Noninvasive detection of spatiotemporal activation-repolarization interactions that prime idiopathic ventricular fibrillation

Matthijs J M Cluitmans*, Laura R Bear, Uyên C Nguyên, Bianca van Rees, Job Stoks, Rachel M A Ter Bekke, Casper Mihl, Jordi Heijman, Kevin D Lau, Edward Vigmond, Jason Bayer, Charly N W Belterman, Emma Abell, Louis Labrousse, Julien Rogier, Olivier Bernus, Michel Haïssaguerre, Rutger J Hassink, Rémi Dubois, Ruben CoronelPaul G A Volders

*Corresponding author for this work

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Abstract

A comprehensive understanding of the interaction between triggers and electrical substrates leading to ventricular fibrillation (VF) and sudden cardiac arrest is lacking, and electrical substrates are difficult to detect and localize with current clinical tools. Here, we created repolarization time (RT) dispersion by regional drug infusion in perfused explanted human (n = 1) and porcine (n = 6) hearts and in a computational model of the human ventricle. Arrhythmia induction was tested with a single ventricular extrastimulus applied at the early or late RT region. Arrhythmias could only be induced from early RT regions. Vulnerability to VF increased with RT gradient steepness and with larger areas of early RT, but not with markers on the body-surface electrocardiogram. Noninvasive electrocardiographic imaging was performed in survivors of idiopathic VF (n = 11), patients with frequent premature ventricular complexes (PVCs) but no history of sudden cardiac arrest (n = 7), and controls (n = 10). In survivors of idiopathic VF, RT gradients were steeper than in controls, without differences in the clinical electrocardiogram, consistent with the ex vivo results. Patients with idiopathic VF also showed local myocardial regions with distinctly early-versus-late RT that were more balanced in size than in controls. Premature beats originated more often from the early RT regions in idiopathic VF survivors than in patients with frequent PVCs only. Thus, idiopathic VF emerges from the spatiotemporal interaction of a premature beat from an early-repolarization region with critical repolarization dispersion in that region. Electrocardiographic imaging can uncover the co-occurrence of these abnormalities.

Original languageEnglish
Article numbereabi9317
Number of pages10
JournalScience Translational Medicine
Volume13
Issue number620
DOIs
Publication statusPublished - 17 Nov 2021

Keywords

  • SUDDEN CARDIAC DEATH
  • DE-POINTES
  • ARRHYTHMIA
  • ABNORMALITIES
  • MECHANISMS
  • ALTERNANS
  • SUBSTRATE
  • REENTRY

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