Abstract
BACKGROUND: Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy with limited treatment options. Barring mineralocorticoid receptor antagonists, most classes of guideline-directed medical therapy including renin-angiotensin-aldosterone inhibitors and beta blockers are avoided in CA due to intolerance and the risk of potentiating orthostatic hypotension. Few studies have explored the safety and utility of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in CA. These agents have demonstrated benefit in most heart failure phenotypes, and individuals with CA may benefit from treatment with them. We report a single-center experience demonstrating the safety of SGLT2is in patients with cardiac amyloidosis. METHODS: We conducted a retrospective study including patients with CA from January 2020 to March 2023 who were treated with empagliflozin at doses of 10 mg or 25 mg daily or dapagliflozin at a dose of 10 mg daily. Patients were monitored clinically for the development of adverse effects including urinary tract infections and orthostatic hypotension as well as through laboratory monitoring for acute kidney injury and for changes in microalbuminuria. RESULTS: Our cohort comprised 53 patients with cardiac amyloidosis treated with an SGLT2i, 38 (72%) of whom were male, with a mean participant age of 81±8 years and left ventricular ejection fraction of 50%. Urinary tract infections were observed in three participants (6%). Acute kidney injury occurred in two participants. No participant experienced orthostatic hypotension. There was a trend toward improved functional status, reduced hospitalizations (decrease from median 1 to 0.6 per patient-year, p=0.18), and microalbuminuria (mean albumin:creatinine ratio of 53.8 mg/g improved to 29.2 mg/g, p=0.32), although these differences were not statistically significant. CONCLUSIONS: Within our cohort of individuals with cardiac amyloidosis, SGLT2i therapy appeared to be well-tolerated and may have clinical benefit in the form of reduced hospitalizations and improvements in microalbuminuria. Notably, the differences in outcomes were not statistically significant. By demonstrating safety and tolerance, we hope to stimulate prospective randomized studies that may definitively explore the utility of SGLT2i therapy in enhancing clinical outcomes.