The impact of varying autonomic states on the dynamic beat-to-beat QT-RR and QT-TQ interval relationships.
The beat-to-beat dynamicity of the QT-RR interval relationship is difficult to assess with the use of traditional correction factors (QTc) and changes in QTc do not accurately reflect or quantify arrhythmogenic risk. Further, the interpretation of arrhythmogenic risk is influenced by autonomic state. To visualize the QT-RR interval dynamics under varying conditions of autonomic state from impaired repolarization, we have developed a system to sequentially plot the beat-to-beat confluence of ECG data or 'clouds' obtained from conscious dogs and humans. To represent the non-uniformity of the clouds, a bootstrap sampling method that computes the mathematical centre of the uncorrected beat-to-beat QT value (QTbtb) and defines the upper and lower 95% confidence bounds is used. The same method can also be used to examine heterogeneity, hysteresis (both acceleration and deceleration) and restitution (beat-to-beat QT-TQ interval relationship). Impaired repolarization with the combination of E-4031 and L-768,673 (inhibitor of IKs current) increased heterogeneity of restitution at rest 55-91%; increased hysteresis during heart rate acceleration after isoproterenol challenge by approximately 40-60%; and dramatically diminished the minimum TQ boundary by 72% to only 28 ms. Impaired repolarization alters restitution during normal sinus rhythm and increases hysteresis/heterogeneity during heart rate acceleration following sympathetic stimulation. These findings are supported by similar clinical observations in LQT1 and LQT2 syndromes. Therefore, the assessment of the dynamic QT-RR and QT-TQ interval relationships through quantification of heterogeneity, hysteresis and restitution may allow a more accurate non-invasive evaluation of the conditions leading to cardiac arrhythmia.
Fossa
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Cardiovascular Safety, iCardiac Technologies Inc, Rochester, NY 14618, USA. anthony.fossa@icardiac.com
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001341:Autonomic Nervous System / Q000378:metabolism*; D064420:Drug-Related Side Effects and Adverse Reactions; D004562:Electrocardiography / Q000379:methods*; D006321:Heart / Q000502:physiology* / Q000503:physiopathology; D006801:Humans; D018570:Risk Assessment / Q000379:methods