Efficacy and Safety of Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2i) in Cardiac Amyloidosis: A Systematic Review: Study protocol

Abstract

BACKGROUND: Sodium-glucose transport protein 2 inhibitors (SGLT2i) have revolutionized the management of heart failure and renal dysfunction. Cardiac amyloidosis, an underdiagnosed cause of heart failure, primarily results from light-chain (AL) or transthyretin (ATTR) deposition. Emerging evidence suggests that SGLT2i may improve cardiac and renal outcomes in these patients. However, data on their efficacy and safety in cardiac amyloidosis remain limited. This study aimed to conduct a systematic review to evaluate the efficacy and safety of SGLT2i in cardiac amyloidosis. METHODS: This systematic review and meta-analysis followed PRISMA guidelines and was registered on PROSPERO (CRD42024584183). A comprehensive search was performed across PubMed, Embase, Google Scholar, ScienceDirect, and Cochrane Library databases, including studies involving adult patients with AL or ATTR cardiac amyloidosis. Outcomes analyzed included cardiovascular mortality, heart failure hospitalizations, New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF), NT-proBNP, renal parameters, and adverse events. Data were synthesized using a random-effects model to account for heterogeneity, with effect measures expressed as risk ratios (RR) or mean differences (MD) and 95% confidence intervals (CIs). RESULTS: Preliminary findings indicate that SGLT2i use in cardiac amyloidosis is associated with significant improvements in LVEF, NT-pro BNP levels, and renal parameters such as eGFR and albuminuria progression. A reduction in heart failure hospitalizations and stabilization of NYHA functional class were also observed. Adverse events, including genitourinary infections and orthostatic hypotension, were reported but were consistent with known SGLT2i safety profiles. However, heterogeneity in study designs and small sample sizes limit definitive conclusions. CONCLUSION: This systemic review highlights the potential of SGLT2i to improve functional and cardiovascular outcomes in cardiac amyloidosis while maintaining an acceptable safety profile. Despite these promising results, further randomized controlled trials are necessary to confirm the findings and define the role of SGLT2i in managing cardiac amyloidosis. Until then, clinicians should cautiously integrate SGLT2i into treatment strategies based on individual patient characteristics and clinical context.