Association of atrial fibrillation risk alleles and response to acute rate control therapy.

OBJECTIVES: Given the sparse evidence for selection of first-line therapy for acute atrial fibrillation (AF) based on clinical factors alone, incorporation of genotype data may improve the effectiveness of treatment algorithms and advance the understanding of interpatient heterogeneity. We tested whether candidate nucleotide polymorphisms (SNPs) related to AF physiologic responses are associated with ventricular rate control after intravenous diltiazem in the emergency department (ED). METHODS: We conducted an analysis within a prospective observational cohort of ED patients with acute symptomatic AF, ventricular rate >110 beats per minute within the first 2 hours, initially treated with intravenous diltiazem, and who had DNA available for analysis. We evaluated 24 candidate SNPs that were grouped into 3 categories based on their phenotype response (atrioventricular nodal [AVN] conduction, resting heart rate, disease susceptibility) and calculated 3 genetic scores for each patient. Our primary outcome was maximum heart rate reduction within 4 hours of diltiazem administration. Multivariable regression was used to identify associations with the outcome while adjusting for age, sex, baseline heart rate, and diltiazem dose. RESULTS: Of the 142 patients, 127 had complete data for the primary outcome. None of the genetic scores for AVN conduction, resting heart rate, or AF susceptibility showed a significant association with maximal heart rate response. CONCLUSION: Using a candidate SNP approach, screening for genetic variants associated with AVN conduction, resting heart rate, or AF susceptibility failed to provide significant data for predicting successful rate control response to intravenous diltiazem for treating acute AF in the ED.

Gender differences in management and clinical outcomes of atrial fibrillation patients.

BACKGROUND: Prior research has identified gender differences in the epidemiology and clinical management of atrial fibrillation (AF). The primary aim of this study is to systematically analyze a cohort of AF men and women and evaluate their baseline demographics, treatment, and clinical outcomes by gender. METHODS: We examined the records of 5976 (42% women) consecutive AF patients who were prescribed at least one anti-arrhythmic drug between 2006 and 2013. From this cohort, 4311 (72%) patients had anticoagulation data available and were included in the final analysis. Time to clinical events was assessed using survival analysis and adjusted for covariates using Cox regression. RESULTS: Compared to men, women were older (73 years vs. 67 years, p<0.001), had higher CHADS2 scores (1.9 vs. 1.5, p<0.001), and fewer cardiac comorbidities. Compared to men, women were more often prescribed sotalol and less often dofetilide (p<0.001). Women were also less likely to be anticoagulated (76.8% vs. 82.5%, p<0.001). Over a mean follow-up of 40 months, women were more likely to die (HR 1.21, p=0.037) or to have an ischemic stroke (HR 1.35, p=0.058). Women also had higher rates of atrioventricular-nodal ablation (adjusted HR 2.11, p<0.001) and pacemaker implantation (adjusted HR 1.69, p<0.001) procedures, but lower rates of electrical cardioversions, AF ablations, and maze surgeries. CONCLUSIONS: There are significant gender differences in baseline demographics and clinical outcomes of AF patients. Women have higher mortality and ischemic strokes and are less often prescribed anticoagulation therapy despite higher CHADS2 scores. These data have important clinical implications.