BackgroundOmega-3 polyunsaturated fatty acids (n3-PUFAs) might have antiarrhythmic properties, but data conflict on whether n3-PUFAs reduce rates of atrial fibrillation (AF) after coronary artery bypass graft surgery (CABG). We hypothesized that n3-PUFAs would reduce post-CABG AF, and we tested this hypothesis in a well-powered, randomized, double-blind, placebo-controlled, multicenter clinical trial.Methods and ResultsPatients undergoing CABG were randomized to pharmaceutical-grade n3-PUFAs 2 g orally twice daily (minimum of 6 g) or a matched placebo ≥24 hours before surgery. Gas chromatography was used to assess plasma fatty acid composition of samples collected on the day of screening, day of surgery, and postoperative day 4. Treatment continued either until the primary end point, clinically significant AF requiring treatment, occurred or for a maximum of 2 weeks after surgery. Two hundred sixty patients were enrolled and randomized. Before surgery, n3-PUFA dosing increased plasma n3-PUFA levels from 2.9% to 4% and reduced the n6:n3-PUFA ratio from 9.1 to 6.4 (both P<0.001). Similar changes were noted on postoperative day 4. There were no lipid changes in the placebo group. The rate of post-CABG AF was similar in both groups (30% n3-PUFAs versus 33% placebo, P=0.67). The post-CABG AF odds ratio for n3-PUFAs relative to placebo was 0.89 (95% confidence interval 0.52–1.53). There were no differences in any secondary end points.ConclusionsOral n3-PUFA supplementation begun 2 days before CABG did not reduce AF or other complications after surgery.Clinical Trial Registrationurl: http://www.clinicaltrials.gov Unique identifier: NCT00446966. (J Am Heart Assoc. 2012;1:e000547 doi: 10.1161/JAHA.111.000547.)

There has been sustained focus on the secondary prevention of coronary heart disease and heart failure; yet, apart from stroke prevention, the evidence base for the secondary prevention of atrial fibrillation (AF) recurrence, AF progression, and AF‐related complications is modest. Although there are multiple observational studies, there are few large, robust, randomized trials providing definitive effective approaches for the secondary prevention of AF. Given the increasing incidence and prevalence of AF nationally and internationally, the AF field needs transformative research and a commitment to evidenced‐based secondary prevention strategies. We report on a National Heart, Lung, and Blood Institute virtual workshop directed at identifying knowledge gaps and research opportunities in the secondary prevention of AF. Once AF has been detected, lifestyle changes and novel models of care delivery may contribute to the prevention of AF recurrence, AF progression, and AF‐related complications. Although benefits seen in small subgroups, cohort studies, and selected randomized trials are impressive, the widespread effectiveness of AF secondary prevention strategies remains unknown, calling for development of scalable interventions suitable for diverse populations and for identification of subpopulations who may particularly benefit from intensive management. We identified critical research questions for 6 topics relevant to the secondary prevention of AF: (1) weight loss; (2) alcohol intake, smoking cessation, and diet; (3) cardiac rehabilitation; (4) approaches to sleep disorders; (5) integrated, team‐based care; and (6) nonanticoagulant pharmacotherapy. Our goal is to stimulate innovative research that will accelerate the generation of the evidence to effectively pursue the secondary prevention of AF.

ObjectiveCreeping fat, the wrapping of mesenteric fat around the bowel wall, is a typical feature of Crohn’s disease, and is associated with stricture formation and bowel obstruction. How creeping fat forms is unknown, and we interrogated potential mechanisms using novel intestinal tissue and cell interaction systems.DesignTissues from normal, UC, non-strictured and strictured Crohn’s disease intestinal specimens were obtained. The muscularis propria matrisome was determined via proteomics. Mesenteric fat explants, primary human preadipocytes and adipocytes were used in multiple ex vivo and in vitro cell migration systems on muscularis propria muscle cell derived or native extracellular matrix. Functional experiments included integrin characterisation via flow cytometry and their inhibition with specific blocking antibodies and chemicals.ResultsCrohn’s disease muscularis propria cells produced an extracellular matrix scaffold which is in direct spatial and functional contact with the immediately overlaid creeping fat. The scaffold contained multiple proteins, but only fibronectin production was singularly upregulated by transforming growth factor-β1. The muscle cell-derived matrix triggered migration of preadipocytes out of mesenteric fat, fibronectin being the dominant factor responsible for their migration. Blockade of α5β1 on the preadipocyte surface inhibited their migration out of mesenteric fat and on 3D decellularised intestinal tissue extracellular matrix.ConclusionCrohn’s disease creeping fat appears to result from the migration of preadipocytes out of mesenteric fat and differentiation into adipocytes in response to an increased production of fibronectin by activated muscularis propria cells. These new mechanistic insights may lead to novel approaches for prevention of creeping fat-associated stricture formation.

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