Prevention of post-operative atrial fibrillation
SANTIAGO, CHILE. Oxidative stress has been implicated as a major factor in the development and promotion of atrial fibrillation (AF). The main reactive oxygen species (ROS) involved in causing oxidative stress are the superoxide anion, singlet oxygen, nitrogen dioxide (peroxynitrite) and hydroxyl radicals. They share the dubious distinction of being able to cause inflammation and inflict considerable damage in tissues, cells and individual DNA strands.

Under normal circumstances any ROS attacking the heart lining or adjacent lung tissue would quickly be rendered harmless by the body's own antioxidants or by antioxidants obtained through the diet. However, if antioxidant defenses are inadequate, the immune system is compromised, or if the autonomic nervous system is highly dysfunctional or stressed, it is likely that the ROS could get the upper hand and initiate an inflammatory response and subsequent arrhythmia.

Inflammation of the heart lining has also been linked to the development and promotion of AF and a strong association between severity of AF and the level of the inflammation biomarker CRP (C-reactive protein) has been established. There is also evidence that omega-3 polyunsaturated fatty acids (fish oils) materially reduce inflammation and CRP level.

A group of Chilean and Greek researchers now reports that pre-procedure supplementation with a combination of antioxidants (vitamins C and E) and fish oil is effective in reducing the incidence of post-operative AF in patients undergoing valve surgery or coronary artery bypass surgery. Their clinical trial involved 203 patients scheduled for on-pump cardiac surgery. The average age of the patients was 60 years, 86% were male and all were in normal sinus rhythm and had no previous history of arrhythmia.

The patients were randomized to receive placebo or supplementation with 2 grams/day of fish oil (DHA:EPA ratio of 2:1), 1 gram/day of vitamin C and 400 IU/day of vitamin E. Fish oil supplementation was initiated 7 days prior to the procedure and supplementation with vitamins C and E was started 2 days before. All supplementation was discontinued upon discharge from hospital. ECG or Holter monitoring was carried out until discharge with ECG-documented AF for at least 60 seconds being classified as post-operative atrial fibrillation (POAF). POAF occurred in 9.7% of supplement group members and in 32% of placebo group members – a statistically highly significant difference. The mean time to POAF occurrence (from completion of surgery) was 3.3 days in the supplement group and 2.9 days in the placebo group.

Oxidative stress was assessed as malondialdehyde (MDA) level in blood throughout the trial and in right atrial tissue during surgery. After 5 days of fish oil supplementation, blood levels of MDA were an average 59.6% higher than baseline level and 45.6% higher than the average level in the placebo group. However, after the addition of vitamins C and E there was no longer any difference in pre-surgery MDA levels. MDA levels, not surprisingly, increased after surgery, but to a much lesser degree in the supplement group. CRP levels also increased after surgery but significantly less so in the supplement group than in the placebo group (2.2-fold vs. 3.6-fold increase).

The researchers also noted a significantly higher activity of the endogenous antioxidant enzymes catalase, superoxide dismutase and glutathione peroxidase in the atrial tissue of supplemented patients. They conclude that supplementation with a combination of antioxidants (vitamins C and E) and fish oils reduces the incidence of post-operative AF in cardiac surgery patients by about 66%. Supplementation also increases antioxidant potential and decreases oxidative stress and inflammation. They note that using a fish oil supplement with a ratio of DHA (docosahexaenoic acid) to EPA (eicosapentaenoic acid) of 2:1 may be important in short term trials as there is evidence that DHA is incorporated more rapidly into human atrial tissue than is EPA.

Rodrigo, R, et al. A randomized controlled trial to prevent postoperative atrial fibrillation by antioxidant reinforcement. Journal of the American College of Cardiology, July 8, 2013 [Epub ahead of print]

Editor's comment: This study adds to existing evidence that vitamin C is useful in preventing postoperative atrial fibrillation in coronary artery bypass surgery[1]. There is also evidence that vitamin C prevents early recurrence following cardioversion of persistent AF and is effective in reducing levels of inflammatory markers and fibrinogen[2]. The finding that fish oil supplementation on its own increases oxidative stress is not surprising and supports my position that fish oil should always be taken in combination with vitamins C and E.
[1] Carnes, CA, et al. Ascorbate attenuates atrial pacing-induced peroxynitrite formation and electrical remodelling and decreases the incidence of postoperative atrial fibrillation. Circulation Research, Vol. 89, September 14, 2001, pp. e32-e38
[2] Korantzopoulos, P, et al. Oral vitamin C administration reduces early recurrence rates after electrical cardioversion of persistent atrial fibrillation and attenuates associated inflammation. International Journal of Cardiology, Vol. 102, No. 2, July 10, 2005, pp. 321-26