Validation of a Demography-Based Adaptive QT Correction Formula Using Pediatric and Adult Datasets Acquired From Humans and Guinea Pigs.

Abstract

Background: QT correction (QTc) formulae are widely used in clinical and research settings but often underperform, possibly due to demographic influences on the QT-heart rate (HR) relationship. To address this limitation, we developed an adaptive QTc (QTcAd) formula, which adjusts for demographic factors like age, and compared its efficacy to other standard formulae.

Methods: The QTcAd formula was tested across diverse age groups with different HR in both humans and guinea pigs. Using retrospective ECG data from 1819 pediatric patients at Children's National Hospital and 2400 subjects from the Pediatric Heart Network database, alongside in vivo (n=55) and ex vivo (n=66) guinea pig ECG recordings, we evaluated the formula's effectiveness. Linear regression fit parameters of QTc-HR (slope and R²) were utilized for performance assessment. To evaluate the accuracy of the predicted QTc, we acquired epicardial electrical and optical voltage data from Langendorff-perfused guinea pig hearts.

Results: In both human subjects and guinea pigs, the QTcAd formula (QTcAd=QT+(|m|×(HR-HR_mean)) consistently outperformed other formulae across all age groups. For instance, in a 20-year-old human group, the QTcAd formula successfully nullified the inverse QT-HR relationship (R²=5.1×10^-10, slope=-3.5×10^-5), whereas the Bazett formula failed to achieve comparable effectiveness (R²=0.21, slope=0.91). Moreover, the QTcAd formula exhibited better accuracy than the age-specific Benatar QTc formula, which overcorrected QTc (1-week human QT: 263.8±14.8 ms, QTcAd: 263.8±7.3 ms, P=0.62; Benatar QTc: 422.5±7.3 ms, P<0.0001). The optically measured pseudo-QT interval (143±22.5 ms, n=44) was better approximated by QTcAd (180.6±17.0 ms) compared with all other formulae. Furthermore, we demonstrated that the QTcAd formula was not inferior to individual-specific QTc formulae.

Conclusions: The demography-based QTcAd formula showed superior performance across human and guinea pig age groups, which may enhance the efficacy of rate-corrected QTc for cardiovascular disease diagnosis, risk stratification, and drug safety testing in children and adults.