Article Text

Download PDFPDF
  1. J. C. Somberg1,
  2. Z. Molnar1,
  3. V. Ranade1,
  4. I. Cvetanovic1,
  5. J. Molnar1
  1. *Rush University, Chicago, IL, and American Institute of Therapeutics, Lake Bluff, IL


Background Drug-induced Q-T prolongation may precipitate life-threatening cardiac arrhythmias; therefore, evaluation of the Q-T prolonging effect of new pharmaceutical agents in a “thorough Q-T/Q-Tc study” is being mandated by the FDA. The purpose of this study was to evaluate the feasibility of a 12-lead digital Holter system for a thorough Q-T/Q-Tc study.

Methods Five healthy volunteers underwent 24-hour digital Holter monitoring (NorthEast Monitoring, Maynard, MA). The system provides automated Q-T analysis (AQA) and the option of onscreen manual over read (MOR) of automatic Q-T determinations. Each recording underwent a fully AQA followed by an onscreen complete MOR by an expert observer. The MOR was used as the reference standard for the validation of AQA. Each recording underwent a second analysis at 2 weeks following the first analysis to evaluate reproducibility. The effect of data sampling (5-min segment/hour), the system sensitivity to detect 5 ms increase in Q-T, and the ability to assess circadian variation were also evaluated.

Results The fully AQA resulted in identical QT for the first and second analyses, but with obvious errors in Q-T measurements. Compared to the complete onscreen MOR, the 24-hour mean Q-T was longer with AQA (416 ± 41 vs 387 ± 30 ms, p < .001, r = .3). The reproducibility of automatic analysis with complete MOR was very good (Q-T: 387 ± 30 vs 387 ± 30 ms), coefficient of variation (CV) = 0.2%, r = .986, p < .001. The 5-minute mean Q-T intervals correlated well with the hourly mean Q-T intervals (r = .994, p < .001, CV = 1 ms) and both showed a similar circadian variation. The system was sensitive to detect a 5 ms change in Q-T intervals (5 ± 2 ms, CV = 0.6%, r = .998, p < .001). Conclusions. The fully automatic Q-T analysis is not an acceptable method, while the automatic analysis with MOR is a highly sensitive and reproducible method. Data sampling by analyzing 5-minute segments per hour is also sensitive and reproducible. The 12-lead digital Holter technique is suitable for Q-T analysis and may have advantage compared to the serial recordings of large number of standard 12-lead ECGs in the evaluation of drug effects on the Q-T interval.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.