Reduced Incidence of Vagally Induced Atrial Fibrillation and Expression Levels of Connexins by n-3 Polyunsaturated Fatty Acids in Dogs

Background-n-3 polyunsaturated fatty acids (n-3 PUFAs) exert antiarrhythmic effects and reduce sudden cardiac death.However, their role in the prevention of atrial fibrillation remains controversial. We aimed to determine the effect of n-3 PUFAs in addition to amiodarone and a renin-angiotensin-aldosterone system inhibitor on the maintenance of sinus rhythm after direct current cardioversion in patients with persistent atrial fibrillation. Methods and Results-We conducted a randomized, double-blind, placebo-controlled, parallel-arm trial in patients with persistent atrial fibrillation, with at least 1 relapse after cardioversion, and treated with amiodarone and a renin-angiotensin-aldosterone system inhibitor. Participants were assigned to placebo or n-3 PUFAs 2 g/d and then underwent direct current cardioversion 4 weeks later. The primary end point was the probability of maintenance of sinus rhythm at 1 year after cardioversion. Of 254 screened patients, 199 were found to be eligible and randomized. At the 1-year follow up, the probability of maintenance of sinus rhythm was significantly higher in the n-3 PUFAs-treated patients compared with the placebo group (hazard ratio, 0.62 [95% confidence interval, 0.52 to 0.72] and 0.36 [95% confidence interval, 0.26 to 0.46], respectively; Pϭ0.0001). Conclusions-In patients with persistent atrial fibrillation on amiodarone and a renin-angiotensin-aldosterone system inhibitor, the addition of n-3 PUFAs 2 g/d improves the probability of the maintenance of sinus rhythm after direct current cardioversion. Our data suggest that n-3 PUFAs may exert beneficial effects in the prevention of atrial fibrillation recurrence. Further studies are needed to confirm and expand our findings. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01198275.

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“…34 These electrophysiological properties have been confirmed at the organ level in animal models of atrial remodeling. [35][36][37][38] …”

Section: Potential Mechanisms Of N-3 Polyunsaturated Fatty Acids In Amentioning

confidence: 99%

n-3 Polyunsaturated Fatty Acids in the Prevention of Atrial Fibrillation Recurrences After Electrical Cardioversion

et al. 2011

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“…Most experimental studies support the atrial antiarrhymic Erdogan ( effect of omega-3 fatty acids (11)(12)(13)(14)(15). This may be partly attributed to the fact that positive results of animal experiments are more likely to be published.…”

Section: Discussionmentioning

confidence: 97%

Omega-3 Fatty Acids in the Prevention of Atrial Fibrillation Recurrences after Cardioversion: A Meta-analysis of Randomized Controlled Trials

et al. 2012

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Backgroud Previous randomized studies have reported conflicting results on the efficacy of omega-3 fatty acids in preventing atrial fibrillation (AF) recurrences after cardioversion. Objective A systematic review and meta-analysis of the role of omega-3 fatty acids in the prevention of atrial fibrillation recurrences after cardioversion was conducted. Methods PubMed, Cochrane Library, Elsevier, Science Online database were searched up to the end of January 2012 to identify all of the studies in human subjects that reported the effects of omega-3 fatty acids on the prevention of atrial fibrillation recurrences after cardioversion. Results Overall, omega-3 fatty acids had no significant effect on the prevention of AF recurrences after cardioversion (OR: 0.63,95% CI 0.35-1.13; p=0.12). The heterogeneity among the studies was significant (p= 0.01, I 2 =66%). Subgroup analysis showed that by administering omega-3 fatty acids at least 4 weeks prior to cardioversion and continuing thereafter, the recurrence rate of AF is significantly low (OR: 0.39, 95% CI 0.25-0.61; p<0.0001). Conclusion In the subgroup administered omega-3 fatty acids at least 4 weeks prior to cardioversion and continued thereafter, the recurrence rate of AF was significantly low. More double-blind, randomized, placebo-controlled, multicenter studies with high quality and longer follow-up periods are needed to affirm our conclusion.

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“…Treatment with n-3 PUFA reduced vulnerability to induction of AF in a dog model by reducing atrial expression of connexin. 73 Furthermore, a cell membrane shift in the balance of n-3 PUFA to n-6 PUFA might attenuate the production of n-6 PUFA-derived eicosanoids, including thromboxane A2 and prostaglandins, which have been suggested to promote arrhythmias. 74,75 Finally, omega-3 EEs may reduce arrhythmic events modulating autonomic tone.…”

Section: Arrhythmiasmentioning

confidence: 99%

Uses and benefits of omega-3 ethyl esters in patients with cardiovascular disease

Levantesi

Silletta²,

Marchioli³

2010

JMDH

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Much evidence on the favorable effects of omega-3 ethyl esters on cardiovascular morbidity and mortality has been obtained in studies performed in healthy subjects and in different clinical settings. Here the clinical effects of omega-3 ethyl ester administration in patients with previous myocardial infarction or heart failure are reviewed, together with a discussion of underlying mechanisms of action. The pharmacokinetic and pharmacodynamic properties of omega-3 ethyl esters, as well as evidence concerning their safety and tolerability, are also reported.

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Reduced Incidence of Vagally Induced Atrial Fibrillation and Expression Levels of Connexins by n-3 Polyunsaturated Fatty Acids in Dogs

Abstract: Oral treatment with fish oils increased atrial n-3 PUFA levels and reduced vulnerability to induction of AF in this dog model. Modulation of cardiac CX by n-3 PUFAs probably contributes to the antiarrhythmic effects of fish oils.

Cited by 94 publications

References 37 publications

n-3 Polyunsaturated Fatty Acids in the Prevention of Atrial Fibrillation Recurrences After Electrical Cardioversion

n-3 Polyunsaturated Fatty Acids in the Prevention of Atrial Fibrillation Recurrences After Electrical Cardioversion

Omega-3 Fatty Acids in the Prevention of Atrial Fibrillation Recurrences after Cardioversion: A Meta-analysis of Randomized Controlled Trials

Uses and benefits of omega-3 ethyl esters in patients with cardiovascular disease

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