Role of inflammation in early atrial fibrillation recurrence.
ABSTRACT Outcome of rhythm control in atrial fibrillation (AF) is still poor due to various mechanisms involved in the initiation and perpetuation of AF. Differences in timing of AF recurrence may depend on different types of mechanisms. The aim of this study was to assess the mechanisms involved in early AF recurrence in patients with short-lasting AF.
Patients with short-lasting persistent AF undergoing rhythm control (n= 100) were included. Markers of mechanisms involved in the initiation and perpetuation of AF were assessed, including clinical factors, echocardiographic parameters, and biomarkers. Primary endpoint was early AF recurrence (recurrence <1 month). Secondary endpoint was progression to permanent AF. Median total AF history was short: 4.2 months. Early AF recurrences occurred in 30 patients (30%) after a median of 6 (inter-quartile range 2-14) days. Baseline log(2) interleukin (IL)-6 [adjusted hazard ratio (HR) 1.3, 95% confidence interval (CI) 1.0-1.7, P= 0.02] and present or previous smoking (adjusted HR 3.6, 95% CI 1.2-10.9, P= 0.03) were independently associated with early AF recurrence, suggesting that inflammation played an important role in early recurrences. Atrial fibrillation became permanent in 29 patients (29%). Baseline transforming growth factor-β1, left ventricular ejection fraction, and early AF recurrence were independently associated with progression to permanent AF.
In patients with short-lasting AF, early AF recurrence seemed to be associated with inflammation as represented by IL-6. Treatment aimed against inflammation may therefore prevent early AF recurrences, which can improve rhythm control outcome.
- [show abstract] [hide abstract]
ABSTRACT: Apelin is the endogenous ligand for the previously orphaned G protein-coupled receptor, APJ. This novel peptidic signalling pathway is widely represented in the heart and vasculature, and is emerging as an important regulator of cardiovascular homeostasis. In preclinical models, apelin causes nitric oxide-dependent vasodilatation, reduces ventricular preload and afterload, and increases cardiac contractility in rats with normal and failing hearts. Apelin-APJ signalling also attenuates ischemic myocardial injury and maintains cardiac performance in ageing and chronic pressure overload. Downregulation of apelin and APJ expression coincides with declining cardiac performance raising the possibility that diminished apelin-APJ activity may have pathophysiologic implications. At present, data from human studies is limited but changes in apelin and APJ expression in patients with chronic heart failure parallel those seen in preclinical models. Detailed clinical investigation is now required to establish the role of apelin in human cardiovascular physiology and pathophysiology, and to determine the therapeutic potential of augmenting apelin signalling in patients with heart failure.Biochemical pharmacology 06/2008; 75(10):1882-92. · 4.25 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: 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. The purpose of this study was to investigate the effect of atrial fibrillation on inflammatory markers drawn from intracardiac and extracardiac chambers. 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). 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. 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.Heart rhythm: the official journal of the Heart Rhythm Society 10/2009; 7(2):149-54. · 4.56 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: The VERDICT (Verapamil Versus Digoxin and Acute Versus Routine Serial Cardioversion Trial) is a prospective, randomized study to investigate whether: 1) acutely repeated serial electrical cardioversions (ECVs) after a relapse of atrial fibrillation (AF); and 2) prevention of intracellular calcium overload by verapamil, decrease intractability of AF. Rhythm control is desirable in patients suffering from symptomatic AF. A total of 144 patients with persistent AF were included. Seventy-four (51%) patients were randomized to the acute (within 24 h) and 70 (49%) patients to the routine serial ECVs, and 74 (51%) patients to verapamil and 70 (49%) patients to digoxin for rate control before ECV and continued during follow-up (2 x 2 factorial design). Class III antiarrhythmic drugs were used after a relapse of AF. Follow-up was 18 months. At baseline, there were no significant differences between the groups, except for beta-blocker use in the verapamil versus digoxin group (38% vs. 60%, respectively, p = 0.01). At follow-up, no difference in the occurrence of permanent AF between the acute and the routine cardioversion groups was observed (32% [95% confidence intervals (CI)] 22 to 44) vs. 31% [95% CI 21 to 44], respectively, p = NS), and also no difference between the verapamil- and the digoxin-randomized patients (28% [95% CI 19 to 40] vs. 36% [95% CI 25 to 48] respectively, p = NS). Multivariate Cox regression analysis revealed that lone digoxin use was the only significant predictor of failure of rhythm control treatment (hazard ratio 2.2 [95% CI 1.1 to 4.4], p = 0.02). An acute serial cardioversion strategy does not improve long-term rhythm control in comparison with a routine serial cardioversion strategy. Furthermore, verapamil has no beneficial effect in a serial cardioversion strategy.Journal of the American College of Cardiology 10/2006; 48(5):1001-9. · 14.09 Impact Factor