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Benefits of sodium glucose cotransporter 2 inhibitors across the spectrum of cardiovascular diseases
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  • Published on:
    The rationale for the proposed beneficial effect of SGLT2 inhibitors in diastolic heart failure and in mitigating the risk of occurrence of atrial fibrillation

    The observation that SGLT-2 inhibitors might favourably modify the natural history of heart failure with preserved ejection fraction(HFpEF) and might also mitigate the risk of onset of atrial fibrillation(AF)(1) might have, as its rationale, the fact that both disorders are characterised by the presence of myocardial fibrosis, the latter a probable consequence of an obesity-related proinflammatory cascade which is potentially amenable to mitigation by SGLT-2 inhibitor therapy.
    Adipose tissue is a source of proinflammatory cytokines such as tumor necrosis factor-alpha(TNF-alpha), Interleukin 1(IL-1), and Interleukin 6(IL-6), all three of which are secreted in increased amounts in response to obesity(2). Accordingly the presence of myocardial fibrosis either in the atria or in the ventricles might be the end result of a proinflammatory cascade originating in adipose tissue. Atrial fibrosis has been documented in obese subjects(body mass index > 30 kg/metre squared) who do not have AF(3) and and also in subjects who have established AF(4). In the former category there are, arguably, some individuals who will subsequently develop AF.
    The relevance of SGLT-2 inhibitors to the association of myocardial fibrosis and either HFpEF or AF has emerged from the study which showed an anti-inflammatory effect of SGLT2 inhibitor therapy in the normoglycemic rabbit model of atherosclerosis. In that study the inflammatory content of atherosclerotic plaqu...

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    Conflict of Interest:
    None declared.