Differences between QT and RR intervals in digital and digitized paper electrocardiograms: contribution of the printer, scanner, and digitization process.
ABSTRACT Prints of electrocardiograms (ECGs) are often sent to core laboratories, where they are scanned, converted to a digital format, and read on-screen. These ECGs may differ from the original ECG because of variability introduced by the printer, scanner, or digitization software.
Digital ECGs were recorded in 50 volunteers simultaneously using electrocardiographs from 2 different manufacturers. QT and RR intervals were measured on-screen on the digitized ECGs. To study the contribution of individual steps in the digitization process, differences in RR interval between 2 prints each of 50 digital ECGs, 2 scanned files of 50 prints, 2 digitized files from 50 scanned files, and 2 readings of 50 digitized ECGs (intrareader variability) were analyzed.
Repeatability coefficient for RR interval measurement was 18.5 milliseconds for machine 1 and 21 milliseconds for machine 2. Contributions of the printer were 6.5 milliseconds for machine 1 and 9.0 milliseconds for machine 2, digitization process was 5.5 milliseconds, and reader variability was 8.0 milliseconds. Variability of the scanner was negligible.
The printer and digitization process account for significant differences in interval measurements in digitized ECGs.
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ABSTRACT: Following reports of death from cardiac arrhythmias with drugs like terfenadine and cisapride, the International Conference for Harmonization formulated a guidance (E14) document. This specifies that all new drugs must undergo a 'thorough QT/QTc' (TQT) study to detect drug-induced QT prolongation, a surrogate marker of ventricular tachycardia, especially torsades de pointes (TdPs). With better understanding of data from several completed TQT studies, regulatory requirements have undergone some changes since the E14 guidance was implemented in October 2005. This article reviews the implications of the E14 guidance and the changes in its interpretation including choice of baseline QT, demonstration of assay sensitivity, statistical analysis of the effect of new drug and positive control, and PK-PD modelling. Some issues like use of automated QT measurements remain unresolved. Pharmaceutical companies too are modifying Phase 1 studies to detect QTc liability early in order to save time and resources. After the E14 guidance, development of several drugs that prolong QTc by >5 ms is being abandoned by sponsors. However, all drugs that prolong the QT interval do not increase risk of TdP. Researchers in regulatory agencies, academia and industry are working to find better biomarkers of drug-induced TdP which could prevent many useful drugs from being prematurely abandoned. Drug-induced TdP is a rare occurrence. With fewer drugs that prolong QT interval reaching the licensing stage, knowing which of these drugs are torsadogenic is proving to be elusive. Thus, paradoxically, the effectiveness of the E14 guidance itself has made prospective validation of new biomarkers difficult.British Journal of Pharmacology 09/2009; 159(1):34-48. · 5.07 Impact Factor