Measure of the QT-RR Dynamic Coupling in Patients with the Long QT Syndrome

Background: The patients with the long QT syndrome type-1 (LQT-1) have an impaired adaptation of the QT interval to heart rate changes. Yet, the description of the dynamic QTRR coupling in genotyped LQT-1 has never been thoroughly investigated. Method: We propose a method to model the dynamic QTRR coupling by defining a transfer function characterizing the relationship between a QT interval and its previous RR intervals measured from ambulatory Holter recordings. Three parameters are used to characterize the QTRR coupling: a fast gain (GainF), a slow gain (GainL), and a time constant (t). We investigated the values of these parameters across genders, and in genotyped LQT-1 patients with normal QTc interval duration (QTc < 470 ms). Results: The QTRR dynamic profiles are significantly different between LQT-1 patients (97) and controls (154): LQT-1 have longer QTc interval (453 +/- 35 vs. 384 +/- 26 ms, P < 0.0001), and an increased dependency of the QT interval to previous RR changes revealed by a larger GainL (0.22 +/- 0.06 vs. 0.18 +/- 0.07, P < 0.0001) and GainF (0.05 +/- 0.02 vs. 0.03 +/- 0.01, P < 0.0001). Importantly, LQT-1 patients have a faster QT dynamic response to previous RR changes described by t: 122 +/- 44 vs. 172 +/- 92 beats (P < 0.0001). This faster QT dynamic response of the QTRR dynamic coupling remained in LQT-1 patients with QTc in a normal range (<430 ms). Conclusions: The measurement of QTRR dynamic coupling could be used in patients suspected to carry a concealed form of the LQT-1 syndrome, or to provide insights into the types of arrhythmogenic triggers a patient may be prone to.