Preventing Atrial Flutter by Preventing Inflammation

Abstract

Editorial CommentAlthough atrial arrhythmias are the most common tachyarrhythmias encountered in clinical practice, affecting several million patients in the United Stated alone, the exact etiology remains unknown.1 Several risk factors have been established and are well known, including older age, hypertension, or the postoperative state, 2 but the mechanistic connection between these demographic, disease, or situational conditions and a propensity to develop atrial arrhythmias is largely missing.Recently, the case for an important association between inflammation and arrhythmias in human subjects has been building, both for postoperative 3 and spontaneous arrhythmia. 4 The beginnings of the biological plausibility that motivated much of this work arose from the canine sterile pericarditis model first introduced by Dr. Waldo in 1986. 5 This contribution was significant not only in providing a model wherein atrial arrhythmias could be reliably induced, but also in demonstrating that inflammation was sufficient to make an animal prone to sustained atrial flutter (AFL) and atrial fibrillation (AF). In this issue of the Journal, Goldstein et al. take this model a step further: by examining the effects of steroids on the induction of atrial arrhythmias in the sterile pericarditis model, the authors enter the critical arena of novel therapeutics. 6 The authors have elegantly and clearly proven that the intense inflammatory response is indeed proarrhythmic. Moreover, they showed that the consistent findings of inducible sustained AFL were well correlated with an intense inflammatory response and elevated CRP levels in the control animals. These experiments are very persuasive. Indeed, the primary purpose of understanding the etiology of these arrhythmias should be to develop efficacious and safe treatments that can readily address the root cause underlying the disease.In their study, sterile pericarditis was created in 23 dogs, 11 of whom were pretreated with oral prednisone (40 mg twice daily). The drug was continued in the treatment group until the fourth postoperative day. The primary positive finding of the study was the inability to induce sustained AFL in the dogs treated with prednisone. Consistent with previous studies from the same group, sustained AFL was induced in all of the control dogs. In interpreting these data, two points bear emphasizing: first, neither AF nor AFL occurred spontaneously using the sterile pericarditis model (electrical stimulation was required). Second, sustained AFL was defined as AFL lasting > 10 minutes-importantly, at least one of This finding is particularly important because it demonstrates that inflammation can result in a sustained arrhythmia with a persistent (presumably single) electrical circuit and that this circuit can be prevented from forming with steroids. The concept that AF arises due to an abnormal atrial substrate (at least in some patients) is generally well accepted; 7,8 however, other more stable or single-circuit arrhythmias are typically thought to require a...