The function of the right ventricle (RV) is dependent on preload, end-systolic elastance (afterload), and intrinsic RV contractility. RV dysfunction comprises dilatation and hypertrophy, leading to RV failure and commonly death despite advances in medical treatments. This systematic review summarizes current and future interventional treatments to mechanically unload the RV. First, this review focuses on targeting pulmonary vascular afterload by addressing 1. Catheter-directed treatment for acute pulmonary embolism, 2. Balloon Pulmonary Angioplasty for chronic thromboembolic pulmonary hypertension, and 3. Pulmonary Artery Denervation for pulmonary hypertension. Second, mechanical support systems for enhancing RV contractility and interventions targeting tricuspid regurgitation as a cause of RV failure are discussed.

On 2nd December 2024, a systematic search for publications between 2022 and 2025 was performed, using MEDLINE, EMBASE, Cochrane, and SCOPUS. The primary outcome was an improvement in hemodynamic measurements. Secondary outcomes included in-hospital mortality and complications. Meta-analyses, randomized controlled trials and for newer devices, observational studies and case series were included.

Of 32,852 screened studies, 80 were included. All treatments demonstrated various degrees of RV unloading.

Novel treatments directed at mechanical RV unloading may improve survival, but further research is needed to examine long-term effects.

CRD42024616310.

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.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive form of pulmonary hypertension characterized by unresolved thromboembolic occlusion of pulmonary arteries, leading to increased pulmonary arterial pressure and right heart failure. This review examines recent advances in the pathophysiology, diagnosis, and management of CTEPH, focusing on expanding disease concepts and evolving therapeutic approaches. The incidence of CTEPH has been revised upward with improved diagnostic techniques revealing a higher prevalence than previously recognized. Advances in surgical and interventional therapies, particularly pulmonary endarterectomy and balloon pulmonary angioplasty, have significantly improved outcomes. Emerging medical therapies, including pulmonary vasodilators like riociguat, have offered new hope for inoperable cases. The understanding of CTEPH has broadened, leading to better diagnostic strategies and more comprehensive treatment options that significantly enhance patient outcomes. Multidisciplinary team approaches are crucial in managing the disease effectively.

Balloon pulmonary angioplasty (BPA) has emerged as a crucial intervention for patients with chronic thromboembolic pulmonary hypertension (CTEPH) unsuitable for surgery. However, the complexity of pulmonary vasculature in CTEPH necessitates advanced imaging techniques for precise procedural diagnosis and planning. This review highlights the role of cone-beam CT pulmonary angiography (CBCT-PA) in enhancing the visualization and characterization of the pulmonary vasculature. Specific advantages over traditional imaging methods like digital subtraction angiography and CT pulmonary angiography are discussed. CBCT-PA provides detailed three-dimensional roadmaps, optimizing procedural parameters that can improve safety and efficacy. Despite these advantages, standardized protocols for CBCT-PA are lacking, underscoring the need for structured guidelines to fully integrate this technology into BPA programs for better clinical outcomes in CTEPH patients.

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.

Primary pulmonary hypertension (PPH), now known as pulmonary arterial hypertension (PAH), has induced significant treatment breakthroughs in the past decade. Treatment has focused on improving patient survival and quality of life, and delaying disease progression. Current therapies are categorized based on targeting different pathways known to contribute to PAH, including endothelin receptor antagonists (ERAs), phosphodiesterase-5 inhibitors (PDE-5 inhibitors), prostacyclin analogs, soluble guanylate cyclase stimulators, and activin signaling inhibitors such as Sotatercept. The latest addition to treatment options is soluble guanylate cyclase stimulators, such as Riociguat, which directly stimulates the nitric oxide pathway, facilitating vasodilation. Looking to the future, advancements in PAH treatment focus on precision medicine involving the sub-stratification of patients through a deep characterization of altered Transforming Growth Factor-β(TGF-β) signaling and molecular therapies. Gene therapy, targeting specific genetic mutations linked to PAH, and cell-based therapies, such as mesenchymal stem cells, are under investigation. Besides prevailing therapies, emerging PH treatments target growth factors and inflammation-modulating pathways, with ongoing trials assessing their long-term benefits and safety. Hence, this review explores current therapies that delay progression and improve survival, as well as future treatments with curative potential.

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.

Registry data suggest women are less likely than men to undergo pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension despite a similar proportion of proximal vs distal disease. We hypothesized that sex-specific differences could be elicited with a computed tomography pulmonary angiography analysis beyond proximal vs distal.

Preoperative computed tomography pulmonary angiography of patients who underwent pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension from January 2017 to September 2021 was analyzed. The pulmonary vascular tree was divided into 32 named vessels with chronic thromboembolism presence and lesion type recorded for each vessel. If no lesion was identified in a segmental vessel, subsegmental disease was recorded when present.

One hundred forty-four patients (mean age 57 ± 15 years, 78 women) were included. There were no sex differences in baseline hemodynamics. Men had more vessels involved than women (mean 20.3 vs 17.1, p = 0.004) and had fewer disease-free pulmonary segments (mean 4.9 ± 4.3 vs 7.6 ± 5.5, p = 0.001). Men had a greater number of webs, eccentric thickening, and occlusions. The distribution of lesion type did not significantly differ between sexes at the main or lobar level but men had significantly more lesions in the segmental vasculature while women had a higher proportion of subsegmental lesions (p < 0.001).

Sex-specific differences in chronic thromboembolic pulmonary hypertension are demonstrated on computed tomography pulmonary angiography in overall distribution and lesion type at the segmental and subsegmental level with women having fewer and more distal lesions despite similar hemodynamics.

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.

Three mutually exclusive entities can underlie a postpulmonary embolism syndrome (PPES): not obstructed postpulmonary embolism syndrome (post-PE dyspnea), chronic thromboembolic pulmonary disease (CTEPD), and chronic thromboembolic pulmonary hypertension (CTEPH). Cardiorespiratory impairment in CTEPH and CTEPD underlies respiratory and hemodynamic mechanisms, either at rest or at exercise. Gas exchange is affected by the space effect, the increased blood velocity, and, possibly, intracardiac right to left shunts. As for hemodynamic effects, after a period of compensation, the right ventricle dilates and fails, which results in retrograde and anterograde right heart failure. Little is known on the pathophysiology of post-PE dyspnea, which has been reported in highly comorbid with lung and heart diseases, so that a "two-hit" hypothesis can be put forward: it might be caused by the acute myocardial damage caused by pulmonary embolism in the context of preexisting cardiac and/or respiratory diseases. More than one-third of PE survivors develops PPES, with only a small fraction (3-4%) represented by CTEPH. A value of ≈3% is a plausible estimate for the incidence of CTEPD. Growing evidence supports the role of CTEPD as a hemodynamic phenotype intermediate between post-PE dyspnea and CTEPH, but it still remains to be ascertained whether it constantly underlies exercise-induced pulmonary hypertension and if it is a precursor of CTEPH. Further research is needed to improve the understanding and the management of CTEPD and post-PE dyspnea.

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%.

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.

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.

Decreased diffusing capacity of the lungs for carbon monoxide (DLco) is associated with microvascular damage in chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) is an effective treatment for CTEPH, but the efficacy of BPA in patients with CTEPH with low DLco remains unclear because BPA does not directly address microvascular damage. This study investigates the influence of microvasculopathy on BPA in CTEPH according to DLco.

We retrospectively analysed data from patients with inoperable CTEPH who underwent BPA at the University of Tokyo Hospital from July 2011 to August 2023. The patients were classified into two groups based on their preprocedural DLco (normal DLco (ND) and low DLco (LD) groups), with a DLco cut-off value of 80%. We compared the patient characteristics and effectiveness of BPA between the groups.

Among the 75 patients, 36 were in the LD group. The LD group had a shorter 6-minute walking distance (324±91 vs 427±114 m) than the ND group but the mean pulmonary artery pressure (mPAP) was similar (38.9±7.3 vs 41.1±9.2 mm Hg) before BPA. BPA improved the haemodynamic status and exercise tolerance in both groups. The LD group exhibited a higher mPAP (25.1±7.4 vs 21.5±5.6 mm Hg) and required more sessions of BPA (median 6 vs 4). Based on the analysis of covariance adjusted for baseline values, low DLco significantly correlated with mPAP (sβ=-0.304, 95% CI -7.015 to -1.132, p=0.007) and pulmonary vascular resistance (sβ=-0.324, 95% CI -141.0 to -29.81, p=0.003).

BPA was associated with an improvement in the haemodynamic status and exercise tolerance in patients with CTEPH even with low DLco. However, low DLco may attenuate the effect of BPA on mPAP and pulmonary vascular resistance and require more treatment sessions.

This research evaluates the effect of balloon pulmonary angioplasty (BPA) on cardiac electrophysiological changes in patients with chronic thromboembolic pulmonary hypertension (CTEPH).

Involving a retrospective analysis of 39 CTEPH patients (average age 61 ± 11), who had at least two BPAs and paired ECGs pre- and post-surgery, we examined changes in ECG indicators of right ventricular hypertrophy and their correlation with hemodynamic results.

BPA yielded marked improvements in cardiac function and hemodynamics. ECG parameters, specifically the Lewis criteria and Butler-Leggett score, correlated strongly with hemodynamics and were predictive of a mean pulmonary arterial pressure (mPAP) ≥ 35mmHg. Notably, QRS complex axis normalization was observed in 25 patients, with 14 fully normalizing (range - 30° to + 90°). The qR pattern in V1 vanished in 9 cases, and 75% of the patients in qR pattern in V1 group had QRS complex electrical axis completely returned to normal range. The qR V1 group had higher mPAP and pulmonary vascular resistance (PVR), and lower cardiac output and index compared to the non-qR V1 group, alongside a higher Butler-Leggett score.

BPA enhances cardiac function and hemodynamics in CTEPH patients, with certain ECG measures such as Lewis criteria and Butler-Leggett score reflecting the severity of hemodynamic impairment. The reversal of QRS axis deviation and the disappearance of the qR pattern in lead V1 may serve as valuable indicators for assessing post-BPA satisfaction in CTEPH patients.

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.

Sleep-disordered breathing (SDB) and nocturnal hypoxemia were known to be present in patients with chronic thromboembolic pulmonary hypertension (CTEPH), but the difference between SDB and nocturnal hypoxemia in patients who have chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) at rest remains unknown.

Patients who had CTEPH (n = 80) or CTEPD without PH (n = 40) and who had undergone sleep studies from July 2020 to October 2022 at Shanghai Pulmonary Hospital were enrolled. Nocturnal mean SpO2 (Mean SpO2) <90% was defined as nocturnal hypoxemia, and the percentage of time with a saturation below 90% (T90%) exceeding 10% was used to evaluate the severity of nocturnal hypoxemia. Logistic and linear regression analyses were performed to investigate the difference and potential predictor of SDB or nocturnal hypoxemia between CTEPH and CTEPD without PH.

SDB was similarly prevalent in CTEPH and CTEPD without PH (P = 0.104), both characterised by obstructive sleep apnoea (OSA). Twenty-two patients with CTEPH were diagnosed with nocturnal hypoxemia, whereas only three were diagnosed with CTEPD without PH (P = 0.021). T90% was positively associated with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance in patients with CTEPH and CTEPD without PH (P < 0.001); T90% was also negatively related to cardiac output in these patients. Single-breath carbon monoxide diffusing capacity, sex and mPAP were all correlated with nocturnal hypoxemia in CTEPH and CTEPD without PH (all P < 0.05).

Nocturnal hypoxemia was worse in CTEPD with PH; T90%, but not SDB, was independently correlated with the hemodynamics in CTEPD with or without PH.

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.

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a severe and complex condition that evolves from unresolved pulmonary embolism, leading to fibrotic obstruction of pulmonary arteries, pulmonary hypertension, and potential right heart failure. The cornerstone of CTEPH management lies in a multifaceted therapeutic approach tailored to individual patient profiles, reflecting the disease's heterogeneity. This review delves into the current therapeutic strategies for CTEPH, including surgical pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA), and targeted pharmacological treatments such as PDE5 inhibitors, endothelin receptor antagonists, sGC stimulators, and prostanoids. Lifelong anticoagulation is also highlighted as a preventive strategy against recurrent thromboembolism. Special emphasis is placed on the interdisciplinary nature of CTEPH care, necessitating collaboration among PEA surgeons, BPA interventionists, PH specialists, and thoracic radiologists to ensure comprehensive treatment planning and execution. The review underscores the importance of selecting an appropriate treatment modality based on the patient's specific disease characteristics and the evolving landscape of CTEPH treatment, aiming to improve patient outcomes through integrated care strategies.

Background/Objectives: The literature reports high complication rates in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who undergo balloon pulmonary angioplasty (BPA), especially in patients with poor pulmonary hemodynamics. Here, we describe the complications of BPA based on the new definitions. Methods: All patients with CTEPH who completed BPA treatment before 15 September 2023 were selected from the CTEPH database. Peri-procedural complications were collected and classified according to the 2023 consensus paper on BPA treatment. Complications were analyzed in subgroups of patients with pulmonary vascular resistance (PVR), ≤ or >6.6 WU, and mean pulmonary artery pressure (mPAP), ≤ or >45 mmHg, at first BPA. Results: In this analysis, 87 patients (63% women; mean age 61.1 ± 14.0 years; 62% on dual PH targeted medical therapy) underwent 426 (mean 4.9 ± 1.6 per patient) BPAs. Only non-severe complications occurred in 14% of BPA treatments and in 47% of the patients; 31% patients had a thoracic complication. The thoracic complications were mild (71%) or moderate (29%). Patients with a PVR > 6.6 WU (n = 8) underwent more BPA treatments (6.6 ± 1.5 versus 4.6 ± 1.5, p = 0.002), had more complications (88% versus 41% of patients, p = 0.020), and had more thoracic complications (17% vs. 7% of BPAs, p = 0.013) than patients with PVR ≤ 6.6 WU. Patients with mPAP > 45 mmHg (n = 13) also had more BPA treatments (6.5 ± 1.7 versus 4.6 ± 1.4, p < 0.001), more complications (77% versus 44% of patients, p = 0.027) and more thoracic complications (14% versus 8% of BPAs, p = 0.039) than patients with mPAP ≤ 45 mmHg. Conclusions: Complications occurred in 14% of BPAs and were mostly mild. Patients with severe pulmonary hemodynamics suffered more (thoracic) complications.

Therapies for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) include balloon pulmonary angioplasty (BPA) and PH-specific medical therapy. This study compares survival and its predictors before and after the introduction of BPA. BPA was independently associated with survival; however, there was no difference in overall survival between the two cohorts.

The present study aimed to evaluate the efficacy of long-term riociguat sequentially combined with balloon pulmonary angioplasty (BPA) for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Eight inoperable CTEPH patients were enrolled in this study, who have been administrated riociguat 2.5 mg three times daily for about 8 years, then underwent several sessions of BPA procedures. Data are prospectively collected to evaluate clinical outcomes, hemodynamics, exercise capacity, and right heart size and function by echocardiography at baseline, 8 years after riociguat, and 3 months after the final BPA. Eight patients (mean age 54.9 ± 11.4 years) were treated with riociguat 2.5 mg three times daily for 95.0 ± 10.7 months. Cardiac index (CI) (1.5 ± 0.5 L/min/m2 to 2.4 ± 0.6 L/min/m2, p = 0.005), 6 min walking distance (6MWD) (329.6 ± 87.5 m to 418.1 ± 75.8 m, p = 0.016), and pulmonary vascular resistance (PVR) (1336.9 ± 320.2 dyn·s·cm-5 to 815.4 ± 195.6 dyn·s·cm-5, p = 0.008) were significant improvement after riociguat treatment. Mean 4.1 ± 1.6 additional combinational BPA sessions and mean 18.8 ± 8.1 balloon dilations were performed. Mean pulmonary artery pressure (54.1 ± 11.1 mmHg to 33.6 ± 7.7 mmHg, p = 0.002) and PVR (815.4 ± 195.6 dyn·s·cm-5 to 428.3 ± 151.2 dyn·s·cm-5, p＜0.001) were further decreased. CI (2.4 ± 0.6 L/min/m2 to 2.7 ± 0.7 L/min/m2, p = 0.028) and 6MWD (418.1 ± 75.8 m to 455.7 ± 100.0 m, p = 0.038) were increased significantly. After long-term riociguat treatment, sequential combination with BPA delivered considerably incremental benefits on exercise capacity and pulmonary hemodynamics, as well as right heart size and function of technically inoperable CTEPH patients.

Natural hemodynamic changes after balloon pulmonary artery angioplasty (BPA) in a unified state without oxygen administration in patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains undetermined. This study aimed to clarify the delayed changes in the hemodynamics after BPA in patients with CTEPH. We analyzed 73 consecutive patients with CTEPH who underwent BPA between July 2014 and December 2022. We extracted and evaluated hemodynamic data of the right heart catheter without oxygen administration immediately before and after the first BPA; and immediately before the second BPA, as the "post-delayed changes" after BPA. BPA significantly improved the mean pulmonary artery pressure (mPAP, mmHg) and pulmonary vascular resistance (PVR, dyn-s/cm5) from 36 (32-43) mmHg and 449 (312-627) dyn-s/cm5 before the first BPA to 28 (23-32) mmHg and 275 (217-366) dyn-s/cm5 immediately after BPA, and further significantly improved the values to 23 (20-28) mmHg and 225 (175-301) dyn-s/cm5 post-delayed changes after BPA, respectively. Improvement observed on account of delayed changes was observed both with and without pulmonary hypertension drugs. The delayed changes were observed during a period of 5-180 days, which did not correlate with the changes in mPAP and PVR. Hemodynamic improvement owing to BPA was observed immediately after BPA; however, further improvement was observed as a result of delayed changes. mPAP improved by 3.4 ± 5.2 mmHg and PVR by 53 (10-99) dyn-s/cm5 as delayed improvement. mPAP and PVR showed delayed improved by approximately 10% of their values before BPA.