Introduction The prognostic significance of beat-to-beat variability of spatial heterogeneity of repolarization measured from standard 12-lead ECG is not well-understood. Methods We measured the short-term variability of repolarization parameters, such as T-wave heterogeneity in leads V4–V6 (TWH) and QT interval (QT), from five consecutive beats of previously recorded standard 12-lead ECG in 200 victims of unexpected sudden cardiac death (SCD) confirmed to be due to complicated atherosclerotic coronary artery disease (CAD) in medico-legal autopsy and 200 age- and sex-matched controls with angiographically confirmed CAD. The short-term variability of repolarization heterogeneity was defined as the standard deviation (SD) of the measured repolarization parameters. All ECGs were in sinus rhythm, and no premature ventricular contractions were included in the measured segment. Results TWH-SD and QT-SD were significantly higher in SCD victims than in subjects with CAD (6.9 ± 5.6 μV vs. 3.8 ± 2.6 μV, p = 1.8E-11; 8.3 ± 13.1 ms vs. 3.8 ± 7.1 ms, p = 0.00003, respectively). After adjusting in the multivariate clinical model with factors, such as diabetes, RR interval, and beta blocker medication, TWH-SD and QT-SD retained their significant power in discriminating between the victims of SCD and the patients with CAD ( p = 0.00003, p = 0.006, respectively). TWH-SD outperformed QT-SD in identifying the SCD victims among the study subjects (area under the curve in the receiver operating characteristics curve 0.730 vs. 0.679, respectively). Conclusion Increased short-term variability of repolarization heterogeneity measured from standard 12-lead ECG is associated with SCD.

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Background The possible relationship between temporal variability of electrocardiographic spatial heterogeneity of repolarisation and the risk of sudden cardiac death (SCD) in patients with coronary artery disease (CAD) is not completely understood. Purpose To investigate the prognostic value of temporal variability of T-wave spatial heterogeneity in SCD in patients with CAD. Methods The Innovation to reduce Cardiovascular Complications of Diabetes at the Intersection (ARTEMIS) study population consisted of 1,946 patients with angiographically verified CAD. T-wave morphology dispersion (TMD), which estimates the average angle between all reconstruction vector pairs in T-wave loop based on leads I-II and V2-V6, was analysed on beat-to-beat basis from 10 minutes period of the baseline electrocardiographic recording in 1,678 study subjects. The temporal variability of TMD was evaluated by standard deviation of TMD (TMD-SD). Results After on average of 7.4±2.0 years of follow-up, a total of 47 of the 1,678 study subjects (2.8%) had experienced SCD or were resuscitated from sudden cardiac arrest (SCA). TMD-SD was significantly higher in patients who had experienced SCD/SCA compared with those who remained alive (3.64±2.57 vs. 2.65±2.54, p<0.01, respectively), but did not differ significantly between the patients who had experienced non-sudden cardiac death (n=40, 2.4%) and those who remained alive (2.98±2.43 vs. 2.67±2.55, p=0.45, respectively) or between the patients who succumbed to non-cardiac death (n=88, 5,2%) and those who stayed alive (2.74±2.44 vs. 2.67±2.55, p=0.81). After adjustments with relevant clinical risk indicators of SCD/SCA, such as left ventricular ejection fraction, diabetes, left bundle branch block and Canadian Cardiac Society class, TMD-SD still predicted SCD/SCA (HR 1.113, 95% CIs 1.028–1.206, p<0.01). The discrimination and reclassification accuracy increased significantly (p=0.02, p=0.033) and the C-index increased from 0.733 to 0.741 when TMD-SD was added to the clinical risk model of SCD/SCA. The Kaplan-Meier survival curves show proportional probabilities of event-free survival for different modes of death for patients classified according to the optimised TMD-SD cut-off point (Figure). Figure 1 Conclusions Temporal variability of electrocardiographic spatial heterogeneity of repolarisation represented by TMD-SD independently predicts long-term risk of SCD/SCA in patients with CAD. Acknowledgement/Funding Sigrid Juselius Foundation and Finnish Foundation for Cardiovascular Research