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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., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Heart failure (HF) with reduced ejection fraction (HFrEF) is a risk factor for drug-induced QT interval prolongation. It is unknown if HF with preserved ejection fraction (HFpEF) is also associated with an increased risk. Dofetilide and sotalol are potent QT interval-prolonging agents that are frequently used in patients with HFpEF, in whom atrial fibrillation is a common comorbidity. We tested the hypothesis that the risk of QT interval prolongation associated with dofetilide and sotalol is increased in patients with HFpEF. We conducted a retrospective cohort study conducted using electronic health records from the Indiana Network for Patient Care (January 31, 2010 -May 3, 2021). After removing patients with overlapping diagnoses of HFpEF and HFrEF, no diagnosis code, and absence of QT interval records, we identified patients taking dofetilide or sotalol among three groups: HFrEF (n = 138), HFpEF (n = 109), and no HF (n = 729). QT prolongation was defined as heart rate-corrected QT (QTc) > 500 ms during dofetilide/sotalol therapy. Unadjusted odds ratios (OR) for QT prolongation were determined by univariate analysis. Adjusted ORs were determined by generalized estimating equations (GEE) with logit link to account for an individual cluster with different times of hospitalization and covariates. QTc prolongation associated with dofetilide or sotalol occurred in 53.2%, 71.7% and 30.0% of patients with HFpEF, HFrEF, and patients with no HF, respectively. After adjusting for age, sex, race, serum potassium and magnesium concentrations, kidney function, concomitant drug therapy, and comorbid conditions, the adjusted odds of QTc prolongation were significantly higher in patients with HFpEF [OR = 1.98 (95% CI 1.17-3.33)], and in those with HFrEF [OR = 5.23, (3.15-8.67)], compared to those with no evidence of HF. The odds of QT prolongation among inpatients receiving dofetilide or sotalol were increased in patients with HFpEF and HFrEF compared to those who did not have HF., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Long QT syndrome (LQTS) has been reported in older patients with advanced non-small cell lung cancer (NSCLC) following the use of osimertinib, the third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). However, there have not been analytic epidemiology studies on this topic. We aimed to compare the risk of LQTS between osimertinib and first/second-generation EGFR-TKIs in older patients with advanced NSCLC., Research Design and Methods: This retrospective observational study used the 2006-2019 Surveillance, Epidemiology, and End Results (SEER)-Medicare data and included older patients with advanced NSCLC who were treated with either osimertinib or first/second-generation EGFR-TKIs during 2007-2017. Inverse probability of treatment weighting (IPTW) was used to balance the two groups with propensity scores estimated based on the patients' socioeconomic and clinical characteristics. Crude incidence rate (IR) and adjusted hazard ratio (HR) of the primary outcome, incident LQTS, were estimated., Results: A total of 545 and 1,135 patients were included in the osimertinib and first/second-generation EGFR-TKI groups, which increased to 1,614 and 1,659, respectively, after IPTW. The osimertinib group had a higher IR of LQTS (2.62 per 100 person-years, 95% CI 2.03-3.38) compared to the first/second-generation EGFR-TKI group (1.33 per 100 person-years, 95% CI 0.92-1.92). After adjusting for covariates, the osimertinib group had a higher risk of LQTS than the first/second-generation EGFR-TKI group, with an HR of 1.94 (95% CI 1.23-3.08). The increased LQTS risk in the osimertinib group was even higher in females, whites and patients aged ≥ 75., Conclusions: Given the elevated risk of LQTS associated with osimertinib user, close monitoring for cardiac rhythm irregularities of high-risk patients following initiation of EGFR-TKI is recommended.

Cardiovascular disease is a major global burden and a leading cause of premature death among patients with severe mental illness. Over time, research and clinical practice have paid increased attention to the impact of psychiatric medications on cardiac repolarization. In a resource-limited setting, it is common for psychotropic medications to be initiated and maintained in an outpatient setting without baseline or follow up ECG. This study evaluated the determinants and predictors of QT abnormalities among patient taking psychotropic drugs. We conducted a cross-sectional study in a population of 150 psychiatric patients on psychotropics and 75 controls. We studied the effects of various psychotropic drugs on QT dispersion (QTd) and corrected QT interval (QTc) as well as correlation with the types and dosages of psychotropic drugs used. All the subjects had detailed clinical examination and resting electrocardiogram (ECG) at 25 mm/sec done. QTc was determined using Bazett formula and QTd was determined by subtracting shortest from longest QT in 12-lead ECG. The prevalence of prolonged QTc and QTd as well as the mean QTc and QTd were significantly higher in patients than the control group. The mean QTc was significantly higher in patient on typical antipsychotics compared to those on atypical antipsychotics. Age, heart rate and antipsychotic dose in chlorpromazine equivalent were predictors of QTc with the heart rate being the most powerful predictor among them. Psychotropic drugs use is associated with QTc and QTd prolongation with age, heart rate and antipsychotic dose as predictors of QTc., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Drug-induced QT interval prolongation has been reported to be related to life-threatening polymorphic ventricular tachycardia (torsade de pointes). Proton pump inhibitors (PPIs) are prescribed widely for hospitalized patients; the QT interval prolongation and torsade de pointes caused by PPIs were reported. We conducted a study to determine the association between PPI treatment and QT interval prolongation in critically ill patients., Methods: This study included patients with electrocardiography (ECG) reports from the Medical Information Mart for Intensive Care III database (MIMIC-III). Patients younger than 18 years, missing baseline laboratories and with QT interval prolongation before intensive care unit (ICU) admission were excluded. The end point was the diagnosis of QT interval prolongation reported by ECG., Results: This study included 24,512 ICU patients. Of them, 11,327 patients were treated with PPIs, 4181 with histamine 2 receptor antagonists (H 2 RAs) and 6351 without acid suppression therapy (non-AST); the incidence of QT interval prolongation were 8.5%, 3.3% and 3.4% respectively. After adjustment for demographics, electrolytes, comorbidities and medications, PPIs were associated a higher risk of QT interval prolongation compared with H 2 RAs (OR 1.66, 95% CI 1.36 - 2.03) and non-AST (OR 1.54, 95% CI 1.31 - 1.82), while there was not significant difference between H 2 RAs and non-AST (OR 0.93, 95% CI 0.73 - 1.17). In the propensity score matching population, the results were consistent. Pantoprazole (OR 2.14, 95% CI 1.52 - 3.03) and lansoprazole (OR 1.80, 95% CI: 1.18 - 2.76) showed a higher QT prolongation risk than omeprazole. Several drugs caused higher QT prolongation risk when used in combination with PPIs., Conclusion: In ICU patients, the association between PPI prescription and increased risk of QT interval prolongation was independent of known QT-prolonging factors; pantoprazole and lansoprazole had a higher risk compared with omeprazole. The combination of PPIs and other QT-prolonging drugs should be avoided., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Many antipsychotic drugs have been associated with QTc prolongation, which is a risk factor for sudden death. We studied the prevalence and predictors of QTc prolongation in treatment-resistant schizophrenia patients who were receiving clozapine in a real-world setting., Methods: Data were extracted from the records of all schizophrenia patients aged 18-65 years, enrolled in a clozapine clinic in metropolitan Australia during October 2020 to April 2022, for whom ECG data were available., Results: There were 104 eligible patients. The mean age of the sample was 42 years. The sample was 56 % male. About a third of patients were receiving antipsychotic and antidepressant drugs in addition to clozapine. The mean (standard deviation) QTc was 437.0 (24.8) ms in men and 445.8 (28.5) ms in women. QTc prolongation was present in 36.5 % of the sample. In univariate analysis, higher heart rate and higher clozapine levels were significantly associated with QTc prolongation; in multivariable logistic regression analysis, nonsignificant statistical trends were observed for male sex, higher heart rate, and higher serum clozapine level., Conclusions: QTc prolongation may be common in schizophrenia patients who receive clozapine in real world settings; this is a matter of much concern. Potential predictors of QTc prolongation need to be identified and these predictors and their interactions require to be explored in studies with greater statistical power., Competing Interests: Declaration of competing interest We have no conflicts to declare with regard to the contents of this manuscript., (Crown Copyright © 2023. Published by Elsevier B.V. All rights reserved.)

Aim: QTc interval prolongation is a growing global issue which can cause torsades de pointes, a potentially fatal arrhythmia. We aimed to identify risk factors for prolonged QT interval in men and women., Methods: The Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort study collected electrocardiogram interval data. QT was corrected for heart rate using the Bazett's formula. Ordinal logistic regression with crude (univariable) and adjusted (multivariate) association analyses in the form of odds ratio and corresponding 95% confidence interval (CI) were used to identify the factors associated with QTc prolongation., Results: A total of 8878 individuals including 5318 females and 3560 males, aged 35 to 65 years, were included in this cross-sectional study. Participants with QTc prolongation were more likely to be older and have hypercholesterolemia, hypertension (HTN), and Type 2 diabetes mellitus (T2DM), but to have lower levels of physical activity (P < 0.05). Age (OR = 1.68, 95%CI = 1.18-2.39), hypercholesterolemia (OR = 1.77, 95%CI = 1.24-2.51), HTN (OR = 1.36, 95%CI = 1.06-1.73), T2DM (OR = 1.59, 95%CI = 1.19-2.13), severe anxiety (OR = 1.80, 95%CI = 1.05-3.11) and mild depression (OR = 1.38, 95%CI = 1.01-1.88) were independent risk factors for prolonged QTc interval in men. For women, only HTN (OR = 1.29, 95%CI = 1.02-1.63) and T2DM (OR = 1.50, 95%CI = 1.14-1.97) were independent risk factors., Conclusions: Older age, Hypercholesterolemia, HTN, T2DM, severe anxiety and mild depression in men, and HTN and T2DM in women were associated with high risk of prolonged QTc interval. Healthcare practitioners should be aware of the risk factors of QTc interval prolongation and should exercise caution in the management of certain patients., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Case reports suggest that quetiapine or haloperidol use is associated with severe QT prolongation (SQTP) and torsades de pointes., Objective: The purpose of this study was to examine the incidences, risk factors, and outcomes of SQTP in quetiapine and haloperidol users., Methods: This study accessed electronic medical records from a multicenter health-care hospital system in Taiwan and included patients who received quetiapine or haloperidol therapy and had both baseline and follow-up electrocardiograms. SQTP was defined as a posttreatment corrected QT (QTc) interval exceeding 500 ms or an increase in QTc interval of >60 ms compared with the baseline value. We analyzed the risk factors and outcomes of SQTP using multivariate logistic regression., Results: Mean increases in QTc interval were +8.3 ± 51.8 and +8.9 ± 44.0 ms after the administration of quetiapine (n = 8832) and haloperidol (n = 2341). Among these users, 1149 (13.0%) and 333 (14.2%) developed SQTP, respectively. Common risk factors for SQTP included old age, heart failure, hypokalemia, amiodarone use, and baseline QTc interval. SQTP in quetiapine users was significantly associated with ventricular arrhythmias (odds ratio 2.84; 95% confidence interval 1.95-4.13) and sudden cardiac death (odds ratio 2.29; 95% confidence interval 1.44-3.66)., Conclusion: More than 10% of patients receiving quetiapine or haloperidol therapy developed SQTP, and many of them were exposed to risk factors for SQTP. SQTP in quetiapine users was significantly associated with increased risks of ventricular arrhythmias and sudden cardiac death. Clinicians should be vigilant for ventricular arrhythmias in quetiapine users who have risk factors for SQTP., Competing Interests: Disclosures All authors have no conflicts to disclose., (Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Although accumulating data indicate that IL-6 (interleukin-6) can promote heart rate-corrected QT interval (QTc) prolongation via direct and indirect effects on cardiac electrophysiology, current evidence comes from basic investigations and small clinical studies only. Therefore, IL-6 is still largely ignored in the clinical management of long-QT syndrome and related arrhythmias. The aim of this study was to estimate the risk of QTc prolongation associated with elevated IL-6 levels in a large population of unselected subjects., Methods and Results: An observational study using the Veterans Affairs Informatics and Computing Infrastructure was performed. Participants were US veterans who had an ECG and were tested for IL-6. Descriptive statistics and univariate and multivariate regression analyses were performed to study the relationship between IL-6 and QTc prolongation risk. Study population comprised 1085 individuals, 306 showing normal (<5 pg/mL), 376 moderately high (5-25 pg/mL), and 403 high (>25 pg/mL) IL-6 levels. Subjects with elevated IL-6 showed a concentration-dependent increase in the prevalence of QTc prolongation, and those presenting with QTc prolongation exhibited higher circulating IL-6 levels. Stepwise multivariate regression analyses demonstrated that increased IL-6 level was significantly associated with a risk of QTc prolongation up to 2 times the odds of the reference category of QTc (e.g. QTc >470 ms men/480 ms women ms: odds ratio, 2.28 [95% CI, 1.12-4.50] for IL-6 >25 pg/mL) regardless of the underlying cause. Specifically, the mean QTc increase observed in the presence of elevated IL-6 was quantitatively comparable (IL-6 >25 pg/mL:+6.7 ms) to that of major recognized QT-prolonging risk factors, such as hypokalemia and history of myocardial infarction., Conclusions: Our data provide evidence that a high circulating IL-6 level is a robust risk factor for QTc prolongation in a large cohort of US veterans, supporting a potentially important arrhythmogenic role for this cytokine in the general population.

Background: Acquired prolonged corrected QT (QTc) interval can lead to life-threatening Torsade de Pointes (TdP) arrhythmia. Multiple risk factors including medications, comorbidities, and electrolyte imbalances contribute significantly to acquired manifestations of the QTc prolongation. Critically ill patients are particularly more vulnerable to TdP due to complex medical conditions, aging, and polypharmacy., Objective: This study aimed to assess the prevalence of TdP-associated medication prescribing, identify risk factors for QTc prolongation and TdP, and determine primary predictors of high TdP medication usage in critically ill patients in Jordan., Methods: We conducted a retrospective cross-sectional analysis of electronic medical records for patients from King Abdullah University Hospital who were admitted to Intensive Care Unit (ICU) between (July 2012-July 2022). We collected data on patients' demographics, clinical characteristics, comorbidities, laboratory results, and prescribed medications. Medications were categorized into three TdP risk levels according to CredibleMeds ® assessment tool. Data were analyzed using descriptive statistics and a binary logistic regression model., Results: Of the 13,300 patients (58.2% male, median age 62 years). Prescribing prevalence for medications with known TdP risk was 19%, possible risk (24.7%), conditional risk (21.6%), and confirmed conditional risk (8.3%). Common comorbidities included hypertension (40.9%), diabetes (33.3%), and cancer (15.4%). Drugs with known TdP risk included citalopram, amiodarone, clarithromycin, and ciprofloxacin. A binary regression model revealed that as age increased, the odds of TdP associated medication prescribing decreased (OR = 0.989, p < 0.001), while patients on more than five medications had higher odds (OR = 4.281, p < 0.001)., Conclusion: The study identified a notable prevalence of prescribing for medications with QTc prolongation/TdP risk in critically ill patients. Healthcare providers in the ICU should exercise caution to minimize the inadvertent prescription of TdP associated medications especially among older patients and those with polypharmacy., Competing Interests: The authors declare no competing interest in this work., (© 2024 Al-Azayzih et al.)

Background: Drug-drug interactions (DDIs) are considered an emerging threat to the patients if undetected. DDIs can prolong QT interval, leading to fatal ventricular arrhythmia. Antipsychotics and antidepressants prescribed commonly to psychiatric patients have the propensity to prolong QT interval and can precipitate Torsades de pointes (TdP). This review aimed to summarize the prevalence of QT interval prolonging DDIs in psychiatric patients. Methods: This meta-analysis was carried out following the MOOSE (Meta-analysis of Observational Studies in Epidemiology) statement. Databases like Pubmed/MEDLINE, Google Scholar and Research gate were scanned for English language papers. Indexed terms from Medical Subject (MeSH) and other search terms for "QT prolongation", "Drug interactions", and "Psychiatry" were used to identify the articles. All published articles available until the day of the collection were considered. Outcome measures were analyzed with meta package in R language. Results: A total of 5 studies were eligible for inclusion. From the included studies, QT-prolonging DDIs were found in 14806 patients out of 30122 patients. The prevalence of QT-prolonging DDIs in psychiatric patients was found to be 42% (95% confidence interval: 21%, 66%). The factors associated with potential drug-drug interactions were related to patient characteristics such as polypharmacy, age and comorbid disease. Conclusion: This review concluded that psychiatric patients were prescribed the drugs/drug combinations which can prolong QT interval and can cause adverse effects on the cardiovascular system. Hence, it is important to implement precautionary safety interventions, be vigilant and prevent QT prolongation and adverse cardiac effects in clinical practice., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Benzodiazepine (BDZ) addiction is a widespread and multifaceted phenomenon. For many patients, especially females, the concomitant use of other drugs also increases their risk of QTc prolongation, possibly leading to complications such as seizures and even sudden death. However, the relationship between BDZ use and QTc prolongation is currently unclear. The present study aims to examine patterns of polysubstance use among a sample of Italian adults with BDZ dependence in relation with their QTc prolongation risk. We used Latent Class Analysis (LCA) on data collected from 251 inpatients of the Addiction Medicine Unit in Verona to group patients into three classes according to their substance use and their QTc prolongation risk. Results showed no significant relationship between QTc prolongation and BDZ use in any of the classes considered. We conclude that BDZs, even if used long-term and at high dosages, can be considered safe in terms of cardiovascular complications for patients., (© 2024. The Author(s).)

Background: Indigenous women have higher rates of chronic disease than Indigenous men and non-Indigenous women. Long QT syndrome (LQTS) can be inherited or acquired; the latter may occur with chronic disease. A prolonged corrected QT value (QTc) is an independent risk factor for ventricular arrhythmias and sudden death, but few studies have quantified the impact of chronic disease on the QTc. We assessed the association between chronic disease and QTc prolongation in a population of First Nations women previously ascertained to study a high rate of inherited LQTS due to a unique genetic (founder) variant in their community., Methods: This substudy focusing on women expands on the original research where patients with clinical features of LQTS and their relatives were assessed for genetic variants discovered to affect the QTc. Medical records were retrospectively reviewed and chronic diseases documented. Using multivariate linear regression, adjusting for the effect of genetic variants, age, and QTc-prolonging medications, we evaluated the association between chronic disease and the QTc., Results: In total, 275 women were included. After adjustments, a prolonged QTc was associated with coronary artery disease (26.5 ms, 95% confidence interval [CI] 9.0-44.1 ms; P = 0.003), conduction system disease (26.8 ms, 95% CI 2.2-51.4 ms; P = 0.033), rheumatoid arthritis (28.9 ms, 95% CI 12.7-45.1 ms; P = 0.001), and type 2 diabetes mellitus (17.9 ms, 95% CI 3.6-32.3 ms; P = 0.015)., Conclusions: This quantification of the association between chronic disease and QTc prolongation in an Indigenous cohort provides insight into the nongenetic determinants of QTc prolongation. Corroboration in other populations will provide evidence for generalisability of these results., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The inhibition of human ether-a-go-go-related gene (hERG) channels is a known cause of QT prolongation triggered by antipsychotic drugs. Our previous studies suggest that P-glycoprotein (P-gp)-mediated drug interactions may lead to increased gastrointestinal absorption of pimozide and its accumulation in cardiomyocytes, thereby enhancing the inhibitory effect of hERG channels. There is a paucity of epidemiological studies examining the risk of QT prolongation by antipsychotic drugs in terms of P-gp-mediated interactions with concomitant drugs. Therefore, using the Japanese Adverse Event Reporting Database, we investigated whether the risk of QT prolongation triggered by antipsychotic drugs associated with hERG inhibition is affected by the concomitant use of selective serotonin reuptake inhibitors (SSRIs) associated with P-gp inhibition. The results showed that the frequency of QT prolongation increased when the antipsychotic drugs quetiapine and sulpiride, which are P-gp substrates, were combined with SSRIs with P-gp inhibition. In contrast, no association with QT prolongation was observed in patients on non-P-gp-substrate antipsychotics, irrespective of the P-gp inhibitory effect of the concomitant SSRI. These results suggest that P-gp-mediated interactions are a risk factor for antipsychotic-induced QT prolongation. There is a need for further investigation into the risks of specific drug combinations., (© 2023, The American College of Clinical Pharmacology.)

Introduction: Patients with SARS-CoV-2 infection may present cardiovascular involvement including myocarditis, arrhythmias and QT interval prolongation. Our objective was to evaluate the impact of COVID-19 and its treatment on ventricular repolarization and development of arrhythmias in critically ill patients., Methods: Retrospective cohort study of critically ill COVID-19 patients during a 3-month period in whom at least one ECG was available. Relevant clinical data and specific treatment administered for COVID-19 were recorded. Prolonged QTc was considered prolonged when it measured ≥ 460 ms in women and ≥450 ms in men. The incidence and type of arrhythmias during the same period were recorded., Results: A total of 77 patients with a mean age of 62 ± 13 years, 20 women and 57 men, were evaluated. Sixty percent of the patients were hypertensive, 52% had a BMI > 30, and 70% developed acute renal failure during admission. Some 56% of the patients presented QTc prolongation. Forty-four percent presented some type of arrhythmia during their stay in the ICU, 21% of which were atrial arrhythmias. Overall mortality was 53%, with no differences between patients with or without prolonged QTc., Conclusions: In our series, a high proportion of critical patients with COVID-19 presented prolonged QTc and arrhythmias. The factors involved have been related to the elevation of cardiac biomarkers, the myocardial involvement of the virus and concomitant medication received in the ICU., (Copyright © 2023. Publicado por Elsevier España, S.L.U.)

Background: Fluoroquinolones, crucial components of treatment regimens for drug-resistant tuberculosis (TB), are associated with QT interval prolongation and risks of fatal cardiac arrhythmias. However, few studies have explored dynamic changes in the QT interval in patients receiving QT-prolonging agents., Methods: This prospective cohort study recruited hospitalized patients with TB who received fluoroquinolones. The study investigated the variability of the QT interval by using serial electrocardiograms (ECGs) recorded four times daily. This study analyzed the accuracy of intermittent and single-lead ECG monitoring in detecting QT interval prolongation., Results: This study included 32 patients. The mean age was 68.6 ± 13.2 years. The results revealed mild-to-moderate and severe QT interval prolongation in 13 (41%) and 5 (16%) patients, respectively. The incremental yields in sensitivity of one to four daily ECG recordings were 61.0%, 26.1%, 5.6%, and 7.3% in detecting mild-to-moderate QT interval prolongation, and 66.7%, 20.0%, 6.7%, and 6.7% in detecting severe QT interval prolongation. The sensitivity levels of lead II and V5 ECGs in detecting mild-to-moderate and severe QT interval prolongation exceeded 80%, and their specificity levels exceeded 95%., Conclusion: This study revealed a high prevalence of QT interval prolongation in older patients with TB who receive fluoroquinolones, particularly those with multiple cardiovascular risk factors. Sparsely intermittent ECG monitoring, the prevailing strategy in active drug safety monitoring programs, is inadequate owing to multifactorial and circadian QT interval variability. Additional studies performing serial ECG monitoring are warranted to enhance the understanding of dynamic QT interval changes in patients receiving QT-prolonging anti-TB agents., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Objective: Individuals receiving hemodialysis have high rates of sudden cardiac death (SCD). This study characterized oral atypical antipsychotic use and compared the cardiac safety of atypical antipsychotics with QT prolongation FDA warnings to that of atypical antipsychotics without such warnings among outpatients receiving hemodialysis., Methods: Data for this active-comparator, new-user cohort study were obtained from the U.S. Renal Data System (2007-2019). The primary outcome was 1-year SCD risk. Fine and Gray proportional subdistribution hazard models with inverse probability of treatment weighting were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI)., Results: The quetiapine vs . atypical antipsychotic without QT prolongation warning cohort included 18,943 quetiapine new-users and 19,571 non-warning atypical antipsychotic new-users. When compared to new-use of atypical antipsychotics without QT prolongation warnings, quetiapine new-use was not associated with the risks of SCD (aHR (95% CI) = 1.00 (0.93, 1.07)) or broader cardiac outcomes. Comparisons of all atypical antipsychotics with QT prolongation warnings vs . atypical antipsychotics without warnings generated similar results., Conclusions: Quetiapine, which carries an FDA warning for QT prolongation, did not associate with cardiac risk compared to atypical antipsychotics without warnings among hemodialysis outpatients. Findings may inform prescriber selection of atypical antipsychotics in this population., Competing Interests: In the last 2 years, JEF has received honorarium from the American Society of Nephrology and served on a medical advisory board for Fresenius Kidney Care, North America and a scientific advisory board and Data and Safety Monitoring Committee for the NIDDK. Other authors have nothing to disclose.

Background: Health care resource utilization (HCRU) and costs are important metrics of health care burden, but they have rarely been explored in the setting of cardiac ion channelopathies., Hypothesis: This study tested the hypothesis that attendance-related HCRUs and costs differed between patients with Brugada syndrome (BrS) and congenital long QT syndrome (LQTS)., Methods: This was a retrospective cohort study of consecutive BrS and LQTS patients at public hospitals or clinics in Hong Kong, China. HCRUs and costs (in USD) for Accident and Emergency (A&E), inpatient, general outpatient and specialist outpatient attendances were analyzed between 2001 and 2019 at the cohort level. Comparisons were made using incidence rate ratios (IRRs [95% confidence intervals])., Results: Over the 19-year period, 516 BrS (median age of initial presentation: 51 [interquartile range: 38-61] years, 92% male) and 134 LQTS (median age of initial presentation: 21 [9-44] years, 32% male) patients were included. Compared to LQTS patients, BrS patients had lower total costs (2 008 126 [2 007 622-2 008 629] vs. 2 343 864 [2 342 828-2 344 900]; IRR: 0.857 [0.855-0.858]), higher costs for A&E attendances (83 113 [83 048-83 177] vs. 70 604 [70 487-70 721]; IRR: 1.177 [1.165-1.189]) and general outpatient services (2,176 [2,166-2,187] vs. 921 [908-935]; IRR: 2.363 [2.187-2.552]), but lower costs for inpatient stay (1 391 624 [1 391 359-1 391 889] vs. 1 713 742 [1 713 166-1 714 319]; IRR: 0.812 [0.810-0.814]) and lower costs for specialist outpatient services (531 213 [531 049-531 376] vs. 558 597 [558268-558926]; IRR: 0.951 [0.947-0.9550])., Conclusions: Overall, BrS patients consume 14% less health care resources compared to LQTS patients in terms of attendance costs. BrS patients require more A&E and general outpatient services, but less inpatient and specialist outpatient services than LQTS patients., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background: QTc prolongation is one of the possible complications in patients with schizophrenia taking antipsychotics, which leads to malignant cardiac arrhythmia. No meta-analysis has been reported assessing the prevalence and correlated risk factors for QTc prolongation., Methods: This meta-analysis aimed to assess the evidence for the prevalence of QTc prolongation and correlated risk factors in patients with schizophrenia taking antipsychotics. Web of Science and PubMed were searched according to preset strategy. The quality of research was assessed by the Newcastle-Ottawa Scale (NOS)., Results: In all, 15 studies covering 15,540 patients with schizophrenia taking antipsychotics were included. Meta-analysis showed that the prevalence of QTc prolongation in patients with schizophrenia taking antipsychotics was about 4.0% (95% confidence interval (CI): 3.0%-5.0%, p  < 0.001). The prevalence was about 4.0% in Asia (95%CI: 3.0%-6.0%, p  < 0.001), about 5.0% in Europe (95%CI: 2.0%-7.0%, p  < 0.001), and about 2.0% in America (95%CI: 1.0%-3.0%, p  < 0.001). Sensitivity analyses indicated the robustness of the result. Publication bias analysis reported a certain publication bias ( t  = 3.37, p  = 0.012). Meta-regression suggested that female and elderly patients were clinically associated with a higher prevalence of QTc prolongation. According to included studies, smoking, comorbidity of cardiovascular disease, and abnormal levels of high-density lipoprotein/low-density lipoprotein might be related to QTc prolongation in patients with schizophrenia taking antipsychotics., Conclusions: The prevalence of QTc prolongation in patients with schizophrenia taking antipsychotics was about 4.0%. Female and elderly patients were more likely to experience QTc prolongation. Close electrocardiogram monitoring was suggested in these at-risk populations., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Depression diagnoses have surged recently, and selective serotonin reuptake inhibitors (SSRIs) are the go-to treatment. However, studies indicate that long-term use of SSRIs can increase cardiovascular risk without systematic evaluation of the drug class. To offer clinical guidance, we performed an evaluation of the association between the six most commonly prescribed SSRIs and cardiovascular adverse events. Using the FDA Adverse Event Reporting System (FAERS) from Q1 2004 to Q2 2022, we conducted a disproportionality analysis and determined the magnitude of significant signals using statistical shrinkage transformations. Our study revealed that arrhythmias, torsades de pointes/QT prolongation, cardiomyopathy, and hypertension were among the most prevalent adverse events linked to SSRIs. Our analysis also showed a significant association between SSRIs and the aforementioned adverse events, with higher incidence in middle-aged and elderly patients and women. We further observed a rising trend in the incidence of arrhythmias, torsades de pointes/QT prolongation, and hypertension, highlighting the need for heightened cardiac monitoring in patients on SSRIs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Importance: Syncope is the most powerful predictor for subsequent life-threatening events (LTEs) in patients with congenital long QT syndrome (LQTS). Whether distinct syncope triggers are associated with differential subsequent risk of LTEs is unknown., Objective: To evaluate the association between adrenergic (AD)- and nonadrenergic (non-AD)-triggered syncopal events and the risk of subsequent LTEs in patients with LQT types 1 to 3 (LQT1-3)., Design, Setting, and Participants: This retrospective cohort study included data from 5 international LQTS registries (Rochester, New York; the Mayo Clinic, Rochester, Minnesota; Israel, the Netherlands, and Japan). The study population comprised 2938 patients with genetically confirmed LQT1, LQT2, or LQT3 stemming from a single LQTS-causative variant. Patients were enrolled from July 1979 to July 2021., Exposures: Syncope by AD and non-AD triggers., Main Outcomes and Measures: The primary end point was the first occurrence of an LTE. Multivariate Cox regression was used to determine the association of AD- or non-AD-triggered syncope on the risk of subsequent LTE by genotype. Separate analysis was performed in patients with β-blockers., Results: A total of 2938 patients were included (mean [SD] age at enrollment, 29 [7] years; 1645 [56%] female). In 1331 patients with LQT1, a first syncope occurred in 365 (27%) and was induced mostly with AD triggers (243 [67%]). Syncope preceded 43 subsequent LTEs (68%). Syncopal episodes associated with AD triggers were associated with the highest risk of subsequent LTE (hazard ratio [HR], 7.61; 95% CI, 4.18-14.20; P < .001), whereas the risk associated with syncopal events due to non-AD triggers was statistically nonsignificant (HR, 1.50; 95% CI, 0.21-4.77; P = .97). In 1106 patients with LQT2, a first syncope occurred in 283 (26%) and was associated with AD and non-AD triggers in 106 (37%) and 177 (63%), respectively. Syncope preceded 55 LTEs (56%). Both AD- and non-AD-triggered syncope were associated with a greater than 3-fold increased risk of subsequent LTE (HR, 3.07; 95% CI, 1.66-5.67; P ≤ .001 and HR, 3.45, 95% CI, 1.96-6.06; P ≤ .001, respectively). In contrast, in 501 patients with LQT3, LTE was preceded by a syncopal episode in 7 (12%). In patients with LQT1 and LQT2, treatment with β-blockers following a syncopal event was associated with a significant reduction in the risk of subsequent LTEs. The rate of breakthrough events during treatment with β-blockers was significantly higher among those treated with selective agents vs nonselective agents., Conclusion and Relevance: In this study, trigger-specific syncope in LQTS patients was associated with differential risk of subsequent LTE and response to β-blocker therapy.

Background Long-QT syndrome (LQTS) is a cardiac repolarization abnormality that can lead to sudden cardiac death. The most common causes are rare coding variants in the genes KCNQ1 , KCNH2 , and SCN5A . The data on LQTS epidemiology are limited, and information on expressivity and penetrance of pathogenic variants is sparse. Methods and Results We screened for rare coding variants associated with the corrected QT (QTc) interval in Iceland. We explored the frequency of the identified variants, their penetrance, and their association with severe events. Twelve variants were associated with the QTc interval. Five in KCNQ 1, 3 in KCNH2 , 2 in cardiomyopathy genes MYBPC3 and PKP2 , and 2 in genes where coding variants have not been associated with the QTc interval, ISOC1 and MYOM2. The combined carrier frequency of the 8 variants in the previously known LQTS genes was 530 per 100 000 individuals (1:190). p.Tyr315Cys and p.Leu273Phe in KCNQ1 were associated with having a mean QTc interval longer than 500 ms ( P =4.2×10 -7 ; odds ratio [OR], 38.6; P =8.4×10 -10 , OR, 26.5; respectively), and p.Leu273Phe was associated with sudden cardiac death ( P =0.0034; OR, 2.99). p.Val215Met in KCNQ1 was carried by 1 in 280 Icelanders, had a smaller effect on the QTc interval ( P =1.8×10 -44 ; effect, 22.8 ms), and did not associate with severe clinical events. Conclusions The carrier frequency of associating variants in LQTS genes was higher than previous estimates of the prevalence of LQTS. The variants have variable effects on the QTc interval, and carriers of p.Tyr315Cys and p.Leu273Phe have a more severe disease than carriers of p.Val215Met. These data could lead to improved identification, risk stratification, and a more precise clinical approach to those with QTc prolongation.

Background It was Dissertenne who first described a cardiac phenomenon known as the Torsades de Pointes (TdP). QT prolongation caused by drugs is one of the most important causes for acquired QT prolongation syndrome. Objective To observe the prescribing practices of QT interval prolonging drugs among a highrisk population of critically ill older adults in a tertiary care hospital in South India The objectives were to identify the most commonly prescribed QT prolonging drugs, to analyse types of QT prolonging drugs based on risk of causing QT prolongation, to study the frequency of occurrence of common risk factors for QT prolongation and to identify presence of any significant relationships among the study variables. Method We have conducted a one-year cross-sectional descriptive study of the prescribing practices of QT interval prolonging drugs among 319 critically ill older adults in a tertiary care hospital in South India. Data was analysed to categorize the most common drugs which prolong QT interval; the type and frequency of use of QT interval prolonging drugs and to find the most common risk factors for QT prolongation in this study population. Result In this study, ondansetron, clarithromycin, azithromycin,and amiodarone were the most prescribed among the drugs with known risk of QTc (Corrected QT interval) prolongation. Among the drugs with conditional risk of QTc prolongation, pantoprazole, frusemide, piperacillin-tazobactam and esomeprazole were the most prescribed. The most common risk factors for QTc prolongation that were identified in this study were bradycardia, acute kidney injury, chronic kidney disease and low serum potassium. Conclusion This study helps to inform our physicians regarding the commonly prescribed QT interval prolonging drugs so that they may reduce co prescription of multiple QT prolonging drugs in high-risk patients. It identifies kidney injury, low potassium, and bradycardia as common risk factors for QT interval prolongation in these patients.

Objective: Recent evidence suggests that hydroxychloroquine use is not associated with higher 1-year risk of long QT syndrome (LQTS) in patients with rheumatoid arthritis (RA). Less is known about its long-term risk, the examination of which was the objective of this study., Methods: We conducted a propensity score-matched active-comparator safety study of hydroxychloroquine in 8,852 veterans (mean age 64 ± 12 years, 14% women, 28% Black) with newly diagnosed RA. A total of 4,426 patients started on hydroxychloroquine and 4,426 started on another nonbiologic disease-modifying antirheumatic drug (DMARD) and were balanced on 87 baseline characteristics. The primary outcome was LQTS during 19-year follow-up through December 31, 2019., Results: Incident LQTS occurred in 4 (0.09%) and 5 (0.11%) patients in the hydroxychloroquine and other DMARD groups, respectively, during the first 2 years. Respective 5-year incidences were 17 (0.38%) and 6 (0.14%), representing 11 additional LQTS events in the hydroxychloroquine group (number needed to harm 403; [95% confidence interval (95% CI)], 217-1,740) and a 181% greater relative risk (95% CI 11%-613%; P = 0.030). Although overall 10-year risk remained significant (hazard ratio 2.17; 95% CI 1.13-4.18), only 5 extra LQTS occurred in hydroxychloroquine group over the next 5 years (years 6-10) and 1 over the next 9 years (years 11-19). There was no association with arrhythmia-related hospitalization or all-cause mortality., Conclusions: Hydroxychloroquine use had no association with LQTS during the first 2 years after initiation of therapy. There was a higher risk thereafter that became significant after 5 years of therapy. However, the 5-year absolute risk was very low, and the absolute risk difference was even lower. Both risks attenuated during longer follow-up. These findings provide evidence for long-term safety of hydroxychloroquine in patients with RA., (© 2022 American College of Rheumatology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Aims: Patients with solid tumours were treated with the anti-PD-1 antibody dostarlimab in the Phase I GARNET trial. This study aimed to examine dostarlimab's effect on corrected QT (QTc) interval and the systemic concentration-QTc interval relationship., Methods: In GARNET Part 2B, patients received 500 mg dostarlimab every 3 weeks (Q3W) for four cycles, then 1000 mg Q6W. Triplicate 12-lead ECGs were recorded and time-matched pharmacokinetic (PK) samples collected at screening, on Day 1 of Cycles 1, 4, 5, 8, 12 (pre-dose and 0.5 h after infusion end), and at treatment end. Concentration-change from baseline QTcF (ΔQTcF) analysis using a linear mixed effects model, summary statistics, incidence of clinically noteworthy ECG values and rhythm abnormalities were evaluated., Results: A total of 377 patients were considered for evaluation (n = 15 excluded from concentration-ΔQTcF). There was a non-significant concentration-ΔQTcF relationship (0.001589 ms/μg/mL; P = .5906). Mean ΔQTcF increase was <6 ms (upper-bound two-sided 90% confidence interval [CI], <10 ms at all post-dose timepoints). Highest geometric mean concentration was 414.1 μg/mL (Cycle 5 Day 1, 0.5 h) with predicted mean ∆QTcF of 3.064 ms (upper-bound two-sided 90% CI: 5.071). Mean QTcF prolongation (all concentrations) was 2.4 ms. QTcF prolongation ≥500 ms occurred in five patients (1.3%); 51 (13.6%) and nine patients (2.4%) had ΔQTcF ≥30 ms and ≥60 ms, respectively. Ten patients (2.7%) reported rhythm abnormalities. No U-wave abnormalities, torsades de pointes, ventricular tachycardia or ventricular fibrillation/flutter were observed., Conclusions: Dostarlimab does not cause clinically significant QTcF prolongation exceeding the regulatory concern threshold., (© 2023 GSK. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Introduction: Bupropion toxicity can cause cardiogenic shock, ventricular dysrhythmias, and death. Clinical and electrocardiographic factors associated with adverse cardiovascular events in bupropion toxicity have not been well-studied. This study aimed to identify factors associated with adverse cardiovascular events in adult patients with isolated bupropion exposures., Methods: This retrospective cohort study queried the National Poison Data System from 2019 through 2020. We included patients 20 years or older with acute or acute-on-chronic single-agent bupropion exposures evaluated in a healthcare facility. Exclusion criteria were confirmed non-exposure, withdrawal as a reason for exposure, lack of follow-up, documentation that exposure was probably not responsible for the effects, and missing data. The primary outcome was adverse cardiovascular events, defined as the presence of any of the following: vasopressor use, ventricular dysrhythmia, myocardial injury, or cardiac arrest. Independent variables were age, the intentionality of exposure, seizures, tachycardia, QRS widening, and QTc prolongation. Multivariable logistic regression was performed to test for independent associations between independent variables and adverse cardiovascular events., Results: Of 4,640 patients included in the final analysis (56.7% female, 56.5% suspected suicidal intent), 68 (1.47%) experienced an adverse cardiovascular event. Age (odds ratio 1.03; 95% confidence intervals 1.02-1.05), single seizure (odds ratio 9.18; 95% confidence intervals 4.24-19.9) and complicated seizures (odds ratio 38.9; 95% confidence intervals 19.3-78.1), QRS widening (odds ratio 3.01; 95% confidence intervals 1.62-5.59), and QTc prolongation (odds ratio 1.76; 95% confidence intervals 1.00-3.10) were independently associated with adverse cardiovascular events. No patients with unintentional exposure experienced adverse cardiovascular events, prohibiting intentionality from inclusion in the regression model. In the post hoc subgroup analysis of intentional exposures, age, single and complicated seizures, and QRS widening remained independently associated with adverse cardiovascular events., Conclusions: Increasing age, seizures, QRS widening, and QTc prolongation were associated with adverse cardiovascular events in bupropion exposures. Adverse cardiovascular events did not occur in unintentional exposures. Further research is needed to develop screening tools and treatments for bupropion cardiotoxicity.

Objective: The purpose of this study was to analyze the occurrence characteristics, clinical manifestations, medication distribution, and incidence of drug-induced arrhythmias in a real-world inpatient population., Methods: According to the inclusion and exclusion criteria as well as the ADR evaluation criteria, we retrospectively evaluated hospitalized patients in 2019 using the arrhythmia module of the Adverse Drug Event Active Surveillance and Assessment System-II (ADE-ASAS-II). A detailed analysis was performed on the demographic data, ADR manifestations, and medication distribution of 2097 patients with drug-induced arrhythmias and QT interval prolongation., Results: Of the 167,546 hospitalized patients, there were 1809 cases of drug-induced arrhythmias, with an incidence of 1.08%. The ADRs in 45.35% of positive patients occurred within 3 days after medication administration, and 46.73% of the patients were 65 years old or older. The predominant ADRs identified in this study were extrasystole, tachycardia, and QT interval prolongation, of which the incidence was 0.20%. Levofloxacin was the most involved drug, and levofloxacin-associated rates of incidence of arrhythmia and QT interval prolongation were 1.24% and 0.44%, respectively. The risk factors for drug-induced arrhythmias were male sex, advanced age, emaciation, obesity, and underlying illnesses such as cardiovascular diseases, diabetes mellitus, cerebrovascular diseases, and hepatic and renal inadequacy (P < 0.05)., Conclusion: The incidence of drug-induced arrhythmias was in the range of common, while QTc interval prolongation was occasional. It is necessary to pay attention to patients with risk factors., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: Few studies have investigated linezolid (LZD)-associated cardiotoxicity. This study explored the potential association between LZD and QT interval prolongation., Methods: Adverse event reports of QT interval prolongation associated with LZD from the Food and Drug Administration Adverse Event Reporting System from January 2013 to December 2021 were analysed and the reporting odds ratio (ROR) with 95% confidence intervals were calculated., Results: A total of 6738 adverse event reports of LZD as the primary and secondary suspected drug were obtained from the database, including 192 reports with electrocardiogram QT prolonged (QTp), and the ROR value was 26.1 (95% CI = 22.6-30.2). There were 8 reports of long QT syndrome, ROR 14.2 (95% CI = 7.1-28.5); 5 reports of torsade de pointes, ROR 3.2 (95% CI = 1.3-7.6); and 5 reports of ventricular tachycardia, ROR 1.9 (95% CI = 0.8-4.5). Subgroup analysis revealed that patients with tuberculosis treated with LZD had a higher reporting rate among all QTp reports, exhibiting an odds ratio of 330.0 (95% CI = 223.1-488.1). The odds ratios of QTp associated with LZD treatments in patients with and without tuberculosis were 4.2 (95% CI = 3.4-5.3) and 1.2 (95% CI = 0.8-1.6), respectively., Conclusion: The study showed an association between LZD and QT interval prolongation. In the report on patients with tuberculosis, the incidence of QTp was higher when treated with LZD., (© 2022 British Pharmacological Society.)

Background: QTc interval prolongation has been reported when combining fluoroquinolones and triazoles for chemoprophylaxis in cancer patients. Herein, we aimed to identify the prevalence and contributing factors to QTc prolongation in hematopoietic cell transplantation (HCT) recipients who received these agents during the neutropenic phase., Methods: This is a retrospective medical chart review conducted at a university hospital in Lebanon from 2017 to 2020. It included all adult HCT inpatients on antimicrobial prophylaxis with fluoroquinolones and triazoles and whose baseline ECG monitoring done prior to chemoprophylaxis administration, then on day-3 and day-6 of therapy, were available., Results: Overall, 68 HCT recipients met our inclusion criteria, of which 22% developed QTc prolongation. Based on bivariate analysis, female gender contributed to QTc prolongation ( P  = 0.001). There was a trend to QTc prolongation in patients with predisposing thyroid disease ( P  = 0.12), grade 2 vomiting and diarrhea ( P  = 0.16, P  = 0.46, respectively), baseline hypokalemia ( P  = 0.18) and hypocalcemia ( P  = 0.3), hypomagnesemia on day-3 ( P  = 0.21) and day-6 hyponatremia ( P  = 0.36). Patients receiving two or more drugs with a known or probable risk of QTc prolongation (other than the fluoroquinolone/ triazole combination) were more prone to experience a prolonged QTc interval ( P  = 0.09). None of the patients that had QTc prolongation died or developed serious arrhythmias., Conclusion: The prevalence of QTc prolongation was 22% among HCT recipients on fluoroquinolone and triazole prophylaxis, yet we did not identify any independent risk factors for this issue. None of the patients that had QTc interval prolongation died or developed serious arrhythmias.

Background: Conflicting findings have described the association between prolonged heart rate-corrected QT interval (QTc) and cardiovascular disease., Aims: To identify articles investigating the association between QTc and cardiovascular disease morbidity and mortality, and to summarize the available evidence for the general and type 2 diabetes populations., Methods: A systematic search was performed in PubMed and Embase in May 2022 to identify studies that investigated the association between QTc prolongation and cardiovascular disease in both the general and type 2 diabetes populations. Screening, full-text assessment, data extraction and risk of bias assessment were performed independently by two reviewers. Effect estimates were pooled across studies using random-effect models., Results: Of the 59 studies included, 36 qualified for meta-analysis. Meta-analysis of the general population studies showed a significant association for: overall cardiovascular disease (fatal and non-fatal) (hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.33-2.12; I 2 =69%); coronary heart disease (fatal and non-fatal) in women (HR 1.27, 95% CI 1.08-1.50; I 2 =38%; coronary heart disease (fatal and non-fatal) in men (HR 2.07, 95% CI 1.26-3.39; I 2 =78%); stroke (HR 1.59, 95% CI 1.29-1.96; I 2 =45%); sudden cardiac death (HR 1.60, 95% CI 1.14-2.25; I 2 =68%); and atrial fibrillation (HR 1.55, 95% CI 1.31-1.83; I 2 =0.0%). No significant association was found for cardiovascular disease in the type 2 diabetes population., Conclusion: QTc prolongation was associated with risk of cardiovascular disease in the general population, but not in the type 2 diabetes population., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Gefitinib (GEF) may increase the risk of corrected QT prolongation (QTc). We aimed to evaluate whether gefitinib increases the risk of corrected QT interval (QTc) prolongation and analyze the associated risk factors.A total of 122 cases of advanced EGFR-mutated non-small cell lung cancer (NSCLC) who received gefitinib therapy from January 2015 to December 2020 were evaluated. The results of at least two resting 12-lead electrocardiogram before and after gefitinib treatment were obtained. The Bazett and Fridericia formulas were used to calculate the QTc interval, and the changes of QTc interval values before and after treatment were evaluated. The correlation between gefitinib and QTc interval prolongation and related risk factors were analyzed.After gefitinib-targeted therapy, 23 patients (18.9%) had a prolonged QTc interval, which increased from a mean of 446 ± 25 ms at baseline to 478 ± 18 ms (P < 0.001). Three of the patients met criteria for Grade 3 QTc prolongation in the common term V5.0 for clinical adverse events. Univariate analysis showed that age (ORR, 1.054; 95% confidence interval [CI], 1.003-1.107; P = 0.038), history of hypertension (ORR, 3.409; 95% CI, 1.334-8.713; P = 0.01), CCB medication history (ORR, 0.259; 95% CI, 0.094-0.712; P = 0.009), history of lung cancer surgery (ORR, 0.231; 95% CI, 0.064-0.829; P = 0.025), and baseline QT interval (ORR, 0.978; 95% CI, 0.964-0.993; P = 0.004) were important predictors of QTc interval prolongation in patients treated with gefitinib. The results of multivariate analysis showed that the history of lung cancer surgery and the baseline QT interval were important factors affecting QTc interval prolongation in patients treated with gefitinib.Gefitinib increases the risk of QTc prolongation in NSCLC patients, which may be more pronounced in patients with advanced age, hypertension, CCB therapy, lung cancer surgery, and a long QT interval at baseline.

Rationale: While meta-analyses of clinical trials found that lurasidone and partial dopamine agonists (brexpiprazole and aripiprazole) were the antipsychotics less likely to cause QTc prolongation, and sertindole, amisulpride, and ziprasidone were the most frequently associated with this adverse drug reaction; no real-world studies have investigated this risk between the different antipsychotics., Objectives and Methods: Using data recorded from 1967 to 2019 in VigiBase®, the World Health Organization's Global Individual Case Safety Reports database, we performed disproportionality analysis to investigate the risk of reporting QT prolongation between 20 antipsychotics., Results: Sertindole had the highest risk of reporting QT prolongation, followed by ziprasidone and amisulpride. Lurasidone was associated with the lowest risk. First-generation antipsychotics were associated with a greater QT prolongation reporting risk (ROR, 1.21; 95%CI, 1.10-1.33) than second-generation antipsychotics. A positive correlation was found between the risk of reporting QT prolongation and affinity for hERG channel (R 2  = 0.14, slope = Pearson coefficient = 0.41, p value = 0.1945)., Conclusions: This large study in a real-world setting suggests that sertindole and ziprasidone were the antipsychotics drugs associated with the highest risk of QT prolongation reporting. Our results suggest that lurasidone is less associated with QT interval prolongation reports. Our study also suggests that antipsychotics with the higher hERG affinity are more associated with to QT prolongations reports., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/aims: QT prolongation is a known risk factor for ventricular fibrillation and ventricular tachycardia. Therefore, more refined management is necessary to reduce sudden cardiac death secondary to such arrhythmias., Methods: Electrocardiographic findings were reviewed in 224 patients, and the associations of QT prolongation with various clinical parameters were examined, including the nutritional state. Correlations were also examined between QT prolongation and body composition measurements determined by multifrequency bioelectrical impedance analysis., Results: Prolongation of the corrected QT (QTc) interval over 0.44 s was seen in 140 patients (62.5%). QT prolongation was independent of age and dialysis therapy duration and was more frequent in diabetics (70.1%) than in nondiabetics (54.2%, p = 0.014) and more frequent in women (78.8%) than in men (53.5%, p < 0.001). Serum levels of albumin (p < 0.001) and Cr (p < 0.001) and the Geriatric Nutritional Risk Index (GNRI, p < 0.001) were negatively correlated with QTc interval; no significant correlation was noted with total protein, urea nitrogen, or uric acid. Negative correlations with QTc interval were found for BMI(p < 0.01), percent total body water (%TBW; p < 0.05), and percent intracellular water (%ICW; p < 0.01) but not with the percent extracellular water/TBW ratio or edema ratio. The longer the QTc interval, the lower the fat-free mass (FFM; p < 0.01) and muscle mass (MM; p < 0.01), but there was no significant correlation with percent fat., Conclusion: These results suggest that QT prolongation is a common complication and is more frequent in women and diabetic patients. The decreases in serum albumin and Cr levels, GNRI, BMI, %TBW, %ICW, FFM, and MM together coincided with malnutrition and thus suggest a close relationship of QT prolongation with malnutrition. Management of QT prolongation may be achieved better in the future by understanding these biochemical and biophysical changes, particularly those regarding malnutrition., (© 2021 S. Karger AG, Basel.)

Aim: β-blockers are the first line of treatment in patients with congenital long QT syndrome (cLQTS) (class I or II recommendation) in order to prevent malignant arrhythmias. Hence, we examined long-term β-blocker adherence and associated risk factors among patients with cLQTS., Methods and Results: Danish patients with cLQTS claiming a prescription for any β-blocker after their cLQTS diagnosis were identified using data from nationwide registries and specialized inherited cardiac disease clinics (1995-2017). Patients were followed for up to 5 years. Treatment breaks >60 days were assessed (i.e. proxy for reduced adherence). Multivariable Cox regression was used to identify risk factors associated with breaks of >60 days in β-blocker treatment. Overall, 500 out of 633 (79%) patients with cLQTS claimed at least one prescription for any β-blocker after cLQTS diagnosis. During follow-up, 38.4% had a treatment break. Risk factors significantly associated with treatment breaks were implantable cardioverter defibrillator (ICD) [hazard ratio (HR) = 1.65, 95% confidence interval (CI): 1.08-2.53], β-blocker side effects (HR = 2.69, 95% CI: 1.75-4.13), and psychiatric disease (HR = 1.63, 95% CI: 1.04-2.57). In contrast, patients presenting with ventricular tachycardia/syncope as cLQTS disease manifestation were less likely to have a treatment break compared with asymptomatic patients (HR = 0.55, 95% CI: 0.33-0.92)., Conclusion: Reduced β-blocker adherence was common with more than a third of patients having a treatment break >60 days after cLQTS diagnosis. Patients with psychiatric disease, self-reported β-blocker side effects, and an ICD were more likely to display reduced adherence, whereas a severe cLQTS disease manifestation was associated with optimal β-blocker adherence., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

At the beginning of the COVID-19 pandemic, worldwide attempts were made to identify potential drugs effective against the COVID-19. Hydroxychloroquine was among the first receiving attention. However, following its use in therapy, it has been shown that hydroxychloroquine was not only ineffective but probably, due to its known side effects, even responsible of increased mortality of patients. The objective of this study was to review the safety profile of hydroxychloroquine used off-label for the treatment of COVID-19. We analyze the reports of suspected adverse drug reactions (ADRs) collected in EudraVigilance, the European database of ADR reports. We collected 2266 reports for 2019 and 6525 for 2020. The most reported ADRs during 2020 were those relating to cardiac, hepatic, renal toxicity such as QT prolongation with 400 cases in 2020 (of which, 345 cases-9.97%-with COVID-19 as a therapeutic indication) versus 1 case only in 2019 (0.01%), long QT syndrome: 38 cases in 2020 (36 as COVID-19 treatment) versus 0 in 2019, hepatitis: 13 cases in 2019 (0.11%) and 132 in 2020, and 32 cases (24, 0.69%) of acute kidney injury in 2020 and only 3 cases in 2019. Moreover, some important vision-related ADRs also increased significantly during 2020, such as retinal toxicity with 92 cases in 2020 versus 7 in 2019. Even though with its intrinsic limitations, our results may be added to the most recent scientific evidence to confirm the unfavorable risk profile of hydroxychloroquine in its off-label use in the treatment of COVID-19 disease., (© 2022 The Authors. Fundamental & Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of Société Française de Pharmacologie et de Thérapeutique.)

Objective: To assess the prevalence, and factors associated with QTc interval prolongation, among 383 virologically suppressed people with HIV (PWH), without evidence of cardiovascular disease and active opportunistic infections in Thailand., Design: Cross-sectional study., Methods: Resting 12-lead digital ECGs were performed in 2019. QT interval corrected for heart rate (QTc) >450 ms in males and >460 ms in females was defined as QTc interval prolongation. We used multivariable logistic regression to investigate factors associated with QTc interval prolongation., Results: Mean (standard deviation) age was 56 (5.5) years and 42% were female. The median current CD4+ was 619 (interquartile range [IQR] 487, 769) cells/mm 3 . The median duration of antiretroviral therapy (ART) was 11.9 (IQR 7.1-16.1) years. Commonly used ART were rilpivirine (37.9%), efavirenz (20.1%), atazanavir/ritonavir (15.7%), lopinavir/ritonavir (12.3%) and dolutegravir (5%). The prevalence of QTc interval prolongation was 22.7%. In multivariable analysis, older age (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02-1.12, P  = 0.005), female sex (OR 1.69, 95% CI 1.01-2.82, P  = 0.046) and increasing BMI (OR 1.08, 95% CI 1.01-1.15, P  = 0.03) were associated with QTc interval prolongation. With every 1-year increase in age, the odds of QTc interval prolongation increased by 7%., Conclusions: In this well-suppressed aging Asian HIV cohort, the prevalence of QTc interval prolongation was relatively high, and associated with increasing age, female sex, and higher BMI. For PLWH with these characteristics, QTc interval should be monitored before and after initiating any medications known to prolong QTc intervals, to prevent fatal cardiac arrhythmias., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Takotsubo syndrome is associated with life threatening arrhythmias, and the apical ballooning pattern is characterized by a peculiar QT prolongation and particularly high-risk of arrhythmias., Objectives: The aim of the study was to determine the association of QT interval on electrocardiogram for ventricular arrhythmic complications in patients with apical ballooning Takotsubo syndrome in a diverse population at a large urban hospital in the U.S., Methods: We reviewed 105 cases of apical ballooning Takotsubo syndrome in patients admitted between 2011 and 2017. Two cardiologists reviewed the electrocardiograms to measure QT interval, adjusted for rate using the Fridericia formula (QT C F), and ventricular arrhythmic complications during the hospitalization. Data are reported as median and interquartile range or number and percentage., Results: Of the 105 patients, 86 (82%) were female, and 34 (32%) were self-reported Black or African American. The mean age was 65 years (range: 58-72 years). Left ventricular ejection fraction was 25% (range: 25%-35%). Heart rate was 101 beats/min (range: 83-121 beats/min). Ten (11%) patients experienced a ventricular arrhythmic complication and had significantly longer QT C F (470 [range: 422-543] milliseconds) than did those without complications (417 [range: 383-456] milliseconds, P = 0.031). The area under the curve for QT C F was 0.708 (95% CI: 0.536-0.880; P = 0.031). Twenty-eight (27%) patients had a QT C F ≥460 milliseconds and significantly more arrhythmic complications (21% vs 5%, odds ratio 4.997 [95% CI: 1.288-19.237], P = 0.021). QT C F was an independent predictor of ventricular arrhythmias: odds ratio 1.090 for each 10-millisecond increase in QT C F (95% CI: 1.004-1.183; P = 0.040, corrected for sex)., Conclusions: In a diverse population of patients with apical ballooning Takotsubo syndrome admitted to a large urban hospital in the United States, QT C F at admission ≥460 milliseconds identifies patients at high risk for in-hospital arrhythmic complications. Further studies are needed to determine strategies aimed at shortening QT interval to potentially prevent life-threatening arrhythmic events., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The objective of this study is to determine the prevalence of an abnormal electrocardiogram showing a prolonged QTc greater than 450 ms in infants with unilateral or bilateral sensorineural hearing loss. We conducted a prospective study of healthy term infants (≥37 weeks gestational age) who failed their newborn auditory brainstem response hearing screen, were seen by an audiologist and diagnosed as having sensorineural hearing loss during follow-up to 1 year of age. In infants with a diagnosis of hearing loss, we collected a detailed family history and performed an ECG between 2 and 6 months of age. We obtained follow-up for 1 year by calling the parent requesting the hearing and cardiac status of their child. Two of the 40 infants with sensorineural hearing loss (5%) had a QTc greater than 450 ms. Both had mild bilateral hearing loss and genetic testing did not identify a known mutation for long QT syndrome. The remaining 38 infants had QTc intervals of ≤ 450 ms. One patient diagnosed with bilateral severe sensorineural hearing loss had a normal ECG (QTc = 417 ms). Several months after the ECG was performed, the infant's mother contacted the study cardiologist after she learned that the infant's maternal grandmother was diagnosed with a cardiomyopathy and arrhythmias. Genetic testing was recommended even though the child was asymptomatic and was positive for a pathogenic mutation in the KCNQ1 gene. We speculate that molecular genetic testing in infants with hearing loss may become the standard of care rather than targeted electrocardiograms.Clinical Trial Registration NCT02082431 https://www.clinicaltrials.gov/ct2/show/NCT02692521?cond=NCT02692521&rank=1 ., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Patients with Williams syndrome (WS) have a 25- to 100-fold higher risk of sudden death and prolonged heart rate-corrected QT (QTc). A recent study using the Fridericia formula for QT correction suggested that prolongation is principally an issue of heart rate. We used multiple published heart rate correction formulas to reevaluate the prevalence of QTc prolongation in our original dataset from our 2010 study at the Children's Hospital of Philadelphia. The ninety-eighth centile for QTc and corrected JT Interval (JTc) of the control population for each formula were used to set the threshold for prolongation. Prevalence comparison was done with Fisher's exact test. Predictors of longer QTc/JTc were assessed using linear regression models adjusting for age, gender, and heart rate. Adjusted odds of QTc/JTc prolongation were evaluated with conditional logistic regression models matched based on age and heart rate. There were 482 electrocardiograms from 188 patients with WS and 1,522 from normal controls. Patients with WS were younger, with higher heart rates and shorter RR and QRS intervals. WS was associated with longer QTc/JTc compared with controls. There were higher odds of prolonged QTc/JTc in patients with WS than controls using both Bazett and Fridericia formulas. In conclusion, this study confirms the higher prevalence of QTc prolongation in WS compared with controls and highlights the importance of setting appropriate formula-specific upper thresholds for QTc prolongation for accurate diagnosis., (Published by Elsevier Inc.)

Aims: Sports practice, especially in competition, is usually restrained in patients diagnosed with long QT syndrome (LQTS). Although data are scarce, a low incidence of cardiac arrhythmic events (CAEs) during sports practice is reported. We aim to evaluate the incidence of CAE during sports practice in LQTS patients., Methods and Results: All consecutive patients above 18 years of age diagnosed with LQTS and prospectively followed at the referral centre for inherited arrhythmia syndrome received a survey to retrospectively assess their sports practice prior to and after the diagnosis of LQTS. Two hundred and forty-six patients were included (57% females). The median age was 43 years, and the median QTc was 457 ms (428; 482). Patients reported a total of 4092 years [1376 (34%) after diagnosis] of sports practice: 2905 (77%) [1138 (39%) after diagnosis] years of leisure practice and 1187 (23%) [238 (20%) after diagnosis] years of competitive practice. One hundred and eighty (73%) patients practiced sport prior to the diagnosis of LQTS and 170 (69%) after. Prior to the diagnosis, four (2%) patients presented a CAE during leisure sports practice and one during competition. After diagnosis, only one patient presented a CAE, appropriately treated by an implantable cardioverter defibrillator discharge, in the context of beta-blocker non-compliance. The CAE event rate was 0.0007 events/year in the 1376 years of total sports practice after the diagnosis of LQTS., Conclusion: After the diagnosis of LQTS, the occurrence of CAE is very low during sports practice, even in competitive practice. There was no CAE in patients properly treated with beta-blocker therapy with good compliance., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Coronavirus disease 2019 (COVID-19) is a global pandemic. Hydroxychloroquine (HCQ)-associated cardiovascular adverse events (CVAEs) have been increasingly reported., Aim: This study aimed to present an observational, retrospective, and comprehensive pharmacovigilance analysis of CVAE associated with HCQ in patients with and without COVID-19 using the US Food and Drug Administration Adverse Events Reporting System (FAERS) data from January 2020 to December 2020., Method: We identified 3302 adverse event reports from the FAERS database in the year 2020 and divided them into COVID-19 and non-COVID-19 groups, respectively. Then we analyzed whether there were differences in CVAEs between the two groups., Results: We found that CVAE was higher in cases with COVID-19 compared to those without COVID-19, odds ratio (OR) of 1.26 and a 95% confidence interval (95% CI) of 1.02-1.54. Cases with COVID-19 treated with HCQ exhibited relatively higher proportions of torsade de points (TdP) and QT prolongation (OR 3.10, 95% CI 2.24-4.30), shock-associated TdP (OR 2.93, 95% CI 2.13-4.04), cardiac arrhythmias (OR 2.07, 95% CI 1.60-2.69), cardiac arrhythmia terms (including bradyarrhythmias and tachyarrhythmias) (OR 2.15, 95% CI 1.65-2.80), bradyarrhythmias (including conduction defects and disorders of sinus node function) (OR 2.56, 95% CI 1.86-3.54), and conduction defects (OR 2.56, 95% CI 1.86-3.54)., Conclusion: Our retrospective observational analysis suggested that the proportion of CVAE associated with HCQ, especially TdP and QT prolongation, was higher in patients with COVID-19. Understanding the effects of COVID-19 on the cardiovascular system is essential to providing comprehensive medical care to patients receiving HCQ treatment., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Many drugs carry some risk of QT interval prolongation, which can lead to life-threatening dysrhythmias including Torsades de Pointes (TdP). CredibleMeds.org identifies medications categorized as "Known Risk of TdP" but does not stratify risk in acute supratherapeutic ingestions. We sought to determine the proportion of cases exhibiting QTc prolongation and life-threatening dysrhythmias including ventricular tachycardia (VT)/ventricular fibrillation (VF), TdP, and asystole in patients exposed to these substances. Retrospective chart review of cases reported to our Regional Poison Center from 2014 to 2019 of exposures to one or more of the "Known Risk" substances was performed. Demographics, therapies, clinical effects, and medical outcome for each case were analyzed. There were 1125 exposures, of which 760 had a documented QTc interval. QTc ≥ 500 ms was reported in 138 (18.2%) of the 760 cases. The most common "Known Risk" substances were citalopram, escitalopram and cocaine. Although not in the "Known Risk" category, mirtazapine, amitriptyline, diphenhydramine, and trazodone had a statistically significant association with QTc > 500 ms. Life-threatening dysrhythmias occurred in 13 cases, with VT/VF in 6 of the 760 (0.8%) cases, and one case of TdP. Flecainide (OR 11.1, 95% CI 2.2-55.8) and methadone (OR 7.1, 95% CI 2.1-23.4) were associated with increased risk of all life-threatening dysrhythmias. Exposures to medications on the Credible Meds list of "Known Risk of TdP" QTc prolongation is common, but life-threatening dysrhythmias are rare. Mirtazapine, amitriptyline, diphenhydramine, and trazodone were associated with prolonged QTc. Flecainide and methadone had the highest associated risk of life-threatening dysrhythmias., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In-vitro evidence suggests hydroxychloroquine could be a potential immunomodulator for the inflammatory carditis of acute rheumatic fever (ARF). Hydroxychloroquine used as an anti-inflammatory agent has a low side effect profile but its use in the Covid-19 pandemic raised concerns about QTc interval prolongation and cardiac arrhythmias. The prolongation of QTc in ARF appears benign but has not been widely studied. We aim to report QTc intervals in a contemporary ARF population and consider implications for hydroxychloroquine use in ARF. The study cohort was 197 children <15 years of age with a clinical diagnosis of ARF. The QTc mean (SD) was 445 msec (28), range 370-545 msec. Eighteen percent of the cohort had a QTc > 99th percentile for normal by age and 8 patients (4%) had a QTc over 500 msec. There was no difference of QTc by age or gender. Inter-observer repeatability for QTc (n = 33) was 35 msec. The QTc is often prolonged in the early phase of ARF, meaning that QT prolonging medications should be used with caution in this setting. Serial ECG monitoring of the QT interval is recommended if hydroxycholoroquine is used in ARF., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Individual case reports describe trazodone overdose resulting in QTc prolongation and cardiac arrhythmias. The clinical effects and outcomes associated with trazodone exposures on a large-scale basis are less well known., Objective: The primary objective was to characterize the severity of single substance trazodone exposures and identify any relationships that may exist between dose of trazodone and severity of exposure. The secondary objective was to describe these exposures from a demographic and clinical symptom standpoint., Methods: A retrospective review of single-substance trazodone exposures reported to the National Poison Data System (NPDS) from 1 January 2000 to 31 December 2019 was performed. The primary objective was to characterize the severity of trazodone exposures and relationships between ingested dose and level of care required or medical outcome., Results: A total of 118,773 cases were included in the analysis of demographics and level of care required. A majority (59.5%) of cases did not require medical admission. Of the 81,698 cases with known medical outcomes, the most common clinical effects included mild-moderate CNS depression (49.7%), QTc prolongation (12.2% of cases in 2019), vomiting (9.0%), hypotension (7.0%), and tachycardia (7.0%). The median ingested dose associated with treatment, and release from the emergency department was 600 mg compared to 1500 mg in those admitted to the intensive care unit (ICU). Regarding medical outcome, median ingested dose ranged from 600 mg in those experiencing no effect to 1500 mg in those experiencing major effects. Cardiac-related clinical effects and the need for cardiac-specific interventions were overall infrequent. A dose-response relationship was identified for level of care and medical outcome., Conclusions: Many trazodone exposures can be characterized as low severity due to the infrequent need for healthcare facility admission and large proportion of cases that experienced no effects or only minor effects.

In adults, alcohol intoxication is associated with prolongation of the QT interval corrected for heart rate (QTc). The QTc is influenced by age and sex. Although alcohol intoxication is increasingly common in adolescents, there are no data on the prevalence of QTc prolongation in adolescents with alcohol intoxication. This study aimed to determine the prevalence of QTc prolongation in adolescents with alcohol intoxication and identify at-risk adolescents. In this observational study including adolescents aged 10-18 years, heart rate and QT interval were automatically assessed from an electrocardiogram (ECG) at alcohol intoxication using a validated algorithm. The QTc was calculated using both the Bazett formula (QTc B ) and Fridericia formula (QTc F ). If present, an ECG recorded within 1 year of the date of admission to the emergency department was obtained as a reference ECG. A total of 317 adolescents were included; 13.3% had a QTc B and 7.9% a QTc F longer than the sex- and age-specific 95th-percentile. None of the adolescents had a QTc B or QTc F  > 500 ms, but 11.8% of the adolescents with a reference ECG had a QTc B prolongation of > 60 ms, while no adolescents had a QTc F prolongation of > 60 ms. QTc prolongation was mainly attributable to an increase in heart rate rather than QT prolongation, which underlies the differences between QTc B and QTc F . Male sex and hypokalaemia increased the likelihood of QTc prolongation.Conclusion: QTc prolongation was seen in approximately 10% of the adolescents presenting with alcohol intoxication, and although no ventricular arrhythmias were observed in this cohort, QTc prolongation increases the potential for malignant QT-related arrhythmias. Clinicians must be aware of the possibility of QTc prolongation during alcohol intoxication and make an effort to obtain an ECG at presentation, measure the QT interval, and give an adequate assessment of the findings. We advocate admitting adolescents with alcohol intoxication and QTc prolongation. During hospital admission, we recommend limiting exposure to QTc-prolonging medication, increasing potassium levels to a high-normal range (4.5-5.0 mmol/L) and obtaining a reference ECG at discharge., (© 2022. The Author(s).)

Objective: To examine workforce attachment among patients with congenital long QT syndrome (cLQTS) following diagnosis and identify factors associated with workforce attachment., Methods and Results: In this nationwide cohort study, all patients diagnosed with cLQTS in Denmark between 1996 and 2016 aged 18-60 years at diagnosis were identified using nationwide registries. Patients attached to the workforce at diagnosis were included. Attachment to the workforce 1 year after cLQTS diagnosis was examined and compared with a background population matched 1:4 on age, sex and employment status. Multiple logistic regression was performed to identify factors associated with 1-year workforce detachment among patients with cLQTS. 298 patients fulfilled the inclusion criteria. Six months after cLQTS diagnosis, 90.9% of patients with cLQTS were attached to the workforce compared with 95.0% in the background population (p=0.006 for difference). One year after diagnosis, 93.3% of patients with cLQTS were attached to the workforce compared with 93.8% in the background population (p=0.26). Among patients with cLQTS, a severe cLQTS disease manifestation was associated with workforce detachment 1 year after diagnosis (compared with asymptomatic patients; aborted cardiac arrest OR 20.4 (95% CI, 1.7 to 249.9); ventricular tachycardia/syncope OR 10.9 (95% CI, 1.1 to 110.5)). No other associated factors were identified., Conclusions: More than 90% of patients with cLQTS remained attached to the workforce 1 year after diagnosis, which was similar to a matched background population. Patients with a severe cLQTS disease manifestation were less likely to be attached to the workforce 1 year after diagnosis., Competing Interests: Competing interests: CT-P reports grant from Bayer for randomised trials and from Novo Nordisk for epidemiological study, all unrelated to the present work. GG reports grants from Boehringer Ingelheim, Bristol-Myers Squibb and Pfizer, unrelated to the present work. HKJ is supported by grants from Novo Nordisk Foundation, Denmark (NNF18OC0031258 and NNF20OC0065151) and received lecture fees from Abbott, Denmark and Biosense Webster, Europe, all unrelated to the present work. JHB reports advisory honoraria from Bayer, outside the present work. LK reports honorarium form Novo, Novartis, AstraZeneca and Boehringer, unrelated to this manuscript. All remaining authors have declared no conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)