We found that sildenafil dramatically reduced the incidence and delayed the occurrence of afterdepolarizations, premature ventricular complexes (PVCs), and Torsades de Pointes (TdP) in vivo, and these effects were attributable to a PKG-dependent effect on Ca2+ waves and involved a reduction in SR Ca2+ content. The gene discussed is PRKG1; the disease is ventricular ectopy.