Search Results (969)

Background: Cardiac surgery patients with pre- or post-operative atrial fibrillation are at an increased risk for thromboembolic stroke, often due left atrial appendage (LAA) thrombus. Surgical LAA exclusion (LAAE) can be performed and must be complete to avoid increased thrombus formation. Methods: This prospective, multi-center, post-market study (NCT05101993) evaluated the long-term safety and performance of the epicardial V-shape AtriClip device. Patients ≥18 years who had received V-shape AtriClip devices during non-emergent cardiac surgery consented to a prospective 12-month follow-up visit and LAA imaging. The primary performance was LAAE without residual left atrium-LAA communication, assessed by imaging at the last follow-up visit. The primary safety was device- or implant procedure-related serious adverse events (SAEs) (death, major bleeding, surgical site infection, pericardial effusion requiring intervention, myocardial infarction) within 30 days. Results: Of 155 patients from 11 U.S. centers, 151 patients had evaluable imaging. Complete LAAE was obtained in all patients. Primary performance in the intent-to-treat population was met, with 97% (95% CI 93.52%, 99.29%; p = 0.0001) complete LAAE. Primary safety was met, with 100% (95% CI 97.75%, 100%; p < 0.0001) of patients free from pre-defined SAEs within 30 days. One device-related SAE was reported, which resolved intraprocedurally. Conclusions: AtriClip V-Clip showed safe and successful LAAE through 12 months of follow-up. Full article

Heart failure (HF) poses a substantial global burden due to its high morbidity, mortality, and healthcare costs. Accurate prognostication is crucial for optimizing treatment, resource allocation, and patient counseling. Prognostic tools range from simple clinical scores such as ADHERE and MAGGIC to more complex models incorporating biomarkers (e.g., NT-proBNP, sST2), imaging, and artificial intelligence techniques. In acute HF, models like EHMRG and STRATIFY aid early triage, while in chronic HF, tools like SHFM and BCN Bio-HF support long-term management decisions. Despite their utility, most models are limited by poor generalizability, reliance on static inputs, lack of integration into electronic health records, and underuse in clinical practice. Novel approaches involving machine learning, multi-omics profiling, and remote monitoring hold promise for dynamic and individualized risk assessment. However, these innovations face challenges regarding interpretability, validation, and ethical implementation. For prognostic models to transition from theoretical promise to practical impact, they must be continuously updated, externally validated, and seamlessly embedded into clinical workflows. This review emphasizes the potential of prognostic models to transform HF care but cautions against uncritical adoption without robust evidence and practical integration. In the evolving landscape of HF management, prognostic models represent a hopeful avenue, provided their limitations are acknowledged and addressed through interdisciplinary collaboration and patient-centered innovation. Full article

Aortic valve diseases affect a significant percentage of the population, and with the extension of survival expectancy, they are expected to increase furthermore. Surgical treatment of aortic valve diseases mainly includes valve replacement and, rarely, its repair. The technology of both surgical and transcatheter valves is evolving, and new prosthetic valves with improved characteristics are available, e.g., longer lifespan, faster implantation, better hemodynamic performance with better effective orifice area, suitable for small aortic annuli, etc. Minimally invasive surgical techniques are constantly evolving and spreading. New access sites are used for transcatheter valve implantation. The Heart Team determines the most appropriate intervention for each patient based on their anatomical and clinical profiles, aiming to optimize long-term outcomes. Full article

Objectives: Circulating tumor DNA (ctDNA) has emerged as a reliable prognostic biomarker in both early- and late-stage non-small cell lung cancer (NSCLC) patients. However, its role in NSCLC with pleural dissemination (M1a), a subset of disease with indolent biology, remains to be elucidated. Methods: We collected 41 M1a patients with serial ctDNA and CEA monitoring. Progression-free survival (PFS) was assessed between patients with different levels of ctDNA and CEA. An independent cohort of 61 M1a patients was included for validation. Results: At the diagnostic landmark, the detection rates for ctDNA and CEA were 22% and 55%, respectively. Among patients who experienced disease progression with pleural metastases, only ten had detectable ctDNA in longitudinal timepoints, resulting in a sensitivity of 50%. Moreover, there was no significant difference in PFS between patients with longitudinally detectable and undetectable ctDNA (HR: 0.86, 95% CI 0.33–2.23, p = 0.76). In contrast, patients with a decreasing CEA trend within 3 months after diagnosis were associated with an improved PFS (HR: 0.22; 95% CI, 0.03–1.48, p = 0.004). This finding is confirmed in an independent M1a patient cohort. Conclusions: Together, our findings suggest that M1a NSCLC with isolated pleural dissemination may represent a “non-shedding” tumor type, where ctDNA shows limited diagnostic and prognostic value. Monitoring early changes in CEA could be a more cost-effective predictor of disease progression. Full article

Background/Objectives: Currently, the transfemoral approach is recognized as the primary method for accessing transcatheter aortic valve implantation (TAVI). However, alternative techniques are needed when the transfemoral access is not suitable. We proposed that a modified transaxillary approach through the distal left axillary artery is both viable and safe for conducting TAVI, potentially offering benefits for patients. Methods: From December 2018 to February 2024, a total of 24 patients (7 women, average age 77.9 ± 8 years) received TAVI using transaxillary access via the left axillary artery. The participants suffered from symptomatic severe aortic stenosis and were deemed TAVI candidates with iliofemoral anatomy unsuitable for a transfemoral route. The patient group displayed a high perioperative risk profile, with significant peripheral artery disease or severe obstructive infrarenal aortic conditions. The implantation of the aortic prosthesis was carried out through the left distal axillary artery. A balloon-expandable valve was used in every instance. Results: In the examined cohort, the 30-day mortality rate was 4.2%. A new pacemaker was necessary for four patients (16.7%). One case exhibited a new moderate neurological dysfunction. Additionally, one patient required surgical revision of the access point due to ischemia. Conclusions: Our findings indicate that transaxillary TAVI via the distal left axillary artery has yielded encouraging outcomes. This approach is practicable and safe, does not prolong the procedure, minimizes surgical trauma, ensures excellent access regardless of chest anatomy, and is sparing for the brachial plexus. As a single-center pilot study, our findings require confirmation in larger, prospective cohorts with extended follow-up to fully validate the safety and long-term efficacy of this technique. Full article

Background: The Da Silva Cone procedure for Ebstein anomaly has dramatically improved tricuspid valve competence and clinical outcomes. However, preoperative left ventricular (LV) dysfunction and immediate postoperative right ventricular (RV) systolic dysfunction are frequently observed. While excellent valve outcomes are well established, recovery of biventricular function following the Cone remains less defined. This study aimed to evaluate longitudinal changes in RV and LV function postoperatively and over a minimum of six months post-Cone operation. Methods: A single center retrospective review of 134 patients who underwent Cone repair for Ebstein’s anomaly from 2016 to 2024 was performed. Echocardiograms were analyzed at three time points: preoperative (Time 1), hospital discharge (Time 2), and ≥6 months postoperative (Time 3). RV parameters included fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), and tricuspid S′. LV parameters included left ventricular ejection fraction (LVEF), end-diastolic volume indexed to body surface area (LVEDVi), left ventricular stroke volume (LVSVi), and mitral E/E′. Subgroup analyses examined outcomes by prior Glenn, Starnes procedure, and degree of RV dilation. Paired two sample t-tests were used to compare serial measures. Results: Median age at surgery was 7.8 years (IQR: 2.3–17.7). All patients had discharge echocardiograms; 70 had follow-up studies at ≥6 months. RV function declined postoperatively with reductions in FAC (35% to 21%), TAPSE (2.0 to 0.8 cm), and S′ (13 to 5 cm/s), all p < 0.001. By Time 3, these measures improved (FAC to 29%, TAPSE to 1.3 cm, S′ to 7 cm/s) but did not fully return to baseline. LVEDVi and LVSVi increased significantly by Time 3 (LVEDVi: 47 to 54 mL/m²; LVSVi: 30 to 34 mL/m²; p < 0.001), while LVEF remained unchanged. Patients with prior Glenn or Starnes had greater Time 1 LV volumes and lower RV function, but by Time 3, most differences resolved. Moderate–severe preoperative RV dilation was associated with worse RV function at Time 2 and normalized by Time 3. Conclusions: The Da Silva Cone procedure leads to early postoperative RV dysfunction with partial recovery over the mid-term follow-up. Concurrently, LV filling and stroke volume improve, reflecting favorable interventricular interaction. These findings support echocardiographic surveillance to guide functional recovery post-Cone and inform patient counseling. Full article

Background: The transapical off-pump NeoChord procedure is a recognized minimally invasive surgical approach for the treatment of severe degenerative mitral regurgitation. This study aims to report the initial Greek experience with the NeoChord procedure, presenting mid-term clinical and echocardiographic outcomes from a single cardiothoracic surgical center, with a median follow-up duration of 20 months. Methods: In this study, 42 symptomatic patients with moderate to severe and severe primary mitral regurgitation underwent mitral valve repair with the Neochord procedure between March 2018 and December 2024. All patients were evaluated clinically and echocardiographically by the Heart team preoperatively, after 1 month, and at the last follow-up (end of 2024). The primary endpoint was established as the presence of a major clinical event (all-cause mortality, reintervention due to deterioration of MR, and cardiac-related rehospitalization). Results: The median age of patients was 69 [61.75–79.25] years, and 69% of patients were men. The median EuroScore II was 1.79 [1.32–2.48], and the STS-PROM MV repair score was 3.18 [2.28–4.66]. Regarding the preprocedural mitral valve anatomical evaluation, 35 patients had type A (83.3%),4 had type B(9.5%), whereas only two patients had type C and 1 with type D anatomy. The median of LAI was 1.2 [1.15–1.25], whereas the CI was 4 [2.15–5]. More than two neochordae were implanted in 34 patients (81%). MR severity improved at 1-month (<moderate:92.85%) and at the last follow-up (<moderate:92.1%). NYHA class decreased within 1 month (I + II: 95.23%) after the procedure and was maintained at the last follow-up (I + II: 94.73%). The median left ventricular ejection fraction (LVEF) before the procedure was 63 [58–67]%, which significantly decreased to 57 [53–61]% at the 1-month follow-up (2-sided p < 0.001). At the final follow-up, LVEF increased to 65 [60–68]%, however, this change was not statistically significant compared to the preprocedural value. During the follow-up period, four deaths were documented—three due to non-cardiac and one attributable to a cardiac cause. Two cases proceeded to reoperation for surgical valve implantation due to recurrent mitral valve regurgitation 6 months and 8 months after the NeoChord procedure. Conclusions: Transapical off-pump NeoChord implantation offers a minimally invasive alternative to conventional surgery for symptomatic patients with moderate-to-severe or severe primary mitral regurgitation. Among patients with suitable mitral valve anatomy, the procedure has demonstrated a favorable safety profile and promising mid-term outcomes, in terms of cardiac mortality, as well as freedom from reoperation and rehospitalization. Full article

Acute myocardial hypoxia/ischemia is associated with abnormal accumulation of myocardial lipids, including dihydroceramides. Here, we characterized how dihydroceramides are remodeled in response to hypoxia and assessed how dihydroceramide remodeling correlates to human cardiac pathophysiology. Hypoxia resulted in a marked accumulation of very-long-chain (VLC)-dihydroceramides in cultured HL-1 cardiomyocytes. In humans, we identified a correlation between the abundance of VLC-dihydroceramides in myocardial biopsies and arrhythmias and heart failure and showed that cardiac expression of CERS2, coding for an enzyme that promotes synthesis of VLC-dihydroceramides, was associated with signaling pathways linked to cardiac arrhythmia and cardiomyopathy. In cultured HL-1 cardiomyocytes, we showed that CerS2 knockdown reduced accumulation of VLC dihydroceramides and altered the expression of mediators regulating Ca²⁺ cycling and electrical conduction. In conclusion, our findings indicate that increased abundance of VLC-dihydroceramides, promoted by increased activity of CerS2 in response to hypoxia, could play a role in cardiac arrhythmias and heart failure. Full article

Background/Objectives: Epicardial adipose tissue (EAT) is metabolically active and is in dynamic crosstalk with the surrounding cardiomyocytes, modulating their function and metabolism. Oxidative stress is a key contributor to cell death and cardiac remodeling, is a hallmark of diabetes (DM) and cardiovascular disease, such as coronary artery disease (CAD). However, little is known about these processes in EAT from patients undergoing cardiac surgery. This study investigates changes in mitochondrial dynamics, reactive oxygen species (ROS) production, and antioxidant defense levels in EAT compared to subcutaneous adipose tissue (SAT) in patients undergoing cardiac surgery, with a focus on the impact of DM and CAD. Methods: Adipose tissue biopsies were collected from 128 patients undergoing surgical cardiac intervention. Mitochondrial dynamics and oxidative stress markers were analyzed. Results: EAT exhibited increased expression of mitochondrial fusion markers [mitofusin 1 (p ≤ 0.001), mitofusin 2 (p = 0.038), and optic atrophy 1 (p ≤ 0.001)], as well as fission markers [fission 1 (p ≤ 0.001) and dynamin-related protein 1 (p ≤ 0.001)] relative to SAT. Additionally, ROS levels (dihydroethidium, p = 0.004) were elevated, while lipid peroxidation (malondialdehyde, p ≤ 0.001) was reduced in EAT compared to SAT. Reduced glutathione (GSH) levels (p ≤ 0.001) and the redox buffer ratio between reduced and oxidized glutathione (GSH/GSSG, p ≤ 0.001) were significantly increased in EAT. Interestingly, glutathione peroxidase activity (p ≤ 0.001) and the antioxidant defense markers catalase (p ≤ 0.001) and superoxide dismutase 2 (p = 0.001) were significantly reduced in EAT compared to SAT. Conclusions: The findings provide a unique molecular insight into the mitochondrial dynamics and oxidative stress profiles of EAT, highlighting potential avenues for a novel diagnostic method and therapeutic strategies for cardiac disease. Full article

Primary graft dysfunction (PGD) remains a major complication after lung transplantation. Donor lung ischemia followed by reperfusion drives oxidative stress and inflammatory responses. The pathophysiology is influenced by various donor-, procedure-, and recipient-related factors, which complicates the identification of biomarkers for evaluation of donor lung injury or therapeutic interventions to minimize PGD. This review provides an overview of the molecular pathways that contribute to PGD pathophysiology, including those involved in loss of endothelial–epithelial membrane integrity, neutrophil infiltration, and the development of pulmonary edema. Full article

Living myocardial slices (LMSs) have shown great promise in cardiac research, allowing multicellular and complex interplay analyses with disease and patient specificity, yet their wider clinical use is limited by the large tissue sizes usually required. We therefore produced mini-LMSs (<10 mm²) from routine human cardiac surgery specimens and compared them with medium (10–30 mm²) and large (>30 mm²) slices. Size effects on biomechanical properties were examined with mathematical modeling, and viability, contraction profiles, and histological integrity were followed for 14 days. In total, 34 mini-, 25 medium, and 30 large LMS were maintained viable, the smallest measuring only 2 mm². Peak twitch force proved to be size-independent, whereas time-to-peak shortened as slice area decreased. Downsized LMSs displayed excellent contractile behavior for five to six days, after which a gradual functional decline and micro-architectural changes emerged. These findings confirm, for the first time, that mini-LMSs are feasible and viable, enabling short-term, patient-specific functional studies and pharmacological testing when tissue is scarce. Full article

Mechanotransduction plays an essential role in the fate determination of alveolar cells within the pulmonary system by translating mechanical forces into intricate biochemical signals. This process exclusively governs differentiation, phenotypic stability, and maintenance of alveolar epithelial cell subtypes, primarily the alveolar AT1/AT2 cells. Perturbed mechanical tension proportionally impacts alveolar cell phenotypic identity and their functional characteristics. The fundamental influence of respiratory mechanics on alveolar cell lineage commitment and sustenance is undeniable. AT1 cells are recognized as principal mechanosensors within the alveolus, directly perceiving and responding to mechanical forces imposed by respiration through cell–matrix interactions. These mechanical forces instigate a profound reorganization of the actin cytoskeleton within cells, indispensable for signal transduction and perpetuation of their differentiated phenotype, orchestrated by integrins and cell adhesion molecule-mediated signaling. The dysregulated mechanotransduction in the pulmonary system intrinsically contributes to the etiology and progression of various diseases, exemplified by pulmonary fibrosis. This review systematically elucidates the profound impact of mechanotransduction on alveolar cell differentiation and fate sustenance and underscores how its dysregulation contributes to the initiation and perpetuation of lung diseases. Full article

Inhibitors of the ubiquitin–proteasome system increase proteotoxic stress and have achieved clinical success for multiple myeloma but not for solid cancers such as hepatocellular carcinoma. Our objective is to identify a combination with proteasome inhibitors that enhances proteotoxic stress and apoptotic cell death in hepatocellular carcinoma but with less toxicity to non-cancer cells. We found that rencofilstat, a pan-cyclophilin inhibitor, combined with ixazomib, a proteasome inhibitor, increased apoptotic cell death in hepatocellular carcinoma but not in umbilical vein or dermal fibroblast non-cancer cells. We then analyzed the effects of rencofilstat + ixazomib on XBP1s and PERK, critical factors in the unfolded protein response used by cells to survive proteotoxic stress. Rencofilstat + ixazomib maintained higher expression of XBP1s and genetic models suggested that XBP1s was a pro-survival protein early and pro-death protein at later times. Simultaneously, decreased PERK expression prevented the block in protein synthesis via phospho-eIF2α and likely further amplified proteotoxic stress. Rencofilstat + ixazomib did not have effects on XBP1s or PERK in non-cancer cells. Further genetic experiments revealed the pro-survival roles for cyclophilin A and B in mediating rencofilstat + ixazomib-induced cell death. In the Hep3B xenograft model, rencofilstat + ixazomib significantly inhibited tumor volumes/weights without general toxicity. We conclude that rencofilstat + ixazomib amplified proteotoxic stress in hepatocellular carcinoma past a threshold pro-survival pathways could not tolerate, whereas non-cancer cells were less affected. Full article

Emerging evidence highlights the role of the tumor microbiome, including Fusobacterium nucleatum (Fn), in a wide range of gastrointestinal cancers. Fn purportedly contributes to tumorigenesis by activating oncogenic pathways and modulating immune responses. Although the prevalence and impact of Fn has been extensively studied in colorectal cancer, no previous systematic or in situ studies have been performed in appendiceal cancer (AC). The aim of this study was to evaluate the prevalence and association of Fn density in AC with clinical factors and oncologic outcomes. Archival tissue from 54 patients with AC was assessed for Fn density using RNA in situ hybridization. Clinicopathological variables were obtained for each case through electronic medical record review, and the immune microenvironment was characterized in each case using immunohistochemistry to quantify CD3+ and CD8+ T lymphocytes and M1-/M2-like tumor-associated macrophages. In AC, Fn density was associated with patient age, tumor grade, and histologic subtype. Fn was negatively associated with CD3+ and CD8+ T lymphocytes and positively associated with M2-like TAMs in low-grade AC. Interestingly, tumor Fn content was associated with better overall and progression-free survival, even when controlling for tumor grade. In this exploratory study, we found that Fn is prevalent in AC. Fn is associated with a number of clinical, pathologic, immunologic, and prognostic variables in AC that are distinct from the corresponding observed associations in colorectal cancer. Further research is warranted to validate these findings and explore the mechanistic contributions of Fn to AC pathogenesis or immune response. Full article

Unplanned postoperative coronary angiography (uCAG) following isolated coronary artery bypass grafting (CABG) represents a significant clinical challenge, reflecting postoperative myocardial ischemia (PMI) with substantial impact on outcomes. The incidence of uCAG varies from 0.39 to 5.3%, depending on institutional protocols and diagnostic thresholds. Elevated cardiac biomarkers (high-sensitivity troponin and CK-MB), ECG changes, and hemodynamic instability are key indicators guiding uCAG. While associated with increased short-term mortality and morbidity, timely identification and treatment of graft-related complications via uCAG can improve midterm survival. Percutaneous coronary intervention (PCI) often emerges as the preferred therapeutic strategy over redo CABG. Future efforts should focus on refining risk stratification models, expanding the role of non-invasive imaging modalities, and validating early intervention strategies through prospective studies. Establishing standardized criteria for diagnosing and managing PMI remains critical to enhance outcomes and healthcare efficiency. Full article