Chronic Thromboembolic Pulmonary Hypertension Patients Research Articles

Cardiothoracic Imaging for Outcome Prediction in Chronic Thromboembolic Pulmonary Hypertension after Pulmonary Endarterectomy or Balloon Pulmonary Angioplasty: A Scoping Review.

There has been a rapid expansion in centers performing balloon pulmonary angioplasty (BPA) and pulmonary thromboendarterectomy (PTE) for chronic thromboembolic pulmonary hypertension (CTEPH). The purpose of this scoping review was to identify cardiothoracic imaging predictors of outcomes and to identify gaps to address in future work. A scoping review was conducted using the framework outlined by Arksey and O'Malley and Levac et al. in MEDLINE and EMBASE. The study protocol was preregistered in OSF Registries and performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) guidelines. There were 1117 identified studies, including 48 involving pulmonary thromboendarterectomy (n = 25) and balloon pulmonary angioplasty (n = 23). CT was the most common preoperative imaging modality used (n = 21) and CT level of disease was the most reported imaging predictor of outcomes for pulmonary thromboendarterectomy. Although must studies evaluated hemodynamic improvements, imaging was of additional use in predicting clinically significant procedural complications after balloon pulmonary angioplasty, as well as mortality and long-term outcome after pulmonary endarterectomy. Predictors reported in MRI and digital subtraction angiography were less commonly reported and warrant multicenter validation. Cardiothoracic imaging may predict clinically significant outcomes after balloon pulmonary angioplasty and pulmonary thromboendarterectomy. Radiologists involved in the assessment of CTEPH patients should be aware of key predictors and future investigations could focus on multicenter validation and new technologies.

Low nailfold capillary density in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: biomarker of clinical outcome?

Nailfold capillary density is lower in patients with pulmonary arterial hypertension (PAH). It is unclear whether this observation signifies a unique systemic manifestation of PAH, or reflects microcirculatory dysfunction secondary to pulmonary hypertension (PH). Capillary density and loop dimensions were measured by nailfold-capillaroscopy (NC) in 30 PAH (23 idiopathic, or iPAH, 7 hereditary, or hPAH), 17 chronic thromboembolic PH (CTEPH) patients and 48 controls. NC-Measurements were repeated after pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) in CTEPH patients. We examined whether NC-measurements were related to markers of disease severity and predictive of time to clinical worsening (TTCW) as tested by univariate linear/logistic regression and cox-regression analysis, respectively. Capillary density was significantly lower in PAH (7.5 ± 1.1, p < 0.001) and in CTEPH (8.4 ± 1.5, p < 0.001) compared to asymptomatic controls (10.3 ± 1.0 capillaries/mm). Capillary density was similar in iPAH and hPAH and unrelated to hemodynamics in either PAH or CTEPH. A lower capillary density was predictive of clinical worsening in PAH (p 0.05). After normalization of pulmonary artery pressures by PEA or BPA, capillary density remained reduced in CTEPH patients. Capillary loop apex, capillary and venous- and arterial limb diameter were increased in patients with PAH and CTEPH compared to controls. Nailfold capillary density is reduced to a similar extent in iPAH, hPAH and CTEPH. Normalization of hemodynamics by PEA or BPA does not lead to a restoration of capillary density in CTEPH. Capillary dimensions were increased in both patients with PAH and CTEPH. Lower capillary density was predictive of clinical worsening in PAH. Our findings indicate that a loss of peripheral capillaries is not specific to PAH and is not related to the hemodynamic disturbance per se, but that shared mechanisms may account for a simultaneous development of a systemic microangiopathy and pulmonary vascular remodeling.

ECG changes following balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension: a retrospective study

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

Kidney Dysfunction, Hepatic Impairment, and Lipid Metabolism Abnormalities in Patients with Precapillary Pulmonary Hypertension.

Pulmonary hypertension (PH) is a global health issue that has profound medical and research implications. This retrospective study examined changes in renal and liver function, as well as lipid metabolism, over a 12-month period in 49 adult patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). All cases were admitted, managed, and followed up with in the PH Center, County Emergency Clinical Hospital of Targu Mures, Romania. Kidney dysfunction was observed in 12.24% of cases at baseline, decreasing to 8.16% at 12 months, and CTEPH patients were more affected. In particular, CTEPH patients exhibited an improvement in renal function, confirmed by an increase in their glomerular filtration rates. Hepatic impairment was present in 57.14% of subjects at baseline, declining to 42.86% at 12 months, with significant improvements noted in the PAH group. Lipid metabolic dysregulations were experienced by 22.45% of all patients at baseline, decreasing to 16.33% at 6 months, with a slow elevation to 24.49% at 12 months, but with no statistically significant differences. Pharmacological regimens were adjusted in accordance with the PH groups, a patient's functional and clinical response, and laboratory tests. Our results demonstrate the multi-organ damage in PH and the importance of individualized treatment approaches.

Chronic Thromboembolic Pulmonary Hypertension

: While the majority of patients have complete resolution of their acute pulmonary embolism (PE) after an adequate course of anticoagulation, some patients remain symptomatic with evidence of chronic PE. Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Chronic Thromboembolic Pulmonary Disease (CTEPD) are terms that describe symptomatic patients with chronic thromboembolic occlusions of the pulmonary arteries with or without pulmonary hypertension, respectively. Here, we review the definitions, epidemiology, pathobiology, diagnosis and management of CTEPH. The chronic PE in CTEPH is essentially a scar in the pulmonary vasculature and is accompanied by a pulmonary arteriolar vasculopathy. Ventilation-perfusion scanning is the most sensitive screening test for CTEPH, and diagnosis must be confirmed by right heart catheterization (RHC). Treatment decisions require a multidisciplinary team and guidance from additional imaging, usually CT or pulmonary angiography. While pulmonary endarterectomy (PEA) to remove the chronic PE surgically is still the first-line treatment for appropriate candidates, there is an expanding role for balloon pulmonary angioplasty (BPA) and medical treatment, as well as multimodality treatment approaches that incorporate all of those options. New imaging modalities and treatment strategies hold the promise to improve our care and management of CTEPH patients in the future.

Outcomes of Chronic Thromboembolic Pulmonary Hypertension After Balloon Pulmonary Angioplasty and Pulmonary Endarterectomy

BackgroundThe contemporary outcome of balloon pulmonary angioplasty (BPA) and pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) are unclear. ObjectivesThis study aimed to clarify the characteristics and outcomes of CTEPH patients treated with BPA and PEA in Japan. MethodsAmong 1,270 participants enrolled between 2018 and 2023 in the CTEPH AC (Chronic Thromboembolic Pulmonary Hypertension Anticoagulant) registry, a Japanese nationwide CTEPH registry, 369 treatment-naive patients (BPA strategy: n = 313; PEA strategy: n = 56) and 690 on-treatment patients (BPA strategy: n = 561; PEA strategy: n = 129) were classified according to the presence of prior reperfusion therapy. Morbidity and mortality events (all-cause death, rescue mechanical reperfusion therapy, and/or initiation of parenteral pulmonary vasodilators), pulmonary hemodynamics, exercise tolerance, and relevant laboratory test results were evaluated. ResultsThe BPA strategy was chosen in older patients than the PEA strategy (mean age, BPA vs PEA: 66.5 ± 12.6 years vs 62.5 ± 11.8 years; P = 0.028). Median follow-up period was 615 (Q1-Q3: 311-997) days in treatment-naive patients and 1,136 (Q1-Q3: 684-1,300) days in on-treatment patients. BPA strategy had as acceptable morbidity and mortality as PEA strategy (5-year morbidity and mortality event rate, BPA vs PEA: 10.2% [95% CI: 5.2%-19.5%] vs 16.1% [95% CI: 4.3%-50.6%] in treatment-naive patients; 9.7% [95% CI: 6.7%-13.8%] vs 6.9% [95% CI: 2.7%-17.3%] in on-treatment patients), with greater improvement of renal function; glomerular filtration rate in propensity score-matched population (difference between change: 4.9 [95% CI: 0.5-9.3] mL/min/1.73 m2; P = 0.030). ConclusionsBPA strategy was more frequently chosen in older patients compared with PEA strategy and showed acceptable outcomes for efficacy with greater advantage for improvement in renal function. (Multicenter registry of chronic thromboembolic pulmonary hypertension in Japan; UMIN000033784)

Haemolytic Anaemia-Related Pulmonary Hypertension.

Haemolytic anaemia represents a risk factor for the development of pulmonary hypertension (PH), currently classified as World Health Organization group 5 PH, and data regarding appropriate therapeutic strategy are limited. A total of 28 patients, 85.7% with thalassaemia and 14.3% with sickle cell disease, with a diagnosis of PH confirmed by right heart catheterization were included in the study. The patients were divided into three groups according to the PH haemodynamic definition and overall diagnostic approach: 42.9% had precapillary PH (pulmonary arterial hypertension-PAH group), 25% had post-capillary PH, and 32.1% had chronic thromboembolic PH (CTEPH) (29% of b-thalassemia and 50% of SCD patients). The therapeutic approach in each group and its impact on the outcome and haemodynamics were recorded. PAH-specific drug therapy received 82.1% of patients, and balloon pulmonary angioplasty (BPA) was performed in six patients with CTEPH. There were statistically significant differences in baseline mPAP and PVR values between the CTEPH-haemolytic anaemia group and other groups. PAH-specific drug therapy resulted in haemodynamic improvement for the PAH group. Patients who underwent BPA had improved pulmonary haemodynamics. The median survival time was 162 months, and the survival rate was 1 year-100%; 2, 3, 4, 5, and 6 years-96%; 9 years-90%; and 13 years-78%. In patients with haemolytic anaemia, the wide spectrum of induced PH highlighted the importance of a correct predominant diagnosis. BPA in CTEPH patients and specific-PAH drug therapy for PAH patients represent potential therapeutic strategies; however, the management should be offered in expert PH centres under individualized approaches for patients.

Differences in Exercise Capacity, Ventilatory Efficiency, and Gas Exchange between Patients with Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension Residing at High Altitude.

Cardiopulmonary exercise testing (CPET) assesses exercise capacity and causes of exercise limitation in patients with pulmonary hypertension (PH). At altitude, changes occur in the ventilatory pattern and a decrease in arterial oxygen pressure in healthy; these changes are increased in patients with cardiopulmonary disease. Our objective was to compare the response to exercise and gas exchange between patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) residing at the altitude of Bogotá (2640 m). All patients performed an incremental CPET with measurement of oxygen consumption ( ), dead space (VD/VT), ventilatory equivalents (VE/ ), and alveolar-arterial oxygen gradient ( ). test and one-way analysis of variance were used for comparisons between PAH and CTEPH. We included 53 patients, 29 with PAH, 24 with CTEPH, and 102 controls as a reference of the normal response to exercise at altitude. CTEPH patients had a higher New York Health Association (NYHA) functional class than PAH (p = 0.037). There were no differences between patients with PAH and CTEPH in hemodynamics and % of predicted (67.8 18.7 vs. 66.0 19.8, p 0.05), but those with CTEPH had higher dyspnea, VD/VT (0.36 0.09 vs. 0.23 0.9, p 0.001), VE/ (45.8 7.1 vs. 39.3 5.6, p 0.001), and (19.9 7.6 vs. 13.5 7.6, p 0.001) than PAH patients. At altitude, patients with PH present severe alterations in gas exchange during exercise. There were no differences in exercise capacity between PAH and CTEPH, but patients with CTEPH had more dyspnea and greater alterations in gas exchange during exercise. CPET made it possible to identify alterations related to the pathophysiology of CTEPH that could explain the functional class and dyspnea in these patients.

Better efficacy of sequential combination with balloon pulmonary angioplasty after long-term riociguat for patients with inoperable chronic thromboembolic pulmonary hypertension.

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.

Riociguat as bridging therapy to pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension: a retrospective cohort study.

In operable chronic thromboembolic pulmonary hypertension (CTEPH) patients, the utilization of bridging therapy with targeted medications prior to pulmonary endarterectomy (PEA) remains a topic of controversy, despite being common in cases of severe hemodynamic impairment. This study aims to assess the impact of riociguat as a bridging therapy on postoperative hemodynamics and outcomes. We conducted a retrospective study involving patients undergoing PEA from December 2016 to November 2023. Patients were categorized into two groups based on the use of riociguat before PEA. Pulmonary vascular resistance (PVR) following riociguat administration was assessed pre-PEA. Postoperative outcomes, including mortality, complications, and hemodynamics, were compared, employing propensity score matching analysis. Among the patients, 41.8% (n=56) received riociguat as bridging therapy. In patients with PVR ≥800 dynes·sec·cm-5, riociguat resulted in a reduction in PVR {1,207 [974-1,698] vs. 1,125 [928-1,486] dynes·sec·cm-5, P<0.01}, while no significant difference was observed in patients with PVR <800 dynes·sec·cm-5 {641 [474-740] vs. 600 [480-768] dynes·sec·cm-5, P=0.46}. After propensity score matching, each group included 26 patients. The overall perioperative mortality rate was 2.6%. Postoperative PVR {326 [254-398] vs. 361 [290-445] dynes·sec·cm-5, P=0.35} was similar in the riociguat group compared to the control group. The incidence of residual pulmonary hypertension (PH) and other postoperative outcomes were also comparable. The use of riociguat as bridging therapy demonstrated hemodynamic improvement before PEA in patients with high preoperative PVR. However, no additional benefits in postoperative mortality or hemodynamics were observed.

Direct oral anticoagulants in the treatment of chronic thromboembolic pulmonary hypertension patients: A retrospective cohort study

IntroductionDirect 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. MethodsFrom 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. ResultsAfter 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). ConclusionIn anticoagulation of CTEPH patients, DOACs have similar survival rate, similar risk of bleeding but higher risk of VTE recurrence than warfarin.

Notch ratio in pulmonary flow predicts long-term survival after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension

BackgroundAssessment of the pattern of the RV outflow tract Doppler provides insights into the hemodynamics of chronic thromboembolic pulmonary hypertension (CTEPH). We studied whether pre-operative assessment of timing of the pulmonary flow systolic notch by Doppler echocardiography is associated with long-term survival after pulmonary endarterectomy (PEA) for CTEPH.MethodsFifty-nine out of 61 consecutive CETPH patients (mean age 53 ± 14 years, 34% male) whom underwent PEA between June 2002 and June 2005 were studied. Clinical, echocardiographic and hemodynamic variables were assessed pre-operatively and repeat echocardiography was performed 3 months after PEA. Notch ratio (NR) was assessed with pulsed Doppler and calculated as the time from onset of pulmonary flow until notch divided by the time from notch until end of pulmonary flow. Long-term follow-up was obtained between May 2021 and February 2022.ResultsPre-operative mean pulmonary artery pressure (mPAP) was 45 ± 15 mmHg and pulmonary vascular resistance (PVR) was 646 ± 454 dynes.s.cm-5. Echocardiography before PEA showed that 7 patients had no notch, 33 had a NR < 1.0 and 19 had a NR > 1.0. Three months after PEA, echocardiography revealed a significant decrease in sPAP in long-term survivors with a NR < 1.0 and a NR > 1.0, while a significant increase in TAPSE/sPAP was only observed in the NR < 1.0 group. Mean long-term clinical follow-up was 14 ± 6 years. NR was significantly different between survivors and non-survivors (0.73 ± 0.25 vs. 1.1 ± 0.44, p < 0.001) but no significant differences were observed in mPAP or PVR. Long-term survival at 14 years was significantly better in patients with a NR < 1.0 compared to patients with a NR > 1.0 (83% vs. 37%, p = < 0.001).ConclusionPre-operative assessment of NR is a predictor of long-term survival in CTEPH patients undergoing PEA, with low mortality risk in patients with NR < 1.0. Long-term survivors with a NR < 1.0 and NR > 1.0 had a significant decrease in sPAP after PEA. However, the TAPSE/sPAP only significantly increased in the NR < 1.0 group. In the NR < 1.0 group, the 6-min walk test increased significantly between pre-operative and at 1-year post-operative follow-up. NR is a simple echocardiographic parameter that can be used in clinical decision-making for PEA.

Safety and Outcomes with Direct Oral Anticoagulants Versus Vitamin-K Antagonists in Chronic Thromboembolic Pulmonary Hypertension: A Systematic Review, Meta-Analysis, and Meta-Regression.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a subtype of pulmonary hypertension characterized by organized thrombi inside the pulmonary vasculature, leading to an increase in pulmonary artery pressure. CTEPH is seen in about 3-4% of patients with acute pulmonary embolism and is associated with poor outcomes. Apart from surgical intervention, lifelong anticoagulation is the mainstay of CTEPH management. Traditionally, CTEPH is managed with vitamin-K antagonists (VKA); however, direct oral anticoagulants (DOACs) are recently gaining popularity. However, the current literature comparing DOACs versus VKAs in CTEPH has inconsistent results. An electronic search of the major bibliographic databases was performed to retrieve studies comparing DOACs versus VKAs in CTEPH patients. For dichotomous outcomes, the odds ratio (ORs) with 95% confidence intervals (CI) were pooled using the DerSimonian and Laird random-effects model to generate forest plots. Statistical significance was considered at P < 0.05. Ten studies were included with 3936 patients (1269 in the DOAC group and 2667 in the VKA group). Treatment with DOAC was associated with no statistically significant difference in the risk of all-cause mortality (OR, 0.78; 95% CI, 0.35-1.71; P < 0.53), venous thromboembolism (OR, 1.19; 95% CI, 0.59-2.40; P = 0.63), major bleeding (OR, 0.68; 95% CI, 0.38-1.22; P = 0.20), and clinically relevant nonmajor bleeding (OR, 1.22; 95% CI, 0.80-1.86; P = 0.37). Our analysis demonstrates that DOACs are noninferior to VKAs in terms of their safety and outcomes profile in CTEPH. Further trials are needed to evaluate more robust evidence and to compare additional outcomes.

Novel Liver Injury Phenotypes and Outcomes in Clinical Trial Participants with Pulmonary Hypertension.

Rationale: 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 resulting from PAH and CTEPH have not been well studied. Objectives: We aimed to identify underlying patterns of liver injury in a cohort of patients with PAH and CTEPH 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. Measurements and Main 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 6-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 with placebo. The role of liver disease (often subclinical) in determining outcomes warrants prospective studies.

The impact of right ventricular energy failure on the results of pulmonary endarterectomy and balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension

Objective: We aimed to investigate the effect of right ventricular energy failure (RVEF) on hemodynamic and clinical outcomes in patients diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing pulmonary endarterectomy (PEA) surgery or balloon pulmonary angioplasty (BPA). Patients and Methods: A total of 100 CTEPH patients planned for PEA or BPA were included in the study. Based on the presence of RVEF during diagnosis, patients divided into two groups. Hemodynamic data from right heart catheterization (RHC) were compared before and after procedures in 3-6 months follow up period. Results: Patients with RVEF revealed a decrease in mean pulmonary artery pressure (mPAP) from 54.67±12.27 mmHg to 36.12±11.76 mmHg (p:&amp;lt;0.001), mean right atrial pressure (mRAP) from 13.40±4.08 mmHg to 9.76±4.56 mmHg (p:0.003), and pulmonary vascular resistance (PVR) from 11.36±5.15 Wood Units (WU) to 5.46±3.30 WU (p &amp;lt;0.001). In the non-RVEF group, mPAP decreased from 38.82±12.61 mmHg to 30.81±10.57 mmHg (p:&amp;lt;0.001), mRAP from 7.09±3.02mmHg to 7.15±3.07mmHg (p: 0.917), and PVR from 6.33±3.65 WU to 4.09±2.31 WU (p:&amp;lt;0.001). Conclusion:The presence of RVEF at the time of diagnosis in CTEPH patients does not have a negative impact on early perioperative and 3-month postoperative outcomes following PEA or BPA. This high-risk patient group demonstrated significant hemodynamic and clinical benefits from both PEA and BPA.

Endothelial cells in chronic thromboembolic pulmonary hypertension exhibit cytoskeletal alteration

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Health Research Fund (Fondo de Investigación Sanitaria [FIS]) from the Instituto de Salud Carlos III Introduction Endothelial dysfunction (ED) is pivotal in Chronic Thromboembolic Pulmonary Hypertension (CTEPH) due to structural and functional alterations in endothelial. Previous studies have shown the critical function of cytoskeletal elements, particularly actin microfilaments and microtubules, along with associated cell adhesion complexes, in the endothelial integrity. Nevertheless, precise alterations in the cytoskeletal elements of endothelial cells (ECs) in CTEPH patients remain unclear. Purpose This study aims to investigate the cytoskeleton changes in CTEPH-ECs compared to healthy ECs, characterizing morphological and structural differences. Objectives involve assessing microtubules and microfilaments expression, and their influence on ECs migratory capacity. Finally, our study aims to gain novel insights into the spatial organization of cytoskeleton components in CTEPH patients. Methods CTEPH-ECs were isolated from freshly resected pulmonary endarterectomy specimens of CTEPH patients, while human pulmonary artery ECs (HPAE) were used as healthy controls. Fluorescence immunocytochemistry assessed phenotypic and compositional characteristics of the cytoskeleton. Morphometric analysis described morphology and filament organization of cytoskeletal proteins using a custom-built pipeline. X-ray microscopy examined the phenotype and cytoskeletal components distribution. The migration assay evaluated how these structural differences affected ECs migratory capacity and the cytoskeletal elements expression. Results CTEPH-ECs exhibited larger surface area (1352 vs 662µm2, p&amp;lt;0.01) and a more stellate morphology (0.365 vs 0.289, p&amp;lt;0.01) than HPAE-ECs. Immunostaining indicated altered cytoskeletal composition in CTEPH-ECs with significantly higher tubulin expression, expressed in microtubules, (3327 vs 2238AU, p&amp;lt;0.01) and F-actin microfilaments (2068 vs 1300AU, p&amp;lt;0.01) compared to HPAE. Similarly, CTEPH-ECs showed reduced G-actin expression (3002 vs 7461AU, p&amp;lt;0.01). Morphometric analysis demonstrated that microfilaments were thinner (0.623 vs 0.831AU, p&amp;lt;0.01), more straight (0.135 vs. 0.172, p&amp;lt;0.01) and more aligned (0.132 vs. 0.156, p&amp;lt;0.01) in CTEPH-ECs. Microtubule thickness decreased compared to HPAE-ECs (0.341 vs 1.371AU, p&amp;lt;0.01). CTEPH-ECs showed impaired wound healing (60 vs 89% closure, p&amp;lt;0.05). CTEPH group showed an increase in microtubules and microfilaments expression during wound healing, but with irregular patterns, unlike the constant levels in HPAE. TXM-technology revealed spatial organization differences, especially expansive microtubules distribution in CTEPH-ECs (4.2*10^7 vs. 8.7*10^6 nm³, p&amp;lt;0.05). Conclusion These preliminary findings highlight significant structural and compositional differences in CTEPH-ECs, along with altered wound healing capacity, suggesting dynamic cytoskeletal and cellular changes in CTEPH. Understanding these alterations is crucial for advancing CTEPH knowledge and identifying potential therapeutic targets.

Laterality of CT-measured hepatic extracellular volume fraction in patients with chronic thromboembolic pulmonary hypertension.

This study examines the hepatic extracellular volume fraction (ECV) disparity between the left and right lobes (ECV_left and ECV_right) in patients with chronic thromboembolic pulmonary hypertension (CTEPH), its association with right heart catheterization (RHC) metrics, and with intolerance to increased pulmonary hypertension (PH)-targeted medication dosages. We retrospectively analyzed 72 CTEPH-diagnosed patients who underwent equilibrium-phase abdominal dual-energy CT (DECT) and RHC. Hepatic ECVs, derived from DECT's iodine maps using circular regions of interest in the liver and aorta, were correlated with RHC parameters via Spearman's rank correlation and lobe differences through the Wilcoxon signed-rank test. Logistic regression assessed cases with ECV_left exceeding ECV_right by > 0.05, while receiver operating characteristic curve analysis gauged ECVs' predictive power for medication intolerance. Of the 72 patients (57 females; median age 69), ECV_total (0.24, IQR 0.20-0.27) moderately correlated with RHC parameters (rs = 0.28, -0.24, 0.3 for mean pulmonary arterial pressure, cardiac index [CI], and pulmonary vascular resistance index, respectively). ECV_left significantly surpassed ECV_right (0.25 vs. 0.22, p < 0.001), with a greater ECV_left by > 0.05 indicating notably lower CI (p < 0.001). In 27 patients on PH medication, ECV_left effectively predicted medication intolerance (AUC = 0.84). In CTEPH patients, hepatic ECV correlated with RHC metrics, where elevated left lobe ECV suggested reduced CI and potential medication intolerance.

Serum ASGR2 level: an efficacy biomarker for balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension.

This study aimed to employ plasma proteomics to investigate the molecular changes, pathway alterations, and potential novel biochemical markers associated with balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Pre- and post-BPA plasma samples from five CTEPH patients in the PRACTICE study were analyzed to identify differentially expressed proteins. Proteomic and bioinformatics analyses were conducted, and the identified proteins were further validated using ELISA assays in a separate cohort of the same study. Correlation and multivariate regression analyses were performed to investigate the associations between these differentially expressed proteins and clinical parameters. Significantly higher serum levels of asialoglycoprotein receptor 2 (ASGR2) were detected in 5 CTEPH patients compared to those in healthy individuals but decreased significantly after successful BPA procedures. The decrease in serum levels of ASGR2 after the completion of BPA procedures was further validated in a separate cohort of 48 patients with CTEPH [0.70 (0.51, 1.11) ng/mL vs. 0.38 (0.27, 0.59) ng/mL, P < 0.001]. Significant associations were found between the pre-BPA ASGR2 level and clinical parameters, including neutrophil percentage (R = 0.285, P < 0.05), platelet (PLT) count (R = 0.386, P < 0.05), and high-density lipoprotein cholesterol (HDL-C) before BPA (R = -0.285, P < 0.05). Significant associations were detected between post-BPA serum ASGR2 levels and lymphocyte percentage (LYM%) (R = 0.306, P < 0.05), neutrophil-to-lymphocyte ratio (R = -0.294, P < 0.05), and pulmonary vascular resistance after BPA (R = -0.35, P < 0.05). Multivariate stepwise regression analysis revealed that pre-BPA ASGR2 levels were associated with HDL-C and PLT count (both P < 0.001), while post-BPA ASGR2 levels were associated with LYM% (P < 0.05). Serum levels of ASGR2 may be a biomarker for the effectiveness of BPA treatment in CTEPH patients. The pre-BPA serum level of ASGR2 in CTEPH patients was associated with HDL-C and the PLT count. The post-BPA serum level of ASGR2 was correlated with the LYM%, which may reflect aspects of immune and inflammatory status.

Insufficiency of quality of life as the treatment endpoint for balloon pulmonary angioplasty in inoperable chronic thromboembolic pulmonary hypertension.

The ability of a quality of life (QoL) to guide balloon pulmonary angioplasty (BPA) among patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) has not been fully investigated. This study explored the relationship between QoL scores and hemodynamics in CTEPH patients after BPA and examined whether QoL could be applied as a treatment endpoint. This cohort study included patients with inoperable CTEPH who had undergone at least four sessions of BPA. The patients' demographic and clinical data as well as hemodynamic parameters and scores from the RAND 36-item short-form QoL questionnaire were recorded and compared before and after BPA. After BPA treatments, clinical characteristics, hemodynamic parameters, as well as QoL score improved significantly. A physical component summary (PCS) score of 35 or 46 can be used as the cutoff value for predicting better World Health Organization functional classification (WHO FC). Patients who had a higher PCS would have longer 6-min walk distance (6MWD), lower pulmonary vascular resistance (PVR), and better cardiac output (CO) both before and after BPA. However, 19 patients (55.9%) with a higher PCS score after BPA did not achieve the goal of mean pulmonary arterial pressure (mPAP) ≤30 mmHg. During the follow-up period, a significant reduction of PVR was observed, but the PCS score improved a little. QoL is a useful tool for assessing the exercise endurance of patients with inoperable CTEPH treated with BPA, but is insufficient to serve as a treatment endpoint for BPA.

Comorbidities, Treatment and Survival Rates of Chronic Thromboembolic Pulmonary Hypertension in a Regional Centre.

Background/Objectives: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by a multitude of underlying causes, treatment modalities and prognostic outcomes. Our aim was to evaluate the underlying causes, comorbidities and survival rates of CTEPH patients. Methods: A retrospective analysis was conducted regarding the evolution of CTEPH patients confirmed by right heart catheterization under treatment with specific vasodilator medication in our centre between 2008 and 2023. Results: We treated 14 CTEPH patients, 78.57% female, 52.79 ± 13.64 years at inclusion, representing 11.29% of our pulmonary arterial hypertension registry. Initially, the distribution of patients' NYHA class was II-14.28%, III-71.42% and IV-14.28%. In total, 71.42% of these patients were technically operable due to the central location of the thrombus, but 42.85% presented severe comorbidities and 28.57% refused the surgery or it was financially inaccessible. Only four patients were operated on by pulmonary endarterectomy (PEA). Unfortunately, all the post-PEA patients had persistent pulmonary hypertension and had to continue vasodilator treatment. Overall, 64.28% of patients had monotherapy, 21.42% double therapy and 14.28% triple therapy. Regarding underlying causes and comorbidities, we found the following incidences: 78.57% chronic venous insufficiency, 42.85% obesity, 35.71% thyroid disease, hypertension and hyperuricemia, 21.42% thrombophilia and ischemic heart disease, 14.28% atrial fibrillation, vasculitis and lung disease, and 14.28% neoplastic history and diabetes. Seven patients died (50%), six of whom were unoperated and one of whom was lost (abandoned the program). The survival rates at 1, 3, 5 and 7 years for unoperated patients were 100%, 58.3%, 29.2% and 29.2% versus 100%, 75%, 75% and 75% in post-PEA patients. Conclusions: CTEPH, marked by delayed diagnosis, multiple comorbidities and limited intervention options, requires proactive screening and comprehensive multimodal therapies, including PEA, to improve survival rates.