A real world experience: Sodium-glucose co-transporter-2 (SGLT2) inhibitors in cancer therapy related cardiac dysfunction (CTRCD)

Abstract Introduction Cardiac dysfunction is a common cardiotoxicity amongst patients receiving cancer treatment4. SGLT2i may be efficacious in this high-risk subgroup of patients2. However, patients with active malignancy were often excluded from landmark trials1,7-8,11 There are also concerns of potential side effects and intolerance of SGLT2i in these patients. This study aims to provide a real-world experience into the use of SGLT2i in patients with chemotherapy related cardiac dysfunction. Methods This is a single centre, retrospective observational cohort study performed at our Cardio-Oncology unit between August 2021 to January 2024. Patients were included if they were receiving anti-cancer therapy and had symptomatic heart failure or asymptomatic CTRCD. Results SGLT2i were started in 57 patients. 11 (19%) had type 2 diabetes mellitus. Breast and haematological malignancies were most common (18 (32%) and 15 (26%)). Forty-five (79%) patients received chemotherapy, of which 24 (42%) had anthracyclines and 16 (28%) received HER2 targeted therapies. 42 (74%) presented with symptomatic heart failure. The mean high sensitive Troponin I and BNP were elevated at 62+114ng/L and 438+540ng/L. 52 (91%) patients were on an angiotensin converting enzyme inhibitor, angiotensin receptor blocker or angiotensin receptor neprilysin inhibitor. 49 (86%) and 36 (63%) received a beta-blocker and mineralocorticoid receptor antagonist. Dapagliflozin was prescribed in 50 (88%) patients. There was a significant reduction in left ventricular end diastolic volumes, improvement in left ventricular ejection fraction and global longitudinal strain with medical therapy (133+52mls vs 71+25mls, p0.05, 42+14% vs 47+11%, p0.05, and -11.4+3.0% vs -18.6+2.4%, p0.05). Four (7%) patients had a documented adverse drug reaction (dizziness, hypotension and urinary symptoms) to SGLT2i. Only 2 patients discontinued SGLT2i while the rest could continue the drug. There was 0 cardiovascular death and heart failure admissions. Conclusion Numerous trials have demonstrated the effectiveness of SGLT2i in heart failure1,7-8,11. Recent guidelines have strongly recommended the use of SGLT2i to reduce cardiovascular mortality and heart failure hospital admissions5-6. In vitro and animal studies have suggested extension of the cardioprotective effects of SGLT2i in CTRCD9-10 , and there is increasing suggestion that SGLT2i can improve outcomes in CTRCD2-3. Our study adds to the growing body of evidence that SGLT2i may improve left ventricular systolic function, reduce heart failure admissions and cardiovascular death, and is also well tolerated in this high-risk group of patients. Limitations The authors acknowledge the limitations of the small sample size in this study. A significant proportion of the patients were also started on guideline directed medical therapy around the same time, and direct causation with improvement in cardiac function cannot be sought for SGLT2i alone.Figure 1 Figure 2