ECG analysis of ventricular fibrillation dynamics reflects ischaemic progression subject to variability in patient anatomy and electrode location

Background: Ventricular fibrillation (VF) is the deadliest arrhythmia, often caused by myocardial ischaemia. VF patients require urgent intervention planned quickly and non-invasively. However, the accuracy with which electrocardiographic (ECG) markers reflect the underlying arrhythmic substrate is unknown. Methods: We analysed how ECG metrics reflect the fibrillatory dynamics of electrical excitation and ischaemic substrate. For this, we developed a human-based computational modelling and simulation framework for the quantification of ECG metrics, namely, frequency, slope, and amplitude spectrum area (AMSA) during VF in acute ischaemia for several electrode configurations. Simulations reproduced experimental and clinical findings in 21 scenarios presenting variability in the location and transmural extent of regional ischaemia, and severity of ischaemia in the remote myocardium secondary to VF. Results: Regional acute myocardial ischaemia facilitated re-entries, potentially breaking up into VF. Ischaemia in the remote myocardium modulated fibrillation dynamics. Cases presenting a mildly ischaemic remote myocardium yielded sustained VF, enabled by the high proliferation of phase singularities (PS, 11–22) causing remarkably disorganised activation patterns. Conversely, global acute ischaemia induced stable rotors (3–12 PS). Changes in frequency and morphology of the ECG during VF reproduced clinical findings but did not show a direct correlation with the underlying wave dynamics. AMSA allowed the precise stratification of VF according to ischaemic severity in the remote myocardium (healthy: 23.62–24.45 mV Hz; mild ischaemia: 10.58–21.47 mV Hz; moderate ischaemia: 4.82–11.12 mV Hz). Within the context of clinical reference values, apex-anterior and apex-posterior electrode configurations were the most discriminatory in stratifying VF based on the underlying ischaemic substrate. Conclusion: This in silico study provides further insights into non-invasive patient-specific strategies for assessing acute ventricular arrhythmias. The use of reliable ECG markers to characterise VF is critical for developing tailored resuscitation strategies.