AimsSodium-glucose co-transporter 2 (SGLT2) inhibition reduces heart failure hospitalizations in patients with diabetes, irrespective of glycaemic control. We examined the effect of SGLT2 inhibition with empagliflozin (EMPA) on cardiac function in non-diabetic rats with left ventricular (LV) dysfunction after myocardial infarction (MI).Non-diabetic male Sprague-Dawley rats underwent permanent coronary artery ligation to induce MI, or sham surgery. Rats received chow containing EMPA that resulted in an average daily intake of 30 mg/kg/day or control chow, starting before surgery (EMPA-early) or 2 weeks after surgery (EMPA-late). Cardiac function was assessed using echocardiography and histological and molecular markers of cardiac remodelling and metabolism were assessed in the left ventricle. Renal function was assessed in metabolic cages. EMPA increased urine production by two-fold without affecting creatinine clearance and serum electrolytes. EMPA did not influence MI size, but LV ejection fraction (LVEF) was significantly higher in the EMPA-early and EMPA-late treated MI groups compared to the MI group treated with vehicle (LVEF 54%, 52% and 43%, respectively, all P < 0.05). EMPA also attenuated cardiomyocyte hypertrophy, diminished interstitial fibrosis and reduced myocardial oxidative stress. EMPA treatment reduced mitochondrial DNA damage and stimulated mitochondrial biogenesis, which was associated with the normalization of myocardial uptake and oxidation of glucose and fatty acids. EMPA increased circulating ketone levels as well as myocardial expression of the ketone body transporter and two critical ketogenic enzymes, indicating that myocardial utilization of ketone bodies was increased. Together these metabolic changes were associated with an increase in cardiac ATP production.

We demonstrate that the presence of HF is associated with enhanced tumor growth and that this is independent of hemodynamic impairment and could be caused by cardiac excreted factors. A diagnosis of HF may therefore be considered a risk factor for incident cancer.

Aims Adipose tissue and inflammation may play a role in the pathophysiology of patients with heart failure (HF) with mildly reduced or preserved ejection fraction. We therefore investigated epicardial fat in patients with HF with preserved (HFpEF) and mid‐range ejection fraction (HFmrEF), and related this to co‐morbidities, plasma biomarkers and cardiac structure. Methods and results A total of 64 HF patients with left ventricular ejection fraction >40% and 20 controls underwent routine cardiac magnetic resonance examination. Epicardial fat volume was quantified on short‐axis cine stacks covering the entire epicardium and was related to clinical correlates, biomarkers associated with inflammation and myocardial injury, and cardiac function and contractility on cardiac magnetic resonance. HF patients and controls were of comparable age, sex and body mass index. Total epicardial fat volume was significantly higher in HF patients compared to controls (107 mL/m 2 vs. 77 mL/m 2 , P <0.0001). HF patients with atrial fibrillation and/or type 2 diabetes mellitus had more epicardial fat than HF patients without these co‐morbidities (116 vs. 100 mL/m 2 , P =0.03, and 120 vs. 97 mL/m 2 , P =0.001, respectively). Creatine kinase‐MB, troponin T and glycated haemoglobin in patients with HF were positively correlated with epicardial fat volume (R =0.37, P =0.006; R =0.35, P =0.01; and R =0.42, P =0.002, respectively). Conclusion Heart failure patients had more epicardial fat compared to controls, despite similar body mass index. Epicardial fat volume was associated with the presence of atrial fibrillation and type 2 diabetes mellitus and with biomarkers related to myocardial injury. The clinical implications of these findings are unclear, but warrant further investigation.