Omega‐3 Fatty Acids and Heart Rhythm, Rate, and Variability in Atrial Fibrillation

Baumgartner, Philipp; Reiner, Martin F.; Wiencierz, Andrea; Coslovsky, Michael; Bonetti, Nicole R.; Filipovic, Mark G; Aeschbacher, Stefanie; Kühne, Michael; Zuern, Christine S.; Rodondi, Nicolas; Oberle, Jolanda; Moschovitis, Giorgio; Lüscher, Thomas F.; Camici, Giovanni G.; Oßwald, Stefan; Conen, David; Beer, Jürg H.

doi:10.1161/jaha.122.027646

Cited by 3 publications

(3 citation statements)

References 39 publications

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“…We considered that the serum EPA level was associated with the degree of parasympathetic nervous tone because previous studies have reported that a high n‐3 PUFA level increases the parasympathetic nervous tone 37 and decreases the heart rate. 38 In fact, we confirmed a lower heart rate during sinus rhythm after ablation among the high EPA/AA, EPA alone, EPA + DHA, and EPA/DHA groups. Regarding the higher risk of EPA on AF recurrence, a study reported that AF could be induced by simultaneous sympathetic and parasympathetic nervous stimulation.…”

Section: Discussionsupporting

confidence: 66%

Eicosapentaenoic Acid and the Outcomes in Older Patients Undergoing Atrial Fibrillation Ablation

Sudo,

Morimoto,

Tsushima

et al. 2024

JAHA

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Background A lower serum eicosapentaenoic acid (EPA) to arachidonic acid (AA) ratio (EPA/AA) level correlates with cardiovascular events. Nevertheless, elevated serum EPA levels increase the risk of new‐onset atrial fibrillation (AF) in older patients. The relationship between the EPA/AA and outcomes post‐AF ablation remains unclear. This study investigated the impact of the EPA/AA on AF recurrence and cardiovascular events after AF ablation in older patients. Methods and Results This retrospective cohort study examined consecutive patients with AF aged ≥65 years who underwent a first‐time AF ablation. We compared the 3‐year AF recurrence and 5‐year major adverse cardiovascular event (MACE) rates between patients divided into high and low EPA/AA levels defined as above and below the median EPA/AA value before ablation. MACE was defined as heart failure hospitalizations, strokes, coronary artery disease, major bleeding, and cardiovascular death. Among the 673 included patients, the median EPA/AA value was 0.35. Compared with the low EPA/AA group, the high EPA/AA group had a significantly higher cumulative incidence of AF recurrence (39.3% versus 27.6%; log‐rank P =0.004) and lower cumulative incidence of MACE (13.8% versus 25.5%, log‐rank P =0.021). A high EPA/AA level was determined as an independent predictor of AF recurrence (hazard ratio [HR], 1.75 95% CI, 1.24–2.49; P =0.002) and MACE (HR, 0.60 [95% CI, 0.36–0.99]; P =0.046). Conclusions The EPA/AA was associated with AF recurrence and MACE after ablation in patients with AF aged ≥65 years.

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Section: Discussionsupporting

confidence: 66%

Eicosapentaenoic Acid and the Outcomes in Older Patients Undergoing Atrial Fibrillation Ablation

Sudo,

Morimoto,

Tsushima

et al. 2024

JAHA

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“…The latter finding is in line with a previous analysis of the Swiss AF study, showing no significant association of total n -3 FAs with the type of AF. In patients with known AF, neither total nor individual fish- or plant-derived n -3 FAs showed a significant correlation with an increased AF burden, i.e., non-paroxysmal AF [ 36 ]. Whether n -3 FA supplementation in low or high dosages affects the burden of AF in patients with known AF remains to be determined in future randomized controlled trials.…”

Section: Discussionmentioning

confidence: 99%

Omega-3 Fatty Acids and Markers of Thrombosis in Patients with Atrial Fibrillation

Reiner,

Bertschi,

Werlen

et al. 2024

Nutrients

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Omega-3 fatty acids (n-3 FAs) are associated with a lower risk of ischemic stroke in patients with atrial fibrillation (AF). Antithrombotic mechanisms may in part explain this observation. Therefore, we examined the association of n-3 FAs with D-dimer and beta-thromboglobulin (BTG), markers for activated coagulation and platelets, respectively. The n-3 FAs eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and alpha-linolenic acid (ALA) were determined via gas chromatography in the whole blood of 2373 patients with AF from the Swiss Atrial Fibrillation cohort study (ClinicalTrials.gov Identifier: NCT02105844). In a cross-sectional analysis, we examined the association of total n-3 FAs (EPA + DHA + DPA + ALA) and the association of individual fatty acids with D-dimer in patients with detectable D-dimer values (n = 1096) as well as with BTG (n = 2371) using multiple linear regression models adjusted for confounders. Median D-dimer and BTG levels were 0.340 ug/mL and 448 ng/mL, respectively. Higher total n-3 FAs correlated with lower D-dimer levels (coefficient 0.94, 95% confidence interval (Cl) 0.90–0.98, p = 0.004) and lower BTG levels (coefficient 0.97, Cl 0.95–0.99, p = 0.003). Likewise, the individual n-3 FAs EPA, DHA, DPA and ALA showed an inverse association with D-dimer. Higher levels of DHA, DPA and ALA correlated with lower BTG levels, whereas EPA showed a positive association with BTG. In patients with AF, higher levels of n-3 FAs were associated with lower levels of D-dimer and BTG, markers for activated coagulation and platelets, respectively. These findings suggest that n-3 FAs may exert antithrombotic properties in patients with AF.

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“…DHA and total n-3 PUFA level, but not EPA level, was associated with a slower heart rate. 127 Several observational studies have shown that increased serum and red blood cell membrane levels of EPA, but not DHA, are associated with AF. 116,128 A recent multinational pooled meta-analysis of 54 799 community-dwelling individuals free from CVD or at relatively low risk, from 17 prospective cohort studies, with a median follow-up of 13.3 years, including 7720 cases of incident AF, found that levels of docosapentaenoic acid, DHA, and EPA+DHA, but not EPA alone, were associated with lower incidence of AF (HR, 0.89 [95% CI, 0.83-0.95]; HR, 0.90 [95% CI, 0.85-0.96]; and HR, 0.93 [95% CI, 0.87-0.99], respectively).…”

Section: N-3 Pufa and Af: Epidemiologic Studiesmentioning

confidence: 99%

Omega-3 Fatty Acids and Arrhythmias

Marcus,

Link

2024

Circulation

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The pro- and antiarrhythmic effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been extensively studied in preclinical and human trials. Despite early evidence of an antiarrhythmic role of n-3 PUFA in the prevention of sudden cardiac death and postoperative and persistent atrial fibrillation (AF), subsequent well-designed randomized trials have largely not shown an antiarrhythmic benefit. Two trials that tested moderate and high-dose n-3 PUFA demonstrated a reduction in sudden cardiac death, but these findings have not been widely replicated, and the potential of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to reduce arrhythmic death in combination, or as monotherapy, remains uncertain. The accumulated clinical evidence does not support supplementation of n-3 PUFA for postoperative AF or secondary prevention of AF. Several large, contemporary, randomized controlled trials of high-dose n-3 PUFA for primary or secondary cardiovascular prevention have demonstrated a small, significant, dose-dependent increased risk of incident AF compared with mineral oil or corn oil comparator. These findings were reproduced with both icosapent ethyl monotherapy and a mixed EPA+DHA formulation. The proarrhythmic mechanism of increased AF in contemporary cohorts exposed to high-dose n-3 PUFA is unknown. EPA and DHA and their metabolites have pleiotropic cardiometabolic and pro- and antiarrhythmic effects, including modification of the lipid raft microenvironment; alteration of cell membrane structure and fluidity; modulation of sodium, potassium, and calcium currents; and regulation of gene transcription, cell proliferation, and inflammation. Further characterization of the complex association between EPA, EPA+DHA, and DHA and AF is needed. Which formulations, dose ranges, and patient subgroups are at highest risk, remain unclear.

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Omega‐3 Fatty Acids and Heart Rhythm, Rate, and Variability in Atrial Fibrillation

Cited by 3 publications

References 39 publications

Eicosapentaenoic Acid and the Outcomes in Older Patients Undergoing Atrial Fibrillation Ablation

Eicosapentaenoic Acid and the Outcomes in Older Patients Undergoing Atrial Fibrillation Ablation

Omega-3 Fatty Acids and Markers of Thrombosis in Patients with Atrial Fibrillation

Omega-3 Fatty Acids and Arrhythmias

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