Rationale and study design of the MINERVA study: Multicentre Investigation of Novel Electrocardiogram Risk markers in Ventricular Arrhythmia prediction-UK multicentre collaboration

Abstract

Introduction: The purpose of this study is to assess the ability of two new ECG markers (Regional Repolarisation Instability Index (R2I2) and Peak Electrical Restitution Slope) to predict sudden cardiac death (SCD) or ventricular arrhythmia (VA) events in patients with ischaemic cardiomyopathy undergoing implantation of an implantable cardioverter defibrillator for primary prevention indication.

Methods and analysis: Multicentre Investigation of Novel Electrocardiogram Risk markers in Ventricular Arrhythmia prediction is a prospective, open label, single blinded, multicentre observational study to establish the efficacy of two ECG biomarkers in predicting VA risk. 440 participants with ischaemic cardiomyopathy undergoing routine first time implantable cardioverter-defibrillator (ICD) implantation for primary prevention indication are currently being recruited. An electrophysiological (EP) study is performed using a non-invasive programmed electrical stimulation protocol via the implanted device. All participants will undergo the EP study hence no randomisation is required. Participants will be followed up over a minimum of 18 months and up to 3 years. The first patient was recruited in August 2016 and the study will be completed at the final participant follow-up visit. The primary endpoint is ventricular fibrillation or sustained ventricular tachycardia >200 beats/min as recorded by the ICD. The secondary endpoint is SCD. Analysis of the ECG data obtained during the EP study will be performed by the core lab where blinding of patient health status and endpoints will be maintained.

Ethics and dissemination: Ethical approval has been granted by Research Ethics Committees Northern Ireland (reference no. 16/NI/0069). The results will inform the design of a definitive Randomised Controlled Trial (RCT). Dissemination will include peer reviewed journal articles reporting the qualitative and quantitative results, as well as presentations at conferences and lay summaries.

Trial registration number: NCT03022487.

Keywords: heart failure; ischaemic heart disease; pacing & electrophysiology.

Conflict of interest statement

Competing interests: The University of Leicester has applied for a patent for the R2I2 and PERS ECG markers on behalf of WBN and GAN. GAN reports research fellow support from Boston Scientific Ltd and Abbott Ltd.AM’s salary is supported by Abbott (formerly St Jude Medical).

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Study flow chart. EP, electrophysiological; ICD, implantable cardioverter-defibrillator; PI, Principal Investigator.

Figure 2

Example of captured stimulus. For valid data, the final two S1 of the drive train and S2 must successfully capture in succession, or else the drive train should be repeated.

Figure 3

Derivation of Regional Restitution Instability Index (R2I2) and Peak ECG Restitution Slope (PERS). (A) Stimulation protocol demonstrating the fiducial points of TpeakQ and QTpeak (blue) which are required to plot on the restitution curve (B) gradients are fitted for each 40 ms overlapping least square linear segment. The mean of the SD of gradient differences from the mean gradient is taken as the R2I2. The mean of the peak restitution curve slope is calculated to be the PERS value (reproduced with permission from Nicolson 2014).