Search Results (184)

Emerging evidence suggests that deoxyribonucleic acid (DNA) methylation may be linked to progression from acute pulmonary embolism (APE) to chronic thromboembolic pulmonary hypertension (CTEPH), especially in genes regulating vascular tone. We investigated the association between tachykinin precursor 1 (TAC1) promoter methylation and the APE-to-CTEPH transition in a 6-month ambispective cohort study of 110 patients with confirmed APE. We recorded clinical, laboratory, and hemodynamic parameters at hospital admission and collected 4 mL of peripheral blood for DNA extraction. We quantified the percentage of TAC1 promoter methylation using bisulfite conversion and methylation-specific polymerase chain reaction (PCR), also assessing TAC1 gene expression by quantitative PCR. During the 6-month follow-up, 7.2% of patients developed CTEPH. Patients who later progressed to CTEPH had a significant 0.4-fold increase in TAC1 promoter methylation compared to those who did not. Increased methylation was associated with a 1.5-fold decrease in TAC1 gene expression in whole-blood leukocytes from CTEPH patients. TAC1 methylation significantly correlated with mixed venous oxygen saturation (SvO2), D-dimer, and B-type natriuretic peptide concentrations. TAC1 promoter hypermethylation is associated with progression from APE to CTEPH and concurs with TAC1 gene repression, probably compromising systemic oxygenation, thrombus resolution, and cardiac strain. Full article

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

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder that confers an increased risk of venous thromboembolism (VTE) and subsequent pulmonary embolism (PE). The risk stems from chronic systemic inflammation promoting endothelial dysfunction and hypercoagulability. Data on specific inpatient outcomes and procedural needs in patients with IBD with acute PE remains limited. This study explores these outcomes at a national level. Methods: We conducted a Nationwide Inpatient Sample (NIS) database analysis (2016–2020). Adult hospitalizations for acute PE were identified using ICD-10-CM codes and stratified based on IBD status. Multivariable regression analysis was performed to determine independent associations between IBD status and in-hospital mortality, length of stay (LOS), cardiac complications, and ICU-level interventions (intubation, central venous catheterization (CVC), arterial line placement, requirement of vasopressors), and blood transfusion. Results: Among 377,143 acute PE hospitalizations, 4123 (1.1%) had IBD. Patients with IBD were younger (58.72 vs. 62.78 years, p < 0.001) and had lower prevalence of diabetes mellitus, hypertension, end-stage renal disease (ESRD), dyslipidemia, overweight/obesity, coronary artery disease and smoking status (p < 0.05). Despite a favorable baseline profile, patients with IBD had a longer length of stay (LOS) (8.82 vs. 7.30 days, p < 0.001) but no significant association with in-hospital mortality (aOR = 0.93, p = 0.281). Multivariable analysis showed patients with IBD had higher odds of requiring CVC placement (OR = 1.42, p < 0.001), vasopressors (OR = 1.22, p = 0.05), and blood transfusions (OR = 1.78, p < 0.001). Conversely, they had lower odds of cardiac arrest (OR = 0.64, p < 0.001) and cor pulmonale (OR = 0.32, p = 0.012). Conclusions: patients with IBD with acute PE represent a complex population with high resource utilization. Future research is needed the development of IBD-specific PE risk stratification, targeted management, prophylactic and therapeutic anticoagulation guidelines. 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

Pulmonary hypertension (PH) can be defined as a mean pulmonary artery pressure (mPAP) greater than 20 mm Hg at rest during right heart catheterization (RHC). The reported prevalence of PH throughout the globe has been estimated to impact approximately 1% of the total population, with a majority of those afflicted being women more than men. Numerous etiologies give rise to the pathophysiology of PH, including heart disease (i.e., left-sided heart failure), lung diseases, and other unclear causes related to chronic stages and complications surrounding long-standing pulmonary thromboembolisms, side effects of certain medications, and genetic and environmental factors. Untreated PH can lead to severe morbidities such as cardio-renal syndrome and congestive hepatopathy (cardiac cirrhosis). Management of PH focuses on decreasing pulmonary pressures by using vasodilators such as prostanoids, and phosphodiesterase type 5 (PDE-5) inhibitors, as well as newer treatments such as sotatercept, which inhibits activin signaling, thereby inhibiting excessive cell growth in the pulmonary artery vasculature and down-regulating the pro-proliferative pathways. 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

Background: Massive pulmonary hemorrhage is a life-threatening complication of pulmonary endarterectomy (PEA) with limited evidence to guide standardized management. Methods: We retrospectively evaluated consecutive PEA procedures performed at a high-volume center and analyzed the incidence, perioperative characteristics, management strategies, and early outcomes of patients who developed massive pulmonary hemorrhage. Results: Among 1123 patients who underwent PEA, massive pulmonary hemorrhage occurred in 51 (4.54%) and developed intraoperatively after completion of PEA and separation from total circulatory arrest. Primary suturing achieved hemostasis in 12 patients (23.5%), and bronchial isolation was applied in 18 (35.3%). Local adjuncts included intraoperative bronchial clamping in 1 patient (2.0%) and biological glue occlusion in 2 (3.9%). Extracorporeal membrane oxygenation (ECMO) was required in 25 patients (49.0%), initiated intraoperatively in 22 and postoperatively in 3. Overall in-hospital mortality was 41.2%, while 30 patients (58.8%) survived to hospital discharge; among survivors, mean hospital length of stay was 16.1 ± 6.8 days. Conclusions: Massive pulmonary hemorrhage after PEA remains associated with substantial early mortality and resource utilization; a stepwise institutional algorithm combining bronchoscopy-guided localization, targeted airway/surgical control, and timely ECMO support may help standardize management in this critical setting. 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/Objectives: Atrial fibrillation (AF) is the most common sustained arrhythmia in adults, with a prevalence that increases with age. In older patients, its clinical impact is particularly relevant due to higher mortality and greater comorbidity burden. This study aimed to compare patients aged ≥80 years with younger patients in a large AF cohort. Methods: The REGUEIFA registry is an observational, prospective, multicentre study including consecutive patients with AF managed by cardiologists. Baseline clinical characteristics, comorbidities, complementary test findings, AF type, therapeutic strategies, anticoagulation patterns, and patient-reported outcomes were compared. Results: A total of 1007 patients were included, of whom 18.2% were aged ≥80 years. Older patients showed a higher prevalence of hypertension, renal dysfunction, conduction disorders, chronic obstructive pulmonary disease, and neoplastic disease, along with higher thromboembolic (CHA₂DS₂-VASc 3.7 ± 1.04 vs. 2.1 ± 1.49; p < 0.001) and haemorrhagic risk (HAS-BLED 1.3 ± 0.8 vs. 0.6 ± 0.7; p < 0.001). Permanent AF was more frequent, whereas rhythm control strategies and antiarrhythmic drug use were less common, and quality of life was poorer. Anticoagulation rates were high in both groups (≈90%), with greater use of vitamin K antagonists (VKAs) in older patients, although anticoagulation control was similar. Patients treated with direct-acting oral anticoagulants reported a lower treatment burden and greater perceived benefit than those receiving VKAs. Conclusions: Patients aged ≥80 years with AF exhibit greater comorbidity, poorer perceived health status, and higher thromboembolic and haemorrhagic risk. Their management is more often oriented towards rate control strategies and VKA use, while rhythm control approaches are more common in younger patients. 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

Chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) increasingly co-occur in low- and middle-income countries and aging populations. Prior pulmonary TB is a robust, smoking-independent determinant of COPD and is linked to persistent systemic inflammation, endothelial dysfunction, dyslipidemia, and hypercoagulability axes that also amplify cardiovascular disease (CVD) risk. We conducted a targeted narrative non-systematic review (2005–2025) of PubMed/MEDLINE, Embase, Scopus, and Web of Science, selecting studies for clinical relevance across epidemiology, clinical phenotypes, pathobiology, biomarkers, risk scores, sleep-disordered breathing, and management. No quantitative synthesis or formal risk-of-bias assessment was performed. Accordingly, findings should be interpreted as a qualitative synthesis rather than pooled estimates. Prior TB is associated with a distinctive COPD phenotype characterized by mixed obstructive–restrictive defects, reduced diffusing capacity (DLCO), radiographic sequelae, and higher exacerbation/hospitalization burden. Mechanistic insights: Convergent mechanisms chronic immune activation, endothelial injury, prothrombotic remodeling, molecular mimicry, and epigenetic reprogramming provide biologic plausibility for excess CVD, venous thromboembolism, and pulmonary hypertension. Multimarker panels spanning inflammation, endothelial injury, myocardial strain/fibrosis, and coagulation offer incremental prognostic value beyond clinical variables. While QRISK4 now includes COPD, it does not explicitly model prior TB or COPD-TB outcomes, but data specific to post-TB cohorts remain limited. Clinical implications: In resource-constrained settings, pragmatic screening, prioritized PAP access, guideline-concordant pharmacotherapy, and task-shifting are feasible adaptations. A history of TB is a clinically meaningful modifier of cardiopulmonary risk in COPD. An integrated, multimodal assessment history, targeted biomarkers, spirometry/lung volumes, DLCO, 6 min walk test, and focused imaging should guide individualized care while TB-aware prediction models and implementation studies are developed and validated in high-burden settings. Full article

The acute phase of pulmonary embolism (PE) may be a severe and potentially life-threatening condition. Moreover, long-term consequences following the acute phase can significantly impact a patient’s daily life. A systematic approach to PE follow-up can identify potential complications following acute PE. Post-PE syndrome (PPES) is a common occurrence among survivors experiencing persistent dyspnea and impaired functional status. While the exact definition is evolving, it encompasses a spectrum of disease phenotypes that may occur following an acute PE, which ranges from dyspnea, functional limitation, or cardiac impairment to chronic thromboembolic disease and chronic thromboembolic pulmonary hypertension. This review will describe the different PPES phenotypes, including their physiological basis, diagnosis and workup, and management following acute PE. Full article