Search Results (245)

Obesity and obstructive sleep apnea (OSA) frequently coexist and synergistically contribute to cardiovascular disease through interconnected mechanical, metabolic, and autonomic mechanisms. This interplay promotes myocardial electrical instability and structural remodeling, favoring the development and persistence of cardiac arrhythmias, particularly atrial fibrillation. Among the key mediators linking obesity to arrhythmogenesis, epicardial adipose tissue has emerged as a relevant factor that may contribute to local pro-inflammatory, pro-fibrotic, and autonomic effects on the myocardium. In parallel, OSA-related intermittent hypoxia and intrathoracic pressure swings further amplify electrical instability and autonomic imbalance, reinforcing a self-sustaining arrhythmogenic substrate. Therapeutic strategies are increasingly shifting toward upstream interventions targeting these underlying mechanisms. Metabolic therapies, including the dual GIP/GLP-1 receptor agonist tirzepatide, have demonstrated substantial weight reduction and improvement in OSA severity, with potential indirect benefits on arrhythmic risk through modulation of visceral adiposity, inflammation, and metabolic dysfunction. On the electrophysiological side, cardioneuroablation has emerged as a potentially investigational option in selected patients with vagally mediated bradyarrhythmias, although its role remains to be fully defined. Overall, these observations support an integrated, phenotype-driven approach combining respiratory therapy, metabolic modulation, and targeted electrophysiological interventions. This framework may help redefine therapeutic priorities, shifting from symptom control toward modification of the underlying arrhythmogenic substrate and improvement of long-term cardiovascular outcomes. Full article

Background: H1-antihistamines are widely used for allergic and upper respiratory conditions; however, several agents included in this class have been associated with cardiac electrophysiological adverse effects, including QT interval prolongation and torsades de pointes (TdP). These effects are largely exposure-dependent and mechanistically linked to inhibition of cardiac ion channels. Chlorpheniramine maleate (CPM), a first-generation H1-antihistamine, has been implicated in arrhythmic events primarily under conditions of increased systemic exposure, prompting interest in whether alternative routes of administration may lower cardiac risk. Methods: This narrative review integrates mechanistic, preclinical, clinical, pharmacokinetic, and regulatory evidence. Information was extracted from PubMed, Google Scholar, and Scielo using search terms such as cardiotoxicity, chlorpheniramine, QT prolongation, intranasal administration, and cardiac arrhythmias, with no language restriction. Results: Comparative pharmacokinetic evidence shows that, on a dose-normalized basis, intranasal and oral chlorpheniramine exhibit comparable bioavailability; however, in a clinical context, intranasal doses (1.12–2.24 mg) are lower than oral daily doses (4–12 mg/day), resulting in a lower systemic exposure (Cmax and AUC) with intranasal administration. Available pharmacovigilance or epidemiological data have not specifically evaluated intranasal chlorpheniramine, and the number of dedicated safety trials remains limited. Conclusions: Preclinical, in vitro, mechanistic studies suggest that intranasal administration of chlorpheniramine should confer superior cardiac safety compared to the oral route. However, clinical data from human studies directly comparing the cardiac safety of intranasal chlorpheniramine versus systemic chlorpheniramine is extremely limited. More data from clinical trials, case–control studies, and regulatory databases are needed to validate these theoretical claims. Full article

Background/Objectives: Electroanatomic mapping (EAM) provides high-resolution spatial and electrogram information, but the prognostic utility of quantitative EAM features has not been systematically evaluated with contemporary artificial intelligence (AI) methods. We investigated whether an AI analysis of quantitative EAM exports from the CARTO system enhances the prediction of major arrhythmic events (MAEs). Methods: In this retrospective, multicenter cohort study, 248 consecutive patients undergoing left ventricular EAM at four tertiary electrophysiology centers were analyzed. Numerical EAM descriptors (spatial coordinates, unipolar/bipolar voltages, local activation time, impedance) were transformed into derived metrics, including local activation heterogeneity (GR), late-potential extent (LAT), bipolar–unipolar discrepancy (VLT), and low-amplitude scar extent (Scar Areas), and were spatially normalized via spherical projection. Clinical, anamnestic, and imaging variables were integrated. Machine learning and deep learning models were trained with an 80:20 train/test split and evaluated using three-fold cross-validation. Performance metrics included area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and precision. Results: Models incorporating both clinical and AI-processed EAM features achieved high discriminatory performance (test AUC up to 0.92; accuracy up to 0.896). Specificity was consistently high (≈0.97–0.998), whereas sensitivity remained modest (≈0.39–0.58). Among the EAM-derived features, GR was the most consistently informative predictor across algorithms and analyses; VLT, LAT, and Scar Areas also contributed substantially. Regionally, basal sub-mitral, subaortic, and posterolateral basal-to-mid zones exhibited the strongest associations with MAEs. Conclusions: AI-driven quantitative analysis of left ventricular EAM exports augments risk stratification for MAEs beyond conventional clinical and binary EAM descriptors. Reflecting local conduction heterogeneity, GR emerged as the dominant EAM predictor. Prospective validation in larger, disease-specific cohorts and real-time integration within EAM platforms are warranted. Full article

Cardiac arrest is a way of demise of patients who are affected by heart failure (HF), being more frequent in those with HF with a reduced left ventricular ejection fraction (HFrEF), and is, as such, responsible for 30–50% of cardiac death. Specific data on the risk of sudden cardiac death (SCD) related to HF with a preserved ejection fraction (HFpEF) and HF with a mildly reduced ejection fraction (HFmrEF) are lacking, as well as data regarding ventricular arrhythmias in this population. Considering the 0.3% person/year incidence rate of investigator-reported ventricular tachycardia (VT) and ventricular fibrillation (VF), the rate of SCD in the analyzed population seems to be 1.3% per year. Age, gender, history of diabetes and myocardial infarction, left bundle branch block (LBBB) on electrocardiogram (ECG), and a natural logarithm of N-terminal pro B-type natriuretic peptide (NT-proBNP), identified a subgroup of HFpEF patients with a higher risk (5-year cumulative incidence of 11%) of sudden death (SD). In HFpEF patients, both glifozins and finerenone did not demonstrate a beneficial effect on SCD incidence in comparison to placebo. A significantly lower rate of SCD emerged in patients who were treated with dapaglifozin (10 vs. 26 pts) among patients with HF with an improved ejection fraction (HFimpEF), who were defined as patients with a previous left ventricular ejection fraction (LVEF) < 40%. Promising methods discussed include cardiac magnetic resonance, myocardial scintigraphy, genetic assessment, and electrophysiologic studies for predicting SCD in those patients. In conclusion, arrhythmic SCD in HFpEF patients should not be considered merely as an effect of VT/VF; bradyarrhythmia is probably more frequent and dangerous. The effects of drugs in preventing SCD in HFpEF have not been demonstrated yet. Full article

Background: Pacemakers enable continuous long-term surveillance of atrial fibrillation detected by implanted devices. Circulating biomarkers reflecting endothelial dysfunction, inflammation, and myocardial stress may help identify patients at risk for atrial fibrillation (AF) progression and higher arrhythmic burden. Methods: This analysis included patients from the prospective ACaSA study (NCT05127720) with a dual chamber pacemaker (Microport^® BOREA DR or TEO DR) and monitored weekly via remote monitoring technology (SMARTVIEW^®). Individuals with permanent AF or single-chamber systems were excluded. Baseline plasma concentrations of angiopoietin-2 (ANGPT2), growth differentiation factor-15 (GDF-15), fibroblast growth factor-23 (FGF-23), bone morphogenetic protein-10 (BMP10), and tumor necrosis factor–related apoptosis-inducing ligand receptor-2 (TRAIL-R2) were quantified using enzyme-linked immunosorbent assays. N-terminal pro-B-type natriuretic peptide (NT-proBNP) was measured using electrochemiluminescence immunoassay. Biomarkers were log₂-transformed, with values below assay detection limits imputed at half the lower limit of detection. Two endpoints were assessed following a 30-day blanking period: (1) progression to persistent AF, defined as ≥7 consecutive days with >99% daily AF burden, analyzed using Cox regression; and (2) AF burden, calculated as total AF time normalized to monitored days and categorized as <25%, 25–75%, or >75%, analyzed using multinomial logistic regression. Multivariable models were adjusted for age, sex, heart failure, diabetes, and prior myocardial infarction; Cox models were limited to age, sex, and heart failure due to fewer events. Results: A total of 223 patients were included (median age 75 years; 37.2% women). During follow-up, 28 patients (13.3%) progressed to persistent AF. Higher baseline ANGPT2 was the strongest predictor of progression (HR per doubling 1.83, 95% CI 1.27–2.66, p = 0.001), followed by GDF-15 (HR 1.52, 95% CI 1.03–2.24, p = 0.036). In the burden analysis, ANGPT2 demonstrated a pronounced graded relationship with arrhythmic load, with markedly increased odds of high (>75%) AF burden (OR 8.31, 95% CI 2.63–26.26, p < 0.001). GDF-15 independently predicted both medium (OR 2.05, p = 0.025) and high burden (OR 2.32, p = 0.037). NT-proBNP displayed a borderline association with high burden (OR 2.02, p = 0.061). No significant associations were observed for FGF-23, BMP10, or TRAIL-R2. Conclusions: In continuously monitored pacemaker patients, ANGPT2 and GDF-15 emerged as key biomarkers associated with AF disease severity. ANGPT2 was strongly linked to both progression to persistent AF and high AF burden, whereas GDF-15 consistently predicted higher AF burden and also contributed to risk of progression. These findings highlight endothelial and inflammatory pathways as potential markers of atrial disease progression. Full article

Kv11.1 (hERG1) channels, encoded by KCNH2, mediate the rapid delayed rectifier potassium current (I_Kr) crucial for cardiac repolarization. Disruptions, via mutations or antiarrhythmic drugs like dofetilide cause severe arrhythmogenic disorders, including Long QT Syndrome Type 2 (LQT2), Brugada Syndrome (BrS), and Torsades de Pointes (TdP). While Kv11.1’s role in channelopathies and drug-induced arrhythmias is established, understanding its complex regulation and therapeutic targeting remains a challenge. This review synthesizes the structural, functional, and regulatory aspects of Kv11.1 channels and their clinical implications. Recent studies using iPSC-derived cardiomyocytes highlight regulation by PI3K/Akt, PKC, and PKA signaling via phosphorylation (Ser283, Ser890) and interactions with proteins like 14-3-3. Beyond electrophysiology, Kv11.1 influences pathological hypertrophy and non-cardiac functions including insulin secretion. Pharmacological efforts focus on activators to shorten action potential duration and suppress TdP, and blockers with overdose risks. Mutation heterogeneity, exemplified by trafficking impairment (G785D) in LQT2 and gain-of-function (R397C) in BrS, complicates precision therapy. Clinically, systematic risk stratification using electrocardiographic parameters and genotype-specific approaches enables personalized management. Beta-blockers remain first-line therapy for LQTS2, while rigorous avoidance of QT-prolonging medications and electrolyte monitoring form the cornerstones of preventive care. Advancing Kv11.1-targeted therapies with approaches like CRISPR-Cas9 and pharmacological chaperones (e.g., lumacaftor) holds promise for personalized treatments, ultimately reducing arrhythmic events and sudden cardiac death. Full article

Background: Sudden cardiac death (SCD) is a major challenge in dilated (DCM) and non-dilated left ventricular cardiomyopathy (NDLVC). Current management strategies, based on left ventricular ejection fraction (LVEF), the presence or extent of myocardial scar, and selected high-risk genetic variants, are insufficient to accurately identify patients at risk. Mechanical dispersion (MD), derived from speckle-tracking echocardiography, is a potential marker of arrhythmic risk that reflects variability in regional myocardial contraction timing. Aim: The purpose of this narrative review is to synthesize current evidence on the predictive role of MD for ventricular arrhythmias (VA) and SCD in DCM and NDLVC, with particular emphasis on its relationship to myocardial fibrosis (MF) and established echocardiographic markers. Results: Across prospective and retrospective cohorts of DCM patients, increased MD has consistently identified individuals at higher arrhythmic risk, often independently of LVEF and global longitudinal strain (GLS). Reported threshold values for risk prediction range from 50 ms to 90 ms, with hazard ratios confirming incremental prognostic accuracy. The relationship between MD and MF assessed by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) remains uncertain: some patients experience VA in the absence of LGE, while others display elevated MD despite no detectable focal MF, suggesting that additional mechanisms contribute to the arrhythmogenic substrate in DCM and NDLVC. Conclusions: MD may enhance SCD risk stratification in DCM and NDLVC by reflecting components of the arrhythmic substrate that are not detected by conventional markers. Full article

Climate change has transformed extreme heat from a transient environmental perturbation into a persistent threat that worsens cardiovascular outcomes. Epidemiological studies show a lag between heat exposure and peaks in acute myocardial infarction (AMI) mortality, indicating a subclinical, latent vulnerability. This latent vulnerability likely originates at the level of the microvasculature, as cardiac microvascular endothelial cells (CMECs)—the heart’s primary “thermal sensors”—are uniquely susceptible to proteotoxic stress. The existing literature suggests that this sensitivity may be mediated by thermodynamically gated activation of the activating transcription factor 6 (ATF6) branch of the unfolded protein response (UPR), which could function as a master switch that reprograms endothelial cells from a pro-repair to a maladaptive, anti-angiogenic phenotype. However, this mechanism is derived primarily from preclinical studies and lacks direct validation in humans. The resulting “endothelial memory” is sustained by epigenetic modifications and organelle uncoupling; it persists beyond the initial insult and impairs subsequent neovascularization. As a result, ischemia occurs later in a compromised microenvironment, promoting a fibrosis–conduction mismatch that drives infarct expansion and arrhythmic risk. Thus, the post-exposure latent phase emerges as a novel therapeutic window: Precision targeting of the ER stress–angiogenesis axis during this period offers a focused strategy to protect heat-vulnerable individuals Full article

Inherited cardiomyopathies associated with high-risk genotypes, are characterized by a disproportionate risk of malignant ventricular arrhythmias and sudden cardiac death, often independent of left ventricular systolic dysfunction or advanced structural remodeling. Traditional surveillance strategies based on intermittent electrocardiography and phenotype-driven risk assessment are insufficient to capture the dynamic and often silent progression of electrical instability in these populations. This narrative review evaluates the emerging role of artificial intelligence (AI)-enabled sensor technologies in remote arrhythmic monitoring of genetically defined cardiomyopathy cohorts. Wearable ECG devices, implantable cardiac monitors, multisensor cardiac implantable electronic device algorithms, pulmonary artery pressure sensors, and contact-free systems enable continuous acquisition of electrophysiological and hemodynamic data, generating digital biomarkers that may reflect early arrhythmic vulnerability and subclinical decompensation. AI-driven analytics enhance signal processing, automated event detection, and remote data triage, with the potential to reduce clinical workload while preserving diagnostic sensitivity. However, current evidence predominantly derives from heterogeneous heart failure or general arrhythmia populations, and prospective validation in genotype-specific cohorts remains limited. Key challenges include algorithm generalizability, signal quality in ambulatory environments, data governance, interpretability of AI models, and integration into structured remote-care pathways. The convergence of genotype-informed risk stratification and multimodal AI-enabled sensing represents a promising strategy to transition from reactive device-based protection to proactive, precision-guided arrhythmic prevention. Dedicated genotype-focused studies and standardized digital endpoints are required to support safe and effective implementation in inherited cardiomyopathies. Full article

Inherited cardiomyopathies represent a major cause of ventricular arrhythmias (VA) and sudden cardiac death (SCD), frequently occurring in the absence of advanced systolic dysfunction. Traditional strategies for the primary prevention of SCD have relied predominantly on left ventricular ejection fraction (LVEF), an approach that fails to capture the substantial biological and clinical heterogeneity of non-ischemic cardiomyopathies. Over the past decade, advances in cardiac genetics and cardiac magnetic resonance imaging have identified specific genotypes associated with a disproportionate arrhythmic risk, which often precedes overt ventricular remodeling. The 2023 European Society of Cardiology (ESC) Guidelines on cardiomyopathies formalize this paradigm shift by integrating etiology, myocardial substrate, and electrical phenotype into contemporary risk stratification. In this narrative review, we focus on cardiomyopathy-associated genotypes consistently linked to high arrhythmic risk—LMNA, truncating variants in FLNC, RBM20, PLN p.Arg14del, and desmosomal genes—and examine their molecular mechanisms, phenotypic trajectories, and arrhythmogenic profiles. We discuss how genotype-specific patterns of myocardial fibrosis, conduction disease, and VA inform implantable cardioverter-defibrillator (ICD) decision-making beyond LVEF-based thresholds. By synthesizing genetic, imaging, and clinical evidence in light of ESC 2023 recommendations, this review highlights the evolving role of genotype-informed strategies in the personalized prevention of SCD and underscores remaining gaps in evidence and risk prediction. Full article

Type 2 diabetes mellitus is associated with major cardiovascular complications, including cardiac autonomic neuropathy, which contributes to sympathetic–parasympathetic imbalance and increases susceptibility to arrhythmias and sudden cardiac death. Heart rate variability, assessed through R–R intervals on electrocardiography and 24 h Holter monitoring, represents a sensitive, non-invasive marker of autonomic dysfunction and arrhythmogenic risk. In patients with type 2 diabetes mellitus, chronic hyperglycaemia, oxidative stress, and metabolic inflammation lead to early impairment of the autonomic nervous system, manifested by consistent reductions in SDNN, RMSSD, pNN50, total power, and the high-frequency component, indicating diminished parasympathetic tone and sympathetic predominance. Nonlinear HRV indices demonstrate a loss of complexity and fractal organisation, providing additional prognostic value beyond conventional time- and frequency-domain analyses. Reduced HRV correlates with the severity of cardiac autonomic neuropathy, duration of diabetes, and poor glycaemic control, identifying patients with increased arrhythmogenic vulnerability. HRV analysis enables prediction of arrhythmic risk, facilitating the identification of high-risk individuals and guiding personalised interventions. The integration of HRV assessment into routine clinical practice may improve the early detection of subclinical autonomic neuropathy and optimise cardiovascular risk stratification and management in patients with type 2 diabetes mellitus. Full article

Sudden cardiac death (SCD) is a major global health issue, defined as sudden natural death presumed to be of cardiac cause. While in the elderly SCD is commonly associated with coronary artery disease, in the younger population it is linked to inherited cardiomyopathies or channelopathies, even though SCD can remain unexplained even after a comprehensive autopsy in a substantial proportion of cases. In this context, genetic testing has gained importance, supported by the widespread availability of techniques such as next-generation and whole-exome/genome sequencing and their reduced costs. This state-of-the-art review summarizes the genetic bases of sudden cardiac death among cardiomyopathies, channelopathies and in sudden unexplained death presumed to be of arrhythmic cause. Among the structural causes, inherited cardiomyopathies such as hypertrophic, dilated, non-dilated left ventricular, arrhythmogenic right ventricular and restrictive ones represent major substrates for malignant ventricular arrhythmias mostly arising from variants in sarcomeric or desmosomal genes. Channelopathies (long or short QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia) are caused by variants in genes encoding cardiac ion channels and/or regulatory proteins, which equally predispose to high risk of life-threatening ventricular arrhythmias. In sudden arrhythmic death syndrome, with a structurally normal heart, post-mortem genetic testing (molecular autopsy) can uncover an underlying inherited condition. However, variants of uncertain significance are detected in more than half of the cases, underscoring the need for a multidisciplinary approach. Genetic testing also plays a key role in cascade screening of first-degree relatives. While monogenic variants drive risk in inherited cardiac disorders, emerging evidence suggests that polygenic contributions may modulate SCD susceptibility, highlighting future roles for polygenic risk scores in risk stratification. Full article

Background: Hypertrophic cardiomyopathy (HCM) is associated with an elevated risk of ventricular arrhythmias and sudden cardiac death (SCD) despite contemporary therapy. Cardiac myosin inhibitors directly target sarcomeric hypercontractility and have demonstrated consistent symptomatic, hemodynamic, and structural benefits in randomized controlled trials (RCTs). However, their effects on malignant ventricular arrhythmias and SCD remain uncertain. This meta-analysis aimed to evaluate the incidence of ventricular arrhythmias and SCD with cardiac myosin inhibitor therapy in HCM. Methods: We conducted a meta-analysis of RCTs evaluating mavacamten or aficamten in patients with HCM. PubMed was systematically searched through September 2025. Eligible trials randomized myosin inhibitors versus control and reported ventricular tachycardia (VT), ventricular fibrillation (VF), or SCD. Results: Seven RCTs including 1519 patients (779 myosin inhibitor; 740 control) were analyzed. Eight composite VT/VF/SCD events (1.03%) occurred in the treatment group compared with twelve (1.62%) in controls. Time-standardized incidence rates were 1.48 versus 2.36 per 100 patient-years, respectively. The pooled RR was 0.69 (95% CI 0.27–1.74; I² = 0%), indicating no statistically significant difference. Sensitivity analyses yielded concordant results despite low event counts. Conclusions: No statistically significant increase in ventricular arrhythmia or SCD risk was observed. However, limited events and short follow-up preclude firm conclusions regarding the arrhythmic safety of myosin inhibitors. Full article

Background: Atrial arrhythmias represent a frequent long-term complication in patients with atrial septal defects (ASDs). Interatrial block (IAB), reflecting delayed or impaired conduction across Bachmann’s bundle, has been proposed as an electrophysiological substrate predisposing to atrial arrhythmogenesis. However, evidence regarding its prevalence and clinical correlates in pediatric patients with ASD remains limited. The present study aimed to characterize interatrial conduction patterns and assess the occurrence of IAB in children with large secundum ASD undergoing percutaneous closure. Methods: Between January 2020 and March 2024, 37 consecutive pediatric patients (median age 6 years, range 5–11) with large ostium secundum ASD were included in a retrospective analysis of a prospectively maintained institutional database. Standard 12-lead electrocardiograms were recorded before and within 24 h after defect closure. P-wave morphology and duration were systematically analyzed, and IAB was classified according to the Bayés de Luna criteria. Results: The median Qp/Qs ratio was 1.69 (1.32–2.24), with a mean pulmonary artery pressure of 19 mmHg (17–22). IAB was identified in 24.3% of patients before the procedure, predominantly as first-degree IAB. Following device implantation, IAB prevalence (29.7%) and P-wave parameters remained unchanged, with no significant differences compared with baseline. No associations were observed between IAB and defect size, hemodynamic burden, or device characteristics, whereas anthropometric variables, including weight, height, and body surface area, showed a significant correlation with IAB occurrence. During a median follow-up of 199 days, no atrial arrhythmias were documented. Conclusions: In this pediatric cohort with large ASD, IAB was present in approximately one quarter of patients and appeared unrelated to anatomical or procedural factors, supporting the hypothesis of an underlying congenital conduction abnormality. Early recognition of IAB may therefore have implications for long-term arrhythmic risk stratification in this population. Full article

Hot springs, hot-water bathing, and saunas are widely practiced forms of acute heat exposure and are often perceived as health-promoting. However, emergency clinicians frequently encounter patients in whom these exposures precipitate syncope, hypotension, drowning/aspiration, heat-related illness, and renal or electrolyte disturbances. This narrative review integrates these modalities within a unified “acute heat exposure” framework and summarizes pathophysiology and clinical implications from an emergency medicine perspective. We searched PubMed/MEDLINE from inception to January 2026 using controlled vocabulary and free-text terms related to heat stress, thermoregulation, hot-water immersion, sauna exposure, and acute clinical outcomes; evidence was synthesized qualitatively. Across modalities, acute heat exposure induces shared physiological responses—peripheral vasodilation, relative hypovolemia, circulatory stress, and internal heat storage—that can trigger diverse emergency presentations. We classify acute heat exposure–related illness into four domains: (1) cardiovascular events, including syncope, hypotension, and arrhythmic/ischemic complications in vulnerable individuals; (2) the heat-illness spectrum from exhaustion to heat stroke with organ dysfunction; (3) renal and electrolyte disturbances related to dehydration and hypoperfusion; and (4) neurological and traumatic complications, including falls, drowning, and aspiration. This framework may support risk stratification, evaluation, management, and prevention after hot spring, hot bath, or sauna use. Full article