Beneficial Effects of Intravenously Administered N-3 Fatty Acids for the Prevention of Atrial Fibrillation after Coronary Artery Bypass Surgery: A Prospective Randomized Study

Abstract

Background: Atrial fibrillation (AF) is a common complication after coronary artery bypass grafting operation (CABG). Experimental data have shown antiarrhythmic effects of n-3 polyunsaturated fatty acids (PUFA) on myocardial cells. Orally administered PUFA could significantly reduce the rate of postoperative AF. We assessed the efficacy of PUFA for the prevention of AF after CABG. PUFA were given intravenously to prevent variation in bioavailability.

Methods and Results: 52 patients were randomized to the interventional group, 50 served as controls. In the control group free fatty acids (100 mg soya oil/kg body weight/day) were infused via perfusion pump, starting on admission to hospital and ending at discharge from intensive care. In the interventional group PUFA were given at a dosage of 100 mg fish oil/kg body weight/day. Primary end point was the postoperative development of AF, documented by surface ECG. Secondary end point was the length of stay in the ICU. The demographic, clinical and surgical characteristics of the patients in the two groups were similar. Postoperative AF occurred in 15 patients (30.6 %) in the control and in 9 (17.3 %) in the PUFA group (p < 0.05). After CABG, the PUFA patients had to be treated in the ICU for a shorter time than the control patients. No adverse effects were observed.

Conclusions: Perioperative intravenous infusion of PUFA reduces the incidence of AF after CABG and leads to a shorter stay in the ICU and in hospital. Our data suggest that perioperative intravenous infusion of PUFA should be recommended for patients undergoing CABG.

cardiovascular surgery - coronary bypass surgery - heart disease

References

• 1 Jahangiri A, Leifert W R, Patten G S, McMurchie E J. Termination of asynchronous contractile activity in rat atrial myocytes by n-3 polyunsaturated fatty acids.  Mol Cell Biochem. 2000;  206 33-41
• 2 Leaf A, Kang J X, Xiao Y F, Billman G E, Voskuyl R A. The antiarrhythmic and anticonvulsant effects of dietary N-3 fatty acids.  J Membr Biol. 1999;  172 1-11
• 3 Villa B, Calabresi L, Chiesa G, Rise P, Galli C, Sirtori C R. Omega-3 fatty acid ethyl esters increase heart rate variability in patients with coronary disease.  Pharmacol Res. 2002;  45 475
• 4 Bruins P, te Velthuis H, Yazdanbakhsh A P, Jansen P G, van Hardevelt F W, de Beaumont E M, Wildevuur C R, Eijsman L, Trouwborst A, Hack C E. Activation of the complement system during and after cardiopulmonary bypass surgery: postsurgery activation involves C-reactive protein and is associated with postoperative arrhythmia.  Circulation. 1997;  96 3542-3548
• 5 Gaudino M, Andreotti F, Zamparelli R, Di Castelnuovo A, Nasso G, Burzotta F, Iacoviello L, Donati M B, Schiavello R, Maseri A, Possati G. The − 174 G/C interleukin-6 polymorphism influences postoperative interleukin-6 levels and postoperative atrial fibrillation. Is atrial fibrillation an inflammatory complication?.  Circulation. 2003;  108 (Suppl. 1) II195-II199
• 6 Frost L, Vestergaard P. n-3 Fatty acids consumed from fish and risk of atrial fibrillation or flutter: the Danish Diet, Cancer, and Health Study.  Am J Clin Nutr. 2005;  81 50-54
• 7 de Lorgeril M, Renaud S, Mamelle N, Salen P, Martin J L, Monjaud I, Guidollet J, Touboul P, Delaye J. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease.  Lancet. 1994;  343 1454-1459
• 8 Burr M L, Fehily A M, Gilbert J F, Rogers S, Holliday R M, Sweetnam P M, Elwood P C, Deadman N M. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART).  Lancet. 1989;  2 757-761
• 9 Siscovick D S, Raghunathan T E, King I, Weinmann S, Wicklund K G, Albright J, Bovbjerg V, Arbogast P, Smith H, Kushi L H et al. Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest.  JAMA. 1995;  274 1363-1367
• 10 Mozaffarian D, Psaty B M, Rimm E B, Lemaitre R N, Burke G L, Lyles M F, Lefkowitz D, Siscovick D S. Fish intake and risk of incident atrial fibrillation.  Circulation. 2004;  110 368-373
• 11 Gohlke H. [Prevention of coronary disease and sudden death by nutrition].  Z Kardiol. 2004;  93 (Suppl. 2) II21-II25
• 12 Gohlke H, Kubler W, Mathes P, Meinertz T, Schuler G, Gysan D B, Sauer G. [Position paper on primary prevention of cardiovascular diseases. Current edition of 25 March 2003 by the governing body of the German Society of Cardiology – Heart- and Cardiovascular Research, revised by request of the governing body via the Prevention Project Group].  Z Kardiol. 2004;  93 (Suppl. 2) II43-II45
• 13 De Backer G, Ambrosioni E, Borch-Johnsen K, Brotons C, Cifkova R, Dallongeville J, Ebrahim S, Faergeman O, Graham I, Mancia G, Manger Cats V, Orth-Gomer K, Perk J, Pyorala K, Rodicio J L, Sans S, Sansoy V, Sechtem U, Silber S, Thomsen T, Wood D. European guidelines on cardiovascular disease prevention in clinical practice. Third joint task force of European and other societies on cardiovascular disease prevention in clinical practice.  Eur Heart J. 2003;  24 1601-1610
• 14 Marchioli R, Barzi F, Bomba E, Chieffo C, Di Gregorio D, Di Mascio R, Franzosi M G, Geraci E, Levantesi G, Maggioni A P, Mantini L, Marfisi R M, Mastrogiuseppe G, Mininni N, Nicolosi G L, Santini M, Schweiger C, Tavazzi L, Tognoni G, Tucci C, Valagussa F. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione.  Circulation. 2002;  105 1897-1903
• 15 Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis.  Lancet. 2007;  369 1090-1098
• 16 Calder P C. Polyunsaturated fatty acids, inflammation, and immunity.  Lipids. 2001;  36 1007-1024
• 17 Harbige L S. Fatty acids, the immune response, and autoimmunity: a question of n-6 essentiality and the balance between n-6 and n-3.  Lipids. 2003;  38 323-341
• 18 Mori T A, Beilin L J. Omega-3 fatty acids and inflammation.  Curr Atheroscler Rep. 2004;  6 461-467
• 19 Thies F, Garry J M, Yaqoob P, Rerkasem K, Williams J, Shearman C P, Gallagher P J, Calder P C, Grimble R F. Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomized controlled trial.  Lancet. 2003;  361 477-485
• 20 Young-Xu Y, Jabbour S, Goldberg R, Blatt C M, Graboys T, Bilchik B, Ravid S. Usefulness of statin drugs in protecting against atrial fibrillation in patients with coronary artery disease.  Am J Cardiol. 2003;  92 1379-1383
• 21 Kris-Etherton P M, Griel A E, Psota T L, Gebauer S K, Zhang J, Etherton T D. Dietary stearic acid and risk of cardiovascular disease: intake, sources, digestion, and absorption.  Lipids. 2005;  40 1193-1200
• 22 Kris-Etherton P M, Harris W S, Appel L J. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease.  Circulation. 2002;  106 2747-2757
• 23 Nilsen D W, Albrektsen G, Landmark K, Moen S, Aarsland T, Woie L. Effects of a high-dose concentrate of n-3 fatty acids or corn oil introduced early after an acute myocardial infarction on serum triacylglycerol and HDL cholesterol.  Am J Clin Nutr. 2001;  74 50-56
• 24 Calo L, Bianconi L, Colivicchi F, Lamberti F, Loricchio M L, de Ruvo E, Meo A, Pandozi C, Staibano M, Santini M. N-3 fatty acids for the prevention of atrial fibrillation after coronary artery bypass surgery: a randomized, controlled trial.  J Am Coll Cardiol. 2005;  45 1723-1728