Evaluation of a 12-Lead Digital Holter System for 24-Hour QT Interval Assessment

Abstract

Background: Drug induced QT prolongation may precipitate life threatening cardiac arrhythmias. Evaluation of the QT prolonging effect of new pharmaceutical agents in a ‘thorough QT/QTc study’ is being mandated by FDA. The purpose of this study was to evaluate an automated 12-lead digital Holter system for a thorough QT/QTc study. Methods: Five healthy volunteers underwent 24-hour digital Holter monitoring. Each recording underwent a fully automated QT analysis (AQA) followed by an onscreen complete manual over read (MOR). Each recording was analyzed twice at least 2 weeks apart. The effect of data sampling (5-min segment/hour), the system sensitivity to detect 5-ms increase in QT, and the ability to assess circadian variation were evaluated. Results: The AQA resulted in identical QT for the first and second analyses, but with obvious errors in QT measurements. Compared to the complete onscreen MOR, the mean QT was longer with AQA (416 ± 41 vs. 387 ± 30 ms, p < 0.001), correlation; r = 0.3. The reproducibility of AQA with complete MOR was very good (QT: 387 ± 30 vs. 387 ± 30 ms, coefficient of variation: 0.2%, r = 0.986. The 5-min mean QT intervals correlated well with the hourly mean QT intervals (r = 0.994, p < 0.001, coefficient of variation = 1 ms) and both showed a similar circadian variation. The system was sensitive to detect a 5-ms change in QT intervals (5 ± 2 ms, coefficient of variation = 0.6%, r = 0.998, p < 0.001). Conclusions: The AQA is not an acceptable method, while the automatic analysis with complete MOR is a highly sensitive and reproducible method. Data sampling by analyzing 5-min segments per hour is sensitive and reproducible.

QT interval prolongation during spontaneous episodes of hypoglycaemia in type 1 diabetes: the impact of heart rate correction

“…In outpatient settings using fully automatic measurements of QT and CGM, QTc has been reported to lengthen to a greater degree than seen in this study [4,13]. However, the use in these studies of fully automatic measurements of QT without manual over-read has been associated with significantly longer QT intervals and measurement errors [15]. Therefore, results obtained using automatic measurements without manual review should be interpreted with caution.…”

“…Hypoglycaemia can increase heart rate [14], and a significant change in QTc during hypoglycaemia could merely reflect overcorrection by Bazett's formula. In addition, fully automatic measurements of QT intervals from Holter monitor data without visual inspection by a human observer, as has been done in some studies [4,13], might lead to significant errors [15].…”

Holter Monitoring in the Evaluation of Congenital Long QT Syndrome

“…In addition, there may be some utility for Holter monitoring as a noninvasive assessment of appropriate β‐blockade; however, this likely can be assessed using other methods. There have been some reports of newer ambulatory measurement devices, which may be more accurate in assessment of QTc, and the potential utility of these devices remains unclear 26 …”

A Rapid Method to Evaluate Cardiac Repolarization Changes: The Effect of Two Coffee Strengths on the QT Interval

“…The position of the cursors indicating the beginning of the QRS complex and the end of the T wave were visually evaluated and their positions adjusted (if needed). The system has been validated for QT/QTc analysis [15]. RR and QT intervals were determined for every 30-min period and transferred to an electronic database for further analysis.…”