Endothelin-1 concentrations in the left atrium increase in both AF and heart failure (Mayyas et al., 2010) and this may act locally to enhance diastolic leak and ectopy via inositol 1,4,5-triphosphate signaling (Proven et al., 2006; Tinker et al., 2016), as well as by upregulating profibrotic pathways implicated in structural remodeling (Ruwhof and van der Laarse, 2000; Burstein et al., 2008). The gene discussed is EDN1; the disease is atrial fibrillation.