Chronic Thromboembolic Pulmonary Hypertension Patients Research Articles

Predominance of M2 macrophages in organized thrombi in chronic thromboembolic pulmonary hypertension patients.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating disease characterized by thrombotic occlusion of pulmonary arteries and vasculopathy, leading to increased pulmonary vascular resistance and progressive right-sided heart failure. Thrombotic lesions in CTEPH contain CD68+ macrophages, and increasing evidence supports their role in disease pathogenesis. Macrophages are classically divided into pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages, which are involved in wound healing and tissue repair. Currently, the phenotype of macrophages and their localization within thrombotic lesions of CTEPH are largely unknown. In our study, we subclassified thrombotic lesions of CTEPH patients into developing fresh thrombi (FT) and organized thrombi (OT), based on the degree of fibrosis and remodeling. We used multiplex immunofluorescence histology to identify immune cell infiltrates in thrombotic lesions of CPTEH patients. Utilizing software-assisted cell detection and quantification, increased proportions of macrophages were observed in immune cell infiltrates of OT lesions, compared with FT. Strikingly, the proportions with a CD206+INOS- M2 phenotype were significantly higher in OT than in FT, which mainly contained unpolarized macrophages. Taken together, we observed a shift from unpolarized macrophages in FT toward an expanded population of M2 macrophages in OT, indicating a dynamic role of macrophages during CTEPH pathogenesis.

(18)F-fluorodeoxyglucose uptake by positron emission tomography in patients with IPAH and CTEPH.

Pulmonary arterial hypertension (PAH) is driven by pathologies associated with increased metabolism such as pulmonary revascularization, vasoconstriction and smooth muscle cell proliferation in pulmonary artery wall. 18-fluorodeoxyglucose positron emission tomography (18FDG-PET) is an imaging technique sensitive to glucose metabolism and might be considered as a non-invasive method for diagnosis due to significant role of inflammation in idiopathic pulmonary artery hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH). The present study aimed to investigate the role of PET/CT imaging of patients with IPAH and CTEPH as an alternative diagnosis method. Demographic characteristics, FDG uptake in lungs, pulmonary artery and right ventricle (RV) of 17 patients (10 IPAH, 7 CTEPH), and 30 controls were evaluated. PET scanning, 6-min walk test, pro-BNP level, right heart catheterization of patients were performed both at the onsert and after 6-month PAH specific treatment. IPAH and CTEPH patients had significantly higher left lung FDG (p = 0.006), right lung FDG (p = 0.004), right atrial (RA) FDG (p < 0.001) and RV FDG (p < 0.001) uptakes than controls. Positive correlation was detected between the RV FDG uptake and the mean pulmonary artery pressure (mPAP) (r = 0.7, p = 0.012) and between the RA FDG uptake and the right atrial pressure (RAP) (r = 0.5, p = 0.02). Increased RV FDG and RA FDG uptakes predicts the presence of pulmonary hypertension and correlates with mPAP and RAP, respectively, which are important indicators in the prognosis of PAH. Further studies are required whether FDG PET imaging can be used to diagnose or predict the prognosis of pulmonary hypertension.

The Initial Experience of Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension in Latvia

Background: Treatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent pulmonary hypertension after pulmonary endarterectomy (PEA) include targeted medical therapy and balloon pulmonary angioplasty (BPA). BPA is an emerging treatment modality that has been reported to improve functional capacity, pulmonary hemodynamics, and right ventricular function. Reports from expert centers are promising, but more data are needed to make the results more generalizable. Materials and Methods: We conducted a prospective analysis of nine consecutive CTEPH patients who underwent balloon pulmonary angioplasty (BPA) sessions at Pauls Stradins Clinical University Hospital in Riga, Latvia between 1 April 2022 and 1 July 2023. We assessed World Health Organization (WHO) functional class, 6 min walk distance (6MWD), blood oxygen saturation (SpO2), brain natriuretic peptide (BNP) level at baseline and 3 months after the first BPA session. For two patients on whom repeated BPA sessions were performed, we additionally assessed cardiac output (CO), pulmonary vascular resistance (PVR), and mean pulmonary artery pressure (mPAP). Results: A total of 12 BPA procedures for nine patients were performed; repeated BPA sessions were performed for two patients. Our results show a reduction in BNP levels and improvement in WHO functional class, 6MWD, and SpO2 after the first BPA session. Improvement in 6MWD was statistically significant. Additionally, an improvement in pulmonary hemodynamic parameters was observed. Conclusions: Our data show that BPA is an effective interventional treatment modality, improving both the pulmonary hemodynamics and functional status. Moreover, BPA is safe and excellently tolerated.

Post-Pulmonary Embolism Syndrome: An Update Based on the Revised AWMF-S2k Guideline.

In survivors of acute pulmonary embolism (PE), the post-PE syndrome (PPES) may occur. In PPES, patients typically present with persisting or progressive dyspnea on exertion despite 3 months of therapeutic anticoagulation. Therefore, a structured follow-up is warranted to identify patients with chronic thromboembolic pulmonary disease (CTEPD) with normal pulmonary pressure or chronic thromboembolic pulmonary hypertension (CTEPH). Both are currently understood as a dual vasculopathy, that is, secondary arterio- and arteriolopathy, affecting the large and medium-sized pulmonary arteries as well as the peripheral vessels (diameter < 50 µm). The follow-up algorithm after acute PE commences with identification of clinical symptoms and risk factors for CTEPH. If indicated, a stepwise performance of echocardiography, ventilation-perfusion scan (or alternative imaging), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level, cardiopulmonary exercise testing, and pulmonary artery catheterization with angiography should follow. CTEPH patients should be treated in a multidisciplinary center with adequate experience in the complex therapeutic options, comprising pulmonary endarterectomy, balloon pulmonary angioplasty, and pharmacological interventions.

Effect of off-label targeted drugs on long-term survival in chronic thromboembolic pulmonary hypertension: Insights from a national multicentre prospective registry.

Off-label pulmonary arterial hypertension (PAH)-targeted drugs are commonly prescribed for non-operated chronic thromboembolic pulmonary hypertension (CTEPH), but their effect on the long-term prognosis of CTEPH remains unknown. This study investigated the effect of off-label PAH-targeted drugs on the long-term survival of CTEPH patients. CTEPH patients were enrolled from a prospective multicentre national registry. Except for licensed riociguat and treprostinil, other PAH-targeted drugs were off-label. In the original and propensity score-matched (PSM) samples, five-year survival was compared in two groups: (a) patients not receiving off-label PAH-targeted drugs (control) versus (b) patients receiving off-label PAH-targeted drugs (treatment). The latter group was investigated for the effect of started off-label PAH-targeted drugs at baselines (initial) or during follow-up (subsequent). Of 347 enrolled patients, 212 were treated with off-label PAH-targeted drugs initially (n = 173) or subsequently (n = 39), and 135 were untreated. The 1-, 2-, 3- and 5-year survival of the treatment group was significantly higher than that of the control group (97.1% vs. 89.4%, 92.3% vs. 82.1%, 83.2% vs. 75.1% and 71.1% vs. 55.3%, respectively, log-rank test, p = 0.005). Initial treatment was correlated with better 5-year survival after excluding patients with subsequent treatment to reduce the immortal-time bias (hazard ratio: 0.611; 95% CI: 0.397-0.940; p = 0.025). In PSM samples, patients given initial treatment showed significantly better 5-year survival than untreated patients (68.9% vs. 49.3%, log-rank test, p = 0.008). Off-label targeted drugs contributed to improved long-term survival in CTEPH patients receiving pharmacotherapies.

Pelvic Vein Obstruction in Chronic Thromboembolic Pulmonary Hypertension: A Novel Association.

Background: Pelvic venous obstruction (PVO), defined as greater than 50% stenosis or occlusion of pelvic veins, is a known risk factor for deep vein thrombosis (DVT). DVT is a known risk factor for chronic thromboembolic pulmonary hypertension (CTEPH), but the prevalence of PVO in CTEPH is unknown. Methods: This cross-sectional study at Temple University's tertiary referral center for Pulmonary Hypertension, Right Heart Failure, and CTEPH sought to identify the presence of PVO in patients with CTEPH who underwent cardiac catheterization, pulmonary angiography, and venography. Results: A total of 193 CTEPH patients were referred for pulmonary angiography, and among these, 148 underwent venography. PVO was identified in 65 (44%) patients. Lower extremity (LE) DVT was associated with PVO (p = 0.004). The severity of pulmonary hypertension was similar with and without PVO (mean pulmonary artery pressure 43.0 ± 10.3 mm Hg vs. 43.8 ± 12.4 mm Hg, p = 0.70), as was the need for pulmonary thromboendarterectomy (69.2% vs. 61.4%, p = 0.32). Conclusions: Pelvic vein obstruction is common and a novel clinical association in patients with CTEPH, particularly in patients with a history of LE DVT. PVO and its role in CTEPH warrants further study, including the potential role of revascularization to mitigate further risk.

Prognostic value of tricuspid valve regurgitation in patients with pulmonary arterial hypertension and CTEPH: A longitudinal study

AimsThe prognostic value of functional tricuspid valve regurgitation (TR) in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (CTEPH) remains undetermined. This study primarily aims to quantify the prognostic role of TR in relation to right ventricle (RV) dysfunction on clinical outcomes and secondarily the evolution of TR and RV dysfunction over time. MethodsAdult PAH or CTEPH patients diagnosed by right heart catheterization were included. Exclusion criteria were prevalent patients and age < 18 years.The primary endpoint was a composite of death or lung transplantation. Longitudinal evolution of TR and RV dysfunction were modelled with generalized mixed-effect models, which were inserted in a cox model under the joint-modelling framework in order to investigate the association of TR and RV dysfunction with the endpoint. ResultsWe included 76 PAH and 44 CTEPH patients (median age:59, females:62 %), with a mean follow-up of 3.2 ± 2.1 years. 31 patients reached the endpoint (2 transplant, 29 mortality). On average the probability of moderate-to-severe TR decreased during follow-up, whereas the probability of moderate-to-severe RV dysfunction remained stable. The cumulative effect of moderate-to-severe TR (HRper day 1.01 95 %CI[1.00–1.01],P < 0.001) and moderate-to-severe RV dysfunction (HRper day: 1.01 95 %CI[1.00–1.01],P < 0.001) was associated with the endpoint in univariable joint-models. In a multivariable joint-model with both the evolutions of TR and RV dysfunction only TR remained significant (HR per day: 1.01 95 %CI[1.00–1.01],P < 0.001). ConclusionPersistent moderate-to-severe tricuspid valve regurgitation during follow-up predicts adverse outcomes and might be a better predictor of lung transplantation and mortality compared to right ventricle dysfunction.

[Hemodynamic changes with serial balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension].

Objective: To monitor hemodynamic changes during serial balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension (CTEPH). Methods: General clinical data of CTEPH patients diagnosed from October 2017 to January 2022 in Beijing Chaoyang Hospital were collected, and 83 patients who underwent at least 1 BPA treatment were included to analyze their 6 min walking distance, WHO functional class, N-terminal B-type natriuretic peptide precursor (NT-proBNP), troponin I (cTnI) and haemodynamic indices. Baseline and follow-up after the final BPA clinical data and hemodynamics, functional status and serial hemodynamics before each series of BPA were collected to evaluate the efficacy of BPA for CTEPH patients. Complications and managements were documented to confirm the safety of BPA for CTEPH patients. Results: Three hundred and forty BPA procedures were performed in 83 CTEPH patients. The median number of BPA procedures was 4.0 and a total of 2104 vessels were dilated. In general, mPAP [from 50.0(42.0-55.25) mmHg(1 mmHg=0.133 kPa) to 32.0(27.0-42.0) mmHg, P<0.001], PVR[from (806.6±323.2) dyn·s·cm-5 to 420.0(295.0-613.5) dyn·s·cm-5, P<0.001] were significantly improved compared with baseline, but not CO and CI. Functional parameters including WHO functional class Ⅰ/Ⅱ/Ⅲ/Ⅳ (from 0/35/34/14 to 43/32/7/1, P<0.001), 6MWD [from 364.5(300.0-429.5)m to 461.0(409.0-501.0)m, P<0.001], NT-proBNP [from 1 357.0(232.0-2 715.0) ng/L to 141.0(57.0-627.8) ng/L,P<0.001] were significantly improved compared with baseline. A cumulative (compared to baseline) and serial (compared to preceding BPA session) analysis of the sequential BPA session confirmed that a major hemodynamic improvement in PVR and mPAP occurred in the first 3 serial BPA treatments. There was a dose-response relationship: the more segments that were treated, the greater were the subsequent reduction in PVR and mPAP. There were 32.0 complications (9.4%) associated with BPA procedures, and the most common complication was pulmonary hemorrhage caused by catheter-related vascular injury. Conclusions: BPA is an effective and safe alternative for technically non-operable CTEPH patients. The hemodynamic benefits of BPA in CTEPH patients were cumulative and correlated with the total number of vessels successfully dilated.

Patients with CTEPH and mild hemodynamic severity of disease improve to a similar level of exercise capacity after pulmonary endarterectomy compared to patients with severe hemodynamic disease.

The correlation between hemodynamics and degree of pulmonary vascular obstruction (PVO) is known to be poor in chronic thromboembolic pulmonary hypertension(CTEPH), which makes the selection of patients eligible for pulmonary endarterectomy (PEA) challenging. It can be postulated that patients with similar PVO but different hemodynamic severity have different postoperative hemodynamics and exercise capacity. Therefore, we aimed to assess the effects of PEA on hemodynamics and exercise physiology in mild and severe CTEPH patients. We retrospectively studied 18 CTEPH patients with a mild hemodynamic profile (mean pulmonary arterial pressure[mPAP] between 25 and 30 mmHg at rest) and CTEPH patients with a more severe hemodynamic profile (mPAP > 30 mmHg), matched by age, gender, and PVO. Cardiopulmonary exercise testing parameters were evaluated at baseline and 18 months following PEA. At baseline, exercise capacity, defined as oxygen uptake, was less severely impaired in the mild CTEPH group compared to the severe CTEPH group. After PEA, in the mild CTEPH group, ventilatory efficiency and oxygen pulse improved significantly (p < 0.05), however, the change in ventilatory efficiency and oxygen pulse was smaller compared to the severe CTEPH group. Only in the severe CTEPH group exercise capacity improved significantly (p < 0.001). Hence, in the present study, postoperative hemodynamic outcome and the CPET-determined recovery of exercise capacity in mild CTEPH patients did not differ from a matched group of severe CTEPH patients.

Refined balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension - reference center experience.

Chronic thromboembolic pulmonary hypertension (CTEPH), characterized by thromboembolic changes affecting the pulmonary bed, leads to ventricular function deterioration and premature death. The introduction of balloon pulmonary angioplasty (BPA) has significantly improved the prognosis of CTEPH patients. The authors of this article decided to summarize the experience of the BPA program, conducted between 2014 and 2022, at the reference center. Among 111 CTEPH patients, 55 were included in the analysis. A total of 226 sessions were performed, with a significant percentage of intravascular imaging and pressure catheter use. Mean pulmonary pressure decreased significantly from 42 (22-66) to 26.5 mm Hg (11-54) (p < 0.05). Pulmonary vascular resistance and natriuretic peptide concentration decreased from 6.67 (1.66-14) to 3.295 Wood units (1.09-11.11), respectively, and from 1934 (60-16963) to 296 (21-9901) ng/ml (p < 0.05). There was also an improvement in the functional class (WHO) from 2.85 ±0.61 to 2.15 ±0.62 and an increase in the 6-minute walking distance from 300 ±131 to 367 ±154 m (p < 0.05). There were no in-hospital deaths or within 30 days of the procedure. Arterial damage occurred during nine sessions (n = 9/226, 4%), while 0.9% (n = 2/226) were complicated by acute right ventricular failure. Post-reperfusion pulmonary edema (RPE 0 - none) was observed in almost 90% of the sessions, grade 1 to 3 RPE occurred in 10.2%, and grade 4 RPE was not noted. BPA programs conducted in experienced centers are a safe and effective treatment option for inoperable CTEPH patients.

Safety and efficacy of balloon pulmonary angioplasty for technically operable chronic thromboembolic pulmonary hypertension.

Balloon pulmonary angioplasty (BPA) has been proven effective for addressing technically inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, the effectiveness of BPA in technically operable CTEPH patients who, for various reasons, did not undergo the procedure remains an area requiring exploration. This study sought to assess the safety and efficacy of BPA in such cases. We collected and reviewed data from CTEPH patients who underwent BPA in a consecutive manner. Following multidisciplinary team (MDT) decisions, patients were classified into two groups: technically inoperable (group A) and operable (group B). Group B comprised patients deemed technically suitable for pulmonary endarterectomy (PEA) but who did not undergo the procedure for various reasons. All patients underwent a comprehensive diagnostic work-up, including right heart categorization at baseline and the last intervention. This study compared changes in hemodynamic parameters, functional capacity, and quality of life between the two groups. In total, 161 patients underwent 414 procedures at our center, with Group A comprising 112 patients who underwent 282 BPA sessions and group B comprising 49 patients who underwent 132 BPA sessions. Significantly, both groups exhibited improvements in hemodynamics, functional capacity, and quality of life. The occurrence rate of complications, including hemoptysis and lung injury, was similar [12 (63.2%) vs. 7 (36.8%), p = 0.68]. BPA demonstrated favorable outcomes in patients with proximal CTEPH who did not undergo pulmonary endarterectomy. However, the clinical impact of BPA in technically operable CTEPH was found to be less significant than in inoperable cases.

The Utility of a Resting Electrocardiogram (ECG-PH Index) in Evaluating the Efficacy of Pulmonary Endarterectomy in Chronic Thromboembolic Pulmonary Hypertension.

The ECG-PH index (PH-ECG score) has been proposed as a valuable ECG-derived method of evaluating the effectiveness of balloon pulmonary angioplasty (BPA) in chronic thromboembolic pulmonary hypertension (CTEPH). Pulmonary endarterectomy (PEA) is the main form of therapy for CTEPH with a proximal clot location. The objective of this study was to assess the clinical utility of a resting electrocardiogram (ECG-PH index) in assessing the effectiveness of PEA in CTEPH patients. The retrospective analysis included 73 patients who underwent PEA. Their ECG-PH index values were calculated using four ECG parameters: R-wave amplitude V1 + S-wave amplitude V5/V6 > 10.5 mm, QRS-wave axis > 110 degrees, R-wave amplitude V1 > S-wave amplitude V1, and SIQIII pattern. PH-ECG scores were assessed after a median time of 13 months (IQR: 8-31 months) had passed since the PEA procedures. The current analysis documented that ECG-PH index = 0 is a good reflection of mPAP < 25mmHg (sensitivity 76.1%; specificity 66.7%; positive predictive value 79.5%; negative predictive value 62.1%) or mPAP ≤ 20 mmHg (sensitivity 69.6%; specificity 70.6%; positive predictive value 88.6%; negative predictive value 41.4%) after PEA. The values of the area under the ROC curve for ECG-PH index were 0.772 (95% CI: 0.676-0.867) and 0.743 (95% CI: 0.637-0.849) for the mPAP < 25 mmHg and mPAP ≤ 20 mmHg patient groups, respectively. The ECG-PH index may be useful for monitoring the haemodynamic effect of PEA in CTEPH patients.

Subject-specific one-dimensional fluid dynamics model of chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) develops due to the accumulation of blood clots in the lung vasculature that obstructs flow and increases pressure. The mechanobiological factors that drive progression of CTEPH are not understood, in part because mechanical and hemodynamic changes in the small pulmonary arteries due to CTEPH are not easily measurable. Using previously published hemodynamic measurements and imaging from a large animal model of CTEPH, we applied a subject-specific one-dimensional (1D) computational fluid dynamic (CFD) approach to investigate the impact of CTEPH on pulmonary artery stiffening, time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) in extralobar (main, right, and left) pulmonary arteries and intralobar (distal to the extralobar) arteries. Our results demonstrate that CTEPH increases pulmonary artery wall stiffness and decreases TAWSS in extralobar and intralobar arteries. Moreover, CTEPH increases the percentage of the intralobar arterial network with both low TAWSS and high OSI, quantified by the novel parameter φ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\varphi$$\\end{document}, which is related to thrombogenicity. Our analysis reveals a strong positive correlation between increases in mean pulmonary artery pressure (mPAP) and φ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\varphi$$\\end{document} from baseline to CTEPH in individual subjects, which supports the suggestion that increased φ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\varphi$$\\end{document} drives disease severity. This subject-specific experimental–computational framework shows potential as a predictor of the impact of CTEPH on pulmonary arterial hemodynamics and pulmonary vascular mechanics. By leveraging advanced modeling techniques and calibrated model parameters, we predict spatial distributions of flow and pressure, from which we can compute potential physiomarkers of disease progression. Ultimately, this approach can lead to more spatially targeted interventions that address the needs of individual CTEPH patients.

Acute effect of balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension

Abstract Background Pulmonary endarterectomy is known to improve hemodynamics in the early postoperative period on chronic thromboembolic pulmonary hypertension (CTEPH). However, there are no reports of early hemodynamic changes after balloon pulmonary angioplasty (BPA) for CTEPH. Purpose The aim of this study was to clarify early hemodynamic changes of BPA. Furthermore, we investigated whether the early hemodynamic changes were related to the chronic phase hemodynamics after final BPA. Methods We retrospectively enrolled 43 consecutive CTEPH patients placed Swan-Ganz catheter for hemodynamic monitoring at first BPA. Hemodynamics were evaluated immediately before (Pre), immediately after (Post), 3 hours, 6 hours, 9 hours, 12 hours, and 1 week after BPA. The hemodynamics in the chronic phase after final BPA were confirmed in each group in which the mean pulmonary artery pressure (mPAP) did not decrease immediately after BPA and 12 hours later. Results Although mPAP improved immediately after BPA, no change were observed thereafter and significant improvement were observed after 6 hours (Figure). While, cardiac output rose immediately and reached a peak 6 hours later. Then, it decreased and returned to value of Post after 1 week (Figure). MPAP/CO continued to decrease after BPA until 12 hours later (Figure). There were 16 and 8 cases in which mPAP did not decrease immediately after BPA and 12 hours later. However, mPAP in 16 and 8 cases became less than 20mmHg in the chronic phase (mPAP: Post; 28.5±7.3 to 19.6±5.6 mmHg, P&amp;lt;0.001, 12 hours; 26.0±7.8 to 17.8±3.5, P=0.02) Conclusion While mPAP after BPA decreased after 6 hours, there were a temporary rise in CO. Improvement can be obtained in the chronic phase after final BPA even if mean PAP did not decrease during the acute phase.

Clinical impact of residual pulmonary hypertension based on revised criteria after balloon pulmonary angioplasty

Abstract Background Balloon pulmonary angioplasty (BPA) improves haemodynamics, exercise capacity, and prognosis in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, the treatment goal of BPA is not well established. The European Society of Cardiology guidelines published in 2022 revised the diagnosis of pulmonary hypertension from resting mean pulmonary arterial pressure (mPAP) ≥25 mmHg to mPAP &amp;gt;20 mmHg because mild elevation of pulmonary hypertension has decreased exercise capacity and worsened the prognosis. The clinical impact of normalization in resting pulmonary hypertension after balloon pulmonary angioplasty is not investigated. Purpose The purpose of this study is to clarify the clinical impact of mPAP normalization after BPA as a treatment goal in patients with CTEPH. Methods We retrospectively reviewed consecutive 236 CTEPH patients (68 [55,75] yrs., Male 52 (22%)) who completed BPA procedures from July 2009 to December 2020 and had haemodynamics evaluation after the procedures and had mPAP &amp;lt;30 mm Hg after BPA. We extracted two groups with mPAP &amp;lt;20 mmHg (Non-PH group) and 21≤ mPAP &amp;lt;30 mmHg (Residual-PH group) after BPA. Results The median follow-up period from the final BPA session was 38 [22,61] months. In both the Non-PH and Residual-PH groups, BPA significantly improved mPAP (37 [29,43] to 18 [16,19] mmHg, P&amp;lt;0.01 and 38 [34,45] to 23 [22,26], P&amp;lt;0.01, respectively) and cardiac index (CI) (2.15 [1.86,2.63] to 2.39 [2.11,2.80] L/min/m2, P&amp;lt;0.01 and 2.25 [1.87,2.63] to 2.50 [2.23,2.88] L/min/m2, P&amp;lt;0.01, respectively). There were no significant differences in CI after BPA between the Non-PH and Residual-PH groups. The 6-minute walk distance (6MWD) after BPA was shorter in the Residual-PH group than in the Non-PH group (435m and 480m, P&amp;lt;0.01). However, the estimated 5-year survival in the Non-PH and Residual-PH groups was comparable (96.3% and 99.1%, P=0.23, Figure 1). Patients in the Residual-PH group showed significantly shorter 6MWD and higher mPAP before BPA, and required more procedures (P&amp;lt;0.01, 0.02, 0.03, respectively). Additional multivariate logistic regression analysis revealed that shorter 6MWD before BPA was a significant predictor of residual PH (odds ratio=1.03, P=0.04). Conclusions The Residual-PH group had lower exercise capacity than the Non-PH group, although the prognosis in the Residual-PH group was similar to that in the Non-PH group.Figure 1

Abstract 13192: Anti-Factor Xa Activity in Patients With Chronic Thromboembolic Pulmonary Disease With or Without Pulmonary Hypertension Treated With Factor Xa Inhibitors

Introduction and Hypothesis: Data on the efficacy and safety of factor Xa (FXa) inhibitors in chronic thromboembolic pulmonary disease (CTEPD) patients, especially in chronic thromboembolic pulmonary hypertension (CTEPH) patients, remain limited. Here, we aimed to evaluate the effect of FXa inhibitors by measuring anti-factor Xa activity (AXA) in both patients with CTEPD without pulmonary hypertension (PH) and CTEPH. Methods: Twenty-five CTEPD patients without PH and 52 CTEPH patients, treated with either of the FXa inhibitors were enrolled. AXA was measured by using HemosIL heparin calibrator. Blood samples were collected two times at the same day: immediately before the drug administration (trough) and 2-3 h after drug administration (peak). Results: In all 77 patients, median age was 66 (Interquartile range [IQR] 51–73) years, and 43% were male. In addition, 47% of the patients received rivaroxaban of 15 mg/day, 27% received apixaban of 10 mg/day, 14% received edoxaban of 60mg/day, and 12% received edoxaban of 30 mg/day. The median peak AXA of all 77 patients was 1.92 IU/mL and was comparable between CTEPD without PH and CTEPH patients. Significant difference of trough and peak AXA was shown among four different prescribed drugs (P &lt; .001 and P = .006, respectively). During the observational period of median 519 (IQR 364–1118) days, major and clinically relevant non-major bleeding occurred in six patients. ROC analysis to predict bleeding events revealed that the sensitivity and specificity of the cutoff point of a peak AXA of 2.1 IU/mL were 67% and 66%, respectively (AUC 0.66). The cumulative rate of major and clinically relevant non-major bleeding tended to be higher in patients with peak AXA ≥ 2.1 IU/mL than in patients with values below this point (p = .092, Figure). Conclusion: Measuring AXA could be a useful method to evaluate the effect of FXa inhibitors in CTEPD with or without PH patients.

Abstract 17842: 3D Visualization and Quantitative Assessment of the Pulmonary Arteries on CT Using Deep Learning Segmentation

Introduction: Assessment of the pulmonary arteries (PA) on CT scan is typically qualitative and requires review of hundreds of images. PA segmentation would enable creation of 3D reconstructions that visualize the entire pulmonary arterial tree in a single image, similar to catheter angiography, and also enable quantification of pathophysiologic changes. Manual segmentation is very time-consuming, but deep-learning (DL) can automate the process. Hypothesis: A DL segmentation algorithm can be used to automatically generate 3D reconstructions of the PAs and quantify morphologic changes seen in Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Pulmonary Arterial Hypertension (PAH). Methods: A DL algorithm based on a 3D U-Net architecture which segments PAs larger than 2 mm was trained and validated on a total of 250 contrast-enhanced CT chest. The study group included 15 CTEPH and 15 PAH patients seen consecutively in pulmonary hypertension (PH) clinic in 2022 with prior CT chest and right heart catheterization, and 10 additional patients with prior CT chest and no evidence of PH on same day echo (normal). After running the DL algorithm on CTs, 3D renderings were created from segmentations and the relative volume of the central, interlobar, and segmental/subsegmental PAs was derived. Results: 3D renderings of PAH and CTEPH patients showed larger central and interlobar PAs compared with those of normal patients, whereas segmental and subsegmental PAs were smaller and pruned in CTEPH patients (Figure). Quantitatively, the volume of the central and interlobar PAs was higher in CTEPH and PAH compared to normal (p &lt; 0.05). The combined volume of segmental/subsegmental PAs was smaller in CTEPH patients relative to normal and PAH patients (p &lt; 0.005). Conclusions: DL segmentation enables intuitive visualization and quantification of the morphologic changes to the PAs seen in conditions causing PH. This method may improve diagnosis and assessment of PH on CT.

Abstract 13407: Long-Term Outcomes of Chronic Thromboembolic Pulmonary Hypertension Treated With Pulmonary Endarterectomy and Balloon Pulmonary Angioplasty: Results From the Japanese Prospective CTEPH Registry (CTEPH AC Registry)

Introduction: In Japan, balloon pulmonary angioplasty (BPA) is more commonly adopted in patients with chronic thromboembolic pulmonary hypertension (CTEPH) compared to European countries or US due to their expertise. However, there are no reports from regions where BPA is extensively practiced. Aims: This study aims to explore the treatment outcomes in Japan. Methods: The study involved a nationwide, prospective, observational registry that included all patients diagnosed with CTEPH from August 2018 to February 2023 in Japan. Patients were categorized as naïve or prevalent cases based on their previous reperfusion therapy (pulmonary endarterectomy and/or BPA) at the time of enrollment. Each case was further classified as operable or BPA group. The primary outcome measure was morbidity and mortality (MM) events since enrollment, which comprised all-cause death, CTEPH-related hospitalization, rescue reperfusion therapy, initiation of parenteral pulmonary vasodilators, and worsening of CTEPH characterized by a decrease in 6-minute walk distance greater than 15% and deterioration of the WHO functional class. Results: A total of 1194 patients, including naïve cases (operable: n = 54, BPA: n = 293) and prevalent cases (operable: n=125, BPA: n = 532), were identified. Among the naïve cases, there were no significant differences in age or disease severity between the operable and BPA groups. Among the prevalent cases, the BPA group was older (63 ± 13 vs. 58 ± 14 years old, p &lt; 0.0001) and had higher pulmonary vascular resistance (364 ± 279 vs. 293 ± 206 dyne*sec/cm5, p = 0.001) compared to the operable group. The results of primary outcome measures were comparable between both the groups (Figure). Conclusions: BPA as well as pulmonary endarterectomy is considered as safety and effective therapeutic option in CTEPH patients.

Abstract 13633: Modern Treatment Patterns in Incident Pulmonary Arterial Hypertension (PAH) Patients: Real-World Data From the Pulmonary Hypertension Association (PHA) Registry

Purpose: New 2022 European Society of Cardiology/European Respiratory Society PAH guidelines recommend treatment guided by a multi-parameter risk assessment. 1 Patients with low/intermediate risk without cardiopulmonary comorbidities should start dual PAH combination therapy; those with cardiopulmonary comorbidities should be reassessed early for rapid escalation to dual therapy. Initial triple therapy is recommended for high-risk patients. We examined use of dual and triple PAH therapy in the US (before guideline update). Methods: We used the Pulmonary Hypertension Association Registry (PHAR), a prospective US registry of pulmonary hypertension (PH) patients, enrolled within 6 months of their first outpatient visit at one of 54 participating PH care centers in the US, between Sep 2015-Jun 2022. We included adults (≥18 years at enrollment) with incident PAH (newly diagnosed and treated within 6 months of enrollment) and ≥1 follow-up clinic visit post baseline visit. Chronic thromboembolic PH patients were excluded. Results: We analyzed (descriptive statistics) 794 incident patients (baseline characteristics in Table 1). Treatment patterns at baseline (n=794)/last follow-up visit (n=610) were 289 (36.4%)/102 (16.7%) on monotherapy, 419 (52.8%)/314 (51.5%) on dual combination, 83 (10.5%)/179 (29.3%) on triple combination therapy, respectively. Mean time from enrollment to dual and triple combination therapy was 86.1 (standard deviation [SD]: 209.0) and 346.1 days (SD: 430.8), respectively. Conclusions: Among incident PHAR patients, half received initial dual and 10% triple upfront combination therapy. At last follow-up, most (&gt;80%) patients had escalated to dual/triple combination therapies. Clinical Implications: At PH care centers, most incident PHAR patients are escalated to dual and triple therapy (at last follow-up) per current guidelines. Reference 1. Humbert M, et al. Eur Heart J. 2022;43:3618-731.

Dual-layer dual-energy CT-derived pulmonary perfusion for the differentiation of acute pulmonary embolism and chronic thromboembolic pulmonary hypertension.

To evaluate dual-layer dual-energy computed tomography (dlDECT)-derived pulmonary perfusion maps for differentiation between acute pulmonary embolism (PE) and chronic thromboembolic pulmonary hypertension (CTEPH). This retrospective study included 131 patients (57 patients with acute PE, 52 CTEPH, 22 controls), who underwent CT pulmonary angiography on a dlDECT. Normal and malperfused areas of lung parenchyma were semiautomatically contoured using iodine density overlay (IDO) maps. First-order histogram features of normal and malperfused lung tissue were extracted. Iodine density (ID) was normalized to the mean pulmonary artery (MPA) and the left atrium (LA). Furthermore, morphological imaging features for both acute and chronic PE, as well as the combination of histogram and morphological imaging features, were evaluated. In acute PE, normal perfused lung areas showed a higher mean and peak iodine uptake normalized to the MPA than in CTEPH (both p < 0.001). After normalizing mean ID in perfusion defects to the LA, patients with acute PE had a reduced average perfusion (IDmean,LA) compared to both CTEPH patients and controls (p < 0.001 for both). IDmean,LA allowed for a differentiation between acute PE and CTEPH with moderate accuracy (AUC: 0.72, sensitivity 74%, specificity 64%), resulting in a PPV and NPV for CTEPH of 64% and 70%. Combining IDmean,LA in the malperfused areas with the diameter of the MPA (MPAdia) significantly increased its ability to differentiate between acute PE and CTEPH (sole MPAdia: AUC: 0.76, 95%-CI: 0.68-0.85 vs. MPAdia + 256.3 * IDmean,LA - 40.0: AUC: 0.82, 95%-CI: 0.74-0.90, p = 0.04). dlDECT enables quantification and characterization of pulmonary perfusion patterns in acute PE and CTEPH. Although these lack precision when used as a standalone criterion, when combined with morphological CT parameters, they hold potential to enhance differentiation between the two diseases. Differentiating between acute PE and CTEPH based on morphological CT parameters is challenging, often leading to a delay in CTEPH diagnosis. By revealing distinct pulmonary perfusion patterns in both entities, dlDECT may facilitate timely diagnosis of CTEPH, ultimately improving clinical management. • Morphological imaging parameters derived from CT pulmonary angiography to distinguish between acute pulmonary embolism and chronic thromboembolic pulmonary hypertension lack diagnostic accuracy. • Dual-layer dual-energy CT reveals different pulmonary perfusion patterns between acute pulmonary embolism and chronic thromboembolic pulmonary hypertension. • The identified parameters yield potential to enable more timely identification of patients with chronic thromboembolic pulmonary hypertension.