Effects of chronic omega-3 polyunsaturated fatty acid supplementation on human atrial mechanical function after reversion of atrial arrhythmias to sinus rhythm: Reversal of tachycardia-mediated atrial cardiomyopathy with fish oils

doi:10.1016/j.hrthm.2011.01.014

Heart Rhythm

Volume 8, Issue 5, May 2011, Pages 643-649

https://doi.org/10.1016/j.hrthm.2011.01.014 Get rights and content

Background

Atrial mechanical stunning is a form of tachycardia-mediated atrial cardiomyopathy that manifests after reversion of persistent atrial arrhythmias to sinus rhythm.

Objectives

This study sought to examine whether chronic omega-3 polyunsaturated fatty acid supplementation with fish oils can reverse atrial mechanical stunning.

Methods

Patients undergoing reversion of persistent atrial fibrillation (AF) or atrial flutter (AFL) to sinus rhythm were randomized to a control group (n = 26) or an omega-3 group (n = 23). The latter were prescribed 6 g/day of fish oil for ≥1 month prior to the procedure. Parameters of left atrial appendage function were compared immediately before and immediately after reversion.

Results

After fish oil intake for a mean of 70 days, the following were noted favoring the omega-3 group among both AF and AFL patients: (1) 2-fold higher serum omega-3 levels (P < .001), (2) less mean decrease in emptying velocity (e.g., AF: 8% vs. 32%, P = .02), (3) less mean decrease in appendage emptying fraction (e.g., AFL: 7% vs. 60%, P = .002), (4) lower incidence of new or increased spontaneous echocardiographic contrast (e.g., AF: 11% vs. 62.5%, P = .003), and (5) lower incidence of atrial mechanical stunning (e.g., AFL: 20% vs. 100%, P = .001). Omega-3 intake conferred protection against stunning in a multivariable analysis (odds ratio 0.18, P = .02).

Conclusion

Chronic fish oil ingestion in humans attenuates atrial mechanical stunning after reversion of atrial arrhythmias to sinus rhythm. This suggests that fish oils may target or even reverse underlying cellular and/or structural remodeling that occurs in response to persistent atrial arrhythmias.

Introduction

The reversion of atrial fibrillation (AF) or atrial flutter (AFL) to sinus rhythm with internal or external cardioversion, pharmacological therapy, or radiofrequency ablation of AFL is associated with transient mechanical dysfunction of the left atrium and left atrial appendage (LAA) known as stunning.1, 2, 3, 4, 5, 6, 7 Stunning is implicated in the heightened risk of thromboembolic complications, failure of improvement in cardiac output and exercise tolerance, and increased risk of recurrence after restoration of AF/AFL to sinus rhythm.1, 2, 3, 4, 5, 6, 7, 8, 9, 10 Stunning is a form of tachycardia-mediated atrial cardiomyopathy that develops in response to arrhythmia persistence. Abnormalities in calcium cycling, atrial myolysis, cellular dedifferentiation, and atrial fibrosis are thought to occur in response to arrhythmia persistence and are responsible for the development of stunning.¹¹ Pacing and use of isoprenaline or calcium have been shown to reverse atrial mechanical stunning, providing evidence that there is a functional contractile apparatus within the atrium that is structurally remodeled as a result of arrhythmia persistence and that reversibility is possible.12, 13, 14

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) in fish oils have been shown to modulate calcium cycling in the sarcoplasmic reticulum15, 16 and attenuate atrial structural remodeling in response to atrial arrhythmias, resulting in a marked reduction toward vulnerability and in the perpetuation of AF in animal models.17, 18, 19 On the basis of these observations, the aim of this study was to test the hypothesis that chronic fish oil supplementation in humans may reverse atrial mechanical stunning after reversion of atrial arrhythmias to sinus rhythm.

Section snippets

Methods

This was a prospective, randomized, single-blinded study that recruited patients scheduled to undergo reversion of either persistent AF or persistent right AFL to sinus rhythm with either external or internal cardioversion, or in the case of persistent right AFL, termination with radiofrequency ablation. Inclusion criteria were: (1) age 18 to 75 years, (2) arrhythmia present for >1 month confirmed on electrocardiogram on 2 separate occasions at least 2 weeks apart. Exclusion criteria were: (1)

Baseline characteristics

A total of 49 patients constituted the study population (23 omega-3 and 26 control patients) (Figure 1). There were no significant differences between the groups' baseline characteristics, except that duration of preceding arrhythmia was longer (9 ± 12 vs. 14 ± 20 months, P = .23), body mass index was higher (33 ± 11 vs. 28 ± 4, P = .06), and more patients with AF were in the omega-3 group (78% vs. 62%, P = .23); however, these differences were not statistically significant. No patient was on

Discussion

The present study provides important new information on the effect of chronic n-3 PUFA supplementation on left atrial/appendage function after reversion of persistent atrial arrhythmias to sinus rhythm. The control group in our study had features typical of left atrial stunning after reversion to sinus rhythm, namely, depressed LAAEV and LAAEF, and new/increased SEC, that were similar in incidence and severity to those noted by previous studies.1, 2, 3, 4, 5, 6, 7 However, patients supplemented

Conclusion

Chronic n-3 PUFA supplementation in humans results in attenuation or even reversal of left atrial mechanical stunning after reversion of persistent atrial arrhythmias to sinus rhythm. These results implicate that n-3 PUFAs may target underlying cellular and/or structural abnormalities that occur in response to persistent atrial arrhythmias.

Acknowledgments

The authors thank Dr. Anuradha Aggarwal, Dr. Anthony Yapanis, Dr. James Wong, and Associate Professor Leeanne Grigg for their invaluable assistance with echocardiographic data collection. We also thank the following: Numega Ingredients Pty. Ltd. for the supply of fish oil capsules; David Apps, Fatty Acid Lab, University of Adelaide, and Ms. Maria Bisignano, Clinical Trial Unit, The Royal Melbourne Hospital, for her assistance with the study.

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Cited by (24)

Left atrial appendage segmentation and quantitative assisted diagnosis of atrial fibrillation based on fusion of temporal-spatial information
2018, Computers in Biology and Medicine
In this paper, we present an approach for left atrial appendage (LAA) multi-phase fast segmentation and quantitative assisted diagnosis of atrial fibrillation (AF) based on 4D-CT data.
We take full advantage of the temporal dimension information to segment the living, flailed LAA based on a parametric max-flow method and graph-cut approach to build 3-D model of each phase. To assist the diagnosis of AF, we calculate the volumes of 3-D models, and then generate a “volume-phase” curve to calculate the important dynamic metrics: ejection fraction, filling flux, and emptying flux of the LAA's blood by volume. This approach demonstrates more precise results than the conventional approaches that calculate metrics by area, and allows for the quick analysis of LAA-volume pattern changes of in a cardiac cycle. It may also provide insight into the individual differences in the lesions of the LAA. Furthermore, we apply support vector machines (SVMs) to achieve a quantitative auto-diagnosis of the AF by exploiting seven features from volume change ratios of the LAA, and perform multivariate logistic regression analysis for the risk of LAA thrombosis.
The 100 cases utilized in this research were taken from the Philips 256-iCT. The experimental results demonstrate that our approach can construct the 3-D LAA geometries robustly compared to manual annotations, and reasonably infer that the LAA undergoes filling, emptying and re-filling, re-emptying in a cardiac cycle. This research provides a potential for exploring various physiological functions of the LAA and quantitatively estimating the risk of stroke in patients with AF.
The use of omega-3 polyunsaturated fatty acids (n-3 PUFAS) in atrial fibrillation
2016, Handbook of Lipids in Human Function: Fatty Acids
The efficacy and safety of omega-3 polyunsaturated fatty acids (n-3 PUFAs) for the prevention of atrial fibrillation (AF) is a source of ongoing debate in the current literature. This chapter will review the potential protective mechanisms of n-3 PUFA, as demonstrated by promising animal studies. It will then summarize the major studies performed in humans, considering paroxysmal, persistent, and postoperative AF as separate entities. The many factors contributing to the mixed results in human studies will be debated before concluding that n-3 PUFA supplements should not be recommended for the prevention of AF, as they have the potential to cause harm.
Effects of long-term omega-3 polyunsaturated fatty acid supplementation on paroxysmal atrial tachyarrhythmia burden in patients with implanted pacemakers: Results from a prospective randomised study
2013, International Journal of Cardiology
Citation Excerpt :
Fish oil patients were prescribed and dispensed a triglyceride preparation containing a total of 6 g/day of omega-3 polyunsaturated fatty acids of which 1.8 g/day were eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA), the active components of fish oil (1.02 g EPA and 0.72 g DHA). This dose was chosen to maximise treatment effects, whilst maintaining patient tolerability [15–18]. The duration of supplementation was chosen to maximise myocardial membrane incorporation of EPA and DHA, which is known to occur after 30 days of supplementation [19].
Sino-atrial node disease and aging increase AF risk. We investigated if long-term fish oil supplementation reduces paroxysmal atrial tachycardia/fibrillation (AT/AF) burden in patients aged ≥ 60 years with sinoatrial node disease and dual chamber pacemakers.
Following a run-in period of 6 months (p1) where AT/AF burden was logged,78 patients were randomised to control or fish oil group(total omega-3 6 g/d) and AT/AF burden evaluated after 6 months(p2; 39 controls, 39 fish oil) and 12 months (p3; 39 controls; 18 fish oil). A subset of 21 fish oil patients crossed over to controls in the final 6 months (crossover group).
Median AT/AF burden increased significantly in controls (1.5%, 3.2%, 4.3%, P < .001) but not in fish oil patients at 6 months (1.4% to 2%, P = .46) or those continuing for 12 months (1.5%, 0.98%, 1%, P = .16). Time to first episode of AT/AF > 1 min was not significantly different between the groups (P = .9). There was a rebound increase in AT/AF burden in p3 in cross over patients (2.2% to 5.8%, P = .01) reaching a level similar to controls (crossover vs. controls, 5.8% vs. 4.3%, P = .63) and higher than those who continued fish oil for 12 months (crossover vs. continued intake 5.8% vs. 1.2%, P = .02). Fish oil patients had shorter duration episodes of AT/AF with no difference in frequency compared to controls.
Long-term fish oil supplementation did not suppress AT/AF burden but may have attenuated its temporal progression related to aging and sinus node disease.
Effects of high dose intravenous fish oil on human atrial electrophysiology: Implications for possible anti- and pro-arrhythmic mechanisms in atrial fibrillation
2013, International Journal of Cardiology
Citation Excerpt :
Fatty acids in the phospholipid fraction represent the incorporated form and are a good surrogate for cardiac membrane fatty acids [18]. Intracardiac catheters were positioned as follows: (1) a 10-pole coronary sinus (CS) catheter (2-5-2 mm inter-electrode spacing) with the proximal bipole positioned at the CS ostium as determined in the best septal left anterior oblique position; (2) a quadripolar catheter with 5-mm inter-electrode distance placed in the His-bundle region; (3) 20-pole deflectable catheter positioned along the lateral right atrium (LRA) and (4) mapping and ablation catheter positioned for ablation and then moved to the right atrial appendage (RAA) for the research protocol [8,15,19]. Patients undergoing AF ablation had all of the aforementioned catheters placed with the exception of the 20-pole deflectable catheter.
Intravenous omega-3 polyunsaturated fatty acids (ω-3 PUFAs) may prevent atrial fibrillation (AF) inducibility and perpetuation in animal models. We examined the effect of high dose IV ω-3 PUFAs on human atrial electrophysiology.
We randomised 88 patients with no structural heart disease to receive saline (control group) or high dose IV ω-3 PUFA infusion prior to detailed atrial electrophysiologic evaluation. Biologically active components, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were measured in total lipids, free fatty acid and phospholipid (membrane incorporated) fraction pre and post infusion. Compared to pre-infusion values, EPA and DHA increased significantly in the total lipids and free fatty acid but were unchanged in the phospholipid fraction. IV ω-3 did not alter atrial refractory periods, however it slowed right, left and global atrial conduction (P < .05). Inducible AF was significantly less likely in ω-3 patients compared to controls (AF ≥ 5 min, 20% vs. 58%, P = .02) and was non-sustained (mean AF duration: 14 s vs. 39 s, P < .001), however inducible and sustained atrial flutter was more common (≥ 5 min: 28% vs. 0%, P = .01). Organisation of AF into flutter was observed in a greater proportion of inductions in the ω-3 group (8.5% vs. 0.6%, P < .001).
IV ω-3 PUFAs (as free fatty acids) cause acute atrial conduction slowing, suppress AF inducibility, organise AF into atrial flutter and enhance atrial flutter inducibility. These findings provide a novel insight into potential anti and pro-arrhythmic mechanisms of fish oils in human AF.
Long-term omega-3 polyunsaturated fatty acid supplementation reduces the recurrence of persistent atrial fibrillation after electrical cardioversion
2012, Heart Rhythm
Citation Excerpt :
Persistent AF is associated with progressive atrial electrical, structural, and contractile remodeling, which increases the risk of AF recurrence in the days to weeks following restoration of sinus rhythm.22 Long-term fish oil supplementation in humans prolongs atrial refractoriness, reduces vulnerability to inducible AF, and attenuates atrial mechanical stunning after reversion of persistent AF to sinus rhythm.13–15 In animal models of atrial cardiomyopathy, fish oils attenuate conduction abnormalities by reducing atrial fibrosis.
Persistent atrial fibrillation (AF) is associated with a high risk of recurrence after electrical cardioversion.
We examined if long-term supplementation with omega-3 polyunsaturated fatty acids in fish oils commenced >1 month prior to electrical cardioversion and continued thereafter reduces recurrence of persistent AF.
This was an open-label, randomized study of 178 patients with persistent AF >1-month duration. Participants were assigned to control group (n = 87) or omega-3 group (6 g/d fish oil; n = 91) and underwent cardioversion 1 month later. Concurrent antiarrhythmic use of sotalol or amiodarone was permitted. Fish oil was continued till return of persistent AF or a maximum of 1 year. Intention-to-treat analysis was performed for the primary end point defined as the recurrence of persistent AF.
Mean duration of fish oil intake was 56 days precardioversion and a total of 242 days in follow-up. Eicosapentaenoic acid and docosahexaenoic acid, the active components of fish oils, were 1.8-fold and 2.1-fold higher, respectively, in the omega-3 group compared with controls at the time of cardioversion (P <.001). At 90 days, 38.5% of the patients receiving omega-3 fatty acid supplement had AF recurrence compared with 77.5% of the controls (hazard ratio [omega-3 vs control] 0.38; 95% confidence interval 0.27−0.56; P <.001). Omega-3 intake was associated with a significant reduction in AF recurrence with or without concurrent antiarrhythmic drugs.
Omega-3 polyunsaturated fatty acid supplementation commenced >1 month prior to electrical cardioversion and continued thereafter reduces the recurrence of persistent AF. Randomized controlled trials on long-term fish oil supplementation are needed to confirm these findings.
Cardiovascular Benefits of Icosapent Ethyl in Patients With and Without Atrial Fibrillation in REDUCE-IT
2023, Journal of the American Heart Association

View all citing articles on Scopus

: ClinicalTrials.gov identifier: NCT00232232.

: This study was funded in part by the National Heart Foundation and the Pfizer Cardiovascular Lipid Research Grant. Dr. Kumar is the recipient of a postgraduate research scholarship cofunded by the National Health and Medical Research Council and the National Heart Foundation of Australia (Grant ID 622896). Drs. Teh is a recipient of the postgraduate research scholarship funded by the National Heart Foundation. Dr. Lee is a recipient of the postgraduate research scholarship from the Cardiac Society of Australia and New Zealand.

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ClinicalAtrial fibrillationEffects of chronic omega-3 polyunsaturated fatty acid supplementation on human atrial mechanical function after reversion of atrial arrhythmias to sinus rhythm: Reversal of tachycardia-mediated atrial cardiomyopathy with fish oils

Background

Objectives

Methods

Results

Conclusion

Introduction

Section snippets

Methods

Baseline characteristics

Discussion

Conclusion

Acknowledgments

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Chest

Am J Cardiol

Am Heart J

Eur J Pharmacol

Heart Rhythm

Am J Clin Nutr

Clinical
Atrial fibrillation
Effects of chronic omega-3 polyunsaturated fatty acid supplementation on human atrial mechanical function after reversion of atrial arrhythmias to sinus rhythm: Reversal of tachycardia-mediated atrial cardiomyopathy with fish oils