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

BACKGROUND: Direct oral anticoagulants (DOACs) are increasingly prescribed for life-long anticoagulation in chronic thromboembolic pulmonary hypertension (CTEPH) patients, despite not being recommended in the guidelines. This study aims to evaluate the efficacy and safety of DOACs in CTEPH patients.
METHODS: From May 2013 to December 2022, patients who were first diagnosed with CTEPH in Fuwai Hospital and started long-term anticoagulation treatment with warfarin or DOACs were retrospectively included and followed up until (1) death, (2) transition to other kinds of anticoagulants, or (3) discontinuation of anticoagulation. Propensity score matching was used to balance confounding bias of baseline characteristics. All-cause death, major bleeding, clinically relevant nonmajor bleeding and venous thromboembolism (VTE) recurrence were obtained and analysed.
RESULTS: After propensity score matching, 115 patients taking warfarin and 206 patients taking DOACs were included in our study and followed up for 5.5 [3.4, 7.1] years. There was no significant difference of survival between the warfarin and the DOAC group (p = 0.77). The exposure adjusted event rate of major bleeding (0.3 %/person-year vs 0.4 %/person-year, p = 0.705) and clinically relevant nonmajor bleeding (3.1 %/person-year vs 3.2 %/person-year, p > 0.999) was similar between two groups. The exposure adjusted rate of VTE recurrence was significantly higher in the DOAC group (1.5 %/person-year vs 0.3 %/person-year, p = 0.030).
CONCLUSIONS: In anticoagulation of CTEPH patients, DOACs have similar survival rate, similar risk of bleeding but higher risk of VTE recurrence than warfarin.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive pulmonary vascular disorder with substantial morbidity and mortality, also a disease underdiagnosed and undertreated. It is potentially curable by pulmonary endarterectomy (PEA) in patients with surgically accessible thrombi. Balloon pulmonary angioplasty (BPA) and targeted medical therapy are options for patients with distal lesions or persistent/recurrent pulmonary hypertension after PEA. There is an urgent need to increase the awareness of CTEPH. Qualified CTEPH centers are still quite limited. Baseline characteristics, management pattern and clinical outcome of CTEPH in China needs to be reported.
METHODS: The CHinese reAl-world study to iNvestigate the manaGEment pattern and outcomes of chronic thromboembolic pulmonary hypertension (CHANGE) study is designed to provide the multimodality treatment pattern and clinical outcomes of CTEPH in China. Consecutive patients who are ≥ 14 year-old and diagnosed with CTEPH are enrolled. The diagnosis of CTEPH is confirmed in right heart catheterization and imaging examinations. The multimodality therapeutic strategy, which consists of PEA, BPA and targeted medical therapy, is made by a multidisciplinary team. The blood sample and tissue from PEA are stored in the central biobank for further research. The patients receive regular follow-up every 3 or 6 months for at least 3 years. The primary outcomes include all-cause mortality and changes in functional and hemodynamic parameters from baseline. The secondary outcomes include the proportion of patients experiencing lung transplantation, the proportion of patients experiencing heart and lung transplantation, and changes in health-related quality of life. Up to 31 December 2023, the study has enrolled 1500 eligible patients from 18 expert centers.
CONCLUSIONS: As a real-world study, the CHANGE study is expected to increase our understanding of CTEPH, and to fill the gap between guidelines and the clinical practice in the diagnosis, assessment and treatment of patients with CTEPH. REGISTRATION NUMBER IN CLINICALTRIALS.GOV: NCT05311072.

BACKGROUND: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) cause right ventricular dysfunction which can impact other solid organs. However, the profiles and consequences of hepatic injury due to PAH and CTEPH have not been well-studied.
OBJECTIVE: We aimed to identify underlying patterns of liver injury in a cohort of PAH and CTEPH patients enrolled in 15 randomized clinical trials conducted between 1998 and 2014.
METHODS: We used unsupervised machine learning to identify liver injury clusters in 13 trials and validated the findings in two additional trials. We then determined whether these liver injury clusters were associated with clinical outcomes or treatment effect heterogeneity.
RESULTS: Our training dataset included 4,219 patients and our validation dataset included 1,756 patients with serum total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and albumin data. Using k-means clustering, we identified phenotypes with no liver injury, hepatocellular injury, cholestatic injury, and combined injury patterns. Patients in the cholestatic injury liver cluster had the shortest time to clinical worsening and the highest risk of mortality. The cholestatic injury group also experienced the greatest placebo-corrected treatment effect on six-minute walk distance. Randomization to the experimental arm transitioned patients to a healthier liver status.
CONCLUSIONS: Liver injury was associated with adverse outcomes in patients with PAH and CTEPH. Randomization to active treatment had beneficial effects on liver health compared to placebo. The role of liver disease (often subclinical) in determining outcomes warrants prospective studies.

BACKGROUND: Balloon pulmonary angioplasty (BPA) improves the prognosis of chronic thromboembolic pulmonary hypertension (CTEPH). Right ventricle (RV) is an important predictor of prognosis in CTEPH patients. 2D-speckle tracking echocardiography (2D-STE) can evaluate RV function. This study aimed to evaluate the effectiveness of BPA in CTEPH patients and to assess the value of 2D-STE in predicting outcomes of BPA.
METHODS: A total of 76 patients with CTEPH underwent 354 BPA sessions from January 2017 to October 2022. Responders were defined as those with mean pulmonary artery pressure (mPAP) ≤ 30 mmHg or those showing ≥ 30% decrease in pulmonary vascular resistance (PVR) after the last BPA session, compared to baseline. Logistic regression analysis was performed to identify predictors of BPA efficacy.
RESULTS: BPA resulted in a significant decrease in mPAP (from 50.8 ± 10.4 mmHg to 35.5 ± 11.9 mmHg, p < 0.001), PVR (from 888.7 ± 363.5 dyn·s·cm-5 to 545.5 ± 383.8 dyn·s·cm-5, p < 0.001), and eccentricity index (from 1.3 to 1.1, p < 0.001), and a significant increase in RV free wall longitudinal strain (RVFWLS: from 15.7% to 21.0%, p < 0.001). Significant improvement was also observed in the 6-min walking distance (from 385.5 m to 454.5 m, p < 0.001). After adjusting for confounders, multivariate analysis showed that RVFWLS was the only independent predictor of BPA efficacy. The optimal RVFWLS cutoff value for predicting BPA responders was 12%.
CONCLUSIONS: BPA was found to reduce pulmonary artery pressure, reverse RV remodeling, and improve exercise capacity. RVFWLS obtained by 2D-STE was an independent predictor of BPA outcomes. Our study may provide a meaningful reference for interventional therapy of CTEPH.

UNASSIGNED: The 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.
UNASSIGNED: Adult 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.
UNASSIGNED: We 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).
UNASSIGNED: Persistent 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.

BACKGROUND: Balloon pulmonary angioplasty (BPA) has beneficial effects on pulmonary hemodynamics, exercise capacity, and quality of life (QOL) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Recently, emerging evidence suggests a relationship between CTEPH and psychiatric disorders (PD). However, data on the clinical efficacy of BPA in CTEPH patients with PD are lacking.
METHODS: We retrospectively analyzed 75 patients with inoperable/residual CTEPH who underwent BPA and right-sided heart catheterization before the initial BPA and within 1 year after the last procedure. QOL was evaluated using the European Quality of Life Five Dimension (EQ-5D) scale in 27 patients before and after BPA sessions. Baseline and post-procedural hemodynamic, functional, and QOL parameters were compared between the patients with and without PD.
RESULTS: Among the 75 participants, 22 (29.3%) patients were categorized in the PD group. Although PD group had a similar mean pulmonary artery pressure level compared with non-PD group (40 ± 7 vs. 41 ± 9 mmHg, p = 0.477), they tended to have unfavorable QOL status (0.63 ± 0.22 vs. 0.77 ± 0.19, p = 0.102). BPA significantly improved pulmonary hemodynamics, laboratory parameters and exercise tolerance in both groups. BPA also significantly improved EQ-5D scores in the non-PD group (from 0.77 ± 0.19 to 0.88 ± 0.13, p < 0.001), but the scores remained unchanged in the PD group (from 0.63 ± 0.22 to 0.67 ± 0.22, p = 0.770). During the long-term period [1,848 (1,055-2,565) days], both groups experienced similar mortality rates (PD 4.6% vs. non-PD 5.7%, p = 1.000).
CONCLUSIONS: BPA improved hemodynamic and functional parameters irrespective of PD, but its effect on QOL was limited in patients with PD.

We aimed to follow a nationwide cohort of patients with pulmonary embolism (PE) without any exclusions to generate information regarding long-term symptoms, investigational findings and to determine the prevalence of chronic thromboembolic pulmonary hypertension (CTEPH). We hypothesized that this approach would yield generalizable estimates of CTEPH prevalence and incidence. All individuals diagnosed with acute PE in Sweden in 2005 were identified using the National Patient Register. In 2007, survivors were asked to complete a questionnaire regarding current symptoms. Those with dyspnea were referred for further examinations with laboratory tests, electrocardiogram (ECG), and a ventilation/perfusion scan (V/Q scan). If CTEPH was suspected, a referral to the nearest pulmonary arterial hypertension-center was recommended. Of 5793 unique individuals with PE diagnosis in 2005, 3510 were alive at the beginning of 2007. Altogether 53% reported dyspnea at some degree whereof a large proportion had V/Q scans indicating mismatched defects. Further investigation revealed 6 cases of CTEPH and in parallel 18 cases were diagnosed outside this study. The overall prevalence of CTEPH was 0.4% (95% confidence interval [CI]: 0.2%-0.6%) and 0.7% (95% CI: 0.4%-1.0%) among the survivors. The cumulative incidence of CTEPH in the group of patients who underwent a V/Q scan was 1.1% (95% CI: 0.2%-2.0%). There was a high mortality following an acute PE, a high proportion of persistent dyspnea among survivors, whereof several had pathological findings on V/Q scans and echocardiography. Only a minority developed CTEPH, indicating that CTEPH is the tip of the iceberg of post-PE disturbances.

To investigate the value of ventilation/perfusion (V/Q) scanning and CT pulmonary angiography (PA) in predicting CTEPH development after acute pulmonary embolism (APE). This study was performed in APE patients who had undergone both V/Q and CT PA after 3-month anticoagulation. The residual pulmonary obstructions were assessed based on V/Q and CT PA, and then recorded as pulmonary perfusion detect score (PPDs) and CT pulmonary artery obstruction index (PAOI). The predictive performance of PPDs and CT PAOI for CTEPH were determined and risk factors for predicting CTEPH development were identified. A total of 235 patients with initial diagnosis of APE were included in this study. ROC analysis showed that the AUCs of the PPDs and CT PAOI were 0.957 and 0.895, with corresponding cut-off values of 20.50% and 17.50% for predicting CTEPH development. Neither sensitivity nor specificity differed significantly between PPDs and CT PAOI (Sensitivity: 92.00% vs. 80.00%, P = 0.25; Specificity: 88.10% vs. 89.52%, P = 0.69). The univariable and multivariable logistic regression analysis demonstrated that pulmonary arterial hypertension confirmed by echocardiography at initial APE diagnosis (OR: 6.16, 95%CI: 1.31-29.02, P = 0.02), a PPDs of > 20.50% (OR: 22.95, 95%CI: 2.37-222.19, P = 0.007), and a CT PAOI of > 17.50% (OR: 9.98, 95%CI: 2.06-48.49, P = 0.004) were associated with CTEPH development. Both V/Q and CT PA after 3-month anticoagulation for APE showed great performance in predicting CTEPH development, and V/Q scanning has a tendency to be more sensitive but less specific than CT PA. The residual pulmonary embolism detected by V/Q and CT PA was associated with an increased risk of CTEPH development.

Chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE) is a morbid complication with suboptimal treatment. We aimed to evaluate the biomarker profile and functional outcomes in patients with submassive PE (sPE) treated with catheter-directed thrombolysis (CDT) compared with anticoagulation alone (ACA). We performed a secondary biomarker and survey analysis of the SUNSET sPE (standard vs ultrasound-assisted catheter thrombolysis for submassive pulmonary embolism) randomized trial comparing standard CDT to ultrasound-assisted thrombolysis in patients with sPE.
As a part of the SUNSET sPE study, patients who did not receive an intervention were enrolled in the medical (ACA) arm. The biomarkers associated with CTEPH in the literature (ie, CCL2, CXCL10, PTX3, GDF-15, RAGE, BCA-1, TFPI) were collected and measured using a multiplex assay at diagnosis, discharge, and 3-month follow-up. Patients underwent a 6-minute walk test and answered quality-of-life questionnaires (pulmonary embolism quality of life; University of California, San Diego, shortness of breath questionnaire; 36-item short-form survey) at 3 months after diagnosis. Comparisons were made using the Student t test. Nonparametric tests were used when the distributions were not normal. Significance was set at P ≤ .05.
A total of 72 patients (age, 56 ± 15 years; 40.3% women) were included in the present analysis. Of these 72 patients, 53 underwent CDT and 19 were included in the ACA arm. The baseline right ventricle/left ventricle ratios were similar between the two groups (CST, 1.8; ACA, 1.7). The survival and complication rates were similar between the two groups. At discharge, CXCL10 (768.9 ± 148.6 pg/mL vs 3032.0 ± 1201.0 pg/mL; P = .018) and PTX3 (3203.5 ± 1298.0 pg/mL vs 12,716.2 ± 6961.5 pg/mL; P = .029) were lower in the CDT group and displayed a quicker return to baseline than in the ACA group. This trend, although not significant, was also seen with the other biomarkers. At 3 months, the 6-minute walking distance and quality-of-life scores were similar between both groups.
In patients with sPE, the biomarkers of CTEPH were lower with CDT compared with ACA. At 3 months, both groups demonstrated similar biomarker levels, 6-minute walking distances, and quality-of-life scores.