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Mechanisms Underlying QT Interval Adaptation behind Heart Rate during Stress Test

Abstract:

QT interval adaptation lag after heart rate (HR) has been proposed as an arrhythmic risk marker. The delay between QT and HR in a stress test has been shown to progressively reduce when approaching the stress peak, but the underlying mechanisms are yet unclear. We used a cell model coupling an electrophysiological human ventricular cardiomyocyte model with a beta- adrenergic signaling model to gain insight into these mechanisms. We paced the cell according to HR time series measured from patients' stress test recordings and we searched for the beta -adrenergic stimulation pattern making the action potential duration (APD) response to HR changes best replicate the corresponding QT response. After adjusting the beta -adrenergic stimulation pattern, the simulated APD trends presented similar behavior to the measured QT trends for the same HR time series. The optimal pattern involved a sharp increase in beta -adrenergic stimulation close to the stress test peak. During stress test recovery, the almost constant delay between QT and HR could be explained by a fast return from high beta -adrenergic stimulation to baseline levels. In conclusion, time-varying beta -adrenergic stimulation patterns with high stimulation levels around the stress peak contribute to explain the characteristics of QT adaptation to HR during stress tests.