WHY IT IS TIME TO ABANDON THE ALMOST 100 YEAR OLD WAYS TO ADJUST THE QT INTERVAL FOR HEART RATE AND ADOPT A NEW MODERN APPROACH



Simon W. Rabkin, M.D., University of British Columbia, Vancouver, BC, Canada

Assessment of the QT interval is an important marker for drug-induced cardiac toxicity and risk of sudden death. The most frequently used formulae to correct the QT for heart rate (QTc) were developed, almost 100 years ago in 1920 by Bazett (QTcBZT) using the square root of the heart rate and Fridericia (QTcFRD) using the cubed root of the heart rate. These equations are not optimal because (i) they assume a certain formula for the QT-RR relationship that may not be valid across the heart rate range (ii) they poorly correct for the effect of heart rate on the QT interval in large epidemiologic data bases such as the US National Health and Nutrition Examination Survey (NHANES) (iii) data from the same patient with increased heart rate produced by exercise showed discordant changes between QTcBZT and QTcFRD (iv) using QTcBZT or QTcFRD ignores the impact of age on QTc.

A new approach, the spline QT correction, was developed, from 13,627 ECGs in the NHANES data, using a cubic regression spline with four knots with an adjustment for gender and sex. Regression analysis showed the lack of relationship between heart rate and the spline QTc. The spline QTc was superior (significantly more flat i.e. no relationship with heart rate) compared to QTcBZT or QTcFRD. Age and sex factors were built into the new formula, if needed, providing the percentile of the QTc from this population data. Increasing heart rate with exercise showed little effect on QTc spline while QTcBZT increased and QTcFRD decreased with exercise.

Conclusion: It is time to adopt a new modern approach based on a functionally agnostic modeling of population ECG data. QTc spline can be readily applied to a specific patient, considers their age and sex, and indicates the percentile ranking in the population.