BACKGROUND
In 1997 Dr. Andrea Frustaci, MD and colleagues at the Catholic University of Rome made a fascinating discovery. They performed biopsies of the right atrium in 12 patients with LAF and found that 8 (67%) of them had evidence of a current or past inflammation in the heart tissue (myocarditis). They also checked 11 control subjects and found that none of their biopsy samples showed any signs of inflammation. The Italian researchers concluded that inflammation and its aftermath (fibrotic tissue) is a likely cause of LAF.

The inflammation was found to be active in 3 of the 8 patients. These patients were treated with the anti-inflammatory medication prednisone. They had no further LAF episodes over a 2-year follow-up. The remaining patients were treated with propafenone, sotalol, flecainide or amiodarone and had numerous LAF episodes over the next 2 years.

Through correspondence with Dr. Frustaci I learned that 2 more patients had later shown signs of active inflammation and had been successfully treated with prednisone. Dr. Frustaci concurred that a relapse of atrial inflammation could result in new episodes of LAF and that it is quite possible that all of the 12 LAF patients actually had signs of inflammation, but that the biopsy missed them in four of the cases[1,2].

In January 2002 Cleveland Clinic researchers reported that patients with AF, with or without structural heart disease, had significantly higher blood levels of the inflammation marker, C-reactive protein (CRP), than did controls (median value of 0.21 mg/dL versus 0.096 mg/dL). The average value for LAF patients was 0.21 mg/dL, which was not significantly lower than that found in AF patients with structural heart disease (0.23 mg/dL). CRP levels were generally higher if the patients were actually in atrial fibrillation or had come out of an episode within 24 hours of sampling. These patients had average CRP values of 0.30 mg/dL as compared to 0.15 mg/dL for AF patients in sinus rhythm. It was also clear that patients with persistent AF had higher CRP values than patients with paroxysmal AF (0.34 mg/dL versus 0.18 mg/dL). The researchers concluded that AF might induce or be induced by an inflammation, which in turn may promote the persistence of AF[3].

Also in 2002 Greek researchers tested CRP levels in 50 paroxysmal AF patients who were actually in fibrillation at the time of sampling and compared results to those obtained for 50 people in normal sinus rhythm. The AF patients had a median CRP level of 0.80 mg/dL as compared to 0.04 mg/dL for controls. The researchers observed that AF patients who could not be cardioverted had a much higher average CRP level (2.12 mg/dL) than did patients who were successfully cardioverted (0.50 mg/dL). They also noted that patients with an enlarged left atrium had considerably less success in being cardioverted. They concluded that high CRP levels are strongly associated with the presence of AF and with a lower chance of successful cardioversion[4].

Although the preponderance of evidence relating to the association between inflammation and AF favour the hypothesis that inflammation causes AF, Prof. Haissaguerre and his group in Bordeaux did report in 2006 that being in sinus rhythm after catheter ablation was associated with a significant decline in CRP[5]. This would support the idea that AF causes inflammation. Nevertheless, the general consensus today is that inflammation is indeed the causative agent. This is further supported by the observation made by Finnish researchers that the incidence of AF following cardiac surgery can be significantly reduced by treatment with corticosteroids[6].

References

1. Frustaci, Andrea, et al. Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation, Vol. 96, August 19, 1997, pp. 1180-84
2. Frustaci, Andrea. Personal communication to Hans Larsen, July 23, 2001
3. Chung, Mina K., et al. C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation. Circulation, Vol. 104, December 11, 2001, pp. 2886-91
4. Dernellis, J. and Panaretou, M. C-reactive protein and paroxysmal atrial fibrillation: evidence of the implication of an inflammatory process in paroxysmal atrial fibrillation. Acta Cardiol, Vol. 56, No. 6, December 2001, pp. 375-80
5. Rotter, M, et al. Decline in C-reactive protein after successful ablation of long-lasting persistent atrial fibrillation. Journal of the American College of Cardiology, Vol. 47, No. 6, March 21, 2006, pp. 1231-33
6. Halonen, J, et al. Corticosteroids for the prevention of atrial fibrillation after cardiac surgery. Journal of the American Medical Association, Vol. 297, No. 14, April 11, 2007, pp. 1562-67

ABSTRACT
TSUKUBA, JAPAN. Japanese researchers report that post-ablation therapy with corticosteroids can reduce the incidence of AF recurrence both short- and long-term. Their randomized, double-blind study involved 125 paroxysmal afibbers 80% of whom had no structural heart disease (lone AF). The average age of the patients was 61 years, 80% were male, and the average number of years since diagnosis was 7. All patients underwent a pulmonary vein isolation (PVI) procedure using the double Lasso technique without a three-dimensional mapping system. Ten patients needed an additional roof line lesion and 7 needed isolation of the superior vena cava in order to terminate AF. All patients also underwent a right atrial flutter ablation.

Immediately following the procedure half the patients received an injection of placebo (0.9% saline) while the other half received an injection of hydrocortisone. Oral prednisolone was also administered to the hydrocortisone group for 3 days following the procedure.

During the first month following the ablation, 49% of the patients in the placebo group experienced AF recurrence as compared to only 27% in the corticosteroid group. The recurrence happened within the first 3 days post-procedure in 31% of the placebo group versus only 7% of the corticosteroid group. At the end of the 14-month follow-up period, 71% of the patients in the placebo group were free of AF without the use of antiarrhythmics as compared to 85% in the corticosteroid group. The Japanese researchers also measured CRP levels and body (armpit) temperature in the study participants and made several interesting observations:

• During the initial 3 days following PVI the CRP and maximum body temperature were both significantly higher in the placebo group, clearly indicating that the corticosteroid therapy did indeed dampen post-procedure inflammation.

• Experiencing AF recurrence within the first 3 days post-procedure was associated with poorer long-term prognosis in the placebo group, but not in the corticosteroid group.

• Elevated post-procedure body temperature and CRP were both related to an increased incidence of immediate AF recurrence.

• Early AF recurrences occurring within 4 days to 1 month post-ablation were not associated with an inflammatory response indicating that a relatively short (3 days) course of corticosteroids is sufficient to markedly reduce long-term recurrence risk.

Koyama, T, et al. Prevention of atrial fibrillation recurrence with corticosteroids after radiofrequency catheter ablation. Journal of the American College of Cardiology, Vol. 56, No. 18, October 26, 2010, pp. 1463-72

Editor�s comment: The Japanese study clearly confirms our long held conviction that it is very important to curtail inflammation after a PVI procedure. The hydrocortisone/prednisolone approach is certainly an excellent idea and should ideally be followed by an anti-inflammatory protocol using fish oil, Zyflamend, curcumin, beta-sitosterol, Boswellia or other natural anti-inflammatories.

Another important anti-inflammatory measure one should take is to avoid strenuous exercise for at least 4-6 weeks after the ablation. Strenuous and prolonged physical activity will markedly �fan the flames� of an inflammation and may also deplete important electrolytes, especially potassium and magnesium. Swedish sports medicine experts are adamant that exercise should be totally avoided whenever myocarditis (inflammation of the heart tissue) is suspected[1]. Very recently Greek researchers found that participants in a 36-hour long distance run experienced a 152-fold increase in CRP levels and an 8000-fold increase in the level of interleukin-6 (IL-6), another important marker of systemic inflammation. They conclude that the increases in the inflammation markers noted, �amount to a potent systemic inflammatory response�[2].

While not many afibbers will run a 36-hour marathon following their ablation, the Greek study, nevertheless, clearly supports the contention that prolonged, heavy exercise is very detrimental when it comes to preventing or combating an inflammation. I would suggest that no exercise at all would be the best approach for the first two weeks after the ablation followed by one or two daily walks for the next month or so. Jumping right into a strenuous physical activity program right after an ablation is, in my opinion, a very unwise thing to do and will more than likely lead to the need for another ablation.

In conclusion, I strongly believe that ensuring an adequate potassium intake, following a suitable anti-inflammatory protocol, and going very easy on the exercise for the first month, at least, can go a long way to preventing a miserable recovery period and may even help ensure the success of the ablation.

References

1. Friman, G and Wesslen, L. Special feature for the Olympics: effects of exercise on the immune system: infections and exercise in high-performance athletes. Immunol Cell Biol, Vol. 78, No. 5, October 2000, pp. 510-22
2. Margeli, A, et al. Dramatic elevations of interleukin-6 and acute phase reactants in athletes participating in the ultradistance foot race �Spartathlon�: severe systemic inflammation and lipid and lipoprotein changes in protracted exercise. J Clin Endocrinol Metab, Vol. 90, No. 7, July 2005, pp. 3914-18