TNF and heart failure: Inflammation plays a significant role in the pathogenesis and progression of heart failure through a variety of mechanistic pathways, driving myocardial fibrosis, hypertrophy, and dysfunction.64 Activation of Toll-like receptor 4 by damage- and pathogen-associated molecular patterns initiates the NLRP3 inflammasome, leading to increased levels of proinflammatory cytokines, such as TNF-α and IL-6.64 Endothelial inflammation disrupts nitric oxide bioavailability, stiffens titin, and accelerates fibrosis.