Individual-Specific QT Interval Correction for Drugs With Substantial Heart Rate Effect Using Holter ECGs Extracted Over a Wide Range of Heart Rates.

Journal of Clinical Pharmacology
Gopi Krishna PanickerDilip R Karnad

Abstract

Although fixed QT correction methods are typically used to adjust for the effect of heart rate on the QT interval in thorough QT/QTc studies, individual-specific QT correction (QTcI = QT/RRI ) is advisable for drugs that increase the heart rate by >5 to 10 beats/minute (bpm). QTcI is traditionally derived using resting drug-free electrocardiograms (ECGs) collected at prespecified times. However, the resting heart rate range in healthy individuals is narrow, and extrapolation of inferences from these data to higher heart rates could be inappropriate. Accordingly, the QTcI derived from triplicate ECGs extracted at prespecified times (the traditional [T] method, yielding QTcIT) was compared with QTcIs obtained using ECGs with a wider heart rate range (alternative Holter [H] method, yielding QTcIH) from 24-hour Holter recordings from 40 healthy individuals selected from a central ECG laboratory database. For QTcIH, 10-second ECGs were extracted at stable heart rates in the ranges of 51-60, 61-70, 71-80, and 81-90 bpm (9 ECGs in each bin = 36 ECGs). An independent set of 40 ECGs with heart rates from 51 to 90 bpm was extracted from each individual to validate the accuracy of QTcI by the 2 methods. For the validation set, the QTcIH w...Continue Reading

References

Apr 12, 2003·Pacing and Clinical Electrophysiology : PACE·Peter SmetanaMarek Malik
Jul 25, 2008·Clinical Pharmacology and Therapeutics·M MalikM Braun
Sep 2, 2008·Journal of Clinical Pharmacology·Marek MalikDavid Madge
Jan 28, 2010·Journal of Clinical Pharmacology·Antonia PericlouCharles Lindamood
Jul 22, 2010·Circulation. Heart Failure·Michael G LinkPeter R Kowey
Mar 13, 2016·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Marek MalikNorman Stockbridge
Apr 1, 2017·European Heart Journal. Cardiovascular Pharmacotherapy·J Rick TurnerSnehal Kothari

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Citations

Jun 7, 2018·Journal of Clinical Pharmacology·Marek Malik
Jun 9, 2020·Clinical and Translational Science·Katarina IlicPatrick Martin

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