Everett Thomas H, Olgin Jeffrey E
Division of Cardiology and the Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143-1354, USA.
Heart Rhythm. 2007 Mar;4(3 Suppl):S24-7. doi: 10.1016/j.hrthm.2006.12.040. Epub 2006 Dec 28.
Atrial fibrillation (AF) is commonly associated with congestive heart failure (CHF), and CHF has been shown to be associated with atrial structural remodeling resulting in fibrosis. Atrial interstitial fibrosis has been seen in patients with CHF and in animal models of pacing-induced heart failure. With atrial fibrosis, conduction abnormalities result in increased AF vulnerability. The mechanism of AF associated with CHF is under debate, as both focal and reentrant mechanisms have been observed in animal models of CHF. However, recent studies using frequency-domain analysis have shown that the AF within this model is characterized by discrete, stable, high-frequency areas. The precise signaling processes involved in the development of atrial fibrosis are unknown. Angiotensin appears to play a role, as inhibition of angiotensin-converting enzyme (or angiotensin-receptor blocker) blunts atrial fibrosis in animal models of heart failure and decreases the incidence of AF in patients with heart failure. Transforming growth factor-beta (TGF-beta) also appears to play an important role. Mouse models that overexpress TGF-beta1 have profound atrial fibrosis and AF (with normal ventricles). Heart failure in canine models also produces increases in atrial TGF-beta1 expression, and inhibition of this expression prevents atrial fibrosis and the development of a substrate for AF. Atrial fibrosis appears to play a role in the development of a vulnerable substrate for AF, especially in the setting of CHF.
心房颤动（AF）通常与充血性心力衰竭（CHF）相关，并且已表明CHF与导致纤维化的心房结构重塑有关。在CHF患者和起搏诱导的心力衰竭动物模型中均可见心房间质纤维化。随着心房纤维化，传导异常导致AF易感性增加。与CHF相关的AF机制仍存在争议，因为在CHF动物模型中已观察到局灶性和折返性机制。然而，最近使用频域分析的研究表明，该模型中的AF具有离散、稳定、高频区域的特征。心房纤维化发展过程中涉及的精确信号传导过程尚不清楚。血管紧张素似乎起作用，因为在心力衰竭动物模型中抑制血管紧张素转换酶（或血管紧张素受体阻滞剂）可减轻心房纤维化，并降低心力衰竭患者的AF发生率。转化生长因子-β（TGF-β）似乎也起重要作用。过度表达TGF-β1的小鼠模型有严重的心房纤维化和AF（心室正常）。犬模型中的心力衰竭也会导致心房TGF-β1表达增加，抑制这种表达可预防心房纤维化和AF底物的形成。心房纤维化似乎在AF易损底物的形成中起作用，尤其是在CHF的情况下。
