Proarrhythmic atrial structural and molecular remodeling with advancing age. Implications for post-coronary artery bypass grafting atrial fibrillation occurrence

Abstract

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by a grant of the Romanian Ministry of Education and Research, CNCS-UEFISCDI Background Advancing age has been identified as a strong predictor of post-coronary artery bypass grafting (CABG) atrial fibrillation (AF). However, the exact substrate underlying this increased aging-related propensity to post-CABG AF remains insufficiently understood. Purpose We aimed to assess whether a preexisting electrical, structural, autonomic, and/or molecular remodeling could explain the increased risk of elderly individuals for post-CABG AF occurrence. Methods Thirty-one consecutive patients free of AF history scheduled for an elective CABG procedure were prospectively evaluated. All patients underwent continuous ECG monitoring prior to and following the CABG procedure, up to the day of discharge. The occurrence of post-CABG AF was recorded. The right atrial appendage, normally considered "surgical waste", was collected and divided into 3 samples that were used for single cell action potential recordings using the microelectrode technique, for histological, and mRNA analysis. Electrical remodeling preexistent to CABG was assessed by P-wave analysis (i.e., amplitude, duration, fragmentation) using 12-lead surface ECG and Lewis leads recordings and atrial action potential analysis (i.e., amplitude, duration). Atrial structural remodeling was evaluated using echocardiographic (i.e., left atrial [LA] area and antero-posterior diameter) and histological (i.e., fibrosis and fat tissue infiltration) parameters. Autonomic remodeling was evaluated using heart rate variability analysis based on the pre-CABG Holter ECG recordings. Molecular remodeling was assessed by mRNA analysis of several genes previously incriminated in AF occurrence (i.e., CACNA1C, GJA5, KCNE2, KCNJ2, KCNQ1, and SCN5A). Results Post-CABG AF occurred in 11 (35.4%) patients. Patients with post-CABG AF were significantly older than their non-arrhythmic counterparts (65.2 ± 5.8 years vs. 58.0 ± 10.4 years; p = 0.04). Age above 59 years predicted post-CABG AF with 81.8% sensitivity and 57.9% specificity. All analyzed electrical and autonomic parameters were similar between patients above and below the age of 59 years (all p >0.05). However, patients >59 years had significantly higher LA area and diameter (both p< 0.01), more important atrial fatty infiltration (p = 0.02), and significantly lower mRNA expression of SCN5A (p = 0.01). Conclusion In the present cohort, post-CABG AF occurrence was 3.4-fold more common in patients >59 years than in their younger peers. Although there was no evidence of aging-related cellular electrical or autonomic remodeling, elderly individuals presented significantly more important LA dilation and atrial fatty infiltration, and significantly lower expression of SCN5A, encoding for Na+ channels. These changes could contribute to the increased aging-related propensity to post-CABG AF by altering intra-atrial conduction and promoting reentry.