Abstract 2114: Impaired Repolarization Adaptation to Heart-Rate Changes Identifies IKr-Inhibition in the Congenital and Acquired form of the long QT Syndrome
Background: Prolongation of the QTc is not a perfect surrogate marker of the presence of an increased risk for arrhythmic events. In the congenital form of the long QT syndrome (LQTS), 10 to 15 % of patients carrying a HERG mutation do not have QT prolongation. In the acquired LQTS, polymorphic ventricular tachycardia occurs in individuals on Ikr-blocking drugs, often with minimal QT prolongation. Thus, we investigated the role of repolarization adaptation to heart rate changes for identifying the presence of abnormal Ikr kinetics in the congenital and acquired form of the LQTS.
Method: Our investigation is based on 5 study groups: genotyped LQT1 patients (n=49, 35f), genotyped LQT2 (n=25, 19f), healthy individuals (n=37, 11f) on and off sotalol after a single (SD:160 mg, n=37) and a double dose (DD:320 mg, n=21). Twelve-lead digital Holter ECGs were acquired in LQTS patients and during periods on and off drug in the healthy groups. The analysis was performed in all leads during the diurnal period. We investigated various repolarization parameters and their heart rate dependency including QT interval and T-wave amplitude.
Results: The results from lead II reveal a loss of heart rate dependency of the amplitude of the T-wave as a common feature in individuals with decreased Ikr kinetics (LQT2 and subjects receiving sotalol).The table⇓ provides the values of T-amplitude/RR and QT/RR slopes in all groups. The impaired adaptation induced by sotalol was dose dependent. QT/RR slope was not signifcantly different between the LQTS mutations.
Conclusion: Impaired adaptation of T-wave amplitude is a common electrocardiographic feature associated with HERG mutation and the Ikr-blocking drug sotalol. This ECG marker may play an important role in the future of assessment of both the penetrance of HERG-mutation and the Ikr-related cardiotoxicity of drugs.