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Background: Atrial fibrillation is the most prevalent cardiac arrhythmia, presenting symptomatic patients with diminished quality of life and worsening of heart failure. Dofetilide, a class 3 antiarrhythmic agent, is a proven and safe rhythm control medication. Initial risk of QT prolongation leading to torsade de pointes (TdP) necessitates a standard protocol mandating hospitalization for three days for initiation. Objectives: To assess safety when adhering to initiation protocol and identify traits for susceptibility to TdP in elective dofetilide admissions. Methods: We conducted a retrospective study involving patients admitted to Mayo Clinic sites across four states for elective inpatient initiation of dofetilide between 2003 and 2022. Patients' charts underwent review, focusing on dofetilide-related TdP occurrences, baseline characteristics including QT intervals, laboratory values, comorbidities, and concomitant medications. Patients who experienced TdP were subjected to further evaluation to identify potential risk factors. Results: Of 2036 patients identified, mean age 66.4 ± 11.4 years, and 67.2 % male, 16 experienced dofetilide-related TdP (incidence rate 0.79%). Notably, 81% (13/16) of TdP cases occurred in patients who deviated from the FDA/manufacturer algorithm protocol. The concomitant use of active intravenous diuretic therapy, digoxin, and QT-prolonging drugs emerged as identifiable risk factors. Additionally, females exhibited a higher incidence of TdP (1.5%) than males (0.44%) {odd ratio [OR] 3.46; P = 0.017}. Conclusion: Overall incidence of TdP related to dofetilide initiation was low (0.79%). Adherence to protocol during elective hospital admissions appears extraordinarily safe. Patients who did not require concurrent use of intravenous diuretics, digoxin, or QT prolonging drugs exhibited lower risk of TdP.

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Background: Osimertinib is a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor that has become the first-line treatment for non-small cell lung cancer harboring EGFR mutations, with the potential risk of QT prolongation and heart failure. However, few cases have reported malignant ventricular arrhythmias. Here, we report a case of recurrent ventricular fibrillation (VF) and Torsade de Pointes (TdP) secondary to QT prolongation and heart failure induced by osimertinib. Case summary: A 70-year-old woman presented with chest tightness and dyspnea for 1 week and ventricular fibrillation upon admission, with a medical history of lung adenocarcinoma harboring an EGFR exon 21 p.L858R mutation. She was under osimertinib for 3 months. Electrocardiography after defibrillation suggested QTc prolongation (655 ms) and T wave alternans. Ultrasound cardiography displayed left ventricular ejection fraction (LVEF) of 29% and severe mitral regurgitation. Laboratory tests indicated elevated N-terminal pro-B-type natriuretic peptide and hypokalemia. Genetic testing suggested no pathogenic mutations. We considered acquired long QT syndrome and heart failure with reduced ejection fraction induced by osimertinib as the chief causes of ventricular arrhythmia and hypokalemia as an important trigger. Despite intubation, sedation, and the administration intravenous magnesium and potassium and lidocaine, the patient presented with recurrent TdP, which was managed by a low dose of isoproterenol (ISO, 0.17 ug/min). An implantable cardioverter defibrillator was declined. The patient is surviving without any relapse, with QTc of 490 ms and LVEF of 42% after a 6-month follow up. Conclusion: Regular monitoring is required during osimertinib administration, considering the risk of life-threatening cardiac events, such as malignant arrhythmias and heart failure. ISO, with an individual dose and target heart rate, may be beneficial for terminating TdP during poor response to other therapies.

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BACKGROUND: Little is known about the role of atrial arrhythmias (AAs) in triggering Torsade de Pointes (TdP) in patients with long-QT syndrome (LQTS). The aim of this study was to examine the contribution of AAs to the development of TdP in acquired LQTS patients. METHODS: The initiation patterns of 81 episodes of TdP obtained from 34 consecutive acute acquired LQTS patients (14 men, median age, 69 years; median QTc, 645.5 ms) with documented TdP were analyzed. The initiation mode of TdP was divided into 3 categories: (1) preceding short-long sequence (SLS); (2) sudden R-on-T phenomenon without preceding SLS; and (3) increased atrial rate. The patients were divided into 2 groups based on the presence or absence of AAs-induced TdP; AAs-induced (n=18) and non-AAs-induced (n=16) groups. The association of clinical/ECG characteristics and TdP frequency after initiating conventional therapy with AAs-induced TdP was evaluated. The groups were compared using the Mann-Whitney U test or Fisher exact test. RESULTS: AAs-induced group comprised 52.9% (18/34) of the patients studied. TdP was preceded by AAs-initiated SLSs in 41.2% (14/34) of the patients and was directly induced by R-on-T AAs (AAs coincidentally encountered a vulnerable repolarizing region during the T wave) in 23.5% (8/34). AAs triggered 48 (59.3%) of the 81 TdP episodes. AAs-initiated SLSs in 67.8% (40/59) of the SLS-induced TdP episodes. R-on-T AAs accounted for 23.5% (19/81) of the TdP episodes. AAs-induced group experienced TdP after initiating therapy more frequently than non-AAs-induced group (2.5 versus 1 event, P=0.008). AAs-induced group exhibited macroscopic T-wave alternans more frequently than non-AAs-induced group (6 versus 0, P=0.02). CONCLUSIONS: AAs play a key role in triggering TdP in more than half of patients with acute acquired LQTS and can increase TdP frequency after initiating therapy. Thus, AAs are not benign but rather can be life-threatening in patients with acute acquired LQTS.

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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.

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Risperidone is a second-generation antipsychotic for treating schizophrenia and bipolar disorder. It can potently inhibit IKr, but is classified into conditional risk for torsade de pointes (TdP) by CredibleMeds®. Our previous studies using chronic atrioventricular block dogs showed that risperidone alone did not induce TdP, and that dl-sotalol (ß-adrenoceptor blockade plus IKr inhibition) induced TdP three times more frequently than d-sotalol (IKr inhibition alone). Since risperidone can block α1-adrenoceptor and decrease blood pressure, the resulting reflex-mediated increase of sympathetic tone on ß-adrenoceptor might protect the heart from its IKr inhibition-associated TdP. To validate this hypothesis, risperidone was administered to chronic atrioventricular block dogs after ß-adrenoceptor blocker atenolol infusion with monitoring J-Tpeak and Tpeak-Tend, which are proarrhythmic surrogate markers of "substrate" and "trigger" toward TdP, respectively. Atenolol alone induced TdP in 1 out of 5 dogs; moreover, an additional infusion of risperidone induced TdP in 3 out of 4 dogs. Risperidone prolonged QT interval, J-Tpeak and Tpeak-Tend in animals that induced TdP. These findings indicate that ß-adrenoceptor blockade can diminish repolarization reserve to augment risperidone's torsadogenic potential, thus advising caution when using ß-adrenoceptor blockers in patients with IKr inhibition-linked labile repolarization.

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Phosphoinositide 3-kinase (PI3K) inhibitors have shown synergistic anticancer effects with endocrine therapy against ER+/PIK3CA-mutated breast cancer. PI3K inhibitors for cancer therapy are becoming more common. There is an increasing need to understand their cardiac adverse events. In this report, we describe the features of near-fatal mixed arrhythmias in a patient who was undergoing a phase Ib clinical study of PI3Kα inhibitor with fulvestrant. Subsequently, the patient survived by cardiopulmonary resuscitation and therefore did not die. This case highlights that PI3K inhibitors can induce QT/QTc prolongation and predispose patients to TdP. The combination of QT/QTc prolongation in combination with prolonged cardiac repolarization, such as an AV block during treatment with PI3Kα inhibitor, may aggravate the occurrence of TdP. It is likely to be a safer strategy to adjust the standard of discontinuing drugs and continuing drugs (QTc interval was <500 and <60 ms at baseline) or choose other types of alternative treatment options. This report provided some ideas for clinicians to identify early and prevent the occurrence of fatal arrhythmias during anticancer treatment.

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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.

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Atrial fibrillation (AF) is the most common cause of tachycardia-induced cardiomyopathy (TIC). A 75-year-old woman was referred to our hospital for catheter ablation for persistent AF. On admission, transthoracic echocardiography (TTE) revealed diffuse left ventricular (LV) hypokinesis, which was suspected to be due to TIC. Catheter ablation was performed on the fifth day of hospitalization, and Torsade de Pointes (TdP) appeared on the sixth day. The serum concentration of bepridil and potassium was below the reference level. An electrocardiogram revealed marked QT prolongation, giant-negative T waves, and T-wave alternans on the seventh day of hospitalization. Cardiac magnetic resonance imaging with no contrast indicated diffuse mild LV hypokinesis, mild prolonged native T1, and no evidence of myocardial edema at T2. Coronary angiography revealed normal coronary arteries, and the ergonovine stress test results were negative. The results for five long QT syndrome susceptibility genes, including the three major genes, were negative. Subsequently, QT prolongation, giant-negative T waves, and LV dysfunction improved without treatment. This case report highlights the importance of risk management for AF patients with TIC scheduled for catheter ablation and carefully evaluating the risks of QT prolongation. Moreover, patients with TIC can experience marked QT prolongation and TdP during the perioperative period of catheter ablation. Therefore, caution should be required.

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Opioid dependence is a common problem, and therapeutic alternatives are scarce and ineffective. Ibogaine, illegal in several countries, has been reported as a possible therapy in alternative clinics and it is also used as a recreational drug, despite its cardiotoxic potential, including QT prolongation. We report a case of long QT leading to multiple episodes of cardiac arrest after a single dose of ibogaine (200mg, 2.6mg/Kg) in a patient without structural heart disease. This case highlights the fact that even low doses of ibogaine can be lethal and warns us about the consequences of its use.

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Although morphine has been used for treatment-resistant dyspnea in end-stage heart failure patients, information on its cardiovascular safety profile remains limited. Morphine was intravenously administered to halothane-anesthetized dogs (n=4) in doses of 0.1, 1 and 10 mg/kg/10 min with 20 min of observation period. The low and middle doses attained therapeutic (0.13 µg/mL) and supratherapeutic (0.97 µg/mL) plasma concentrations, respectively. The low dose hardly altered any of the cardiovascular variables except that the QT interval was prolonged for 10-15 min after its start of infusion. The middle dose reduced the preload and afterload to the left ventricle for 5-15 min, then decreased the left ventricular contractility and mean blood pressure for 10-30 min, and finally suppressed the heart rate for 15-30 min. Moreover, the middle dose gradually but progressively prolonged the atrioventricular conduction time, QT interval/QTcV, ventricular late repolarization period and ventricular effective refractory period without altering the intraventricular conduction time, ventricular early repolarization period or terminal repolarization period. A reverse-frequency-dependent delay of ventricular repolarization was confirmed. The high dose induced cardiohemodynamic collapse mainly due to vasodilation in the initial 2 animals by 1.9 and 3.3 min after its start of infusion, respectively, which needed circulatory support to treat. The high dose was not tested further in the remaining 2 animals. Thus, intravenously administered morphine exerts a rapidly appearing vasodilator action followed by slowly developing cardiosuppressive effects. Morphine can delay the ventricular repolarization possibly through IKr inhibition in vivo, but its potential to develop torsade de pointes will be small.

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Torsades de pointes (TdP) is a type of ventricular arrhythmia that can lead to sudden cardiac death. Drug-induced TdP has been an important concern for researchers and international regulatory boards. The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative was proposed that integrates in vitro testing and computational models of cardiac ion channels and human cardiomyocyte cells to evaluate the proarrhythmic risk of drugs. The TdP risk classification performance using only a single TdP metric may require some improvements because of information limitations and the instability of generalizing results. This study evaluates the performance of TdP metrics from the in silico simulations of the Tomek-O'Hara Rudy (ToR-ORd) ventricular cell model for classifying the TdP risk of drugs. We utilized these metrics as an input to an artificial neural network (ANN)-based classifier. The ANN model was optimized through hyperparameter tuning using the grid search (GS) method to find the optimal model. The study outcomes show an area under the curve (AUC) value of 0.979 for the high-risk category, 0.791 for the intermediate-risk category, and 0.937 for the low-risk category. Therefore, this study successfully demonstrates the capability of the ToR-ORd ventricular cell model in classifying the TdP risk into three risk categories, providing new insights into TdP risk prediction methods.

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BACKGROUND: Cholinesterase inhibitors (ChEIs) are regularly used in Alzheimer's disease. Of the three ChEIs approved for dementia, donepezil is among the most prescribed drugs in the United States with nearly 6 million prescriptions in 2020; however, it is classified as a "known risk" QT interval-prolonging medication (QTPmed). Given this claim is derived from observational data including single case reports, we aimed to evaluate high-quality literature on the frequency and nature of proarrhythmic major adverse cardiac events (MACE) associated with donepezil. METHODS: We searched Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Central from 1996 onwards for randomized controlled trials (RCTs) involving patients age ≥18 years comparing donepezil to placebo. The MACE composite included mortality, sudden cardiac death, non-fatal cardiac arrest, Torsades de pointes, ventricular tachyarrhythmia, seizure or syncope. Random-effects meta-analyses were performed with a treatment-arm continuity correction for single and double zero event studies. RESULTS: Sixty RCTs (n = 12,463) were included. Twenty-five of 60 trials (n = 5886) investigated participants with Alzheimer's disease and 33 trials monitored electrocardiogram data. The mean follow-up duration was 31 weeks (SD = 36). Mortality was the most commonly reported MACE (252/331, 75.8% events), the remainder were syncope or seizures, with no arrhythmia events. There was no increased risk of MACE with exposure to donepezil compared to placebo (risk ratio [RR] 1.08, 95% CI 0.88-1.33, I2 = 0%) and this was consistent in the subgroup analysis of trials including participants with cardiovascular morbidities (RR 1.14, 95% CI 0.88-1.47). Subgroup analysis suggested a trend toward more events with donepezil with follow-up ≥52 weeks (RR: 1.32, 0.98-1.79). CONCLUSIONS: This systematic review with meta-analysis found donepezil may not be arrhythmogenic. Donepezil was not associated with mortality, ventricular arrhythmias, seizure or syncope, although longer durations of therapy need more study. Further research to clarify actual clinical outcomes related to QTPmed is important to inform prescribing practices.

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In silico modeling offers an opportunity to supplement and accelerate cardiac safety testing. With in silico modeling, computational simulation methods are used to predict electrophysiological interactions and pharmacological effects of novel drugs on critical physiological processes. The O'Hara-Rudy's model was developed to predict the response to different ion channel inhibition levels on cardiac action potential duration (APD) which is known to directly correlate with the QT interval. APD data at 30% 60% and 90% inhibition were derived from the model to delineate possible ventricular arrhythmia scenarios and the marginal contribution of each ion channel to the model. Action potential values were calculated for epicardial, myocardial, and endocardial cells, with action potential curve modeling. This study assessed cardiac ion channel inhibition data combinations to consider when undertaking in silico modeling of proarrhythmic effects as stipulated in the Comprehensive in Vitro Proarrhythmia Assay (CiPA). As expected, our data highlight the importance of the delayed rectifier potassium channel (IKr) as the most impactful channel for APD prolongation. The impact of the transient outward potassium channel (Ito) inhibition on APD was minimal while the inward rectifier (IK1) and slow component of the delayed rectifier potassium channel (IKs) also had limited APD effects. In contrast, the contribution of fast sodium channel (INa) and/or L-type calcium channel (ICa) inhibition resulted in substantial APD alterations supporting the pharmacological relevance of in silico modeling using input from a limited number of cardiac ion channels including IKr, INa, and ICa, at least at an early stage of drug development.

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Aim: Drug-induced long QT syndrome (diLQTS), an adverse effect of many drugs, can lead to sudden cardiac death. Candidate genetic variants in cardiac ion channels have been associated with diLQTS, but several limitations of previous studies hamper clinical utility. Materials & methods: Thus, the purpose of this study was to assess the associations of KCNE1-D85N, KCNE2-I57T and SCN5A-G615E with diLQTS in a large observational case-control study (6,083 self-reported white patients treated with 27 different high-risk QT-prolonging medications; 12.0% with diLQTS). Results: KCNE1-D85N significantly associated with diLQTS (adjusted odds ratio: 2.24 [95% CI: 1.35-3.58]; p = 0.001). Given low minor allele frequencies, the study had insufficient power to analyze KCNE2-I57T and SCN5A-G615E. Conclusion: KCNE1-D85N is a risk factor for diLQTS that should be considered in future clinical practice guidelines.

Some medications can lead to a condition called drug-induced long QT syndrome (diLQTS), which can be a serious abnormal heart rhythm in some patients. In our research, we explored three specific changes in DNA related to the electrical function of the heart (KCNE1-D85N, KCNE2-I57T, SCN5A-G615E) and their link to diLQTS. Our study revealed a connection between KCNE1-D85N and diLQTS. This study emphasized the importance of including KCNE1-D85N in the medical guidelines to help identify patients at risk of diLQTS. We were unable to identify the connection of KCNE2-I57T and SCN5A-G615E with diLQTS, due to a low number of carriers in the study.

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Postpartum electrical storm due to torsade de pointes is a rare but life-threatening condition. The uniqueness of this case lies in the use of cabergoline to suppress postpartum ventricular arrhythmias in absence of heart disease. Timely multidisciplinary management is crucial to achieve final diagnosis, deliver proper treatment and improve prognosis.

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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.

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Ventricular arrhythmias in cardiac channelopathies are linked to autonomic triggers, which are sub-optimally targeted in current management strategies. Improved molecular understanding of cardiac channelopathies and cellular autonomic signalling could refine autonomic therapies to target the specific signalling pathways relevant to the specific aetiologies as well as the central nervous system centres involved in the cardiac autonomic regulation. This review summarizes key anatomical and physiological aspects of the cardiac autonomic nervous system and its impact on ventricular arrhythmias in primary inherited arrhythmia syndromes. Proarrhythmogenic autonomic effects and potential therapeutic targets in defined conditions including the Brugada syndrome, early repolarization syndrome, long QT syndrome, and catecholaminergic polymorphic ventricular tachycardia will be examined. Pharmacological and interventional neuromodulation options for these cardiac channelopathies are discussed. Promising new targets for cardiac neuromodulation include inhibitory and excitatory G-protein coupled receptors, neuropeptides, chemorepellents/attractants as well as the vagal and sympathetic nuclei in the central nervous system. Novel therapeutic strategies utilizing invasive and non-invasive deep brain/brain stem stimulation as well as the rapidly growing field of chemo-, opto-, or sonogenetics allowing cell-specific targeting to reduce ventricular arrhythmias are presented.

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QT prolongation and the potentially fatal arrhythmia Torsades de Pointes are common causes for withdrawing or restricting drugs; however, little is known about similar liabilities of environmental chemicals. Current in vitro-in silico models for testing proarrhythmic liabilities, using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), provide an opportunity to address this data gap. These methods are still low- to medium-throughput and not suitable for testing the tens of thousands of chemicals in commerce. We hypothesized that combining high-throughput population- based in vitro testing in hiPSC-CMs with a fully in silico data analysis workflow can offer sensitive and specific predictions of proarrhythmic potential. We calibrated the model with a published hiPSC-CM dataset of drugs known to be positive or negative for proarrhythmia and tested its performance using internal cross-validation and external validation. Additionally, we used computational down-sampling to examine three study designs for hiPSC-CM data: one replicate of one donor, five replicates of one donor, and one replicate of a population of five donors. We found that the population of five donors had the best performance for predicting proarrhythmic potential. The resulting model was then applied to predict the proarrhythmic potential of environmental chemicals, additionally characterizing risk through margin of exposure (MOE) calculations. Out of over 900 environmental chemicals tested, over 150 were predicted to have proarrhythmic potential, but only seven chemicals had a MOE < 1. We conclude that a high-throughput in vitro-in silico approach using population-based hiPSC-CM testing provides a reasonable strategy to screen environmental chemicals for proarrhythmic potential.

This article discusses a new method for testing the potential harmful effects of environmental chemicals on the heart. We used human heart cells grown in a lab to test the chemicals and developed a computer model to predict their potential to cause dangerous heart rhythms. This method could help identify harmful chemicals more quickly and accurately than current testing methods. The study has the potential to improve evaluation of chemical risks and protect public health without the use of animals.

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Coronavirus disease 2019 (COVID-19) is associated with cardiovascular complications; however, Takotsubo cardiomyopathy (TCM) with QT prolongation and Torsade de pointes has been reported only rarely. We present a case of TCM after QT prolongation and Torsade de pointes. A 58-year-old woman was admitted because of COVID-19-related pneumonia. Seven days after admission, she developed sudden loss of consciousness without any indication of cardiovascular disease. A monitoring electrocardiogram indicated Torsade de pointes and a prolonged QT interval. Emergency cardiac catheterization revealed TCM. She was treated with favipiravir and steroids, followed by rehabilitation, and her condition improved. To detect asymptomatic TCM, routine electrocardiography screening should be considered for patients with COVID-19.

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