Effect of Intravenous Iron Combined With Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) on Ventricular Function and Myocardial Iron Content in Patients With Heart Failure With Reduced Ejection Fraction-Rationale for the COMBINED-HF Study.

BACKGROUND: Treatment with intravenous iron has been shown to improve symptoms, functional capacity, and quality of life in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency. However, the mechanisms underlying these beneficial effects remain unknown. Sodium-glucose cotransporter-2 inhibitor (SGLT2i) seems to alter hematocrit and other hematologic markers of iron content. This study aims to measure cardiac magnetic resonance changes in myocardial iron content after the administration of intravenous iron with or without SGLT2i and to assess changes in left ventricular function in patients with HFrEF and iron deficiency.

METHODS: Outpatients with symptomatic HFrEF, left ventricular ejection fraction (LVEF) <40%, SGLT2i-naive, and iron deficiency will be assigned to receive intravenous iron + SGLT2i; intravenous iron + a placebo of SGLT2i; or placebo of both therapies for 30 days. The total sample size was calculated to be 99 patients. Myocardial iron will be evaluated by T2-star cardiac magnetic resonance sequence before intravenous iron infusion. After 30 days, all patients will be reassessed with T2-star cardiac magnetic resonance sequencing. The primary endpoint will be changes in LVEF and myocardial iron content at 30 days. Secondary endpoints will include correlations of these changes with myocardial iron content, functional capacity, quality of life, and cardiac biomarkers.

CONCLUSIONS: This study will determine the effect of ferric carboxymaltose and its combination with SGLT2i on LVEF and its relationship with measures of myocardial iron content, functional capacity, and biomarkers in HFrEF and iron deficiency.