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Omega-3 Fatty Acids and Their Role in Cardiac Arrhythmogenesis: Research Challenges and Opportunities
The National Heart, Lung, and Blood Institute convened a Workshop on August 29-30, 2005, in Washington, District of Columbia to: (1) review the epidemiological evidence and data from NHLBI-supported randomized trials on the role of omega-3 (n-3) fatty acids in susceptibility to cardiac arrhythmias and sudden cardiac death; (2) explore the basic mechanisms by which n-3 fatty acids affect cardiac excitability at the cellular and organ level; (3) identify gaps and barriers in basic understanding of the effects of n-3 fatty acids on cardiac electrical activity at the cellular, tissue, and whole body levels; and (4) provide prioritized recommendations to the NHLBI for additional research studies of the role of n-3 fatty acids in cardiac arrhythmogenesis.
Workshop members reviewed the present state of knowledge related to n-3 fatty acids and cardiac arrhythmia mechanisms. Dietary sources and quantification of n-3 fatty acids, competition between n-3 and n-6 fatty acids, pathways for production of tissue n-3 and n-6 highly unsaturated fatty acids, and the importance of adequate measurements in clinical trials were reviewed. Evidence was presented that the risk of either cardiac arrest or sudden death is associated with low dietary intake and blood levels of polyunsaturated fatty acids and that a fish diet (the DART study) or dietary supplementation with polyunsaturated fatty acids (the GISSI-Prevenzione study) decrease mortality and/or sudden death following myocardial infarction. Although the NHLBI-supported, randomized, double blind Antiarrhythmic Effects of N-3 Fatty Acids study showed no benefit of dietary n-3 fatty acids, a trend toward increased arrhythmias in patients who had high arrhythmic risk and implantable cardioverter defibrillators (ICDs) was observed. By contrast, the NHLBI-supported Fatty Acid Antiarrhythmic Trial (FAAT) did show a strong trend toward benefit in a similar population. A review of animal models showed fewer ischemia- and reperfusion-induced arrhythmias in rats fed n-3 fatty acids (EPA or DHA), but highlighted the limited scope of the animal models studied to date. The evidence for several different mechanisms by which n-3 fatty acids may alter arrhythmias was discussed in detail, including potential effects on cardiac sodium channels, calcium channels, the sodium-calcium exchanger, lipid rafts, calcium release from the sarcoplasmic reticulum, kinases (including PKA and CaMKII), and myocardial oxygen stress. Potential anti-inflammatory properties of n-3 fatty acids and the relationship of inflammatory changes to both atrial and ventricular arrhythmias were discussed. Current gaps in our knowledge include the absence of proof that n-3 fatty acids decrease arrhythmias in patients at risk for sudden death, uncertainty as to which patients may benefit most from supplementation, limited mechanistic data from animal models, and no definitive understanding as to which basic mechanisms transduce effects on cardiac electrogenesis.
David A. Lathrop, Ph.D, NHLBI, NIH
Isabella Liang, Ph.D. NHLBI, NIH
Last updated: November 28, 2007