INTRODUCTION
Sudden cardiac death (SCD) is a major cause of preventable mortality,
estimated to be responsible for over 6 million deaths per year
worldwide.1{{86 Myerburg, M Risk stratification of
patients for implantable cardioverter defibrillator (ICD) therapy has
major limitations, particularly for patients at risk due to a
non-ischemic cardiomyopathy, who make up 20% of SCD
cases.2 Current electrophysiological (EP) and
non-invasive predictive methods for the identification of non-ischemic
patients at high risk for SCD have been shown to be
inaccurate.3 The recent DANISH study has further
highlighted the need for better risk stratification in this patient
group.4
Action potential duration (APD) restitution describes the property that
myocardial APD is determined by the length of the preceding diastolic
interval (DI). In silico models suggest that abnormal APD
restitution is arrhythmogenic through two mechanisms: increased
heterogeneity of APD restitution and increased APD restitution slope
steepness.5–8 Body surface electrocardiogram (ECG)
surrogates for APD and DI have been used to successfully plot APD
restitution in dog and swine models and have been shown to correlate
with epicardial unipolar electrograms.9,10 Our
research group has developed two novel, independent, high resolution
12-lead ECG measures of APD restitution pathology: Regional Restitution
Instability Index (R2I2, a measure of APD restitution heterogeneity) and
Peak Electrocardiogram Restitution Slope (PERS, a measure of APD
restitution slope).11 R2I2 and PERS have been shown to
be predictive of ventricular arrhythmia (VA)/death in three cohorts of
patients with ischemic cardiomyopathy, and to be independent of standard
risk markers.11,12 The aim of this study was to
explore the application of R2I2 and PERS as risk stratification markers
in a cohort of patients with non-ischemic cardiomyopathy.