Intracardiac and extracardiac markers of inflammation during atrial fibrillation

Abstract

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.

Figure 1

Median levels of C-Reactive Protein (CRP) in mg/dL and interleukin-6 (IL-6) in ng/ml compared between those with and without an AF history, paroxysmal versus chronic atrial fibrillation, in atrial fibrillation versus in sinus rhythm at the time of the blood draw, in atrial fibrillation versus in sinus rhythm at the time of the blood draw only among those with a history of atrial fibrillation, and in atrial fibrillation versus in sinus rhythm at the time of the blood draw only among those with a history of paroxysmal atrial fibrillation. Y-error bars denote interquartile ranges.

Figure 2

Adjusted odds ratios of logCRP and logIL-6 each adjusted for left atrial volume and a history of paroxysmal versus persistent atrial fibrillation as predictors of the presence of atrial fibrillation versus sinus rhythm at the time of the blood draw among 105 consecutive patients presenting for curative atrial fibrillation ablation. The odds ratios for left atrial volume as a predictor of the presence of atrial fibrillation versus sinus rhythm after adjustment for a history of paroxysmal versus persistent atrial fibrillation and either logCRP or logIL-6 are also shown. Y error bars denote 95% confidence intervals.

Figure 3

Median levels of C-Reactive Protein (CRP) in mg/dL and interleukin-6 (IL-6) in ng/ml compared between atrial fibrillation ablation patients in atrial fibrillation (n=20) versus in sinus rhythm (n=26) at the time of the blood draw assessed from the femoral vein, coronary sinus, femoral artery, and left atrium. Y error bars denote interquartile ranges. *Coronary sinus levels were available in 10 patients in atrial fibrillation and 12 patients in sinus rhythm.

Figure 4

The trans-cardiac (left atrial minus coronary sinus) and trans-femoral (femoral artery minus femoral vein) gradients in median C-Reactive Protein (CRP) and interleukin-6 (IL-6) levels in those in atrial fibrillation (n=20) versus sinus rhythm (n=26) at the time of the blood draw. Y error bars denote interquartile ranges. * Coronary sinus levels were available in 10 patients in atrial fibrillation and 12 patients in sinus rhythm.