Time-dependent variation in the cardiac conduction system assessed in young healthy individuals at weeks' interval: implications for clinical trials.
The time-dependent physiologic variations of the cardiac conduction system were evaluated at repeated invasive studies in 10 healthy individuals. Their mean age was 28 years (range 22 to 34) and they volunteered to undergo two electrophysiologic studies at intervals of 14 to 63 days (mean 25). The coefficients of variation, repeatability and reproducibility, which should be the preferred statistics when assessing the reproducibility of continuous variables, were calculated. The mean sinus cycle length had a high reproducibility, with coefficients of variation between 2% and 6%. The mean and maximal sinus node recovery times, however, varied considerably. The reproducibility was very high for ventricular depolarization and repolarization (QRS, JT, QT), with coefficients of variation between 2% and 6%. The coefficients of variation were below the acceptable 10% value for intraatrial conduction, atrioventricular (AV) node conduction, His-Purkinje conduction as well as the Wenckebach point; for the effective refractory period of the AV node, it was 12%. Repeat invasive electrophysiologic testing is a safe and reproducible method for evaluating and comparing cardioactive drug effects in healthy subjects. The same statistical analyses were applied to previously published studies on continuous electrophysiologic variables, which allowed comparisons among different groups of healthy and sick persons, as well as among different electrophysiologic variables and procedures. Furthermore, the minimal actual treatment differences that can be detected with a reasonable (80%) probability at a predetermined (5%) significance level using a crossover design were estimated for different electrophysiologic variables. These data will assist in the calculation of the necessary sample size for clinical trials and related purposes.
Bergfeldt
L
L
Department of Medicine, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
Melander
H
H
Schenck-Gustafsson
K
K
D000328:Adult; D006328:Cardiac Catheterization; D002304:Cardiac Pacing, Artificial; D002986:Clinical Trials as Topic; D004594:Electrophysiology; D005260:Female; D006329:Heart Conduction System / Q000502:physiology*; D006801:Humans; D008297:Male; D015203:Reproducibility of Results; D012494:Sampling Studies; D013997:Time Factors