4,547 results match your criteria Torsade de Pointes


Assessment of the risk of QT-interval prolongation associated with potential drug-drug interactions in patients admitted to Intensive Care Units.

Saudi Pharm J 2019 Feb 10;27(2):229-234. Epub 2018 Nov 10.

Department of Pharmacy, Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.

Objectives: To evaluate the relationship between drug interactions and QT-interval prolongation in patients admitted to a general intensive care unit (ICU).

Methods: This study was approved by the Institutional Review Board and written informed consent was obtained from all patients. From May 2015 to July 2016, all patients over 18 years-old admitted to the ICU for more than 24 h and in whom the QT-interval on the ECG could be read were prospectively included in this observational, cross-sectional study. Read More

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http://dx.doi.org/10.1016/j.jsps.2018.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362170PMC
February 2019

QT-prolonging agents with risk of torsades de pointes.

Australas Psychiatry 2019 02;27(1):92

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http://dx.doi.org/10.1177/1039856218794875DOI Listing
February 2019

Navigating the Minefield of QTc Interval-Prolonging Therapy in Nursing Facility Residents.

J Am Geriatr Soc 2019 Feb 12. Epub 2019 Feb 12.

College of Pharmacy, Purdue University, School of Medicine, Indiana University, Indianapolis, Indiana.

Background: The exponential increase in the number of medications associated with clinically important prolongation of the heart rate-corrected QT interval (QTc) places older adults at increased risk of arrhythmias including life-threatening torsade de pointes (TdP) and sudden death. Risk factors, other than age older than 65 years and female sex, include multiple concurrent drugs that prolong QTc and a variety of underlying predisposing conditions. Although electronic medical records and pharmacy dispensing systems can alert clinicians to the risk of QTc-prolonging therapy, more than 95% of safety alerts are overridden, and many systems have deactivated QTc drug interaction alerts. Read More

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http://doi.wiley.com/10.1111/jgs.15810
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http://dx.doi.org/10.1111/jgs.15810DOI Listing
February 2019
2 Reads

Rescue Sedation When Treating Acute Agitation in the Emergency Department With Intramuscular Antipsychotics.

J Emerg Med 2019 Feb 8. Epub 2019 Feb 8.

Department of Emergency Medicine, Hennepin County Medical Center, Minneapolis, Minnesota.

Background: Rapid treatment of agitation in the emergency department (ED) is critical to avoid injury to patients and providers. Treatment with intramuscular antipsychotics is often utilized, but there is a paucity of comparative effectiveness evidence available.

Objective: The purpose of this investigation was to compare the effectiveness of droperidol, olanzapine, and haloperidol for treating agitation in the ED. Read More

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http://dx.doi.org/10.1016/j.jemermed.2018.12.036DOI Listing
February 2019
1 Read

Effect of beta-blockade on quantitative microvolt T-wave alternans in 24-hour continuous 12-lead ECG recordings in patients with long QT syndrome.

Ann Noninvasive Electrocardiol 2019 Feb 6:e12640. Epub 2019 Feb 6.

Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Background: The aim of study was to investigate effects of beta-blockade on microvolt T-wave alternans (TWA), a precursor of lethal arrhythmia, in patients with long QT syndrome (LQTS).

Methods: Eleven consecutive LQTS patients, types 1 (n = 6), 3 (n = 2), and "non-1, non-2, non-3" (n = 3) were enrolled. All patients underwent 24-hr continuous 12-lead ECG monitoring before and after initiation of beta-blockade therapy. Read More

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http://dx.doi.org/10.1111/anec.12640DOI Listing
February 2019
1 Read

Funny Lumps, Flaming Pheo, and a Broken Heart: A Rare Case of Pheochromocytoma.

Cureus 2018 Nov 28;10(11):e3646. Epub 2018 Nov 28.

Radiology, Florida Hospital-Orlando, Orlando, USA.

Pheochromocytoma is the underlying etiology in 0.1% of hypertensive cases. However, it may be present in up to 5. Read More

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http://dx.doi.org/10.7759/cureus.3646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351109PMC
November 2018
2 Reads

Measurement of J-Tc along with QT-Interval Prolongation May Increase the Assay Sensitivity and Specificity for Predicting the Onset of Drug-Induced Torsade de Pointes: Experimental Evidences Based on Proarrhythmia Model Animals.

Cardiovasc Toxicol 2019 Feb 2. Epub 2019 Feb 2.

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

dl-Sotalol which can block both K channel and ß-adrenoceptor has been shown to prolong the J-Tc of electrocardiogram in beagle dogs but tended to shorten it in microminipigs, although the drug prolonged the QT interval in both animals under physiologically maintained experimental condition. In order to estimate how the changes in the J-Tc in the normal hearts would be reflected in the pathologic hearts, we compared proarrhythmic effects of dl-sotalol by using proarrhythmia models of beagle dogs and microminipigs, of which atrioventricular node had been ablated > 2 months and 8-9 weeks before, respectively (n = 4 for each species). dl-Sotalol in an oral dose of 10 mg/kg induced torsade de pointes in three out of four beagle dogs, which degenerated into ventricular fibrillation. Read More

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http://dx.doi.org/10.1007/s12012-019-09506-zDOI Listing
February 2019
2 Reads

Safety of Rapid-Switching from Amiodarone to Dofetilide in Atrial Fibrillation Patients with Implantable Cardioverter Defibrillators.

Heart Rhythm 2019 Jan 30. Epub 2019 Jan 30.

Kansas City Heart Rhythm Institute & Research Foundation, Overland Park, KS. Electronic address:

Background: Dofetilide is a commonly used class III anti-arrhythmic drug for atrial fibrillation. Drug guidelines mandates waiting for 3-month prior to initiating dofetilide after amiodarone use. It is not known if patients with implantable cardioverter defibrillator (ICD) can be rapidly switched from amiodarone to dofetilide. Read More

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http://dx.doi.org/10.1016/j.hrthm.2019.01.028DOI Listing
January 2019
4 Reads

Twenty-Four-Hour Measures of Heart Rate-Corrected QT Interval, Peak-to-End of the T-Wave, and Peak-to-End of the T-Wave/Corrected QT Interval Ratio During Antipsychotic Treatment.

J Clin Psychopharmacol 2019 Jan 30. Epub 2019 Jan 30.

Beasley Pharmaceutical and Biotechnology Consulting, LLC, Indianapolis, IN.

Purpose/background: Prolonged ventricular repolarization, measured by heart rate-corrected QT interval (QTc) prolongation, might be a biomarker for risk of torsade de pointes (TdP) and sudden cardiac death. However, the predictive value of QTc has been challenged, and a component of QTc, peak-to-end of the T-wave (Tpe), and a high Tpe/QT ratio might be superior biomarkers because they better reflect increased transmural dispersion of ventricular myocyte repolarization, which can lead to TDP. The purpose of this pilot study was to provide the first measurements of heart rate, QTc, Tpe, Tpe/QTc, and their variability over 24 hours in medication-free patients with schizophrenia, during treatment with ziprasidone or other antipsychotic drugs, and healthy controls. Read More

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http://dx.doi.org/10.1097/JCP.0000000000001003DOI Listing
January 2019
2 Reads

Cardiac toxicity of combined vemurafenib and cobimetinib administration
.

Int J Clin Pharmacol Ther 2019 Feb 1. Epub 2019 Feb 1.

Vemurafenib and cobimetinib are extremely effective in treating V600E-mutated metastatic melanoma, but their use is associated with toxic cardiac effects. Vemurafenib-induced prolonged QTc interval may be associated with ventricular fibrillation and sudden cardiac death. Cobimetinib-induced myocardial damage may lead to severely reduced heart function and lethal heart failure. Read More

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http://dx.doi.org/10.5414/CP203379DOI Listing
February 2019
1 Read

Cardiac arrhythmia considerations of hormone cancer therapies.

Cardiovasc Res 2019 Jan 30. Epub 2019 Jan 30.

Department of Medicine and Clinical Pharmacology, Cardio-Oncology Program, Vanderbilt University Medical Center, Nashville, TN, USA.

Breast and prostate cancers are among the most prevalent cancers worldwide. Estradiol and progesterone are major drivers for breast cancer proliferation, as well as androgens for prostate cancer. Endocrine therapies are drugs that interfere with hormone-activated pathways to slow cancer progression. Read More

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https://academic.oup.com/cardiovascres/advance-article/doi/1
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http://dx.doi.org/10.1093/cvr/cvz020DOI Listing
January 2019
6 Reads

Emergency department patients with a prolonged corrected QT interval do not have increased thirty-day mortality.

Acad Emerg Med 2019 Jan 29. Epub 2019 Jan 29.

Department of Emergency Medicine, Hennepin County Medical Center and the University of Minnesota, Minneapolis, MN.

Prolonged QT interval (long QTc) predisposes to torsades de pointes, which can present with seizures, syncope, and sudden death. (1) While one-third of emergency department (ED) patients may have a prolonged corrected QT (QTc) interval, (2) often discovered incidentally, clinical significance is uncertain. In hospitalized patients or long-term community studies, long QTc is associated with increased mortality. Read More

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http://dx.doi.org/10.1111/acem.13702DOI Listing
January 2019
1 Read

Amiodarone-induced life-threatening torsade de pointes in an end-stage lung cancer patient receiving gefitinib.

Oxf Med Case Reports 2019 Jan 24;2019(1):omy122. Epub 2019 Jan 24.

Department of Cardiovascular Medicine, First Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, China.

The risk factors of acquired long QT syndrome (aLQTS) are sometimes overlooked in clinics. Drugs, hypokalemia, age and female sex are well-known risk factors of QT prolongation-dependent torsade de pointes (TdP), which explains the high incidence of sudden cardiac death in LQT patients. Here, we report a case of an elderly female patient with lung cancer who was in poor condition, for whom amiodarone was mistakenly prescribed to rectify premature ventricular contractions. Read More

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http://dx.doi.org/10.1093/omcr/omy122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345081PMC
January 2019
1 Read

Evaluation of the effects on the QT-interval of 4 artemisinin-based combination therapies with a correction-free and heart rate-free method.

Sci Rep 2019 Jan 29;9(1):883. Epub 2019 Jan 29.

Cardiabase, 84 avenue du XXème Corps, 54000, Nancy, France.

Several antimalarial drugs are known to prolong ventricular repolarization as evidenced by QT/QTc interval prolongation. This can lead to Torsades de Pointes, a potentially lethal ventricular arrhythmia. Whether this is the case with artemisinin-based combination therapies (ACTs) remains uncertain. Read More

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http://dx.doi.org/10.1038/s41598-018-37113-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351684PMC
January 2019
1 Read
5.078 Impact Factor

Effects of Dihydroartemisinin-Piperaquine Phosphate and Artemether-Lumefantrine on QTc Interval Prolongation.

Sci Rep 2019 Jan 28;9(1):777. Epub 2019 Jan 28.

Sigma-tau Industrie Farmaceutiche Riunite S.p.A., Pomezia, (Rome), Italy.

QT/QTc interval prolongation reflects delayed cardiac repolarization which can lead to Torsade de Pointes and sudden death. Many antimalarial drugs prolong QT/QTc interval. However, due to confounding factors in patients with malaria, the precise extent of this effect has been found to be highly variable among studies. Read More

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http://dx.doi.org/10.1038/s41598-018-37112-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349839PMC
January 2019
2 Reads
5.078 Impact Factor

A current understanding of drug-induced QT prolongation and its implications for anticancer therapy.

Authors:
Dan M Roden

Cardiovasc Res 2019 Jan 23. Epub 2019 Jan 23.

Departments of Medicine, Pharmacology, and Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN.

The QT interval, a global index of ventricular repolarization, varies among individuals and is influenced by diverse physiologic and pathophysiologic stimuli such as gender, age, heart rate, electrolyte concentrations, concomitant cardiac disease, and other diseases such as diabetes. Many drugs produce a small but reproducible effect on QT interval but in rare instances this is exaggerated and marked QT prolongation can provoke the polymorphic ventricular tachycardia "torsades de pointes", which can cause syncope or sudden cardiac death. The generally accepted common mechanism whereby drugs prolong QT is block of a key repolarizing potassium current in heart, IKr, generated by expression of KCNH2, also known as HERG. Read More

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http://dx.doi.org/10.1093/cvr/cvz013DOI Listing
January 2019
2 Reads

Compounds commonly used in equine medicine inhibits the voltage-gated potassium channel K11.1.

Res Vet Sci 2019 Jan 8;123:239-246. Epub 2019 Jan 8.

Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.

Background: The voltage-gated K-channel K11.1 has a central role in cardiac repolarization. Blockage of K11. Read More

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http://dx.doi.org/10.1016/j.rvsc.2019.01.009DOI Listing
January 2019
4 Reads

Lesson of the month 1: Prolonged QT syndrome due to donepezil: a reversible cause of falls?

Clin Med (Lond) 2019 Jan;19(1):80-81

Airedale General Hospital, Keighley, UK.

Prolonged QT syndrome precipitates cardiac arrhythmias such as torsades de pointes (TdP) resulting in cardiogenic syncope or sudden death. We report a case of prolonged QT syndrome caused by donepezil which resulted in a fall and hip fracture. In this case female sex, advanced age and diuretic use may have increased the risk of recurrent syncope and potential underlying TdP. Read More

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http://dx.doi.org/10.7861/clinmedicine.19-1-80DOI Listing
January 2019
2 Reads

A literature-based algorithm for the assessment, management, and monitoring of drug-induced QTc prolongation in the psychiatric population.

Authors:
M Zolezzi L Cheung

Neuropsychiatr Dis Treat 2019 24;15:105-114. Epub 2018 Dec 24.

Pharmacy Department, Grey Nuns Community Hospital, Edmonton, AB, Canada.

Background: Certain psychotropics and a number of other medications used to treat medical conditions in psychiatric patients can increase the risk of prolonging the corrected QT (QTc) interval on the electrocardiogram, which puts patients at risk of life-threatening ventricular arrhythmias such as torsades de pointes. Pharmacists are often consulted about medications which are known to prolong the QTc interval. Although this information is often accessible, advising how to identify, assess, manage, and refer psychiatric patients at risk for drug-induced QTc prolongation is more challenging. Read More

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http://dx.doi.org/10.2147/NDT.S186474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309020PMC
December 2018
1 Read

Torsades de Pointes in Intravenous Drug Abuse-Associated Infective Endocarditis.

Heart Surg Forum 2018 Dec 19;21(6):E507-E512. Epub 2018 Dec 19.

Northeast Ohio Medical University, Rootstown, OH, USA.

Intravenous drug abuse rates in the United States have increased exponentially in recent years. Ohio is one of 5 states with the highest age-adjusted drug overdose death rates, with drug overdose causing 39.1 of every 100,000 deaths. Read More

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http://dx.doi.org/10.1532/hsf.2167DOI Listing
December 2018
3 Reads

Idiopathic short-coupled ventricular tachyarrhythmias: Systematic review and validation of electrocardiographic indices.

Egypt Heart J 2018 Dec 22;70(4):301-306. Epub 2018 Jun 22.

Prince Sultan Cardiac Centre, Military hospital, Riyadh, Saudi Arabia.

Introduction: Idiopathic short-coupled ventricular tachyarrhythmias make up a considerable proportion of ventricular tachyarrhythmias in structurally normal hearts and are the cause of 5-10% of unexpected sudden cardiac deaths. There is disparity in the literature regarding their description and a lack of formal diagnostic criteria to define them.

Objective: To validate ECG indices for the diagnosis of these ventricular tachyarrythmias and to subsequently unify their differing descriptions in the literature under a new terminology: . Read More

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http://dx.doi.org/10.1016/j.ehj.2018.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303349PMC
December 2018
2 Reads

Simultaneous Occurrence of Dysrhythmia and Seizure as a Diagnostic Difficulty; a Case Report.

Emerg (Tehran) 2018 8;6(1):e49. Epub 2018 Aug 8.

Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran.

Torsades de pointes (TdP) is a rare but hazardous ventricular dysrhythmia caused by an increase in the QT interval of the heart rhythm and is categorized into congenital or acquired types. Signs and symptoms of TdP include syncope, seizure, ventricular fibrillation, and even sudden death. According to statistics, among these symptoms, syncope and the seizure can be considered as signs that make the TdP diagnosis difficult. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289149PMC
August 2018
5 Reads

Isoproterenol suppresses recurrent torsades de pointes in a patient with long QT syndrome type 2.

HeartRhythm Case Rep 2018 Dec 5;4(12):576-579. Epub 2018 Sep 5.

Penn State Heart & Vascular Institute, Penn State Hershey Health, Hershey, Pennsylvania.

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https://linkinghub.elsevier.com/retrieve/pii/S22140271183024
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http://dx.doi.org/10.1016/j.hrcr.2018.08.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6301889PMC
December 2018
2 Reads

Recurrent Torsades with Refractory QT Prolongation in a 54-Year-Old Man.

Am J Case Rep 2018 Dec 20;19:1515-1518. Epub 2018 Dec 20.

Critical Care Services, Tripler Army Medical Center, Honolulu, HI, USA.

BACKGROUND QT prolongation is a common, easily overlooked clinical problem with potentially dire consequences. Drug-induced and congenital forms are not mutually exclusive, but are treated differently. Here, we present a case of cryptogenic underlying congenital long QT syndrome (cLQTS) successfully treated with isoproterenol, a drug contraindicated in most congenital forms of this condition. Read More

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https://www.amjcaserep.com/abstract/index/idArt/912326
Publisher Site
http://dx.doi.org/10.12659/AJCR.912326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322060PMC
December 2018
9 Reads

A Proof-of-Concept Evaluation of JTPc and Tp-Tec as Proarrhythmia Biomarkers in Preclinical Species: A Retrospective Analysis by an HESI-Sponsored Consortium.

Int J Toxicol 2018 Dec 19:1091581818813601. Epub 2018 Dec 19.

1 GREPAQ (Groupe de recherche en pharmacologie animale du Québec), Université de Montréal, St-Hyacinthe, Quebec, Canada.

Introduction:: Based on the ICH S7B and E14 guidance documents, QT interval (QTc) is used as the primary in vivo biomarker to assess the risk of drug-induced torsades de pointes (TdP). Clinical and nonclinical data suggest that drugs that prolong the corrected QTc with balanced multiple ion channel inhibition (most importantly the l-type calcium, Cav1.2, and persistent or late inward sodium current, Nav1. Read More

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http://journals.sagepub.com/doi/10.1177/1091581818813601
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http://dx.doi.org/10.1177/1091581818813601DOI Listing
December 2018
7 Reads

ISMP Adverse Drug Reactions: Lithium-Induced Cardiomyopathy Fixed Drug Eruption Due to Cetirizine, Levocetirizine, and Hydroxyzine Nivolumab-Induced Myasthenia Gravis Nivolumab-Induced Cholangitic Liver Disease Torsade de Pointes Caused by Psychiatric Polypharmacy Trichotillomania Associated With Aripiprazole.

Hosp Pharm 2018 Dec 27;53(6):371-375. Epub 2018 Aug 27.

Temple University School of Pharmacy, Philadelphia, PA, USA.

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. E-mail Dr. Read More

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http://dx.doi.org/10.1177/0018578718795225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6293386PMC
December 2018
2 Reads

Anesthetic Considerations for Pediatric Patients With Congenital Long QT Syndrome.

J Cardiothorac Vasc Anesth 2018 Nov 12. Epub 2018 Nov 12.

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Johns Hopkins All Children's Hospital, St. Petersburg, FL.

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http://dx.doi.org/10.1053/j.jvca.2018.11.005DOI Listing
November 2018
2 Reads

Identification of Patients At-Risk of QT Interval Prolongation during Medication Reviews: A Missed Opportunity?

J Clin Med 2018 Dec 10;7(12). Epub 2018 Dec 10.

Faculty of Health, University of Canberra, Bruce, ACT 2617, Australia.

The prolongation of the QT interval is a relatively rare but serious adverse drug reaction. It can lead to torsade de pointes, which is potentially life-threatening. The study's objectives were: determine the use of QT interval-prolonging drugs in an elderly community-dwelling population at risk of medication misadventure and identify recommendations regarding the risk of QT interval prolongation made by pharmacists when performing medication reviews. Read More

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http://dx.doi.org/10.3390/jcm7120533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306817PMC
December 2018

[ECG pearl: acquired long QT syndrome].

Orv Hetil 2018 Sep;159(39):1607-1610

I. Belgyógyászati Osztály - Kardiológia, Uzsoki utcai Kórház Budapest.

Authors report the case of a patient with drug-induced long QT syndrome. This case highlights the importance of ECG signs of LQTS that may lead to torsade de pointes tachycardia. The patient received the QT prolonging moxifloxacine and the QT remained long even after the offending drug was discontinued. Read More

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http://dx.doi.org/10.1556/650.2018.31021DOI Listing
September 2018

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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http://dx.doi.org/10.1016/j.stemcr.2018.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294263PMC
December 2018
1 Read

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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http://dx.doi.org/10.1016/j.jsps.2018.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260490PMC
December 2018
2 Reads

QTc Prolongation Associated With Psychiatric Medications: A Retrospective Cross-Sectional Study of Adult Inpatients.

J Clin Psychopharmacol 2019 Jan/Feb;39(1):72-77

Office of Graduate Medical Education Research, University of Arizona College of Medicine, Phoenix Campus Banner-University Medical Center Phoenix, Phoenix, AZ.

Objective: The aim of our study was to assess the impact of psychiatric medications and concomitant risk factors on the prevalence of QTc prolongation and torsades de pointes (TdP) in hospitalized subjects. We examined the association between individual risk scores and QTc prolongation and proposed an evidence-based protocol for electrocardiogram monitoring on psychotropic medications.

Method: Electrocardiograms (ECGs) of subjects hospitalized over a 1-year period were analyzed for QTc prolongation, associated risk factors, and use of medications. Read More

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http://dx.doi.org/10.1097/JCP.0000000000000992DOI Listing
December 2018
2 Reads

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

Eur J Pharmacol 2019 Feb 6;844:130-138. 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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http://dx.doi.org/10.1016/j.ejphar.2018.12.009DOI Listing
February 2019
2 Reads

Interleukin-6 inhibition of hERG underlies risk for acquired long QT in cardiac and systemic inflammation.

PLoS One 2018 6;13(12):e0208321. Epub 2018 Dec 6.

Cardiovascular Research Program, VA New York Harbor Healthcare System, Brooklyn, New York, United States of America.

Increased proinflammatory interleukin-6 (IL-6) levels are associated with acquired long QT-syndrome (LQTS) in patients with systemic inflammation, leading to higher risks for life-threatening polymorphic ventricular tachycardia such as Torsades de Pointes. However, the functional and molecular mechanisms of this association are not known. In most cases of acquired LQTS, the target ion channel is the human ether-á-go-go-related gene (hERG) encoding the rapid component of the delayed rectifier K current, IKr, which plays a critical role in cardiac repolarization. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208321PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283635PMC
December 2018
2 Reads

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

Int Heart J 2019 Jan 5;60(1):193-198. 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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https://www.jstage.jst.go.jp/article/ihj/advpub/0/advpub_18-
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http://dx.doi.org/10.1536/ihj.18-127DOI Listing
January 2019
5 Reads

Concomitant use of levofloxacin and fluconazole leading to possible torsades de pointes.

J Oncol Pharm Pract 2018 Nov 30:1078155218815743. Epub 2018 Nov 30.

1 College of Pharmacy, University of Illinois at Chicago, Chicago, USA.

Prolongation of the corrected QT interval can lead to the deadly arrhythmia torsades de pointes. There are many risk factors for corrected QT prolongation, one being medication. The goal of this case report is to add to the limited literature surrounding the possibility of torsades de pointes when levofloxacin and fluconazole are used concomitantly. Read More

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http://dx.doi.org/10.1177/1078155218815743DOI Listing
November 2018
2 Reads

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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http://dx.doi.org/10.1016/j.jelectrocard.2018.08.035DOI Listing
August 2018
3 Reads

Predicting critical drug concentrations and torsadogenic risk using a multiscale exposure-response simulator.

Prog Biophys Mol Biol 2018 Oct 25. Epub 2018 Oct 25.

Department of Mechanical Engineering, Stanford University, Stanford, CA, 94305, United States. Electronic address:

Torsades de pointes is a serious side effect of many drugs that can trigger sudden cardiac death, even in patients with structurally normal hearts. Torsadogenic risk has traditionally been correlated with the blockage of a specific potassium channel and a prolonged recovery period in the electrocardiogram. However, the precise mechanisms by which single channel block translates into heart rhythm disorders remain incompletely understood. Read More

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http://dx.doi.org/10.1016/j.pbiomolbio.2018.10.003DOI Listing
October 2018
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Voriconazole-induced QTc prolongation in a paediatric population.

Acta Paediatr 2018 Nov 20. Epub 2018 Nov 20.

Department of Pediatrics A, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Aim: To evaluate Corrected QT (QTc) interval prolongation (QTcP) in paediatric patients treated with voriconazole (VRC) and identify its associated risk factors in this setting.

Methods: Clinical, VRC-related and QTc interval data were collected retrospectively from the electronic medical records of VRC-treated paediatric patients attending a large tertiary medical centre in 2011-2016 who underwent electrocardiography before and during therapy. Paired comparison of QTc intervals before and during VRC treatment was performed, adjusted for concurrent medications, electrolyte disturbances and co-morbidities. Read More

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http://dx.doi.org/10.1111/apa.14652DOI Listing
November 2018
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Evaluation of QTc Interval Prolongation Among Patients With Cancer Using Enteral Methadone.

Am J Hosp Palliat Care 2019 Mar 14;36(3):177-184. Epub 2018 Nov 14.

2 The Arthur G. James Cancer Hospital, Richard Solove Research Institute, The Ohio State University, Columbus, OH, USA.

Context:: The effect of methadone on corrected QT interval (QTc) in patients with cancer pain is not well-known.

Objectives:: To describe and characterize the effect of low-, moderate-, and high-dose enteral methadone on QTc interval in patients with cancer.

Methods:: Retrospective cohort study including patients prescribed enteral methadone during the 27-month study period. Read More

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http://dx.doi.org/10.1177/1049909118811904DOI Listing
March 2019
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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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https://www.aerjournal.com/articles/antidepressant-antipsych
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http://dx.doi.org/10.15420/aer.2018.29.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141916PMC
August 2018
9 Reads

Development of torsadogenic risk assessment using human induced pluripotent stem cell-derived cardiomyocytes: Japan iPS Cardiac Safety Assessment (JiCSA) update.

J Pharmacol Sci 2018 Dec 24;138(4):233-239. Epub 2018 Oct 24.

Japan iPS Cardiac Safety Assessment (JiCSA), Japan; The University of Tokyo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Cardiac safety assessment is challenging because a better understanding of torsadogenic mechanisms beyond hERG blockade and QT interval prolongation is necessary for patient safety. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide a new human cell-based platform to assess cardiac safety in non-clinical testing during drug development. The multi-electrode array (MEA) platform is a promising electrophysiological technology to assess QT interval prolongation and proarrhythmic potential of drug candidates using hiPSC-CMs. Read More

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http://dx.doi.org/10.1016/j.jphs.2018.10.010DOI Listing
December 2018
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Comparison of Electrocardiographic Biomarkers for Differentiating Drug-Induced Single vs. Multiple Cardiac Ion Channel Block.

Clin Transl Sci 2018 Nov 10. Epub 2018 Nov 10.

VivaQuant, St. Paul, Minnesota, USA.

Since introduction of the International Conference on Harmonization proarrhythmia guidelines in 2005, no new marketed drugs have been associated with unacceptable risk of Torsade de Pointes. Although cardiac safety improved, these guidelines had the unintended consequence of eliminating potentially beneficial drugs from pipelines early in development. More recently, it has been shown that a corrected QT (QTc) prolonging drug may be safe if it impacts multiple ion channels vs. Read More

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http://dx.doi.org/10.1111/cts.12596DOI Listing
November 2018
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The arrhythmogenic cardiotoxicity of the quinoline and structurally related antimalarial drugs: a systematic review.

BMC Med 2018 11 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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https://bmcmedicine.biomedcentral.com/articles/10.1186/s1291
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http://dx.doi.org/10.1186/s12916-018-1188-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220451PMC
November 2018
9 Reads

Electrophysiological evaluation of pentamidine and 17-AAG in human stem cell-derived cardiomyocytes for safety assessment.

Eur J Pharmacol 2019 Jan 1;842:221-230. Epub 2018 Nov 1.

Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda, Tokyo 101-0062, Japan; Organization for University Research Initiatives, Waseda University, 3-14-9 Okubo, Shinjuku, Tokyo 169-0072, Japan; Waseda Bioscience Research Institute in Singapore (WABOIS), Helios, 11 Biopolis Way, 138667, Singapore; Department of Pure and Applied Physics, Graduate School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku, Tokyo 169-8555, Japan; Department of Physics, School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku, Tokyo 169-8555, Japan.

Human ether-a-go-go-related gene (hERG) trafficking inhibition is known to be one of the mechanisms of indirect hERG inhibition, resulting in QT prolongation and lethal arrhythmia. Pentamidine, an antiprotozoal drug, causes QT prolongation/Torsades de Pointes (TdP) via hERG trafficking inhibition, but 17-AAG, a geldanamycin derivative heat shock protein 90 (Hsp90) inhibitor, has not shown torsadogenic potential clinically, despite Hsp90 inhibitors generally being hypothesized to cause TdP by hERG trafficking inhibition. In the present study, we investigated the underlying mechanisms of both drugs' actions on hERG channels using hERG-overexpressing CHO cells (hERG-CHOs) and human embryonic stem cell-derived cardiomyocytes (hES-CMs). Read More

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http://dx.doi.org/10.1016/j.ejphar.2018.10.046DOI Listing
January 2019
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Fluoroquinolones and Cardiovascular Risk: A Systematic Review, Meta-analysis and Network Meta-analysis.

Drug Saf 2018 Oct 27. Epub 2018 Oct 27.

Division of Clinical Pharmacy, School of Pharmacy, The Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, 9112001, Jerusalem, Israel.

Introduction: Several fluoroquinolone antibiotics have been associated with cardiac adverse effects, leading to the withdrawal of some of these agents from the market. Cardiac side effects such as QT prolongation and torsades de pointes (TdP) have also been observed with fluoroquinolones currently on the market. In order to evaluate the cardiac risk of fluoroquinolones as a class, and the comparative risk for each individual drug, we conducted a systematic review, meta-analysis, and network meta-analysis. Read More

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http://dx.doi.org/10.1007/s40264-018-0751-2DOI Listing
October 2018
12 Reads