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Number of ECG Replicates Influences the Estimated QT Prolonging Effect of a Drug

van der Wall, H.E.C.1,3; Gal, P.1; Kemme, M.J.B.1,2; van Westen, G.J.P.3; Burggraaf, J.*,1,3,4

doi: 10.1097/FJC.0000000000000657
Original Article: PDF Only

Introduction: The present analysis addressed the effect of the number of ECG replicates extracted from a continuous ECG on estimated QT interval prolongation for different QT correction formulas.

Methods: For one hundred healthy volunteers, who received a compound prolonging the QT interval, 18 ECG replicates within a 3 minute window were extracted from 12-lead Holter ECGs. Ten QT correction formulas were deployed and the QTc interval was controlled for baseline and placebo and averaged per dose level.

Results: The mean prolongation difference was >4 ms for single and > 2 ms for triplicate ECG measurements compared to the 18 ECG replicate mean value. The difference was <0.5ms after 14 replicates. In contrast, concentration-effect analysis was independent of replicate count and also of QT correction formula.

Conclusion: The number of ECG replicates impacted the estimated QT interval prolongation for all deployed QT correction formulas. However, concentration-effect analysis was independent of both the replicate number and correction formula.

1Centre for Human Drug Research, Leiden, the Netherlands

2VU Medical center, Department of Cardiology, Amsterdam, the Netherlands

3Leiden Academic Centre for Drug Research, Leiden, the Netherlands

4Leiden University Medical Center, Leiden, the Netherlands

Address for correspondence: Prof. dr. J. Burggraaf Centre for Human Drug Research Zernikedreef 8 2333 CL Leiden E: kb@chdr.nl T: + 31 71 5246 400F: + 31 71 5246 499

Conflict of Interest: No

Funding: No

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