BPA) in patients with CTEPH.

We retrospectively analyzed 93 patients with CTEPH who underwent BPA by analyzing the RNF213 p.Arg4810Lys variant. Clinical parameters and hemodynamics following BPA were compared between RNF213 p.Arg4810Lys variant carriers and noncarriers, along with BPA-related complications.

Among 93 patients, 7 (8%) were heterozygous RNF213 p.Arg4810Lys variant carriers and 86 (92%) were noncarriers. Both groups showed significant improvements in mean pulmonary artery pressure and pulmonary vascular resistance following BPA. However, the 6-minute walk distance, symptoms, cardiac index, and right ventricular function did not significantly improve in heterozygous RNF213 variant carriers, whereas noncarriers showed notable improvements. Group differences in mean change from baseline to follow-up were significant in cardiac index (0.4 L/min per m2 [95% CI, 0.1-0.8]; P=0.019), 6-minute walk distance (70 m [95% CI, 6-135]; P=0.036), and right ventricular ejection fraction (9% [95% CI, 5-12]; P<0.001), all favoring noncarriers. Of the 515 BPA procedures, complications were significantly higher in variant carriers than in noncarriers (25% versus 8%; P<0.001). Multivariate logistic regression analysis indicated a significant association between the RNF213 p.Arg4810Lys variant and BPA complications (adjusted odds ratio, 7.0 [95% CI, 1.1-44.4]; P=0.038).

Heterozygous RNF213 p.Arg4810Lys variant carriers exhibited a poor response to BPA, suggesting that the RNF213 p.Arg4810Lys variant could be a risk factor for BPA complications.

Cone beam CT pulmonary angiography (CBCT-PA) has proven to be a valuable technique during balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension (CTEPH) in established centres. This study aimed to demonstrate the safety and efficacy of CBCT-PA-guided BPA for CTEPH during the initial period of a BPA program. CBCT-PA improves procedural accuracy by visualising distal thromboembolic lesions and providing real-time guidance, which is critical during program initiation.

This single-centre, single-arm study prospectively evaluated patients with CTEPH undergoing BPA from 2017 to 2022. Outcomes of interest included pre-BPA and post-BPA 6-minute walking distance, New York Heart Association Functional Classification (NYHA-FC), mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), N-terminal pro B-type natriuretic peptide (NT-proBNP), and BPA-related adverse events (AEs). Statistical analysis compared pre-BPA and post-BPA results. CBCT-PA was used for three-dimensional (3D) vascular mapping and precise lesion targeting.

Ninety BPA sessions were performed on 19 patients under CBCT-PA guidance. Significant improvements were observed in mPAP (37.0 mmHg [interquartile range (IQR): 28.0-46.0] vs 25.5 [IQR: 22.8-31.5]; P<0.001), PVR (5.5 Wood units [IQR: 3.4-8.5] vs 3.3 [IQR: 2.7-4.6]; P < 0.001), NYHA-FC I-II rate (8 [42%] vs 18 [94%]; P = 0.04), and NT-proBNP (165 pg/mL [IQR: 82-1146] vs 127.0 [IQR: 57-216]; P = 0.014). Overall AE rate was 14.4%, and major AE rate was 7.7% (all Cardiovascular and Interventional Radiology Society of Europe [CIRSE] grade 3). The haemoptysis rate was 4.4%. No periprocedural deaths were reported.

BPA performed under CBCT-PA guidance appeared to be an effective and safe approach in the program's initial period, helping achieving similar results as established centres.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe and progressive condition caused by unresolved pulmonary arterial obstructions, leading to secondary microvasculopathy and poor hemodynamics. Pulmonary endarterectomy (PEA) is the first-line treatment for operable patients. Balloon pulmonary angioplasty (BPA) has emerged as a promising treatment option for patients considered inoperable due to distal lesions, comorbidities, or residual pulmonary hypertension (PH) after PEA. Following the development of the BPA in safety and efficacy, it has been widely adopted and utilized across the globe.

This review covers the historical development of BPA, its clinical role, and technical methodologies. Medical therapies as an adjunctive role in CTEPH management are also discussed. Finally, we present recent BPA experiences from our institution, highlighting hemodynamic outcomes and survival rates.

BPA is a transformative treatment for patients with CTEPH, particularly those ineligible for PEA. Procedural refinements have significantly improved safety and efficacy. However, challenges remain, including the standardization of decision-making processes for management and the establishment of optimal treatment goals. Ongoing research continues to refine the role of BPA to improve outcomes and enhance the quality of life for patients with CTEPH. [Figure: see text].

Chronic thromboembolic pulmonary hypertension (CTEPH) is a consequence of unresolved organized thromboembolic obstruction of the pulmonary arteries, which can cause pulmonary hypertension and right ventricular failure. Owing to its subtle signs, determining its exact incidence and prevalence is challenging. Furthermore, CTEPH may also present without any prior venous thromboembolic history, contributing to underdiagnosis and undertreatment. Diagnosis requires a high degree of suspicion and is ruled out by a normal ventilation/perfusion ratio scintigraphy. Additional imaging by computed tomography and/or conventional angiography, as well as right heart catheterization, are required to confirm CTEPH and formulate treatment plans. Pulmonary thromboendarterectomy is the treatment of choice for eligible patients and can be potentially curative. Pulmonary thromboendarterectomy has a low mortality rate of 1% to 2% at expert centers and offers excellent long-term survival. Furthermore, recent advances in the techniques allow distal endarterectomy with comparable outcomes. Alternative treatment options are available for those who may not be operable or have prohibitive risks, providing some benefit. However, CTEPH is a progressive disease with low long-term survival rates if left untreated. Given excellent short- and long-term outcomes of surgery, as well as the benefits seen with other treatment modalities in noncandidate patients, it is crucial that precapillary pulmonary hypertension and CTEPH are ruled out in any patient with dyspnea of unexplained etiology. These patients should be referred to expert centers where accurate operability assessment and appropriate treatment strategies can be offered by a multidisciplinary team.

 Balloon pulmonary angioplasty (BPA) is a promising interventional treatment for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Evidence in favor of BPA is growing, but long-term data remain scarce. The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is validated for the assessment of patients with pulmonary hypertension within three domains: symptoms, activity, and quality of life (QoL). The aim of the present study was to evaluate the long-term effects of BPA on these domains in patients with inoperable CTEPH.

 Between March 2014 and August 2019, technically inoperable patients with target lesions for BPA were included in this prospective, observational study. CAMPHOR scores were compared between baseline (before the first BPA) and 6 months after the last intervention and also for scores assessed at annual follow-ups.

 A total of 152 patients had completed a full series of BPA interventions and a 28 (interquartile range [IQR]: 26-32) week follow-up. Further follow-up assessments including the CAMPHOR score were performed 96 (IQR: 70-117) weeks, 178 (IQR: 156-200) weeks, and 250 (IQR: 237-275) weeks after the last intervention. From baseline to the last follow-up, CAMPHOR scores for symptoms, activity, and QoL improved from 9 (IQR: 6-14) to 3 (IQR: 0-9) (p < 0.001), 8 (IQR: 5-12) to 4 (IQR: 2-8) (p < 0.001), and 5 (IQR: 2-9) to 1 (IQR: 0-5) (p < 0.001).

 BPA leads to long-lasting, significant improvement of symptoms, physical capacity, and QoL in inoperable CTEPH patients.

Balloon pulmonary angioplasty (BPA) is an innovative treatment for chronic thromboembolic pulmonary hypertension (CTEPH). We retrospectively examined the clinical outcomes and complications of BPA at Yokohama City University Hospital (YCUH) between 2012 and 2018. In 2012, we began to conduct BPA sessions in 46 patients with inoperable CTEPH; 34 completed the BPA scheme and the follow-up plan. A longitudinal sub-analysis was performed with cohorts 1 and 2 receiving BPA before and after April 2015. Significant improvements in the mean pulmonary arterial pressure, pulmonary vascular resistance, and other parameters were detected after BPA. The total rate of thoracic complications was 25%. Specifically, the increase in SaO2 and home oxygen therapy discontinuation rate, and oral riociguat discontinuation rate was significantly higher in cohort 2 (+ 7.7, 75, and 59%) compared to cohort 1 (+ 3.1, 27, and 10%) (P < 0.05). Moreover, the need for non-invasive positive pressure ventilation was significantly lower: 0% (cohort 2) vs. 7% (cohort 1) (P < 0.05). The BPA sessions conducted at the YCUH resulted in significant improvements in patients with CTEPH. This study demonstrates a clear learning curve regarding the effectiveness of BPA both in normalizing SaO2 and facilitating the cessation of home oxygen therapy, as well as in reducing the incidence of severe complications.

Endovascular intervention is a safe, effective treatment modality in the management of diverse pulmonary vascular pathologies, including acute or chronic thromboembolic disease, pulmonary arteriovenous malformations (pAVMs), pulmonary artery or bronchial artery hemorrhage, and foreign body retrieval. This article reviews indications, contraindications, techniques, and outcomes in endovascular management of common pulmonary vascular pathologies, with the goal of improving operator familiarity and facility with these procedures.

Chronic thromboembolic pulmonary hypertension (CTEPH) is part of group 4 of the pulmonary hypertension (PH) classification and generally affects more than a third of patients referred to PH centers. It is a three-compartment disease involving proximal (lobar-to-segmental) and distal (subsegmental) pulmonary arteries that are obstructed by persistent fibrothrombotic material, and precapillary pulmonary arteries that can be affected as in pulmonary arterial hypertension. It is a rare complication of pulmonary embolism (PE), with an incidence of around 3% in PE survivors. The observed incidence of CTEPH in the general population is around six cases per million but could be three times higher than this, as estimated from PE incidence. However, a previous venous thromboembolic episode is not always documented. With advances in multimodality imaging and therapeutic management, survival for CTEPH has improved for both operable and inoperable patients. Advanced imaging with pulmonary angiography helps distinguish proximal from distal obstructive disease. However, right heart catheterization is of utmost importance to establish the diagnosis and hemodynamic severity of PH. The therapeutic strategy relies on a stepwise approach, starting with an operability assessment. Pulmonary endarterectomy (PEA), also known as pulmonary thromboendarterectomy, is the first-line treatment for operable patients. Growing experience and advances in surgical technique have enabled expansion of the distal limits of PEA and significant improvements in perioperative and mid- to long-term mortality. In patients who are inoperable or who have persistent/recurrent PH after PEA, medical therapy and/or balloon pulmonary angioplasty (BPA) are effective treatment options with favorable outcomes that are increasingly used. All treatment decisions should be made with a multidisciplinary team that includes a PEA surgeon, a BPA expert, and a chest radiologist.

Riociguat and balloon pulmonary angioplasty (BPA) improve hemodynamics in inoperable chronic thromboembolic pulmonary hypertension. Importantly, comparative effects of riociguat and BPA on different components of right ventricular (RV) afterload and function remain not fully elucidated.

We conducted a post hoc analysis including patients from the RACE trial (Riociguat Versus Balloon Pulmonary Angioplasty in Non-Operable Chronic Thromboembolic Pulmonary Hypertension) with complete data for the primary end point assessment (49 riociguat and 51 BPA). Symptomatic patients with a residual pulmonary vascular resistance >4 WU received add-on riociguat after BPA (n=18) or add-on BPA after riociguat (n=36) and were included in an ancillary 26-week follow-up study with hemodynamic reassessment at week 52.

Cardiac output, stroke volume, and RV afterload improved significantly with riociguat and BPA, and the relative changes in RV afterload from baseline to week 26 were more pronounced in the BPA group (all P<0.001). Change in RV afterload was primarily mediated by decreased mean pulmonary arterial pressure in the BPA group, while increased cardiac output was the main driver in the riociguat group. Key parameters of RV function (RV stroke work and right atrial pressure) improved only in the BPA group. The ancillary follow-up study confirmed that relative change in RV afterload from week 26 to week 52 was more pronounced with add-on BPA, and improved RV function was only observed in the add-on BPA group.

Both riociguat and BPA are effective in improving RV afterload in inoperable chronic thromboembolic pulmonary hypertension. However, BPA provided a more substantial impact on RV afterload reduction, and RV function only improved with BPA.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT02634203.

Background/Objectives: Several studies describe the sex-specific differences in cardiovascular diseases. However, there is still limited research reporting the difference between men and women with chronic thromboembolic pulmonary hypertension (CTEPH) treated with balloon pulmonary angioplasty (BPA). The aim of this study was to evaluate sex-specific differences in patients with CTEPH treated with BPA. Methods: This retrospective study included CTEPH patients treated with BPA. The patients' hemodynamic and clinical parameters were assessed at baseline and 3 months after completion of BPA treatment. Results: This study included 94 patients (44 women, 46.8%). At baseline, women had higher systolic pulmonary arterial pressure (sPAP) (76 ± 18.5 vs. 85 ± 17.6 mmHg; p = 0.03) and pulmonary vascular resistance (8.21 [5.55-10.17] vs. 9.89 [6.31-14.06] Wood Units; p = 0.03) compared to men. There were no differences in clinical characteristics between the sexes. At follow-up, women had lower sPAP (49 [41-54] vs. 43 [37-49] mmHg; p = 0.04) and pulmonary capillary wedge pressure (10 [9-14] vs. 9 [8-11] mmHg; p = 0.03), but a higher cardiac index (2.57 ± 0.53 vs. 2.82 ± 0.50 L/min/m2; p = 0.03), as well as better Dyspnea Borg Scale outcomes, compared to men. Women had a greater reduction in mean pulmonary artery pressure (-43% vs. -37%; p = 0.049) than men. Conclusions: At baseline, women with CTEPH had worse hemodynamic parameters than men despite similar clinical symptoms. However, the hemodynamic status of women was better after BPA therapy. Hence, women seem better adapted to the disease at baseline and respond better to BPA. Further data are needed to investigate whether the management of CTEPH patients should be sex-differentiated.

Chronic thromboembolic pulmonary disease (CTEPD) and chronic thromboembolic pulmonary hypertension (CTEPH) are debilitating complications of acute pulmonary embolism (PE) that are characterized by fibrosis and organization of the thrombotic material within pulmonary artery branches. This pathology leads to increased right ventricular afterload and dead space ventilation, posing a risk of progressive pulmonary hypertension, right-sided heart failure, and potentially death if left untreated. Pulmonary endarterectomy (PTE) is a technically complex open-heart surgery considered to be a first-line treatment as it is a potentially curative therapy. Although PTE is highly successful in proximal disease, it may not reach the very distal branches. On the other hand, pulmonary vasodilator therapy is very effective in improving microvasculopathy but does not address the obstructive fibrotic component of the larger vessels. Balloon pulmonary angioplasty (BPA) is a novel percutaneous revascularization therapy in which traditional angioplasty techniques are used to relieve obstruction in the pulmonary arteries. This review discusses the currently accepted indications, patient selection, technical considerations, outcomes, and complications of contemporary BPA. This review will address knowledge gaps and future perspectives in BPA research.

A significant number of patients with chronic thromboembolic pulmonary hypertension (CTEPH) are not eligible for pulmonary endarterectomy and may be treated with balloon pulmonary angioplasty (BPA). Although BPA programs have recently been developed in Brazil, no results have yet been published. The objective of this study was to assess the clinical and hemodynamic progression of the first patients treated with BPA at our center.

This was an observational study of 23 patients with CTEPH enrolled in the BPA program of a specialized center in Brazil between 2015 and 2020.

After a mean of 5.6 ± 1.3 sessions and 11 ± 2.8 treated segments/patient (at a mean of 6.7 ± 2.9 months post-BPA), there was a 26% decrease in mean pulmonary artery pressure (51 ± 11 vs. 38 ± 11 mmHg; p < 0.0001), a 43% decrease in pulmonary vascular resistance (10 ± 3.7 vs. 5.7 ± 3.3 WU; p < 0.0001), and a 22.5% increase in the cardiac index (2.38 ± 0.6 vs. 2.95 ± 0.6 L/min/m2; p < 0.0001). There was an increase in the six-minute walk distance and an improvement in functional class. Acute lung injury with clinical manifestations was observed after 7% of the BPA sessions. None of the patients required intubation. During a mean outpatient follow-up period of 38 ± 22 months, two patients were referred for additional BPA sessions due to clinical worsening and new hospitalizations. Two deaths were recorded (due to CTEPH progression and gastrointestinal bleeding, respectively).

Among this first group of patients treated with BPA in Brazil, there was significant short- and long-term clinical improvement, together with a low frequency of complications.

Pulmonary endarterectomy (PEA) is the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH), while balloon pulmonary angioplasty (BPA) is an alternative for inoperable patients. We aimed to compare right ventricular (RV) remodelling and late survival after PEA and BPA.

In this prospective observational cohort study, we performed echocardiography at baseline and follow-up in patients with CTEPH treated with PEA (n=54) or BPA (n=44) between 2011 and 2022.

Follow-up echocardiography was performed at 5 months (IQR 4-7) after PEA and 3 months (IQR 2-4) after the last BPA. Both groups showed significant improvements in left ventricular end-systolic eccentricity index, RV basal diameter and RV fractional area change (RV FAC). Tricuspid regurgitation pressure decreased by 26±18 mm Hg after PEA and 13±21 mm Hg after BPA (p=0.02 for between-group difference). Tricuspid annular systolic excursion (TAPSE) decreased by 4±5 mm after PEA but increased by 1±4 mm after BPA (p<0.001). The TAPSE/systolic pulmonary artery pressure ratio improved similarly in both groups. Five-year survival was 96% (95% CI 86% to 99%) for PEA and 79% (95% CI 61% to 89%) for BPA (p=0.25). Change in RV FAC was an independent predictor of survival (HR 0.9, 95% CI 0.82 to 0.99, p=0.03).

Both PEA and BPA led to significant RV reverse remodelling, with no clear evidence of a difference in survival rates. Improvement in RV function, particularly RV FAC, was associated with better outcomes, highlighting the importance of RV recovery in CTEPH treatment.

Prognosis of chronic thromboembolic pulmonary hypertension (CTEPH) has improved after the availability of balloon pulmonary angioplasty (BPA) and approved drugs. However, the clinical effects of cancer, which is one of the associated medical conditions of CTEPH, remain unclear. We aimed to investigate prognosis in patients with CTEPH and comorbid cancer.

Between January 2011 and December 2022, data of 264 consecutive patients with CTEPH who were treated with pulmonary endarterectomy, BPA, or medical therapy were retrospectively analyzed. The patients were allocated, based on the comorbidity of cancer as of December 2022, into the cancer (n = 47) and non-cancer (n = 217) groups. In the cancer group, active and non-active cancers were identified in 30 (64%) and 17 (36%) patients, respectively.

The baseline characteristics, hemodynamics, and treatments were similar between the groups. More than half of the cancer were diagnosed within two years before or after CTEPH diagnosis. Twenty-seven patients died during the study period. Among them, 13 (48%) and 7 (26%) died of cancer and right heart failure, respectively. The 5-year survival rate was lower in the cancer group than in the non-cancer group (67.8% vs. 94.5%, p < 0.001). In the active cancer group, the 5-year survival rate was also lower than that in the non-active cancer and non-cancer groups (52.0% vs. 99.5%, p < 0.001 and 52.0% vs. 92.3%, p < 0.001, respectively). Multivariate Cox hazard analysis revealed that hemodialysis (p < 0.001) and cancer (p < 0.001) were independently associated with poor survival.

Patients with CTEPH rarely die of right heart failure, even if hemodynamically severe at diagnosis in the modern management era. However, patients with CTEPH frequently have comorbid cancer, which may be a strong prognostic factor.

Pulmonary embolism (PE) is a life-threatening medical condition caused by the thrombotic occlusion of one or more branches of the lung vasculature, which represents the third most common cause of cardiovascular mortality after myocardial infarction and stroke. PE treatment requires a tailored approach based on accurate risk stratification and personalized treatment decision-making. Anticoagulation is the cornerstone of PE management, yet patients at higher clinical risk may require more rapid reperfusion therapies. In recent years, transcatheter treatment has emerged as a valuable option for patients with intermediate-high or high-risk PE who have contraindications to systemic thrombolysis. Recent advancements in catheter-directed therapies, such as catheter-directed thrombolysis (CDT) and catheter-directed mechanical thrombectomy (CDMT), provide minimally invasive options for swift symptom relief and hemodynamic stabilization. This review aims to provide a practical approach for optimal patient selection and management for PE percutaneous therapies, supported by a thorough evaluation of the current evidence base supporting these procedures. A focus on post-procedural management, the prevention of recurrence, and monitoring for long-term complications such as chronic pulmonary hypertension and post-PE syndrome is also specifically tackled.

Among survivors of acute pulmonary embolism (PE), roughly half report persistent dyspnea, impaired functional status, and decreased quality of life. Post-pulmonary embolism syndrome (PPES) is a broad condition which has been increasingly recognized in recent years and may be due to post-pulmonary embolism functional impairment, chronic thromboembolic disease, or the most severe long-term complication of PE, chronic thromboembolic pulmonary hypertension. Despite guideline recommendations for appropriate follow-up for post-pulmonary embolism patients, PPES remains underrecognized and diagnostic testing underutilized. Patients with symptoms suggestive of PPES at follow-up should undergo a transthoracic echocardiogram to screen for the presence of pulmonary hypertension; additional testing, such as a ventilation/perfusion scan, right heart catheterization, and cardiopulmonary exercise testing may be indicated. The pathophysiology of post-pulmonary embolism syndrome is complex and heterogeneous. In chronic thromboembolic pulmonary hypertension, the pathophysiology reflects persistent pulmonary arterial thrombi and a progressive small vessel vasculopathy. In patients with chronic thromboembolic disease or chronic thromboembolic pulmonary hypertension, medical therapy, balloon pulmonary angioplasty, or pulmonary thromboendarterectomy should be considered, and in cases of chronic thromboembolic pulmonary hypertension, pulmonary thromboendarterectomy significantly improves mortality. In all causes of post-pulmonary embolism syndrome, rehabilitation is a safe treatment option that may improve quality of life.

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.

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.

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.

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.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT02656238.

Some patients with chronic thromboembolic pulmonary hypertension (CTEPH) exhibit exercise intolerance due to reduced cardiac output (CO) even after successful balloon pulmonary angioplasty (BPA). Medical therapy is a potential option for such cases; however, it is unclear which patients necessitate it even after BPA.

This study included 286 patients with CTEPH who underwent BPA and right heart catheterization 1 year after the final BPA and classified them into no-medication and withdrawal groups. The no-medication group comprised patients without pulmonary hypertension (PH) medications before and after BPA, while the withdrawal group included patients who received PH medications before BPA and discontinued them after BPA. We assessed differences in the changes in CO after BPA from baseline (ΔCO) between the 2 groups. Additionally, we evaluated the ΔCO among different age categories within each group: younger (<60 years), middle-aged (60-70 years), and older adults (≥70 years).

After adjusting baseline covariates, overall CO did not differ significantly. However, ΔCO was significantly positive in the no-medication group but negative in the withdrawal group (0.32 and -0.33, difference in ΔCO: -0.65, 95% confidence intervals: -0.90 to -0.40). A significantly positive effect on ΔCO was observed in younger and middle-aged individuals, with a significant interaction between age and ΔCO in no-medication groups.

Increasing CO with BPA alone may be challenging with age in patients with CTEPH. Given that discontinuation of PH medication after BPA decreased CO more than the effect of BPA, medical therapy might be necessary even after successful BPA.

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%.

Although surgical and interventional therapy has emerged as the primary treatment for patients with chronic thromboembolic pulmonary hypertension (CTEPH), there remains a subset of patients who need medication therapy. This study aimed to evaluate the efficacy and safety outcomes of prostacyclin pathway vasodilators, providing further insight for clinical decision-making. A literature search was conducted in PubMed, Embase, and CENTRAL databases from inception to December 2023. Literature screening and quality assessment were carried out with the Cochrane Risk of Bias Tool. Data analysis was conducted using RevMan 5.4 software. We included 6 randomized controlled trials with 387 patients. Prostacyclin pathway vasodilators demonstrated a significant improvement in PVR (-125.26 dynes·sec·cm-5, 95%CI: -219.29 to -31.23, Z = 2.61, and p < 0.009), RAP (-0.78 mmHg, 95%CI: -1.52 to -0.04, Z = 2.06, and p = 0.04), cardiac index (0.62, 95%CI: 0.54 to 0.69, Z = 16.13, and p < 0.00001), and the number of patients showing improvement in WHO functional class (3.86, 95%CI: 1,92 to 7.77, Z = 3.79, and p = 0.0002) compared to controls, moreover, a trend towards improvement was observed in mPAP, 6MWD, and NT-proBNP. Regarding the safety endpoints, no significant difference was found in both groups in terms of serious adverse events and all-cause deaths. The prostacyclin pathway vasodilators present therapeutic potential for CTEPH patients with inoperable or persistent/recurrent PH after PEA/BPA primarily characterized by distal small-vessel and microvasculopathy. However, the current clinical evidence remains insufficient and controversial, necessitating further validation.

Overnight inpatient monitoring is common following balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension (CTEPH). We describe our institutional experience in same-day discharge (SDD) after BPA. Across 78 BPA sessions, there were only 2 (2.6%) admissions for hemoptysis with no reperfusion lung injury or deaths at 30 days.

Right ventricle (RV)-to-pulmonary artery (PA) coupling measured by the ratio of echocardiography-derived tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP) is a meaningful prognostic marker in pulmonary hypertension (PH). It's unclear if balloon pulmonary angioplasty (BPA) treatment of chronic thromboembolic pulmonary hypertension (CTEPH) alters RV-PA coupling measured by TAPSE/PASP. We reviewed CTEPH patients treated with BPA at our institution who had a transthoracic echocardiogram (TTE) before BPA and a follow-up TTE at any point during BPA. TAPSE was obtained from the initial and lattermost TTE; hemodynamics were obtained before each BPA session. Between March 2015 to October 2023, there were 228 patients treated with BPA. After excluding post-PTE patients and those without PH, 67 were included. Initial TAPSE/PASP was 0.39 ± 0.21 mm/mmHg. Using previously defined TAPSE/PASP tertiles in PH (<0.19, 0.19-0.32, >0.32 mm/mmHg), there were 6 patients (9%) in low, 30 (45%) in middle, and 31 (46%) in the high tertiles at baseline. The lower TAPSE/PASP tertiles had more severe baseline hemodynamics (p < 0.001) compared to the high TAPSE/PASP cohort. At follow-up, TAPSE/PASP improved to 0.47 ± 0.20 mm/mmHg (p = 0.023), with 2 (3%), 13 (19%), and 52 (78%) patients in the low, middle, high TAPSE/PASP tertiles, respectively. As patients progress through BPA sessions, the TAPSE/PASP ratio increases, possibly reflecting improved RV mechanics and RV-PA coupling. TAPSE/PASP ratio as a marker of RV-PA coupling can improve with BPA treatment and may be an important measure to follow during treatment of CTEPH.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism and a major cause of chronic pulmonary hypertension leading to right heart failure and death. While pulmonary endarterectomy is the treatment of choice, some patients might benefit from medical therapy or balloon pulmonary angioplasty. Sex differences in outcomes of these therapies are not well characterized.

We conducted a systematic review and meta-analysis to investigate sex differences in outcomes of various therapies for CTEPH. We searched MEDLINE, PubMed, Embase, CINAHL and the Cochrane Library databases between January 1, 2010 and April 30, 2021, published in English. We pooled incidence estimates using random-effects meta-analyses. We evaluated heterogeneity using the I2 statistic. We assessed publication bias using Begg's and Egger's tests. This study is registered in PROSPERO, CRD42021268504.

A total of 19 studies met the eligibility criteria, but only 3 trials provided separate outcomes for women and men. Two studies evaluated the efficacy of BPA, and one study evaluated the efficacy of riociguat (129 patients). Overall, 57.3% of patients were women and 62.6% were in functional class III. Mean time of follow-up was 55.5 (SD 26.1) weeks. Women showed a significantly better response in cardiac index (mean difference [MD], 0.10L/min/m2; 95% confidence interval [CI], 0.04-0.16; I2=0%; P=0.001). Alternatively, the reduction of pulmonary vascular resistances was significantly higher for men than for women (MD, 161.17dynscm-5; 95% CI, 67.99-254.35; I2=0%; P=0.0007).

Women and men might show different hemodynamic responses to riociguat or BPA for CTEPH.

Over the last decades, significant progress has been achieved in the pulmonary hypertension (PH) field. Pathophysiology of PH has been studied, leading to the classification of PH patients into five groups, while the hemodynamic definition has been recently revised. A diagnostic algorithm has been established and awareness has been raised in order to minimize diagnosis delay. The pulmonary arterial hypertension (PAH) treatment strategy includes the established three pathways of endothelin, nitric oxide-phosphodiesterase inhibitor, and prostacyclin pathway, but new therapeutic options are now being tested. The aim of this review is to summarize the existing practice and to highlight the novelties in the field of PH.

Balloon pulmonary angioplasty (BPA) is an effective intervention for patients with chronic thromboembolic pulmonary disease (CTEPD). We aimed to identify the patient group with a low success rate or high complication rate of BPA, which is still unclear.

Both CTEPD patients with or without pulmonary hypertension (CTEPH and NoPH-CTEPD) were included. CTEPH patients were divided into groups with or without pulmonary endarterectomy (PEA-CTEPH and NoPEA-CTEPH). The efficacy and safety of BPA were compared among the groups.

There were 450, 66, and 41 sessions in the NoPEA-CTEPH, PEA-CTEPH, and NoPH-CTEPD groups, respectively. The success rate (≥1 degree improvement in flow grade) in the PEA-CTEPH group was 94.5%, significantly lower than that in the NoPEA-CTEPH (97.1%) and NoPH-CTEPD (98.4%) groups (p = 0.014). The percentage of complete flow recovery in treated vessels was also lower in PEA-CTEPH group. BPA-related complication rate in NoPEA-CTEPH, PEA-CTEPH, and NoPH-CTEPD patients was 6.1%, 6.0%, and 0.0%, respectively (p = 0.309). One BPA-related death occurred (solely in NoPEA-CTEPH). Mean pulmonary artery pressure ≥41.5 mm Hg was a predictor of BPA-related complications. NoPEA-CTEPH patients had more improvement in 6-min walk distance (6MWD, 87 ± 93 m NoPEA-CTEPH vs. 40 ± 43 m PEA-CTEPH vs. 18 ± 20 m NoPH-CTEPD, p = 0.012).

BPA was safe and effective for all CTEPD groups with less improvement for the PEA-CTEPH and NoPH-CTEPD groups. The success rate of BPA was lower in the PEA-CTEPH group and the complication rate was lower in the NoPH-CTEPD group. Pre-BPA treatment to lower pulmonary artery pressure should not be overlooked in CTEPD patients.

Ring finger protein 213 (RNF213) p.Arg4810Lys is a susceptibility gene for moyamoya disease, peripheral pulmonary artery stenosis (PPS), and other vascular diseases and thrombosis. We investigated the prevalence and clinical characteristics of RNF213 variant carriers diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH).

We retrospectively analyzed the prevalence of the RNF213 p.Arg4810Lys variant in patients diagnosed with CTEPH (n=112) and PPS (n=10). Clinical and angiographic characteristics were evaluated between RNF213 variant carriers diagnosed with CTEPH and noncarriers with CTEPH and homozygous variant carriers with PPS. Eight heterozygous RNF213 p.Arg4810Lys variant carriers (7.1%) were identified among patients diagnosed with CTEPH, while 5 patients with PPS (50%) carried the homozygous variant. The clinical characteristics of heterozygous variant carriers with CTEPH were not remarkably different from those of noncarriers with CTEPH. All heterozygous variant carriers with CTEPH showed webs/bands lesions at the segmental/subsegmental level, with 75% showing distal tortuous vessels. None of the heterozygous variant carriers with CTEPH exhibited the string-of-beads pattern or elongated stenosis. Homozygous variant carriers with PPS showed the string-of-beads pattern, elongated stenosis, and distal tortuous vessels without webs/bands lesions.

A subset of patients diagnosed with CTEPH (7.1%) carried the heterozygous RNF213 p.Arg4810Lys variant. Clinical and angiographic characteristics of heterozygous variant carriers were not remarkably different from those of noncarriers of CTEPH. However, both heterozygous variant carriers with CTEPH and homozygous variant carriers with PPS showed tortuous vessels on angiography.

Knowledge of the anatomy of pulmonary arteries is essential in many invasive procedures concerning pulmonary circulation. In the diagnosis and treatment of chronic thromboembolic pulmonary hypertension (CTEPH), two-dimensional (2D) pulmonary angiography is used. Recognizing the topographic course of the pulmonary arteries and understanding the status in three dimensions (3D) is paramount. This study aimed to evaluate and describe the branching variant of pulmonary arteries in a single case, as well as morphological parameters of the segmental arteries, like length, diameter and branching angles.

One pair of embalmed human cadaver lungs was dissected by a scalpel and surgical forceps and was measured up to the subsegmental arteries.

The diameters (ranging from 3.04 to 9.29 mm) and lengths (ranging from 9.09 to 53.91 mm) of the pulmonary segmental arteries varied. The proximal branching angles were wide and close to perpendicular, while distally, the angles between the segmental and subsegmental arteries were narrower (30-45°). Upon evaluating the branching, rare variations were identified and delineated, notably in the lower lobes of both lungs.

Utilizing knowledge and data in clinical settings is instrumental for effectively diagnosing and treating CTEPH. Further research is required to explore the complications in invasive procedures related to various anatomical variations.

Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension (CTEPH) is limited by a lack of safe and effective tools for crossing these lesions. We aim to identify a safety window for an intraluminal crossing device in this vascular bed by studying the piercing properties of pulmonary arterial vessel walls and intraluminal CTEPH lesion specimens. As a secondary objective, we also describe the histopathologic features of CTEPH lesions.

Specimens were procured from 9 patients undergoing pulmonary endarterectomy. The specimens were subsampled and identified grossly as arterial wall or intraluminal CTEPH lesions. The force needed for tissue penetration was measured using a 0.38-mm (0.015-in) diameter probe in an ex vivo experimental model developed in our lab. Concurrent histology was also performed.

The mean force needed to penetrate the arterial wall and intraluminal CTEPH lesions was 1.75 ± 0.10 N (n = 121) and 0.30 ± 0.04 N (n = 56), respectively (P < .001). Histology confirmed the presence of intimal hyperplasia with calcium and hemosiderin deposition in the arterial wall as well as an old, organized thrombus in the lumen.

The pulmonary arterial wall is friable and prone to perforation during instrumentation with workhorse coronary guide wires. However, the results of this study demonstrate that a much lower force is needed for the 0.38-mm (0.015-in) probe to penetrate an intraluminal CTEPH lesion compared to pulmonary arterial intima. This finding suggests the existence of a safety window for lesion-crossing devices, enabling effective balloon pulmonary angioplasty.