TNF and heart failure: Downregulation of iNOS, TNF-α, IL6 and IRF4 in activated macrophages (219).It blocks NF-κB in cardiac myocytes through HDAC inhibition and increasing histone acetylation (220, 221),It blocks pyroptosis by attenuating NOD-, LRR- and NLRP3 inflammasome pathway in hypoxic-induced heart cells (221).It prevents cardiac dysfunction in pre-clinical animal models of heart failure (222–225).