TY - JOUR
T1 - Noninvasive detection of spatiotemporal activation-repolarization interactions that prime idiopathic ventricular fibrillation
AU - Cluitmans, Matthijs J.M.
AU - Bear, Laura R.
AU - Nguyên, Uyên C.
AU - van Rees, Bianca
AU - Stoks, Job
AU - ter Bekke, Rachel M.A.
AU - Mihl, Casper
AU - Heijman, Jordi
AU - Lau, Kevin D.
AU - Vigmond, Edward
AU - Bayer, Jason
AU - Belterman, Charly N.W.
AU - Abell, Emma
AU - Labrousse, Louis
AU - Rogier, Julien
AU - Bernus, Olivier
AU - Haïssaguerre, Michel
AU - Hassink, Rutger J.
AU - Dubois, Rémi
AU - Coronel, Ruben
AU - Volders, Paul G.A.
N1 - Publisher Copyright: © 2021 The Author.
PY - 2021/11/17
Y1 - 2021/11/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85121973019&partnerID=8YFLogxK
U2 - https://doi.org/10.1126/scitranslmed.abi9317
DO - https://doi.org/10.1126/scitranslmed.abi9317
M3 - Article
C2 - 34788076
SN - 1946-6234
VL - 13
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 620
M1 - abi9317
ER -