Search Results (145)

Background: The coexistence of systemic prothrombotic disorders, chronic thromboembolic pulmonary hypertension (CTEPH), chronic hypoxia, and cerebrovascular thrombosis creates complex diagnostic and therapeutic challenges. Case summary: We report the case of a 52-year-old woman with JAK2V617F-positive polycythemia vera, inherited thrombophilic abnormalities, recurrent pulmonary thromboembolism progressing to severe CTEPH, chronic hypoxemia, cerebral venous sinus thrombosis, and right vertebral artery occlusion. Management challenge: The case illustrates persistent thrombotic risk despite anticoagulation, the need for disease-directed cytoreduction, limited access to CTEPH-directed interventional treatment, neurological vulnerability despite preserved brain parenchymal integrity, and the narrow therapeutic margin created by the combined use of anticoagulant, cytoreductive, and pulmonary vasodilator therapy. Particular emphasis is placed on the competing risks of recurrent thrombosis and hemorrhagic complications, especially in the cerebrovascular territory. Conclusion: This case highlights the need for repeated multidisciplinary reassessment in patients with overlapping hematological, pulmonary, and neurological vascular disease. Improved survival in patients with severe multisystemic conditions may increase the clinical relevance of complex presentations requiring coordinated management. Further evidence is needed to support safer, more standardized treatment strategies for patients requiring simultaneous control of thrombosis, pulmonary vascular disease, myeloproliferation, hypoxia, and treatment-related bleeding risk. Full article

Non-invasive methods used for PH detection in clinical practice have several limitations. The combination of high spatiotemporal sensitivity magnetocardiography (MCG) and artificial intelligence algorithms may offer an accurate approach for PH detection. In this study, we develop a convolutional neural network (CNN) model based on the 64-channel MCG time-series data. This exploratory study enrolled patients undergoing 64-channel MCG, including right-heart-catheterization confirmed PH patients and symptomatic controls with low echocardiographic probability of PH. After data preprocessing, a temporal CNN integrating MCG signals with age, sex, and body mass index was developed and compared with conventional machine learning models. The CNN model achieved strong discrimination, with area under the curve (AUC) values of 0.939 (95% confidence interval [CI]: 0.913–0.961) in the development out-of-fold evaluation and 0.974 (95% CI: 0.944–0.994) in the hold-out test set, outperforming conventional machine learning models. Decision curve analysis showed the greatest net benefit at clinically relevant thresholds. Attribution analysis indicated that spatial QRS morphology redistribution contributed substantially to PH classification. The temporal CNN model based on raw 64-channel MCG signals showed promising performance for non-invasive PH detection and outperformed conventional machine learning approaches in this exploratory single-center cohort enriched for PAH and CTEPH. Full article

Background: Pulmonary arterial hypertension (PAH) is a rare and progressive disorder characterized by increased pulmonary vascular resistance and vascular remodeling. Genetic polymorphisms, epigenetic modifications, and ion channel dysregulation are increasingly recognized as key contributors to disease pathogenesis. Anoctamin-1 (ANO1/TMEM16A), a calcium-activated chloride channel, plays a critical role in vascular tone regulation. Objective: This study aimed to investigate the association between ANO1 gene polymorphisms (rs7127129 and rs2509153), promoter methylation status, and serum chloride levels in patients with idiopathic pulmonary arterial hypertension (IPAH), congenital heart disease (CHD), and chronic thromboembolic pulmonary hypertension (CTEPH). Methods: A total of 106 IPAH patients, 40 CHD patients, and 30 CTEPH patients, together with 125 healthy controls, were included. The control group had a comparable age distribution, with a balanced sex ratio, whereas females predominated in all three PH groups. Genotyping was performed using TaqMan-based real-time PCR. Promoter methylation was analyzed using bisulfite conversion followed by quantitative real-time PCR. Serum chloride levels were measured using an ion-selective electrode method. Results: No significant association was observed between rs7127129 and rs2509153 polymorphisms and IPAH or CTEPH (p > 0.05). However, rs7127129 showed a significant association with CHD (p < 0.05). After excluding hypertensive patients, both polymorphisms remained significantly associated with CHD. Serum chloride levels differed significantly among groups (p < 0.001), with higher levels observed particularly in the CTEPH and CHD groups compared to controls, while IPAH patients exhibited intermediate but still elevated levels relative to controls. In contrast, promoter methylation levels were significantly lower in all patient groups compared to controls. An inverse relationship between chloride levels and methylation status was observed. Conclusions: ANO1 polymorphisms are not major determinants of IPAH or CTEPH but may contribute to CHD susceptibility. Increased serum chloride levels, together with decreased promoter methylation, suggest a potential mechanistic link between ion channel dysregulation and epigenetic alterations in pulmonary hypertension. Further large-scale and functional studies are warranted. Full article

Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease that occurs due to fibrotic remodeling of the pulmonary vessels. This leads to increased pressure overload onto the right ventricle, resulting in complications such as heart failure. Pulmonary endarterectomy (PEA) remains the gold standard of treatment for CTEPH, yet many patients experience life-threatening perioperative complications, including refractory right ventricular failure, reperfusion pulmonary edema, and endobronchial hemorrhage. Extracorporeal membrane oxygenation (ECMO) has been used as a form of mechanical circulatory support to aid recovery in patients with perioperative complications in the context of CTEPH. This review identifies preoperative risk factors, including pulmonary vascular resistance, high body mass index, and elevated neutrophil-to-lymphocyte ratios. It also identifies differences in ECMO configuration, with veno-arterial ECMO preferred for hemodynamic instability and veno-venous ECMO for respiratory failure. Finally, we posit that, based on contemporary literature, the implementation of early ECMO in decompensated patients may be associated with reduced hospital mortality, and in those who survive beget excellent mid-term survival. Full article

Background: Cancer and pulmonary circulation disorders represent increasingly intersecting clinical entities. The prevalence of malignancy in patients with pulmonary hypertension (PH), particularly those with chronic thromboembolic pulmonary hypertension (CTEPH), is higher than in the general population. Moreover, cancer and antineoplastic therapies have been implicated in the development of PH through multiple mechanisms. Methods: We performed a systematic review and meta-analysis of the literature focusing on the prevalence of cancer in patients with PH. Mortality incidence and mortality risk were also evaluated for patients with PH with or without cancer. Specific sub-analyses for patients with CTEPH were also performed. Finally, we evaluated the prevalence of PH and its risk of mortality in patients with cancer. Results: Overall, 12 studies including 4402 patients were selected in the quantitative analysis. All the included studies had an observational design. The prevalence of cancer in patients with any PH group was 13% (95% CI: 11–16%); mortality incidence in patients with any PH group and cancer was 41% (95% CI: 26–58%), compared to 10% (95% CI: 1–48%) in those without cancer. The association was even stronger when considering only patients with CTEPH, with a mortality incidence of 4% (95% CI: 2–9%) in those without cancer compared to 19% (95% CI: 8–37%) in patients with cancer (p for difference: <0.01). Finally, prevalence of any PH group in patients with cancer was 22% (95% CI: 15–31%). Conclusions: We observed a possible correlation between PH and cancer, with a significant impact on mortality in patients with PH, particularly those with CTEPH. This association suggests the need for a close clinical surveillance for early detection of cancer and PH. Full article

Pulmonary endarterectomy (PEA) specimens provide a unique source of endothelial cells (ECs) to model chronic thromboembolic pulmonary hypertension (CTEPH) in vitro. This study investigates the impact of chronic hypoxia on PEA-derived ECs, focusing on mechanisms of endothelial dysfunction and vascular remodeling. ECs from PEA specimens (EC-CTEPH) and controls were exposed to normoxia, hypoxia, and reoxygenation. Cell morphology, proliferation, migration, and expression of angiogenic and hypoxia-responsive genes were assessed. Pharmacological HIF stabilization with dimethyloxalylglycine (DMOG) was compared with hypoxia. Oxidative stress responses were evaluated using hydrogen peroxide. EC-CTEPH showed impaired adaptation to hypoxia, with reduced induction of glycolytic and angiogenic genes, altered morphology, delayed wound closure, and persistent oxidative stress after reoxygenation, consistent with defective hypoxia sensing. DMOG partially restored metabolic gene expression, indicating improved adaptation through HIF stabilization. Despite elevated basal ROS levels, oxidative challenge did not trigger adaptive glycolytic or angiogenic responses and induced distinct transcriptional profiles compared with controls. CTEPH endothelial cells display an altered response to hypoxia and oxidative stress, consistent with impaired hypoxia sensing and stress adaptation. This model highlights maladaptive endothelial features and provides a framework for future studies exploring HIF-targeted approaches in CTEPH. Full article

Pulmonary embolism (PE) is biologically heterogeneous. Despite guideline-directed anticoagulation, a subset of patients develops recurrent venous thromboembolism, persistent exertional limitation, residual perfusion defects, and progression to chronic thromboembolic pulmonary disease (CTEPD) or chronic thromboembolic pulmonary hypertension (CTEPH). Conventional risk factors explain much of the index event but incompletely account for thrombus non-resolution and chronic sequelae. Clonal hematopoiesis of indeterminate potential (CHIP)—the age-associated expansion of hematopoietic clones carrying somatic mutations—defines a measurable thrombo-inflammatory endophenotype that is strongly genotype- and clone-size (variant allele frequency; VAF)-dependent. Across human studies, JAK2-CHIP and TET2-CHIP show the most consistent associations with VTE/PE, whereas isolated DNMT3A-CHIP is frequently neutral, and larger clones tend to confer stronger effects. Mechanistically, CHIP can bias myeloid cells toward inflammasome/IL-1β signaling and endothelial activation, increase monocyte tissue factor activity, and promote immunothrombosis with neutrophil extracellular trap (NET) formation. NET-rich thrombi may adopt a dense fibrin–DNA–histone architecture that resists endogenous fibrinolysis, favoring organization and persistence. CTEPH offers a translational window to interrogate this model because thrombotic material and deep phenotyping are accessible. We synthesize genotype- and VAF-resolved clinical and mechanistic evidence using a structured strength-of-evidence framework and propose a pragmatic phenotyping roadmap with testable predictions for prospective post-PE validation. CHIP testing in PE/CTEPH remains investigational and should not currently change standard care. Full article

Background: Lung perfusion SPECT/CT is central to the diagnostic evaluation of chronic thromboembolic pulmonary hypertension (CTEPH), yet current assessments remain qualitative. This pilot study aimed to explore a standardized quantitative method for lung perfusion SPECT/CT to differentiate CTEPH from non-CTEPH patients. Methods: We retrospectively analyzed lung perfusion SPECT/CT studies obtained over a three-year period in patients assessed for suspected CTEPH. Perfusion counts were divided into ten equal intervals from zero to the maximum perfusion counts, and each decile was used as a threshold to define perfusion defects. Perfusion defect fraction was quantified, and group differences, diagnostic performance, and correlations with mean pulmonary arterial pressure (mPAP) were evaluated. Results: CTEPH patients showed significantly higher perfusion defect fraction than non-CTEPH controls. The 10% threshold demonstrated the best diagnostic performance, with an optimal cutoff of 20.6%, yielding a sensitivity of 75% and specificity of 100% for identifying CTEPH. Patients with distal-type disease or small, localized perfusion defects exhibited perfusion defect fraction overlapping with controls. Perfusion defect fraction correlated significantly and positively with mPAP. Conclusions: In this pilot study, quantitative analysis of lung perfusion SPECT/CT demonstrated feasibility as a complementary method to visual interpretation. While promising, these findings are preliminary and require validation in larger populations to establish their clinical utility for CTEPH diagnosis. Full article

Pulmonary embolism (PE) is one of the most serious complications of antiphospholipid syndrome (APS), a systemic autoimmune disorder defined by thrombotic events and persistent antiphospholipid antibodies (aPLA). PE occurs in 11–20% of patients and may constitute the initial clinical manifestation. Young and middle-aged women are most frequently affected, and triple-positive aPLA profiles markedly increase the risk of recurrence and long-term morbidity, including chronic thromboembolic pulmonary hypertension (CTEPH). This review article summarizes current evidence on the epidemiology, pathophysiology, diagnostic approach, and management of PE in APS. Key mechanisms include anti-β2-glycoprotein I-mediated endothelial and platelet activation, complement engagement, and neutrophil extracellular trap formation, resulting in immunothrombosis. Diagnostic pathways follow standard PE algorithms; however, chronically elevated D-dimer levels and lupus anticoagulant-related aPTT prolongation require careful interpretation and consideration. Long-term vitamin K antagonist therapy remains the standard of care, whereas direct oral anticoagulants are not recommended in high-risk APS. Future directions include improved risk stratification through detailed aPLA profiling and the use of emerging biomarkers, early screening for CTEPH, and the development of targeted therapies such as complement inhibition and anti-NETosis strategies. Full article

Balloon pulmonary angioplasty (BPA) has become an established treatment modality for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), particularly in those with distal pulmonary artery lesions or significant comorbidities precluding pulmonary endarterectomy. BPA provides significant improvement in pulmonary hemodynamics, right ventricular function, exercise tolerance, and quality of life. Recent randomized controlled trials, including the RACE and MR-BPA trials, have demonstrated that BPA results in greater reduction in pulmonary vascular resistance and mean pulmonary arterial pressure compared to riociguat, although with a higher incidence of procedure-related complications. Ancillary follow-up data further suggest that a sequential strategy combining medical therapy and BPA may optimize outcomes and reduce adverse events. Advances in procedural techniques, imaging guidance, and patient selection have substantially improved the safety profile of BPA. International registries and expert consensus guidelines now support its incorporation into the multimodal management of CTEPH. This review synthesizes current evidence on the efficacy, safety, and practical aspects of BPA, while highlighting ongoing challenges, including long-term outcome data, standardization of treatment endpoints, and the role of combination therapy. BPA is poised to play an increasingly central role in personalized care strategies for CTEPH. Full article

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are characterized by high morbidity and mortality. We retrospectively analyzed 468 hospital admissions from 80 patients to evaluate the prognostic value of inflammation-based hematologic indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil-percentage-to-albumin ratio (NPAR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII). All biomarker–outcome associations were specified a priori as exploratory in this hypothesis-generating design. In PAH, both NPAR and SII were associated with in-hospital mortality (odds ratio [OR] 1.129, 95% confidence interval [CI] 1.011–1.261, p = 0.031; OR 1.001, 95% CI 1.000–1.002, p = 0.002), post-discharge mortality (NPAR OR 1.181, 95% CI 1.062–1.313, p = 0.002), and poorer overall survival (log-rank p = 0.002 and p = 0.012, respectively). Higher LMR was associated with reduced in-hospital mortality (OR 0.291, 95% CI 0.108–0.790, p = 0.015), while NLR predicted increased in-hospital mortality. In CTEPH, NLR and LMR were the strongest predictors, correlating with worse survival (log-rank p = 0.007 and p = 0.044) and higher post-discharge mortality (NLR OR 1.289, 95% CI 1.029–1.615, p = 0.027). Receiver operating characteristic (ROC) analysis suggests the potential value of SII in PAH and the promising performance of NPAR in CTEPH. Inflammation-based hematologic indices, particularly NPAR, SII, and NLR, may provide valuable prognostic information and may serve as practical, non-invasive tools for predicting hospitalization duration and mortality in PAH and CTEPH. Full article

Background/Objectives: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease, in which multiple genetic and environmental factors may contribute. This study aimed to identify potential genetic determinants in patients with CTEPH and to compare their occurrence to a control group, which included patients with pulmonary embolism who had not developed CTEPH. Methods: Tier 1 and 2 genes related to coagulation, fibrinolysis and platelet disorders—as recommended by the International Society on Thrombosis and Haemostasis—and genes associated with vascular conditions were analyzed in n = 15 patients with CTEPH and n = 17 controls using next-generation sequencing. Non-synonymous, rare variants were collected and interpreted. Results: As expected, no single gene or variant was consistently present among CTEPH patients. Instead, individuals carried different mutations and combinations of variants. We identified several variants that were not found in the control group. Candidate variants were detected in F12, F13A1, F13B, F5, KNG1, SERPIND1, THBD, ADAMTS13, VWF, STIM1, ETV6, THPO, MPL, SERPINA1, ENG, RASA1, ACVRL1, GDF2, NFE2, SOX17 and RNF213. We did not detect exclusive variants in FGA, CPB2, and BMPR2 although they were suggested as candidates in previous studies. Elevated factor VIII and von Willebrand factor in CTEPH could not be explained by mutations in VWF and F8. Conclusions: Our study supports the hypothesis of heterogeneous genetic background in CTEPH, involving multiple pathways such as coagulation, altered fibrinolysis and impaired angiogenesis. These results provide a basis for more detailed investigations into specific genes and variants potentially associated with CTEPH in larger cohorts. Full article

Chronic thromboembolic pulmonary hypertension (CTEPH) is a type of pulmonary hypertension due to unresolved thromboembolic disease that presents with signs of pulmonary artery obstruction and right heart dysfunction. Pulmonary thromboendoarterectomy (PTE) with deep hypothermic circulatory arrest remains the standard of care for the treatment of CTEPH, with significant improvements in symptoms and functional status after surgery. This review outlines the diagnostic workup, considerations during operative planning, surgical technique, and postoperative management of CTEPH patients. Full article