22Combining a novel electrical restitution based biomarker with heart rate variability analysis improves prediction of sudden cardiac death risk

Abstract

Introduction: Sudden cardiac death (SCD) remains a significant cause of mortality worldwide. Current SCD risk markers have substantial limitations. Peak Electrical Restitution Slope (PERS) is a promising new SCD risk marker. PERS uses the surface 12-lead ECG to measure peak restitution gradient, a property of myocardium known to play a role in ventricular arrhythmogenesis. By combining PERS with heart rate variability (HRV) analysis, we sought to improve SCD risk prediction in patients with ischaemic cardiomyopathy (ICM). Methods: Blinded, prospective, observational study of 44 ICM patients (>18 years of age) undergoing risk stratification for an implantable cardioverter defibrillator. Patients underwent programmed ventricular stimulation for determination of PERS. Surface ECG surrogates for action potential duration (QRS-onset to T-peak) and diastolic interval (T-peak to QRS-onset) were used to measure peak restitution gradient. Patients underwent 24-hour ambulatory ECG monitoring to determine time-domain HRV (standard deviation of normal to normal RR intervals [SDNN]). A pre-defined SDNN cut off (100ms) was combined with an optimal PERS cut-off (1.21) to determine if combining these risk markers could improve SCD risk stratification. Results: During median follow up of 22 months, 11 patients experienced ventricular arrhythmia (VA)/SCD. PERS was significantly higher in patients experiencing VA/SCD than those not (mean±SEM:1.73±0.27 vs 1.07±0.08, p=0.002). PERS was independent of age, gender, left ventricular ejection fraction, QRS duration and SDNN in prediction of endpoint (Cox model, p=0.002). Patients with low SDNN (<100ms) experienced a non-significantly higher rate of VA/SCD than those with high SDNN (33% vs 19%, p=0.24). Patients with PERS ≥ 1.21 and SDNN<100ms had a hazard ratio for VA/SCD 17.4 times that of patients negative for both (Cox model, p=0.01). Kaplan Meier analysis (Figure 1) showed significant separation in rates of VA/SCD in patients stratified by PERS and SDNN (log-rank, p=0.002). Conclusions: Combining PERS with SDNN identifies patients at particularly high risk of ventricular arrhythmia/SCD. A combined PERS + SDNN risk marker may improve SCD risk stratification in patients with ischaemic cardiomyopathy. ![Graphic][1] Figure 1 Kaplan-Meier curves illustrating rates of VA/SCD in patients stratified using PERS and SDNN. [1]: /embed/inline-graphic-1.gif