Abstract 16499: Preamyloid Oligomers are Present in Human Atrium and Are Associated With Post-Operative Atrial Fibrillation
The basic pathophysiology of atrial fibrillation (AF) remains poorly understood. In a cellular model of AF, we observed transcriptional upregulation of proteins implicated in amyloidosis, a pathological finding also observed in human AF. Current evidence indicates that preamyloid oligomers (PAOs) are the primary cytotoxic species in amyloidosis, although not detectable by Congo red staining. We hypothesized that PAOs can develop in human atrium, and that their occurrence is linked to the development of AF. Atrial tissue was harvested from 72 patients undergoing elective cardiac surgery with preserved left ventricular function (LVEF>40%) and no history of heart failure, arrhythmias, or systemic/cardiac amyloidosis. Immunostaining was performed using A-11, a conformation-specific antibody to detect PAOs, and a myocardial-specific antibody (MF-20). Using confocal imaging, a reproducible method was developed to quantify PAO (green) distribution relative to myocardial surface area (red), or green/red [G/R] ratio. Mean age of the group was 61 years (median 63, range 21-80). Surgical procedures included aortic valve replacement (n=46), mitral valve replacement/repair (n=22), and coronary artery bypass grafting (n=18; some patients had multiple procedures). Imaging revealed that when PAOs were present, their distribution was heterogeneous within an atrial sample. Using a general linear model analysis, we found that the G/R ratio was significantly higher in patients who developed post-operative AF compared to those who did not (mean 0.117 [95% confidence intervals 0.101 - 0.132] versus 0.090 [0.079 - 0.100]; P=0.004, n=22, 50). While there was a trend for PAO burden to increase with hypertension, this was not statistically significant, and no relationship was evident for diabetes mellitus or sex. Our results are the first report to identify PAOs in human atrium. Moreover, in this cohort, we found that PAO burden is increased in patients who develop post-operative AF. These data support the hypothesis that preamyloid oligomers play a role in the genesis of AF.
- © 2011 by American Heart Association, Inc.