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Title: Prospective evaluation of two novel ECG-based restitution biomarkers for prediction of sudden cardiac death risk in ischaemic cardiomyopathy.
Authors: Nicolson, William B.
McCann, Gerry P.
Smith, Matthew I.
Sandilands, Alastair J.
Stafford, Peter J.
Schlindwein, Fernando S.
Samani, Nilesh J.
Ng, G. André
First Published: 4-Aug-2014
Publisher: BMJ Publishing Group, British Cardiovascular Society
Citation: Heart, 2014, 100 (23), pp. 1878-1885
Abstract: OBJECTIVE: To improve prediction of sudden cardiac death (SCD) in patients with ischaemic cardiomyopathy (ICM). Electrical heterogeneity is known to contribute to risk of SCD. We have previously developed Regional Restitution Instability Index (R2I2), an ECG-based biomarker, which quantifies cardiac electrical instability by measuring heterogeneity in electrical restitution, and demonstrated its potential utility for risk stratification in a retrospective analysis of patients with ICM. Here, we examined R2I2 in a prospective ICM cohort and also tested the predictive value of another ECG-based biomarker, Peak ECG Restitution Slope (PERS). METHODS: Prospective, blinded, observational study of 60 patients with ICM undergoing implantable cardioverter defibrillator risk stratification. R2I2 was calculated from an electrophysiological study (EPS) using ECG surrogates for action potential duration and diastolic interval. R2I2 quantifies inter-lead electrical restitution heterogeneity. PERS was the peak restitution curve slope taken as a mean across the 12 ECG leads. Endpoints were ventricular arrhythmia (VA)/SCD. RESULTS: Over median follow-up of 22 months, 16 (26.6%) patients achieved endpoint. R2I2 was significantly higher in these patients compared with those without an event (mean ± SEM: 1.11 ± 0.09 vs 0.84 ± 0.04, p=0.003) as was PERS (median(IQR): 1.35(0.60) vs 1.08(0.52), p=0.014). R2I2≥1.03, the cut-off used in our previous study, identified patients with a significantly higher risk of VA/SCD independent of EPS result, LVEF or QRS duration with a relative risk of 6.5 (p=0.008). Patients positive for R2I2 and PERS had a relative risk of VA/SCD 21.6 times that of those negative for R2I2 and PERS (p<0.0001). CONCLUSIONS: R2I2 and PERS each independently and in combination, identify patients with ICM that are at high risk of developing ventricular arrhythmias (VA). R2I2/PERS represent promising risk markers for SCD discrimination. TRIAL REGISTRATION NUMBER: Identifier: NCT01944514.
DOI Link: 10.1136/heartjnl-2014-305672
eISSN: 1468-201X
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2014, BMJ Publishing Group, British Cardiovascular Society. Deposited with reference to the publisher’s open access archiving policy. (
Description: Additional material is published online only. To view please visit the journal online (
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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