Risk Stratification of Sudden Cardiac Death – ULTIMATE: Utilising LifeMap to Investigate Malignant Arrhythmia ThErapy

Risk stratification of sudden cardiac death (SCD) remains a challenge. Action potential duration (APD) restitution abnormalities have been shown to be key mechanisms underlying ventricular arrhythmias (VAs) that cause SCD.The Regional Restitution Instability Index (R2I2) and Peak ECG Restitution Slope are novel ECG markers for risk stratification of SCD due to ventricular arrhythmia. They have previously identified patients with ischaemic cardiomyopathy (ICM) at high risk of VA and SCD in both retrospective and prospective studies. However, this technology, which forms part of a clinical tool termed LifeMap, currently requires an invasive approach. The aim of this work was to develop and evaluate noninvasive forms of LifeMap. A technique for programmed electrical stimulation (PES) non-invasively via the device was developed along with an exercise protocol in order to acquire digital surface ECG recordings that could be used to develop noninvasive risk markers of SCD. Special software developed in MATLAB was used to facilitate processing of raw ECG data, ECG measurements and data analysis. A technique for simplifying exercise ECG data to construct restitution curves was also developed and scripted into MATLAB. The PES protocol was successfully applied to a cohort of patients with ICM and implantable cardioverter defibrillators (ICDs) to derive measurements that confirmed the efficacy of R2I2 and PERS that has previously been seen in the prediction of SCD, even when derived using non-invasive electrical stimulation via the ICD.

Non-invasive forms of R2I2 and PERS (R2I2-NI and PERS-NI) were developed and applied to the same cohort of patients. Both R2I2-NI and PERS-NI were higher in patients reaching the endpoint of VA or SCD and were predictive of VA or SCD in this patient group. Non-invasive methods of measuring APD restitution as performed by R2I2 and PERS via PES and R2I2-NI and PERS-NI via exercise have potential clinical utility as markers of SCD risk.