Search Results (27)

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 and Objectives: The interaction between the brain and heart has become more interesting in the last 20 years. The most common cardiac complications after stroke are myocardial infarction, heart failure, arrhythmias, electrocardiographic disturbances, repolarization disorders, and sudden cardiac death. The prolonged Tpeak–Tend interval is an indicator of the electrical heterogeneity of the myocardium (abnormal repolarization) that causes malignant arrhythmias. We aimed to investigate whether the Tpeak–Tend interval, which reflects the heterogeneity of repolarization, is prolonged in stroke and its relationship with short-term mortality. Materials and Methods: Individuals over the age of 18 who presented with hemorrhagic or ischemic stroke were included in the study. Demographic characteristics, laboratory and imaging findings of the patients were recorded. ECGs were obtained at the time of admission to the hospital and 24 h later. Patients were followed for in-hospital mortality. Results: 89 (82.4%) of the patients had ischemic stroke, 19 (17.6%) had hemorrhagic stroke. It was determined that Tp-eV2 and Tp-eV5 at hospital admission were significantly longer than the 24th hour values. A total of 92.01 (16.3) ms at Tp-eV2 admission, 84.1 (16.3) ms after 24 h (p = 0.003), 91.9 (7.3) msTp-eV5 at admission, and 81.6 (17.8) ms (p = 0.000) after 24 h. In multivariate logistic regression analysis of in-hospital mortality, Tp-eV2 (HR: 0.96 (95% CI 0.93–0.99) p = 0.008) was determined as an independent predictor among cardiovascular parameters. Conclusions: Tp-e intervals were prolonged in both leads V2 and V5 in patients with stroke. Prolongation of lead V2 in the Tp-e interval is an independent indicator of short-term mortality among cardiovascular parameters. Full article

Type 2 diabetes mellitus and prediabetes often develop silently and may remain undiagnosed for years. This is particularly relevant in regions where laboratory-based screening is not always readily accessible. Against this background, the present work explores whether multilead electrocardiography can provide physiologically meaningful markers potentially associated with disturbances in glucose metabolism. We developed and tested an upgraded wearable 12-lead ECG system capable of synchronized multichannel recording under controlled conditions. ECG signals were acquired in sitting and standing positions, with a sampling frequency of 500 Hz and a recording duration of one minute per posture. The hardware architecture included a high resolution analog front-end and wireless data transmission; the accompanying software provided acquisition control, preprocessing, visualization, and data storage within a unified framework. Signal processing focused on the extraction of rhythm-related and morphological parameters, with particular attention to ventricular repolarization indices. QT interval, heart rate–corrected QT (QTc), and QT dispersion (QTd) were calculated across leads, as these parameters are known to reflect heterogeneity of repolarization and autonomic influences on myocardial electrophysiology. The analysis was structured to ensure reproducible boundary detection and systematic feature formation rather than isolated parameter measurement. The study had a pilot character and included a limited and unbalanced sample (healthy n = 10; prediabetes n = 1; T2DM n = 1). For this reason, the results are presented descriptively and should be regarded as preliminary observations. In representative cases, differences in QT-related indices were noted between categories of glycemic status; however, the potential influence of age, sex, and other confounders cannot be excluded. A pilot expert comparison of T-wave end detection demonstrated close agreement between the automated algorithm and cardiologist assessment (mean Δ$T_{end}$ approximately −1 to −2 ms; MAE 10–24 ms). Diagnostic performance metrics such as ROC/AUC, sensitivity, and specificity were not calculated at this stage, as validation in a larger cohort with biochemical confirmation (HbA1c, OGTT) is required. The study demonstrates the technical feasibility of combining synchronized 12-lead wearable acquisition with structured multilead repolarization analysis. The proposed system should therefore be considered a research platform intended to support further clinical validation and methodological development rather than a finished screening solution. Full article

Background: Ischemic heart disease is the primary contributor to global mortality. The QRS-T angle at the anterior aspect of the heart serves as a significant biomarker of the heterogeneity in myocardial repolarization and the electrophysiological instability of the cardiac myocytes. A wide frontal QRS-T angle is associated with proximal vascular disease, coexistence of three-vessel disease, and increased mortality. Hereby, we aimed to examine the relationship between collateral circulation and frontal QRS-T angle in patients with chronic total occlusion (CTO). Methods: A cohort comprising 120 patients (17 females, 14.1%) who received a diagnosis of chronic total occlusion (CTO) subsequent to the administration of coronary angiography conducted for the evaluation of stable angina pectoris was incorporated into the investigation. The electrocardiographs of the patients were evaluated in detail, and the frontal QRS-T angle was calculated. The patients were categorized into two groups: subjects exhibiting an increased frontal QRS-T angle (>110° for men, >90° for women) and those presenting with a normative frontal QRS-T angle. Coronary angiographies of the patients were analyzed, and coronary collateral circulation was classified according to Rentrop classification. Results: Serum albumin level (OR = 0.711, 95% CI 0.564–0.896; p = 0.004) and poor collateral flow (OR = 17.7, 95% CI 12.2–85.3; p < 0.001) were significant predictors of raised frontal QRS-T angle. Conclusions: The frontal QRS-T angle is a novel parameter that is more reliable, consistent, and less sensitive to miscalculation and misidentification than other conventional electrocardiographic myocardial repolarization parameters. Revealing the bad collateral relationship with the frontal QRS-T angle may enable physicians to take more stringent precautions and change the risk factors related to the increased QRS-T angle in advance. Full article

Background: Thyroid dysfunction is a prevalent endocrine disorder with significant cardiovascular consequences, particularly through its effects on cardiac electrophysiology. Electrocardiography (ECG), as a widely available and cost-effective diagnostic tool, provides valuable insight into these alterations. This systematic review and meta-analysis aimed to evaluate the relationship between thyroid hormone imbalance and ECG parameters. Methods: A comprehensive search of PubMed, ScienceDirect, and Google Scholar identified 1099 studies, of which 121 underwent full-text analysis. Ultimately, 37 studies with complete datasets were included in the quantitative synthesis, encompassing 167,074 participants across overt hyperthyroidism, subclinical and overt hypothyroidism, and euthyroid control groups. Results: Meta-analysis revealed significant alterations in key electrophysiological markers. Overt hyperthyroidism was associated with QTc and Tp-e prolongation, consistent with increased repolarization heterogeneity and arrhythmic risk. In overt hypothyroidism, QTc and Tp-e intervals were also prolonged, accompanied by reduced heart rate variability, reflecting autonomic imbalance. Subclinical forms demonstrated more variable results, though trends toward conduction and repolarization disturbances were observed. Importantly, several studies indicated that levothyroxine therapy or surgical treatment normalized abnormal ECG findings, underscoring their reversible nature. Conclusions: These results highlight the strong association between thyroid hormone abnormalities and ECG alterations, which may serve as early markers of arrhythmic risk and sudden cardiac death. Incorporating ECG screening into thyroid disease management could improve early detection, risk stratification, and cardiovascular prevention strategies. Full article

Background/Objectives: Pregnancy is associated with profound physiological alterations that, together with anemia and spinal anesthesia, may influence myocardial repolarization. The frontal QRS-T [f(QRS-T)] angle has emerged as a reliable electrocardiographic parameter for evaluating repolarization heterogeneity. Materials and Methods: This observational prospective study included 100 term pregnant women [18–45 years, American Society of Anaesthesiologists (ASA) II] undergoing elective cesarean delivery under spinal anesthesia at Sanliurfa Training and Research Hospital between May and August 2025. Participants were divided into two groups: anemic (Hb < 10.5 g/dL, n = 50) and non-anemic (Hb ≥ 10.5 g/dL, n = 50). Standard monitoring and 12-lead ECGs were performed preoperatively and postoperatively. The f(QRS-T) angle was calculated as the absolute difference between QRS and T axes; values > 180° were adjusted by subtracting from 360°. Results: Demographic variables were comparable between groups. No significant differences were observed in mean arterial pressure or heart rate. Preoperative QTc and f(QRS-T) angle values did not differ significantly. However, postoperative QTc was prolonged in the anemic group compared with non-anemic women (426.3 ± 19.2 ms vs. 417.2 ± 20.7 ms, p = 0.026). Likewise, the postoperative f(QRS-T) angle was significantly higher in anemic patients (29.5 [16.0–45.3] vs. 20.5 [9.8–34.5], p = 0.017). Within-group analysis revealed significant postoperative increases in both QTc (p < 0.001) and f(QRS-T) angle (p < 0.001) in the anemic group, but not in controls. Hemoglobin levels correlated negatively with postoperative QTc (r = −0.267, p = 0.008) and f(QRS-T) angle (r = −0.264, p = 0.008). Conclusions: In anemic patients undergoing cesarean delivery under spinal anesthesia, the postoperative QTc interval and f(QRS-T) angle increased significantly compared with both baseline values and non-anemic counterparts. Assessment of the f(QRS-T) angle, a simple and inexpensive ECG-derived parameter, may aid in perioperative risk stratification and enhance patient safety. Full article

Background/Objectives: Race-based cardiac screening criteria in sports cardiology, including the “Black athlete’s heart” concept, assume biological distinctions that may not reflect physiological reality. This systematic review evaluates whether geographic ancestry provides more clinically relevant predictors of cardiac adaptation than racial categorization. Methods: PubMed was searched (January 2005–July 2025) for studies examining cardiac adaptations in athletes by ethnicity. Data extraction captured demographics, geographic origin, cardiac assessments, and outcomes. Narrative synthesis was employed due to methodological heterogeneity. Results: Forty-seven studies (n = 66,130) revealed substantial within-race heterogeneity. The “Black athlete repolarization variant” prevalence ranged from 1.8% (Brazilian) to 30% (Ghanaian) Black athletes. Left ventricular wall thickness >12 mm (normal <11 mm) occurred in 7.1% of Black versus 0.4% of White athletes, yet varied significantly within Black populations—10.8 ± 1.2 mm in Sub-Saharan versus 9.4 ± 1.1 mm in African-American athletes (p < 0.001). Relative wall thickness ≥0.44 (normal ≤0.42) was presented in 43% of West/Middle African, 23% of East African, and 7% of White athletes. T-wave inversion showed four-fold variation within Black populations (3.6–8.5% West African versus 0.5–2.0% African-American/Caribbean). Current International Criteria demonstrated inequitable specificity: 3.3% false-positive rate in Black versus 1.4% in White athletes. Conclusions: Geographic ancestry explains more cardiac variation than racial categories, supporting contemporary understanding of race as a sociopolitical construct. The persistent diagnostic disparities in ECG screening specificity highlight the need for reform. Transitioning toward protocols incorporating continental origin, anthropometric factors, and social determinants of health—while eliminating terminology like “Black athlete’s heart”—represents an important step toward achieving equity in cardiovascular care for diverse athletic populations. Full article

Background and Objectives: Obstructive sleep apnea syndrome (OSAS) and heart failure (HF) frequently coexist, amplifying cardiovascular risk through mechanisms involving chronic inflammation and autonomic dysfunction. This study investigates the impact of systemic inflammation, measured by the systemic immune-inflammation index (SII), and OSAS severity, assessed by the apnea–hypopnea index (AHI), on myocardial repolarization heterogeneity in patients with both conditions. Materials and Methods: In this retrospective study, 160 patients with HF and polysomnography-confirmed OSAS (AHI ≥ 5 events/h) were evaluated between January 2018 and November 2024. Patients were stratified by QT dispersion (QTd < 40 ms vs. ≥40 ms) to assess electrical heterogeneity. SII was calculated from neutrophil, platelet, and lymphocyte counts, and electrocardiographic markers (QTd, frontal QRS-T angle, T wave peak-to-end interval [TPEI]) were measured. Logistic regression and receiver operating characteristic (ROC) analyses were used to identify predictors of repolarization heterogeneity and ventricular arrhythmias. Results: Patients with QTd ≥ 40 ms (n = 78) exhibited higher SII (p < 0.001) and AHI (p < 0.001) compared to those with QTd < 40 ms (n = 82). SII and AHI independently predicted increased QTd in multivariate analysis (p = 0.01 and p < 0.001, respectively). ROC analysis identified SII ≥ 625.4 (sensitivity 73.1%, specificity 72%) and AHI ≥ 22.4 (sensitivity 79.5%, specificity 79.3%) as optimal cut-offs for predicting repolarization heterogeneity. SII, QTd, and TPEI were significantly associated with ventricular arrhythmias (p < 0.05). Patients with moderate-to-severe OSAS (AHI ≥ 15) had higher rates of ventricular tachyarrhythmias (17.8% vs. 5.7%, p = 0.03) and sudden cardiac death (9.3% vs. 1.9%, p = 0.05). Conclusions: Elevated SII and AHI are independent predictors of myocardial repolarization heterogeneity in patients with HF and OSAS, contributing to increased arrhythmic risk. These findings highlight the potential use of SII and AHI as accessible biomarkers for risk stratification, particularly in patients with a preserved ejection fraction, and underscore the need for targeted interventions to mitigate inflammation and OSAS severity. Full article

In metabolic syndrome, cardiomyocyte changes induced by metabolic and proinflammatory factors impair repolarization and exacerbate the heterogeneity of the transmural dispersion of repolarization, and this is proarrhythmogenic. Limited data in the literature on the capabilities of speckle tracking echocardiography for assessing proarrhythmogenicity in metabolic syndrome exists. 71 patients with newly diagnosed metabolic syndrome, aged 35–55 years, were studied. Ischemic heart disease was excluded in all patients with stress test cycle ergometry, CT-angiography or selective coronary angiography. All patients underwent a 48-h Holter ECG recording. Based on the latter, they were divided into two groups: 38 patients (53.5%) with a high arrhythmogenic load (supraventricular or ventricular tachycardia, atrial fibrillation/flutter, ventricular extrasystoles over 10%, frequent supraventricular extrasystoles > 500/24 h are included); and 33 patients (46.5%) with low arrhythmogenic load (no significant rhythm disturbances are included). Echocardiography was performed with a GE Vivid T9 emphasizing global longitudinal strain, mechanical dispersion index and left atrium strains. Statistically significant differences in the global longitudinal strain, mechanical dispersion index, and left atrium strain were found between the group with low arrhythmogenicity and the group with high arrhythmogenicity (p < 0.0001). The index of mechanical dispersion has the most optimal sensitivity and specificity of all investigated echocardiographic markers. These results support the mechanical dispersion index as an additional tool for assessing proarrhythmogenicity in metabolic syndrome. Full article

Aim: The frontal QRS-T (fQRS-T) angle serves as an electrocardiography indicator that visually represents the disparity between the frontal QRS axis and the T axis. The heterogeneity between cardiac depolarization and repolarization rises with an increase in the fQRS-T angle. Prior research has demonstrated a relationship between the fQRS-T angle and the extent of atherosclerosis, along with the risk of cardiovascular mortality. The non-alcoholic fatty liver disease fibrosis score (NFS) is a non-invasive scoring tool used to quantify the degree of liver fibrosis in individuals with non-alcoholic fatty liver disease (NAFLD). Non-alcoholic fatty liver disease increases the risk of atherosclerotic cardiovascular disease, which can be predicted using the NFS. The objective of this study is to examine the potential correlation between the fQRS-T angle and NFS in patients with stable angina pectoris. Materials and Methods: This cross-sectional study included 177 (48 women) non-alcoholic patients who underwent coronary angiography due to stable angina pectoris. Individual NFS values were calculated using clinical and laboratory data. Patients were categorized into two groups based on a NFS threshold value of 0.67. Following a minimum fasting period of 12 h, biochemical laboratory parameters were acquired using a peripheral venous sample, and electrocardiographic data were recorded. Results: The univariate logistic regression analysis revealed significant associations between hypertension (p = 0.018), coronary artery disease (p = 0.014), neutrophil (p = 0.024), hemoglobin (p = 0.038), and low-density lipoprotein (LDL, p = 0.007) with the NFS. The electrocardiographic variables related to the score included the QRS duration (p = 0.015), Pmax (p = 0.026), QTC interval (p = 0.02), and fQRS-T angle (p < 0.001). In the multivariate logistic regression analysis, NFS was independently associated with LDL (OR: 0.984, 95% CI: 0.970–0.998, p = 0.024) and fQRS-T angle (OR: 3.472, 95% CI: 1.886–6.395, p < 0.001). Conclusions: The FQRS-T angle may exhibit a distinct correlation with NAFLD. Extensive investigations should validate this link, since the fibrosis score can serve as an effective tool for monitoring patients prior to the onset of clinical symptoms associated with liver fibrosis. Full article

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare disease with variable clinical manifestations. MELAS is most often caused by the human mitochondrial DNA (mtDNA) m.3243A>G variant. We describe cardiac magnetic resonance (CMR) imaging findings and clinical features of 22 subjects with the m.3243A>G mutation and endeavored to discover the role of CMR in MELAS cardiomyopathy diagnostics. The clinical symptoms, ECG findings, and laboratory tests were retrospectively collected from the electronic medical record. Ten subjects (46%) had cardiac symptoms, and eighteen subjects (82%) had some clinical symptoms or signs of MELAS. Seventeen subjects (77%) showed cardiac findings compatible with MELAS. An ECG showed a short PR interval in six subjects (27%). Two patients had a first-degree atrioventricular block. Repolarization changes in the ECG were observed in thirteen subjects (59%), whereas left ventricular hypertrophy voltage criteria were only observed in one subject. Patients with ECG abnormalities had a strong link between proBNP value and cardiac tissue composition (T1 relaxation, p < 0.02) and showed decreased CMR-based strain (p < 0.025). The CMR findings are heterogeneous in subjects with m.3243A>G. Cardiac MELAS may include left ventricular hypertrophy, which mimics sarcomericcardiomyopathy but maypredispose individuals to severe heart failure episodes triggered by acute critical situations. CMR may be used to clarify ECG findings. This study indicates that the genetic testing of MELAS should be considered in new cases of HCM or sudden heart failure phenotypes of unknown etiology. Full article

Objectives: This study aimed to examine the effects of endurance and high-intensity resistance training on arterial stiffness and ventricular repolarization in elite athletes. Methods: A total of 50 male athletes from different sports disciplines (volleyball, football, judo, and wrestling) and a sedentary group of 30 males participated in this study. Data collected from all participants included age, height, body weight, cardiovascular hemodynamic parameters, arterial stiffness parameters, and ECG measurements. Results: There was no significant age difference between the athlete group (20.42 ± 1.903 years) and the control group (20.97 ± 1.771 years) (p > 0.05). However, body mass index (BMI) values in the control group (24.83 ± 2.22 kg/m²) were significantly different from those in the athlete group (22.39 ± 2.663 kg/m²) (p < 0.05). Significant differences were found between the athlete and control groups in QT dispersion, systolic blood pressure, pulse pressure, and central pulse pressure values (p < 0.05), while similar results were obtained for arterial stiffness parameters (p > 0.05). Conclusions: The lack of a difference in pulse wave velocity and augmentation index (AIx) values between the athletes and the control group suggests that athletes do not bear additional risks regarding arterial stiffness. However, increased systolic blood pressure, pulse pressure, and central pulse pressure, among the hemodynamic parameters, indicate potential variations in vascular wall compliance and hemodynamic responses in the cardiovascular system. The increase in QT dispersion suggests that athletes may exhibit a heterogeneous repolarization process and an elevated risk of ventricular arrhythmias compared to the general population. Full article

Cenobamate is a novel third-generation antiepileptic drug used for the treatment of focal onset seizures and particularly for multi-drug-resistant epilepsy; it acts on multiple targets: GABA_A receptors (EC₅₀ 42–194 µM) and persistent neuronal Na⁺ currents (IC₅₀ 59 µM). Side effects include QT_c interval shortening with >20 ms, but not <300 ms. Our in vitro cardiac safety pharmacology study was performed via whole-cell patch-clamp on HEK293T cells with persistent/inducible expression of human cardiac ion channel isoforms hNav1.5 (I_Na), hCav1.2 (α1c + β2 + α2δ1) (I_CaL), hKv7.1 + minK (I_Ks), and hKv11.1 (hERG) (I_Kr). We found IC50 of 87.6 µM (peak I_Na), 46.5 µM (late I_Na), and 509.75 µM (I_CaL). In experiments on Ncyte^® ventricular cardiomyocytes, APD90 was reduced with 28.6 ± 13.5% (mean ± SD) by cenobamate 200 µM. Cenobamate’s marked inhibition of I_Na raises the theoretical possibility of cardiac arrhythmia induction at therapeutic concentrations in the context of preexisting myocardial pathology, in the presence of action potential conduction and repolarization heterogeneity. This hypothetical mechanism is consistent with the known effects of class Ib antiarrhythmics. In simulations with a linear strand of 50 cardiomyocytes with variable inter-myocyte conductance based on a modified O’Hara–Rudy model, we found a negligible cenobamate-induced conduction delay in normal tissue, but a marked delay and also a block when gap junction conduction was already depressed. Full article

Catheter ablation for ventricular tachycardia (VT) in patients with systolic heart failure remains a critical yet challenging area of non-pharmacological therapy. Despite positive outcomes in atrial fibrillation, evidence for the efficacy of VT ablation in reducing cardiac mortality is inconclusive due to the absence of standardized ablation strategies. The primary challenges include difficulties in identifying suitable ablation targets and their deep locations within myocardial tissue. Current techniques, such as voltage mapping, provide valuable insights; however, they are limited by the presence of numerous bystander areas and the occurrence of incomplete transmural scarring. Recent advancements in functional substrate mapping have focused on identifying critical isthmuses without requiring hemodynamic stabilization during VT, thereby shifting the emphasis to the analysis of potentials during baseline rhythm. While methods like isochronal late activation mapping have improved target identification, they primarily address conduction abnormalities without adequately considering repolarization heterogeneity. This review highlights emerging technologies that utilize unipolar potentials to assess repolarization heterogeneities and identify VT isthmuses. Furthermore, novel ablation sources such as pulsed-field ablation, bipolar ablation, and ultra-low temperature cryoablation are being explored to create deeper and more durable lesions, addressing the limitations of traditional radiofrequency ablation. These advancements aim to reduce VT recurrence and improve overall treatment efficacy. Ultimately, understanding these innovative strategies is expected to optimize procedural outcomes and significantly enhance the management of patients with scar-related VT. Full article

Artificial intelligence, particularly machine learning, has gained prominence in medical research due to its potential to develop non-invasive diagnostics. Pulmonary hypertension presents a diagnostic challenge due to its heterogeneous nature and similarity in symptoms to other cardiovascular conditions. Here, we describe the development of a supervised machine learning model using non-invasive signals (orthogonal voltage gradient and photoplethysmographic) and a hand-crafted library of 3298 features. The developed model achieved a sensitivity of 87% and a specificity of 83%, with an overall Area Under the Receiver Operator Characteristic Curve (AUC-ROC) of 0.93. Subgroup analysis showed consistent performance across genders, age groups and classes of PH. Feature importance analysis revealed changes in metrics that measure conduction, repolarization and respiration as significant contributors to the model. The model demonstrates promising performance in identifying pulmonary hypertension, offering potential for early detection and intervention when embedded in a point-of-care diagnostic system. Full article