Ventricular Arrhythmia Risk Assessment with Novel Time-Frequency Analysis of Signal-Averaged Electrocardiograms

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Chow, Ryan
Ventricular Arrhythmia , Implantable Cardioverter Defibrillator , Risk Stratification , Electrocardiogram
Background: Ventricular arrhythmia is a prevalent and dangerous cause of sudden cardiac death. Implantable cardioverter defibrillators (ICD) are devices that can detect and terminate ventricular arrhythmia, but current risk stratification methods offer limited prediction of arrhythmic events when selecting patients for ICD implantation. Furthermore, better methods are needed to identify ICD patients at greater risk of ventricular arrhythmia than others. Layered Symbolic Decomposition frequency (LSDf) is a signal processing metric that quantifies abnormal frequency content in signal-averaged electrocardiogram recordings. The aims of this study were to 1) determine if LSDf is predictive of adverse outcomes in an ICD patient cohort 2) identify if LSDf is related to known electrical parameters. Methods and Results: For Aim 1, fifty-two ICD patients were recruited from 2008-2009. These were followed for a mean 8.5±0.4 years for the primary outcome of first appropriately treated ventricular arrhythmia or death. Thirty-four subjects met the primary outcome. LSDf was significantly lower and 12-lead QRS duration was significantly greater in patients meeting the primary outcome (12.14±3.97%, n=34vs. 16.45±3.73% n=18; p=0.001) and (111.59±14.96 ms, n=34 vs. 97.69±13.51 ms, n=18; p=0.012) respectively. A 13.25% LSDf threshold (0.74 sensitivity and 0.85 specificity) was selected based on Receiver Operating Characteristic analysis. Kaplan-Meier analysis was conducted; patients above the 13.25% threshold demonstrated significantly better survival outcomes (p<0.001). Cox multivariate regression analysis compared the LSDf threshold (13.25%) to LVEF (28.5%), 12-lead QRSd (100 ms), age, % male sex, NYHA classification, and antiarrhythmic usage. LSDf was a predictor of the primary outcome (p=0.005) and just ventricular arrhythmia (p=0.002). Subsequent physiological experiments for Aim 2 were conducted to determine if LSDf was related to ventricular conduction velocity (n=7), ventricular effective refractory period (n=13), or the presence of abnormal substrate (n=10) These patients were recruited from June 2011, March 2018, and April 2018, respectively. LSDf did not significantly change in normal patients after administration of procainamide or ibutilide. Patients undergoing catheter ablation for ventricular arrhythmia had significant greater LSDf following ablation (7.78% vs 9.40%, n=10 p<0.001). Electroanatomic mapping of low-voltage areas indicated LSDf may have an association with low-voltage areas in the ventricles (Spearman r= -0.81).
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