High-intensity endurance training is associated with left atrial fibrosis.

INTRODUCTION: Endurance athletes are at higher risk for developing atrial fibrillation as compared to the general population. The exact mechanism to explain this observation is incompletely understood. Our study aimed to determine whether degree of left atrial fibrosis detected by late gadolinium-enhancement magnetic resonance imaging (LGE-MRI) differed between Masters athletes and non-athlete controls. METHODS: We recruited 20 endurance healthy Masters athletes and 20 healthy control subjects who underwent cardiac MRI. Healthy controls were recruited during screening colonoscopies and Masters athletes were recruited through word of mouth and at competitions. The two groups were age and gender matched. None of the participants were known to have an arrhythmia. Fibrosis, as measured by late gadolinium-enhancement, was measured in each participant by blinded readers. The degree of left atrial fibrosis was compared between the two groups. All participants were recruited from the Salt Lake City region and scanned at the University of Utah healthcare complex. RESULTS: Left ventricular function was normal in all study participants. Left atrial volumes were significantly larger in the athletes (74.2 ml ±â€¯14.4) as compared to the healthy control subjects (60.8 mL ±â€¯21.4) (P = .02). Mean left atrial fibrosis score, reported as a percentage of the LA, was 15.5% ±â€¯5.9 in the athlete cohort compared to 9.6% ±â€¯4.9 in the controls (P = .002). CONCLUSIONS: To our knowledge this is the first study that describes, characterizes and specifically quantifies fibrotic changes within the left atrium of highly trained endurance athletes. Increased atrial fibrosis seen in this population may be an early indicator for endurance athletes at risk of developing atrial arrhythmias.

In vivo evaluation of the delivery and efficacy of a sirolimus-laden polymer gel for inhibition of hyperplasia in a porcine model of arteriovenous hemodialysis graft stenosis.

Synthetic arteriovenous (AV) hemodialysis grafts are plagued by hyperplasia resulting in occlusion and graft failure yet there are no clinically available preventative treatments. Here the delivery and degradation of a sirolimus-laden polymer gel were monitored in vivo by magnetic resonance imaging (MRI) and its efficacy for inhibiting hyperplasia was evaluated in a porcine model of AV graft stenosis. Synthetic grafts were placed between the carotid artery and ipsilateral jugular vein of swine. A biodegradable polymer gel loaded with sirolimus (2.5mg/mL) was immediately applied perivascularly to the venous anastomosis, and reapplied by ultrasound-guided injections at one, two and three weeks. Control grafts received neither sirolimus nor polymer. The lumen cross-sectional area at the graft-vein anastomosis was assessed in vivo by non-invasive MRI. The explanted tissues also underwent histological analysis. A specifically developed MRI pulse sequence provided a high contrast-to-noise ratio (CNR) between the polymer and surrounding tissue that allowed confirmation of gel location after injection. Polymer signal decreased up to 80% at three to four weeks after injection, slightly faster than its degradation kinetics in vitro. The MR image of the polymer was confirmed by visual assessment at necropsy. On histological assessment, the mean hyperplasia surface area of the treated graft was 52% lower than that of the control grafts (0.43mm(2) vs. 0.89mm(2); p<0.003), while the minimum cross-sectional lumen area, as measured on MRI, was doubled (5.3mm(2) vs 2.5mm(2); p<0.05). In conclusion, customized MRI allowed non-invasive monitoring of the location and degradation of drug delivery polymer gels in vivo. Perivascular application of sirolimus-laden polymer yielded a significant decrease in hyperplasia development and an increase in lumen area at the venous anastomosis of AV grafts.