Background Atherosclerotic animal models show increased recruitment of inflammatory cells to the heart following myocardial infarction (MI), which impacts ventricular function and remodeling. Objective To determine whether increased myocardial inflammation following MI also contributes to arrhythmias. Methods MI was created in 3 mouse models: 1) atherosclerotic (ApoE−/− on atherogenic diet; n=12), 2) acute inflammation (wild-type [WT] given daily lipopolysaccharide [LPS], 10µg/day; n=7), and 3) WT (n=14). Sham-operated (n=4) mice were also studied. Four days post-MI, an inflammatory protease-activatable fluorescent probe (Prosense680) was injected intravenously to quantify myocardial inflammation on day 5. Optical mapping with voltage-sensitive dye was performed on day 5 to assess electrophysiology and arrhythmia susceptibility. Results Inflammatory activity (Prosense680 fluorescence) was increased approximately 2-fold in ApoE+MI and LPS+MI hearts versus WT+MI (p<0.05) and 3-fold versus Sham (p<0.05). ApoE+MI and LPS+MI hearts also had prolonged action potential duration, slowed conduction velocity, and increased susceptibility to pacing-induced arrhythmias (56% and 71%; vs. 13% for WT+MI and 0% for Sham, respectively, p<0.05 for ApoE+MI and LPS+MI groups versus both WT+MI and Sham). Increased macrophage accumulation in ApoE+MI and LPS+MI hearts was confirmed with immunofluorescence. Macrophages were associated with areas of connexin-43 (Cx43) degradation and a 2-fold decrease in Cx43 expression was found in ApoE+MI versus WT+MI hearts (p<0.05). ApoE+MI hearts also had a 3-fold increase in interleukin-1β expression, an inflammatory cytokine known to degrade Cx43. Conclusions Underlying atherosclerosis exacerbates post-MI electrophysiological remodeling and arrhythmias. LPS+MI hearts fully recapitulate the atherosclerotic phenotype, suggesting myocardial inflammation as a key contributor to post-MI arrhythmia.

URL: http://www.clinicaltrials.gov. Unique identifier: NCT02997254.

OBJECTIVE To investigate mechanisms by which atrial fibrillation (AF) may terminate during ablation near the pulmonary veins before the veins are isolated (PVI). INTRODUCTION It remains unstudied how AF may terminate during ablation before PVs are isolated, or how patients with PV reconnection can be arrhythmia-free. We studied patients in whom PV antral ablation terminated AF before PVI, using 2 independent mapping methods. METHODS We studied patients with AF referred for ablation, in whom bi-atrial contact basket electrograms were studied by both an activation/phase mapping method and by a second validated mapping method reported not to create false rotational activity. RESULTS In 22 patients (age 60.1±10.4, 36% persistent AF), ablation at sites near the PVs terminated AF (77% to sinus rhythm) prior to PVI. AF propagation revealed rotational (n=20) and focal (n=2) patterns at sites of termination by mapping method 1 and method 2. Both methods showed organized sites that were spatially concordant (p<0.001) with similar stability (p<0.001). Vagal slowing was not observed at sites of AF termination. DISCUSSION PV antral regions where ablation terminated AF before PVI exhibited rotational and focal activation by two independent mapping methods. These data provide an alternative mechanism for the success of PVI, and may explain AF termination before PVI or lack of arrhythmias despite PV reconnection. Mapping such sites may enable targeted PV lesion sets and improved freedom from AF.

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