Proarrhythmia of nonantiarrhythmic drugs

Martyn, Robert; Somberg, John C.; Kerin, Nicholas Z.

doi:10.1016/s0002-8703(07)80029-9

Cited by 31 publications

(7 citation statements)

References 40 publications

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“…The potential of arrhythmic death due to non-cardiac drugs has become a major safety issue [10]. In November 2002, the FDA and Health Canada jointly published a regulatory guidance entitled ‘The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmia for Non-Antiarrhythmic Drugs’ [1].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a 12-Lead Digital Holter System for 24-Hour QT Interval Assessment

et al. 2006

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Background: Drug induced QT prolongation may precipitate life threatening cardiac arrhythmias. Evaluation of the QT prolonging effect of new pharmaceutical agents in a ‘thorough QT/QTc study’ is being mandated by FDA. The purpose of this study was to evaluate an automated 12-lead digital Holter system for a thorough QT/QTc study. Methods: Five healthy volunteers underwent 24-hour digital Holter monitoring. Each recording underwent a fully automated QT analysis (AQA) followed by an onscreen complete manual over read (MOR). Each recording was analyzed twice at least 2 weeks apart. The effect of data sampling (5-min segment/hour), the system sensitivity to detect 5-ms increase in QT, and the ability to assess circadian variation were evaluated. Results: The AQA resulted in identical QT for the first and second analyses, but with obvious errors in QT measurements. Compared to the complete onscreen MOR, the mean QT was longer with AQA (416 ± 41 vs. 387 ± 30 ms, p < 0.001), correlation; r = 0.3. The reproducibility of AQA with complete MOR was very good (QT: 387 ± 30 vs. 387 ± 30 ms, coefficient of variation: 0.2%, r = 0.986. The 5-min mean QT intervals correlated well with the hourly mean QT intervals (r = 0.994, p < 0.001, coefficient of variation = 1 ms) and both showed a similar circadian variation. The system was sensitive to detect a 5-ms change in QT intervals (5 ± 2 ms, coefficient of variation = 0.6%, r = 0.998, p < 0.001). Conclusions: The AQA is not an acceptable method, while the automatic analysis with complete MOR is a highly sensitive and reproducible method. Data sampling by analyzing 5-min segments per hour is sensitive and reproducible.

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Section: Introductionmentioning

confidence: 99%

Evaluation of a 12-Lead Digital Holter System for 24-Hour QT Interval Assessment

et al. 2006

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“…10 However, recent studies have also indicated that treatment with class I and class III antiarrhythmic agents, nonsedating histamine H1 receptor antagonists, macrolide antibiotics, and antifungal agents may predispose patients to proarrhythmic events. 19,20 Potassium currents responsible for limiting cardiac action potential duration vary depending on species and cell types. In guinea pig, dog, and human ventricular myocytes, the delayed rectifier current (I K ) is a major outward potassium current responsible for termination of the action potential plateau phase.…”

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confidence: 99%

Block of the Rapid Component of the Delayed Rectifier Potassium Current by the Prokinetic Agent Cisapride Underlies Drug-Related Lengthening of the QT Interval

et al. 1998

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“…That the increase in amiodarone concentration would have minimal effect given its very long half-life and high tissue uptake (great lipophilicity) further suggests that amiodarone is not the offending agent, but rather that zolpidem is responsible due to its inhibition of Ikr, potentiated by the higher than usually achieved concentration due to the co-administration of amiodarone. This hypothesis is further supported by the observation that amiodarone enhances homogeneity of myocardial repolarization and thus is an unlikely agent to cause torsade de pointes [2,3] .That drug interactions can lead to torsades de pointes has been well described [4,5] . When the antihistamine terfenadine was…”

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confidence: 82%