Prediction of sudden and non-sudden cardiac death in post-infarction patients with reduced left ventricular ejection fraction by periodic repolarization dynamics: MADIT-II substudy

AIMS: To test the value of Periodic Repolarization Dynamics (PRD), a recently validated electrocardiographic marker of sympathetic activity, as a novel approach to predict sudden cardiac death (SCD) and non-sudden cardiac death (N-SCD) and to improve identification of patients that profit from ICD-implantation. METHODS AND RESULTS: We included 856 post-infarction patients with left-ventricular ejection fraction (LVEF) ≤30% of the MADIT-II trial in sinus rhythm. Of these, 507 and 348 patients were randomized to ICD or conventional treatment. PRD was assessed from multipolar 10-min baseline ECGs. Primary and secondary endpoints were total mortality, SCD and N-SCD. Multivariable analyses included treatment group, QRS-duration, New York Heart Association classification, blood-urea nitrogen, diabetes mellitus, beta-blocker therapy and LVEF. During follow-up of 20.4 months, 119 patients died (53 SCD and 36 N-SCD). On multivariable analyses, increased PRD was a significant predictor of mortality (standardized coefficient 1.37[1.19–1.59]; P < 0.001) and SCD (1.40 [1.13–1.75]; P = 0.003) but also predicted N-SCD (1.41[1.10–1.81]; P = 0.006). While increased PRD predicted SCD in conventionally treated patients (1.61[1.23–2.11]; P < 0.001), it was predictive of N-SCD (1.63[1.28–2.09]; P < 0.001) and adequate ICD-therapies (1.20[1.03–1.39]; P = 0.017) in ICD-treated patients. ICD-treatment substantially reduced mortality in the lowest three PRD-quartiles by 53% (P = 0.001). However, there was no effect in the highest PRD-quartile (mortality increase by 29%; P = 0.412; P < 0.001 for difference) as the reduction of SCD was compensated by an increase of N-SCD. CONCLUSION: In post-infarction patients with impaired LVEF, PRD is a significant predictor of SCD and N-SCD. Assessment of PRD is a promising tool to identify post-MI patients with reduced LVEF who might benefit from intensified treatment.