The QT interval duration in a surface ECG is dependent on the heart rate as well as the history of heart rate because the QT interval duration requires time to adapt to any heart rate acceleration or deceleration. An increase or decrease in heart rate is followed by up to several minutes of QT interval changes which, if not accounted for, can lead to a significant increase in the variability of measurement. Two important requirements are necessary to obtain valid QTc measurements from standard 10-second ECGs:

1) The QT measurement needs to be performed at repolarization steady-state.
2) The QT measurement needs to be controlled or corrected for heart rate.

In a standard ECG recording, satisfying both conditions is technically challenging because the 10-second ECG recording does not provide enough data to properly account for the effect of heart rate adaptation on QT.

iCardiac Technologies’ TQT Plus Tools identify and flag periods of steady-state repolarization in the QT intervals of continuous ECG recordings. This computerized method provides reproducible, consistent and cost-effective measurements in cardiac safety studies. Additionally, iCardiac’s COMPAS Holter Bin method, provides a reliable method to control for heart rate changes and has proven to be an indispensable tool for the study of drugs that affect heart rate.

Correcting QT intervals for heart rate allows for comparing repolarization measurements obtained at different heart rates, either between subjects or within the same subject. Traditional correction methods (e.g., Bazett’s, Fridericia, pooled or individual formulae) simplify computation, but the utility of these methods for drug safety studies has been widely criticized. Linear correction formulae under-estimate the QT interval at slow heart rates and over-estimate it at fast rates. The use of a mathematical function that characterizes the QT-RR relationship and is generalized to any patient represents a questionable approach because the QT-RR relationship has been reported to be subject dependent. Also, under normal physiologic conditions, such as eating, sleeping, exercising, and changing emotional states the QT-RR relationship can diverge substantially from the linear model (see Figure 4). In the cardiac safety studies of drugs that may affect the heart rate, the mathematical correction method may lead to over- or under-estimated results. If used at all, linear methods should be supplemented by methods that more accurately model QT-RR dynamics (see COMPAS Holter Bin method).

Figure 4. QT/RR slopes for 6 healthy normal subjects. QT/RR relationship is subject dependent. 

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