The Role of n-3 PUFAs in Preventing the Arrhythmic Risk in Patients with Idiopathic Dilated Cardiomyopathy
ABSTRACT N-3 polyunsaturated fatty acids (n-3 PUFAs) intake is associated with a reduction in sudden cardiac death in patients with ischemic heart disease. Their effects in patients with heart failure caused by idiopathic dilated cardiomyopathy (IDC) are unknown.
We compared with placebo the effects of n-3 PUFAs administration in 44 patients with IDC and with frequent or repetitive ventricular arrhythmias at Holter monitoring using a randomized, double-blind design. Arrhythmic risk was assessed by microvolt T-wave analysis (MTWA), signal averaged ECG (SAECG), Holter monitoring, power spectral analysis of heart rate (HR) variability, catecholamine and cytokine plasma levels, at baseline and after 6 months.
At MTWA, 7/12 patients (58%) initially positive became negative after n-3 PUFAs while one patient became positive after placebo (p = 0.019). N-3 PUFAs administration was also associated to normalization of SAECG (11/15 patients, p < 0.0015), decrease in non-sustained ventricular tachycardia (NSVT) episodes (p = 0.0002) and NSVT HR (p = 0.0003), improvement in HR variability and decrease in catecholamine and cytokine plasma levels. The ratio of plasma n-6 PUFAs to n-3 PUFAs decreased from 12.01 to 3.48 after n-3 PUFAs.
N-3 PUFAs administration is associated with favorable effects on parameters related to arrhythmic risk in patients with idiopathic dilated cardiomyopathy. These results are consistent with antiarrhythmic activity independent from their antiischemic effects.
- SourceAvailable from: Duo Li
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- "oil Olive oil CRP 8 wk P 1 . 84 1 . 52 3 . 51 35 55 . 6 0 . 57 27 . 1 Chronic renal impairment Munro et al . 2012 [ 75 ] Fish oil Sunola oil CRP , IL - 6 , TNF - a 14 wk P 0 . 42 1 . 62 2 . 04 29 41 . 3 UN 32 . 8 Obesity Murphy et al . 2007 [ 76 ] Food enriched in fish oil Non - fortified food CRP 6 mon P UN UN 1 74 50 . 3 0 . 48 31 . 9 Overweight Nodari et al . 2009 [ 77 ] Fish oil Olive oil IL - 6 , TNF - a 6 mon P 0 . 54 0 . 9 1 . 44 44 63 0 . 91 UN Idiopathic dilated cardiomyopa - thy Nodari et al . 2011 [ 78 ] Fish oil Olive oil IL - 6 , TNF - a 12 mon P UN UN 1 . 95 133 62 . 5 0 . 9 25 . 8 Chronic heart failure Pooya et al . 2010 [ 80 ] Fish oil High linoleic sunflower oil CRP 2 mon P 1 . 548 "
ABSTRACT: Previous studies did not draw a consistent conclusion about the effects of marine-derived n-3 polyunsaturated fatty acids (PUFAs) on fasting blood level of C-reactive protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). A comprehensive search of Web of Science, PubMed, Embase and Medline (from 1950 to 2013) and bibliographies of relevant articles was undertaken. Sixty-eight RCTs with a total of 4601 subjects were included in the meta-analysis. Marine-derived n-3 PUFAs supplementation showed a lowering effect on Marine-derived n-3 PUFAs supplementation had a significant lowering effect on TNF-α, IL-6 and CRP in three groups of subjects (subjects with chronic non-autoimmune disease, subjects with chronic autoimmune disease and healthy subjects). A significant negative linear relationship between duration and effect size of marine-derived n-3 PUFAs supplementation on fasting blood levels of TNF-α and IL-6 in subjects with chronic non-autoimmune disease was observed, indicating that longer duration of supplementation could lead to a greater lowering effect. A similar linear relationship was also observed for IL-6 levels in healthy subjects. Restricted cubic spline analysis and subgroup analysis showed that the lowering effect of marine-derived n-3 PUFAs on CRP, IL-6 and TNF-α in subjects with chronic non-autoimmune disease became weakened when body mass index was greater than 30 kg/m(2). The effect of marine-derived n-3 PUFAs from dietary intake was only assessed in subjects with chronic non-autoimmune disease, and a significant lowering effect was observed on IL-6, but not on CRP and TNF-α. Marine-derived n-3 PUFAs supplementation had a significant lowering effect on CRP, IL-6 and TNF-α level. The lowering effect was most effective in non-obese subjects and consecutive long-term supplementation was recommended.PLoS ONE 02/2014; 9(2):e88103. DOI:10.1371/journal.pone.0088103 · 3.23 Impact Factor
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- "In addition to these direct effects on the generation and duration of the action potential, other less direct mechanisms of actions have been proposed. There is also evidence for antiarrhythmic effects mediated through a reduced production of proarrhythmic eicosanoids, reduced levels of circulating catecholamines , and a reduced agonist affinity of beta-receptors . The latter observation might be one of the mechanisms responsible for an improvement in the cardiac sympathetic-vagal balance, revealed clinically as a reduction in the mean heart rate (HR)  as well as an increase in HR variability . "
ABSTRACT: This paper reviews the current evidence regarding long-chained marine omega-3 polyunsaturated fatty acids (PUFAs) and cardiovascular disease (CVD), their possible mechanisms of action, and results of clinical trials. Also, primary and secondary prevention trials as studies on antiarrhythmic effects and meta-analyses are summarized. However, the individual bioavailability of n-3 PUFAs along with the highly different study designs and estimations of FAs intake or supplementation dosages in patient populations with different background intake of n-3 PUFAs might be some of the reasons for the inconsistent findings of the studies evaluating the impact of n-3 PUFAs on CVD. The question of an optimum dose of n-3 PUFAs or whether there exists a dose-response relation for n-3 PUFA supplementation is widely discussed. Moreover, the difficulties in interpreting meta-analyses are clearly demonstrated by two recently published meta-analyses (Rizos et al. and Delgado Lista et al.), evaluating the efficacy of n-3 PUFAs on CVD, including 12 common studies, but drawing opposite conclusions. We definitely need more large-scale, randomized clinical trials of long duration, also reporting harmful effects of n-3 PUFAs.12/2012; 2012(8):303456. DOI:10.1155/2012/303456
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- "Extensive studies on the potential effects of fish oil omega-3 poly unsaturated fatty acids (ω-3 PUFA) on cardiac rhythm have provided controversial results (von Schacky, 2008). While some interventional studies reported either no effect or even promotion of arrhythmias in some subgroups of patients with heart disease (Raitt et al., 2005; Coronel et al., 2007; Den Ruijter et al., 2007; Cheng and Santoni, 2008), other studies have reported beneficial effects of ω-3-PUFAs on cardiac rhythm resulting in a reduction in the incidence of sudden cardiac death or mortality (London et al., 2007; Cheng and Santoni, 2008; Nodari et al., 2009). It seems that fish oil fatty acids may exert either pro-or anti-arrhythmic effects, probably depending on different underlying mechanisms for the arrhythmias. "
ABSTRACT: Accumulating evidence has suggested that ω3-polyunsaturated fatty acids (ω3-PUFAs) may have beneficial effects in the prevention/treatment of cardiovascular diseases, while controversies still remain regarding their anti-arrhythmic potential. It is not clear yet whether ω-3-PUFAs can suppress early afterdepolarizations (EADs) induced by oxidative stress. In the present study, we recorded action potentials using the patch-clamp technique in ventricular myocytes isolated from rabbit hearts. The treatment of myocytes with H2O2 (200 μM) prolonged AP durations and induced EADs, which were significantly suppressed by docosahexaenoic acid (DHA, 10 or 25 μM; n = 8). To reveal the ionic mechanisms, we examined the effects of DHA on L-type calcium currents (ICa.L), late sodium (INa), and transient outward potassium currents (Ito) in ventricular myocytes pretreated with H2O2. H2O2 (200 μM) increased ICa.L by 46.4% from control (−8.4 ± 1.4 pA/pF) to a peak level (−12.3 ± 1.8 pA/pF, n = 6, p < 0.01) after 6 min of H2O2 perfusion. H2O2-enhanced ICa.L was significantly reduced by DHA (25 μM; −7.1 ± 0.9 pA/pF, n = 6, p < 0.01). Similarly, H2O2-increased the late INa (−3.2 ± 0.3 pC) from control level (−0.7 ± 0.1 pC). DHA (25 μM) completely reversed the H2O2-induced increase in late INa (to −0.8 ± 0.2 pC, n = 5). H2O2 also increased the peak amplitude of and the steady state Ito from 8.9 ± 1.0 and 2.16 ± 0.25 pA/pF to 12.8 ± 1.21 and 3.13 ± 0.47 pA/pF respectively (n = 6, p < 0.01, however, treatment with DHA (25 μM) did not produce significant effects on current amplitudes and dynamics of Ito altered by H2O2. In addition, DHA (25 μM) did not affect the increase of intracellular reactive oxygen species (ROS) levels induced by H2O2 in rabbit ventricular myocytes. These findings demonstrate that DHA suppresses exogenous H2O2-induced EADs mainly by modulating membrane ion channel functions, while its direct effect on ROS may play a less prominent role.Frontiers in Physiology 11/2012; 3(11):252. DOI:10.3389/fphys.2012.00252 · 3.50 Impact Factor