Chronic Thromboembolic Pulmonary Hypertension Patients Research Articles

Peri-procedural complications in patients with chronic thromboembolic pulmonary hypertension who underwent balloon pulmonary angioplasty

Abstract Background Complication rate in patients with chronic thrombo-embolic pulmonary hypertension (CTEPH) who undergo balloon pulmonary angioplasty (BPA) is high, especially in patients with compromised pulmonary hemodynamics. Purpose Here we describe complications based on the new definition in a cohort of CTEPH patients who underwent BPA. Methods All patients with CTEPH who completed BPA treatments before September 15th 2023 were selected from the CTEPH database. Peri-procedural complications were collected and classified according to the 2023 consensus paper on BPA in CTEPH patients. Complications were analyzed in subgroups of patients with pulmonary vascular resistance (PVR) or >6.6 WU and mean pulmonary artery pressure (mPAP) or >45 mmHg at first BPA. Results In total, 87 patients (63.2% women; mean age 61.1±14.0 years; 62.1% on dual PH targeted medical therapy) underwent 426 (mean 4.9±1.6 per patient) BPAs. Non-severe complications occurred in 59 (13.8%) of the interventions; in 47.1% of the patients; 64.4% were thoracic, and 35.6% were non-thoracic complications. The thoracic complications were mostly mild (71.1%) or moderate (28.9%), and none were severe. Patients with a PVR >6.6 WU (n=8) underwent more BPA-procedures (6.6±1.5 versus 4.6±1.5, p=0.002), had more overall complications (87.5% versus 40.6% of patients, p=0.020), and more thoracic complications (17.0% vs 6.8% of BPAs, p=0.013) than patients with PVR 6.6 WU. Patients with mPAP >45 mmHg (n=13) also had more BPA-procedures (6.5±1.7 versus 4.6±1.4, p<0.001), more overall complications (76.9% versus 43.5% of patients, p=0.027) and more thoracic complications (14.1% versus 7.9% of BPAs, p=0.039) than patients with mPAP 45 mmHg. Conclusions Complications occurred in 13.8% of BPA procedures and were mostly mild. Patients with increased pulmonary hemodynamics at baseline suffered more (thoracic) complications.Overview complications

Targeted medical treatment of patients with chronic thromboembolic pulmonary hypertension who undergo balloon pulmonary angioplasty

Abstract Introduction In patients with chronic thromboembolic pulmonary hypertension (CTEPH) who undergo balloon pulmonary angioplasty (BPA), pre-treatment with PH-targeted medical therapy may be beneficial in improving clinical parameters and pulmonary hemodynamics. Purpose This study aims to describe the clinical results of PH-specific therapy prior to BPA. Methods Patients with CTEPH who underwent BPA treatment were selected from the St. Antonius CTEPH database. Medical treatment strategy, clinical parameters, and pulmonary hemodynamics at time of diagnosis and at the first BPA were collected from medical records. Results In total 93 BPA patients (62.4% women; age 60.4±14.1 years; NYHA FC III/IV 60.9%) were included; the majority of patients received dual PH targeted medical therapy (64.1%). Between diagnosis and the first BPA significant improvements were observed for both clinical parameters (6MWD: 26.8m [5.2 - 48.4], Log NTproBNP: -0.5 pg/ml [-0.8 to -0.2]) and pulmonary hemodynamic (mRAP: -2.2 mmHg [-3.7 to -0.8], mPAP: -6.4mmHg [-8.3 to -4.5], CO: 0.5L/min [0.2 - 0.9] and PVR: -2.6WU [-3.3 to -2]). Dual PH targeted medical therapy resulted in significantly greater improvements in PVR (p = 0.03) in comparison to patients without and mono PH targeted medical therapy (CO and mPAP both p-value: 0.01). Conclusion Between diagnosis and the initial BPA, substantial improvements were observed for 6MWD, NTproBNP and most pulmonary hemodynamics in CTEPH patients who underwent BPA. Patients who received dual PH targeted medical therapy had significantly greater improvements compared to patients without (PVR) and on mono PH targeted medical therapy (CO and mPAP).Clinical parameters: Baseline-1st BPAPH medication: ANOVA Post hoc analyses

Monitoring anti-factor Xa activity in patients with chronic thromboembolic pulmonary hypertension treated with factor Xa inhibitors

Direct oral anticoagulants (DOACs) have been used clinically in patients with chronic thromboembolic pulmonary hypertension (CTEPH) for secondary prevention after acute venous thromboembolism, although the data are limited. We evaluated the effects of DOACs—especially factor Xa (FXa) inhibitors—by measuring anti-factor Xa activity (AXA). Fifty consecutive CTEPH patients treated with rivaroxaban, apixaban, or edoxaban were enrolled. Heparin-calibrated AXA was measured at peak and trough. The median peak heparin-calibrated AXA across all 50 patients was 1.90 IU/mL and was comparable among the three FXa inhibitors. At trough, heparin-calibrated AXA was significantly higher in apixaban-treated patients (median 0.70 IU/mL) than in those given rivaroxaban (median 0.11 IU/mL) or edoxaban (median 0.11 IU/mL, p < 0.001). Peak heparin-calibrated AXA was significantly lower with reduced-dosage FXa inhibitor (edoxaban 30 mg/day) than with the reference dosage (edoxaban 60 mg/day, apixaban 10 mg/day, or rivaroxaban 15 mg/day, p = 0.01). The heparin-calibrated AXA of both rivaroxaban and apixaban was strongly significantly correlated with the plasma concentration of each drug. The cumulative rate of major and clinically relevant non-major bleeding was significantly higher in patients with peak heparin-calibrated AXA ≥ 2.09 IU/mL. Heparin-calibrated AXA could provide useful information for treating CTEPH patients with FXa inhibitors.

Mapping the amplitude and phase of dissolved 129Xe red blood cell signal oscillations with keyhole spectroscopic lung imaging.

To assess the regional amplitude and phase of dissolved 129Xe red blood cell (RBC) signal oscillations in the lung vasculature with keyhole spectroscopic imaging and to compare with previous methodology, which does not account for oscillation phase. 129Xe gas transfer was measured with a four-echo 3D radial spectroscopic imaging sequence. Keyhole reconstruction-based RBC signal oscillation amplitude mapping was applied retrospectively to data acquired from 28 healthy volunteers, 4 chronic thromboembolic pulmonary hypertension (CTEPH) patients, and 5 patients who were hospitalized due to COVID-19 pneumonia and had residual lung abnormalities. Using a sliding window keyhole reconstruction, maps of RBC oscillation amplitude were corrected for regional phase difference. Repeatability of the phase-adjusted oscillation amplitude was assessed in 8 healthy volunteers across three scans. With sliding window keyhole reconstruction, regional phase differences were observed in the RBC signal oscillations: mean phase = (0.27 ± 0.19) rad in healthy volunteers, (0.24 ± 0.13) rad in CTEPH patients, and (0.33 ± 0.19) rad in patients with post-COVID-19 residual lung abnormality. The oscillation amplitude and phase maps were more heterogeneous (i.e., they showed increased coefficient of variation) for the CTEPH patients. The RBC oscillation amplitude was repeatable, and the mean three-scan coefficient of variation was smaller when the phase adjustment was made (0.07 ± 0.04 compared with 0.16 ± 0.05). Sliding window keyhole reconstruction of radial dissolved 129Xe imaging reveals regional phase differences in the RBC oscillations, which are not captured when performing two phase keyhole reconstruction. This regional phase information may reflect the hemodynamic effect of the cardiac pulse wave in the pulmonary microvasculature.

Cost-effectiveness of follow-up algorithms for chronic thromboembolic pulmonary hypertension in pulmonary embolism survivors

IntroductionAchieving an early diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) in pulmonary embolism (PE) survivors results in better quality of life and survival. Importantly, dedicated follow-up strategies to achieve an earlier CTEPH diagnosis involve costs that were not explicitly incorporated in the models assessing their cost-effectiveness. We performed an economic evaluation of 11 distinct PE follow-up algorithms to determine which should be preferred.Materials and methods11 different PE follow-up algorithms and 1 hypothetical scenario without a dedicated CTEPH follow-up algorithm were included in a Markov model. Diagnostic accuracy of consecutive tests was estimated from patient-level data of the InShape II study (n=424). The life-long costs per CTEPH patient were compared and related to Quality-Adjusted Life-Years (QALYs) for each scenario.ResultsCompared to not performing dedicated follow-up, the integrated follow-up algorithms are associated with an estimated increase of 0.89–1.2 QALY against an incremental cost-effectiveness ratio (ICER) of 25 700–46 300 € per QALY per CTEPH patient. When comparing different algorithms with each other, the maximum differences were 0.27 QALY and €27 600. The most cost-effective algorithm was the InShape IV algorithm, with an ICER of €26 700 per QALY compared to the next best algorithm.ConclusionSubjecting all PE survivors to any of the currently established dedicated follow-up algorithm to detect CTEPH is cost-effective and preferred above not performing a dedicated follow-up, evaluated against the Dutch acceptability threshold of €50 000 per QALY. The model can be used to identify the locally preferred algorithm from an economical point-of-view within local logistical possibilities.

Prostacyclin pathway vasodilators in patients with chronic thromboembolic pulmonary hypertension (CTEPH): A systemic review and meta-analysis of randomized controlled trials.

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

Tricuspid annular plane systolic excursion to pulmonary artery systolic pressure ratio in chronic thromboembolic pulmonary hypertension improves with balloon pulmonary angioplasty.

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

Concomitant pulmonary thromboendarterectomy and supracoronary ascending aorta replacement: a case report

Pulmonary thromboendarterectomy (PTE) is the treatment of choice for patients with operable chronic thromboembolic pulmonary hypertension (CTEPH). PTE with additional cardiac procedures has been reported to be safely applicable. However, there are not enough publications in the literature regarding the treatment strategy of CTEPH patients with ascending aortic aneurysms. In this case report, we present a successful case of concomitant PTE and supracoronary ascending aorta replacement.

Role of Optical Coherence Tomography in Vasculitis-Associated Pulmonary Hypertension and Chronic Thromboembolic Pulmonary Hypertension.

Identifying and understanding the microstructural changes within the wall of the pulmonary artery (PA) is crucial for elucidating disease mechanisms and guiding treatment strategies. We assessed the utility of optical coherence tomography (OCT) in identifying such changes within segmental/subsegmental PAs and compared the morphological variations in WHO group 4 pulmonary hypertension associated with Behcet Disease (BD), Takayasu arteritis (TA) and chronic thromboembolic pulmonary hypertension (CTEPH). Idiopathic pulmonary arterial hypertension (IPAH) patients served as controls.Methods and Results: A total of 197 cross-sectional images were analyzed from 20 consecutive patients. BD patients exhibited lower %wall area and mean wall thickness (MWT) compared with CTEPH, TA and, IPAH patients. TA patients showed a notably higher %wall area, which was significant in IPAH and BD patients. Variations in %wall area measurements were observed across distinct cross-sectional segments of the PA within individual patients (22% in CTEPH, 19% in BD, 16% in TA, 23% in IPAH patients). Intravascular webs, bands, and thrombi were observed in BD and CTEPH patients. OCT provided clear delineation of vascular wall calcifications and adventitial vasa vasorum. No procedure-related complications were observed. PA involvement differs among the various etiologies of PH, with the PA being heterogeneously affected. OCT offers promise in elucidating microstructural vascular wall changes and providing insights into disease mechanisms and treatment effects.

An exploration into CTEPH medications: Combining natural language processing, embedding learning, in vitro models, and real-world evidence for drug repurposing.

In the modern era, the growth of scientific literature presents a daunting challenge for researchers to keep informed of advancements across multiple disciplines. We apply natural language processing (NLP) and embedding learning concepts to design PubDigest, a tool that combs PubMed literature, aiming to pinpoint potential drugs that could be repurposed. Using NLP, especially term associations through word embeddings, we explored unrecognized relationships between drugs and diseases. To illustrate the utility of PubDigest, we focused on chronic thromboembolic pulmonary hypertension (CTEPH), a rare disease with an overall limited number of scientific publications. Our literature analysis identified key clinical features linked to CTEPH by applying term frequency-inverse document frequency (TF-IDF) scoring, a technique measuring a term's significance in a text corpus. This allowed us to map related diseases. One standout was venous thrombosis (VT), which showed strong semantic links with CTEPH. Looking deeper, we discovered potential repurposing candidates for CTEPH through large-scale neural network-based contextualization of literature and predictive modeling on both the CTEPH and the VT literature corpora to find novel, yet unrecognized associations between the two diseases. Alongside the anti-thrombotic agent caplacizumab, benzofuran derivatives were an intriguing find. In particular, the benzofuran derivative amiodarone displayed potential anti-thrombotic properties in the literature. Our in vitro tests confirmed amiodarone's ability to reduce platelet aggregation significantly by 68% (p = 0.02). However, real-world clinical data indicated that CTEPH patients receiving amiodarone treatment faced a significant 15.9% higher mortality risk (p<0.001). While NLP offers an innovative approach to interpreting scientific literature, especially for drug repurposing, it is crucial to combine it with complementary methods like in vitro testing and real-world evidence. Our exploration with benzofuran derivatives and CTEPH underscores this point. Thus, blending NLP with hands-on experiments and real-world clinical data can pave the way for faster and safer drug repurposing approaches, especially for rare diseases like CTEPH.

Novel Computed Tomography Angiography Parameter Is Associated with Low Cardiac Index in Patients with Chronic Thromboembolic Pulmonary Hypertension: A Retrospective Analysis.

We completed a retrospective analysis of CTEPH patients in which individuals with low CI (<2.2-L/min/m2) were identified. Both absolute and fractional HU-Δ were derived from pulmonary CTA by subtracting the HU value of the left atrium (LA) and left ventricle (LV) from the main pulmonary artery (MPA) (absolute) and expressing them as a percentage of MPA-HU (fractional) on static axial images. These were compared between low and normal CI. Of the 237 patients, 50.2% were female, 53.2% were White, 36.7% were Black. Hemodynamics were mean pulmonary artery (PA) pressure = 45.4 ± 11.2-mmHg, pulmonary vascular resistance = 9.2 ± 4.4-WU, CI = 2.05 ± 0.48-L/min/m2. There was a higher mean MPA-HU = 391.1 ± 113.6 than LA-HU = 251.6 ± 81. In patients with low CI, the HU-Δ was higher, HU-ΔMPA-LA was 148.9 ± 78.4 vs. 124.5 ± 77.2 (p = 0.02), and HU-ΔMPA-LV was 170.7 ± 87 vs. 140 ± 82 (p = 0.009). A HU-ΔMPA-LA = 118 had a sensitivity of 75.6% and specificity of 77% to detect low CI, AUC 0.61, p = 0.003. A HU-ΔPA-LV = 156 had a sensitivity of 77% and specificity of 53% to detect low CI, AUC = 0.62, p = 0.001. A fractional reduction HU-ΔMPA-LA of 35% had a sensitivity and specificity of 79% and 53%, respectively, to detect low CI (AUC 0.65, p < 0.001). A fractional reduction of the HU-ΔMPA-LV of 40% had a sensitivity and specificity of 80% and 55%, respectively, to detect low CI (AUC 0.65, p < 0.001). HU Δ were highly reproducible (Kappa = 0.9, p < 0.001, 95% CI 0.86-0.95). High HU Δ between MPA-LA and MPA-LV were associated with low CI in patients with CTEPH.

Incidence and clinical course of chronic thromboembolic pulmonary hypertension with or without a history of venous thromboembolism in Denmark

BackgroundA considerable number of patients with chronic thromboembolic pulmonary hypertension (CTEPH) lack a history of venous thromboembolism (VTE). ObjectivesWe aimed to examine the annual incidence and prevalence of CTEPH in Denmark and to compare the rates of VTE, bleeding, and mortality between CTEPH patients with and without a history of VTE. MethodsThe Danish National Patient Registry covering all Danish hospitals was used to identify all CTEPH cases between 2009 and 2018, based on combinations of discharge diagnoses using International Classification of Diseases, 10th Revision codes for CTEPH and relevant diagnostic and/or therapeutic interventions. Incidence rates of CTEPH per 100 000 person-years, rates of VTE and bleeding, and 5-year survival estimates were calculated. ResultsIn total, 509 CTEPH patients were identified, of whom 82% had a history of VTE. The yearly incidence rate of CTEPH was 0.5 to 0.8 per 100 000 person-years during the study period. Patients with a history of VTE experienced a 2.5-fold rate of VTE compared with those without prior VTE (2571 vs 980 per 100 000 person-years), while the rate of bleeding events was lower (5008 vs 7139 per 100 000 person-years). The 5-year survival of CTEPH patients with a VTE history was 65% (95% CI, 58%-71%) compared with 45% (95% CI, 31%-58%) in patients without a history of VTE. ConclusionThe Danish incidence rate of CTEPH was comparable with that of other European countries. We identified notable differences in the prognosis of patients with CTEPH with or without a history of VTE. These findings may support generation of hypotheses regarding the pathophysiology of CTEPH and inform current patient care.

Epidemiology of supplemental oxygen in patients with pulmonary hypertension.

Patients with pulmonary hypertension (PH) may present with hypoxaemia at rest or during daily activities. There is no epidemiological data on the prescription of long-term oxygen therapy (LTOT) in patients with PH. The study sought to analyse the prevalence and incidence of LTOT prescription among patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) in Spain and to determine predictors for this prescription. A retrospective analysis was performed from the Spanish Registry of Pulmonary Arterial Hypertension (REHAP). Collected data included demographics and anthropometric measurements, functional class (FC), arterial blood gases, pulmonary function tests, haemodynamic measurements, six-minute walking distance (6MWD) and LTOT prescription. In addition, we assessed the prevalence and incidence of LTOT prescription by PH group and subtype and potential predictors for LTOT initiation in the first 5 years after diagnosis. We analysed 4533 patients (69.9% PAH and 30.1% CTEPH), mostly female (64.5%), with a mean age of 53.0 ± 18.3 years. The prevalence of LTOT was 19.3% for all patients. The incidence of LTOT prescriptions decreased from 5.6% to 1.6% between 2010 and 2019, respectively. Predictors for LTOT prescription, excluding those that represent the indication for oxygen therapy were: FC (HR: 1.813), 6MWD (HR: 1.002), mean pulmonary arterial pressure (mPAP) (HR: 1.014), cardiac index (CI) (HR: 1.253), pulmonary vascular resistance (PVR) (HR: 1.023) and diffusing capacity of carbon monoxide (DLCO) (HR: 1.294). The prevalence of LTOT in PAH and CTEPH patients is close to 20%. FC, 6MWD, mPAP, CI, PVR and DLCO were predictors for LTOT prescription.

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.