Beat-to-beat repolarization variability in LQTS patients with the SCN5A sodium channel gene mutation

Current techniques evaluating beat-to-beat variability of repolarization re ly on accurate determination of T wave endpoints. This study proposes a T w ave endpoint-independent method to quantify repolarization variability in a standard 12-lead ECG using a wavelet transformation. Our method was used t o identify repolarization variability in long QT syndrome patients (LQTS) w ith the SCN5A sodium channel gene mutation. Using wavelet transformations b ased on the second Gaussian derivative, we evaluated repolarization variabi lity in 11 LOTS patients with the mutation, 13 noncarrier family members, a nd 28 unrelated healthy subjects. Time-domain repolarization variability pa rameters (SDRTo, SDRTm) and wavelet parameters describing temporal (beat-to -beat) variability of repolarization in time (TVT) and in amplitude (TVA) w ere analyzed. Reproducibility of wavelet parameters and relationship of wav elet-based variability with heart rate and preceding RR interval were inves tigated. The wavelet-based method quantified beat-to-beat variability of th e entire repolarization segment (regardless of QT interval identification) providing insight into variability in repolarization morphology. Our method showed that SCN5A carriers have significantly increased repolarization var iability in amplitude (23% +/- 24% vs 8 +/- 4%, P < 0.001) and in time (14 +/- 17 ms vs 3 +/- 2 ms, P < 0.004) compared to noncarriers. Variability of repolarization amplitude was found to be heart rate dependent with variabi lity decreasing with increasing heart rate. Relative error describing repro ducibility of TVA and TVT was less than or equal to 5% and less than or equ al to 10%, respectively. Our method quantifies repolarization variability i n amplitude and in time without the need to identify T or U wave endpoints, wavelet-detected repolarization variability contributes to phenotypic iden tification of SCN5A carriers, with more pronounced beat-to-beat variability in repolarization amplitude than in time.