T-wave morphology as a covariate in drug-induced QTc prolongation

Claus Graff; J. Matz; M. P. Andersen; J. K. Kanters; J. Nielsen; J. Q. Xue; E. Toft; J. J. Struijk

T-wave morphology as a covariate in drug-induced QTc prolongation

Claus Graff^*, J. Matz, M. P. Andersen, J. K. Kanters, J. Nielsen, J. Q. Xue, E. Toft, J. J. Struijk

^*Corresponding author for this work

Abstract

QT interval prolongation is one of the most common causes of delays and non-approvals in drug development due to the qualitative relationship between this interval and Torsade de Pointes (TdP) arrhythmia. However, not all drugs that prolong the QT interval to the same extent carry the same risk for TdP. Other indications, such as abnormal T-wave morphology, may play a role in differentiating between safe and unsafe drugs. We used moxifloxacin and d,l-sotalol to investigate whether concurrent changes for QTc and T-wave morphology could be used to describe the discrepancy in proarrhythmic risk between the two drugs. Our results provide evidence that these drugs have significantly different morphology-duration profiles at similar QTc prolongations. We propose to investigate whether concurrent assessment of QTc and T-wave morphology has general validity for drug safety evaluation.

Original language	English
Title of host publication	Computers in Cardiology 2009, CinC 2009
Number of pages	4
Volume	36
Publication date	1 Dec 2009
Pages	589-592
Article number	5445339
ISBN (Print)	9781424472819
Publication status	Published - 1 Dec 2009
Event	36th Annual Conference of Computers in Cardiology, CinC 2009 - Park City, UT, United States Duration: 13 Sept 2009 → 16 Sept 2009

Conference

Conference	36th Annual Conference of Computers in Cardiology, CinC 2009
Country/Territory	United States
City	Park City, UT
Period	13/09/2009 → 16/09/2009
Sponsor	EMB, IEEE, Medtronic, CareFusion, Biosense Webster

Cite this

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title = "T-wave morphology as a covariate in drug-induced QTc prolongation",

abstract = "QT interval prolongation is one of the most common causes of delays and non-approvals in drug development due to the qualitative relationship between this interval and Torsade de Pointes (TdP) arrhythmia. However, not all drugs that prolong the QT interval to the same extent carry the same risk for TdP. Other indications, such as abnormal T-wave morphology, may play a role in differentiating between safe and unsafe drugs. We used moxifloxacin and d,l-sotalol to investigate whether concurrent changes for QTc and T-wave morphology could be used to describe the discrepancy in proarrhythmic risk between the two drugs. Our results provide evidence that these drugs have significantly different morphology-duration profiles at similar QTc prolongations. We propose to investigate whether concurrent assessment of QTc and T-wave morphology has general validity for drug safety evaluation.",

author = "Claus Graff and J. Matz and Andersen, {M. P.} and Kanters, {J. K.} and J. Nielsen and Xue, {J. Q.} and E. Toft and Struijk, {J. J.}",

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T1 - T-wave morphology as a covariate in drug-induced QTc prolongation

AU - Graff, Claus

AU - Matz, J.

AU - Andersen, M. P.

AU - Kanters, J. K.

AU - Nielsen, J.

AU - Xue, J. Q.

AU - Toft, E.

AU - Struijk, J. J.

PY - 2009/12/1

Y1 - 2009/12/1

N2 - QT interval prolongation is one of the most common causes of delays and non-approvals in drug development due to the qualitative relationship between this interval and Torsade de Pointes (TdP) arrhythmia. However, not all drugs that prolong the QT interval to the same extent carry the same risk for TdP. Other indications, such as abnormal T-wave morphology, may play a role in differentiating between safe and unsafe drugs. We used moxifloxacin and d,l-sotalol to investigate whether concurrent changes for QTc and T-wave morphology could be used to describe the discrepancy in proarrhythmic risk between the two drugs. Our results provide evidence that these drugs have significantly different morphology-duration profiles at similar QTc prolongations. We propose to investigate whether concurrent assessment of QTc and T-wave morphology has general validity for drug safety evaluation.

AB - QT interval prolongation is one of the most common causes of delays and non-approvals in drug development due to the qualitative relationship between this interval and Torsade de Pointes (TdP) arrhythmia. However, not all drugs that prolong the QT interval to the same extent carry the same risk for TdP. Other indications, such as abnormal T-wave morphology, may play a role in differentiating between safe and unsafe drugs. We used moxifloxacin and d,l-sotalol to investigate whether concurrent changes for QTc and T-wave morphology could be used to describe the discrepancy in proarrhythmic risk between the two drugs. Our results provide evidence that these drugs have significantly different morphology-duration profiles at similar QTc prolongations. We propose to investigate whether concurrent assessment of QTc and T-wave morphology has general validity for drug safety evaluation.

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M3 - Article in proceedings

AN - SCOPUS:77952684309

SN - 9781424472819

VL - 36

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BT - Computers in Cardiology 2009, CinC 2009

T2 - 36th Annual Conference of Computers in Cardiology, CinC 2009

Y2 - 13 September 2009 through 16 September 2009

ER -

T-wave morphology as a covariate in drug-induced QTc prolongation

Abstract

Conference

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