Case Of Torsade De Pointes Research Articles

Association of anxiolytic drugs with Torsade de Pointes: a pharmacovigilance study of the Food and Drug Administration Adverse Event Reporting System.

This study aimed to determine the association of Torsade de Pointes (TdP) with anxiolytic drugs and present a detailed overview of anxiolytic-induced cases of TdP reported to the Food and Drug Administration Adverse Event Reporting System (FAERS). All cases of anxiolytic-induced TdP (n = 260) between 1990 and 2020 were retrieved from the FAERS database using the Preferred Term 'Torsade de Pointes, code: 10044066' from the Medical Dictionary for Regulatory Activities (MedDRA version 22). Four data-mining algorithms were used for disproportionality analysis: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Empirical Bayes Geometric Mean (EBGM), and Information Content (IC). Anxiolytics with ≥3 TdP cases were included. Of a total of eight drugs, this study identified seven signals of TdP, of which six signals were new, namely for alprazolam, bromazepam, lorazepam, meprobamate, midazolam, and oxazepam. Based on disproportionality analysis, among new signals, the highest risk of TdP was observed with bromazepam and midazolam. Alprazolam showed the lowest risk for TdP, while diazepam did not reach significant disproportionality. This study identified six new signals of TdP among anxiolytic drugs, so warranting stringent clinical studies to ascertain the actual risk of TdP and ensure patient safety. This study is registered at ClinicalTrials.gov (NCT.gov ID: NCT04293432).

Psychotherapeutic drug-induced life-threatening arrhythmias: A retrospective analysis using the Japanese adverse drug eventreport database.

Drug-induced life-threatening ventricular arrhythmias including torsade de pointes (TdP), ventricular tachycardia (VT), and ventricular fibrillation (VF) are serious cardiac side effects. Psychotherapeutic drugs are known to be risk factors for arrhythmias. The aim of this study was to evaluate psychotherapeutic drugs associated with life-threatening ventricular arrhythmias using the Japanese Adverse Drug Event Report (JADER) database. From the JADER database (April 2004 to September 2022), cases of TdP, VT, VF, and QT prolongation in patients taking psychotherapeutic drugs as 'suspected drugs' were extracted. The adjusted reported odds ratio (aROR) was calculated to identify potential drugs involved in combined TdP/VF/VT or combined QT prolongation/TdP. Of the 4,530,772 cases reported, life-threatening arrhythmia-related adverse events were reported in 1760 cases (QT prolongation 1261, TdP 192, VF 108, VT 199) among 909 patients; 58.9% of patients were female, and the highest incidence was among patients aged 80-89 years (18.6%), followed by patients aged 70-79 years (15.4%). The highest aROR for TdP/VF/VT was found for trazodone (17.1), followed by sulpiride (10.8), haloperidol (9.8), donepezil (9.1), and fluvoxamine (7.9). The highest aROR for QT prolongation/TdP was found for guanfacine (87.8), followed by sultopride (60.1), escitalopram (21.0), trazodone (12.8), and donepezil (9.3). This study showed that typical antipsychotics, antidepressants, and antidementia drugs were associated with life-threatening arrhythmia-related adverse events in a Japanese clinical setting. These events were more frequent in women and elderly individuals.

Increased ventricular ectopy precedes Torsades de Pointes in patients with prolonged QT.

Torsades de Pointes (TdP) is a potentially lethal ventricular tachydysrhythmia. Prolonged heartrate corrected QT interval (QTc) predicts TdP; however, with poor specificity. We performed this study to identify other predictors of TdP among patients with prolonged QTc. We performed a retrospective case control study with 2:1 matching at an urban academic hospital. We searched our hospital electrocardiogram (ECG) database for tracings with heartrate ≤ 60, QTc≥500, and QRS<120, followed by a natural language search for electronic records with "Torsades," "polymorphic VT," or similar to identify TdP cases from 2005 to 19. We identified controls from a similar ECG database search matching for QTc, heartrate, age, and sex. We compared cardiologic and historical factors, medications, laboratory values, and ECG measurements including ectopy using univariate statistics. For those cases with saved telemetry strips that included preceding beats or TdP onset, we compared ectopy and TdP onset characteristics between the ECG and telemetry strips using mixed linear modeling. Seventy-five cases including 50 with telemetry strips and 150 controls were included. Historical, pharmacologic, laboratory, and cardiologic testing results were similar between cases and controls. The proportion of telemetry tracings with premature ventricular contractions (PVC's) preceding TdP was 0.78 compared to 0.16 for case ECG's (difference 0.62(95%CI 0.44-0.75)) and 0.10 for control ECGs (difference 0.68(95%CI 0.56-0.80)). Average telemetry heartrate was 72 and QTc 549 immediately preceding TdP, similar to the ECG values. Clinical factors don't differentiate patients with long QTc who develop TdP, however, an increase in PVC's in patients with prolonged QTc may usefully predict imminent TdP.

Correcting the QTc and fixing torsade’s, what can’t steroids do!

Introduction: Long QT syndrome (LQTS) is the congenital or acquired prolongation of the QT interval on an electrocardiogram (ECG). It is well-known that the QT interval is prolonged in adrenal insufficiency (AI) but rarely prolonged enough to cause Torsade de Pointes (TdP). Case Report: Here we report a case of TdP and cardiac arrest in a patient with adrenal insufficiency. The patient had a return of spontaneous circulation after a successful cardiopulmonary resuscitation (CPR). Electrocardiograms persistently showed prolonged QT corrected for heart rate (QTc) prior to and at the time of cardiac arrest, some exceeding 600 milliseconds (ms). The QT interval improved significantly upon administration of steroids and the episodes of TdP resolved. Conclusion: This case highlights the importance of recognizing adrenal insufficiency (AI) as a potentially reversible cause of prolonged QT and TdP.

Abstract 15535: A Case of Suspected Menstruation Induced QTc Prolongation Leading to Torsades De Pointes

Estrogen is known to produce changes in cardiac electrophysiology specifically in premenopausal women, increasing the risk of arrhythmias. We report a case of Torsades de Pointes (TdP) in a young premenopausal female. A 25-year-old female with a history of anxiety presented to the emergency room (ED) with several days of vomiting. While in the ED, she had an unwitnessed syncopal event, and was found to be in pulseless ventricular fibrillation (V-Fib) . She required one defibrillation to obtain return of spontaneous circulation (ROSC). Initial work up showed calcium 7.6 mg/dl, phosphorous 1.1 mg/dl, magnesium 2.4 mg/dl, potassium 4.0 mg/dl. Remainder of electrolytes were normal. Toxicology screen was positive for cannabinoids. Post ROSC EKG showed sinus tachycardia at a rate of 103bpm with a prolonged QTc of 531ms. Patient was not on any medications outpatient. On further discussion, patient reported no prior history of syncopal episodes, palpitations, and denied any family history of sudden cardiac death. She did report she was presently on her menses. Shortly after admission, she had recurrent polymorphic ventricular tachycardia which degenerated to TdP. She was loaded with magnesium. Echocardiogram showed an ejection fraction (EF) of 35-39% and global hypokinesis. Diagnostic left heart catheterization was performed revealing clean coronaries. Cardiac MRI revealed EF of 43% without any late gadolinium enhancement. Her QTc remained prolonged even with electrolyte normalization. She underwent successful ICD placement and remained event free during the remainder of the hospital course. She will undergo genetic work up for long QT syndrome. Female sex hormones, specifically estrogen, have been described in literature as pro-arrhythmic given its effects on QT prolongation and ion gated channels. Prior cases of menstruation dependent arrhythmias have speculated that the abrupt reduction in estradiol prior to menstruation is associated with increased cyclic adenosine monophosphate dependent arrhythmogenicity. This case highlights the multifactorial etiology of sudden V-Fib arrest in a young female, and the importance of understanding the role that sex hormones play in the underlying pathogenesis.

Drug-induced torsades de pointes: Disproportionality analysis of the United States Food and Drug Administration adverse event reporting system.

This study aimed to identify the most common and top drugs associated with the risk of torsades de pointes (TdP) based on the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. We used OpenVigil 2.1 to query FAERS database and data from the first quarter of 2004 to the third quarter of 2021 were retrieved. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify TdP cases. We listed the most common drugs associated with the reported TdP cases. Then, the reporting odds ratio (ROR) and the proportional reporting ratio (PRR) for the reporting association between different drugs and TdP risk were calculated. Meanwhile, comparisons were conducted with the QT drug lists of CredibleMeds® in an attempt to identify drugs with a potential risk of TdP that were not on the list. A total of 9,217,181 adverse event reports were identified, of which 3,807 (0.04%) were related to TdP. TdP was more likely to occur in the elderly and females. Amiodarone (464 cases) was associated with most cases of TdP. According to the disproportionality analysis, the top five drugs with the highest ROR and PRR were tolazoline (ROR 1615.11, 95% confidence interval [CI] 455.59-5725.75, PRR 969.46, χ2 2960.10), levomethadyl (ROR 1211.01, 95% CI 302.75-4844.04, PRR 807.67, χ2 1677.03), ibutilide (ROR 1118.74, 95% CI 425.00-2944.91, PRR 765.77, χ2 3845.27), halofantrine (ROR 660.55, 95% CI 184.21-2368.69, PRR 519.22, χ2 1076.31), and isoproterenol (ROR 352.20, 95% CI 227.19-546.00, PRR 307.82, χ2 6692.53). Approximately half of the top 50 drugs (22 for ROR, 30 for PRR) were not outlined on the QT drug lists of CredibleMeds®. Approximately half of the top risk drugs (22 for ROR, 30 for PRR) were not outlined in the QT drug lists of CredibleMeds®. Notably, potential risks are of great importance and should be closely monitored in clinical practice. Also, further research is needed to investigate the association between these drugs and TdP.

Torsade de Pointes Due to Hypokalemia and Hypomagnesemia.

This scenario was developed to educate emergency medicine (EM) interns but can be used to educate medical students and junior residents. Torsade de Pointes (TdP) is a rare but potentially fatal arrythmia if not quickly diagnosed and properly treated. TdP is defined as a polymorphic ventricular tachycardia (VT) characterized by an oscillatory change in amplitude around an isoelectric line that is associated with a QTc prolongation on the electrocardiogram (ECG).1 It has been well described to predispose to ventricular fibrillation and arrhythmic death. QTc prolongation can be congenital or acquired. Between 1 in 2000 to 20,000 have the genetic mutation for QTc prolongation.1 Acquired QTc is most commonly drug related leading to electrolyte abnormalities. 2 Around 28% of cases of TdP are associated with hypokalemia and hypomagnesemia.2 Several European centers estimate 0.8 to 1.2 per million people per year are drug induced.1 Patients with TdP most commonly presents with syncope, palpitations, and dizziness.2 While 50% are asymptomatic, up to 10% of patients will present in cardiac arrest.1 It is imperative for EM physicians to be able to recognize TdP as it can quickly decompensate into a ventricular fibrillation and sudden death. These patients require management of electrolyte abnormalities, ventricular dysrhythmias, and cardiac death.2 This simulation case will demonstrate treatment strategies for TdP with electrolyte repletion, antiarrhythmics, and defibrillation. By the end of this simulation session, learners will be able to: 1) formulate appropriate work-up for altered mental status (AMS) 2) recognize hypokalemia and associated findings on ECG 3) address hypomagnesemia in a setting to hypokalemia 4) manage pulseless VT by following advanced cardiac life support (ACLS) 5) recognize and address TdP 6) provide care after return of spontaneous circulation (ROSC) 7) consult intensivist and admit to intensive care unit (ICU). This session was conducted using high-fidelity simulation, which was immediately followed by an in-depth debriefing session. Each session had three EM first-year residents and six observers. There was one simulation instructor running the session and one simulation technician who acted as a nurse. After the simulation and debriefing session was complete, an online survey was sent via surveymonkey.com to all the participants. The survey collected responses to the following questions: (1) was the case believable? (2) did the case have the right amount of complexity? (3) did the case help improve medical knowledge and patient care? (4) did the simulation environment gave a real-life experience? (5) did the debriefing session after simulation help improve knowledge? A Likert scale was used to collect the responses. This case was performed once a year for 2 years in a row. There was a total of 19 respondents from both years. One hundred percent of them either agreed or strongly agreed that the case was beneficial in learning and in improving medical knowledge and patient care. All of them found the post-session debrief to be very helpful. Two of them felt neutral about the case being realistic. This high-fidelity simulation was a realistic way of educating learners on how to manage hypokalemia and hypomagnesemia leading to TdP. Cost-effectiveness varies depending on what is available at individual simulation laboratories. Learners are forced to start with a broad differential for the patient who presents with AMS. As they manage the case, the patient quickly decompensates into a fatal arrhythmia due to electrolyte abnormalities. Learners enforced their knowledge on leading ACLS, intubation skills, and treating TdP with electrical conversion and electrolyte repletion. Hypokalemia, hypomagnesemia, torsades de pointes, altered mental status, medical simulation.

QTc Prolongation in Poison Center Exposures to CredibleMeds List of Substances with "Known Risk of Torsades de Pointes".

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 ≥ 500ms 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 > 500ms. 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.

Rare case of Torsades de Pointes in severe hypothyroidism: literature review and challenges in management

BackgroundHypothyroidism can manifest as several important cardiac abnormalities. There are few reports of ventricular dysrhythmias (VDs) in hypothyroidism. We described a rare case of VDs in severe hypothyroidism and reviewed the literature behind its management.Case presentationA 67-year-old gentleman, with poor compliance to treatment for Hashimoto’s thyroiditis, presented with palpitations to the Emergency Department. He had runs of non-sustained ventricular tachycardia (NSVT). He was treated with intravenous (IV) amiodarone and admitted to the intensive care unit for observation. He then developed recurrent Torsades de Pointes (Tdp) despite treatment with several anti-arhythmics. He required electrical cardioversion and eventual transvenous overdrive pacing (OP). VT recurred while he was on OP. VT resolved and he was weaned off OP only after adequate thyroid hormone replacement.ConclusionsVDs, including NSVT, Tdp, and VT, are rare and potentially lethal in hypothyroidism. Our case demonstrates important challenges in the management of severe hypothyroidism. Here, VDs are often refractory to treatment with drugs and electrical means. The choice(s) of anti-arrhthymics requires careful consideration and can be difficult before thyroid function tests are known. Amiodarone use should be cautioned as it is associated with thyroid dysfunction and QT interval prolongation.There is no literature to guide thyroid hormone replacement in this disease. Aggressive replacement is associated with adverse cardiovascular effects. Our case showed a fine balance between the risk of rapid thyroid hormone replacement and the urgency to terminate VDs. Its administration should be carefully monitored amidst bridging strategies like electrical cardioversion and OP to manage life-threatening VDs.

C99. Torsade de pointes in coronavirus disease 2019 patient: hypopotassemia, cardiac injury, and drug-induced arrhythmia

Abstract Background Coronavirus disease 2019 (COVID-19) is a viral disease with wide spectrum of clinical manifestation. Malignant arrhythmia had been reported, however the exact mechanism remains unclear. We present a case of Torsade de Pointes (TdP) in COVID-19 patient. Case Description A 28 years old female, post caesarean section, confirmed COVID-19, was consulted to cardiology department due to acute lung oedema and premature ventricular complex (PVC) bigeminy. Oxygen saturation dropped to 78% with non-rebreathing mask, so she was intubated. She got furosemide and amiodarone drip. Later on, she developed pulseless ventricular tachycardia, TdP. Defibrillation 200 J was done and MgSO4 2 gram intravenous bolus was delivered. The rhythm converted to normal sinus rhythm, with prolonged QT Interval (503 ms). Potassium level was 2.7, hs-troponin I level was 510.6, and IL-6 level was 33.95. Echocardiogram showed global normokinetic with EF 64% on dobutamin. Amiodarone was stopped. She got MgSO4 drip and potassium chloride drip. Discussion Cardiac involvement in COVID-19 are common. Possible mechanisms are systemic inflammation and cytokine storm, as shown by increased IL-6. Cardiac injury, marked by increased hs-troponin I, causes abnormal conduction and prolonged repolarization due to interstitial edema and cardiac fibrosis, with abnormal Ca2+ handling and down regulation of K+ channels. These, together with QT-prolonging effect of amiodarone and hypokalemia, hypoxia, or neurohormonal stress, can induce TdP. Early treatment, ECG monitoring, and correcting electrolyte imbalance are very crucial in COVID-19. Once lethal arrhythmia ensues, proper anti-arrhythmia administration and withdrawal of contributing medications can prevent mortality.

C99. Torsade de pointes in coronavirus disease 2019 patient: hypopotassemia, cardiac injury, and drug-induced arrhythmia

Abstract Background Coronavirus disease 2019 (COVID-19) is a viral disease with wide spectrum of clinical manifestation. Malignant arrhythmia had been reported, however the exact mechanism remains unclear. We present a case of Torsade de Pointes (TdP) in COVID-19 patient. Case Description A 28 years old female, post caesarean section, confirmed COVID-19, was consulted to cardiology department due to acute lung oedema and premature ventricular complex (PVC) bigeminy. Oxygen saturation dropped to 78% with non-rebreathing mask, so she was intubated. She got furosemide and amiodarone drip. Later on, she developed pulseless ventricular tachycardia, TdP. Defibrillation 200 J was done and MgSO4 2 gram intravenous bolus was delivered. The rhythm converted to normal sinus rhythm, with prolonged QT Interval (503 ms). Potassium level was 2.7, hs-troponin I level was 510.6, and IL-6 level was 33.95. Echocardiogram showed global normokinetic with EF 64% on dobutamin. Amiodarone was stopped. She got MgSO4 drip and potassium chloride drip. Discussion Cardiac involvement in COVID-19 are common. Possible mechanisms are systemic inflammation and cytokine storm, as shown by increased IL-6. Cardiac injury, marked by increased hs-troponin I, causes abnormal conduction and prolonged repolarization due to interstitial edema and cardiac fibrosis, with abnormal Ca2+ handling and down regulation of K+ channels. These, together with QT-prolonging effect of amiodarone and hypokalemia, hypoxia, or neurohormonal stress, can induce TdP. Early treatment, ECG monitoring, and correcting electrolyte imbalance are very crucial in COVID-19. Once lethal arrhythmia ensues, proper anti-arrhythmia administration and withdrawal of contributing medications can prevent mortality.

Torsade de pointes: A nested case-control study in an integrated healthcare delivery system.

BackgroundTdP is a form of polymorphic ventricular tachycardia which develops in the setting of a prolonged QT interval. There are limited data describing risk factors, treatment, and outcomes of this potentially fatal arrhythmia.ObjectiveOur goals were as follows: (1) to validate cases presenting with Torsade de Pointes (TdP), (2) to identify modifiable risk factors, and (3) to describe the management strategies used for TdP and its prognosis in a real‐world healthcare setting.MethodsCase–control study (with 2:1 matching on age, sex, and race/ethnicity) nested within the Genetic Epidemiology Research on Aging (GERA) cohort. Follow‐up of the cohort for case ascertainment was between January 01, 2005 and December 31, 2018.ResultsA total of 56 cases of TdP were confirmed (incidence rate = 3.6 per 100,000 persons/years). The average (SD) age of the TdP cases was 74 (13) years, 55 percent were female, and 16 percent were non‐white. The independent predictors of TdP were potassium concentration <3.6 mEq/L (OR = 10.6), prior history of atrial fibrillation/flutter (OR = 6.2), QTc >480 ms (OR = 4.4) and prior history of coronary artery disease (OR = 2.6). Exposure to furosemide and amiodarone was significantly greater in cases than in controls. The most common treatment for TdP was IV magnesium (78.6%) and IV potassium repletion (73.2%). The in‐hospital and 1‐year mortality rates for TdP cases were 10.7% and 25.0% percent, respectively.ConclusionsThese findings may inform quantitative multivariate risk indices for the prediction of TdP and could guide practitioners on which patients may qualify for continuous ECG monitoring and/or electrolyte replacement therapy.

Torsade de pointes associated with chloroquine, hydroxychloroquine, and azithromycin: a retrospective analysis of individual case safety reports from VigiBase.

PurposeTo analyze the cases of torsade de pointes (TdP) and related symptoms reported in association with chloroquine (CQ), hydroxychloroquine (HCQ), and azithromycin (AZT) to the World Health Organization (WHO) global database of individual case safety reports (ICSRs) for drug monitoring (VigiBase) using qualitative and quantitative pharmacovigilance approaches.MethodsThe main characteristics of the ICSRs reporting TdP with CQ, HCQ, and AZT have been summarized. Co-reported drugs with risk to cause QT prolongation have been described. Reporting odds ratios (RORs) as a measure of disproportionality for reported TdP and individual drugs have been calculated.ResultsOne hundred seventy ICSRs reporting TdP in association with the drugs of interest were identified (CQ: 11, HCQ: 31, CQ + HCQ: 1, HCQ + AZT: 27, AZT: 100). From these, 41 (24.3%) were received during the pandemic period (December 2019 to February 2021). The median age of the patients was 63, 53, and 63 years old for CQ, HCQ, and AZT, respectively. Reports included concomitant use of other QT-prolonging drugs (CQ 25.0%, HCQ 71.2%, AZT 64.6%). A proportion of the cases were fatal (CQ 25.0%, HCQ 8.6%, AZT 16.1%). Increased disproportionality has been found for the individual drugs and TdP: CQ (ROR: 7.41, 95% confidence interval (CI): 3.82, 12.96), HCQ (ROR: 8.49, 95% CI: 6.57, 10.98), azithromycin (ROR: 8.06, 95% CI: 6.76, 9.61). Disproportionality was also found for other related symptoms, Standardized MedDRA Query for torsade de pointes/QT prolongation (narrow): CQ (ROR: 11.95, 95% CI: 10.04–14.22); HCQ (ROR: 20.43, 95% CI: 19.13, 21.83), AZT (ROR: 7.78, 95% CI: 7.26, 8.34).ConclusionsThe prescription of CQ, HCQ, and AZT should be restricted to therapeutic indications with established positive benefit/risk profile. Doctors and patients should be aware of this potential adverse reaction especially when several risk factors are present.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00228-021-03133-w.

Torsade De Pointes: A Nested Case Control Study in an Integrated Health Care Delivery System

Objectives: 1) To validate cases presenting with Torsade de Pointes (TdP) and compare these cases to age-, sex-, and race/ethnicity (2 to 1) matched-controls in order to identify modifiable risk factors; and 2) Describe the management strategies used for TdP and its prognosis in a real-world health care setting. Background: TdP is a form of polymorphic ventricular tachycardia which develops in the setting of a prolonged QTc interval. There is limited data describing risk factors, treatment and outcomes of this potentially fatal arrhythmia. Results: Using the Genetic Epidemiology Research on Aging (GERA) cohort (n=110,266) and follow-up between 01/01/2005 and 12/31/2018, a total of 56 cases of TdP were confirmed (incidence rate= 3.6 per 100,000 persons/year. The average (SD) age of the TdP cases was 74 (13) years, 55 percent were female and 16 percent non-white. The independent predictors of TdP were prior history of heart failure (OR=5.7), supraventricular arrhythmias (OR=3.6) and potassium concentration < 3.6 mEq/L (OR=10). On average, TdP cases were preceded by 48 ms prolongation of the QTc. Exposure to furosemide and amiodarone were significantly greater in cases than in controls. The most common treatment for TdP was IV magnesium (78.6%) and IV potassium repletion (73.2%). The in-hospital and 1-year mortality rates for TdP cases were 10.7% and 25.0% percent, respectively. Conclusions: These findings may inform quantitative multivariate risk indices for the prediction of TdP and could guide practitioners on which patients may qualify for continuous ECG monitoring and/or electrolyte replacement therapy.

Risk Assessment of Drug-Induced Long QT Syndrome for Some COVID-19 Repurposed Drugs.

The risk‐benefit ratio associated with the use of repurposed drugs to treat severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2)‐related infectious coronavirus disease 2019 (COVID‐19) is complicated because benefits are awaited, not proven. A thorough literature search was conducted to source information on the pharmacological properties of 5 drugs and 1 combination (azithromycin, chloroquine, favipiravir, hydroxychloroquine, remdesivir, and lopinavir/ritonavir) repurposed to treat COVID‐19. A risk assessment of drug‐induced long QT syndrome (LQTS) associated with COVID‐19 repurposed drugs was performed and compared with 23 well‐known torsadogenic and 10 low torsadogenic risk compounds. Computer calculations were performed using pharmacokinetic and pharmacodynamic data, including affinity to block the rapid component of the delayed rectifier cardiac potassium current (IKr) encoded by the human ether‐a‐go‐go gene (hERG), propensity to prolong cardiac repolarization (QT interval) and cause torsade de pointes (TdP). Seven different LQTS indices were calculated and compared. The US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database was queried with specific key words relating to arrhythmogenic events. Estimators of LQTS risk levels indicated a very high or moderate risk for all COVID‐19 repurposed drugs with the exception for azithromycin, although cases of TdP have been reported with this drug. There was excellent agreement among the various indices used to assess risk of drug‐induced LQTS for the 6 repurposed medications and 23 torsadogenic compounds. Based on our results, monitoring of the QT interval shall be performed when some COVID‐19 repurposed drugs are used, as such monitoring is possible for hospitalized patients or with the use of biodevices for outpatients.

COVID-19 and cardiac arrhythmias: a global perspective on arrhythmia characteristics and management strategies.

BackgroundCardiovascular and arrhythmic events have been reported in hospitalized COVID-19 patients. However, arrhythmia manifestations and treatment strategies used in these patients have not been well-described. We sought to better understand the cardiac arrhythmic manifestations and treatment strategies in hospitalized COVID-19 patients through a worldwide cross-sectional survey.MethodsThe Heart Rhythm Society (HRS) sent an online survey (via SurveyMonkey) to electrophysiology (EP) professionals (physicians, scientists, and allied professionals) across the globe. The survey was active from March 27 to April 13, 2020.ResultsA total of 1197 respondents completed the survey with 50% of respondents from outside the USA, representing 76 countries and 6 continents. Of respondents, 905 (76%) reported having COVID-19-positive patients in their hospital. Atrial fibrillation was the most commonly reported tachyarrhythmia whereas severe sinus bradycardia and complete heart block were the most common bradyarrhythmias. Ventricular tachycardia/ventricular fibrillation arrest and pulseless electrical activity were reported by 4.8% and 5.6% of respondents, respectively. There were 140 of 631 (22.2%) respondents who reported using anticoagulation therapy in all COVID-19-positive patients who did not otherwise have an indication. One hundred fifty-five of 498 (31%) reported regular use of hydroxychloroquine/chloroquine (HCQ) + azithromycin (AZM); concomitant use of AZM was more common in the USA. Sixty of 489 respondents (12.3%) reported having to discontinue therapy with HCQ + AZM due to significant QTc prolongation and 20 (4.1%) reported cases of Torsade de Pointes in patients on HCQ/chloroquine and AZM. Amiodarone was the most common antiarrhythmic drug used for ventricular arrhythmia management.ConclusionsIn this global survey of > 1100 EP professionals regarding hospitalized COVID-19 patients, a variety of arrhythmic manifestations were observed, ranging from benign to potentially life-threatening. Observed adverse events related to use of HCQ + AZM included prolonged QTc requiring drug discontinuation as well as Torsade de Pointes. Large prospective studies to better define arrhythmic manifestations as well as the safety of treatment strategies in COVID-19 patients are warranted.Electronic supplementary materialThe online version of this article (10.1007/s10840-020-00789-9) contains supplementary material, which is available to authorized users.

Chloroquine-induced torsades de pointes in a patient with coronavirus disease 2019

Chloroquine-induced torsades de pointes in a patient with coronavirus disease 2019

Drug use and torsades de pointes cardiac arrhythmias in Sweden: a nationwide register-based cohort study

ObjectiveTo study the occurrence of torsades de pointes (TdP) ventricular tachycardia in relation to use of drugs labelled with TdP risk, using two nationwide Swedish registers.DesignProspective register-based cohort study.SettingEntire Sweden.ParticipantsPersons...

A case of Torsade de Pointes during and after total laparoscopic hysterectomy

A case of Torsade de Pointes during and after total laparoscopic hysterectomy

Determinants of cardiac repolarization and risk for ventricular arrhythmias during mild therapeutic hypothermia

PurposeWe aimed to investigate the factors that modulate the extent of QTc prolongation and potential arrhythmogenic consequences during mild therapeutic hypothermia (MTH). MethodsWe studied 205 patients after out-of-hospital cardiac arrest (131 underwent MTH). QTc was measured at baseline, 3h, 6h, 12h, 24h (end of hypothermia), 48h and 72h, and ventricular arrhythmias quantified. ResultsDuring MTH, the QTc interval increased progressively peaking at 12h (mean increase 42ms, 95% CI 30–55). There was a strong gender effect (P<0.001) and a significant gender-by-MTH interaction (P=0.004). At 12h, the QTc interval was markedly longer in women as compared with men (mean difference 50ms [95% CI 27–73]. Anoxic brain injury (P=0.002) was also positively associated with QTc prolongation. The risk for ventricular arrhythmic events was not higher with MTH compared with no hypothermia (incidence rate ratio 0.57, 95% CI 0.32–1.02, P=0.06). However, typical cases of Torsade de pointes occurred in association with AV block and LQT2. ConclusionQTc prolongation during MTH is strongly affected by female gender and moderately by concomitant anoxic brain injury. Although the overall risk for ventricular arrhythmias is not greater with MTH, Torsade de pointes may develop when other contributing factors coexist.