Background Atrial fibrillation (AF) is commonly associated with congestive heart failure (CHF). The autonomic nervous system is involved in the pathogenesis of both AF and CHF. We examined the role of autonomic remodeling in contributing to AF substrate in CHF. Methods and Results Electrophysiological mapping was performed in the pulmonary veins (PVs) and left atrium (LA) in 38 rapid-ventricular paced dogs (CHF group) and 39 controls under the following conditions: vagal stimulation, isoproterenol infusion, β-adrenergic blockade, acetylcholinesterase (AChE) inhibition (physostigmine), parasympathetic blockade, and double autonomic blockade. Explanted atria were examined for nerve density/distribution, muscarinic receptor (MR) and beta-adrenergic receptor (βAR) densities, and AChE activity. In CHF dogs, there was an increase in nerve bundle size, parasympathetic fibers/bundle, and density of sympathetic fibrils and cardiac ganglia, all preferentially in the posterior LA/PVs. Sympathetic hyperinnervation was accompanied by increases in β1AR density and in sympathetic effect on ERPs and activation direction. β-adrenergic blockade slowed AF dominant frequency. Parasympathetic remodeling was more complex, resulting in increased AChE activity, unchanged MR density, unchanged parasympathetic effect on activation direction, and decreased effect of vagal stimulation on ERP (restored by AChE inhibition). Parasympathetic blockade markedly decreased AF duration. Conclusions In this heart failure model autonomic and electrophysiologic remodeling occurs involving the posterior left atrium and pulmonary veins. Despite synaptic compensation, parasympathetic hyperinnervation contributes significantly to AF maintenance. Parasympathetic and/or sympathetic signaling may be possible therapeutic targets for AF in CHF.

Background It is known that expanded epicardial fat is associated with atrial fibrillation (AF). However, infiltrated intraatrial fat has not been previously quantified in individuals at risk as determined by the ARIC AF risk score. Methods Patients in sinus rhythm (N=90, age 57±10y; 55 men [63.2%]), in 3 groups at risk of AF as determined by the ARIC AF risk score [low (≤11 points; n=15), moderate (12–18 points; n=40), high (≥19 points; n=23) risk of AF], and paroxysmal AF (n=12) underwent cardiac magnetic resonance study. Intraatrial and epicardial fat was analyzed with a Dark-blood DIR-prepared Fat-Water-separated sequence in the horizontal longitudinal axis. OsiriX DICOM viewer (Geneva, Switzerland) was used to quantify the intraatrial fat area. Width of the cephalad portion of the interatrial septum was measured at the level of the fossa ovalis. Results Intraatrial fat monotonically increased with growing AF risk in study groups (low AF risk 16±4 vs. moderate AF risk 32±18 vs. high AF risk 81±83 mm2; ANOVA P=0.012). Log-transformed intraatrial fat predicted ARIC AF risk score in multivariate ordered probit regression after adjustment for sex, race, left and right atrial area indices, and body mass index (β-coefficient 0.50 [95%CI 0.03–0.97]; P=0.037), whereas epicardial fat did not. Interatrial septum width showed similar association (3.0±1.4 vs. 5.0±1.8 vs. 7.1±2.7 mm; ANOVA P<0.001; adjusted β-coefficient 2.80 [95%CI 1.19–4.41]; P=0.001). Conclusions Infiltrated intraatrial fat characterizes evolving substrate in individuals at risk of AF.

Introduction-Craniosynostosis is typically corrected surgically within the first year of life through cranial vault reconstruction. These procedures often leaves open calvarial defects at the time of surgery, which are anticipated to close over time in a large proportion of cases. However, residual calvarial defects may result as long-term sequelae from cranial vault remodeling. When larger defects are present, they may necessitate further reconstruction for closure.Better understanding of the calvarial osseous healing process may help to identify which defects will resolve or shrink to acceptable size and which will require further surgery. Our study aims to assess the long-term changes in defect size after cranial vault reconstruction for craniosynostosis.Methods-One year post-operative and long-term computed tomography scans were retrieved from the craniofacial anomalies archive. Analysis used custom software. All defects above the size of 1 cm 2 were analyzed and tracked for calvarial location, surface area, and circularity. Monte Carlo simulation was performed to model the effect of initial defect size on the rate of defect closure.Results-We analyzed a total of 74 defects. The average initial defect surface area was 3.27 ± 3.40 cm 2 . The average final defect surface area was 1.71 ± 2.54 cm 2 . The average percent decrease was 55.06 ± 28.99 %. There was a significant difference in the percentage decrease of defects in the parietal and fronto-parietal locations: 68.4% and 43.7%, respectively (p = 0.001). Monte Carlo simulation results suggest that less than 10% of defects above the size of 9 cm 2 will close to the size of 2.5 cm 2 or less.Conclusions-We describe and make available a novel, validated method of measuring cranial defects. We find that the large majority of initial defects greater than 9cm 2 remain at least one square inch in size (2.5cm 2 ) one year post-operatively. Additionally, there appear to be regional differences in closure rates across the cranium, with front-parietal defects closing more slowly than those in the parietal region. This information will aid surgeons in the decision-making process regarding cranioplasty after craniosynostosis correction.

No abstract