Intracardiac and extracardiac markers of inflammation during atrial fibrillation

Received 25 August 2009; accepted 5 October 2009. published online 12 October 2009.

Background

A decrease in inflammation after cure of atrial arrhythmias suggests that such arrhythmias are proinflammatory, and lower inflammatory marker levels in the coronary sinus suggest that atrial arrhythmias result in intracardiac appropriation of inflammatory cytokines.

Objective

The purpose of this study was to investigate the effect of atrial fibrillation on inflammatory markers drawn from intracardiac and extracardiac chambers.

Methods

We performed a case-control study of 167 AF patients and 207 controls. Blood from intracardiac and extracardiac sites was obtained from a subset of patients undergoing curative AF ablation (n = 46).

Results

No significant differences in C-reactive protein (CRP) or interleukin-6 (IL-6) levels were seen between patients with and those without a history of AF. Both levels were significantly higher when blood was drawn during AF than during sinus rhythm: median CRP 3.1 mg/dL (interquartile range [IQR] 1.0–6.0) versus 1.7 mg/dL (IQR 0.7–3.9, P = .0005); median IL-6 2.3 ng/mL (IQR 1.5–3.9) versus 1.5 ng/mL (IQR 0.7–2.5, P = .007). This finding persisted after adjusting for potential confounders. AF ablation patients in AF exhibited a positive median left atrial minus coronary sinus gradient CRP (0.3 mg/dL, IQR −0.03–1.1), whereas those in sinus rhythm had a negative median left atrial minus coronary sinus gradient CRP (−0.2, IQR −0.8–[−0.02], P = .01). Femoral artery minus femoral vein gradients in AF versus sinus rhythm did not show any differences.

Conclusion

AF at the time of the blood draw, rather than a history of AF, was independently associated with inflammation. Differences in transcardiac gradients suggest that AF results in sequestration of inflammatory cytokines in the heart.

Keywords: Atrial fibrillation, Coronary sinus, C-reactive protein, Inflammation, Interleukin-6, Left atrium

Abbreviations: ACE, angiotensin-converting enzyme, AF, atrial fibrillation, ARB, angiotensin receptor blocker, CRP, C-reactive protein, ELISA, enzyme-linked immunosorbent assay, IL-6, interleukin-6, IQR, interquartile range

a Division of Cardiology, Electrophysiology Section, University of California, San Francisco, San Francisco, California

b Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California

Address reprint requests and correspondence: Dr. Gregory M. Marcus, University of California, San Francisco, 500 Parnassus Avenue, MUE 434, San Francisco, California 94143-1354

This work was made possible by Grant KL2 RR024130 from the National Center for Research Resources (NCRR), a division of the National Institutes of Health (Bethesda, MD), to Dr. Marcus and by an American Heart Association Western States Affiliate Beginning Grant-in-Aid Award (Menlo Park, CA) to Dr. Marcus.

PII: S1547-5271(09)01148-5

doi:10.1016/j.hrthm.2009.10.004

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