Safety of SGLT2-Inhibitors in cardio-oncology patients with heart failure undergoing cancer treatment

Abstract Introduction Sodium-glucose cotransporter 2-Inhibitors (SGLT2i) have demonstrated benefits for patients with heart failure (HF), regardless of their diabetes status and left ventricular ejection fraction (LVEF). Cancer therapy induced cardiac dysfunction (CTRCD) encompasses a broad spectrum of cardiovascular complications resulting from cancer treatments including myocardial ischemia, coronary vasospasm, and arrhythmias. Recent retrospective clinical studies suggest a benefit in cancer patients with diabetes and chemotherapy with concomitanty SGLT-2i therapy (1). Translational studies suggest an anticancer effect e.g. by antiangiogenesis and mitochondrial effects (2). This study aimed to assess the cardiac effectiveness and overall safety of SGLT2 inhibitors in patients undergoing cancer treatment. Methods Prospective cancer patients with different malignancies or survivors of childhood cancer, undergoing cancer treatment with radiotherapy and/or additional chemo- or immune therapy, who received a SGLT2i therapy were evaluated at baseline and at 6 months follow-up. 61 of the 83 patients received chemotherapy with, for example, anthracyclines , alkylating agents and targeted therapy. Transthoracic echocardiography, speckle tracking strain and laboratory assessments were performed in all patients at baseline and follow-up at our cardio-oncology clinic. Here we present preliminary data of the ongoing study. Results A total of 83 Patients (51% female, 49% male, range 28-85 years) with SGLT2i treatment were analyzed. The most common primary cancer types included cancer of the lungs (23 patients, 28%), breast cancer (23 patients, 28%) followed by the hematologic system (15 patients, 18%), the abdominal system (8 patients, 10%), the skin (7 patients, 8%), cancer in the neck area (3 patients, 4%) and the urogenital system (3 patients, 4%). The median NT-proBNP level at baseline was 490.5 pg/mL (IQR 205-1169). During the treatment with SGLT2i the median NT-proBNP decreased to a level of 436.5 pg/mL (IQR 168-1236) (p=0.021). In echocardiography, reduced systolic left ventricular function was present in 63 patients (76%) and reduced right ventricular function was present in 20 patients (24%). During the study period the mean creatinine stayed stable with an average of 0.8 ± 0.55 mg/dL at baseline and 1.1 ± 0.50 mg/dL at follow-up (p=0.299). Conclusion The use of SGLT2-Inhibitors is associated with a tendency to improvement in NT-proBNP levels in patients with heart failure undergoing cancer treatment. The treatment with SGLT2-Inhibitors is well tolerated in patients undergoing cancer treatment and no clinically relevant side effects were observed.Cardioprotective Mechanisms of SGLT2i Strain was highly reduced