Search Results (642)

Background: Persistent left superior vena cava (PLSVC) is the most common congenital anomaly of the thoracic venous system and is generally considered a benign variant. This study aimed to evaluate arrhythmia-related electrocardiographic parameters in children with isolated PLSVC and to assess the relationship with coronary sinus dimensions. Methods: This retrospective cross-sectional study included 26 children with isolated PLSVC and 26 age- and sex-matched healthy controls. All participants underwent transthoracic echocardiography and electrocardiographic analysis. Coronary sinus diameters were measured and indexed to body surface area. Electrocardiographic parameters reflecting atrial conduction and ventricular repolarization heterogeneity, including P-wave dispersion, QTc dispersion, Tp–e interval, and indices of cardiac electrophysiological balance (QT/QRS and QTc/QRS), were evaluated. Results: P-wave dispersion (62.15 ± 14.78 vs. 35.59 ± 10.02 ms, p < 0.001), QTc dispersion (99.66 ± 30.10 vs. 40.45 ± 10.78 ms, p < 0.001), and Tp–e dispersion (67.29 ± 19.10 vs. 38.42 ± 7.13 ms, p < 0.001) were significantly higher in the PLSVC group. QT/QRS (4.33 ± 0.59 vs. 3.78 ± 0.36, p < 0.001) and QTc/QRS (5.48 ± 0.91 vs. 4.61 ± 0.36, p < 0.001) ratios were also increased. Coronary sinus measurements showed weak and inconsistent correlations with electrocardiographic parameters. Conclusions: Children with isolated PLSVC exhibit significant electrocardiographic alterations reflecting atrial and ventricular electrical heterogeneity. These findings suggest that PLSVC may be associated with subclinical electrophysiological abnormalities beyond a benign anatomical variant. Accordingly, increasing clinical awareness of potential arrhythmic risk during follow-up and considering this aspect in patient evaluation may be appropriate. Full article

Atrial cardiomyopathy (ACM) is defined as any complex of structural, architectural, functional, electrophysiological, and molecular changes affecting the atria that may result in clinically significant health consequences. ACM can be caused by a variety of factors, including age-related changes, valvular or vascular disease, genetic diseases, congestive heart failure, metabolic diseases, cardiovascular disease (CVD) risk factors such as arterial hypertension (AH) or obesity, obstructive sleep apnea, and other infectious or noninfectious diseases predisposing to chronic inflammation. The diagnosis of ACM relies on several modalities, including electrocardiography, echocardiography, cardiac magnetic resonance imaging (MRI), computed tomography (CT), electroanatomical mapping (EAM), genetic studies, and biomarkers, which can detect and characterize structural, mechanical, and electrical atrial dysfunction. These changes often include structural atrial remodeling (fibrosis), abnormal structure of the atrial wall and its components, and contractile and electrical dysfunctions. When assessing aspects of ACM, structural changes in the atria such as left atrium (LA) size and fibrosis; LA architectural changes such as the expression of remodeling; changes in LA mechanics such as echocardiographic stress indices; changes in reservoir function and changes in contraction; biological factors determining changes in biomarkers; possible genetic predispositions and higher expression of certain genes encoding certain proteins; and arrhythmogenic factors associated with a higher risk of atrial fibrillation (AF) and stroke and a worse short- and long-term prognosis are very important. When considering the challenges of diagnosing ACM, it should be noted that without standardized diagnostics, most ACM diagnostic situations remain primarily research tools rather than practical clinical diagnostic methods. This review critically evaluates the evidence and translational gaps in the diagnosis of ACM, synthesizing the emerging role of advanced diagnostics and their clinical and prognostic implications as a key future tool for individual risk stratification. Full article

Background/Objectives: Heart rate variability (HRV) and ventricular repolarization are key noninvasive markers of cardiac autonomic regulation and electrical stability. Their physiological relationship in healthy pediatric populations remains incompletely understood. This study evaluated the association between HRV parameters and ventricular repolarization indices and established age-specific reference values for HRV. Methods: This cross-sectional study included 254 healthy children (5–18 years) who underwent 24 h Holter monitoring. HRV parameters (SDNN, SDANN, RMSSD, pNN50, LF, HF, LF/HF ratio) and repolarization indices (QT, QTc, QTd, QTcd) were analyzed. Age-stratified percentile distributions were generated, and multivariable analyses were performed, adjusting for age, sex, and heart rate. Results: All HRV parameters increased significantly with age (p < 0.001), accompanied by a decrease in heart rate. In unadjusted analyses, the QT interval showed positive correlations with HRV indices, particularly SDNN (r = 0.434, p < 0.001). However, these associations were no longer significant after adjustment. QTd remained modestly associated with SDNN, whereas QTc showed no association with HRV; sex was the only independent predictor of QTc. Conclusion: In healthy children, the apparent association between HRV and the QT interval appears to be largely explained by heart rate rather than by an independent physiological relationship. These findings highlight the importance of considering heart rate when interpreting associations between autonomic and ventricular repolarization parameters in pediatric studies. Age-specific HRV reference values may support the clinical interpretation of pediatric autonomic and electrophysiological assessments. Full article

The cardiac sodium channel Na_V1.5, encoded by SCN5A, generates the inward sodium current required for myocardial excitability and impulse conduction. Loss-of-function mutations of Na_V1.5 have been implicated in inherited arrhythmia syndromes, including Brugada syndrome, progressive cardiac conduction disease, and congenital sick sinus syndrome. The common SCN5A polymorphism H558R has reported minor allele frequencies ranging from 9.2% to 29% across ethnic groups, whereas S524Y has been described in individuals of African ancestry with a minor allele frequency of approximately 3.3%. Two splice variants of human SCN5A, one lacking a glutamine at position 1077 (Q1077del) and one containing Q1077, exist in every human in a 2:1 mRNA transcript ratio. We engineered these two polymorphisms in both backgrounds and reported that when S524Y and H558R were expressed in the Q1077del variant, current densities were normal. In the Q1077 variant, however, the current densities showed a dramatic reduction compared to those in the Q1077del variant or WT-Q1077. We previously reported that incubation with the antiarrhythmic drug mexiletine “rescued” expression deficiencies in the Brugada syndrome. Cells expressing S524Y/Q1077 and H558R/Q1077 were incubated for 48 h with or without mexiletine (500 μM), followed by drug washout before electrophysiological assessment. Mexiletine significantly increased current density for both S524Y/Q1077 and H558R/Q1077 compared with untreated cells, restoring current density to levels comparable to WT-Q1077. Flow cytometry using a FLAG-tagged channel demonstrated that mexiletine-mediated rescue was associated with increased cell-surface expression. The magnitude of the expression defects caused by H558R and S524Y in the Q1077 splice background is similar to that observed with arrhythmia-associated SCN5A mutations, and we show for the first time that the defects for both polymorphisms can be rescued with mexiletine. Although it is unknown whether they result in heightened arrhythmia susceptibility in patients homozygous for the minor allele, our result may have implications for therapy for mutations with loss-of-function phenotypes modified by these common polymorphisms. Full article

Chronic heart failure (CHF) is characterized by heightened cardiac sympathetic activity and neuroinflammation within the stellate ganglia (SG), contributing to cardiac arrhythmogenesis. However, the upstream mediators of this neuroimmune interaction remain incompletely defined. This study investigated whether systemic neutralization of granulocyte–macrophage colony-stimulating factor (GM-CSF, an inflammatory cytokine) attenuates SG inflammation and cardiac sympathetic overactivation in a rat model of coronary artery ligation-induced CHF. Male Sprague–Dawley rats underwent myocardial infarction or sham surgery and were treated with a GM-CSF neutralizing antibody or vehicle. Cardiac sympathetic nerve activity (CSNA), heart rate variability (HRV), cytokine expression, and the electrophysiological properties of cardiac sympathetic post-ganglionic (CSP) neurons were assessed. CHF increased the levels of GM-CSF, ionized calcium-binding adaptor molecule 1 (IBA1, an activated macrophage marker) and pro-inflammatory markers (TNF-α, pro IL-1β) in the SG, enhanced neuronal Ca²⁺ currents, cell excitability, and CSNA, and impaired HRV. The GM-CSF neutralizing antibody significantly attenuated SG inflammation, partially normalized Ca²⁺ currents and neuronal firing, decreased CSNA, and improved cardiac autonomic balance. These findings identify GM-CSF as a key regulator of SG neuroinflammation and sympathetic dysregulation in CHF. Targeting this GM-CSF protein may represent a novel therapeutic strategy to mitigate autonomic imbalance and arrhythmic risk. Full article

Cardiovascular diseases (CVDs) remain the foremost cause of death globally, responsible for 19.2 million deaths and 437 million disability-adjusted life years in 2023, with prevalent cases having more than doubled since 1990. No approved therapy restores myocardium lost to infarction. The adult heart replaces cardiomyocytes at approximately 1% per year in young adults, declining to about 0.45% per year with ageing, far below what is needed to recover the more than one billion cells destroyed by a large myocardial infarction. Cell-based regenerative strategies have been investigated for more than two decades, encompassing bone marrow mononuclear cells (BM-MNCs), mesenchymal stromal cells (MSCs), cardiac progenitor cells, cardiosphere-derived cells (CDCs), skeletal myoblasts, and induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Safety has been consistent. Efficacy has been modest and variable: the CADUCEUS trial demonstrated scar mass reduction with CDCs without proportionate ejection fraction improvement; the Phase 1/2 POSEIDON trial confirmed MSC safety in 30 patients; and the Phase 3 DREAM-HF trial, enrolling 537 patients, failed its primary endpoint (HR 1.2, p = 0.406). Mechanistic work has established that transplanted cells engraft poorly and exert their benefit principally through paracrine signalling mediated by secreted extracellular vesicles and exosomes carrying microRNAs, trophic factors, and immunomodulatory proteins. For iPSC-CMs, electrophysiological immaturity and arrhythmogenic risk in primate models remain unresolved barriers. Emerging strategies include CRISPR-engineered hypoimmune iPSC lines, bioengineered cardiac patches, injectable hydrogel scaffolds, and engineered exosome platforms. This review provides a comprehensive synthesis of preclinical and clinical evidence, examines translational barriers, and identifies the scientific and regulatory priorities required before these therapies can enter routine clinical practice. Full article

Radiofrequency catheter ablation is a minimally invasive electrophysiological procedure that utilizes radiofrequency energy to induce targeted thermal injury within arrhythmogenic myocardial tissue, thereby eliminating the substrate responsible for rapid and irregular cardiac rhythm disturbances. Radiofrequency ablation is a method widely used in human medicine for the permanent treatment of arrhythmias. In veterinary medicine, there are only a few centers worldwide that use this treatment method in dogs. This article presents the experiences of a Polish center in treating supraventricular and ventricular arrhythmias using this method. The first electrophysiological study and ablation were performed using an analog electrophysiological system; subsequent procedures were performed with the aid of a computerized system, and the last three procedures were performed using a 3D electroanatomical system. A total of 14 radiofrequency ablation procedures were performed on dogs weighing 10 to 33 kg, aged 9 months to 9 years, of various sexes and breeds. Fifty percent of the dogs that underwent ablation had both clinical and echocardiographic signs of tachycardia-induced cardiomyopathy. Three dogs required a re-ablation procedure. Complete elimination of clinically significant arrhythmias was achieved in 13 of 14 dogs, while one dog showed partial procedural success. No significant or permanent complications were observed in any of the dogs. Radiofrequency ablation procedures for arrhythmias are effective and safe. Full article

Polycyclic aromatic hydrocarbons (PAHs) from the water-soluble fraction (WSF) of crude oil are recognized cardiotoxicants in fish; however, all electrophysiological evidence to date derives from acute exposure experiments. This study examined the effects of prolonged (5–8 h) incubation of isolated ventricular cardiomyocytes from the navaga cod (Eleginus nawaga, Walbaum, 1792) with 10% WSF (total dissolved tricyclic-PAH concentration in the tens-of-nM), 3 µM phenanthrene (Phe), or 3 µM 3-methylphenanthrene (3-MP) on action potential (AP) parameters and the underlying ionic currents using the whole-cell patch-clamp technique. WSF and 3-MP reduced AP amplitude and maximum rate of depolarization through suppression of the fast sodium current (I_Na), whereas Phe and 3-MP shortened AP duration, associated with decreased density and a hyperpolarizing shift in steady-state activation of the rapid delayed rectifier potassium current (I_Kr). The L-type calcium current and inward rectifier potassium current remained unaffected by all treatments. Notably, the effects of prolonged incubation differed qualitatively from previously reported acute responses to the same compounds, suggesting the involvement of indirect mechanisms such as reactive oxygen species production and activation of intracellular signaling cascades. These findings demonstrate that subchronic PAH exposure produces distinct and potentially proarrhythmogenic alterations in fish cardiac electrophysiology that cannot be predicted from acute exposure data alone. Full article

The clinical use of doxorubicin (DOX), an effective chemotherapeutic drug for breast cancer, is limited by off-target nephrotoxicity, which is exacerbated in elderly patients. While excessive mitochondrial fission is known to contribute to DOX-induced cardiotoxicity, its role in DOX-induced nephrotoxicity, particularly in the context of renal aging, remains unclear. To explore this and investigate the therapeutic potential of the mitochondrial fission inhibitor Mdivi-1, female Wistar rats with D-galactose-induced accelerated renal aging were allocated into four groups: vehicle, DOX, DOX+Mdivi-1 co-treatment, and DOX+Mdivi-1 post-treatment. DOX administration resulted in significant renal dysfunction, oxidative stress, inflammation, and histopathological damage. Mitochondrial dysfunction along with the increased expression of fission protein, decreased fusion proteins, and activation of apoptotic markers and PINK1 expression were also evident. Remarkably, both co-treatment and post-treatment with Mdivi-1 comparably and significantly attenuated DOX-induced renal damage. This study suggests that Mdivi-1 mitigates DOX-induced nephrotoxicity in the aged kidney by modulating mitochondrial dynamics, suppressing oxidative stress and inflammation, and inhibiting apoptosis. These findings highlight mitochondrial fission as a promising therapeutic target for the treatment of doxorubicin toxicity and provide further support for the possible use of Mdivi-1 as a therapeutic strategy to protect the kidneys of elderly breast cancer patients undergoing chemotherapy. Full article

Intrauterine fetal death, also termed stillbirth, remains a major clinical challenge, with a substantial proportion of cases unresolved despite standard postmortem evaluation, limiting effective risk stratification and prevention. This structured narrative review synthesizes evidence from genetic, immune-mediated, and pharmacogenetic studies to summarize possible contributors to stillbirth with potential application in precision-oriented diagnostics and prevention of unexplained stillbirth. Integration of cytogenetic and sequencing approaches enhances detection of clinically relevant abnormalities in previously unexplained cases, while exome sequencing reveals additional molecular diagnoses beyond conventional chromosomal analyses. Genetic contributors include chromosomal abnormalities and a wide spectrum of heterogeneous monogenic disorders affecting cardiac electrophysiology, neuromuscular function, metabolic homeostasis, and early developmental processes. Immune-mediated placental dysfunction, particularly obstetric antiphospholipid syndrome, emerges as a clinically actionable mechanism characterized by vascular and inflammatory injury and associated angiogenic imbalance. Emerging pharmacogenetic evidence indicates that genetic variability in drug metabolism and receptor signaling may influence therapeutic response in placenta-mediated complications. Collectively, these findings support an integrated, mechanism-based framework combining genomic, immune, and pharmacogenetic data with phenotypic characterization to advance etiologic resolution, improve recurrence risk assessment, and enable precision-based diagnostic and preventive strategies in stillbirth. Full article

Background/Objectives: Behçet’s disease (BD) is a chronic multisystem inflammatory vasculitis associated with an increased risk of ventricular arrhythmias and sudden cardiac death. The index of cardiac electrophysiological balance (iCEB) and its corrected form (iCEBc) are novel electrocardiographic markers reflecting the balance between ventricular depolarization and repolarization and have been proposed as indicators of arrhythmic risk. This study aimed to evaluate iCEB and iCEBc in patients with BD and to investigate their associations with disease duration and inflammatory activity. Methods: This observational, cross-sectional study included 81 patients with clinically inactive BD (Behçet’s Disease Current Activity Form score 0–1) and 84 age- and sex-matched healthy controls. All participants underwent laboratory testing, transthoracic echocardiography and standard 12-lead electrocardiography. QT, QTc, QRS, iCEB (QT/QRS), and iCEBc (QTc/QRS) values were calculated. Correlation analyses were performed to evaluate the relationships between disease duration and QTc, iCEB, iCEBc, and CRP levels in the Behçet group. Disease duration, age, and CRP levels were subsequently entered into a multivariable linear regression model to identify independent predictors of iCEBc. Results: Patients with BD exhibited significantly higher QTc (431.41 ± 24.18 vs. 410.60 ± 18.65 ms, p < 0.001), iCEB (4.49 ± 0.33 vs. 4.36 ± 0.35, p = 0.016), and iCEBc (5.20 ± 0.47 vs. 4.93 ± 0.33, p < 0.001) values compared with healthy controls. CRP levels were also significantly elevated in the Behçet group (23.34 ± 34.05 vs. 6.07 ± 4.57 mg/L, p < 0.001). Disease duration demonstrated significant positive correlations with QTc (r = 0.539, p < 0.001), iCEB (r = 0.447, p < 0.001), iCEBc (r = 0.747, p < 0.001), and CRP levels (r = 0.419, p < 0.001). In multivariable linear regression analysis, disease duration emerged as the sole independent predictor of iCEBc (β = 0.077, 95% CI: 0.057–0.097, p < 0.001), whereas CRP was not independently associated with iCEBc (p = 0.286). Conclusions: Patients with BD have significantly increased iCEB and iCEBc values, indicating impaired cardiac electrophysiological balance. The strong association between disease duration and iCEBc suggests a relationship between disease duration and electrophysiological alterations associated with ventricular arrhythmia risk. iCEBc may serve as a simple and noninvasive electrocardiographic marker of electrophysiological alterations associated with ventricular arrhythmia risk in patients with BD. Full article

Autoimmune diseases substantially increase the risk of atrial and ventricular arrhythmias and sudden cardiac death through shared immune-mediated mechanisms. Pro-inflammatory cytokines, autoantibodies, and progressive myocardial fibrosis disrupt ion channel function, impair conduction, and create re-entrant substrates. Across systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (SSc), these pathways manifest as atrial fibrillation, ventricular arrhythmias, conduction disease, and heightened arrhythmic mortality. Anti Ro/SSA antibodies, in particular, contribute to QT prolongation and atrioventricular (AV) block, while cytokines such as TNF α, IL 1β, and IL 6 remodel electrophysiological properties and promote fibrosis. Advanced cardiac imaging, especially cardiac magnetic resonance (CMR), detects inflammation and fibrosis even when ejection fraction is preserved, enabling earlier intervention. Management requires a dual approach: standard arrhythmia therapies alongside aggressive control of systemic inflammation with disease-specific immunosuppression. Despite growing evidence, major gaps remain, including the absence of randomized trials targeting immune-driven arrhythmias and the need for integrated risk models incorporating inflammatory biomarkers. Full article

Background: This study evaluated the analgesic efficacy of the serratus posterior superior intercostal plane block (SPSIPB) in patients undergoing CIED implantation. Methods: In this study, 60 patients undergoing primary CIED implantation were randomized to receive either ultrasound-guided SPSIPB (n = 30) or a sham-control group procedure (n = 30). The primary outcome was perioperative pain intensity, assessed using the Visual Analog Scale (VAS) intraoperatively and at 3, 6, 12, and 24 h postoperatively. Secondary outcomes included postoperative sleep quality measured by the Sleep Quality Numeric Rating Scale (SQ-NRS), patient and physician satisfaction scores. Results: SPSIPB significantly reduced pain scores at all time points compared with the control group (all p < 0.001). Clinically significant intraoperative pain (VAS ≥ 4) occurred in 83.3% of controls but in none of the SPSIPB patients (p < 0.001). Postoperatively, clinically significant pain dropped from 93.3% in controls to just 3.3% with SPSIPB (p < 0.001), with the block group maintaining significantly lower pain scores at 3, 6, 12, and 24 h (mean reductions vs. control of 4.70, 4.13, 3.97, and 1.90 points, respectively; p < 0.001). SQ-NRS scores were lower in the SPSIPB group than in the control group (median 2 vs. 7, p < 0.001). Poor sleep quality (SQ-NRS ≥ 6) was observed in 80.0% of controls and in none of the SPSIPB patients. Patient and physician satisfaction were significantly higher in the SPSIPB group (median Likert score: 5 vs. 3, p < 0.001). Conclusions: Preoperative SPSIPB was associated with substantially lower perioperative pain scores and reduced rescue analgesic requirements during the first 24 h after CIED implantation. Improvements in postoperative sleep quality and patient–physician satisfaction were also observed; however, these secondary outcomes should be interpreted as exploratory. Larger multicenter trials are warranted to confirm the magnitude and generalizability of these findings. Full article

Transseptal puncture (TSP) is a critical technique for accessing the left atrium in various structural and electrophysiological cardiac procedures. Originally introduced for diagnostic catheterization in the mid-20th century, it has evolved into a cornerstone of modern interventional cardiology. This article was designed as a targeted narrative review, rather than a systematic or comprehensive review, and synthesizes selected peer-reviewed evidence spanning 1955 to 2025, retrieved through a targeted literature search. We explore the anatomical foundations of TSP, its historical development, and modern refinements such as radiofrequency-assisted puncture, balloon septoplasty, and fluoroless or image-fusion-guided access. Clinical applications—including mitral valve interventions, left atrial appendage closure, and decompression during extracorporeal membrane oxygenation (ECMO)—are reviewed alongside safety considerations and complication management strategies. Advances in imaging modalities, including three-dimensional echocardiography and computed tomography, have enhanced precision and safety. Because of the narrative design, the review emphasizes clinical relevance, procedural applicability, and evidence synthesis without formal risk-of-bias scoring or quantitative evidence grading. Overall, TSP demonstrates a high success rate and low complication profile when performed with appropriate imaging and operator expertise. Ongoing innovation in technique and technology continues to expand its utility across cardiac disciplines. Full article

Older adults and individuals with chronic obstructive pulmonary disease (COPD) are vulnerable to the harmful health effects of fine particulate matter (PM_2.5), which are partly driven by systemic inflammation. This study examined whether older adults with COPD exhibit greater inflammatory responses to PM_2.5 than age-matched healthy controls. We compared circulating high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-alpha in 38 patients with COPD (73.6 ± 7.1 years) and 20 controls (70.9 ± 5.2 years) during high- and low-pollution periods. In the COPD group, 65.8% used inhaled corticosteroids and 42.1% used statins; 65.0% of controls used statins. Mean PM_2.5 concentrations were higher in the high-pollution period than the low-pollution period (79.1 ± 23.3 vs 13.9 ± 3.6 µg/m³; p < 0.001). Across both periods, IL-8 was higher in COPD than in controls, without significant within-group increases during high pollution. These findings indicate higher baseline systemic inflammation in COPD, while pollution-associated increases may be attenuated by anti-inflammatory medications. However, this should be interpreted cautiously given the observational design. Full article