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    1 OF 85

    Drug-induced Fatal Arrhythmias: Acquired long QT and Brugada Syndromes.
    Pharmacol Ther 2017 May 17. Epub 2017 May 17.
    Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan. Electronic address:
    Since the early 1990s, the concept of primary "inherited" arrhythmia syndromes or ion channelopathies has evolved rapidly as a result of revolutionary progresses made in molecular genetics. Alterations in genes coding for membrane proteins such as ion channels or their associated proteins responsible for the generation of cardiac action potentials (AP) have been shown to cause specific malfunctions which eventually lead to cardiac arrhythmias. These arrhythmic disorders include congenital long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, short QT syndrome, progressive cardiac conduction disease, etc. Read More

    Torsade de pointes arrhythmias arise at the site of maximal heterogeneity of repolarization in the chronic complete atrioventricular block dog.
    Europace 2017 May;19(5):858-865
    Department of Medical Physiology, University Medical Center Utrecht, Yalelaan 50, Utrecht 3584 CM, The Netherlands.
    Aims: The chronic complete atrioventricular block (CAVB) dog is highly sensitive for drug-induced torsade de pointes (TdP) arrhythmias. Focal mechanisms have been suggested as trigger for TdP onset; however, its exact mechanism remains unclear. In this study, detailed mapping of the ventricles was performed to assess intraventricular heterogeneity of repolarization in relation to the initiation of TdP. Read More

    Synergistic Effect of Dofetilide and Mexiletine on Prevention of Atrial Fibrillation.
    J Am Heart Assoc 2017 May 18;6(5). Epub 2017 May 18.
    Department of Cardiology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China
    Background: Although atrial fibrillation (AF) is the most common abnormal heart rhythm and its prevalence continues to rise, there is a marked paucity of effective and safe antiarrhythmic drugs for AF. This study was done to test whether combined use of dofetilide and mexiletine exhibits not only a synergistic effect on AF suppression but also a safer profile in drug-induced ventricular proarrhythmias.

    Methods And Results: The effects of dofetilide plus mexiletine on atrial effective refractory period (ERP), AF inducibility, QT, and QT-related ventricular arrhythmias were studied using the isolated arterially perfused rabbit atrial and ventricular wedge preparations. Read More

    A multiscale computational modelling approach predicts mechanisms of female sex risk in the setting of arousal-induced arrhythmias.
    J Physiol 2017 May 18. Epub 2017 May 18.
    Department of Pharmacology, School of Medicine, University of California, Davis.
    Female sex is a risk factor for inherited and acquired Long-QT associated Torsade de Pointes (TdP) arrhythmias, and sympathetic discharge is a major factor in triggering TdP in female Long-QT syndrome patients. We used a combined experimental and computational approach to predict 'the perfect storm' of hormone concentration, IKr block, and sympathetic stimulation that induces arrhythmia in females with inherited and acquired Long-QT. More specifically, we developed mathematical models of acquired and inherited Long-QT syndrome in male and female ventricular human myocytes by combining effects of a hormone and a hERG blocker dofetilide or hERG mutations. Read More

    Thorough QT (TQT) studies: concordance with torsadogenesis and an evolving cardiac safety testing paradigm.
    Drug Discov Today 2017 May 13. Epub 2017 May 13.
    Pharmacoepidemiology and Pharmacoeconomics Unit, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, Str., 30-688 Krakow, Poland; Simcyp (part of Certara), Sheffield S2 4SU, UK.
    Since 2005, when the International Conference on Harmonisation (ICH) E14 guideline was adopted, no drug has been withdrawn because of QTc prolongation or torsade de pointes arrhythmia. There are, however, costs associated with this success. In addition to the time and money invested, thorough QT (TQT) studies have limited the efficiency of the drug development pipeline. Read More

    Amiodarone-Induced Third Degree Atrioventricular Block and Extreme QT Prolongation Generating Torsade Des Pointes in Paroxysmal Atrial Fibrillation.
    J Atr Fibrillation 2016 Oct-Nov;9(3):1502. Epub 2016 Oct 31.
    Department of Health Sciences's Investigation. Sanatorio Metropolitano. Fernando de la Mora. Paraguay. Cardiology Department, Clinic Hospital, Asunción National University, San Lorenzo, Paraguay.
    Amiodarone is still the most potent antiarrhythmic drug in the prevention of life threatening ventricular arrhythmias and demonstrates a very low incidence of torsade de pointes. An unusual case of an 81-year-old woman who developed serious abnormalities of the conduction system of the heart and torsade des pointes during intravenous infusion of amiodarone for the treatment of paroxysmal atrial fibrillation is described. To the best of our knowledge, this is the first case showing an association of intravenous amiodarone-induced third degree atrioventricular block and extreme QT interval prolongation generating torsade des pointes in a patient with paroxysmal atrial fibrillation who required an implantable cardioverter-defibrillator. Read More

    Studies on curative efficacy of monoterpene eugenol on anti- leukemic drug arsenic trioxide induced cardiotoxicity.
    Biomed Pharmacother 2017 May 7;91:559-566. Epub 2017 May 7.
    Physiology Research Laboratory, School of Biosciences, Mahatma Gandhi University, Kerala 686 560, India. Electronic address:
    Background: Arsenic trioxide (As2O3) is emerging as a frontline agent for the treatment of acute promyelocytic leukemia (APL) but the therapeutic application is limited by its toxicity. QT prolongation, torsades de pointes and sudden cardiac death have been implicated in the As2O3 therapy. So eugenol is a monoterpene compound is well known for its antioxidant properties and protective effect on the cardiovascular system. Read More

    Systemic inflammation as a novel QT-prolonging risk factor in patients with torsades de pointes.
    Heart 2017 May 10. Epub 2017 May 10.
    Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy.
    Objective: Increasing evidence indicates systemic inflammation as a new potential cause of acquired long QT syndrome (LQTS), via cytokine-mediated changes in cardiomyocyte ion channels. Torsade de pointes (TdP) is a life-threatening polymorphic ventricular tachycardia occurring in patients with LQTS, usually when multiple QT-prolonging factors are simultaneously present. Since classical risk factors cannot fully explain TdP events in a number of patients, we hypothesised that systemic inflammation may represent a currently overlooked risk factor contributing to TdP development in the general population. Read More

    Domperidone for Lactation: What Health Care Providers Need to Know.
    Obstet Gynecol 2017 May 5. Epub 2017 May 5.
    Office of New Drugs, the Office of Drug Evaluation III, the Division of Bone, Reproductive, and Urologic Products, the Office of Surveillance and Epidemiology, the Office of Pharmacovigilance and Epidemiology, and the Division of Pharmacovigilance II, U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Silver Spring, Maryland.
    This commentary serves to raise health care provider awareness about the regulatory status and available evidence regarding domperidone for insufficient lactation. Breastfeeding provides significant health benefits for mothers and infants, and insufficient milk production remains the most common reason for early weaning. Domperidone, a dopamine receptor antagonist that may increase milk production, is not approved for any human use in the United States. Read More

    Risk of QT prolongation and torsade de pointes associated with exposure to hydroxyzine: re-evaluation of an established drug.
    Pharmacol Res Perspect 2017 Jun 21;5(3):e00309. Epub 2017 Apr 21.
    UCB PharmaBrusselsBelgium.
    Several noncardiac drugs have been linked to cardiac safety concerns, highlighting the importance of post-marketing surveillance and continued evaluation of the benefit-risk of long-established drugs. Here, we examine the risk of QT prolongation and/or torsade de pointes (TdP) associated with the use of hydroxyzine, a first generation sedating antihistamine. We have used a combined methodological approach to re-evaluate the cardiac safety profile of hydroxyzine, including: (1) a full review of the sponsor pharmacovigilance safety database to examine real-world data on the risk of QT prolongation and/or TdP associated with hydroxyzine use and (2) nonclinical electrophysiological studies to examine concentration-dependent effects of hydroxyzine on a range of human cardiac ion channels. Read More

    Citalopram Discontinuation More Harmful Than Gradual Dosage Reduction?
    Am J Psychiatry 2017 May;174(5):485
    From Friesland Mental Health Care Service, Department of Education and Research, Leeuwarden, the Netherlands; the Department of Geriatric Medicine, Medical Center Leeuwarden, Leeuwarden, the Netherlands; and the Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

    Influence of Oral Progesterone Administration on Drug-Induced QT Interval Lengthening: A Randomized, Double-Blind, Placebo-Controlled Crossover Study.
    JACC Clin Electrophysiol 2016 Dec;2(7):765-774
    Krannert Institute of Cardiology, Department of Medicine, School of Medicine, Indiana University, Indianapolis, Indiana.
    Objectives: We tested the hypothesis that oral progesterone administration attenuates drug-induced QT interval lengthening.

    Background: Evidence from preclinical and human investigations suggests that higher serum progesterone concentrations may be protective against drug-induced QT interval lengthening.

    Methods: In this prospective, double-blind, crossover study, 19 healthy female volunteers (21-40 years) were randomized to receive progesterone 400 mg or matching placebo orally once daily for 7 days timed to the menses phase of the menstrual cycle (between-phase washout period = 49 days). Read More

    Cryo-EM Structure of the Open Human Ether-à-go-go-Related K(+) Channel hERG.
    Cell 2017 Apr;169(3):422-430.e10
    Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University and Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA. Electronic address:
    The human ether-à-go-go-related potassium channel (hERG, Kv11.1) is a voltage-dependent channel known for its role in repolarizing the cardiac action potential. hERG alteration by mutation or pharmacological inhibition produces Long QT syndrome and the lethal cardiac arrhythmia torsade de pointes. Read More

    Cardiac voltage-gated ion channels in safety pharmacology: Review of the landscape leading to the CiPA initiative.
    J Pharmacol Toxicol Methods 2017 Apr 11. Epub 2017 Apr 11.
    CiToxLAB North America, 445, Armand-Frappier Boul, Laval H7V 4B3, QC, Canada. Electronic address:
    Voltage gated ion channels are central in defining the fundamental properties of the ventricular cardiac action potential (AP), and are also involved in the development of drug-induced arrhythmias. Many drugs can inhibit cardiac ion currents, including the Na(+) current (INa), L-type Ca(2+) current (Ica-L), and K(+) currents (Ito, IK1, IKs, and IKr), and thereby affect AP properties in a manner that can trigger or sustain cardiac arrhythmias. Since publication of ICH E14 and S7B over a decade ago, there has been a focus on drug effects on QT prolongation clinically, and on the rapidly activating delayed rectifier current (IKr), nonclinically, for evaluation of proarrhythmic risk. Read More

    Recurrent Ventricular Tachycardia Due to Long QT Syndrome.
    J Assoc Physicians India 2016 Dec;64(12):80-81
    Lecturer, Department of Medicine, MLB Medical College, Jhansi, Uttar Pradesh.
    Long QT syndrome (LQTS) is a rare inherited heart condition in which delayed repolarization of the heart following a heartbeat, increases the risk of episodes of Torsades de pointes (TdP, a form of irregular heartbeat that originates from the ventricles). These episodes may lead to palpitations, fainting, and sudden death due to ventricular fibrillation. Episodes may be provoked by various stimuli, depending on the subtype of the condition. Read More

    Short-term variability of repolarization is superior to other repolarization parameters in the evaluation of diverse antiarrhythmic interventions in the chronic AV block dog.
    J Cardiovasc Pharmacol 2017 Mar 31. Epub 2017 Mar 31.
    Department of Medical Physiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
    Short-term variability (STV), to quantify beat-to-beat variability of repolarization (BVR), is a surrogate parameter that reliably identifies proarrhythmic risk in preclinical models. Examples include not only the use in the chronic atrioventricular block (CAVB) dog model whereby it was developed, but also in vulnerable patients with heart failure or drug-induced long QT syndrome. In the CAVB dog model, STV can specifically distinguish between safe and unsafe drugs in proarrhythmic screening. Read More

    Clinical and molecular findings in a Moroccan family with Jervell and Lange-Nielsen syndrome: a case report.
    J Med Case Rep 2017 Apr 2;11(1):88. Epub 2017 Apr 2.
    Département de Génétique Médicale, Institut National d'Hygiène, Rabat, Morocco.
    Background: Jervell and Lange-Nielsen syndrome (Online Mendelian Inheritance in Man 220400) is a rare autosomal recessive cardioauditory ion channel disorder that affects 1/200,000 to 1/1,000,000 children. It is characterized by congenital profound bilateral sensorineural hearing loss, a long QT interval, ventricular tachyarrhythmias, and episodes of torsade de pointes on an electrocardiogram. Cardiac symptoms arise mostly in early childhood and consist of syncopal episodes during periods of stress, exercise, or fright and are associated with a high risk of sudden cardiac death. Read More

    Recent developments in the science of proarrhythmic cardiac safety of new drugs.
    Eur Heart J Cardiovasc Pharmacother 2017 Apr;3(2):118-124
    Cardiac Safety Services, Global Head, Cardiac Safety Center of Excellence, QuintilesIMS, 602 Western Express Highway, Andheri East, Mumbai 400 069, Maharashtra, India.
    Following marketing withdrawals of several drugs due to proarrhythmic safety concerns, the ICH Guidelines S7B and E14 were released in 2005 and have guided pre-approval cardiac safety assessments in multiple regulatory jurisdictions. While this S7B-E14 paradigm has successfully prevented drugs with unanticipated potential for inducing Torsades de Pointes entering the market, it has unintentionally resulted in the termination of development programs for potentially important compounds that could have exhibited a favourable benefit-risk balance. The Comprehensive In vitro Proarrhythmia Assay paradigm is currently attracting considerable attention as a solution to this problem. Read More

    Cases of drug-induced Torsade de Pointes: a review of Belgian cases in the EudraVigilance database.
    Acta Clin Belg 2017 Mar 24:1-6. Epub 2017 Mar 24.
    a Department of Pharmaceutical and Pharmacological Sciences , KU Leuven - University of Leuven , Leuven , Belgium.
    Objectives: Post-marketing surveillance is very important, especially for rare adverse drug reactions like QTc-prolongation and Torsade de Pointes (TdP). The objective of this study was to investigate the characteristics of Belgian cases of drug-related TdP reported in the EudraVigilance database.

    Methods: The EudraVigilance database was searched for Belgian post-marketing cases of TdP reported between December 2001-April 2015. Read More

    Development of a risk score for QTc-prolongation: the RISQ-PATH study.
    Int J Clin Pharm 2017 Apr 9;39(2):424-432. Epub 2017 Mar 9.
    Department of Pharmaceutical and Pharmacological Sciences, Clinical Pharmacology and Pharmacotherapy, KU Leuven, Herestraat 49, Box 521, 3000, Leuven, Belgium.
    Background More than 170 drugs are linked with QTc-prolongation, which in extreme cases can lead to Torsade de Pointes. Monitoring of this potential side effect is an important challenge in clinical practice. Objective To investigate the risk of QTc-prolongation in hospital patients who started a QTc-prolonging drug, and to develop a risk score to identify patients at high/low risk for QTc-prolongation. Read More

    Adverse Drug Event Causality Analysis (ADECA): A Process for Evaluating Evidence and Assigning Drugs to Risk Categories for Sudden Death.
    Drug Saf 2017 Jun;40(6):465-474
    University of Arizona, College of Nursing, 1305 N. Martin Ave, Tucson, AZ, 85721, USA.
    Growing evidence indicates that many drugs have the ability to cause a potentially lethal cardiac arrhythmia, torsades de pointes (TdP). This necessitates the development of a compilation of drugs that have this potential toxicity. Such a list is helpful in identifying the etiology of TdP in patients taking multiple drugs and assists decision making by those caring for patients at high risk of TdP. Read More

    Hypokalemia in women and methadone therapy are the strongest non-cardiologic factors associated with QT prolongation in an emergency department setting.
    J Electrocardiol 2017 Feb 10. Epub 2017 Feb 10.
    Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
    Background: Our primary objective was to determine the adjusted quantitative associations of clinical predictors with QT prolongation, a defining cause of Torsades de Pointes (TdP).

    Methods: A retrospective cohort study was performed on consecutive emergency department patients identified by ECG acquisition date, and heart rate corrected QT (QTc) and QRS durations. QTc was modeled as a function of clinical predictors with multiple linear regression. Read More

    Results of a curtailed randomized controlled trial, evaluating the efficacy and safety of azimilide in patients with implantable cardioverter-defibrillators: The SHIELD-2 trial.
    Am Heart J 2017 Mar 15;185:43-51. Epub 2016 Nov 15.
    Lankenau Medical Center and Lankenau Institute for Medical Research, Wynnewood, PA; Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA. Electronic address:
    Background: Frequent hospital attendances in patients with implantable cardioverter-defibrillators (ICDs) result in significant morbidity and health care costs. Current drugs to reduce ICD shocks and hospital visits have limited efficacy and considerable toxicity. We evaluated the efficacy and safety of azimilide, a novel oral class III antiarrhythmic, for use in ICD patients. Read More

    Practice variation in the re-initiation of dofetilide: An observational study.
    Int J Cardiol 2017 Jun 12;236:221-225. Epub 2017 Feb 12.
    Division of Cardiovascular Diseases, Cardiovascular Research Institute, University of Kansas Hospital & Medical Center, Kansas City, KS, United States. Electronic address:
    Background: Dofetilide is a class III antiarrhythmic drug that has been reported to be safe and efficacious in the treatment of atrial dysrhythmias with a known initial risk of QT prolongation and torsades de pointes (TdP). As a result, the Federal Drug Administration (FDA) mandated in-hospital dofetilide initiation and adherence to a common dosing protocol. However, there is a lack of clarity on how to manage dofetilide re-initiation. Read More

    Acquired prolongation of QT interval as a risk factor for torsade de pointes ventricular tachycardia: a narrative review for the anesthesiologist and intensivist.
    J Anesth 2017 Jun 22;31(3):413-423. Epub 2017 Feb 22.
    Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, Novi Sad, 21000, Serbia.
    More than 70% of intensive care unit (ICU) patients experience heart rhythm disturbances, and these patients have correspondingly higher mortality rates. Consequently, one of the standards of care in ICUs is continuous electrocardiography monitoring. One of the potentially preventable dysrhythmic events is the occurrence of torsade de pointes ventricular tachycardia in the setting of acquired prolonged QT interval. Read More

    Pharmacologic Conversion during Dofetilide Treatment for Persistent Atrial Fibrillation.
    Pacing Clin Electrophysiol 2017 Feb 21. Epub 2017 Feb 21.
    Heart Research Follow-up Program, University of Rochester School of Medicine & Dentistry, Rochester, New York.
    Background: Dofetilide is a pure IKr blocker and is one of the few drugs specifically studied and approved in the United States for the management of persistent atrial fibrillation (AF). Dofetilide has been noted to have a high rate of pharmacologic conversion during initial dosing in prior smaller studies. The intent of the study was to examine the safety of an inpatient loading strategy, and the incidence and patterns of pharmacologic conversion by dofetilide during the treatment of persistent AF in a large consecutive cohort. Read More

    Interaction among hERG channel blockers is a potential mechanism of death in caffeine overdose.
    Eur J Pharmacol 2017 Apr 16;800:23-33. Epub 2017 Feb 16.
    Chinese Herb Medicine Division, The Nurturing Station for the State Key Laboratory of Subtropical Silviculture, Zhejiang Agriculture and Forestry University, 88 North Circle Road, Lin'an 311300, PR China. Electronic address:
    Caffeine overdose death is due to cardiac arrest, but its mechanism has not been explored in detail. In this study, our data showed that caffeine significantly prolonged the heart rate-corrected QT interval (QTc) of rabbits in vivo (P<0.05; n=7). Read More

    Common Genetic Variant Risk Score Is Associated With Drug-Induced QT Prolongation and Torsade de Pointes Risk: A Pilot Study.
    Circulation 2017 Apr 17;135(14):1300-1310. Epub 2017 Feb 17.
    From Office of Clinical Pharmacology, Center for Drug Evaluation and Research (D.G.S., J.V., L.J.) and Office of Science and Engineering Laboratories, Center for Devices and Radiological Health (D.G.S., J.V., L.J., K.B.), US Food and Drug Administration, Silver Spring, MD; BSICoS Group, Aragón Institute for Engineering Research (I3A), IIS Aragón, University of Zaragoza, Spain (J.V.); Department of Clinical Physiology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden (L.J.); Division of Cardiology, University of Utah, Salt Lake City (J.W.M.); Spaulding Clinical Research, West Bend, WI (J.W.M.); Departments of Medicine (P.W., D.R.), Pharmacology (D.R.), and Biomedical Informatics (D.R.), Vanderbilt University Medical Center, Nashville, TN; Department of Cardiology, Copenhagen University Hospital, Gentofte, Denmark (P.W.); Cardiology Clinical Academic Group, St. George's University of London, London, UK (E.R.B.); AZCERT, Inc, Oro Valley, AZ (R.W.); Center for Genomic Medicine and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA (G.K., M.A.R., C.N.-C.); Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge (G.K., M.A.R., C.N.-C.); and Division of Cardiac Electrophysiology, Veterans Administration Hospital System of Boston, Harvard Medical School, West Roxbury, MA (M.A.R.).
    Background: Drug-induced QT interval prolongation, a risk factor for life-threatening ventricular arrhythmias, is a potential side effect of many marketed and withdrawn medications. The contribution of common genetic variants previously associated with baseline QT interval to drug-induced QT prolongation and arrhythmias is not known.

    Methods: We tested the hypothesis that a weighted combination of common genetic variants contributing to QT interval at baseline, identified through genome-wide association studies, can predict individual response to multiple QT-prolonging drugs. Read More

    Electrophysiological measurements that can explain and guide temporary accelerated pacing to avert (re)occurrence of torsade de pointes arrhythmias in the canine chronic atrioventricular block model.
    Heart Rhythm 2017 May 14;14(5):749-756. Epub 2017 Feb 14.
    Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address:
    Background: Pacing at higher rates is known to suppress torsade de pointes (TdP) arrhythmias. Nevertheless, exact application and mechanism need further clarification. In the anesthetized canine chronic atrioventricular block model, ventricular remodeling is responsible for a high and reproducible incidence of TdP upon a challenge with dofetilide. Read More

    Improving the In Silico Assessment of Proarrhythmia Risk by Combining hERG (Human Ether-à-go-go-Related Gene) Channel-Drug Binding Kinetics and Multichannel Pharmacology.
    Circ Arrhythm Electrophysiol 2017 Feb;10(2):e004628
    From the Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD.
    Background: The current proarrhythmia safety testing paradigm, although highly efficient in preventing new torsadogenic drugs from entering the market, has important limitations that can restrict the development and use of valuable new therapeutics. The CiPA (Comprehensive in vitro Proarrhythmia Assay) proposes to overcome these limitations by evaluating drug effects on multiple cardiac ion channels in vitro and using these data in a predictive in silico model of the adult human ventricular myocyte. A set of drugs with known clinical torsade de pointes risk was selected to develop and calibrate the in silico model. Read More

    Study of factors affecting the progression and termination of drug induced Torsade de pointes in two dimensional cardiac tissue.
    J Electrocardiol 2017 May - Jun;50(3):332-341. Epub 2017 Feb 2.
    Biomedical Engineering Group, Department of Applied Mechanics, Indian Institute of Technology Madras, Chennai, India. Electronic address:
    Introduction: To study the conditions leading to the initiation and termination of drug induced Torsade de pointes (TdP) along with QT prolongation.

    Methods: A 2D anisotropic transmural section of the ventricular myocardium is modeled using the TP06 equations and the cells are interconnected with gap junction conductances (GJC). The tissue is remodeled by reducing the repolarization reserve (by increasing calcium current (ICaL)) of all cells thus making them vulnerable to development of early after depolarizations (EADs). Read More

    MicroRNA-135a regulates sodium-calcium exchanger gene expression and cardiac electrical activity.
    Heart Rhythm 2017 May 8;14(5):739-748. Epub 2017 Feb 8.
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada; Department of Medicine, Montreal Heart Institute and Université de Montréal, Montreal, Canada; Institute of Pharmacology, West German Heart and Vascular Center, Faculty of Medicine, University Duisburg-Essen, Essen, Germany. Electronic address:
    Background: Complete atrioventricular block (CAVB) causes arrhythmogenic remodeling and increases the risk of torsades de pointes arrhythmias. MicroRNAs (miRNAs) are key regulators of gene expression that contribute to cardiac remodeling.

    Objective: The purpose of this study was to assess miRNA changes after CAVB and identify novel candidates potentially involved in arrhythmogenic cardiac remodeling. Read More

    Methadone and Corrected QT Prolongation in Pain and Palliative Care Patients: A Case-Control Study.
    J Palliat Med 2017 Feb 10. Epub 2017 Feb 10.
    1 Department of Pharmacy Practice, Wegmans School of Pharmacy, St. John Fisher College , Rochester, New York.
    Background: Methadone (ME) is commonly used in pain and palliative care (PPC) patients with refractory pain or intolerable opioid adverse effects (AEs). A unique ME AE is its corrected QT (QTc) interval prolongation risk, but most evidence exists in methadone maintenance therapy patients.

    Objective: Our goal was to identify QTc interval prolongation risk factors in PPC patients receiving ME and other medications known to prolong the QTc interval and develop a risk stratification tool. Read More

    Severe Proarrhythmic Potential of the Antiemetic Agents Ondansetron and Domperidone.
    Cardiovasc Toxicol 2017 Feb 9. Epub 2017 Feb 9.
    Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
    The potential of ondansetron and domperidone, both clinically established antiemetic agents, to increase the QT-interval has been described in several case reports. Therefore, the aim of the present study was to investigate whether these drugs may provoke polymorphic ventricular tachycardia in a sensitive experimental model of drug-induced proarrhythmia. In 10 female rabbits, ondansetron (1, 5 and 10 µM, n = 10) or domperidone (0. Read More

    CSAHi study: Detection of drug-induced ion channel/receptor responses, QT prolongation, and arrhythmia using multi-electrode arrays in combination with human induced pluripotent stem cell-derived cardiomyocytes.
    J Pharmacol Toxicol Methods 2017 Feb 2. Epub 2017 Feb 2.
    Non-Clinical Evaluation Expert Committee, Drug Evaluation Committee, Japan Pharmaceutical Manufacturers Association (JPMA), 2-3-11 Nihonbashi-Honcho, Chuo-ku, Tokyo 103-0023, Japan; Consortium for Safety Assessment using Human iPS Cells (CSAHi), Japan(1); Biopharmaceutical Assessment Core Function Unit, Medicine Development Center, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan.
    Introduction: The use of multi-electrode arrays (MEA) in combination with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provides a promising method to predict comprehensive cardiotoxicity, including drug-induced QT prolongation and arrhythmia. We previously demonstrated that MEA in combination with hiPSC-CMs could provide a generalizable platform by using 7 reference drugs at 10 testing facilities. Using this approach, we evaluated responses to reference drugs that modulate a range of cardiac ion currents and have a range of arrhythmogenic effects. Read More

    Delayed Normalization of Electrocardiograms in Patients with Takotsubo Cardiomyopathy due to Aneurysmal Subarachnoid Hemorrhage.
    World Neurosurg 2017 Apr 27;100:467-473. Epub 2017 Jan 27.
    Department of Cardiology, Miyazaki Medical Association Hospital, Shinbeppu-cho, Miyazaki, Japan.
    Background: Takotsubo cardiomyopathy (TCM) is caused by excessive physical and mental stress, and sometimes causes potentially fatal arrhythmias such as torsades de pointes. This study characterized the features of TCM due to aneurysmal subarachnoid hemorrhage, particularly the delayed normalization of electrocardiograms compared with that of transthoracic echocardiograms.

    Methods: Ten patients with TCM were selected from the 450 patients with subarachnoid hemorrhage treated in our hospital between January 2007 and November 2015. Read More

    An 18-Year-Old Woman Who Was Found Down.
    Am J Cardiol 2017 Apr 6;119(7):1124-1125. Epub 2017 Jan 6.
    Section of Cardiology, Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana. Electronic address:
    An 18-year-old woman was found unresponsive by her mother. After the patient spontaneously regained consciousness, an electrocardiogram showed a markedly prolonged QT interval thought to be due to congenital long QT1. An implantable cardioverter defibrillator was placed. Read More

    Recurrent takotsubo with prolonged QT and torsade de pointes and left ventricular thrombus.
    J Saudi Heart Assoc 2017 Jan 6;29(1):44-52. Epub 2016 Aug 6.
    Department of Cardiovascular Disease, International Medical Center, Jeddah, Saudi Arabia.
    Takotsubo cardiomyopathy, also known as "takotsubo syndrome," refers to transient apical ballooning syndrome, stress cardiomyopathy, or broken heart syndrome and is a recently recognized syndrome typically characterized by transient and reversible left ventricular dysfunction that develops in the setting of acute severe emotional or physical stress. Increased catecholamine levels have been proposed to play a central role in the pathogenesis of the disease, although the specific pathophysiology of this condition remains to be fully determined. At present, there have been very few reports of recurrent takotsubo cardiomyopathy. Read More

    Torsades de pointes with high-dose loperamide.
    J Electrocardiol 2017 May - Jun;50(3):355-357. Epub 2017 Jan 16.
    Department of Internal Medicine, Vanderbilt University Medical Center, 1161 21st Avenue South, D-3100 Medical Center North, Nashville, TN.
    Case: A 41year-old male presented with torsades de pointes. The patient was taking over 100mg of loperamide per day to self-medicate for chronic pain. Coronary angiography, cardiac magnetic resonance imaging, and genetic testing were negative for pre-disposing ischemia, cardiomyopathy, or genetic variant respectively. Read More

    The possible role of propofol in drug-induced torsades de pointes: A real-world single-center analysis.
    Int J Cardiol 2017 Apr 4;232:243-246. Epub 2017 Jan 4.
    Division of Cardiovascular Diseases, Mayo Clinic, Scottsdale, AZ, United States.
    Background: Torsades de pointes (TdP) is a polymorphic ventricular tachycardia associated with QT prolongation. Propofol is a sedative-anesthetic with proarrhythmic effects on cardiac myocytes. We performed a retrospective study to determine the incidence of TdP following propofol exposure at Mayo Clinic (Rochester, MN) from 08/11/1998-11/20/2015. Read More

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