Arrhythmogenecity and thrombogenicity of the residual left atrial appendage stump following surgical exclusion of the appendage in patients with atrial fibrillation.

INTRODUCTION: It is common to find residual stump after the amputation or clip exclusion of the left atrial appendage (LAA). We evaluated the arrhythmogenic and thrombogenic potential of LAA stumps in atrial fibrillation (AF) patients. METHODS: Consecutive patients undergoing catheter ablation for AF recurrence with LAA stump detected at baseline transesophageal echocardiogram (TEE) were included in the analysis. Nonpulmonary vein (non-PV) triggers were ablated based on operator's discretion. RESULTS: A total of 213 patients with LAA stump were included in the analysis. Firing from the LAA stump was detected in 186 cases, of which 145 received stump isolation (group I) and the stump was not targeted for isolation in 41 (group II) patients. In 27 patients with no firing from the stump (group III) only non-PV triggers from sites other than the LAA stump were targeted for ablation. At 16.7 ± 8.5 months of follow-up, 126 (86.9%) patients from group I, eight (19.5%) from group II, and eight (33.3%) from group III remained arrhythmia-free off antiarrhythmic drugs (AAD) (P < 0.001). Sixty out of 70 patients underwent redo procedure; electrical isolation of the stump and ablation of other non-PV triggers was done in all 60 cases. At 1 year after the repeat procedure, 55 (91.7%) patients remained arrhythmia-free off-AAD. A total of four (1.88%) thromboembolic (TE) events reported, three of which were transient ischemic attacks and all three patients had "smoke" detected in the left atrium. CONCLUSION: LAA stump is arrhythmogenic and electrical isolation improves clinical outcome. TE events are rare and mostly associated with left atrial smoke in this subset of AF population.

APOE genotype regulates pathology and disease progression in synucleinopathy.

Apolipoprotein E (APOE) ε4 genotype is associated with increased risk of dementia in Parkinson's disease (PD), but the mechanism is not clear, because patients often have a mixture of α-synuclein (αSyn), amyloid-ß (Aß), and tau pathologies. APOE ε4 exacerbates brain Aß pathology, as well as tau pathology, but it is not clear whether APOE genotype independently regulates αSyn pathology. In this study, we generated A53T αSyn transgenic mice (A53T) on Apoe knockout (A53T/EKO) or human APOE knockin backgrounds (A53T/E2, E3, and E4). At 12 months of age, A53T/E4 mice accumulated higher amounts of brainstem detergent-insoluble phosphorylated αSyn compared to A53T/EKO and A53T/E3; detergent-insoluble αSyn in A53T/E2 mice was undetectable. By immunohistochemistry, A53T/E4 mice displayed a higher burden of phosphorylated αSyn and reactive gliosis compared to A53T/E2 mice. A53T/E2 mice exhibited increased survival and improved motor performance compared to other APOE genotypes. In a complementary model of αSyn spreading, striatal injection of αSyn preformed fibrils induced greater accumulation of αSyn pathology in the substantia nigra of A53T/E4 mice compared to A53T/E2 and A53T/EKO mice. In two separate cohorts of human patients with PD, APOE ε4/ε4 individuals showed the fastest rate of cognitive decline over time. Our results demonstrate that APOE genotype directly regulates αSyn pathology independent of its established effects on Aß and tau, corroborate the finding that APOE ε4 exacerbates pathology, and suggest that APOE ε2 may protect against αSyn aggregation and neurodegeneration in synucleinopathies.