Regional Heterogeneity in Determinants of Atrial Matrix Remodeling and Association with Atrial Fibrillation Vulnerability Post-Myocardial Infarction -…

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Heart Rhythm. 2022 Jan 20:S1547-5271(22)00092-3. doi: 10.1016/j.hrthm.2022.01.022. Online ahead of print.

ABSTRACT

BACKGROUND: Left ventricular (LV) remodeling following a myocardial infarction (MI) is associated with new onset atrial fibrillation (AF). LV remodeling post-MI is characterized by regional changes in matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs), causing extracellular matrix (ECM) remodeling.

OBJECTIVE: This study tested the hypothesis that a shift in regional atrial MMP activity, MMP/TIMP expression, and ECM remodeling occurs post-MI, which cause increased vulnerability to AF.

METHODS: MI was induced in pigs (25 kg; coronary ligation; n=9), and at approximately 14 days post-MI, an atrial electrical stimulation protocol was performed. Following which, an MMP radiotracer was infused, MMP/TIMP mRNA profiling performed, and ECM collagen assessed by histochemistry. An additional 7 non-MI pigs served as controls.

RESULTS: AF could be induced in 89% (8/9) of the post-MI pigs but none of the controls. MMP activity (MMP radiotracer uptake) increased by approximately 2-fold in most atrial regions post-MI, whereas fibrillar collagen content was unchanged or actually reduced in right atrial regions and increased in left atrial regions. MMP/TIMP profiles revealed a heterogeneous pattern from the left atrial appendage to right atrial regions.

CONCLUSION: AF vulnerability early post-MI was associated with a heterogeneous pattern of atrial ECM remodeling, detectable by non-invasive molecular imaging. Detection of early atrial MMP activation post-MI may help define the myocardial substrate underlying AF.

PMID:35066183 | DOI:10.1016/j.hrthm.2022.01.022

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Regional Heterogeneity in Determinants of Atrial Matrix Remodeling and Association with Atrial Fibrillation Vulnerability Post-Myocardial Infarction -...