Ventricular fibrillation dynamics reveal regional asymmetry in resilience to cardiac arrest and predict clinical outcome

Ventricular fibrillation (VF) is the leading cause of sudden cardiac death. Nevertheless, the mechanisms underlying VF dynamics in structurally normal hearts and infarct-related substrates remain incompletely understood. We aimed to characterize the electrophysiological, structural and molecular properties that explain VF dynamics during early phases (seconds) and long-duration episodes (minutes) in experimental pig models. Additionally, we assessed the clinical impact of VF dynamics on neurological prognosis following resuscitated cardiac arrest.

A total of 72 pigs were included in the study. In vivo multipolar-catheter recordings revealed that early VF dynamics are independent of the infarct-related substrate. Healthy and infarcted animals consistently showed higher activation rates (AR) in the right ventricle (RV) than in the left ventricle (LV), and this gradient further increased during long-duration VF. Ex vivo panoramic optical mapping of long-duration VF episodes resembling cardiac arrest conditions confirmed in vivo findings and revealed earlier electrical depression in the LV. AR gradients during VF were primarily driven by an asymmetric response to the global ischaemia conditions intrinsically associated with VF, during which the RV exhibited greater resilience than the LV. Computational simulations, incorporating experimentally derived electrophysiological properties and region-specific metabolic parameters during ischaemia, demonstrated that the fibrillating RV preserves higher excitability than the LV, creating RV-to-LV AR gradients during VF. The translational relevance of these findings was evaluated in patients with VF events, in whom long-term (>2 min) ECG-derived AR patterns (N = 3) resembled those documented in pigs. Moreover, in 60 patients with out-of-hospital cardiac arrest, ECG-derived ARs prior to the first defibrillation shock for VF were associated with favourable neurological outcome.

VF dynamics are modulated by asymmetric myocardial tolerance to global ischaemia. Among patients admitted after a VF-related cardiac arrest event, higher ARs prior to the first defibrillation shock are predictive of a favourable neurological outcome.