We sought to define the underlying mechanisms for atrial fibrillation (AF) during chronic heart failure (HF).

Preliminary studies showed that 4 months of HF resulted in irreversible systolic dysfunction (n = 9) and a substrate for sustained inducible AF (>3 months, n = 3). We used a chronic (4-month) canine model of tachypacing-induced HF (n = 10) to assess atrial electrophysiological remodelling, relative to controls (n = 5). Left ventricular fractional shortening was reduced from 37.2 ± 0.83 to 13.44 ± 2.63% (P < 0.05). Left atrial (LA) contractility (fractional area change) was reduced from 34.9 ± 7.9 to 27.9 ± 4.23% (P < 0.05). Action potential durations (APDs) at 50 and 90% repolarization were shortened by ∼60 and 40%, respectively, during HF (P < 0.05). HF-induced atrial remodelling included increased fibrosis, increased I_to, and decreased I_K1, I_Kur, and I_Ks (P < 0.05). HF induced increases in LA Kv channel interacting protein 2 (P < 0.05), no change in Kv4.3, Kv1.5, or Kir2.3, and reduced Kir2.1 (P < 0.05). When I_Ca-L was elicited by action potential (AP) clamp, HF APs reduced the integral of I_Ca in control myocytes, with a larger reduction in HF myocytes (P < 0.05). I_CaL measured with standard voltage clamp was unchanged by HF. Incubation of myocytes with N-acetylcysteine (a glutathione precursor) attenuated HF-induced electrophysiological alterations. LA angiotensin-1 receptor expression was increased in HF.

Chronic HF causes alterations in ion channel expression and ion currents, resulting in attenuation of the APD and atrial contractility and a substrate for persistent AF.