Elsevier

Heart Rhythm

Volume 18, Issue 11, November 2021, Pages 1976-1987
Heart Rhythm

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

https://doi.org/10.1016/j.hrthm.2021.07.067Get rights and content
Under a Creative Commons license
open access

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.

Keywords

Action potential
Delayed afterdepolarization
Myocardial infarction
Noncontact electroanatomic mapping
Premature ventricular complex

Cited by (0)

Funding sources: This work was supported by the Fund for Scientific Research-Flanders (FWO Project Grants G.0918.15 and G097021N; Senior Clinical Investigator Fellowship to Dr Willems and Junior Research Fellowship to Dr Amoni); and by the BOF Research Fund of KU Leuven to Drs Willem and Claus). Disclosures: The authors have no conflicts of interest to disclose.

1

Dr Karin R. Sipido and Dr Rik Willems are shared last authors.