Evolution of Substrate for Ventricular Arrhythmias Early Postinfarction: Insights From a Porcine Ischemia-Reperfusion Model

Background: The evolution of myocardial scar and its arrhythmogenic potential postinfarct is incompletely understood.

Objectives: This study sought to investigate scar and border zone (BZ) channels evolution in an animal ischemia-reperfusion injury model using late gadolinium enhancement cardiac magnetic resonance (LGE-CMR).

Methods: Five swine underwent 90-minute balloon occlusion of the mid-left anterior descending artery, followed by LGE-CMR at day (d) 3, d30, and d58 postinfarct. Invasive electroanatomic mapping (EAM) was performed at 2 months. Topographical reconstructions of LGE-CMR were analyzed for left ventricular core and BZ scar, BZ channel geometry, and complexity, including transmurality, orientation, and number of entrances/exits.

Results: LVEF reduced from 48.0% ± 1.8% to 41.3% ± 2.3% postinfarct. Total scar mass reduced over time (P = 0.008), including BZ (P = 0.002) and core scar (P = 0.05). A total of 72 BZ channels were analyzed across all animals and timepoints. Channel length (P = 0.05) and complexity (P = 0.02) reduced progressively from d3 to d58. However, at d58, 64% of channels were newly formed and 36% were midmyocardial. Conserved channels were initially longer and more complex. All LGE-CMR channels colocalized to regions of maximal decrement on EAM, with significantly greater decrement (115 ± 31 ms vs 83 ± 29 ms; P < 0.001) and uncovering of split potentials (24.8% vs 2.6%; P < 0.001) within channels. In total, 3 of 5 animals had inducible VT and tended to have more channels with greater midmyocardial involvement and functional decrement than those without VT.

Conclusions: BZ channels form early postinfarct and demonstrate evolutionary complexity and functional conduction slowing on EAM, highlighting their arrhythmogenic potential. Some channels regress in complexity and length, but new channels form at 2 months' postinfarct, which may be midmyocardial, reflecting an evolving, 3-dimensional substrate for VT. LGE-CMR may help identify BZ channels that may support VT early postinfarct and lead to sudden death.