From the bedside of patients contributing samples to large genome-wide association studies for atrial fibrillation (AF), over 100 AF risk loci have been identified. The top locus is near a gene implicated in pulmonary vein formation; the ostia of the pulmonary veins harbor initiating triggers of AF, and isolation of these areas is the cornerstone of ablation therapies for AF. Transcriptomic studies suggest that AF is associated with impaired or overwhelmed responses to cell stress. A dual risk model proposes that in genetically-susceptible individuals, inadequate transcriptional responses to stress predispose to AF in later life. Drugs targeting metabolic, oxidative, or protein handling stress may be novel upstream agents to bring back to the bedside for study in the prevention of AF.
From the *Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, Cleveland, OH
†Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Cleveland, OH
‡Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
Disclosure: The authors have no conflicts of interest to report.
NIH/NHLBI R01 HL111314. American Heart Association Atrial Fibrillation Strategically Focused Research Network grant, 18SFRN34110067, 18SFRN34170013, 18SFRN34140065, 18SFRN34170442 American Heart Association Atrial Fibrillation Strategically Focused Research Network grant. NIH UL1-RR024989—NIH National Center for Research Resources for Case Western Reserve University and Cleveland Clinic Clinical and Translational Science Award. Center of Excellence in Cardiovascular Translational Functional Genomics, Heart & Vascular Institute and Lerner Research Institute funds. Tomsich Atrial Fibrillation Research Fund. Heart & Vascular Institute and Lerner Research Institute Philanthropy funds.
Correspondence: Mina K. Chung, MD, Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, 9500 Euclid Avenue, J2-2, Cleveland, OH 44195. E-mail: email@example.com.