Electrocardiographic identification of drug-induced QT prolongation: assessment by different recording and measurement methods.
BACKGROUND
Careful assessment of QT interval prolongation is required before novel drugs are approved by regulatory authorities. The choice of the most appropriate method of electrocardiogram (ECG) acquisition and QT/RR interval measurement in clinical trials requires better understanding of the differences among currently available approaches. This study compared standard and Holter-derived 12-lead ECGs for utility in detecting sotalol-induced QT/QTc and RR changes. Manual methods (digitizing pad and digital on-screen calipers) were compared for precision of QT and RR interval measurement.


RESULTS
Sixteen hundred pairs of serial 12-lead digital ECGs were recorded simultaneously by standard resting ECG device and by continuous 12-lead digital Holter over 3 days in 39 healthy male and female volunteers. No therapy was given on the 1st day followed by 160 mg and 320 mg of sotalol on the 2nd and 3rd day, respectively. Holter-derived and standard ECGs produced nearly identical sotalol-induced QT/QTc and RR changes from baseline, as did the manual digipad and on-screen caliper measurements. The variability of on-screen QT measurement in this study was greater than that of digipad.


CONCLUSIONS
Digital 12-lead Holter and standard 12-lead ECG recorders, as well as the manual digitizing pad and digital on-screen calipers, are of equal utility for the assessment of drug-induced change from baseline in QT and RR interval, although the variability of the on-screen method in this study was greater than of the digipad.
Sarapa
Nenad
N
Clinical Pharmacology, Pharmacia Corp., Kalamazoo, Michigan, USA. nenad.sarapa@pfizer.com
Morganroth
Joel
J
Couderc
Jean-Philippe
JP
Francom
Steven F
SF
Darpo
Borje
B
Fleishaker
Joseph C
JC
McEnroe
Janet D
JD
Chen
William T
WT
Zareba
Wojciech
W
Moss
Arthur J
AJ
D004562:Electrocardiography / Q000379:methods*; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced / Q000175:diagnosis*; D008297:Male; D013015:Sotalol / Q000009:adverse effects*
D013015:Sotalol