2,037 results match your criteria Torsade de Pointes


Development of a Human iPSC Cardiomyocyte-Based Scoring System for Cardiac Hazard Identification in Early Drug Safety De-risking.

Stem Cell Reports 2018 Dec;11(6):1365-1377

Global Safety Pharmacology, Non-Clinical Safety, Janssen Research & Development, A Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising cardiac safety platform, demonstrated by numerous validation studies using drugs with known cardiac adverse effects in humans. However, the challenge remains to implement hiPSC-CMs into cardiac de-risking of new chemical entities (NCEs) during preclinical drug development. Here, we used the calcium transient screening assay in hiPSC-CMs to develop a hazard score system for cardiac electrical liabilities. Read More

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December 2018

Ablation of idiopathic ventricular fibrillation targeting short coupled ventricular premature contractions originating from a right ventricular papillary muscle.

J Cardiol Cases 2014 Mar 18;9(3):113-116. Epub 2014 Jan 18.

Department of Cardiovascular Medicine, Tenri Hospital, Tenri, Nara, Japan.

We describe a 38-year-old male who experienced several episodes of syncope after having ventricular fibrillation. The electrocardiographic monitoring after his hospitalization revealed repetitive polymorphic ventricular tachycardias. All polymorphic ventricular tachycardias were consistently initiated by a short-coupled monomorphic ventricular premature contraction (VPC). Read More

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Torsade de pointes associated with the combination of solifenacin and clenbuterol for urinary incontinence.

J Cardiol Cases 2014 Mar 12;9(3):91-93. Epub 2013 Dec 12.

Department of Cardiovascular Medicine, Dokkyo Medical University, Mibu, Tochigi, Japan.

A 79-year-old woman undergoing medical treatment with solifenacin and clenbuterol for urinary incontinence was admitted to our hospital because of recurrent syncope. Her syncope appeared one month after the doses of clenbuterol were increased. Torsade de pointes (TdP) was evident on her Holter electrocardiogram at the time when she developed syncope. Read More

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Prevalence of Torsades de Pointes inducing drugs usage among elderly outpatients in North Jordan Hospitals.

Saudi Pharm J 2018 Dec 29;26(8):1146-1154. Epub 2018 Jul 29.

Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan.

Background: Torsade de Pointes (TdP) is an abnormal cardiac rhythm associated with a prolongation of QT interval. Although in most cases it spontaneously returns to the normal rhythm, TdP can lead to sudden cardiac death. Medications are the main cause of QT-prolongation and subsequent TdP flare, even though the exact mechanism of why some people evoke TdP but others do not is still unknown. Read More

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December 2018

Characteristics of hERG and hNav1.5 channel blockade by sulcardine sulfate, a novel anti-arrhythmic compound.

Eur J Pharmacol 2018 Dec 6. Epub 2018 Dec 6.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

Sulcardine sulfate (sulcardine) is a novel anti-arrhythmic compound, which blocks multiple channels and was shown to be safe and tolerated in clinical trials. The aim of the present study was to investigate the electrophysiological characteristics of sulcardine on the hERG and hNav1.5 channels. Read More

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December 2018

Medical Castration is a Rare but Possible Trigger of Torsade de Pointes and Ventricular Fibrillation.

Int Heart J 2018 Dec 5. Epub 2018 Dec 5.

Department of Cardiovascular Medicine, Faculty of Medical Sciences, University of Fukui.

Prostate cancer is the most common non-cutaneous malignancy in men and has been steadily rising in an aging society. Medical castration therapy is effective for metastatic prostate cancer, but the proarrhythmic properties have not been reported. We present a 71-year-old Japanese man with metastasis prostate cancer that, during medical castration therapy, had torsades de pointes (TdP) with a QT prolongation and ventricular fibrillation (VF). Read More

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December 2018
1 Read

The role of mexiletine in the management of long QT syndrome.

J Electrocardiol 2018 Nov - Dec;51(6):1061-1065. Epub 2018 Aug 31.

Arrhythmia Unit, Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Lankenau Institute for Medical Research, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA. Electronic address:

Congenital long QT syndrome (LQTS) is a hereditary cardiac disorder characterized by QT-interval prolongation and T-wave abnormalities on electrocardiogram (ECG), and is associated with an increased risk of torsade de pointes and sudden cardiac death. Beta-blocker medication is effective in most patients except those with a very slow heart rate. Increased late sodium currents (INa-L) can result in bradycardia-dependent QT prolongation. Read More

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Assessment of Multi-Ion Channel Block in a Phase-1 Randomized Study Design:Results of the CiPA Phase 1 ECG Biomarker Validation Study.

Clin Pharmacol Ther 2018 Nov 17. Epub 2018 Nov 17.

Office of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USA.

Balanced multi-ion channel-blocking drugs have low torsade risk because they block inward currents. The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative proposes to use an in-silico cardiomyocyte model to determine the presence of balanced block, and absence of J-Tpeakc prolongation would be expected for balanced blockers. This study included 3 balanced blockers in a 10-subject per drug parallel-design; lopinavir/ritonavir and verapamil met the primary endpoint of ΔΔJ-Tpeakc upper bound <10 ms, while ranolazine did not (upper bounds of 8. Read More

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November 2018
4 Reads

Mechanisms Underlying the Actions of Antidepressant and Antipsychotic Drugs That Cause Sudden Cardiac Arrest.

Arrhythm Electrophysiol Rev 2018 Aug;7(3):199-209

Lankenau Institute for Medical Research Wynnewood, PA, USA.

A number of antipsychotic and antidepressant drugs are known to increase the risk of ventricular arrhythmias and sudden cardiac death. Based largely on a concern over the development of life-threatening arrhythmias, a number of antipsychotic drugs have been temporarily or permanently withdrawn from the market or their use restricted. While many antidepressants and antipsychotics have been linked to QT prolongation and the development of torsade de pointes arrhythmias, some have been associated with a Brugada syndrome phenotype and the development of polymorphic ventricular arrhythmias. Read More

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August 2018
4 Reads

The arrhythmogenic cardiotoxicity of the quinoline and structurally related antimalarial drugs: a systematic review.

BMC Med 2018 Nov 7;16(1):200. Epub 2018 Nov 7.

Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

Background: Several quinoline and structurally related antimalarial drugs are associated with cardiovascular side effects, particularly hypotension and electrocardiographic QT interval prolongation. A prolonged QT interval is a sensitive but not specific risk marker for the development of Torsade de Pointes-a potentially lethal polymorphic ventricular tachyarrhythmia. The increasing use of quinoline and structurally related antimalarials in mass treatments to eliminate malaria rapidly highlights the need to review their cardiovascular safety profiles. Read More

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November 2018
5 Reads

Withdrawal of prenylamine: perspectives on pharmacological, clinical and regulatory outcomes following the first QT-related casualty.

Ther Adv Drug Saf 2018 Aug 18;9(8):475-493. Epub 2018 Jun 18.

Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, King's College, London, UK.

Prenylamine, an antianginal agent marketed since early 1960, became the first casualty of QT interval related proarrhythmias in 1988 when it was withdrawn from the market. The period of its synthesis and marketing is of particular interest since it antedated, first, any serious clinical safety concern regarding drug-induced prolongation of the QT interval which was, in fact, believed to be an efficient antiarrhythmic mechanism; second, the first description of torsade de pointes as a unique proarrhythmia, typically associated with prolonged QT interval; and third, the discovery and recognition of calcium antagonism as an important cardiovascular therapeutic strategy. This review, 30 years almost to the day following its withdrawal, provides interesting perspectives on clinical, pharmacological and regulatory outcomes that followed. Read More

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August 2018
5 Reads

Antipsychotics and cardiovascular risk: A case/non-case study.

Psychiatry Res 2018 Dec 18;270:341-347. Epub 2018 Sep 18.

Centre for Drug Surveillance (CESME), Valladolid University, Valladolid, Spain.

Severe mental disorders have been reported to be associated with an increased cardiovascular risk. To measure the potential risk excess as compared, not with the baseline cardiovascular risk for the general population, but with the cardiovascular risk associated with drug iatrogenia. 197 reported cases of cardiovascular adverse reaction to antipsychotic drugs as compared to the reported cases of this type of adverse reactions to drugs other than antipsychotics entered in the Spanish Pharmacovigilance System database (FEDRA) (1995-2018) in an observational case/non-case study. Read More

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December 2018
1 Read

Utility of QT interval corrected by Rautaharju method to predict drug-induced torsade de pointes.

Clin Toxicol (Phila) 2018 Sep 27:1-6. Epub 2018 Sep 27.

b Department of Emergency Medicine , Emory University , Atlanta , GA , USA.

Introduction: New QT correction formulae derived from large populations are available such as Rautaharju's [QTcRTH = QT * (120 + HR)/180] and Dmitrienko's [QTcDMT = QT/RR]. These formulae were derived from 57,595 and 13,039 cases, respectively. Recently, a study has shown that they did not experience errors across a wide range of heart rates compared to others. Read More

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September 2018
1 Read

International Multisite Study of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Drug Proarrhythmic Potential Assessment.

Cell Rep 2018 Sep;24(13):3582-3592

AbbVie, North Chicago, IL 60064-6118, USA. Electronic address:

To assess the utility of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as an in vitro proarrhythmia model, we evaluated the concentration dependence and sources of variability of electrophysiologic responses to 28 drugs linked to low, intermediate, and high torsades de pointes (TdP) risk categories using two commercial cell lines and standardized protocols in a blinded multisite study using multielectrode array or voltage-sensing optical approaches. Logistical and ordinal linear regression models were constructed using drug responses as predictors and TdP risk categories as outcomes. Three of seven predictors (drug-induced arrhythmia-like events and prolongation of repolarization at either maximum tested or maximal clinical exposures) categorized drugs with reasonable accuracy (area under the curve values of receiver operator curves ∼0. Read More

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September 2018
1 Read

Sex-related Differences in Drug-induced QT Prolongation and Torsades de Pointes: a New Model System with Human iPSC-CMs.

Toxicol Sci 2018 Sep 22. Epub 2018 Sep 22.

Division of Systems Biology, National Center for Toxicological Research, U.S. FDA, Jefferson, AR.

Numerous drugs have the potential to prolong the QT interval and may cause accidental cardiac arrest (torsade de pointes, TdP). Women are at a higher risk than men for experiencing drug-induced TdP. Due to the lack of appropriate tools, few studies have investigated whether genetic differences between men and women have any effects on drug-induced proarrhythmia. Read More

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September 2018
7 Reads

Ivabradine Aggravates the Proarrhythmic Risk in Experimental Models of Long QT Syndrome.

Cardiovasc Toxicol 2018 Sep 20. Epub 2018 Sep 20.

Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.

Ivabradine has recently been demonstrated to have antiarrhythmic properties in atrial fibrillation. The aim of the present study was to assess the electrophysiologic profile of ivabradine in an experimental whole-heart model of long-QT-syndrome. In 12 isolated rabbit hearts long-QT-2-syndrome (LQT2) was simulated by infusion of D,L-sotalol (100 µM). Read More

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September 2018
7 Reads

Predictive Value of T - T Indices for Adverse Outcomes in Acquired QT Prolongation: A Meta-Analysis.

Front Physiol 2018 3;9:1226. Epub 2018 Sep 3.

Department of Anaesthesia and Intensive Care, Chinese University of Hong Kong, Hong Kong, Hong Kong.

Acquired QT interval prolongation has been linked with malignant ventricular arrhythmias, such as , in turn predisposing to sudden cardiac death. Increased dispersion of repolarization has been identified as a pro-arrhythmic factor and can be observed as longer T - T interval and higher T - T/QT ratio on the electrocardiogram. However, the values of these repolarization indices for predicting adverse outcomes in this context have not been systematically evaluated. Read More

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September 2018
3 Reads

Cochlear implantation in children with congenital long QT syndrome: Introduction of an evidence-based pathway of care.

Cochlear Implants Int 2018 Nov 19;19(6):350-354. Epub 2018 Sep 19.

a Department of Paediatric Anaesthesia , Royal Manchester Children's Hospital , Manchester , UK.

Congenital long QT syndrome (cLQTS) is an inherited cardiac ion channelopathy characterized by a long corrected-QT interval on the ECG, associated with a risk of syncope and sudden death as a result of arrhythmias. The archetypal arrhythmia associated with cLQTS is torsade de pointes which may degenerate into ventricular fibrillation. Children with Jervell and Lange-Neilsen syndrome have the combination of cLQTS and congenital sensorineural deafness and may present for cochlear implantation (CI). Read More

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November 2018
6 Reads

Comprehensive In Vitro Proarrhythmia Assay (CiPA) Update from a Cardiac Safety Research Consortium / Health and Environmental Sciences Institute / FDA Meeting.

Ther Innov Regul Sci 2018 Aug 29:2168479018795117. Epub 2018 Aug 29.

5 Stanford University, Palo Alto, CA, USA.

A Cardiac Safety Research Consortium / Health and Environmental Sciences Institute / FDA-sponsored Think Tank Meeting was convened in Washington, DC, on May 21, 2018, to bring together scientists, clinicians, and regulators from multiple geographic regions to evaluate progress to date in the Comprehensive In Vitro Proarrhythmia Assay (CiPA) Initiative, a new paradigm to evaluate proarrhythmic risk. Study reports from the 4 different components of the CiPA paradigm (ionic current studies, in silico modeling to generate a Torsade Metric Score, human induced pluripotent stem cell-derived ventricular cardiomyocytes, and clinical ECG assessments including J-Tpeakc) were presented and discussed. This paper provides a high-level summary of the CiPA data presented at the meeting. Read More

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An Augmented Negative Force-Frequency Relationship and Slowed Mechanical Restitution Are Associated With Increased Susceptibility to Drug-Induced Torsade de Pointes Arrhythmias in the Chronic Atrioventricular Block Dog.

Front Physiol 2018 8;9:1086. Epub 2018 Aug 8.

Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, Netherlands.

In the chronic AV-block (CAVB) dog model, structural, contractile, and electrical remodeling occur, which predispose the heart to dofetilide-induced Torsade de Pointes (TdP) arrhythmias. Previous studies found a relation between electrical remodeling and inducibility of TdP, while structural remodeling is not a prerequisite for arrhythmogenesis. In this study, we prospectively assessed the relation between markers of contractile remodeling and TdP inducibility. Read More

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August 2018
2 Reads

Update on the ECG component of the CiPA initiative.

Authors:
Jose Vicente

J Electrocardiol 2018 Nov - Dec;51(6S):S98-S102. Epub 2018 Aug 7.

Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA. Electronic address:

The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative is validating a new paradigm for assessing proarrhythmic potential of drugs that goes beyond hERG block and QT prolongation. Based on in vitro data of the drug's effects on multiple cardiac ion channel currents, CiPA's in silico model of the human cardiomyocyte will classify drugs as low, intermediate or high risk for torsade de pointes. Under CiPA, early phase 1 ECG data will be used to determine if there are unexpected ion channel effects in humans compared to the in vitro ion channel data. Read More

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August 2018
9 Reads

Acquired drug-induced long QTc: new insights coming from a retrospective study.

Eur J Clin Pharmacol 2018 Dec 15;74(12):1645-1651. Epub 2018 Aug 15.

Mid-German Heart Center, Department of Internal Medicine III, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, ErnstGrube-Straße 40, 06120, Halle, Germany.

Introduction: Several drug classes (antiarrhythmics, antimicrobials, antidepressants, phenothiazines, opiates, prokinetics of digestive tract, etc.) have been related to ventricular hyperkinetic arrhythmias such as torsade de pointes (TdP). TdPs are usually heralded by an abnormal prolongation of heart rate-corrected QT interval on the electrocardiogram, so-called drug-induced long heart rate-corrected QT (diLQTc). Read More

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December 2018
10 Reads

Domperidone for insufficient lactation in England 2002-2015: A drug utilization study with interrupted time series analysis.

Pharmacoepidemiol Drug Saf 2018 Dec 14;27(12):1316-1324. Epub 2018 Aug 14.

Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.

Purpose: Our aim was to describe trends in the prescription of domperidone for insufficient lactation in England, the characteristics of women prescribed it postpartum, and the impact of a 2014 European Medicines Agency (EMA) recommendation to restrict its use due to a potential increased risk of sudden cardiac death associated with its use.

Methods: We conducted a population-based cohort study with interrupted time series analysis using data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics. We identified women with live births from 2002 to 2015, excluding those with nonlactation indications for domperidone (n = 247 349). Read More

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December 2018
2 Reads

Association of Oral Contraceptives With Drug-Induced QT Interval Prolongation in Healthy Nonmenopausal Women.

JAMA Cardiol 2018 Sep;3(9):877-882

Centres d'Investigation Clinique Paris-Est, Assistance Publique des Hôpitaux de Paris, Department of Pharmacology, Pitié-Salpêtrière Hospital, Paris, France.

Importance: Women are at higher risk of drug-induced torsade de pointes (TdP) than men. Androgens are protective. Influence of oral contraception on drug-induced TdP and QT prolongation is controversial. Read More

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September 2018
15 Reads

Fragmented endocardial signals and early afterdepolarizations during torsades de pointes tachycardia.

Cardiol J 2018 Jul 16. Epub 2018 Jul 16.

First Affiliated Hospital of Xi'an Jiaotong University; Pitié-Salpêtrière Hospital.

Background: Bradycardia-induced torsade de pointes (TdP) tachycardia in patients with spontaneous high-degree atrioventricular block (AVB) is common. The aim of this study was to analyze endocardial recordings during TdP in spontaneous high-degree AVB in humans to better understand the electrophysiological mechanisms underlying this phenomenon.

Methods: The study group consisted of 5 patients with typical episodes of TdP during spontaneous high-degree AVB. Read More

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July 2018
6 Reads

Virtual Thorough QT (TQT) Trial-Extrapolation of In Vitro Cardiac Safety Data to In Vivo Situation Using Multi-Scale Physiologically Based Ventricular Cell-wall Model Exemplified with Tolterodine and Fesoterodine.

AAPS J 2018 Jul 11;20(5):83. Epub 2018 Jul 11.

Simcyp Division, Certara UK Limited, Level 2-Acero, 1 Concourse Way, Sheffield, S1 2BJ, UK.

QT interval prolongation typically assessed with dedicated clinical trials called thorough QT/QTc (TQT) studies is used as surrogate to identify the proarrhythmic risk of drugs albeit with criticism in terms of cost-effectiveness in establishing the actual risk of torsade de pointes (TdP). Quantitative systems toxicology and safety (QSTS) models have potential to quantitatively translate the in vitro cardiac safety data to clinical level including simulation of TQT trials. Virtual TQT simulations have been exemplified with use of two related drugs tolterodine and fesoterodine. Read More

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July 2018
11 Reads

Analysis of torsadogenic and pharmacokinetic profile of E-4031 in dogs bridging the gap of information between in vitro proarrhythmia assay and clinical observation in human subjects.

J Pharmacol Sci 2018 Jun 18;137(2):237-240. Epub 2018 Jun 18.

Department of Pharmacology, Toho University Graduate School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540, Japan; Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540, Japan. Electronic address:

We analyzed torsadogenic and pharmacokinetic profile of E-4031 using chronic atrioventricular block dogs. E-4031 in intravenous doses of 0.03, 0. Read More

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CiPA challenges and opportunities from a non-clinical, clinical and regulatory perspectives. An overview of the safety pharmacology scientific discussion.

J Pharmacol Toxicol Methods 2018 Sep - Oct;93:15-25. Epub 2018 Jun 27.

UCB-Biopharma SPRL, Non-Clinical Development, 1420 Braine L'Alleud, Belgium.

The Safety Pharmacology Society organized a scientific session at its annual conference in 2017 to discuss the challenges and opportunities of the Comprehensive In-Vitro Proarrhythmia Assay (CiPA) paradigm. Our intention was to raise awareness of this initiative with its members and also to gauge the extent to which safety pharmacologists have incorporated the CiPA testing strategy within the pharmaceutical industry. CiPA offers many potential opportunities including 1) a focus on proarrhythmic risk (as opposed to QTc prolongation), 2) providing scientific rationale to support the continued development of compounds that may have a poor selectivity over hERG whilst also blocking other inward currents and 3) reducing the extent of ECG monitoring in clinical trials with a greater influence of the non-clinical studies. Read More

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June 2018
13 Reads

Electrical storm in an infant with short-coupled variant of torsade de pointes.

J Arrhythm 2018 Jun 14;34(3):315-318. Epub 2018 May 14.

Department of Cardiovascular and Respiratory Medicine Shiga University of Medical Science Otsu Shiga Japan.

A 10-month-old infant experienced cardiac arrest caused by ventricular fibrillation (VF). His electrocardiogram (ECG) at rest was within the normal range. Amiodarone was indispensable due to its refractoriness to defibrillation. Read More

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June 2018
5 Reads

Significance of prolonged QTc in acute exacerbations of COPD requiring hospitalization.

Int J Chron Obstruct Pulmon Dis 2018 14;13:1937-1947. Epub 2018 Jun 14.

Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium.

Background: A prolonged QT interval is associated with increased risk of Torsade de Pointes and cardiovascular death. The prevalence and clinical relevance of QT prolongation in acute exacerbations of COPD (AECOPD), with high risk for cardiac morbidity and mortality, is currently unclear.

Methods: A dual cross-sectional study strategy was therefore designed. Read More

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June 2018
11 Reads

Acute Appendicitis as an Unexpected Cause of Inverted Takotsubo Cardiomyopathy.

J Emerg Trauma Shock 2018 Apr-Jun;11(2):143-145

Department of Emergency, Hautepierre Hospital, University Hospital of Strasbourg, Strasbourg, France.

Takotsubo cardiomyopathy (TTC), also known as transient left ventricular ballooning syndrome, is a stress-induced-cardiomyopathy. It is precipitated by emotional or physical stress and is characterized by normal coronary arteries and transient regional wall motion abnormalities. Variants of TTC include apical ballooning syndrome and, less commonly, mid, basal, and local variants. Read More

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June 2018
8 Reads

Sudden cardiac death in young athletes with long QT syndrome: the role of genetic testing and cardiovascular screening.

Br Med Bull 2018 Sep;127(1):43-53

Department of Musculoskeletal Disorders, University of Salerno School of Medicine and Surgery, Salerno, Italy.

Introduction: Sudden cardiac death (SCD) of young athletes during competition or training is a tragic event. The long QT syndrome (LQTS) is an arrythmogenic disorder characterized by prolonged ventricular repolarization leading to torsade de pointes evident at electrocardiogram (ECG). Implantable cardioverter defibrillator is an option to revert ventricular fibrillation to sinus rhythm, although the implantation may result in denial of sports participations to the athlete. Read More

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September 2018
13 Reads

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

J Crit Care 2018 Aug;46:151-156

Department of Cardiology, Rambam Medical Center, Haifa, Israel; Ruth & Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Israel. Electronic address:

Purpose: We aimed to investigate the factors that modulate the extent of QTc prolongation and potential arrhythmogenic consequences during mild therapeutic hypothermia (MTH).

Methods: We 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. Read More

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August 2018
1 Read

[Severe cardiac arrhythmias].

Rev Med Liege 2018 May;73(5-6):251-256

Service de Cardiologie, CHU Sart Tilman, Liège, Belgique.

Cardiac arrhythmias are a common cause of admission in the emergency department. Among these, atrio-ventricular conductive disorders and malignant ventricular arrhythmias are among the most severe, requiring prompt and appropriate management to ensure the best prognosis. Knowledge of the pathophysiology and etiology causing these arrhythmias is mandatory in order to understand its management, acute and chronic, and to facilitate the dialogue between emergency physicians and cardiologists. Read More

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May 2018
4 Reads

Afterdepolarizations and triggered activity as a mechanism for clinical arrhythmias.

Authors:
Andrew L Wit

Pacing Clin Electrophysiol 2018 Jun 19. Epub 2018 Jun 19.

Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York City, NY, USA.

Afterdepolarizations cause triggered arrhythmias. One kind occurs after repolarization is complete, delayed afterdepolarizations (DADs). Another occurs as an interruption in repolarization, early afterdepolarizations (EADs). Read More

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June 2018
1 Read

Sex, drugs, and heart failure: a sex-sensitive review of the evidence base behind current heart failure clinical guidelines.

ESC Heart Fail 2018 10 19;5(5):745-754. Epub 2018 Jun 19.

Beaulieu-Saucier Université de Montréal Pharmacogenomics Centre, Montreal, Quebec, Canada.

Heart failure (HF) is a complex disease, almost as common in women as in men. Nonetheless, HF clinical presentation, prognosis, and aetiology vary by sex. This review summarizes the current state of sex-sensitive issues related to HF drugs included in treatment guidelines and suggests future directions for improved care. Read More

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October 2018
9 Reads

Malignant Ventricular Arrhythmias Resulting From Drug-Induced QTc Prolongation: A Retrospective Study.

J Clin Med Res 2018 Jul 4;10(7):593-600. Epub 2018 Jun 4.

Mid-German Heart Center, Department of Internal Medicine III, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Halle, Martin-Luther-University Halle, D-06120 Halle, Germany.

Background: Several drug classes (antiarrhythmics, antimicrobials, antidepressants, phenothiazines, opiates, prokinetics of digestive tract, etc.) have been related to ventricular hyperkinetic arrhythmias such as torsade de pointes (TdP). TdPs are usually heralded by an abnormal prolongation of heart rate-corrected QT interval on the electrocardiogram, so-called drug-induced long heart rate-corrected QT (diLQTc). Read More

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July 2018
1 Read

Predictive Analytics for Identification of Patients at Risk for QT Interval Prolongation: A Systematic Review.

Pharmacotherapy 2018 Aug 18;38(8):813-821. Epub 2018 Jul 18.

Department of Pharmacy Practice, College of Pharmacy, Purdue University, Indianapolis, Indiana.

Prolongation of the heart rate-corrected QT (QTc) interval increases the risk for torsade de pointes (TdP), a potentially fatal arrhythmia. The likelihood of TdP is higher in patients with risk factors that include female sex, older age, heart failure with reduced ejection fraction, hypokalemia, hypomagnesemia, concomitant administration of two or more QTc interval-prolonging medications, among others. Assessment and quantification of risk factors may facilitate prediction of patients at highest risk for developing QTc interval prolongation and TdP. Read More

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August 2018
29 Reads

Anticancer drugs-related QTc prolongation, torsade de pointes and sudden death: current evidence and future research perspectives.

Oncotarget 2018 May 22;9(39):25738-25749. Epub 2018 May 22.

Department of Cardiology, An Zhen Hospital, Capital Medical University, Beijing, P.R. China.

Anticancer drugs may have proarrhythmic effects including drug-induced QT interval prolongation, which is of particular importance because it can lead to a fatal polymorphic ventricular tachycardia termed torsade de pointes (TdP). QT interval prolongation and TdP are rare life-threatening untoward effects of anticancer therapy, particularly with arsenic trioxides and anthracyclines, and even some novel molecular targeted drugs touted as 'tumor specific'. Several factors that affect myocardial repolarization can further increase the risk of TdP. Read More

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May 2018
10 Reads

Cardiovascular Safety of Psychiatric Agents: A Cautionary Tale.

Angiology 2018 Jan 1:3319718780145. Epub 2018 Jan 1.

3 Third Department of Cardiology, Athens University School of Medicine, Athens, Greece.

Psychiatric agents are among the most commonly prescribed medications. Despite the advent of newer generation agents, patients receiving them still experience cardiovascular (CV) side effects. However, these agents may have heterogeneous properties, calling for an individualized approach based on efficacy and also on the particular side effect profile of each specific agent. Read More

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January 2018
6 Reads

Electrocardiogram Changes of Donepezil Administration in Elderly Patients with Ischemic Heart Disease.

Cardiol Res Pract 2018 23;2018:9141320. Epub 2018 Apr 23.

Department of Pharmacology and Therapeutics, Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.

Objective: Donepezil, a widely used cholinesterase inhibitor for treating Alzheimer's disease, has been reported to induce bradyarrhythmias and torsade de pointes. In this study, we aimed at determining electrocardiogram changes of donepezil administration in elderly patients with ischemic heart disease, who tend to suffer from cognitive disorders.

Methods: Sixty patients with ischemic heart disease and mild cognitive impairment were treated with donepezil (5 mg/day) and followed up for at least four weeks. Read More

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April 2018
4 Reads

Twisting and Turning to Find an Explanation for Torsades de Pointes.

JACC Clin Electrophysiol 2017 Dec 6;3(13):1577-1579. Epub 2017 Nov 6.

Division of Cardiology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada. Electronic address:

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December 2017
3 Reads

Short-Lasting Episodes of Torsade de Pointes in the Chronic Atrioventricular Block Dog Model Have a Focal Mechanism, While Longer-Lasting Episodes Are Maintained by Re-Entry.

JACC Clin Electrophysiol 2017 Dec 18;3(13):1565-1576. Epub 2017 Dec 18.

Department of Physics and Astronomy, Ghent University, Ghent, Belgium.

Objectives: This study investigated the arrhythmogenic mechanisms responsible for torsade de pointes (TdP) in the chronic atrioventricular block dog model, known for its high susceptibility for TdP.

Background: The mechanism of TdP arrhythmias has been under debate for many years. Focal activity as well as re-entry have both been mentioned in the initiation and the perpetuation of TdP. Read More

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December 2017
10 Reads

Paradoxical Effects of Sodium-Calcium Exchanger Inhibition on Torsade de Pointes and Early Afterdepolarization in a Heart Failure Rabbit Model.

J Cardiovasc Pharmacol 2018 Aug;72(2):97-105

Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan.

Calcium homeostasis plays an important role in development of early afterdepolarizations (EADs) and torsade de pointes (TdP). The role of sodium-calcium exchanger (NCX) inhibition in genesis of secondary Ca rise and EAD-TdP is still debated. Dual voltage and intracellular Ca optical mapping were conducted in 6 control and 9 failing rabbit hearts. Read More

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August 2018
3 Reads

Increased long QT and torsade de pointes reporting on tamoxifen compared with aromatase inhibitors.

Heart 2018 Nov 2;104(22):1859-1863. Epub 2018 May 2.

AP-HP, Pitié-Salpêtrière Hospital Department of Pharmacology CIC-1421 Pharmacovigilance Unit INSERM UMR ICAN 1166 Sorbonne Université UPMC, Univ Paris 06, Institute of CArdiometabolism and Nutrition (ICAN), Paris, France.

Objective: A prolonged QTc (LQT) is a surrogate for the risk of torsade de pointes (TdP). QTc interval duration is influenced by sex hormones: oestradiol prolongs and testosterone shortens QTc. Drugs used in the treatment of breast cancer have divergent effects on hormonal status. Read More

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November 2018
10 Reads

Evaluation of the risk factors for ventricular arrhythmias secondary to QT prolongation induced by papaverine injection during coronary flow reserve studies using a 4 Fr angio-catheter.

Heart Vessels 2018 Nov 30;33(11):1358-1364. Epub 2018 Apr 30.

Department of Disease Control and Homeostasis, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan.

Estimation of the fractional flow reserve (FFR) is considered to be an established method by which to assess stable coronary artery stenosis. Induction of maximal coronary hyperemia is important during the FFR procedure. Papaverine has been reported to increase the risk of ventricular arrhythmia (VA). Read More

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November 2018
5 Reads

[Cardiovascular adverse effects of antimuscarinics used in the treatment of overactive bladder in the elderly : A review].

Prog Urol 2018 Jun 16;28(7):361-369. Epub 2018 Apr 16.

GRAPPPA groupe de recherche appliquée à la pathologie pelvi-périnéale des personnes âgées, 75020 ParisFrance.

Aim: The aim of this study was to review the evidence regarding the cardiovascular effects of urinary anticholinergic drugs in the elderly.

Methods: A literature review was conducted in October 2017 using the Medline/Pubmed database limiting the search to works in English or French.

Results: In total, 602 articles between March 1964 and October 2017 have been reported, 60 studies were analyzed, 19 were prospective trials. Read More

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June 2018
1 Read

Drug-induced Proarrhythmia and Torsade de Pointes: A Primer for Students and Practitioners of Medicine and Pharmacy.

J Clin Pharmacol 2018 Apr 19. Epub 2018 Apr 19.

Therapeutic Products Directorate, Health Canada, Ottawa, Ontario, Canada.

Multiple marketing withdrawals due to proarrhythmic concerns occurred in the United States, Canada, and the United Kingdom in the late 1980s to early 2000s. This primer reviews the clinical implications of a drug's identified proarrhythmic liability, the issues associated with these safety-related withdrawals, and the actions taken by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and by regulatory agencies in terms of changing drug development practices and introducing new nonclinical and clinical tests to asses proarrhythmic liability. ICH Guidelines S7B and E14 were released in 2005. Read More

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April 2018
5 Reads

Torsade de pointes and systemic azole antifungal agents: Analysis of global spontaneous safety reports.

Glob Cardiol Sci Pract 2017 Jun 30;2017(2):11. Epub 2017 Jun 30.

Department of Clinical Pharmacology and Toxicology, University & University Hospital Basel, Switzerland.

Literature about torsade de pointes induced by azole antifungal agents is scarce, despite the well-known association. Furthermore, little is known about the latency time between commencing an azole antifungal agent and developing torsade de pointes. The objectives of the present study were therefore to identify all cases of torsade de pointes associated with systemic azole antifungal use reported to the WHO monitoring centre (Uppsala, Sweden) and to determine the latency times between commencing the azole and developing torsade de pointes. Read More

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Molecular determinants of Kv7.1/KCNE1 channel inhibition by amitriptyline.

Biochem Pharmacol 2018 Jun 3;152:264-271. Epub 2018 Apr 3.

Centro Universitario de Investigaciones Biomédicas de la Universidad de Colima, Colima, Col., Mexico. Electronic address:

Amitriptyline (AMIT) is a compound widely prescribed for psychiatric and non-psychiatric conditions including depression, migraine, chronic pain, and anorexia. However, AMIT has been associated with risks of cardiac arrhythmia and sudden death since it can induce prolongation of the QT interval on the surface electrocardiogram and torsade de pointes ventricular arrhythmia. These complications have been attributed to the inhibition of the rapid delayed rectifier potassium current (I). Read More

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June 2018
3 Reads