When the Usual Suspects Turn Up in the ICU: Searching for Genetic Clues to Atrial Fibrillation

OBJECTIVE–: New-onset atrial fibrillation (New AF) during critical illness is an independent risk factor for mortality. The ability to identify patients at high risk for new AF is limited. We hypothesized that genetic susceptibility contributes to risk of new AF in the ICU. DESIGN–: Retrospective sub-study of a prospective observational cohort study. SETTING–: Medical and general surgical ICUs in a tertiary academic medical center. PATIENTS–: 1,369 critically ill patients admitted to the ICU for at least 2 days with no known history of AF who had DNA available for genotyping. INTERVENTIONS–: None. MEASUREMENTS–: We genotyped 21 single nucleotide polymorphisms (SNPs) associated with AF in ambulatory studies using a Sequenom platform. We collected demographics, medical history, and development of new AF during the first four days of ICU admission. MAIN RESULTS–: New AF occurred in 98 (7.2%) patients and was associated with age, male sex, coronary artery disease, and vasopressor use. SNPs associated with new AF were rs3853445 (near PITX2, p = 0.0002), rs6838973 (near PITX2, p = 0.01), and rs12415501 (in NEURL, p = 0.03) on univariate testing. When controlling for clinical factors, rs3853445 (odds ratio [OR]: 0.47, 95% confidence interval [CI]: 0.30–0.73, p = 0.001) and rs12415501 (OR: 1.72, 95% CI: 1.27–2.59 p = 0.01) remained significantly associated with new AF. The addition of genetic variables to clinical factors improved new AF discrimination in a multivariable logistic regression model (C-statistic 0.78 vs 0.82, p = 0.0009). CONCLUSIONS–: We identified several SNPs associated with new AF in a large cohort of critically ill ICU patients, suggesting there is genetic susceptibility underlying this common clinical condition. This finding may provide new targets for future mechanistic studies and additional insight into the application of genomic information to identify patients at elevated risk for a common and important condition in the ICU.