Inter‐ and Intraday Variability in Major Electrocardiogram Intervals and Amplitudes in Healthy Men and Women

Abstract

The ECG may vary during the day (intra-day), and between days (interday), for the same subject. Variability in ECG characteristic measurements between different investigators is well documented and is often large. During days 1-6 of each placebo period of a two-way crossover Phase I study, digital ECGs were recorded at about 8 and 12 AM in 16 healthy volunteers (8 men, 8 women). Two observers independently analyzed leads V2 and V6 using EClysis software. The durations and amplitudes of major ECG waves and the intervals between major electrocardiographic events were analyzed in a mixed model ANOVA, in which subject, observer, time, and day were treated as random factors. The influence of various corrections for heart rate on the variability of QT intervals was investigated. The difference among subjects explained between 44-81% of the total variability in ECG intervals and amplitudes. Overall, inter- and intraday variability was not statistically significant for any variable. The individualized exponential correction of the QT interval for heart rate eliminated the QT interval dependence on the RR interval in all subjects. Changes in T wave morphology and shortening of the QT interval from morning to noon were observed in ten subjects. The interobserver variability was close to zero (SD < 0.005 ms) for all variables except the PQ interval (SD 1.4 ms). The various sources of variability in determinations of ECG wave characteristics should be considered in the design of clinical studies. The use of EClysis software for ECG measurements is this study made the results highly observer independent.

T‐Wave Morphology Parameters Based on Principal Component Analysis Reproducibility and Dependence on T−Offset Position

“…Thus, the circadian differences in T-wave morphology parameters based on PCA may not be related only to circadian heart rate changes. 36 The repeatability of the measure of the TWR was lesser than other PCA parameters. Batdorf et al have already reported that the 1-month reproducibility of TWR is not very high.…”

Clinical Evaluation of QT/QTc Prolongation and Proarrhythmic Potential for Nonantiarrhythmic Drugs: The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use E14 Guideline

“…The same applies to the actual technique of measuring the ECG intervals-having a few skilled readers, whether computer assisted (semiautomatic) or not (fully manual), operating from a central ECG laboratory is generally recommended. Other techniques, including fully automated, [32][33][34] will emerge and can be anticipated to replace manual techniques, once validated.…”

Evaluation of QTc Interval Prolongation in Breast Cancer Patients after Treatment with Epirubicin, Cyclophosphamide, and Docetaxel and the Influence of Interobserver Variation

“…This is supported by our statistics and a study by Darpo et al [23] demonstrating that differences between methods disappear when QT changes are analyzed from baseline. Moreover, in another study, the manual interobserver variability of the QTc interval in healthy individuals was found to be close to 0 [24]. Therefore, treating physicians should be able to manually diagnose a possible increase in QTc interval but should be cautious about relying on automated ECG interpretation software.…”