Medicine and Pharmacology

Abstract: Cardiac rhythm and conduction disturbances may pose a potential safety hazard in occupations requiring sustained attention and rapid decision-making [1, 2]. The aim of our study was to estimate the prevalence of cardiac rhythm and conduction disturbances and examine their association with non-invasive stress markers in a sample of railway workers. Methods: A total of 3,700 male locomotive engineers (mean age 32.5 ± 9.5 years) underwent a comprehensive medical examination including resting ECG, 24-hour ambulatory monitoring, echocardiography, exercise testing, heart rate variability analysis, and psychological assessment. Results: Cardiovascular disturbances were detected in 537 (14.5%) of the examined subjects, 71 of whom (1.9%) had cardiac rhythm and conduction disturbances without any identifiable structural or clinical causes. These 71 patients were divided into three groups: non-athletes with atrial or ventricular tachyarrhythmias (N=55, Group 1), non-athletes with second-degree sinoatrial or atrioventricular block (N=9), and athletes with any rhythm or conduction disturbances (N=7). Compared with the control group, these individuals, and particularly non-athletes, demonstrated higher levels of anxiety, reduced stress tolerance, and altered autonomic nervous system parameters consistent with increased physiological stress. Conduction abnormalities were predominantly functional, with resolution during exercise and no progression to pacemaker indication in a subset of 7/11 patients with baseline sinoatrial/atrioventricular block followed over the long term. Conclusions: In this large occupational cohort, cardiac rhythm and conduction abnormalities were in the absence of structural heart disease were uncommon. Their association with markers of autonomic dysfunction and psychological stress points to a potential contribution of occupational stress in the pathogenesis of idiopathic arrhythmias in otherwise healthy workers.

Abstract: Cardiovascular disease (CVD) is one of the major causes of mortality worldwide and in Romania. Vitis vinifera L. seed extract (GSCE), rich in oligomeric proanthocyanidins (OPCs), has shown cardioprotective activity at the molecular level and on surrogate clinical endpoints. This interdisciplinary narrative review synthesizes the phytochemistry of GSCE, and its cardioprotective mechanisms through a network pharmacology lens, provides the first artificial intelligence (AI)-assisted systematic assessment of GSCE drug interactions in cardiovascular polypharmacy and proposes an exploratory precision-medicine framework based on patient phenotyping, with emphasis on the cultivar ‘Feteasca Neagra’. The review was conducted according to SANRA principles, included 162 studies identified from 2,200 records published between 2000 and 2026 in PubMed/MEDLINE, Scopus and Web of Science. AI tools served exclusively auxiliary roles, with all outputs fully validated by the authors. GSCE simultaneously modulates six interconnected cardioprotective pathways: Nrf2/HO-1 axis activation, suppression of vascular inflammation via NF-κB, stimulation of nitric oxide production through PI3K/Akt/eNOS, limitation of reperfusion injury via MAPK/JNK, protection of LDL from oxidation, and inhibition of platelet aggregation. Published meta-analyses (16 RCTs, n = 810) document reductions in systolic (WMD = − 6.08 mmHg) and diastolic blood pressure (WMD = −2.20 mmHg; p < 0.05) and in heart rate (WMD = − 1.25 bpm; p < 0.05), with high heterogeneity (I² = 88.8%). The first systematic assessment of potential drug interactions identifies warfarin as the highest-risk interaction, based on CYP2C9 inhibition. ‘Feteasca Neagra’ was identified as having the highest theoretical cardioprotective potential among Romanian viticultural cultivars, and is proposed as a priority subject for translational research. This inference cannot support a clinical recommendation without dedicated pharmacological and clinical studies.

Abstract: We evaluated whether complementary coronary sinus (CS) lesions improve rhythm outcomes beyond biatrial cryoablation during mitral valve replacement. This single-center cohort included 180 adults operated on by one senior surgeon between January 2020 and September 2025, with follow-up through May 2026. Left atrial ablation (LA-Abl; n=65), biatrial ablation (BA; n=63), and BA with complementary CS lesions (BA+CS; n=52) were compared. After excluding three early deaths and five patients without follow-up records, 172 patients underwent rhythm assessment. The primary outcome was time to first recorded atrial fibrillation (AF) after discharge. Seventeen AF events were recorded. The primary Cox estimate favored BA+CS over BA without statistical significance (hazard ratio [HR] 0.52; 95% confidence interval [CI] 0.12–2.15); the numerical trend persisted after adjustment for baseline clinical and echocardiographic burden and surgical year (HR 0.54; 95% CI 0.13–2.20). Larger left atrial diameter and lower ejection fraction were associated with AF. Twelve-month sinus rhythm rates were 86.9%, 91.7%, and 94.1%, respectively (p=0.459). Weighted estimates varied by method. Outcome sensitivity analyses showed no significant advantage. An incremental CS benefit was not established; limited events, nonrandomized selection, and intermittent monitoring warrant cautious interpretation and larger studies with standardized surveillance.

Abstract: Background: Type 2 diabetes is a cause of cardiovascular morbidity and mortality. Although gluca-gon-like peptide-1 receptor agonists and dual glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonists improve cardiovascular outcomes, their comparative effects across the class re-main uncertain because direct head-to-head evidence is limited. Objective: To compare these agents for major adverse cardiovascular events (MACE) and establish a treatment hierarchy. Methods: This systematic review and network meta-analysis will include parallel-group randomized controlled trials with at least 52 weeks of follow-up involving adults with type 2 diabetes. Eligible trials will compare a GLP-1 receptor agonist or tirzepatide with placebo, standard care, another eligible in-cretin therapy, or, as connector nodes, an SGLT2 inhibitor or basal insulin. The primary outcome is time to first three-point MACE, comprising cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. MEDLINE, Cochrane CENTRAL, Web of Science, ClinicalTrials.gov, and WHO ICTRP, will be searched without date or language restrictions. Study selection and data extraction will involve human verification, and risk of bias will be assessed using RoB 2. A frequentist ran-dom-effects network meta-analysis will estimate hazard ratios, using placebo as the reference, and rank treatments with P-scores. Transitivity, heterogeneity, and inconsistency will be evaluated through prespecified effect modifiers, node-splitting, and design-by-treatment interaction methods. Confidence in network estimates will be assessed with CINeMA, alongside GRADE for pairwise comparisons. Ethics and dissemination: Ethical approval is unnecessary because only published data will be used. Results, datasets, search strategies, and analytic code will be disseminated through publications, presentations, bilingual summaries, and open repositories.

Abstract: Cardiovascular–kidney–metabolic (CKM) syndrome integrates three major chronic disease burdens — heart failure, chronic kidney disease, and metabolic dysfunction — into a unified pathophysiological framework. Accumulating evidence positions biological aging as the central substrate linking CKM risk factors to organ failure. Cardiac aging promotes mitochondrial dysfunction, diastolic stiffening, and impaired repair capacity; renal aging depletes tubular cell renewal, accelerates fibrosis, and reduces the production of the anti-aging hormone α-Klotho; pancreatic β-cell aging drives p16INK4a-mediated senescence and mitochondrial uncoupling that impair first-phase insulin secretion, constituting a primary metabolic driver of early CKM progression. Klotho, a kidney-derived endocrine factor whose circulating levels decline with CKD progression and metabolic disease, regulates cellular proliferation and mitochondrial homeostasis through the Sirt1–CHK2 signaling axis. Three-dimensional electron microscopy of aged renal tubular mitochondria reveals age-dependent loss of cristae structural integrity associated with reduced expression of the MICOS complex—the protein scaffold that maintains cristae junction architecture. Parallel volumetric electron microscopy of human failing myocardium demonstrates distinct mitochondrial structural phenotypes in heart failure with preserved ejection fraction (HFpEF) versus Heart Failure with Reduced Ejection Fraction (HFrEF), underscoring the specificity of mitochondrial remodeling in the CKM context. Measurement of circulating Klotho, senescence-associated secretory phenotype (SASP) markers, and urinary mitochondrial DNA provides a biological staging dimension that complements standard CKM clinical classification. The mitochondria-targeted peptide elamipretide (SS-31) — the most mature pharmacological intervention targeting inner mitochondrial membrane integrity — has demonstrated tremendous functional benefits in numerous pre-clinical models of heart failure, though the effect in HFpEF trial remains inconclusive. Together, these data outline a personalized medicine approach to CKM syndrome in which biological aging phenotype guides therapeutic strategy.

Abstract: Skeletal muscle electrical stimulation, delivered as neuromuscular electrical stimulation (NMES) or functional electrical stimulation (FES), is one of very few interventions in heart failure that produces sustained contractile work in the periphery without volitional effort and, in low-frequency configurations, without a measurable rise in cardiac output. Its clinical evaluation now spans almost three decades and has produced consistent signals of improved muscle strength, walking distance and quality of life. The physiological rationale that underpins these observations has advanced much less. This review separates what has been demonstrated in human skeletal muscle in heart failure with reduced ejection fraction (HFrEF) from what has been extrapolated from healthy volunteers, chronic obstructive pulmonary disease, critical illness and ageing muscle. We frame stimulation within the muscle hypothesis of chronic heart failure, in which peripheral myopathy drives ergoreflex overactivity, sympathetic excitation and exertional symptoms, and we show that the decisive mechanistic question, whether a programme of stimulation attenuates ergoreflex sensitivity, has never been tested, although two sham-controlled microneurographic studies indicate that stimulation acutely lowers muscle sympathetic nerve activity. Three further gaps are identified: a single biopsy-controlled randomised dataset in advanced heart failure, absence of contemporary molecular phenotyping of anabolic and proteolytic signalling in stimulated HFrEF muscle, and drift of the recent evidence base towards decompensated, frail and older populations with mixed ejection fraction. Against the background of the 2026 European Society of Cardiology guidelines, which recommend exercise-based cardiac rehabilitation for all stable patients and mention electrical muscle stimulation only as an option for very weak patients, we propose a research agenda in which stimulation dose is reported as a biological variable and muscle afferent physiology becomes the primary mechanistic endpoint.

Abstract: Introduction: Genetic variants in the Tenascin-XB (TNXB) gene have been associated with autosomal recessive Ehlers-Danlos Syndrome (classical-like) without vascular features. Here, we report the contribution of two TNXB variants, in cis or trans, to the development of arterial aneurysms and bicuspid aortic valves with or without connective tissue disease features present. Methods: The identification of compound heterozygosity in TNXB (c.8791+1G>A, c.12469+2T>C) in a 52-year-old female with fibromuscular dysplasia, bilateral vertebral artery dissections, and thoracic aortic aneurysm by whole exome sequencing (WES) prompted screening for TNXB variants in an institutional WES registry comprising 350 individuals with aneurysms and/or dissections. Multigene panel testing (MGPT) results from 1844 individuals tested at Ambry Genetics for a personal or family history of aneurysms, dissections, or other connective tissue disease features were used for replication analysis. Random exomes of 26,922 unaffected individuals were used as controls. Statistical analysis using Fisher’s exact test was carried out to compare the frequency of two or more TNXB variants in cases vs. controls. AlphaFold3 structural modeling was used to assess the effects of variants in cis on the 3-D structure and molecular interaction with the TGF-beta-3 proprotein. Results: There were significantly higher numbers of individuals who carried two or more rare, nonsynonymous TNXB variants, in cis or trans, in both WES (n=5/350; 1.4%) and MGPT (n=19/1844, 1.0%) datasets (p<0.01) compared to ethnically matched controls (n=89/26922; 0.14%). Additionally, there was a significantly higher prevalence of bicuspid aortic valve (BAV) in the MGPT cohort compared to the general population (11% vs. <2 % reported). The analysis by AlphaFold3 structural modeling revealed increased distortion of the 3-D structure caused by the presence of two variant(s) in cis vs. one variant in TNXB. Conclusion: This data strongly suggests an association between vascular aneurysm and/or dissection or bicuspid aortic valves and individuals with two TNXB variants.

Abstract: Background: The apnea–hypopnea index (AHI) is the conventional metric for grading obstructive sleep apnea (OSA) severity; however, it poorly reflects the true physiological impact of the disorder. The recently introduced hypoxic burden (HB) quantifies total exposure to intermittent hypoxia by integrating the duration and depth of oxygen desaturations associated with respiratory events. HB has emerged as a more biologically relevant and prognostically powerful biomarker than AHI. Methods: This narrative review summarizes the concept, methodology, and clinical significance of HB. Theoretical foundations, algorithmic approaches, and standardization challenges are discussed, along with evidence from major cohort studies evaluating the relationship between HB, cardiovascular outcomes, and treatment response. Results: HB integrates frequency, duration, and amplitude of desaturations into a continuous measure of nocturnal hypoxemia. Multiple independent cohorts (e.g., MrOS, Sleep Heart Health Study) have demonstrated that HB predicts cardiovascular morbidity and mortality more strongly than AHI. Elevated HB is associated with oxidative stress, endothelial dysfunction, sympathetic activation, and systemic inflammation. Reductions in HB during therapy with continuous positive airway pressure (CPAP), noninvasive ventilation (NIV), or oxygen supplementation correlate with improvements in hemodynamic and inflammatory markers, suggesting its potential as a dynamic therapeutic target. Conclusions: HB represents a major advance in the physiological assessment of OSA, linking sleep-related hypoxemia to biological stress and clinical outcomes. Its clinical integration—through standardized computation and incorporation into digital and AI-driven platforms—may enable personalized, physiology-based sleep medicine and establish HB as a key prognostic and therapeutic biomarker comparable to HbA1c in diabetes.

Abstract: Background: Risk stratification in mitral valve prolapse (MVP) remains challenging, particularly in symptomatic patients without severe mitral regurgitation (MR) or left ventricular (LV) dysfunction. Thoracic geometry is frequently altered in MVP, but the clinical and prognostic significance of directly measured antero-posterior (A-P) thoracic diameter remains poorly defined. Methods: In this single-center retro-prospective observational study, 116 symptomatic adults with echocardiographically confirmed MVP, preserved LV ejection fraction (≥55%), and non-severe primary MR underwent clinical assessment, thoracic morphometry, echocardiography, speckle-tracking analysis, carotid ultrasonography, and exercise stress echocardiography (ESE). Patients were categorized using an a priori A-P diameter threshold of <13 or ≥13 cm (n = 58 each), after age- and sex-matching. Cardiovascular events were assessed separately during a retrospectively reconstructed pre-index period and prospective post-index follow-up. Cox regression, receiver operating characteristic (ROC), and Kaplan–Meier analyses were performed. Results: The <13-cm phenotype had smaller cardiac chambers, lower LV mass, less pronounced MR and mitral annular disjunction, but lower exercise capacity, more symptoms, and greater exercise-induced ST-segment abnormalities, without inducible regional wall-motion abnormalities on ESE. During the pre-index period (4.58 ± 4.37 years), 25 non-fatal cardiovascular events were identified: 4/58 (6.9%) versus 21/58 (36.2%) in the <13- and ≥13-cm groups, respectively. A-P diameter (adjusted HR per 1-cm increase, 1.773; 95% CI, 1.178–2.667; p = 0.006) and more-than-mild peak-exercise MR (adjusted HR, 3.486; 95% CI, 1.273–9.544; p = 0.015) were independently associated with pre-index events. During prospective follow-up (7.32 ± 1.14 months), 14 non-fatal cardiovascular events occurred, with no fatal cardiovascular events: 1/58 (1.7%) versus 13/58 (22.4%), respectively. A-P diameter (adjusted HR per 1-cm increase, 3.234; 95% CI, 1.821–5.745; p < 0.001) and more-than-mild peak-exercise MR (adjusted HR, 5.053; 95% CI, 1.104–23.125; p = 0.037) remained associated with subsequent events. A-P diameter showed high discrimination for post-index events (AUC, 0.952; 95% CI, 0.886–1.000; p < 0.001), and prospective event-free survival differed by the prespecified 13-cm threshold (log-rank p = 0.001). Conclusions: A-P thoracic diameter identifies distinct MVP phenotypes and was associated with both previous and subsequent cardiovascular events. These exploratory prospective findings support thoracic depth as a simple, radiation-free marker potentially complementary to conventional MVP risk assessment, requiring external validation.

Abstract: Background: Dietary risk factors—high-fat, high-salt, high-sugar intake, chronic alcohol use, sugared carbonated beverages, and irregular eating—are epidemiologically associated with abdominal aortic aneurysm (AAA), but whether and through which molecular programs they converge on the aortic wall is poorly defined. No human aortic transcriptome with controlled dietary exposure exists in public repositories, which precludes direct case–control dietary differential-expression analysis in human tissue. Methods: We constructed six dietary-risk gene sets from animal-intervention transcriptomic studies in GEO, curated disease–gene association databases, and targeted literature mining. Human AAA differentially expressed genes (DEGs) were derived from GSE57691 (49 AAA vs. 10 non-aneurysmal donors) and GSE47472 (14 AAA vs. 8 donors) using limma (adjusted P<0.05, |log2FC|≥0.5); genes concordantly DE in both cohorts were retained as the consensus AAA set. Each dietary set was intersected with AAA DEGs; genes hit by ≥3 of six exposures were termed the strict core and genes hit by ≥2 were termed the extended core. Functional enrichment (GO/KEGG), STRING PPI analysis, and marker-based single-sample gene-set enrichment analysis (ssGSEA, GSVA) were performed. A per-sample multi-dietary score (DietScore) was computed in GSE57691 and its association with AAA status, the NLRP3–CASP1–IL1β–MMP9 axis, and marker-based immune signatures was tested by Wilcoxon and Spearman methods. Results: Thirty-six genes were shared between the six dietary sets and AAA DEGs. Seven strict-core genes were hit by ≥3 dietary exposures—IL1B (5 sets), NLRP3 (4), MMP9 (4), and IL6, CCL2, VCAM1, CAT (3 each)—and a further seven (CASP1, NFKB1, EDN1, NCF1, APOB, PPARG, MYH11) were hit by two. Enrichment converged on Lipid and atherosclerosis (P≈3×10⁻¹⁴), AGE–RAGE signaling in diabetic complications, NOD-like receptor (NLRP) signaling, and macrophage/foam-cell differentiation. STRING PPI centered on the NLRP3–CASP1–IL1β–IL6–MMP9 module. DietScore was higher in AAA than donor aorta (Wilcoxon P≈1.6×10⁻⁵) and correlated positively with CASP1 (ρ=0.59), IL1B (ρ=0.57), NLRP3 (ρ=0.47), MMP9 (ρ=0.46), and with macrophage, T-cell, and neutrophil signatures. Conclusions: This computational, hypothesis-generating integration of mostly animal-derived dietary gene sets with the human AAA transcriptome identifies a shared myeloid–inflammatory, NLRP3–IL1β–MMP9 program that is active in human AAA. The DietScore is an internally derived, descriptive computational index; it is not validated as a clinical AAA biomarker and must not be used for patient classification or diagnosis. This work does not establish a causal diet–AAA relationship; it cannot distinguish direct aortic-wall effects from effects mediated through hypertension, dyslipidemia, or diabetes; and the DietScore was derived and evaluated within a single cohort without an independently phenotyped external validation set. All findings require confirmation in dietary-intervention animal models and human AAA cohorts with matched dietary phenotypes.

Abstract: Myocarditis is a dynamic disease and myocardial oedema, injury, ventricular dysfunction, and fibrosis may evolve differently over time. Cardiovascular magnetic resonance (CMR) has become central to its non-invasive assessment, providing complementary information on myocardial tissue through T2-sensitive imaging, native T1, extracellular volume (ECV), and late gadolinium enhancement (LGE). The meaning of these findings, however, depends on when imaging is performed. Follow-up CMR may therefore provide a better understanding of myocardial recovery, helping to distinguish resolving disease from persistent abnormalities or healed injury with residual scar. Based on the temporal evolution of CMR findings, we propose four conceptual patterns of myocardial recovery: near-complete imaging recovery, resolving inflammatory injury, persistent inflammatory imaging abnormalities, and healed injury with residual LGE/scar-like substrate. These patterns are intended as a framework for interpreting serial CMR rather than as formally validated imaging phenotypes. In selected patients, integration with echocardiography, molecular imaging, genetics, and endomyocardial biopsy may provide further insight into the underlying disease process. Whether this longitudinal approach can improve risk stratification and ultimately guide therapeutic decisions remains an important question for future studies.

Abstract: The stress hyperglycemia ratio (SHR) expresses acute glucose relative to estimated background glycemia. Its association with atrial thrombus after ischemic stroke raises a clinically relevant question. Does it identify a thrombogenic atrial substrate, reflect the response to cerebral injury, or capture both? This critical narrative review compares human studies of glycemic disturbance, inflammatory biomarkers and thrombus-related outcomes. Anatomically detected thrombus, composite echocardiographic findings, coronary thrombus burden and laboratory thrombogenicity are evaluated separately. The identified atrial SHR evidence is observational. Coronary studies provide supporting context but examine a different vascular process. C-reactive protein (CRP) and related inflammatory indices also show associations with atrial thrombus, although discrimination and adjustment vary. Experimental hypoglycemia studies demonstrate changes in platelet activity, fibrin structure and ex vivo thrombus formation. They do not establish hypoglycemia-induced atrial thrombosis. Interpretation is further limited by measurement timing, selected imaging populations, possible cohort overlap and imperfect thrombus classification. Neither an adjusted association nor a high multivariable-model area under the curve establishes a causal pathway or a safe imaging rule. Future studies should test whether SHR adds clinically useful information beyond atrial structure, rhythm, inflammation and stroke severity. Current evidence supports mechanistic investigation and prospective validation rather than biomarker-directed anticoagulation or omission of indicated imaging.

Abstract: Background: Acute myocardial infarction (AMI) remains a leading cause of cardiovascu-lar morbidity and mortality worldwide. Accurate early risk stratification upon admission is critical for optimizing therapeutic strategies. The lactate-to-albumin ratio (LAR) has emerged as a novel composite biomarker reflecting metabolic stress, tissue hypoperfusion, and systemic inflammation. This study aimed to evaluate the prognostic value of LAR in predicting in-hospital outcomes in AMI patients undergoing percutaneous coronary in-tervention (PCI) at Nhan Dan Gia Dinh Hospital. Methods: A prospective cohort study was conducted on 121 AMI patients who underwent PCI between January 2026 and June 2026 at Nhan Dan Gia Dinh Hospital. Clinical base-line characteristics, laboratory parameters (including blood lactate and serum albumin upon admission), and in-hospital clinical outcomes were collected. The predictive per-formance of LAR for in-hospital all-cause mortality was evaluated using Receiver Oper-ating Characteristic (ROC) curve analysis. Multivariate logistic regression was performed to determine the independent prognostic value of LAR. Results: Among the 121 enrolled patients, in-hospital all-cause mortality occurred in 8 pa-tients (6.6%). Median LAR levels were significantly higher in non-survivors compared to survivors (1.22 [IQR: 0.72–2.18] vs 0.41 [IQR: 0.29–0.58], p < 0.001). ROC curve analysis demonstrated that LAR had an excellent accuracy in predicting in-hospital mortality with an Area Under the Curve (AUC) of 0.97 (95% CI: 0.93–1.00, p < 0.001). At the optimal cutoff value of 0.65, LAR yielded 100.0% sensitivity, 88.5% specificity, 38.1% positive predictive value, and 100.0% negative predictive value. In univariate analysis, each 0.1-unit increase in LAR was associated with higher odds of mortality (OR = 2.64, 95% CI: 1.35–5.18, p = 0.005). After adjusting for Killip class III–IV (OR = 2.56, p = 0.008), eGFR (OR = 2.75, p = 0.006), and neutrophil count (OR = 2.87, p = 0.022), elevated LAR remained an independ-ent predictor of in-hospital mortality. Conclusions: LAR is a simple, rapidly accessible, and independent biomarker for predict-ing in-hospital mortality in AMI patients undergoing PCI. Integrating LAR into early clin-ical risk assessment can assist in identifying high-risk patients requiring intensive man-agement.

Abstract: Blunt cardiac trauma is rare but potentially fatal, especially when associated with cardiac chamber rupture. We report a case of a 53-year-old female who sustained right atrial rupture and pericardial tear following a motor vehicle collision. The patient presented with clinical signs of tamponade and was transferred urgently for surgical intervention. Emergency sternotomy, initiation of cardiopulmonary bypass, and right atrial repair led to full recovery. This case highlights the critical importance of rapid diagnosis and prompt surgical management in cases of cardiac trauma.

Abstract: No drug has yet been shown to stop an aortic aneurysm (AA, abdominal AAA or thoracic TAA) from enlarging, and many patients are recognised only once the wall is already failing. Alongside the classical risk factors, three conditions that patients and clinicians can actually change—chronic cold exposure, lack of exercise and severe infection—have each been tied to faster progression, although their molecular overlap is rarely discussed together. This narrative review draws on 80 sources from PubMed, Web of Science and CNKI (2003–2026). Upstream the three insults look quite different: cold acts through extracellular cold-inducible RNA-binding protein (eCIRP)–TLR4 signalling and the sympathetic nervous system, inactivity through low and oscillatory wall shear stress, and infection through pathogen-associated molecular patterns. Downstream they meet on NF-κB, MMP-2/9, oxidative stress and loss of vascular smooth muscle cells, with the NLRP3 inflammasome as the shared bottleneck—its caspase-1 both releases IL-1β/IL-18 and cleaves pro-MMP-9 directly. We use this convergence to re-read the still piecemeal single-omics evidence and weigh NLRP3-, IL-1β- and CIRP-directed drugs against exercise, warmth and vaccination. The clearest gaps are multifactorial models, paired multi-omics cohorts and trials that follow expansion rate.

Abstract: Background: Minimally invasive and endoscopic techniques have expanded the surgical options for tricuspid valve repair. Conventional approaches often require manual snaring of the venae cavae, which can increase procedural complexity and invasiveness, especially in redo or advanced heart failure settings. This study describes a snare-free totally endoscopic approach to tricuspid valve repair utilizing percutaneous venous selfexpanding cannulation. Methods: Between 2020 and 2025, 32 consecutive patients with severe tricuspid regurgitation (TR) underwent totally endoscopic tricuspid valve repair using a standardized snare-free technique. Venous drainage was achieved via percutaneous femoral cannulation with a self-expanding venous cannula, providing optimal central venous decompression without external tourniquets or loops. All clinical, intraoperative, and early postoperative parameters were systematically collected and analyzed using descriptive statistical methodology. Results: Endoscopic tricuspid valve repair was successfully completed in all 32 patients. The mean total cardiopulmonary bypass (CPB) time was 145.9 ± 35.8 minutes, and the mean aortic cross-clamp duration was 92.4 ± 24.5 minutes. The early postoperative safety profile was characterized by an all-cause 30-day mortality rate of 3.1% (n = 1) and zero cases of clinically relevant hemolysis (0.0%)The mean intensive care unit stay was 6.0 ± 4.9 days, and the mean total hospital length of stay was 15.4 ± 9.7 days. Conclusion: Snare-free totally endoscopic tricuspid valve repair using a percutaneous self-expanding venous cannulation is a safe, technically feasible, and reproducible technique. This structural approach simplifies right atrial endoscopic visualization, eliminates the complications associated with deep caval-dissection, and demonstrates highly stable early clinical and electrophysiological outcomes.

Abstract: Background: Coronary artery calcification (CAC) is a critical marker of subclinical atherosclerosis, yet its primary diagnostic tool, coronary computed tomography (CT), is limited by cost and radiation. We aimed to develop and validate a robust machine learning framework to identify significant CAC (Agatston score ≥100) using features extracted from routine 12-lead electrocardiograms (ECGs), including legacy archives stored as PDFs. Methods: This retrospective study utilized 382 consecutive patient records. A novel signal-processing pipeline was developed to convert PDF-based ECGs into standardized 500-Hz digital waveforms (WFDB format). From these signals, 360 morphological and temporal features were extracted using the NeuroKit2 library. To ensure clinical reliability and prevent optimistic bias, a Balanced Random Forest (BRF) classifier was integrated into a repeated “inner-outer” nested cross-validation framework combined with Minimum Redundancy Maximum Relevance (mRMR) feature selection. Results: The mRMR-BRF model demonstrated high diagnostic accuracy with a grand mean AUC of 0.8211 (95% CI: 0.8018–0.8404), outperforming standard algorithms. Explainability analysis via SHAP identified age, ST-segment level in lead V4, T/QRS ratio in lead III, and QRS duration dispersion as the most significant predictors. These features suggest that latent electrical signatures of subclinical myocardial remodeling and impaired perfusion are detectable via AI-enhanced ECG analysis. Conclusion: Our framework establishes digitized 12-lead ECGs as a scalable and non-invasive digital biomarker for significant CAC. By enabling the quantitative analysis of legacy PDF archives and providing high predictive stability through nested validation, this approach offers a cost-effective pre-screening tool to prioritize high-risk patients for definitive imaging and early preventive intervention.

Abstract: Fulminant Varicella Zoster Virus (VZV) associated with myocarditis is rare but may result in severe myocardial dysfunction requiring veno-arterial extracorporeal mem-brane oxygenation (VA-ECMO), which itself increases the risk of left ventricular (LV) distension and thrombus formation. We report the case of a 50-year-old woman who developed refractory cardiogenic shock following out-of-hospital ventricular fibrilla-tion cardiac arrest and required peripheral VA-ECMO. VZV DNA was detected in the blood, while coronary angiography demonstrated normal coronary arteries, support-ing a diagnosis of fulminant VZV-associated myocarditis. Despite anticoagulation and multimodal LV unloading with an intra-aortic balloon pump and Rashkind atrial sep-tostomy, persistent LV distension and absence of aortic valve opening were followed by formation of a large and organized LV thrombus. After neurological assessment confirmed preserved responsiveness, surgical thrombectomy was undertaken. Thrombus removal was performed through the aortic valve and mitral valve, followed by pulsed irrigation of the LV cavity and surgical apical venting connected to the ECMO venous circuit. Histopathology demonstrated lymphocytic myocarditis of probable viral origin. The patient subsequently developed multiorgan failure and died on postoperative day six. This case highlights the challenges of thrombus formation during VA-ECMO and the importance of early, individualized ventricular unloading. We additionally review available left ventricular unloading strategies and right ven-tricular unloading techniques in patients requiring VA-ECMO, emphasizing their re-spective indications and technical considerations.

Abstract: New-onset atrial fibrillation (NOAF) is a frequent complication among patients with non-ST-elevation myocardial infarction (NSTEMI) and is associated with adverse outcomes, making early identification of predictors essential for risk stratification and management. This retrospective cohort study evaluated the prognostic value of the Clinical SYNTAX Score (CSS) compared with the anatomical SYNTAX Score (SS), GRACE, and CHA2DS2-VASc scores in predicting in-hospital NOAF and long-term outcomes among 979 NSTEMI patients undergoing coronary angiography. Predictors of NOAF, all-cause mortality, and major adverse cardiovascular events (MACE: death, myocardial infarction, stroke) were identified using logistic and Cox regression models, with receiver operating characteristic (ROC) analysis used to compare the discriminative power of CSS against SS, GRACE, and CHA2DS2-VASc over a median follow-up of 86 months (IQR: 0.1–144). NOAF developed in 80 patients (8.2%), with age, female gender, left atrial diameter, left ventricular diastolic dysfunction, and CSS (p=0.014) identified as independent predictors. CSS demonstrated superior discriminative ability (AUC: 0.724; 95% CI: 0.673–0.775) compared with SS (AUC: 0.644; 95% CI: 0.588–0.699), and a CSS threshold ≥17.77 predicted NOAF with 75% sensitivity and 65% specificity. In Cox regression analysis, in-hospital NOAF, age, hypertension, reduced ejection fraction (<60%), and CSS independently predicted long-term all-cause mortality, while NOAF, EF<60%, age, early AF recurrence, hypertension, and CSS independently predicted MACE; SS was not a significant predictor in either model. These findings indicate that CSS outperforms SS in predicting in-hospital NOAF and long-term outcomes in NSTEMI patients, offering a practical and comprehensive tool for early rhythm monitoring and risk-guided management.

Abstract: Background/Objectives: Competitive esports players spend prolonged periods seated while performing under sustained cognitive demand, creating conditions that may adversely affect cerebrovascular function. Internal carotid artery (ICA) blood flow is a major determinant of cerebral perfusion and may be particularly relevant to the cognitive demands of competitive gaming. To date, no study has evaluated ICA hemodynamics during competitive gaming or the feasibility of repeated Doppler ultrasound assessment in this setting. Therefore, this pilot study aimed to (1) determine the feasibility of measuring ICA hemodynamics during competitive gaming and (2) generate preliminary data on the effects of a 6-minute walking break on ICA blood flow velocity and volume. Methods: Eleven competitive esports players (20.8 ± 2.1 years; 9 male) completed two 2-hour gaming sessions using a randomized crossover design: uninterrupted gaming (continuous condition) and gaming interrupted by a 6-minute walking break at 60 minutes (walking condition). Doppler ultrasound measurements of left ICA blood flow velocity, blood flow volume, and vessel diameter were obtained at baseline and every 30 minutes. Heart rate and blood pressure were also assessed. Feasibility outcomes included recruitment, protocol adherence, and Doppler measurement success. Results: Fourteen participants were screened. Eleven (79%) met eligibility criteria and completed both study visits, resulting in 100% protocol adherence. Doppler ultrasound acquisition was successful in 107 of 110 planned measurements (97.3%). Baseline ICA hemodynamics were similar between conditions. ICA blood flow velocity and vessel diameter did not differ between conditions. In the walking condition, change in ICA blood flow volume improved from −41.0 ± 102.4 mL/min before the walking break to −5.9 ± 132.2 mL/min 30 minutes later, before declining to −43.7 ± 75.9 mL/min at 120 minutes. No significant between-condition differences in ICA blood flow volume were observed. Heart rate was significantly lower following the walking break at 90 minutes (72.7 ± 10.7 vs. 82.2 ± 12.3 beats/min; p = 0.009). Conclusions: Repeated Doppler ultrasound assessment of ICA hemodynamics during competitive gaming is feasible and well tolerated. A transient improvement in ICA blood flow volume following a brief walking break suggests that the physiological benefits of a single break may be short-lived and supports future studies evaluating more frequent movement breaks, such as every 30 minutes, during prolonged gaming.