ClinicalTrials.gov Identifier: NCT01944514.

Introduction Sudden cardiac death (SCD) risk assessment is limited, particularly in patients with nonischemic cardiomyopathies. This is the first application, in patients with cardiomyopathies, of two novel risk markers, regional restitution instability index (R2I2) and peak electrocardiogram restitution slope (PERS), which have been shown to be predictive of ventricular arrhythmias (VA) or death in ischemic heart disease patients. Methods Blinded retrospective study of 50 patients: 33 dilated cardiomyopathy and 17 other; undergoing electrophysiological study (EPS) for SCD risk stratification, and 29 controls with structurally normal hearts undergoing EPS. R2I2 was calculated from an EPS using electrocardiogram surrogates for action potential duration and diastolic interval. Cut‐offs for high and low R2I2/PERS were predefined. Results R2I2 was significantly higher in study than control patients (0.99 ± 0.05 vs. 0.63 ± 0.04, p < .001). PERS showed a trend to higher values in the study group (1.18[0.63] vs. 1.09[0.54], p = .07). During median follow up of 5.6 years [interquartile range 1.9 years], nine study patients reached the endpoint of VA/death. Patients who experienced VA/death showed trends to higher mean R2I2 (1.14 ± 0.07 vs.0.95 ± 0.05, p = .12) and PERS (1.46[0.49] vs. 1.13[0.62], p = .22). A Cox proportional hazards model using grouped markers: R2I2 < 1.03 + PERS < 1.21/either R2I2 ≥ 1.03 or PERS ≥ 1.21/R2I2 ≥ 1.03 + PERS ≥ 1.21; significantly predicted VA/death (p = .02) with a hazard ratio per positive component of 3.2 (95% confidence interval 1.2–8.8). Conclusion R2I2≥ 1.03 + PERS ≥ 1.21 may predict VA/death in patients with cardiomyopathies. R2I2 ≥ 1.03 + PERS ≥ 1.21 have the potential to play an important role in SCD risk stratification in cardiomyopathies but their validity should be confirmed in a larger study.

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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 predefined 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 nonsignificantly 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.

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