Rate-Correction Technique for QT Interval in Long-Term Telemetry ECG Recording in Beagle Dogs.

Abstract

The establishment of a new rate-correction method for the QT interval is presented for long-term telemetry ECG recording in free-moving beagle dogs. First, in order to define the QT-RR relation to derive the correction formula, the diurnal variations of the QT and RR intervals and the influencing factors were analyzed, and the QT-RR regression coefficient beta was estimated under various conditions: steady and non-steady states of animal, light and dark periods, and over 24 h. In the results, the diurnal rhythm of the QT interval was synchronized with the RR interval reflecting the physical and emotional states of the animal. The coefficient beta had considerable variation during the day: beta; 0.276 +/- 0.052 (maximum to minimum: 0.495 to 0.153). Thus, it was considered that the ideal rate-correction technique for telemetry ECG requires the selection of a flexible coefficient beta adjusted to the condition of the measurement. Therefore, rate-correction utilizing analysis of covariance estimating the coefficient beta for each dog, was compared with previously proposed formulas which fix the rate-correction coefficient, based on the capacity to dissociate the effects of heart rate on the QT interval. This was then tested by the levels of discrimination apparent in the QT prolongation caused by a class III antiarrhythmic drug, which ranked the formulas on the levels of correction achieved as follows: covariance adjustment > Matsunaga > Van de Water > Bazett. Thus, the rate-correction method utilizing analysis of covariance is proven adequate for data from telemetry ECG recordings.

Prediction of drug-induced QT interval prolongation in telemetered common marmosets

“…Based on linear regression analysis of QTc interval against RR interval, we found that individual rate correction in accordance with the analysis of covariance (Miyazaki and Tagawa, 2002) best corrected the effect of RR interval on QT interval in comparison with the generic formulas tested. When corrected using the individual correction method, the QT-prolonging drugs tested showed QTc interval prolongation, whereas the non-QT-prolonging drugs did not show QTc interval prolongation, suggesting that the marmoset telemetry model has potential to be utilized in prediction of a drug's liability to lengthen QTc interval in humans.…”

“…However, these standard correction formulas have been shown to have limitations in comparison with the new approach of finding the relationship in an individual (Miyazaki and Tagawa, 2002). As with telemetry studies in other species (Miyazaki and Tagawa, 2002;Kano et al, 2005;Holzgrefe et al, 2007), with common marmosets the individual method showed better corrections than both traditional formulas, although the corrections from Bazett's were nearly comparable. Nifedipine, which has no QT-prolonging risk in clinic, was reported to cause tachycardia and false QTc interval prolongation in a canine telemetry study using Fridericia's formula (Toyoshima et al, 2005).…”

“…General correction formulas from Bazett (Bazett, 1920) and Fridericia (Fridericia, 1920) have been used to evaluate the QT liability of drugs in dogs and monkeys (Toyoshima et al, 2005;Ando et al, 2005;Hanson et al, 2006), however, an individual rate correction was recently proposed to be more appropriate (Miyazaki and Tagawa, 2002;Holzgrefe et al, 2007). However, there has been no information available on this individual QT/RR correction method used with common marmosets.…”

QT PRODACT: Sensitivity and Specificity of the Canine Telemetry Assay for Detecting Drug-Induced QT Interval Prolongation

“…The QT-RR relationship varies depending on each condition of measurement, for example, under the free-moving condition (7), under the restraint condition in a sling (13), and under the anesthetized condition (14). The QT-RR relation also varies depending on the method of data sampling and / or data analysis, for example, averaged QT-RR plots (15) versus beat-to-beat QT-RR plots (16) and QT-RR plots from a group of animals (9) versus QT-RR plots from individual animals (8). Therefore, the previously recommended QT-RR model would not necessarily provide the optimal fit for the telemetry data used in this investigation.…”

“…Although Bazett's and Fridericia's formulas as correc-tion methods are the most frequently used in dogs as well as humans (4 -6), they have been questioned due to the over-correction at faster heart rates and undercorrection at slower heart rates (7 -9). Lately, although the rate-correction optimized for each subject has been recommended for dogs as well as humans (8,10), how much the individual subject correction can improve the sensitivity and specificity compared to the generic QTc formulas has not been evaluated.…”