Figure 2. A proposed mechanism for suppression of AF in the setting of advanced fibrosis in the experimental HF: severe depression of atrial excitability.

A-C: Advanced atrial fibrosis appears to be a marker of prominent electrical depression of the atrium. Atrial enlargement develops much faster during early vs. late stages of HF whereas atrial fibrosis increases progressively during both early and late HF.^{11, 12, 15, 16} A high AF inducibility in early HF is associated with advanced atrial dilatation but moderate fibrosis. A reduction of AF vulnerability in late HF is accompanied by both severe atrial enlargement and fibrosis. Severe atrial fibrosis is associated with a prominent depression of atrial excitability, manifesting as a dramatic prolongation of the atrial effective refractory period (ERP) due to post-repolarization refractoriness (PRR). Advanced rate-dependent depression of atrial excitability acts to reduce AF occurrence. Panels B and C depict transmembrane action potentials illustrating the end of ERP in a healthy atrium and the development of PRR in an atrium with severe fibrosis isolated from a late HF heart. The left part of panel C shows an episode of AF induced by a single extrastimulus. The right part of panel C illustrates an example showing that acceleration of stimulation rate from a pacing cycle length of 500 to 250 ms is associated with a 2:1 activation failure, due to the prolonged PRR. Panels B and C are from Burashnikov et al,¹¹ with permission.