Abstract 19954: Differentially Methylated CpGs Identify Patients at Risk of Post-Operative Atrial Fibrillation After Cardiopulmonary Bypass
Despite advances in anesthesia and surgical techniques, post-operative atrial fibrillation (AF) remains a major risk for patients undergoing cardiac surgery, with an incidence of 27-40% and an association with increased early and late mortality. Published post-op AF prediction models using clinical data have not been broadly implemented and have room for improvement (average area under ROC curve is ~0.70). The objective of this study is to determine whether epigenomic features in the blood, measured in the preoperative period, can add predictive value to stratify patients at risk for AF.
We collected blood samples from 55 adult patients undergoing cardiopulmonary bypass (post-op AF incidence = 36%) and used bisulfite sequencing to map DNA methylation, detecting ~3 million CpGs per sample with 10x coverage. Of the CpGs for which we had coverage in all samples, 2.07% were differentially methylated between patients that developed AF and those that did not. We used the R package Glmnet to perform logistic regression on these CpGs for 40 of the 55 patients using 5-fold cross validation 5,000 times. 381 CpGs were included in 95% of the 5,000 models, suggesting they were stably predictive across patients. With these 381 CpGs as input, we built a final model that incorporated 51 of the CpGs, none of which were significantly correlated with age (corrected p-value ≤0.01), ruling age out as a contributing factor to our model. We tested our model on the remaining 15 patients and found it had 100% sensitivity and 90% specificity.
We compared the methylation differences in the pre-op samples of patients who developed post-op AF versus those who did not. We found 2,415 differentially methylated CpGs (q-value ≤ 0.01, differential of at least 10%), with intergenic regions harboring the largest number of variable CpGs (70% of hyper- and 68% of hypomethylated CpGs). Significant basal methylation differences (p≤0.001 with methylation difference of 10%) were observed in 221 promoters, 219 of which were hypomethylated in the AF incidence group. Our findings demonstrate baseline methylation differences in patients developing post-op AF, suggesting these features may be exploited to improve our understanding of this condition and to develop new therapies.
Author Disclosures: T.H. Kimball: None. E. Monte: None. M. Fischer: None. A. Mahajan: None. T.M. Vondriska: None.
- © 2016 by American Heart Association, Inc.