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Introduction Methods and Results Conclusions Long QT syndrome (LQTS) is a cardiac channelopathy characterized by QT prolongation and a potential for arrhythmic syncope, sudden cardiac arrest or deaths (SCA/SCD). It has been speculated that patients with LQTS might have a primary sinoatrial node (SAN) phenotype of chronotropic insufficiency (CI). This has not been demonstrated convincingly before because of the potentially confounding effects of beta blocker (BB) therapy. Herein, we set out to determine whether untreated patients with LQTS demonstrate intrinsic CI.A retrospective review of all treadmill exercise stress tests (TEST) was performed on patients with one of the three most common LQTS genotypes: LQT1, LQT2, and LQT3. For each patient, the first TEST completed while off BB was analyzed. Patients with prior left cardiac sympathetic denervation (LCSD) therapy were excluded. CI was defined as having an age‐ and gender‐predicted peak heart rate (HR) < 85% and/or a predicted HR reserve (HRR) < 80%. Overall, 463 LQTS patients (245 LQT1, 125 LQT2, and 93 LQT3) were included (267 female [58%]; mean age at time of TEST [29 ± 17 years]). Mean % predicted peak HR for all LQTS patients was 87.6% (range 42.9% ‐ 119.1%) and mean % predicted HRR was 80% (range 19.1% ‐ 153%). Overall, half of all LQTS patients (n = 234; 51%) displayed CI; 64% of patients with LQT1 (n = 157), 37% with LQT2 (n = 46), and 33% with LQT3 (n = 31). Patients with LQT1 were most likely to exhibit CI compared to patients with LQT2 (p < .0001) and LQT3 (p < .0001). CI was significantly more common in LQT1 compared to controls (p < .0001), while there was no difference between LQT2 (p = .5) or LQT3 and controls (p > .9). Presence of CI was not a predictor of LQTS‐associated symptoms, BB side effects or likelihood of future breakthrough cardiac events (BCE).Patients with LQTS, particularly LQT1, demonstrate a SAN phenotype of CI. If assessing BB therapy effect by impact on peak HR, the patient's pretreatment peak HR, rather than an age‐ and gender‐predicted maximum HR, should be used. [ABSTRACT FROM AUTHOR]

Background: The characteristics of electrocardiogram (ECG) abnormalities related to cardiac channelopathies potentially linked to sudden cardiac death (SCD) are not widely recognized in Iran. We examined the prevalence of such ECG patterns and their related factors among adult residents of Tehran, Iran. Methods: The clinical characteristics and 12-lead ECGs of Tehran Cohort Study participants were examined. Long QT intervals, short QT intervals, Brugada syndrome (BrS) patterns, and early repolarization (ER) were evaluated using computer-based assessment software validated by cardiologists. Logistic regression models were employed to identify the factors associated with the prevalence of different ECG patterns. Results: Out of 7678 available ECGs, 7350 were included in this analysis. Long QT interval, ER pattern, BrS patterns, and short QT interval were found in 3.08%, 1.43%, 0.31%, and 0.03% of participants, respectively. The prevalence of long QT interval increased with age, opium consumption, and presence of hypertension. Younger age, lower body mass index (BMI), alcohol use and male sex were independently linked to an elevated prevalence of ER pattern. Most individuals with BrS patterns were men (95%) and had lower BMI, high- and low-density lipoprotein, and total cholesterol compared to those without the BrS pattern. At a mean follow-up of 30.2 ± 5.5 months, all-cause mortality in the group exhibiting abnormal ECG patterns (6.3%) was approximately twice as high as that in the group without such patterns (2.96%). Conclusion: Abnormal ECG patterns corresponding to channelopathies were relatively rare among adult residents of the Tehran population, and their prevalence was influenced by various factors. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Congenital long QT syndrome (LQTS) is a genetic heart disorder, which may lead to life-threatening arrhythmias, especially in children. Here, we reported two children who were initially misdiagnosed with epilepsy and experienced Torsades de Pointes (TdP) cardiac electrical storm (ES). Through whole exome sequencing (WES), we identified two Potassium voltage-gated channel subfamily H member 2 (KCHN2) mutations (c.1841 C > T and c.1838 C > T) respectively in a 6-year-old boy and a 13-year-old girl. Clinical data indicated that the QT interval was significantly prolonged, the T-wave pattern of chest V5-V6 leads and limb leads were inverted. Our study suggests that patients with epilepsy, especially those refractory epilepsy with atypical features, need comprehensive evaluation of cardiovascular function. KCNH2 mutation in pore region, QT interval prolongation and T wave inversion are high risk factors for ES. For LQT2 patients with ES, Nadolol and left cardiac sympathetic denervation are indicated, sometimes with an ICD. [ABSTRACT FROM AUTHOR]

Methadone, a well-known drug used for pain control and as a treatment for opioid addiction, can cause arrhythmias, including torsades de pointes (TdP), which may progress to ventricular fibrillation and sudden death. We present a case of a middle-aged woman with a long history of methadone use who presented to the emergency department after experiencing cardiac arrest at home. During her hospitalization, she experienced multiple episodes of TdP that improved with isoproterenol and potassium correction. The initial diagnosis was methadone-induced prolonged QT. However, even with discontinuation of methadone, her QTc remained prolonged. Congenital long QT syndrome was suspected, and genetic testing was instructed to test in the outpatient setting. She was discharged on nadolol and a LifeVest. [ABSTRACT FROM AUTHOR]

Introduction: Early‐onset atrial fibrillation (AF) has already been observed in approximately 2% of patients with genetically proven long QT syndrome (LQTS). This frequency is higher than population‐based estimates of early‐onset AF. However, the concomitant expression of AF in LQTS is likely underestimated. The purpose of this study was to examine the clinical presentation, genetic background, and outcomes of a cohort of patients with LQTS and early‐onset AF referred to a single tertiary center. Methods: Twenty‐seven patients diagnosed with congenital LQTS were included in the study based on the documentation of early‐onset (age ≤50 years) clinical or subclinical AF episodes in all available medical records, including standard electrocardiograms, wearable monitor or cardiac implantable electronic devices. Results: Seventeen patients experienced clinical AF during the follow‐up period. Subclinical AF was detected in 10 patients through insertable or wearable cardiac monitors. In our series, the mean heart rate during AF episodes was found to be relatively low despite the patients' young age and the low or minimal effective doses of beta‐blockers used for QTc interval control. All patients exhibiting LQTS and early‐onset AF were genotype positive, carrying mutations in the KCNQ1 (66%), KCNH2, KCNE1, and SCN5A genes. Notably, most of these patients carried the same p.(R231C) mutation in the KCNQ1 gene (59%) and were from the same families, suggesting concurrent expression of familial AF and LQTS. Conclusion: LQTS patients are prone to developing clinical and subclinical AF, even at a younger age. The occurrence of early‐onset AF in the LQTS population could be more frequent than previously assumed. AF should be considered as a potential dysrhythmia related to LQTS. Our study emphasizes the importance of carefully researching clinical and/or subclinical episodes of AF through strict heart rhythm monitoring in the LQTS population. [ABSTRACT FROM AUTHOR]

Objectives: To determine the clinical course of fetal isolated non‐immune‐mediated second‐degree atrioventricular block (AVB) and the factors associated with spontaneous recovery in these cases. Methods: Fetuses with isolated non‐immune‐mediated second‐degree AVB were recruited prospectively between 2014 and 2022. These fetuses were divided into two groups: those which recovered spontaneously and those which did not. Maternal and fetal characteristics and intrauterine and postnatal outcomes were compared between the two groups. Results: The study cohort included 20 fetuses with isolated non‐immune‐mediated second‐degree AVB, diagnosed at a median gestational age of 22.0 (range, 17.0–35.0) weeks. In 12 fetuses, 1:1 atrioventricular conduction was restored spontaneously in utero and there was no recurrence during the postnatal follow‐up period. In the remaining eight fetuses, second‐degree AVB was maintained and, in six of these, the pregnancy was terminated on parental request. Of the two liveborn children who had persistent second‐degree AVB prenatally, one had progressed to complete AVB at the latest follow‐up, at the age of 34 months, but was asymptomatic, without heart enlargement or dysfunction. The other child progressed to complete AVB after delivery and was diagnosed with type‐2 long QT syndrome. This infant died aged 2 months. Fetuses in the group that recovered spontaneously had earlier gestational age at diagnosis (median, 20.0 (range, 17.0–26.0) vs 24.5 (range, 18.0–35.0) weeks; P = 0.004) and higher atrial rate at diagnosis (median, 147 (range, 130–160) vs 138 (range, 125–149) bpm; P = 0.006) in comparison with the group that did not recover spontaneously. The best cut‐off values for prediction of failure to recover spontaneously were 22.5 weeks' gestational age at diagnosis and 144 bpm atrial rate at diagnosis, with sensitivities of 87.5% and 75.0%, respectively, and specificities of 92.0% and 87.5%, respectively. Conclusions: The outcome of 60% of fetuses with isolated non‐immune‐mediated second‐degree AVB was favorable. Earlier gestational age and higher atrial rate at diagnosis were associated with spontaneous reversion to normal sinus rhythm. Prenatal genetic testing should be performed in cases with persistent AVB, to exclude heritable disorders including long QT syndrome. These findings provide important information for clinical management and prenatal counseling in these cases. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Background: Azithromycin is a commonly prescribed antibiotic included in many first-line regimens for pneumonia. Azithromycin also carries an FDA warning for increased risk for abnormal cardiac electrical activity, including QTc prolongation. Objective: To examine the effect of intravenous azithromycin on the QT interval in a cohort of patients receiving antibiotic therapy for community acquired pneumonia. Methods: A single-center, retrospective chart review of patients admitted to the Intensive Care Unit (ICU). The primary endpoint was change in QTc 48-72 hours after antibiotic initiation. The primary outcome was analyzed using ANOVA matched comparison. Results: Between 6/1/2019 and 3/31/2020, 241 total ICU patients received doses of either antibiotic. After application of exclusion criteria, the total number of patients included in analysis was 93, including 75 azithromycin patient and 18 doxycycline patients. The baseline QTc in the azithromycin group was 449 (95% CI 438-461) and the 72-hour QTc was 442 (95% CI 427-453) with an average change in QTc of -4 ms (P =.14). No statistically significant difference was found in QTc interval change between azithromycin and doxycycline. Conclusion: In this study, azithromycin use was not associated with a statistically significant increase in QTc interval. Based on these results, for the majority of patients receiving azithromycin, QTc prolongation is not likely a major concern. However, caution may still be warranted in patients considered high risk. [ABSTRACT FROM AUTHOR]

Background and Aims Type 1 long QT syndrome (LQT1) is caused by pathogenic variants in the KCNQ1- encoded Kv7.1 potassium channels, which pathologically prolong ventricular action potential duration (APD). Herein, the pathologic phenotype in transgenic LQT1 rabbits is rescued using a novel KCNQ1 suppression-replacement (SupRep) gene therapy. Methods KCNQ1 -SupRep gene therapy was developed by combining into a single construct a KCNQ1 shRNA (suppression) and an shRNA-immune KCNQ1 cDNA (replacement), packaged into adeno-associated virus serotype 9, and delivered in vivo via an intra-aortic root injection (1E10 vg/kg). To ascertain the efficacy of SupRep, 12-lead electrocardiograms were assessed in adult LQT1 and wild-type (WT) rabbits and patch-clamp experiments were performed on isolated ventricular cardiomyocytes. Results KCNQ1 -SupRep treatment of LQT1 rabbits resulted in significant shortening of the pathologically prolonged QT index (QTi) towards WT levels. Ventricular cardiomyocytes isolated from treated LQT1 rabbits demonstrated pronounced shortening of APD compared to LQT1 controls, leading to levels similar to WT (LQT1-UT vs. LQT1-SupRep, P <.0001, LQT1-SupRep vs. WT, P = ns). Under β-adrenergic stimulation with isoproterenol, SupRep-treated rabbits demonstrated a WT-like physiological QTi and APD90 behaviour. Conclusions This study provides the first animal-model, proof-of-concept gene therapy for correction of LQT1. In LQT1 rabbits, treatment with KCNQ1 -SupRep gene therapy normalized the clinical QTi and cellular APD90 to near WT levels both at baseline and after isoproterenol. If similar QT/APD correction can be achieved with intravenous administration of KCNQ1- SupRep gene therapy in LQT1 rabbits, these encouraging data should compel continued development of this gene therapy for patients with LQT1. [ABSTRACT FROM AUTHOR]

Electromechanical reciprocity – comprising electro‐mechanical (EMC) and mechano‐electric coupling (MEC) – provides cardiac adaptation to changing physiological demands. Understanding electromechanical reciprocity and its impact on function and heterogeneity in pathological conditions – such as (drug‐induced) acquired long QT syndrome (aLQTS) – might lead to novel insights in arrhythmogenesis. Our aim is to investigate how electrical changes impact on mechanical function (EMC) and vice versa (MEC) under physiological conditions and in aLQTS. To measure regional differences in EMC and MEC in vivo, we used tissue phase mapping cardiac MRI and a 24‐lead ECG vest in healthy (control) and IKr‐blocker E‐4031‐induced aLQTS rabbit hearts. MEC was studied in vivo by acutely increasing cardiac preload, and ex vivo by using voltage optical mapping (OM) in beating hearts at different preloads. In aLQTS, electrical repolarization (heart rate corrected RT‐interval, RTn370) was prolonged compared to control (P < 0.0001) with increased spatial and temporal RT heterogeneity (P < 0.01). Changing electrical function (in aLQTS) resulted in significantly reduced diastolic mechanical function and prolonged contraction duration (EMC), causing increased apico‐basal mechanical heterogeneity. Increased preload acutely prolonged RTn370 in both control and aLQTS hearts (MEC). This effect was more pronounced in aLQTS (P < 0.0001). Additionally, regional RT‐dispersion increased in aLQTS. Motion‐correction allowed us to determine APD‐prolongation in beating aLQTS hearts, but limited motion correction accuracy upon preload‐changes prevented a clear analysis of MEC ex vivo. Mechano‐induced RT‐prolongation and increased heterogeneity were more pronounced in aLQTS than in healthy hearts. Acute MEC effects may play an additional role in LQT‐related arrhythmogenesis, warranting further mechanistic investigations. Key points: Electromechanical reciprocity comprising excitation‐contraction coupling (EMC) and mechano‐electric feedback loops (MEC) is essential for physiological cardiac function.Alterations in electrical and/or mechanical heterogeneity are known to have potentially pro‐arrhythmic effects.In this study, we aimed to investigate how electrical changes impact on the mechanical function (EMC) and vice versa (MEC) both under physiological conditions (control) and in acquired long QT syndrome (aLQTS).We show that changing the electrical function (in aLQTS) results in significantly altered mechanical heterogeneity via EMC and, vice versa, that increasing the preload acutely prolongs repolarization duration and increases electrical heterogeneity, particularly in aLQTS as compared to control.Our results substantiate the hypothesis that LQTS is an ‛electro‐mechanical', rather than a 'purely electrical', disease and suggest that acute MEC effects may play an additional role in LQT‐related arrhythmogenesis. [ABSTRACT FROM AUTHOR]

Cancer is the leading public health problem worldwide. However, the side effects accompanying anti‐cancer therapies, particularly those pertaining to cardiotoxicity and adverse cardiac events, have been the hindrances to treatment progress. Long QT syndrome (LQTS) is one of the major clinic manifestations of the anti‐cancer drug associated cardiac dysfunction. Therefore, elucidating the relationship between the LQTS and cancer is urgently needed. Transcriptomic sequencing data and clinic information of 10,531 patients diagnosed with 33 types of cancer was acquired from TCGA database. A pan‐cancer applicative gene prognostic model was constructed based on the LQTS gene signatures. Meanwhile, transcriptome data and clinical information from various cancer types were collected from the GEO database to validate the robustness of the prognostic model. Furthermore, the expression level of transcriptomes and multiple clinical features were integrated to construct a Nomo chart to optimize the prognosis model. The ssGSEA analysis was employed to analysis the correlation between the LQTS gene signatures, clinic features and cancer associated signalling pathways. Our findings revealed that patients with lower LQTS gene signatures enrichment levels exhibit a poorer prognosis. The correlation of enrichment levels with the typical pathways was observed in multiple cancers. Then, based on the 17 LQTS gene signatures, we construct a prognostic model through the machine‐learning approaches. The results obtained from the validation datasets and training datasets indicated that our prognostic model can effectively predict patient outcomes across diverse cancer types. Finally, we integrated this model with clinical features into a nomogram, demonstrating its potential as a valuable prognostic tool for cancer patients. Our study sheds light on the intricate relationship between LQTS and cancer pathways. A LQTS feature based clinic decision tool was developed aiming to enhance precision treatment of cancer. [ABSTRACT FROM AUTHOR]

This study introduces the intelligent learning engine (ILE) optimization technology, a novel approach designed to revolutionize screening processes in bioinformatics, cheminformatics, and a range of other scientific fields. By focusing on the efficient and precise identification of candidates with desirable characteristics, the ILE technology marks a significant leap forward in addressing the complexities of candidate selection in drug discovery, protein classification, and beyond. The study's primary objective is to address the challenges associated with optimizing screening processes to efficiently select candidates across various fields, including drug discovery and protein classification. The methodology employed involves a detailed algorithmic process that includes dataset preparation, encoding of protein sequences, sensor nucleation, and optimization, culminating in the empirical evaluation of molecular activity indexing, homology-based modeling, and classification of proteins such as G-protein-coupled receptors. This process showcases the method's success in multiple sequence alignment, protein identification, and classification. Key results demonstrate the ILE's superior accuracy in protein classification and virtual high-throughput screening, with a notable breakthrough in drug development for assessing drug-induced long QT syndrome risks through hERG potassium channel interaction analysis. The technology showcased exceptional results in the formulation and evaluation of novel cancer drug candidates, highlighting its potential for significant advancements in pharmaceutical innovations. The findings underline the ILE optimization technology as a transformative tool in screening processes due to its proven effectiveness and broad applicability across various domains. This breakthrough contributes substantially to the fields of systems optimization and holds promise for diverse applications, enhancing the process of selecting candidate molecules with target properties and advancing drug discovery, protein classification, and modeling. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) is a pervasive global health concern, with acute decompensated heart failure (ADHF) contributing significantly to morbidity and mortality. Medications used in patients with HF may exacerbate HF or prolong the QT interval, posing additional risks. Objective: The objective is to assess the prevalence and utilization patterns of medications known to cause or exacerbate HF and prolong the QT interval among patients with ADHF. Understanding these patterns is crucial for optimizing patient care and minimizing potential risks. Methods: A retrospective chart review was conducted at Huntsville Hospital, Huntsville, USA, covering 602 patients with ADHF over a 40-month period. Inclusion criteria involved age ≥ 18 years, a history of HF, and ADHF admission. The 2016 American Heart Association Scientific Statement was used to identify drugs that may cause or exacerbate HF and those that could prolong the QT interval Results: Among the 602 patients, 57.3% received medications causing or exacerbating HF, notably albuterol (34.9%) and diabetes medications (20.4%), primarily metformin, followed by urologic agents (14.3%), mostly tamsulosin, and nonsteroidal anti-inflammatory drugs (NSAIDs) (6.1%). Moreover, 82.9% were on medications prolonging the QT interval, with loop diuretics, amiodarone, ondansetron, and famotidine most prevalent. Furthermore, 42.1% of the patients received more than two concomitant medications that prolong the QT interval, which can further exacerbate the risk of torsades de pointes. Conclusion: This study underscores the high prevalence of HF-causing or HF-exacerbating medications and QT-prolonging drugs in patients with ADHF. Healthcare professionals must be cognizant of these patterns, advocating for safer prescribing practices to optimize patient outcomes and reduce the burden of HF-related hospitalizations. [ABSTRACT FROM AUTHOR]

Background Congenital long QT syndrome (LQTS) type 1 is characterized by abnormally prolonged ventricular repolarization caused by inherited defects in cardiac potassium channels. Patients are predisposed to ventricular arrhythmias and even sudden cardiac death. In some cases, foetal sinus bradycardia is the only sign, making prenatal diagnosis challenging. Physicians should be aware of this subtle presentation of LQTS. Early diagnosis and proactive treatment are crucial for preventing unexpected cardiac events. Case summary A healthy and asymptomatic 25-year-old pregnant woman was referred to our institute for cardiac evaluation after persistent foetal sinus bradycardia was detected during repeated ultrasounds, despite the absence of any foetal morphological or functional cardiac anomalies. After a thorough assessment, the mother was diagnosed with LQTS type 1, as confirmed by molecular genetic testing. Appropriate management, including maternal medication and increased surveillance, was initiated. The infant was delivered safely, and his electrocardiogram revealed a significantly prolonged QTc interval. Genetic testing confirmed the maternally inherited variant in KCNQ1 gene, and beta-blocker therapy was started. No arrhythmic events were noted. Discussion Detection and careful stratification of foetal heart rate (FHR) is crucial in every pregnancy. Foetal bradycardia can be caused by both maternal and foetal factors. Persistent low FHR should raise a high suspicion for LQTS. The condition may also present with atrioventricular blocks, torsades de pointes, or sudden intrauterine foetal demise. Accurate and early diagnosis of LQTS is essential for implementing appropriate management strategies, which include vigilant monitoring, effective medical treatment, careful planning of delivery, and post-natal care. [ABSTRACT FROM AUTHOR]

Background: The safety of triple antiemetic therapy consisting of ondansetron, haloperidol, and a steroid, to surgical patients is unknown. Objective: To determine the incidence of torsade de pointes (TdP) or death following perioperative administration of triple antiemetic therapy. Methods: A retrospective cohort study identified 19,874 patients who received 22,202 doses of triple antiemetics during the 2.5-year time frame from March 4, 2020 to September 7, 2022 for surgical nausea prophylaxis or treatment of nausea. These patients above were cross-matched with an electrocardiogram and adverse outcome database; this identified 226 patients with documentation of a QTc > 450 ms, all ventricular tachycardias including TdP within 48 hours of receiving triple antiemetic therapy, or death within 7 days of receiving ondansetron. Results: There were 3 patients who had documented VT (n = 3), but there were no documented incidents of TdP (n = 0). There were 9 codes called on patients within 48 hours of medication administration, and none of them were due to ventricular arrythmias (n = 0). A total of 11 patients died within 7 days of triple antiemetic therapy. Ten of the 11 deaths were determined to not be from the triple antiemetic. One patient died at home within 24 hours of the procedure of an unknown cause (n = 1). Conclusions and Relevance: No episodes of TdP were identified in patients receiving triple antiemetic therapy perioperatively, though the cause of death in 1 patient could not be determined. This suggest that low-dose triple antiemetic therapy is low risk for the development of TdP. [ABSTRACT FROM AUTHOR]

Congenital long QT syndrome (LQTS) diagnosis is complicated by limited genetic testing at scale, low prevalence, and normal QT corrected interval in patients with high-risk genotypes. We developed a deep learning approach combining electrocardiogram (ECG) waveform and electronic health record data to assess whether patients had pathogenic variants causing LQTS. We defined patients with high-risk genotypes as having ≥1 pathogenic variant in one of the LQTS-susceptibility genes. We trained the model using data from United Kingdom Biobank (UKBB) and then fine-tuned in a racially/ethnically diverse cohort using Mount Sinai BioMe Biobank. Following group-stratified 5-fold splitting, the fine-tuned model achieved area under the precision-recall curve of 0.29 (95% confidence interval [CI] 0.28–0.29) and area under the receiver operating curve of 0.83 (0.82–0.83) on independent testing data from BioMe. Multimodal fusion learning has promise to identify individuals with pathogenic genetic mutations to enable patient prioritization for further work up. [ABSTRACT FROM AUTHOR]

Identifying and treating pediatric arrhythmias is essential for pediatric anesthesiologists. Pediatric patients can present with narrow or wide complex tachycardias, though the former is more common. Patients with inherited channelopathies or cardiomyopathies are at increased risk. Since most pediatric patients present for anesthesia without a baseline electrocardiogram, the first identification of an arrhythmia may occur under general anesthesia. Supraventricular tachycardia, the most common pediatric tachyarrhythmia, represents a broad category of predominately narrow complex tachycardias. Stimulating events including intubation, vascular guidewire manipulation, and surgical stimulation can trigger episodes. Valsalva maneuvers are unreliable as treatment, making adenosine or other intravenous antiarrhythmics the preferred acute therapy. Reentrant tachycardias are the most common supraventricular tachycardia in pediatric patients, including atrioventricular reciprocating tachycardia (due to a distinct accessory pathway) and atrioventricular nodal reentrant tachycardia (due to an accessory pathway within the atrioventricular node). Patients with ventricular preexcitation, often referred to as Wolff‐Parkinson‐White syndrome, have a wide QRS with short PR interval, indicating antegrade conduction through the accessory pathway. These patients are at risk for sudden death if atrial fibrillation degenerates into ventricular fibrillation over a high‐risk accessory pathway. Automatic tachycardias, such as atrial tachycardia and junctional ectopic tachycardia, are causes of supraventricular tachycardia in pediatric patients, the latter most typically noted after cardiac surgery. Patients with inherited arrhythmia syndromes, such as congenital long QT syndrome, are at risk of developing ventricular arrhythmias such as polymorphic ventricular tachycardia (Torsades de Pointes) which can be exacerbated by QT prolonging medications. Patients with catecholaminergic polymorphic ventricular tachycardia are at particular risk for developing bidirectional ventricular tachycardia or ventricular fibrillation during exogenous or endogenous catecholamine surges. Non‐selective beta blockers are first line for most forms of long QT syndrome as well as catecholaminergic polymorphic ventricular tachycardia. Anesthesiologists should review the impact of medications on the QT interval and transmural dispersion of repolarization, to limit increasing the risk of Torsades de Pointes in patients with long QT syndrome. This review explores the key anesthetic considerations for these arrhythmias. [ABSTRACT FROM AUTHOR]

BACKGROUND: Drug-induced QT prolongation (diLQT) is a feared side effect that could expose susceptible individuals to fatal arrhythmias. The occurrence of diLQT is primarily attributed to unintended drug interactions with cardiac ion channels, notably the hERG (human ether-a-go-go-related gene) channels that generate the delayed-rectifier potassium current (IKr) and thereby regulate the late repolarization phase. There is an important interindividual susceptibility to develop diLQT, which is of unknown origin but can be reproduced in patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs). We aimed to investigate the dynamics of hERG channels in response to sotalol and to identify regulators of the susceptibility to developing diLQT. METHODS: We measured electrophysiological activity and cellular distribution of hERG channels after hERG blocker treatment in iPS-CMs derived from patients with highest sensitivity (HS) or lowest sensitivity (LS) to sotalol administration in vivo (ie, on the basis of the measure of the maximal change in QT interval 3 hours after administration). Specific small interfering RNAs and CAVIN1-T2A-GFP adenovirus were used to manipulate CAVIN1 expression. RESULTS: Whereas HS and LS iPS-CMs showed similar electrophysiological characteristics at baseline, the late repolarization phase was prolonged and IKr significantly decreased after exposure of HS iPS-CMs to low sotalol concentrations. IKr reduction was caused by a rapid translocation of hERG channel from the membrane to the cytoskeleton-associated fractions upon sotalol application. CAVIN1, essential for caveolae biogenesis, was 2× more highly expressed in HS iPS-CMs, and its knockdown by small interfering RNA reduced their sensitivity to sotalol. CAVIN1 overexpression in LS iPS-CMs using adenovirus showed reciprocal effects. We found that treatment with sotalol promoted translocation of the hERG channel from the plasma membrane to the cytoskeleton fractions in a process dependent on CAVIN1 (caveolae associated protein 1) expression. CAVIN1 silencing reduced the number of caveolae at the membrane and abrogated the translocation of hERG channel in sotalol-treated HS iPS-CMs. CAVIN1 also controlled cardiomyocyte responses to other hERG blockers, such as E4031, vandetanib, and clarithromycin. CONCLUSIONS: Our study identifies unbridled turnover of the potassium channel hERG as a mechanism supporting the interindividual susceptibility underlying diLQT development and demonstrates how this phenomenon is finely tuned by CAVIN1. [ABSTRACT FROM AUTHOR]

BACKGROUND: Whether vigorous exercise increases risk of ventricular arrhythmias for individuals diagnosed and treated for congenital long QT syndrome (LQTS) remains unknown. METHODS: The National Institutes of Health-funded LIVE-LQTS study (Lifestyle and Exercise in the Long QT Syndrome) prospectively enrolled individuals 8 to 60 years of age with phenotypic and/or genotypic LQTS from 37 sites in 5 countries from May 2015 to February 2019. Participants (or parents) answered physical activity and clinical events surveys every 6 months for 3 years with follow-up completed in February 2022. Vigorous exercise was defined as =6 metabolic equivalents for >60 hours per year. A blinded Clinical Events Committee adjudicated the composite end point of sudden death, sudden cardiac arrest, ventricular arrhythmia treated by an implantable cardioverter defibrillator, and likely arrhythmic syncope. A National Death Index search ascertained vital status for those with incomplete follow-up. A noninferiority hypothesis (boundary of 1.5) between vigorous exercisers and others was tested with multivariable Cox regression analysis. RESULTS: Among the 1413 participants (13% <18 years of age, 35% 18-25 years of age, 67% female, 25% with implantable cardioverter defibrillators, 90% genotype positive, 49% with LQT1, 91% were treated with beta-blockers, left cardiac sympathetic denervation, and/or implantable cardioverter defibrillator), 52% participated in vigorous exercise (55% of these competitively). Thirty-seven individuals experienced the composite end point (including one sudden cardiac arrest and one sudden death in the nonvigorous group, one sudden cardiac arrest in the vigorous group) with overall event rates at 3 years of 2.6% in the vigorous and 2.7% in the nonvigorous exercise groups. The unadjusted hazard ratio for experience of events for the vigorous group compared with the nonvigorous group was 0.97 (90% CI, 0.57-1.67), with an adjusted hazard ratio of 1.17 (90% CI, 0.67-2.04). The upper 95% one-sided confidence level extended beyond the 1.5 boundary. Neither vigorous or nonvigorous exercise was found to be superior in any group or subgroup. CONCLUSIONS: Among individuals diagnosed with phenotypic and/or genotypic LQTS who were risk assessed and treated in experienced centers, LQTS-associated cardiac event rates were low and similar between those exercising vigorously and those not exercising vigorously. Consistent with the low event rate, CIs are wide, and noninferiority was not demonstrated. [ABSTRACT FROM AUTHOR]

BACKGROUND: Despite major advances in the clinical management of long QT syndrome, some patients are not fully protected by beta-blocker therapy. Mexiletine is a well-known sodium channel blocker, with proven efficacy in patients with sodium channel-mediated long QT syndrome type 3. Our aim was to evaluate the efficacy of mexiletine in long QT syndrome type 2 (LQT2) using cardiomyocytes derived from patient-specific human induced pluripotent stem cells, a transgenic LQT2 rabbit model, and patients with LQT2. METHODS: Heart rate-corrected field potential duration, a surrogate for QTc, was measured in human induced pluripotent stem cells from 2 patients with LQT2 (KCNH2-p.A561V, KCNH2-p.R366X) before and after mexiletine using a multiwell multi-electrode array system. Action potential duration at 90% repolarization (APD90) was evaluated in cardiomyocytes isolated from transgenic LQT2 rabbits (KCNH2-p.G628S) at baseline and after mexiletine application. Mexiletine was given to 96 patients with LQT2. Patients were defined as responders in the presence of a QTc shortening ≥40 ms. Antiarrhythmic efficacy of mexiletine was evaluated by a Poisson regression model. RESULTS: After acute treatment with mexiletine, human induced pluripotent stem cells from both patients with LQT2 showed a significant shortening of heart rate-corrected field potential duration compared with dimethyl sulfoxide control. In cardiomyocytes isolated from LQT2 rabbits, acute mexiletine significantly shortened APD90 by 113 ms, indicating a strong mexiletine-mediated shortening across different LQT2 model systems. Mexiletine was given to 96 patients with LQT2 either chronically (n=60) or after the acute oral drug test (n=36): 65% of the patients taking mexiletine only chronically and 75% of the patients who performed the acute oral test were responders. There was a significant correlation between basal QTc and ΔQTc during the test (r= -0.8; P<0.001). The oral drug test correctly predicted long-term effect in 93% of the patients. Mexiletine reduced the mean yearly event rate from 0.10 (95% CI, 0.07-0.14) to 0.04 (95% CI, 0.02-0.08), with an incidence rate ratio of 0.40 (95% CI, 0.16-0.84), reflecting a 60% reduction in the event rate (P=0.01). CONCLUSIONS: Mexiletine significantly shortens cardiac repolarization in LQT2 human induced pluripotent stem cells, in the LQT2 rabbit model, and in the majority of patients with LQT2. Furthermore, mexiletine showed antiarrhythmic efficacy. Mexiletine should therefore be considered a valid therapeutic option to be added to conventional therapies in higher-risk patients with LQT2. [ABSTRACT FROM AUTHOR]

The human ether-a-go-go-related gene (hERG) encodes the Kv11.1 (or hERG) channel that conducts the rapidly activating delayed rectifier potassium current (IKr). Naturally occurring mutations in hERG impair the channel function and cause long QT syndrome type 2. Many missense hERG mutations lead to a lack of channel expression on the cell surface, representing a major mechanism for the loss-of-function of mutant channels. While it is generally thought that a trafficking defect underlies the lack of channel expression on the cell surface, in the present study, we demonstrate that the trafficking defective mutant hERG G601S can reach the plasma membrane but is unstable and quickly degrades, which is akin to WT hERG channels under low K+ conditions. We previously showed that serine (S) residue at 624 in the innermost position of the selectivity filter of hERG is involved in hERG membrane stability such that substitution of serine 624 with threonine (S624T) enhances hERG stability and renders hERG insensitive to low K+ culture. Here, we report that the intragenic addition of S624T substitution to trafficking defective hERG mutants G601S, N470D, and P596R led to a complete rescue of the function of these otherwise loss-of-function mutant channels to a level similar to the WT channel, representing the most effective rescue means for the function of mutant hERG channels. These findings not only provide novel insights into hERG mutation-mediated channel dysfunction but also point to the critical role of S624 in hERG stability on the plasma membrane. [ABSTRACT FROM AUTHOR]

Voltage‐gated potassium channels are expressed throughout the human body and are essential for physiological functions. These include delayed rectifiers, A‐type channels, outward rectifiers, and inward rectifiers. They impact electrical function in the heart (repolarization) and brain (repolarization and stabilization of the resting membrane potential). KCNQx and KCNHx encode Kv7.x and Kv11.x proteins, which form delayed rectifier potassium channels. KCNQx and KCNHx channelopathies are associated with both cardiac and neuronal pathologies. These include electrocardiographic abnormalities, cardiac arrhythmias, sudden cardiac death (SCD), epileptiform discharges, seizures, bipolar disorder, and sudden unexpected death in epilepsy (SUDEP). Due to the ubiquitous expression of KCNQx and KCNHx channels, abnormalities in their function can be particularly harmful, increasing the risk of sudden death. For example, KCNH2 variants have a dual role in both cardiac and neuronal pathologies, whereas KCNQ2 and KCNQ3 variants are associated with severe and refractory epilepsy. Recurrent and uncontrolled seizures lead to secondary abnormalities, which include autonomics, cardiac electrical function, respiratory drive, and neuronal electrical activity. Even with a wide array of anti‐seizure therapies available on the market, one‐third of the more than 70 million people worldwide with epilepsy have uncontrolled seizures (i.e., intractable/drug‐resistant epilepsy), which negatively impact neurodevelopment and quality of life. To capture the current state of the field, this review examines KCNQx and KCNHx expression patterns and electrical function in the brain and heart. In addition, it discusses several KCNQx and KCNHx variants that have been clinically and electrophysiologically characterized. Because these channel variants are associated with multi‐system pathologies, such as epileptogenesis, Kv7 channel modulators provide a potential anti‐seizure therapy, particularly for people with intractable epilepsy. Ultimately an increased understanding of the role of Kv channels throughout the body will fuel the development of innovative, safe, and effective therapies for people at a high risk of sudden death (SCD and SUDEP). [ABSTRACT FROM AUTHOR]

Context Energy drinks (EDs) are beverages that contain ingredients that may pose a risk to consumers' cardiovascular health. But current evidence is conflicting and warrants further investigation. Objective A systematic review and meta-analysis was conducted on studies that examined the acute effects of ED consumption on systolic blood pressure (SBP), diastolic blood pressure (DBP), resting heart rate, cardiac output (CO), endothelial function, and QT/QTc interval in healthy adults. Data Sources The databases PubMed, EMBASE, Cochrane, LILACS, Web of Science, SportDiscus, and the gray literature were searched to identify randomized controlled trials (RCTs). Data Extraction Two independent evaluators screened 2014 studies and extracted relevant data from those selected for the analysis. A risk of bias assessment was also performed with the RoB 2 tool and a strength of evidence assessment was performed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Data Analysis A total of 17 RCTs were included in the meta-analysis. With regard to risk of bias, 11 studies were rated as having "some concerns" and 6 as "high risk of bias." The consumption of EDs increased SBP, DBP, and CO in different time frames. More pronounced effects were seen on SBP at 60-80 minutes (4.71 mmHg; 95% CI: 2.97–6.45; GRADE: moderate), DBP at 120 minutes (4.51 mmHg; 95% CI: 2.60–6.42; GRADE: low), and CO at 30-40 minutes after consumption (0.43 L; 95% CI: 0.08–0.77; GRADE: very low). The effects of ED consumption on resting heart rate and QT/QTc interval were not significant (P ≤ 0.05). The assessment of endothelial function effects was not performed due to the absence of any RCTs meeting the inclusion criteria. Conclusions Acute consumption of EDs increases SBP, DBP, and CO in healthy adults. However, no alterations were observed in other cardiovascular parameters. The results should be interpreted with caution due to the limited number of studies included in the analysis. Systematic Review Registration PROSPERO registration no. CRD42022295335. [ABSTRACT FROM AUTHOR]

BACKGROUND: CaM (calmodulin)-mediated long-QT syndrome is a genetic arrhythmia disorder (calmodulinopathies) characterized by a high prevalence of life-threatening ventricular arrhythmias occurring early in life. Three distinct genes (CALM1, CALM2, and CALM3) encode for the identical CaM protein. Conventional pharmacotherapies fail to adequately protect against potentially lethal cardiac events in patients with calmodulinopathy. METHODS: Five custom-designed CALM1-, CALM2-, and CALM3-targeting short hairpin RNAs (shRNAs) were tested for knockdown (KD) efficiency using TSA201 cells and reverse transcription-quantitative polymerase chain reaction. A dualcomponent suppression and replacement (SupRep) CALM gene therapy (CALM-SupRep) was created by cloning into a single construct CALM1-, CALM2-, and CALM3-specific shRNAs that produce KD (suppression) of each respective gene and a shRNA-immune CALM1 cDNA (replacement). CALM1-F142L, CALM2-D130G, and CALM3-D130G induced pluripotent stem cell-derived CMs were generated from patients with CaM-mediated long-QT syndrome. A voltage-sensing dye was used to measure action potential duration at 90% repolarization (APD90). RESULTS: Following shRNA KD efficiency testing, a candidate shRNA was identified for CALM1 (86% KD), CALM2 (71% KD), and CALM3 (94% KD). The APD90 was significantly prolonged in CALM2-D130G (647±9 ms) compared with CALM2-WT (359±12 ms; P<0.0001). Transfection with CALM-SupRep shortened the average APD90 of CALM2-D130G to 457±19 ms (66% attenuation; P<0.0001). Additionally, transfection with CALM-SupRep shortened the APD90 of CALM1-F142L (665±9 to 410±15 ms; P<0.0001) and CALM3-D130G (978±81 to 446±6 ms; P<0.001). CONCLUSIONS: We provide the first proof-of-principle suppression-replacement gene therapy for CaM-mediated long-QT syndrome. The CALM-SupRep gene therapy shortened the pathologically prolonged APD90 in CALM1-, CALM2-, and CALM3-variant CaM-mediated long-QT syndrome induced pluripotent stem cell-derived CM lines. The single CALM-SupRep construct may be able to treat all calmodulinopathies, regardless of which of the 3 CaM-encoding genes are affected. [ABSTRACT FROM AUTHOR]

QTc prolongation and torsade de pointes (TdP) are significant adverse events linked to azole antifungals. Reports on QTc interval prolongation caused by these agents are limited. In this study, we report a case of a 77-year-old male with cardiovascular disease who experienced QTc prolongation and subsequent TdP while being treated with fluconazole for Candida albicans-induced knee arthritis. Additionally, a literature review was conducted on cases where QTc prolongation and TdP were triggered as adverse events of azole antifungal drugs. The case study detailed the patient's experience, whereas the literature review analyzed cases from May 1997 to February 2023, focusing on patient demographics, underlying diseases, antifungal regimens, concurrent medications, QTc changes, and outcomes. The review identified 16 cases, mainly in younger individuals (median age of 29) and women (75%). Fluconazole (63%) and voriconazole (37%) were the most common agents. Concurrent medications were present in 75% of cases, and TdP occurred in 81%. Management typically involved discontinuing or switching antifungals and correcting electrolytes, with all patients surviving. Risk assessment and concurrent medication review are essential before starting azole therapy. High-risk patients require careful electrocardiogram monitoring to prevent arrhythmias. Remote monitoring may enhance safety for patients with implanted devices. Further studies are needed to understand risk factors and management strategies. [ABSTRACT FROM AUTHOR]

Introduction: KCNQ1 and KCNE1 form slowly activating delayed rectifier potassium currents (IKs). Loss-of-function of IKs by KCNQ1 variants causes type-1 long QT syndrome (LQTS). Also, some KCNQ1 variants are reported to cause epilepsy. Segment 4 (S4) of voltage-gated potassium channels has several positively-charged amino acids that are periodically aligned, and acts as a voltage-sensor. Intriguingly, KCNQ1 has a neutral-charge glutamine at the third position (Q3) in the S4 (Q234 position in KCNQ1), which suggests that the Q3 (Q234) may play an important role in the gating properties of IKs. We identified a novel KCNQ1 Q234K (substituted for a positively-charged lysine) variant in patients (a girl and her mother) with LQTS and epileptiform activity on electroencephalogram. The mother had been diagnosed with epilepsy. Therefore, we sought to elucidate the effects of the KCNQ1 Q234K on gating properties of IKs. Methods: Wild-type (WT)-KCNQ1 and/or Q234K-KCNQ1 were transiently expressed in tsA201-cells with KCNE1 (E1) (WT + E1-channels, Q234K + E1- channels, and WT + Q234K + E1-channels), and membrane currents were recorded using whole-cell patch-clamp techniques. Results: At 8-s depolarization, current density (CD) of the Q234K + E1-channels or WT + Q234K + E1-channels was significantly larger than the WT + E1-channels (WT + E1: 701 ± 59 pA/pF; Q234K + E1: 912 ± 50 pA/pF, p < 0.01; WT + Q234K + E1: 867 ± 48 pA/pF, p < 0.05). Voltage dependence of activation (VDA) of the Q234K + E1-channels or WT + Q234K + E1-channels was slightly but significantly shifted to depolarizing potentials in comparison to the WT + E1-channels ([V1/2] WT + E1: 25.6 ± 2.6 mV; Q234K + E1: 31.8 ± 1.7 mV, p < 0.05; WT + Q234K + E1: 32.3 ± 1.9 mV, p < 0.05). Activation rate of the Q234K + E1-channels or WT + Q234K + E1- channels was significantly delayed in comparison to the WT + E1-channels ([half activation time] WT + E1: 664 ± 37 ms; Q234K + E1: 1,417 ± 60 ms, p < 0.01; WT + Q234K + E1: 1,177 ± 71 ms, p < 0.01). At 400-ms depolarization, CD of the Q234K + E1-channels or WT + Q234K + E1-channels was significantly decreased in comparison to the WT + E1-channels (WT + E1: 392 ± 42 pA/pF; Q234K + E1: 143 ± 12 pA/pF, p < 0.01; WT + Q234K + E1: 209 ± 24 pA/pF, p < 0.01) due to delayed activation rate and depolarizing shift of VDA. Conclusion: The KCNQ1 Q234K induced IKs gain-of-function during long (8-s)- depolarization, while loss of-function during short (400-ms)-depolarization, which indicates that the variant causes LQTS, and raises a possibility that the variant may also cause epilepsy. Our data provide novel insights into the functional consequences of charge addition on the Q3 in the S4 of KCNQ1. [ABSTRACT FROM AUTHOR]

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Background and Aims Risk scores are proposed for genetic arrhythmias. Having proposed in 2010 one such score (M-FACT) for the long QT syndrome (LQTS), this study aims to test whether adherence to its suggestions would be appropriate. Methods LQT1/2/3 and genotype-negative patients without aborted cardiac arrest (ACA) before diagnosis or cardiac events (CEs) below age 1 were included in the study, focusing on an M-FACT score ≥2 (intermediate/high risk), either at presentation (static) or during follow-up (dynamic), previously associated with 40% risk of implantable cardioverter defibrillator (ICD) shocks within 4 years. Results Overall, 946 patients (26 ± 19 years at diagnosis, 51% female) were included. Beta-blocker (βB) therapy in 94% of them reduced the rate of those with a QTc ≥500 ms from 18% to 12% (P <.001). During 7 ± 6 years of follow-up, none died; 4% had CEs, including 0.4% with ACA. A static M-FACT ≥2 was present in 110 patients, of whom 106 received βBs. In 49/106 patients with persistent dynamic M-FACT ≥2, further therapeutic optimization (left cardiac sympathetic denervation in 55%, mexiletine in 31%, and ICD at 27%) resulted in just 7 (14%) patients with CEs (no ACA), with no CEs in the remaining 57. Additionally, 32 patients developed a dynamic M-FACT ≥2 but, after therapeutic optimization, only 3 (9%) had C Es. According to an M-FACT score ≥2, a total of 142 patients should have received an ICD, but only 22/142 (15%) were implanted, with shocks reported in 3. Conclusions Beta-blockers often shorten QTc, thus changing risk scores and ICD indications for primary prevention. Yearly risk reassessment with therapy optimization leads to fewer ICD implants (3%) without increasing life-threatening events. [ABSTRACT FROM AUTHOR]

Idiopathic ventricular fibrillation is diagnosed in survivors of sudden cardiac death that has been caused by ventricular fibrillation without known structural or electrical abnormalities, even after extensive investigation. It is a common cause of sudden death in young adults. Although idiopathic ventricular fibrillation is a diagnosis of exclusion, in many cases only a partial investigation algorithm is performed. The aim of this review is to present a comprehensive diagnostic evaluation algorithm with a focus on diagnostic assessment of inherited arrhythmic syndromes and genetic background. [ABSTRACT FROM AUTHOR]

Background: Inherited cardiomyopathies (HCM, DCM, ACM) and cardiac ion channelopathies (long QT/Brugada syndromes, CPVT) are associated with significant morbidity and mortality; however, diagnosis of a familial pathogenic variant in a proband allows for subsequent cascade screening of their at-risk relatives. Aims: We investigated the diagnostic yield from cardiac gene panel testing and reviewed variants of uncertain significance from patients attending three specialist cardiogenetics services in Ireland in the years 2002 to 2020. Results: Reviewing molecular genetic diagnostic reports of 834 patients from 820 families, the initial diagnostic yield of pathogenic/likely pathogenic variants was 237/834 patients (28.4%), increasing to 276/834 patients (33.1%) following re-evaluation of cases with variant(s) of uncertain significance. Altogether, 42/85 patients with VUS reviewed (49.4%) had a re-classification that could change their clinical management. Females were more likely to carry pathogenic/likely pathogenic variants than males (139/374, 37.2% vs 137/460, 29.8%, respectively, p = 0.03), and the diagnostic yields were highest in the 0 to < 2 years age group (6/12, 50.0%) and amongst those tested for cardiomyopathy gene panels (13/35, 37.1%). Variants in the MYBPC3/MYH7 (87/109, 79.8%) and KCNQ1/KCNH2 (91/100, 91.0%) genes were the predominant genetic causes for hypertrophic cardiomyopathy and long QT syndrome, respectively. Conclusion: Our study highlights the importance of collation and review of pre-ACMG genetic variants to increase diagnostic utility of genetic testing for inherited heart disease. Almost half of patients with pre-ACMG VUS reviewed had their variant re-classified to likely pathogenic/likely benign which resulted in a positive clinical impact for patients and their families. [ABSTRACT FROM AUTHOR]

Abstract Background The characteristics of electrocardiogram (ECG) abnormalities related to cardiac channelopathies potentially linked to sudden cardiac death (SCD) are not widely recognized in Iran. We examined the prevalence of such ECG patterns and their related factors among adult residents of Tehran, Iran. Methods The clinical characteristics and 12-lead ECGs of Tehran Cohort Study participants were examined. Long QT intervals, short QT intervals, Brugada syndrome (BrS) patterns, and early repolarization (ER) were evaluated using computer-based assessment software validated by cardiologists. Logistic regression models were employed to identify the factors associated with the prevalence of different ECG patterns. Results Out of 7678 available ECGs, 7350 were included in this analysis. Long QT interval, ER pattern, BrS patterns, and short QT interval were found in 3.08%, 1.43%, 0.31%, and 0.03% of participants, respectively. The prevalence of long QT interval increased with age, opium consumption, and presence of hypertension. Younger age, lower body mass index (BMI), alcohol use and male sex were independently linked to an elevated prevalence of ER pattern. Most individuals with BrS patterns were men (95%) and had lower BMI, high- and low-density lipoprotein, and total cholesterol compared to those without the BrS pattern. At a mean follow-up of 30.2 ± 5.5 months, all-cause mortality in the group exhibiting abnormal ECG patterns (6.3%) was approximately twice as high as that in the group without such patterns (2.96%). Conclusion Abnormal ECG patterns corresponding to channelopathies were relatively rare among adult residents of the Tehran population, and their prevalence was influenced by various factors. Clinical trial number Not applicable.

Background: Long QT syndrome (LQTS) is a rare cardiac disorder characterized by prolonged ventricular repolarization and increased risk of ventricular arrhythmias. This review summarizes current knowledge of LQTS pathogenesis and treatment strategies. Objectives: The purpose of this study was to provide an in-depth understanding of LQTS genetic and molecular mechanisms, discuss clinical presentation and diagnosis, evaluate treatment options, and highlight future research directions. Methods: A systematic search of PubMed, Embase, and Cochrane Library databases was conducted to identify relevant studies published up to April 2024. Results: LQTS involves mutations in ion channel–related genes encoding cardiac ion channels, regulatory proteins, and other associated factors, leading to altered cellular electrophysiology. Acquired causes can also contribute. Diagnosis relies on clinical history, electrocardiographic findings, and genetic testing. Treatment strategies include lifestyle modifications, β-blockers, potassium channel openers, device therapy, and surgical interventions. Conclusion: Advances in understanding LQTS have improved diagnosis and personalized treatment approaches. Challenges remain in risk stratification and management of certain patient subgroups. Future research should focus on developing novel pharmacological agents, refining device technologies, and conducting large-scale clinical trials. Increased awareness and education are crucial for early detection and appropriate management of LQTS.