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Article ; Online: Evaluation of the QT interval in patients with drug-induced QT prolongation and torsades de pointes.

Journal of cardiovascular electrophysiology

2020 Volume 31, Issue 10, Page(s) 2696–2701

Abstract: ... of drug-induced long QT syndrome (diLQTS) with torsades de pointes (TdP) are lacking.: Methods ... wave morphology in each lead and measured the longest QT interval in the limb and chest leads ... 19.6%), and biphasic (15.2%) T waves.: Conclusions: Our results indicate that QT evaluation ...

Abstract	Background: Data on the optimal location of the electrocardiogram (ECG) leads for the diagnosis of drug-induced long QT syndrome (diLQTS) with torsades de pointes (TdP) are lacking. Methods: We systematically reviewed the literature for the ECGs of patients with diLQTS and subsequent TdP. We assessed T wave morphology in each lead and measured the longest QT interval in the limb and chest leads in a standardized fashion. Results: Of 84 patients, 61.9% were female and the mean age was 58.8 years. QTc was significantly longer in chest versus limb leads (mean (SD) 671 (102) vs. 655 (97) ms, p = .02). Using only limb leads for QT interpretation, 18 (21.4%) ECGs were noninterpretable: 10 (11.9%) due to too flat T waves, 7 (8.3%) due to frequent, early PVCs and 1 (1.2%) due to too low ECG recording quality. In the chest leads, ECGs were noninterpretable in nine (10.7%) patients: six (7.1%) due to frequent, early PVCs, one (1.2%) due to insufficient ECG quality, two (2.4%) due to missing chest leads but none due to too flat T waves. The most common T wave morphologies in the limb leads were flat (51.0%), broad (14.3%), and late peaking (12.6%) T waves. Corresponding chest lead morphologies were inverted (35.5%), flat (19.6%), and biphasic (15.2%) T waves. Conclusions: Our results indicate that QT evaluation by limb leads only underestimates the incidence of diLQTS experiencing TdP and favors the screening using both limb and chest lead ECG.
MeSH term(s)	Electrocardiography ; Female ; Humans ; Long QT Syndrome/chemically induced ; Long QT Syndrome/diagnosis ; Middle Aged ; Pharmaceutical Preparations ; Torsades de Pointes/chemically induced ; Torsades de Pointes/diagnosis ; Ventricular Premature Complexes
Chemical Substances	Pharmaceutical Preparations
Keywords	covid19
Language	English
Publishing date	2020-07-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	1025989-2
ISSN	1540-8167 ; 1045-3873
ISSN (online)	1540-8167
ISSN	1045-3873
DOI	10.1111/jce.14687
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Article: Drug-Induced QT Prolongation And Torsades de Pointes.

Li, Matthew / Ramos, Liz G

P & T : a peer-reviewed journal for formulary management

2017 Volume 42, Issue 7, Page(s) 473–477

Abstract: Torsades de pointes (TdP)-an uncommon but life-threatening polymorphic ventricular tachycardia-is ... almost always drug induced. The authors describe the causes, risk factors, symptoms, diagnosis, and ...

Abstract	Torsades de pointes (TdP)-an uncommon but life-threatening polymorphic ventricular tachycardia-is almost always drug induced. The authors describe the causes, risk factors, symptoms, diagnosis, and treatment of TdP.
Language	English
Publishing date	2017-06-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	1036637-4
ISSN	1052-1372
ISSN	1052-1372
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Article ; Online: Optimal location of the QT interval evaluation in patients with drug-induced QT prolongation and torsades de pointes: Limb leads, chest leads, or both?

Lakkis, Bachir / Refaat, Marwan M

Journal of cardiovascular electrophysiology

2020 Volume 31, Issue 10, Page(s) 2702–2703

MeSH term(s)	Electrocardiography ; Humans ; Long QT Syndrome/chemically induced ; Long QT Syndrome/diagnosis ; Pharmaceutical Preparations ; Torsades de Pointes/chemically induced ; Torsades de Pointes/diagnosis
Chemical Substances	Pharmaceutical Preparations
Keywords	covid19
Language	English
Publishing date	2020-07-28
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	1025989-2
ISSN	1540-8167 ; 1045-3873
ISSN (online)	1540-8167
ISSN	1045-3873
DOI	10.1111/jce.14682
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Article ; Online: Predicting drug-induced QT prolongation and torsades de pointes.

Roden, Dan M

The Journal of physiology

2016 Volume 594, Issue 9, Page(s) 2459–2468

Abstract: ... the morphologically distinctive polymorphic ventricular tachycardia ('torsades de pointes'). This syndrome of drug ... by arrhythmogenic afterdepolarizations thought to trigger torsades de pointes. This review describes the evidence ... other conditions can occasionally produce exaggerated prolongation of the QT interval on the electrocardiogram and ...

Abstract	Drugs used to treat cardiovascular disease as well as those used in the treatment of multiple other conditions can occasionally produce exaggerated prolongation of the QT interval on the electrocardiogram and the morphologically distinctive polymorphic ventricular tachycardia ('torsades de pointes'). This syndrome of drug-induced long QT syndrome has moved from an interesting academic exercise to become a key element in the development of any new drug entity. The prevailing view, which has driven both clinical care and drug regulation, holds that cardiac repolarization represents a balance between inward currents (primarily through calcium and sodium channels) and outward currents (primarily through rapid and slowed delayed rectifier potassium channels) and that block of the rapid delayed rectifier (IKr ) is the primary mechanism whereby drugs prolong individual action potentials, manifest on the surface electrocardiogram as QT interval prolongation. Such marked action potential prolongation in individual cardiac cells, in turn, is accompanied by arrhythmogenic afterdepolarizations thought to trigger torsades de pointes. This review describes the evidence in support of this construct, and describes the way in which clinical and whole heart experiments have informed molecular mechanisms and vice versa. New data that challenge these views and that may, as a result, lead to new clinical care and drug screening paradigms, are discussed.
MeSH term(s)	Animals ; Drug-Related Side Effects and Adverse Reactions/genetics ; Drug-Related Side Effects and Adverse Reactions/physiopathology ; Humans ; Long QT Syndrome/chemically induced ; Long QT Syndrome/genetics ; Long QT Syndrome/physiopathology ; Myocytes, Cardiac/physiology ; Torsades de Pointes/chemically induced ; Torsades de Pointes/genetics ; Torsades de Pointes/physiopathology
Language	English
Publishing date	2016-05-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP270526
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Article ; Online: Predicting the Unpredictable: Drug-Induced QT Prolongation and Torsades de Pointes.

Schwartz, Peter J / Woosley, Raymond L

Journal of the American College of Cardiology

2016 Volume 67, Issue 13, Page(s) 1639–1650

Abstract: Drug-induced long QT syndrome (diLQTS) and congenital LQTS (cLQTS) share many features, and ... both syndromes can result in life-threatening torsades de pointes (TdP). Our understanding of their mechanistic ... risk factors predictive of diLQTS and warn when a drug that can cause TdP is prescribed. CDSS have reduced ...

Abstract	Drug-induced long QT syndrome (diLQTS) and congenital LQTS (cLQTS) share many features, and both syndromes can result in life-threatening torsades de pointes (TdP). Our understanding of their mechanistic and genetic similarities has led to their improved clinical management. However, our inability to prevent diLQTS has resulted in removal of many medicines from the market and from development. Genetic and clinical risk factors for diLQTS and TdP are well known and raise the possibility of TdP prevention. Clinical decision support systems (CDSS) can scan the patient's electronic health records for clinical risk factors predictive of diLQTS and warn when a drug that can cause TdP is prescribed. CDSS have reduced prescriptions of QT-prolonging drugs, but these relatively small changes lack the power to reduce TdP. The growing genetic evidence linking diLQTS to cLQTS suggests that prevention of TdP in the future may require inclusion of both genetic and clinical predictors into CDSS.
MeSH term(s)	Adverse Drug Reaction Reporting Systems ; Decision Support Systems, Clinical ; Drug-Related Side Effects and Adverse Reactions ; Electrocardiography ; Genomics ; Humans ; Internet ; Long QT Syndrome/chemically induced ; Risk Factors ; Torsades de Pointes/chemically induced
Language	English
Publishing date	2016-04-05
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	605507-2
ISSN	1558-3597 ; 0735-1097
ISSN (online)	1558-3597
ISSN	0735-1097
DOI	10.1016/j.jacc.2015.12.063
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Zs.A 1846: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 196: Show issues

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Article: Evaluation of the QT Interval in Patients with Drug-induced QT Prolongation and Torsades de Pointes

J. cardiovasc. electrophysiol

Abstract: ... syndrome (diLQTS) with Torsades de Pointes (TdP) are lacking. METHODS: We systematically ... BACKGROUND: Data on the optimal location of the ECG leads for the diagnosis of drug-induced long QT ... and measured the longest QT interval in the limb and chest leads in a standardized fashion. RESULTS ...

Abstract	BACKGROUND: Data on the optimal location of the ECG leads for the diagnosis of drug-induced long QT syndrome (diLQTS) with Torsades de Pointes (TdP) are lacking. METHODS: We systematically reviewed the literature for ECGs of patients with diLQTS and subsequent TdP. We assessed T-wave morphology in each lead and measured the longest QT interval in the limb and chest leads in a standardized fashion. RESULTS: Of 84 patients, 61.9% were female and mean age was 58.8 years. QTc was significantly longer in chest versus limb leads (mean (standard deviation) 671 (102) vs 655 (97) ms, p=0.02). Using only limb leads for QT interpretation, 18 (21.4%) ECGs were non-interpretable: 10 (11.9%) due to too flat T-waves, 7 (8.3%) due to frequent, early PVCs and 1 (1.2%) due to too low ECG recording quality. In the chest leads, ECGs were non-interpretable in 9 (10.7%) patients: 6 (7.1%) due to frequent, early PVCs, 1 (1.2%) due to insufficient ECG quality, 2 (2.4%) due to missing chest leads but none due to too flat T-waves. The most common T-wave morphologies in the limb leads were flat (51.0%), broad (14.3%) and late peaking (12.6%) T-waves. Corresponding chest lead morphologies were inverted (35.5%), flat (19.6%) and biphasic (15.2%) T-waves. CONCLUSIONS: Our results indicate that QT evaluation by limb leads only underestimates the incidence of diLQTS experiencing TdP and favors the screening using both limb and chest lead ECG. This article is protected by copyright. All rights reserved.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #670809
Database	COVID19

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Article ; Online: Corrigendum to "Sex-Related Differences in Drug-Induced QT Prolongation and Torsades de Pointes: A New Model System with Human iPSC-CMs".

Huo, Jianhua / Wei, Feng / Cai, Chengzhong / Lyn-Cook, Beverly / Pang, Li

Toxicological sciences : an official journal of the Society of Toxicology

2019 Volume 168, Issue 1, Page(s) 282

Language	English
Publishing date	2019-01-08
Publishing country	United States
Document type	Journal Article ; Published Erratum
ZDB-ID	1420885-4
ISSN	1096-0929 ; 1096-6080
ISSN (online)	1096-0929
ISSN	1096-6080
DOI	10.1093/toxsci/kfy310
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Article ; Online: Drug-Induced QT Prolongation and Torsades de Pointes: An All-Exclusive Relationship or Time for an Amicable Separation?

Hondeghem, Luc M

Drug safety

2017 Volume 41, Issue 1, Page(s) 11–17

Abstract: ... for torsades de pointes (TdP) instead. Drugs that prolong the QT interval range from having potent torsadogenic activity ... but can also lead to ventricular tachycardia (VT) and ventricular fibrillation (VF). Note that QT prolongation ... induced QT prolongation is a bad surrogate for TdP, VT or VF; it is high time to move away ...

Abstract	QT prolongation was perceived as a major antiarrhythmic mechanism, but soon became a surrogate for torsades de pointes (TdP) instead. Drugs that prolong the QT interval range from having potent torsadogenic activity to no proarrhythmic action and even antiarrhythmic effects. Blockade of hERG channels is the primary cause of TdP, but blockade/activation of other channels can also be torsadogenic. TdP is primarily caused by disturbances of TRIaD, but disturbance of wavelength can also contribute to TdP (where TRIaD is triangulation, reverse use dependence, instability and dispersion, and wavelength equals conduction velocity times effective refractory period). The above proarrhythmic parameters do not only result in TdP, but can also lead to ventricular tachycardia (VT) and ventricular fibrillation (VF). Note that QT prolongation (not listed as a causal factor) yields many false positives (potentially depriving patients from much needed drugs) and false negatives (potentially exposing patients to lethal arrhythmias). Thus, drug-induced QT prolongation is a bad surrogate for TdP, VT or VF; it is high time to move away from an oversimplified and erroneous surrogate.
MeSH term(s)	Anti-Arrhythmia Agents/adverse effects ; Cardiotonic Agents/adverse effects ; Cnidarian Venoms/adverse effects ; Drug-Related Side Effects and Adverse Reactions/prevention & control ; False Positive Reactions ; Humans ; Long QT Syndrome/chemically induced ; Phenethylamines/adverse effects ; Sulfonamides/adverse effects ; Torsades de Pointes/chemically induced
Chemical Substances	Anti-Arrhythmia Agents ; Cardiotonic Agents ; Cnidarian Venoms ; Phenethylamines ; Sulfonamides ; toxin II (Anemonia sulcata) (60748-45-0) ; dofetilide (R4Z9X1N2ND)
Language	English
Publishing date	2017-08-29
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	1018059-x
ISSN	1179-1942 ; 0114-5916
ISSN (online)	1179-1942
ISSN	0114-5916
DOI	10.1007/s40264-017-0584-4
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Article: Optimal Location of the QT Interval Evaluation in Patients with Drug-induced QT Prolongation and Torsades de Pointes: Limb leads, Chest leads or Both?

Lakkis, Bachir / Refaat, Marwan M

J. cardiovasc. electrophysiol

Abstract: ... on the electrocardiogram (ECG). Clinically, LQTS is associated with the development of Torsades de Pointes (TdP), a well ... Long QT syndrome (LQTS) is characterized by prolongation of the QT interval ... defined polymorphic ventricular tachycardia and the development of sudden cardiac death (1). This article ...

Abstract	Long QT syndrome (LQTS) is characterized by prolongation of the QT interval on the electrocardiogram (ECG). Clinically, LQTS is associated with the development of Torsades de Pointes (TdP), a well-defined polymorphic ventricular tachycardia and the development of sudden cardiac death (1). This article is protected by copyright. All rights reserved.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #670836
Database	COVID19

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Article ; Online: Sex-Related Differences in Drug-Induced QT Prolongation and Torsades de Pointes: A New Model System with Human iPSC-CMs.

Huo, Jianhua / Wei, Feng / Cai, Chengzhong / Lyn-Cook, Beverly / Pang, Li

Toxicological sciences : an official journal of the Society of Toxicology

2018 Volume 167, Issue 2, Page(s) 360–374

Abstract: ... arrest (torsades de pointes [TdP]). Women are at a higher risk than men for experiencing drug-induced TdP ... function. In this study, we investigated genetic and hormonal effects on sex differences of drug-induced QT ... between men and women have any effects on drug-induced proarrhythmia. Sex hormones are believed to play ...

Abstract	Numerous drugs have the potential to prolong the QT interval and may cause accidental cardiac arrest (torsades de pointes [TdP]). Women are at a higher risk than men for experiencing drug-induced TdP. Due to the lack of appropriate tools, few studies have investigated whether genetic differences between men and women have any effects on drug-induced proarrhythmia. Sex hormones are believed to play a predominant role in the induction of TdP. Recently, progress in induced pluripotent stem cell (iPSC) technologies has made it possible to utilize human iPSC-derived cardiomyocytes (hiPSC-CMs) to investigate the influence of both genetics and sex hormones on cardiac ion channel gene expression and cardiomyocyte function. In this study, we investigated genetic and hormonal effects on sex differences of drug-induced QT prolongation and TdP with hiPSC-CMs from healthy male and female donors. We found that despite batch variations in beating rates and field potential durations (FPD), female-derived hiPSC-CMs showed steeper slopes of FPD to interspike interval ratios and were more sensitive to IKr blocker-induced FPD prolongation. 17β-estradiol increased FPD and 5α-dihydrotestosterone shortened FPD, but the addition of sex hormones had limited effect on the responses of hiPSC-CMs to IKr blockades. The differential expression of KCNE1 gene and reduced repolarization reserve in female-derived hiPSC-CMs compared with male-derived hiPSC-CMs may partially explain why females are more susceptible to proarrhythmias. Human iPSC-CMs can be a useful new model to study mechanisms of sex differences in cardiomyocyte repolarization processes and aid in the prediction of drug-induced proarrhythmias in both men and women.
MeSH term(s)	Action Potentials/drug effects ; Cells, Cultured ; Drug-Related Side Effects and Adverse Reactions/etiology ; Drug-Related Side Effects and Adverse Reactions/metabolism ; Female ; Healthy Volunteers ; Humans ; Induced Pluripotent Stem Cells/drug effects ; Induced Pluripotent Stem Cells/metabolism ; Ion Channels/antagonists & inhibitors ; Long QT Syndrome/chemically induced ; Long QT Syndrome/metabolism ; Male ; Models, Biological ; Myocytes, Cardiac/drug effects ; Myocytes, Cardiac/metabolism ; Sex Characteristics ; Torsades de Pointes/chemically induced ; Torsades de Pointes/metabolism
Chemical Substances	Ion Channels
Language	English
Publishing date	2018-09-24
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1420885-4
ISSN	1096-0929 ; 1096-6080
ISSN (online)	1096-0929
ISSN	1096-6080
DOI	10.1093/toxsci/kfy239
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