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BACKGROUND - Common single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (rs2200733, rs10033464 near PITX2), 1q21 (rs13376333 in KCNN3), and 16q22 (rs7193343 in ZFHX3) have consistently been associated with the risk of atrial fibrillation (AF). Single-center studies have shown that 4q25 risk alleles predict recurrence of AF after catheter ablation of AF. Here, we performed a meta-analysis to test the hypothesis that these 4 AF susceptibility SNPs modulate response to AF ablation.
METHODS AND RESULTS - Patients underwent de novo AF ablation between 2008 and 2012 at Vanderbilt University, the Heart Center Leipzig, and Massachusetts General Hospital. The primary outcome was 12-month recurrence, defined as an episode of AF, atrial flutter, or atrial tachycardia lasting >30 seconds after a 3-month blanking period. Multivariable analysis of the individual cohorts using a Cox proportional hazards model was performed. Summary statistics from the 3 centers were analyzed using fixed effects meta-analysis. A total of 991 patients were included (Vanderbilt University, 245; Heart Center Leipzig, 659; and Massachusetts General Hospital, 87). The overall single procedure 12-month recurrence rate was 42%. The overall risk allele frequency for these SNPs ranged from 12% to 35%. Using a dominant genetic model, the 4q25 SNP, rs2200733, predicted a 1.4-fold increased risk of recurrence (adjusted hazard ratio,1.3 [95% confidence intervals, 1.1-1.6]; P=0.011). The remaining SNPs, rs10033464 (4q25), rs13376333 (1q21), and rs7193343 (16q22) were not significantly associated with recurrence.
CONCLUSIONS - Among the 3 genetic loci most strongly associated with AF, the chromosome 4q25 SNP rs2200733 is significantly associated with recurrence of atrial arrhythmias after catheter ablation for AF.
© 2015 American Heart Association, Inc.
BACKGROUND - Atrial fibrillation and atrial flutter (AF/AFL) are the most common arrhythmias encountered in clinical practice. Rate versus rhythm control remains a difficult decision, especially in the acute setting. Ibutilide is a class III antiarrhythmic indicated for pharmacological cardioversion of recent-onset AF/AFL. At the University of Texas MD Anderson Cancer Center, restoration of sinus rhythm is desirable because many patients have contraindications to anticoagulation. In addition, most are on multiple medications that prolong the QT interval; therefore, the objective of this study was to establish the safety and efficacy of ibutilide.
METHODS - This was a retrospective chart review of 81 patients who were identified via the pharmacy database as receiving ibutilide for AF/AFL from January 2002 to May 2006. Outcomes including cardioversion rates and effects on the QT interval were recorded.
RESULTS - Ibutilide use was associated with successful cardioversion in 75% of patients. Out of 81 patients, 68 patients (84%) were on at least 1 medication that prolonged the QT interval at the time of ibutilide administration. However, no significant changes in the corrected QT interval pre and post ibutilide cardioversion were noted in any group of patients.
CONCLUSIONS - Overall, ibutilide is safe and effective in cancer patients when used for acute cardioversion of AF/AFL. Despite the use of multiple medications that can potentially prolong the QT interval, no patient experienced serious life-threatening rhythm disturbances or significant QT prolongation during ibutilide administration.
Atrial fibrillation (AF) is more common in those with obstructive sleep apnea (OSA) than in unaffected subjects and recurs more frequently in the presence of severe OSA after electrical cardioversion and AF ablation. However, it is unknown whether the severity of OSA influences the efficacy of antiarrhythmic drug (AAD) therapy in patients with OSA and AF. The aim of this study was to examine the impact of OSA severity on the treatment of patients with symptomatic AF using AADs. Sixty-one patients (mean age 62 ± 15 years, 21 women) treated with AADs for symptomatic AF who underwent overnight polysomnography were studied. Rhythm control was prospectively defined as successful if a patient remained on the same AAD therapy for ≥6 months with ≥75% reduction in symptomatic AF burden. Twenty-four patients (40%) had severe OSA. Thirty patients (49%) were rhythm controlled with AADs. Nonresponders to AADs were more likely to have severe OSA than milder disease (52% vs 23%, p <0.05); those with severe OSA were less likely to respond to AADs than participants with nonsevere OSA (39% vs 70%, p = 0.02). Nonresponders had higher apnea-hypopnea indexes than responders (34 ± 25 vs 22 ± 18 events/hour, p = 0.05), but there were no differences between these groups in minimum oxygen saturation or percentage of time spent in rapid eye movement sleep. In conclusion, patients with severe OSA are less likely to respond to AAD therapy for AF than those with milder forms of OSA.
Copyright © 2012 Elsevier Inc. All rights reserved.
BACKGROUND - The D1275N SCN5A mutation has been associated with a range of unusual phenotypes, including conduction disease and dilated cardiomyopathy, as well as atrial and ventricular tachyarrhythmias. However, when D1275N is studied in heterologous expression systems, most studies show near-normal sodium channel function. Thus, the relationship of the variant to the clinical phenotypes remains uncertain.
METHODS AND RESULTS - We identified D1275N in a patient with atrial flutter, atrial standstill, conduction disease, and sinus node dysfunction. There was no major difference in biophysical properties between wild-type and D1275N channels expressed in Chinese hamster ovary cells or tsA201 cells in the absence or presence of β1 subunits. To determine D1275N function in vivo, the Scn5a locus was modified to knock out the mouse gene, and the full-length wild-type (H) or D1275N (DN) human SCN5A cDNAs were then inserted at the modified locus by recombinase mediated cassette exchange. Mice carrying the DN allele displayed slow conduction, heart block, atrial fibrillation, ventricular tachycardia, and a dilated cardiomyopathy phenotype, with no significant fibrosis or myocyte disarray on histological examination. The DN allele conferred gene-dose-dependent increases in SCN5A mRNA abundance but reduced sodium channel protein abundance and peak sodium current amplitudes (H/H, 41.0±2.9 pA/pF at -30 mV; DN/H, 19.2±3.1 pA/pF, P<0.001 vs. H/H; DN/DN, 9.3±1.1 pA/pF, P<0.001 versus H/H).
CONCLUSIONS - Although D1275N produces near-normal currents in multiple heterologous expression experiments, our data establish this variant as a pathological mutation that generates conduction slowing, arrhythmias, and a dilated cardiomyopathy phenotype by reducing cardiac sodium current.
BACKGROUND - Atrial fibrillation (AF) is the most common sustained arrhythmia affecting over 700,000 individuals in Japan and 2.2 million in the USA. The proper management of patients with AF is critical due to the well-documented association with heart failure and stroke. A strategy to better define the emergency department (ED) management, admission decisions, and spectrum of risk from low to high is needed.
METHODS AND SUBJECTS - The atrial fibrillation and flutter outcomes and risk determination investigation is a prospective, observational cohort study to develop a multivariable clinical prediction rule that accurately estimates risk for adverse outcomes in patients presenting to the ED with symptomatic AF. We will enroll 430 patients at 2 sites who present to the ED with symptomatic AF defined as a new or established diagnosis of AF or atrial flutter that require ED evaluation for a complaint thought related to their rhythm disturbance. The study's endpoint is to develop an accurate, objective, internally validated, reliable clinical prediction rule to risk-stratify ED patients presenting with AF exacerbations. The rule will incorporate patient history and examination findings and laboratory studies obtained upon ED presentation, as well as trends over the first 2 h of care. This investigation's primary outcome is the incidence of any AF-related adverse event at 5 days and 30 days. We expect to complete the study by the end of 2014. The study was registered at Clinicaltrials.gov NCT01138644.
Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
BACKGROUND - Atrial fibrillation (AF) is the most common cardiac dysrhythmia and a source of considerable morbidity and mortality, but lifetime risk for AF has not been estimated.
METHODS AND RESULTS - We included all participants in the Framingham Heart Study who were free of AF at index ages of 40 years and older. We estimated lifetime risks for AF (including atrial flutter) to age 95 years, with death free of AF as a competing event. We followed 3999 men and 4726 women from 1968 to 1999 (176 166 person-years); 936 participants had development of AF and 2621 died without prior AF. At age 40 years, lifetime risks for AF were 26.0% (95% CI, 24.0% to 27.0%) for men and 23.0% (21.0% to 24.0%) for women. Lifetime risks did not change substantially with increasing index age despite decreasing remaining years of life because AF incidence rose rapidly with advancing age. At age 80 years, lifetime risks for AF were 22.7% (20.1% to 24.1%) in men and 21.6% (19.3% to 22.7%) in women. In further analyses, counting only those who had development of AF without prior or concurrent congestive heart failure or myocardial infarction, lifetime risks for AF were approximately 16%.
CONCLUSIONS - Lifetime risks for development of AF are 1 in 4 for men and women 40 years of age and older. Lifetime risks for AF are high (1 in 6), even in the absence of antecedent congestive heart failure or myocardial infarction. These substantial lifetime risks underscore the major public health burden posed by AF and the need for further investigation into predisposing conditions, preventive strategies, and more effective therapies.