Catheter ablation of atrial fibrillation results in significant QTc prolongation in the postoperative period.

BACKGROUND: The corrected QT interval (QTc) is a measure of ventricular repolarization time, and a prolonged QTc increases risk for malignant ventricular arrhythmias. Pulmonary vein isolation (PVI) may increase QTc but its effects have not been well studied. OBJECTIVE: Determine the incidence, risk factors, and outcomes of patients presenting for PVI in sinus and atrial fibrillation with postoperative QTc prolongation in a large cohort. METHODS: We performed a single-center retrospective study of consecutive atrial fibrillation ablations. QTc durations using Bazett correction were obtained from electrocardiograms at different postoperative intervals and compared to preoperative QTc. We studied clinical outcomes including clinically significant ventricular arrhythmia and death. A multivariable model was used to identify factors associated with clinically significant QTc prolongation, defined as ΔQTc ≥60 ms or new QTc duration ≥500 ms. RESULTS: A total of 352 PVIs were included in this study. We observed a statistically significant increase in mean QTc compared to baseline (446.3 ± 37.8 ms) on postoperative day (POD)0 (471.7 ± 38.2 ms, P < .001) and at POD1 (456.5 ± 35.0 ms, P < .001). There was no significant difference at 1 month (452.4 ± 33.5 ms, P = .39) and 3 months (447.3 ± 40.0 ms, P = .78). Sixty-six patients (19.2%) developed ΔQTc ≥60 ms or QTc ≥500 ms on POD0, with 4.1% persisting past 90 days. Female sex (odds ratio [OR] = 1.82, 95% confidence interval [CI] =1.01-3.29, P = .047) and history of coronary artery disease (OR = 2.16, 95% CI = 1.03-4.55, P = .042) were independently predictive of QTc prolongation ≥500 ms or ΔQTc ≥60 ms. There were no episodes of clinically significant ventricular arrhythmia or death attributable to arrhythmia. CONCLUSION: QTc duration increased significantly immediately post-PVI and returned to baseline by 1 month. PVI did not provoke significant ventricular arrhythmias in our cohort.

Pervasive multinucleotide mutational events in eukaryotes.

Many aspects of mutational processes are nonrandom, from the preponderance of transitions relative to transversions to the higher rate of mutation at CpG dinucleotides [1]. However, it is still often assumed that single-nucleotide mutations are independent of one another, each being caused by separate mutational events. The occurrence of multiple, closely spaced substitutions appears to violate assumptions of independence and is often interpreted as evidence for the action of adaptive natural selection [2, 3], balancing selection [4], or compensatory evolution [5, 6]. Here we provide evidence of a frequent, widespread multinucleotide mutational process active throughout eukaryotes. Genomic data from mutation-accumulation experiments, parent-offspring trios, and human polymorphisms all show that simultaneous nucleotide substitutions occur within short stretches of DNA. Regardless of species, such multinucleotide mutations (MNMs) consistently comprise ~3% of the total number of nucleotide substitutions. These results imply that previous adaptive interpretations of multiple, closely spaced substitutions may have been unwarranted and that MNMs must be considered when interpreting sequence data.