Torsades de Pointes

A 53-year-old presented to the emergency department following a fall and was found to have recurrent episodes of torsades de pointes and pulseless ventricular tachycardia on cardiac monitoring. He had been abusing nimetazepam for sleep issues over the preceding one month. Despite correction of electrolytes, the arrhythmias were persistent which necessitated temporary overdrive pacing. The patient made an uneventful recovery and the temporary pacing was successfully removed with no recurrence of the malignant arrhythmias prior to discharge...

BACKGROUND: The aim of this study was to evaluate the association between CDK4/6 inhibitors and QT interval prolongation (QTp) and Torsades de Pointes (TdP) in breast cancer patients. METHOD: The cases with breast cancer from 2015 to 2022 were extracted from the FDA adverse event database (FARES) and further divided into a CDK4/6 inhibitor group and a positive control group. The associations between CDK4/6 inhibitors and QTp and TdP adverse events were evaluated using the reporting odds ratio (ROR) and the information component (IC)...

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...

BACKGROUND: Transvenous pacemaker placement is an integral component of therapy for severe dysrhythmias and a core skill in emergency medicine. OBJECTIVE: This narrative review provides a focused evaluation of transvenous pacemaker placement in the emergency department setting. DISCUSSION: Temporary cardiac pacing can be a life-saving procedure. Indications for pacemaker placement include hemodynamic instability with symptomatic bradycardia secondary to atrioventricular block and sinus node dysfunction; overdrive pacing in unstable tachydysrhythmias, such as torsades de pointes; and failure of transcutaneous pacing...

An injectable anti-influenza drug peramivir has been reported to induce QT-interval prolongation in some phase III studies, although its thorough QT/QTc study was negative. We investigated the discrepancy among those clinical studies using isoflurane-anesthetized beagle dogs (n = 4). Peramivir in doses of 1 mg/kg/10 min (sub-therapeutic dose) followed by 10 mg/kg/10 min (clinically-relevant dose) was intravenously administered. Peramivir prolonged QT interval/QTcV and Tpeak -Tend , and tended to delay ventricular repolarization in a reverse-frequency dependent manner, indicating IKr inhibition in vivo...

BACKGROUND: Patients undergoing dialysis pose therapeutic challenges in terms of polypharmacy, administration of potentially inappropriate drugs, and drugs with the potential risk of toxicity. OBJECTIVE: This study evaluated the use of drugs, potentially inappropriate medicines (PIM), drugs with risk of Torsades de Pointes (TdP), and the complexity of the prescribed regimen using the medication regimen complexity index scale in patients undergoing hemodialysis. METHODS: A retrospective cohort study was carried out amongst patients receiving hemodialysis...

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.

Human iPSC-derived cardiomyocytes (hiPSC-CMs) exhibit functional immaturity, potentially impacting their suitability for assessing drug proarrhythmic potential. We previously devised a traveling wave (TW) system to promote maturation in 3D cardiac tissue. To align with current drug assessment paradigms (CiPA and JiCSA), necessitating a 2D monolayer cardiac tissue, we integrated the TW system with a multi-electrode array. This gave rise to a hiPSC-derived closed-loop cardiac tissue (iCT), enabling spontaneous TW initiation and swift pacing of cardiomyocytes from various cell lines...

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...

BACKGROUND: Women have been under-represented in trials of antipsychotic medications. AIM: Our primary objective was to evaluate five adverse events (AE) associated with first-generation antipsychotics (FGAs) among women relative to men through an analysis of the FDA Adverse Event Reporting System (FAERS). METHOD: We queried 24.6 million AE reports from 2000 to 2023 involving FGAs. The study cohort consisted of chlorpromazine (n = 3317), fluphenazine (n = 1124), haloperidol (n = 16,709), loxapine (n = 3151), perphenazine (n = 816), thioridazine (n = 665), thiothixene (n = 244), and trifluoperazine (n = 360)...

IMPORTANCE: Antipsychotic medications, often prescribed for delirium in intensive care units (ICUs), may contribute to QTc interval prolongation. OBJECTIVE: To determine whether antipsychotics increase the QTc interval in patients with delirium in the ICU. DESIGN, SETTING, AND PARTICIPANTS: An a priori analysis of a randomized clinical trial in medical/surgical ICUs within 16 centers across the US was conducted. Participants included adults with delirium in the ICU with baseline QTc interval less than 550 ms...

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...

Cavutilide (niferidil, refralon) is a new class III antiarrhythmic drug which effectively terminates persistent atrial fibrillation (AF; 84.6% of patients, mean AF duration 3 months) and demonstrates low risk of torsade de pointes (1.7%). ERG channels of rapid delayed rectifier current(IKr ) are the primary target of cavutilide, but the particular reasons of higher effectiveness and lower proarrhythmic risk in comparison with other class III IKr blockers are unclear. The inhibition of hERG channels expressed in CHO-K1 cells by cavutilide was studied using whole-cell patch-clamp...

A 39-year-old man with non-ischemic cardiomyopathy presented for routine right heart catheterization.

BACKGROUND: Sickle cell disease, a common genetic disorder in African Americans, manifests an increased risk of sudden death, the basis of which is incompletely understood. Prolongation of heart rate-corrected QT (QTc) interval on the electrocardiogram, a standard clinical measure of cardiac repolarization, may contribute to sudden death by predisposing to torsades de pointes ventricular tachycardia. METHODS: We established a cohort study of 293 adult and 121 pediatric sickle cell disease patients drawn from the same geographic region as the Jackson Heart Study (JHS) cohort, in which significant correlates of QT duration have been characterized and quantitatively modeled...

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 (ANS) and its impact on ventricular arrhythmias in primary inherited arrhythmia syndromes...

QT prolongation is related to the development of ventricular arrhythmias such as Torsade de Pointes (TdP) that can lead to sudden cardiac death. Several drugs used in the treatment of patients with advanced cancer may induce QT prolongation due to their interference with cardiac ion channels. Some patients may be at higher risk if predisposing factors are present. Herein we present the case of a patient with advanced cancer under anti-tumor treatment with radical intention that developed a reversible drug-induced QT prolongation when simultaneously treated with methadone, haloperidol and fluoxetine that presented with chest pain and bradycardia...

INTRODUCTION: We report the case of an 18-year-old female with recurrent syncope that was discovered to have congenital long QT syndrome (LQTS) and episodes of a transiently short QT interval after spontaneous termination of polymorphic ventricular tachycardia. METHODS & RESULTS: A cardiac event monitor revealed a long QT interval and initiation of polymorphic ventricular tachycardia by a premature ventricular complex on the preceding T-wave. After 1 minute of ventricular fibrillation, her arrhythmia spontaneously terminated with evidence of a short QT interval...

Drug-induced long QT syndrome (LQTS) is defined as prolonged corrected QT interval (QTc ≥460 ms) plus polymorphic ventricular arrhythmia fitting the description of torsades de pointes temporally associated with the administration of a drug or combination of drugs. Amiodarone therapy is a known uncommon cause of acquired QT interval prolongation that should not be underestimated. We present a case of an iatrogenic electrical storm with atrial fibrillation (AF) in which amiodarone was administered to attempt chemical cardioversion, resulting in an unnoticed prolongation of the QT interval, with subsequent repeated polymorphic ventricular tachycardia, managed with isoproterenol...

BACKGROUND: Studies in small animals and human patients have suggested that anthracyclines may prolong cardiac repolarization, or at least inhibit repolarization reserve, predisposing to QT prolongation and dangerous arrhythmias such as Torsades de pointes. This association in humans is difficult to confirm due to multiple confounding variables such as the presence of other medications and concurrent illness. OBJECTIVES: Identify a long-term association between anthracycline administration and repolarization prolongation in nonhuman primates, which can be measured as prolonged QT/QTc intervals on surface electrocardiogram...