Discrete sites of frequent premature ventricular complexes cluster within the infarct border zone and coincide with high frequency of delayed afterdepolarizations under adrenergic stimulation

Autor: Dylan Vermoortele, Sebastian Ingelaere, Karin R. Sipido, Stijn De Buck, Piet Claus, Chandan K. Nagaraju, H. Llewelyn Roderick, Eef Dries, Rik Willems, Matthew Amoni, Bert Vandenberk
Rok vydání: 2021
Předmět:
Zdroj: Heart rhythm. 18(11)
ISSN: 1556-3871
Popis: BACKGROUND: Sympathetic activation in ischemic heart disease can cause lethal arrhythmias. These often are preceded by premature ventricular complexes (PVCs), which at the cellular level could result from delayed afterdepolarizations. OBJECTIVE: The purpose of this study was to identify and map vulnerable areas for arrhythmia initiation after myocardial infarction (MI) and to explore the link between PVCs and cellular events. METHODS: Anterior-septal wall MI was induced by 120 minutes of coronary occlusion followed by reperfusion (27 MI and 16 sham pigs). After 4 weeks, EnSite™ electroanatomic mapping combined with imaging was performed to precisely locate PVC sites of origin and subsequently record monophasic action potentials. Cardiomyocytes were isolated from different regions to study regional cellular remodeling. Isoproterenol was used as a surrogate for adrenergic stimulation both in vivo and in cardiomyocytes. RESULTS: PVCs originated from the MI border zone (BZ) and occurred at discrete areas with clusters of PVCs within the BZ. At these sites, frequent delayed afterdepolarizations and occasional associated spontaneous action potentials translating to a PVC were present. Cardiomyocytes isolated from the MI BZ exhibited more spontaneous action potentials than cardiomyocytes from remote regions. Sensitivity to adrenergic stimulation was increased in MI, in vivo and in cardiomyocytes. In awake, freely moving MI animals, frequent PVCs, ventricular arrhythmia, and sudden cardiac death occurred spontaneously at moderately elevated heart rates. CONCLUSION: Post-MI, arrhythmias initiate from discrete vulnerable areas within the BZ, where delayed afterdepolarizations, related to increased adrenergic response of BZ cardiomyocytes, can generate PVCs. ispartof: HEART RHYTHM vol:18 issue:11 pages:1976-1987 ispartof: location:United States status: published
Databáze: OpenAIRE