Caspase-1 is best known for its role in the NLRP3 inflammasome where it cleaves and processes IL-1β and IL-18.1 The involvement of the NLRP3 inflammasome has been documented in several cardiac contexts including acute myocardial infarction, heart failure and myocardial contractile dysfunction due to sepsis.26, 27, 28 Furthermore, Dox has also been shown to induce the NLRP3/caspase-1/IL-1β pathway in the context of macrophages and dendritic cells.29 However, our findings demonstrate that in cardiac tissue, Dox-induced caspase-1 activation is involved with other non-canonical pathways as well. The gene discussed is NLRP3; the disease is heart failure.