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    1 OF 88

    Torsades de Pointes in patients with polymyalgia rheumatica.
    Curr Pharm Des 2018 Jan 10. Epub 2018 Jan 10.
    Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena. Italy.
    Polymyalgia rheumatica (PMR) represents the most common inflammatory rheumatic disease of the elderly. It is characterized by synovitis of proximal joints and extra-articular synovial structures, along with chronic high-grade systemic inflammation. PMR is closely related to giant cell arteritis (GCA), a large-vessel vasculitis that involves the major branches of the aorta, particularly the extracranial branches of carotid artery including temporal arteries. Read More

    Estradiol up-regulates L-type Ca2+ channels via membrane-bound estrogen receptor / Phosphoinositide-3kinase / Akt / cAMP response element-binding protein signaling pathway.
    Heart Rhythm 2018 Jan 9. Epub 2018 Jan 9.
    Department of Medicine, Heart and Vascular Institute, University of Pittsburgh, PA, 15261. USA. Electronic address:
    Background: In long QT type-2 (LQT2), women are more prone to lethal arrhythmias called Torsade de Pointes (TdP) than men. We previously reported that 17-β-estradiol (E2) upregulates L-type Ca2+-channels and current (ICa,L) (∼30%) in rabbit ventricular myocytes by a classical genomic-mechanism mediated by estrogen-receptor-α (ER)α. In LQT2 ( IKr-blockade or bradycardia), the higher Ca2+ influx via ICa,L, causes Ca2+-overload, spontaneous sarcoplasmic reticulum Ca2+-release, and re-activation of ICa,L that trigger early afterdepolarizations (EADs) and TdP. Read More

    Effect of a single dose of i.v. ondansetron on QTc interval in emergency department patients.
    Am J Health Syst Pharm 2018 Jan 9. Epub 2018 Jan 9.
    Departments of Pharmacy and Emergency Medicine, University of California San Francisco Medical Center, San Francisco, CA, and University of California San Francisco School of Pharmacy, San Francisco, CA.
    Purpose: Results of a study to determine whether i.v. administration of a single dose of 4 mg of ondansetron was associated with QT interval prolongation in emergency department (ED) patients are reported. Read More

    Global Optimization of Ventricular Myocyte Model to Multi-Variable Objective Improves Predictions of Drug-Induced Torsades de Pointes.
    Front Physiol 2017 19;8:1059. Epub 2017 Dec 19.
    Greenberg Division of Cardiology, Department of Medicine, Weill Cornell Medicine, New York, NY, United States.
    In silico cardiac myocyte models present powerful tools for drug safety testing and for predicting phenotypical consequences of ion channel mutations, but their accuracy is sometimes limited. For example, several models describing human ventricular electrophysiology perform poorly when simulating effects of long QT mutations. Model optimization represents one way of obtaining models with stronger predictive power. Read More

    Approach to initiating QT-prolonging oncology drugs in the ambulatory setting.
    J Oncol Pharm Pract 2018 Jan 1:1078155217748735. Epub 2018 Jan 1.
    Provincial Pharmacy, Systemic Therapy Program, BC Cancer Agency, Vancouver, BC, Canada.
    Since the introduction of regulatory drug approval guidance on the evaluation of QT interval prolongation, an increasing number of drug monographs has included cautions on the risk of QT prolongation. For example, QT prolongation is mentioned in the Canadian product monographs of 29 drugs commonly seen in oncology practice. This presents two major challenges. Read More

    Development of models for predicting Torsade de Pointes cardiac arrhythmias using perceptron neural networks.
    BMC Bioinformatics 2017 Dec 28;18(Suppl 14):497. Epub 2017 Dec 28.
    Division of Systems Biology, FDA's National Center for Toxicological Research, Jefferson, AR, 72079, USA.
    Background: Blockage of some ion channels and in particular, the hERG (human Ether-a'-go-go-Related Gene) cardiac potassium channel delays cardiac repolarization and can induce arrhythmia. In some cases it leads to a potentially life-threatening arrhythmia known as Torsade de Pointes (TdP). Therefore recognizing drugs with TdP risk is essential. Read More

    Impact of Pharmacist Intervention on Electrocardiogram Monitoring of Pediatric Patients on Multiple QTc Interval-Prolonging Medications.
    J Pediatr Pharmacol Ther 2017 Nov-Dec;22(6):399-405
    Bloomberg Children's Center (LMH), Johns Hopkins Hospital, Baltimore, Maryland, Nemours/Alfred I. duPont Hospital for Children (JDT, EH), Wilmington, Delaware.
    Objectives: To determine whether dedicated pharmacy services improve the rate of electrocardiogram (ECG) monitoring in patients at risk for medication-induced QTc interval prolongation. In addition, determine how pediatric institutions currently monitor patients at risk for medication-induced QTc interval prolongation.

    Methods: A pharmacist-driven monitoring protocol to detect medication-induced QTc interval prolongation was developed using published literature. Read More

    Safety limits of antidepressant use plus combinations: focus on cardiovascular function.
    Curr Drug Metab 2017 Dec 27. Epub 2017 Dec 27.
    Laboratorio de Neurociencias LIM27, Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP. Brazil.
    Background: Antidepressants have been widely prescribed for depression, anxiety, sleep disorders, and in the management of behavioural symptoms of adult-old patients. Although generally safe, newer generation antidepressants are not devoid of the risk of inducing clinically relevant adverse events.

    Objectives: To investigate the association between newer generation antidepressants and the occurrence of cardiovascular adverse events and electrocardiogram (ECG) abnormalities. Read More

    QT Prolongation, Torsades de Pointes, and Psychotropic Medications: A 5-Year Update.
    Psychosomatics 2017 Nov 3. Epub 2017 Nov 3.
    Harvard Medical School, Boston, MA.
    Background: Some psychotropic medications have been associated with prolongation of the QT interval and QT prolongation, especially in those with medical illness, and are linked to lethal ventricular arrhythmias, such as Torsades de Pointes (TdP). In 2013, we published a review of QT prolongation, TdP, and psychotropic medications.

    Objective: We provide an update over the past 5 years on the specific concerns most relevant to clinicians who see medically ill patients. Read More

    Molecular determinants of loperamide and N-desmethyl loperamide binding in the hERG cardiac K+ channel.
    Bioorg Med Chem Lett 2017 Dec 15. Epub 2017 Dec 15.
    Preclinical Safety, Sanofi US, 55 Corporate Blvd, Bridgewater, NJ 08807, USA.
    Abuse of the common anti-diarrheal loperamide is associated with QT interval prolongation as well as development of the potentially fatal arrhythmia torsades de pointes. The mechanism underlying this cardiotoxicity is high affinity inhibition of the human ether-a-go-go-related gene (hERG) cardiac K+ channel. N-Desmethyl loperamide is the major metabolite of loperamide and is a close structural relative of the parent molecule. Read More

    Necessity to evaluate PI3K/Akt signalling pathway in proarrhythmia.
    Open Heart 2017 10;4(2):e000596. Epub 2017 Dec 10.
    Department of Medical Biochemistry, Federal University Ndufu-Alike, Ikwo, Ebonyi State, Nigeria.
    The incidence of QT prolongation and torsades de pointes is on the rise due to the use of cardiovascular and non-cardiovascular drugs. Robust efforts have been made and are still ongoing to understand the underlying mechanisms that can enhance or prevent the development of drug-induced proarrhythmia. A caveat in the use of antiarrhythmic drugs is the ability to obtain safe action potential prolongation therapeutic effects, through IKr blockade. Read More

    Torsades de Pointes after Ondansetron Infusion in 2 Patients.
    Tex Heart Inst J 2017 Oct 1;44(5):366-369. Epub 2017 Oct 1.
    Drugs that prolong the electrocardiographic QT interval increase the risk of ventricular arrhythmias, particularly torsades de pointes. Ondansetron, a 5-hydroxytryptamine type 3 receptor antagonist antiemetic, is one such drug. We present the cases of 2 patients who were given intravenous ondansetron and subsequently developed torsades de pointes. Read More

    Refractory ventricular fibrillations after surgical repair of atrial septal defects in a patient with CACNA1C gene mutation - case report.
    J Cardiothorac Surg 2017 Dec 19;12(1):118. Epub 2017 Dec 19.
    Department of Cardiovascular Surgery, Ehime University, Shitsukawa, Toon, Ehime, 7910295, Japan.
    Background: Congenital long QT syndrome (LQTS) can cause ventricular arrhythmic events with syncope and sudden death resulting from malignant torsades de pointes (TdP) followed by ventricular fibrillations (VFs). However, the syndrome is often overlooked prior to the development of arrhythmic events in patients with congenital heart diseases demonstrating right bundle branch block on electrocardiogram (ECG). We present a case of an adult patient with congenital heart disease who developed VFs postoperatively, potentially due to his mutation in a LQTS related gene, which was not identified on preoperative assessment due to incomplete evaluation of his family history. Read More

    Ten-year experience in atenolol use and exercise evaluation in children with genetically proven long QT syndrome.
    J Arrhythm 2017 Dec 12;33(6):624-629. Epub 2017 Oct 12.
    Department of Cardiology, Royal Children's Hospital, Melbourne, Australia.
    Background: Due to its availability, atenolol is the primary beta-blocker used in Australia for children with long QT syndrome. There is limited data on long-term follow-up of its use.

    Methods: A single-tertiary-center, retrospective, observational study investigating all children and adolescents who had genetically proven long QT syndrome type 1 (LQT1) and type 2 (LQT2) was conducted. Read More

    QTc prolongation and torsades de pointes due to a coadministration of fluoxetine and amiodarone in a patient with implantable cardioverter-defibrillator: Case report and review of the literature.
    Medicine (Baltimore) 2017 Dec;96(49):e9071
    aDepartment of Pharmacy, Tongji HospitalbDepartment of Endocrinology, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, WuhancDepartment of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
    Rationale: Drug-induced prolongation of the corrected QT interval (QTc) may lead to serious and potentially life-threatening ventricular tachyarrhythmia, such as torsades de pointes (Tdp), which is worthy of clinical attention. Here, we report 1 case of Tdp after a coadministration of fluoxetine and amiodarone.

    Patient Concerns: A 62-year-old Chinese male who placed with the implanted cardioverter-defibrillator (ICD) appeared the QTc prolongation and Tdp after the concurrent administration of fluoxetine and amiodarone. Read More

    Corrigendum: Optimization of an In silico Cardiac Cell Model for Proarrhythmia Risk Assessment.
    Front Physiol 2017 6;8:1025. Epub 2017 Dec 6.
    Division of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, United States.
    [This corrects the article on p. 616 in vol. 8, PMID: 28878692. Read More

    Quantitative Understanding of QTc Prolongation and Gender as Risk Factors for Torsade de Pointes.
    Clin Pharmacol Ther 2018 Feb 8;103(2):304-309. Epub 2017 Dec 8.
    Division of Pharmacometrics, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
    Several risk factors for development of a potentially fatal ventricular arrhythmia, torsade de pointes, have been observed, including female gender. However, in most investigations, only few torsade events were included and/or rarely were postdose heart rate corrected QT (QTc) measurements included, as a surrogate of drug exposure. We developed a multivariate logistic regression model using data from 22,214 patients (33% women) with 84 torsade events (56% women) to evaluate the relationship between risk factors for torsade using data from four anti-arrhythmic drug development programs. Read More

    Incidence, Diagnosis, and Management of QT Prolongation Induced by Cancer Therapies: A Systematic Review.
    J Am Heart Assoc 2017 Dec 7;6(12). Epub 2017 Dec 7.
    Division of Cardiology, Peter Munk Cardiac Centre, Ted Rogers Program in Cardiotoxicity Prevention and Department of Medical Imaging, University Health Network University of Toronto, Toronto, Ontario, Canada
    Background: The cardiovascular complications of cancer therapeutics are the focus of the burgeoning field of cardio-oncology. A common challenge in this field is the impact of cancer drugs on cardiac repolarization (ie, QT prolongation) and the potential risk for the life-threatening arrhythmia torsades de pointes. Although QT prolongation is not a perfect marker of arrhythmia risk, this has become a primary safety metric among oncologists. Read More

    Uncertainty Quantification Reveals the Importance of Data Variability and Experimental Design Considerations for in Silico Proarrhythmia Risk Assessment.
    Front Physiol 2017 21;8:917. Epub 2017 Nov 21.
    Division of Applied Regulatory Science, Center for Drug Evaluation and Research, Office of Translational Sciences, Office of Clinical Pharmacology, Food and Drug Administration, Silver Spring, MD, United States.
    The Comprehensive in vitro Proarrhythmia Assay (CiPA) is a global initiative intended to improve drug proarrhythmia risk assessment using a new paradigm of mechanistic assays. Under the CiPA paradigm, the relative risk of drug-induced Torsade de Pointes (TdP) is assessed using an in silico model of the human ventricular action potential (AP) that integrates in vitro pharmacology data from multiple ion channels. Thus, modeling predictions of cardiac risk liability will depend critically on the variability in pharmacology data, and uncertainty quantification (UQ) must comprise an essential component of the in silico assay. Read More

    In Vitro and In Silico Risk Assessment in Acquired Long QT Syndrome: The Devil Is in the Details.
    Front Physiol 2017 16;8:934. Epub 2017 Nov 16.
    Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia.
    Acquired long QT syndrome, mostly as a result of drug block of the Kv11. 1 potassium channel in the heart, is characterized by delayed cardiac myocyte repolarization, prolongation of the T interval on the ECG, syncope and sudden cardiac death due to the polymorphic ventricular arrhythmia Torsade de Pointes (TdP). In recent years, efforts are underway through the Comprehensive in vitro proarrhythmic assay (CiPA) initiative, to develop better tests for this drug induced arrhythmia based in part on in silico simulations of pharmacological disruption of repolarization. Read More

    Is myocardial repolarization duration associated with repolarization heterogeneity?
    Ann Noninvasive Electrocardiol 2017 Dec 2. Epub 2017 Dec 2.
    General Electric Healthcare, Milwaukee, WI, USA.
    Background: Dispersion of repolarization is theorized as one mechanism by which myocardial repolarization prolongation causes lethal torsades de pointes, (TdP). Our primary purpose was to determine whether prolongation of myocardial repolarization as measured by the heart rate-corrected J-to-T peak interval (JTpkc), is associated with repolarization heterogeneity as measured by transmural dispersion, defined as the median duration from the peak to the end of the T wave (TpTe).

    Methods: A retrospective cohort study was performed at a single urban tertiary ED from July 2011-September 2012. Read More

    Late-onset severe long QT syndrome.
    Ann Noninvasive Electrocardiol 2017 Nov 30. Epub 2017 Nov 30.
    University Clinic of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
    We report a case of torsades de pointes arrhythmia as the first manifestation of congenital Long QT syndrome in a 77-year-old man with family history of sudden unexplained death. This case illustrates the importance of vigilant clinical assessment and genetic counseling in families with sudden death in order to identify properly asymptomatic relatives at risk for cardiac events. It also demonstrates that Long QT syndrome can still manifest with potentially fatal arrhythmias late in life in previously asymptomatic elderly patients. Read More

    A case report: Is mexiletine usage effective in the shortening of QTC interval and improving the T-wave alternans in Timothy syndrome?
    Ann Noninvasive Electrocardiol 2017 Nov 30. Epub 2017 Nov 30.
    Department of Pediatric Cardiology, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Education and Research Hospital, Istanbul Saglik Bilimleri University, Istanbul, Turkey.
    Timothy syndrome (TS) is a multisystemic disease that occurs because of a mutation in CACN1C gene and is characterized by prolonged QT interval. Mexiletine is a Class 1B antiarrhythmic drug that causes the disappearance of T-wave alternans by shortening QTc and peak-to-end of the T wave. It may block the development of torsades de pointes in a prolonged QT. Read More

    Sevoflurane causes greater QTc interval prolongation in chronically hyperglycemic patients than in normoglycemic patients.
    PLoS One 2017 1;12(12):e0188555. Epub 2017 Dec 1.
    Department of Anesthesiology, Kindai University Faculty of Medicine, OsakaSayama, Osaka, Japan.
    QTc interval prolongation is a serious diabetic complication and increases mortality rate. Hyperglycemia inhibits the rapid component of delayed rectifier potassium channel currents (Ikr) and prolongs the QTc interval on electrocardiograms. Sevoflurane also inhibits the Ikr and causes QTc interval prolongation. Read More

    Torsades de Pointes associated with QT prolongation after catheter ablation of paroxysmal atrial fibrillation.
    Indian Pacing Electrophysiol J 2017 Sep - Oct;17(5):146-149. Epub 2017 Jul 13.
    Cardiology Division, Gachon University Gil Medical Center, Incheon, Republic of Korea.
    A 79-year-old woman who underwent catheter ablation for paroxysmal atrial fibrillation presented with Torsades de Pointes (TdP). Aggravation of prolonged QT interval which is most likely due to neural modulation by catheter ablation, played major role in the initiation of TdP. The patient was successfully treated with isoproterenol during acute stage and discharged after stabilization without implantation of permanent pacemaker or implantable cardioverter defibrillator. Read More

    Frequency, characteristics and risk factors of QT interval prolonging drugs and drug-drug interactions in cancer patients: a multicenter study.
    BMC Pharmacol Toxicol 2017 Dec 1;18(1):75. Epub 2017 Dec 1.
    Department of Pharmacy, University of Peshawar, Peshawar, Khyber Pakhtunkhwa, Pakistan.
    Background: Cancer patients may receive a high number of medications with the potential to prolong QT interval and subsequent TdP (torsades de pointes). This study aimed to identify the prevalence of QT prolonging drugs, their TdP risk, QT prolonging drug-drug interactions (QT-DDIs), levels, predictors, and TdP risk of drugs involved in QT-DDIs.

    Methods: This multicenter study included cancer patients from three major tertiary care hospitals of Khyber-Pakhtunkhwa, Pakistan. Read More

    Hypoglycemia and Sudden Death During Treatment With Methadone for Opiate Detoxification.
    Am J Ther 2017 Nov 14. Epub 2017 Nov 14.
    Hofstra Northwell School of Medicine, Hempstead, NY.
    Clinical Features: We present a case of a middle-aged man admitted to an inpatient detoxification facility for withdrawal of intranasal heroin, alprazolam, and ethanol. The patient was placed on methadone and chlordiazepoxide tapers. Ondansetron and trazodone were prescribed as needed for symptom control. Read More

    Novel Two-Step Classifier for Torsades de Pointes Risk Stratification from Direct Features.
    Front Pharmacol 2017 14;8:816. Epub 2017 Nov 14.
    IBM T. J. Watson Research Center, Yorktown Heights, NY, United States.
    While pre-clinical Torsades de Pointes (TdP) risk classifiers had initially been based on drug-induced block of hERG potassium channels, it is now well established that improved risk prediction can be achieved by considering block of non-hERG ion channels. The current multi-channel TdP classifiers can be categorized into two classes. First, the classifiers that take as input the values of drug-induced block of ion channels (direct features). Read More

    Can non-clinical repolarization assays predict the results of clinical thorough QT studies? Results from a research consortium.
    Br J Pharmacol 2017 Nov 27. Epub 2017 Nov 27.
    Non-Clinical Development, UCB-Biopharma SPRL, Braine-l'Alleud, Belgium.
    Background And Purpose: Translation of non-clinical markers of delayed ventricular repolarization to clinical prolongation of the QT interval corrected for heart rate (QTc) (a biomarker for torsades de pointes proarrhythmia) remains an issue in drug discovery and regulatory evaluations. We retrospectively analysed 150 drug applications in a US Food and Drug Administration database to determine the utility of established non-clinical in vitro IKr current human ether-à-go-go-related gene (hERG), action potential duration (APD) and in vivo (QTc) repolarization assays to detect and predict clinical QTc prolongation.

    Experimental Approach: The predictive performance of three non-clinical assays was compared with clinical thorough QT study outcomes based on free clinical plasma drug concentrations using sensitivity and specificity, receiver operating characteristic (ROC) curves, positive (PPVs) and negative predictive values (NPVs) and likelihood ratios (LRs). Read More

    Dysrhythmias with Loperamide Used for Opioid Withdrawal.
    J Am Board Fam Med 2017 Nov-Dec;30(6):832-834
    From the Penn State Health, State College, PA (NDV, CH, RER, MBS); Mount Nittany Physician Group, State College (AFC).
    The antidiarrheal loperamide has had a recent, drastic increase in off-label use as an alternative treatment for symptoms of opioid withdrawal. The concept of this is easily discovered on the Internet and social media, where there are multiple blogs and forums promoting loperamide use at doses of 70 to 200 mg per day. Unfortunately, the serious side effects are not well recognized. Read More

    Risk of Cardiac Events Associated With Antidepressant Therapy in Patients With Long QT Syndrome.
    Am J Cardiol 2018 Jan 13;121(2):182-187. Epub 2017 Nov 13.
    Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester Medical Center, Rochester, New York; Department of Pharmacology & Physiology, University of Rochester Medical Center, Rochester, New York. Electronic address:
    Patients with long QT syndrome (LQTS) are at a high risk of cardiac events. Many patients with LQTS are treated with antidepressant drugs (ADs). We investigated the LQTS genotype-specific risk of recurrent cardiac arrhythmic events (CAEs) associated with AD therapy. Read More

    Incidence of drug-induced torsades de pointes with intravenous amiodarone.
    Indian Heart J 2017 Nov - Dec;69(6):707-713. Epub 2017 Jun 3.
    Sri Jayadeva Institute Of Cardiovascular Sciences and Research, 9th Block Jayanagar, Bannerghatta Road, Bengaluru 560069, India.
    Aim: To define the incidence, presentation, and outcomes of drug-induced Torsades de Pointes (TdP) with intravenous (IV) amiodarone.

    Methods: From January 2014 to August 2016 a total of 268 patients received IV amiodarone, 142 for ventricular tachycardia, 104 for atrial flutter/fibrillation, and 22 for incessant atrial tachycardia. A uniform dosing of amiodarone to yield 1gm/day was used in all patients. Read More

    Risk factors for QTc interval prolongation.
    Eur J Clin Pharmacol 2018 Feb 22;74(2):183-191. Epub 2017 Nov 22.
    Pharmacy Foundation of Haarlem Hospitals, Boerhaavelaan 24, 2035 RC, Haarlem, The Netherlands.
    Purpose: Prolongation of the QTc interval may result in Torsade de Pointes, a ventricular arrhythmia. Numerous risk factors for QTc interval prolongation have been described, including the use of certain drugs. In clinical practice, there is much debate about the management of the risks involved. Read More

    Have the Findings from Clinical Risk Prediction and Trials Any Key Messages for Safety Pharmacology?
    Front Physiol 2017 6;8:890. Epub 2017 Nov 6.
    William Harvey Heart Centre, Barts and The London School of Medicine and Dentistry, London, United Kingdom.
    Anti-arrhythmic drugs are a mainstay in the management of symptoms related to arrhythmias, and are adjuncts in prevention and treatment of life-threatening ventricular arrhythmias. However, they also have the potential for pro-arrhythmia and thus the prediction of arrhythmia predisposition and drug response are critical issues. Clinical trials are the latter stages in the safety testing and efficacy process prior to market release, and as such serve as a critical safeguard. Read More

    An increasing electromechanical window is a predictive marker of ventricular fibrillation in anesthetized rabbit with ischemic heart.
    Exp Anim 2017 Nov 21. Epub 2017 Nov 21.
    QTest Labs, LLC.
    The QTc interval is widely used in Safety Pharmacological studies to predict arrhythmia risk, and the electromechanical window (EMW) and short-term variability of QT intervals (STVQT) have been studied as new biomarkers for drug-induced Torsades de Pointes (TdP). However, the use of EMW and STVQT to predict ventricular fibrillation (VF) has not been elucidated. This study aimed to evaluate EMW and STVQT to predict VF in anesthetized rabbit model of VF. Read More

    Gastroparesis: pharmacotherapy and cardiac risk.
    Scand J Gastroenterol 2017 Nov 20:1-6. Epub 2017 Nov 20.
    a Department of Medical Sciences, Faculty of Medicine , Uppsala University , Uppsala , Sweden.
    Background: Gastroparesis is characterized by abnormal gastric motility and delayed emptying with symptoms of early satiety, postprandial fullness, bloating, nausea, vomiting and abdominal pain. Pharmacological discovery has been lagging because potential drugs often are associated with abnormalities of electrical conduction of the myocardium due to interaction with cardiac ion channels leading to limited pharmaceutical options for development of new drugs.

    Objective: Addresses the safety of drugs for gastroparesis in terms of cardiotoxicity related to the clinical use of prokinetics and antiemetics. Read More

    Sudden cardiac arrest as a rare presentation of myxedema coma: case report.
    J Community Hosp Intern Med Perspect 2017 18;7(5):318-320. Epub 2017 Oct 18.
    Department of Pulmonary Medicine, Interfaith Medical Centre, Brooklyn, NY, USA.
    Myxedema coma is a decompensated hypothyroidism which occurs due to long-standing, undiagnosed, or untreated hypothyroidism. Untreated hypothyroidism is known to affect almost all organs including the heart. It is associated with a decrease in cardiac output, stroke volume due to decreased myocardial contractility, and an increase in systemic vascular resistance. Read More

    Beat-to-beat variations in activation-recovery interval derived from the right ventricular electrogram can monitor arrhythmic risk under anesthetic and awake conditions in the canine chronic atrioventricular block model.
    Heart Rhythm 2017 Nov 13. Epub 2017 Nov 13.
    Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address:
    Background: In the chronic atrioventricular block (CAVB) dog model, beat-to-beat variation of repolarization in the left ventricle (LV) quantified as short-term variability of the left monophasic action potential duration (STVLVMAPD) increases abruptly upon challenge with a proarrhythmic drug. This increase occurs before the first ectopic beat (EB), specifically in subjects who demonstrate subsequent repetitive torsades de pointes arrhythmias (TdP).

    Objective: The purpose of this study was to demonstrate that STV is feasible to monitor arrhythmic risk through use of the intracardiac electrogram (EGM) derived from the right ventricular (RV) lead from pacemakers or implantable cardioverter-defibrillators. Read More

    Ciprofloxacin does not Prolong the QTc Interval: A Clinical Study in ICU Patients and Review of the Literature.
    J Pharm Pharm Sci 2017 ;20(1):360-364
    Pharmacy Foundation of Haarlem Hospitals, Haarlem, the Netherlands. Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht, the Netherlands.
    Purpose: Ciprofloxacin may prolong the QT interval and increase the risk of Torsade de Pointes (TdP). Intravenous administration of ciprofloxacin in patients with additional risks may elevate the risk of QTc interval prolongation. We prospectively assessed whether intravenous ciprofloxacin prolongs the QT interval in patients with additional co-morbidities and risk factors. Read More

    In vivo Analysis of the Anti-atrial Fibrillatory, Proarrhythmic and Cardiodepressive Profiles of Dronedarone as a Guide for Safety Pharmacological Evaluation of Antiarrhythmic Drugs.
    Cardiovasc Toxicol 2017 Nov 14. Epub 2017 Nov 14.
    Department of Pharmacology, Toho University Graduate School of Medicine, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan.
    Anti-atrial fibrillatory, proarrhythmic and cardiodepressive profiles of dronedarone were analyzed using the halothane-anesthetized beagle dogs (n = 4) to create a standard protocol for clarifying both efficacy and adverse effects of anti-atrial fibrillatory drugs. Intravenous administration of dronedarone hydrochloride in doses of 0.3 and 3 mg/kg over 30 s attained the peak plasma concentrations of 61 and 1248 ng/mL, respectively, reflecting sub- to supra-therapeutic ones. Read More

    Microvolt T-wave alternans monitoring in a patient with levofloxacin-induced Torsade de Pointes.
    J Electrocardiol 2017 Sep 27. Epub 2017 Sep 27.
    Division of Cardiovascular Medicine, Gifu University Hospital, 1-1 Yanagido, Gifu, Japan.
    We present the case of a 62-year-old woman with levofloxacin-induced Torsade de Pointes, in whom microvolt T-wave alternans was measured during acute hospitalization and when QT interval was dynamically changing, illustrating a means for monitoring proarrhythmia. Read More

    The congenital long QT syndrome Type 3: An update.
    Indian Pacing Electrophysiol J 2017 Oct 31. Epub 2017 Oct 31.
    Program in Molecular and Integrative Physiological Sciences (MIPS), Department of Environmental Health, Harvard T.H. Chan School of Public Health, USA.
    Congenital long QT syndrome type 3 (LQT3) is the third in frequency compared to the 15 forms known currently of congenital long QT syndrome (LQTS). Cardiac events are less frequent in LQT3 when compared with LQT1 and LQT2, but more likely to be lethal; the likelihood of dying during a cardiac event is 20% in families with an LQT3 mutation and 4% with either an LQT1 or an LQT2 mutation. LQT3 is consequence of mutation of gene SCN5A which codes for the Nav1. Read More

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