Animal models and human tissue studies have shown that various HCN isoforms (HCN1, 2, and 4, depending on the species studied) are upregulated in the atria and ventricles in heart failure as part of the reversion to an embryonic expression profile.9,10,12,35 Thus, a direct block by IVB of If in the ventricle may attenuate hypertrophy, apoptosis, and electrophysiological remodeling.36 One major advantage of the approach we have undertaken is that it disentangles the effects of HR reduction from the other effects of IVB. The gene discussed is HCN1; the disease is heart failure.