Pleiotrope Effekte Empagliflozins auf humanes und murines Myokard
Abstract
Heart failure with preserved ejection fraction (HFpEF) remains a clinical challenge with limited treatment options. Empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, has been shown to reduce cardiovascular mortality and hospitalization in heart failure patients, yet the underlying cardiac mechanisms remain incompletely understood. This dissertation investigates the direct, diabetes-independent effects of empagliflozin on myocardial function using both human and murine myocardial tissue. Human failing hearts and murine myocardial strips were analyzed ex vivo to assess systolic and diastolic parameters under empagliflozin treatment. The results demonstrated that empagliflozin significantly reduced diastolic tension without affecting systolic force development or calcium handling indicators. Notably, no significant differences were observed in post-rest behavior or force-frequency relationships compared to controls. These findings suggest that the beneficial effects of empagliflozin on diastolic function may occur independently of systemic metabolic changes, highlighting a novel therapeutic mechanism in the treatment of HFpEF. This work adds mechanistic insight to the EMPA-REG OUTCOME study and offers a rationale for further translational studies.
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