ArticlebioRxiv : the preprint server for biology2024
Validation of a Demography-Based Adaptive QTc Formula using Pediatric and Adult Datasets Acquired from Humans and Guinea Pigs.
Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: A variety of QT rate-correction (QTc) formulae have been utilized for both clinical and research purposes. However, these formulae are not universally effective, likely due to significant influences of demographic diversity on the QT-HR relationship. To address this limitation, we proposed an adaptive QTc (QTcAd) formula that adjusts to subject demographics (i.e., age). Further, we compared the efficacy and accuracy of the QTcAd formula to other widely used alternatives. Method: Using age as a demographic parameter, we tested the QTcAd formula across diverse age groups with different heart rates (HR) in both humans and guinea pigs. Utilizing retrospective human (n=1360) and guinea pig electrocardiogram (ECG) data from in-vivo (n=55) and ex-vivo (n=66) settings, we evaluated the formula's effectiveness. Linear regression fit parameters of HR-QTc (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 consistently outperformed other formulae across all age groups. For instance, in a 20-year-old human group (n=300), the QTcAd formula successfully nullified the inverse HR-QT relationship (R²=5.1E-09, slope=-3.5E-05), while the Bazett formula (QTcB) failed to achieve comparable effectiveness (R²= 0.20, slope=0.91). Moreover, the QTcAd formula exhibited better accuracy than the age-specific Benatar formula (QTcBe), which overcorrected QTc (1-week human QT: 263.8±14.8 ms, QTcAd: 263.8±7.3 ms, p=0.62; QTcBe: 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 to all other formulae. Furthermore, we demonstrated that the QTcAd formula was not inferior to individual-specific QTc formulae. Conclusion: The demography-based QTcAd formula showed superior performance across human and guinea pig age groups, which may enhance the efficacy of QTc for cardiovascular disease diagnosis, risk stratification, and drug safety testing. What is known: Corrected QT (QTc) is a well-known ECG biomarker for cardiovascular disease risk stratification and drug safety testing. Various QT rate-correction formulae have been developed, but these formulae do not perform consistently across diverse datasets (e.g., sex, age, disease, species). What the study adds: We introduce a novel QTc formula (QTcAd) that adapts to demographic variability, as the parameters can be modified based on the characteristics of the study population. The formula (QTcAd = QT + (|m|*(HR-HR
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