Analyses of dynamic beat-to-beat QT-TQ interval (ECG restitution) changes in humans under normal sinus rhythm and prior to an event of torsades de pointes during QT prolongation caused by sotalol.
BACKGROUND
Restitution through intracardiac pacing has been used to assess arrhythmia vulnerability. We examined whether analyses of sequential beat-to-beat QT and TQ interval measures can be used to quantify ECG restitution changes under normal sinus rhythm.


METHODS
The QT, R-R and TQ intervals were examined 22.5 hour Holter monitoring before and after oral sotalol in normal male and female volunteers. Additionally, comparisons were made to those observed in the time-matched dataset prior to torsades de pointes in a heart diseased patient that received a single dose of sotalol.


RESULTS
Sotalol increased QT, R-R and TQ intervals 71, 101, and 125 ms after 160 mg (n = 38) and 194, 235, and 135 ms after 320 mg (n = 19) during maximum plasma concentrations, respectively. The percentage of beats with a QT/TQ ratio >1 was reduced 25% over the entire 22.5 hours after sotalol and the lower TQ interval boundary (5th quantile) was increased 22-30%. In contrast, 99% of the beats prior to torsades de pointes had a QT/TQ ratio > 1 and the median TQ interval was below the lower 98% confidence bounds of normals before and after sotalol.


CONCLUSIONS
ECG restitution changes are quantifiable under varying states (nocturnally, beta-adrenergic blockade, QT prolongation) in healthy subjects.
Fossa
Anthony A
AA
Pfizer Global Research and Development, Groton, Connecticut 06340, USA. anthony.a.fossa@pfizer.com
Wisialowski
Todd
T
Crimin
Kimberly
K
Wolfgang
Eric
E
Couderc
Jean-Philippe
JP
Hinterseer
Martin
M
Kaab
Stefan
S
Zareba
Wojciech
W
Badilini
Fabio
F
Sarapa
Nenad
N
D000293:Adolescent; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D015716:Electrocardiography, Ambulatory; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D013015:Sotalol / Q000494:pharmacology*; D018709:Statistics, Nonparametric; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000503:physiopathology*
D000889:Anti-Arrhythmia Agents; D013015:Sotalol