T-wave morphology as a covariate in drug-induced QTc prolongation
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T-wave morphology as a covariate in drug-induced QTc prolongation. / Graff, Claus; Matz, J.; Andersen, M. P.; Kanters, J. K.; Nielsen, J.; Xue, J. Q.; Toft, E.; Struijk, J. J.
Computers in Cardiology 2009, CinC 2009. Vol. 36 2009. p. 589-592 5445339.Research output: Chapter in Book/Report/Conference proceeding › Article in proceedings › Research › peer-review
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TY - GEN
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.
UR - http://www.scopus.com/inward/record.url?scp=77952684309&partnerID=8YFLogxK
M3 - Article in proceedings
AN - SCOPUS:77952684309
SN - 9781424472819
VL - 36
SP - 589
EP - 592
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 -
ID: 204299477