Ventricullar Fibrillation Dynamics Reveal Regional Assymmetry in Resilience to Cardiac Arrest and Predict Clinical Outcomes. - Clinical talk
Ventricular Fibrillation (VF) is the leading cause of sudden cardiac death. Despite its significant social and healthcare burden, 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 pigs with and without established myocardial infarction. In vivo multipolar-catheter recordings revealed that VF early maintenance is 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 global ischemia conditions 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 ischemia, 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 further evaluated in patients with VF events, where ECG-derived AR patterns resembled those documented in pigs. Moreover, high ECG-derived ARs prior to first defibrillation-shocks during out-of-hospital VF events were associated with favorable neurological outcomes. In conclusion, VF dynamics are modulated by asymmetric myocardial tolerance to global ischemia, with fast ARs predicting favorable clinical outcomes.