Inflammation in AF: Cause or effect?
HOUSTON, TEXAS. 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 conclude 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[1].
In January 2002 two research papers were published that clearly support the inflammation connection[2,3]. Both papers, one by American researchers (Cleveland Clinic) and one by Greek researchers, report a significant association between the level of C-reactive protein (CRP), a marker of inflammation, and the presence and severity of LAF.
The Cleveland researchers found that patients with AF, with or without structural heart disease, had significantly higher blood levels of 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 conclude that AF might induce or be induced by an inflammation, which in turn may promote the persistence of AF[2].
The 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 conclude that high CRP levels are strongly associated with the presence of AF and with a lower chance of successful cardioversion[3].
In a recent review of these and other studies researchers at Baylor College of Medicine conclude that inflammation plays a significant role in the perpetuation and maintenance of atrial fibrillation. They point out that inflammation is a potent risk factor for stroke and suggest that it would be advisable to reduce it. Statin drugs are known to have anti-inflammatory properties, but their role in actually preventing AF is not clear. The use of glucocorticoids (dexamethasone, cortisone, methylprednisolone) has been found effective in reducing CRP levels and post-operative afib. There is also some evidence that pharmacological conversion with propafenone is more effective and longer lasting if methylprednisolone is added to the protocol. The addition of methylprednisolone was also found to decrease CRP levels by 80%. Finally, it is possible that ACE inhibitors and angiotensin receptor blockers may help prevent inflammation-induced atrial remodeling and thereby reduce the risk of paroxysmal afib becoming permanent.
The Baylor College researchers conclude that the preponderance of evidence supports the conclusion that inflammation is an independent risk factor for the initiation and maintenance of AF, but do caution that it is still not clear whether inflammation causes AF or AF causes inflammation[4].
In order to answer this question Turkish researchers recently carried out an experiment in which an attempt was made to induce atrial fibrillation in 39 patients undergoing an electrophysiologic study for syncope (fainting) of undetermined origin or palpitations with no documented arrhythmias. None of the participants had been diagnosed with afib, or acute or chronic inflammatory diseases. CRP levels were measured before the EP study as well as 6 and 24 hours after the study. The researchers were able to induce afib in 18 patients leaving the remaining 21 patients as a control group. CRP levels at baseline were not significantly different between the two groups (2.8 mg/L vs 4.5 mg/L or 0.28 mg/dL and 0.45 mg/dL).
However, 24 hours after the procedure CRP increased in both groups. To 3.9 mg/L (0.39 mg/dL) in the control group compared to 10.0 mg/L (1.0 mg/dL) in the group in which afib was induced (average episode duration was 4.8 hours). The Turkish researchers conclude that the induction of afib was accompanied by a significant inflammatory process and that even the EPS study by itself caused an increase in CRP (in the control group).[5]
References
In January 2002 two research papers were published that clearly support the inflammation connection[2,3]. Both papers, one by American researchers (Cleveland Clinic) and one by Greek researchers, report a significant association between the level of C-reactive protein (CRP), a marker of inflammation, and the presence and severity of LAF.
The Cleveland researchers found that patients with AF, with or without structural heart disease, had significantly higher blood levels of 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 conclude that AF might induce or be induced by an inflammation, which in turn may promote the persistence of AF[2].
The 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 conclude that high CRP levels are strongly associated with the presence of AF and with a lower chance of successful cardioversion[3].
In a recent review of these and other studies researchers at Baylor College of Medicine conclude that inflammation plays a significant role in the perpetuation and maintenance of atrial fibrillation. They point out that inflammation is a potent risk factor for stroke and suggest that it would be advisable to reduce it. Statin drugs are known to have anti-inflammatory properties, but their role in actually preventing AF is not clear. The use of glucocorticoids (dexamethasone, cortisone, methylprednisolone) has been found effective in reducing CRP levels and post-operative afib. There is also some evidence that pharmacological conversion with propafenone is more effective and longer lasting if methylprednisolone is added to the protocol. The addition of methylprednisolone was also found to decrease CRP levels by 80%. Finally, it is possible that ACE inhibitors and angiotensin receptor blockers may help prevent inflammation-induced atrial remodeling and thereby reduce the risk of paroxysmal afib becoming permanent.
The Baylor College researchers conclude that the preponderance of evidence supports the conclusion that inflammation is an independent risk factor for the initiation and maintenance of AF, but do caution that it is still not clear whether inflammation causes AF or AF causes inflammation[4].
In order to answer this question Turkish researchers recently carried out an experiment in which an attempt was made to induce atrial fibrillation in 39 patients undergoing an electrophysiologic study for syncope (fainting) of undetermined origin or palpitations with no documented arrhythmias. None of the participants had been diagnosed with afib, or acute or chronic inflammatory diseases. CRP levels were measured before the EP study as well as 6 and 24 hours after the study. The researchers were able to induce afib in 18 patients leaving the remaining 21 patients as a control group. CRP levels at baseline were not significantly different between the two groups (2.8 mg/L vs 4.5 mg/L or 0.28 mg/dL and 0.45 mg/dL).
However, 24 hours after the procedure CRP increased in both groups. To 3.9 mg/L (0.39 mg/dL) in the control group compared to 10.0 mg/L (1.0 mg/dL) in the group in which afib was induced (average episode duration was 4.8 hours). The Turkish researchers conclude that the induction of afib was accompanied by a significant inflammatory process and that even the EPS study by itself caused an increase in CRP (in the control group).[5]
References
- Frustaci, Andrea, et al. Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation, Vol. 96, August 19, 1997, pp. 1180-84
- 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
- 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
- Issac, TT, et al. Role of inflammation in initiation and perpetuation of atrial fibrillation. Journal of the American College of Cardiology, Vol. 50, November 20, 2007, pp. 2021-28
- Pirat, B, et al. Comparison of C-reactive protein levels in patients who do and do not develop atrial fibrillation during electrophysiologic study. American Journal of Cardiology, Vol. 100, 2007, pp. 1552-55
The AFIB Report, Forum and Database do not provide medical advice. Do not attempt self-diagnosis or self-treatment based on our reports.
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A third donation method, beyond choosing either the Donate with PayPal or Donate with Credit/Debit card described elsewhere on this site, is for those who prefer to directly mail a check or money order to our business address at: The AFIB Report, A Non-Profit 501(c)(3) Corporation, C/O Shannon Dickson, P.O. Box 1016, Sedona, Arizona 86339. Any of the three donation options are fine with us based on each donor's preference, and with our sincere gratitude!
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