The emerging oral–heart failure axis: Mechanistic plausibility, bidirectionality, and the limits of causal evidence. A state-of-the-art review

Heart failure (HF) is a systemic, multiorgan syndrome in which inflammation, oxidative stress, endothelial dysfunction, metabolic abnormalities, and frailty contribute to disease progression. Periodontitis may represent an additional extracardiac source of inflammatory and microbial exposure, whereas HF itself may promote deterioration of oral health through frailty, malnutrition, impaired self-care, and reduced access to dental treatment. This state-of-the-art review evaluates the emerging oral-HF axis, focusing on systemic inflammation, oxidative stress and mitochondrial dysfunction, endothelial and coronary microvascular dysfunction (CMD), and myocardial fibrosis and remodeling. Epidemiological studies support associations between adverse oral-health indicators and HF, particularly tooth loss and edentulism, but findings for periodontitis are less consistent and remain vulnerable to residual confounding, reverse causation, and heterogeneous exposure definitions. Experimental studies provide biological plausibility for inflammatory, oxidative, endothelial, and fibrotic pathways, yet direct human evidence linking periodontal inflammatory burden to CMD, myocardial remodeling, or HF progression remains limited. Mendelian randomization does not currently support a direct causal effect of periodontitis on HF, and periodontal treatment has not been shown to reduce HF hospitalization or mortality. The oral-HF axis should therefore be regarded as a biologically plausible, bidirectional framework in which periodontitis may act as a disease modifier rather than an established independent cause of HF.