Department of Cardiovascular, Neural and Metabolic Sciences, Istituto Auxologico Italiano IRCCS, Ospedale San Luca, Milano, Italy. Department of Management, Information and Production Engineering, University of Bergamo, Dalmine (BG), Italy. Centro Cardiologico Monzino, IRCCS, Milan, Italy. Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy. MultiMedica IRCCS, Milan, Italy. Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
BACKGROUND Intravenous iron therapy can improve symptoms in patients with heart failure, anemia and iron deficiency. The mechanisms underlying such an improvement might involve chemoreflex sensing and nocturnal breathing patterns. METHODS Patients with heart failure, reduced left ventricular ejection fraction, anemia (hemoglobin <13 g/dL in men; <12 g/dL in women) and iron deficiency (ferritin <100 or 100-299 mcg/L with transferrin saturation <20%) were 2:1 randomized to patients-tailored intravenous ferric carboxymaltose dose or placebo. Chemoreflex sensitivity cardiorespiratory sleep study, symptom assessment and cardiopulmonary exercise test were performed before and two weeks after the last treatment dose. RESULTS Fifty-eight patients (38 active arm / 20 placebo arm) completed the study. Intravenous iron was associated
with less severe symptoms, higher hemoglobin (12.5±1.4 vs. 11.7±1.0mg/dl p<0.05) and improved hematinic parameters. Ferric carboxymaltose improved the central hypercapnic ventilatory response (-25.8%, p<0.05 vs. placebo), without changes in peripheral chemosensitivity. In particular, the central hypercapnic ventilatory responses passed from 4.6±6.5 to 2.9±2.9 L/min/mmHg after ferric carboxymaltose and from 4.4±4.6 to 4.6±3.9 L/min/mmHg after placebo (p(treatment*condition) =0.046). In patients presenting with sleep-related breathing disorder, apnea-hypopnea index was reduced with active treatment as compared to placebo (12±11 vs. 19±13 events/h, p<0.05). After ferric carboxymaltose, but not after placebo, both peak oxygen uptake (VO2) increased (Δ1.1±2.0 mL/Kg/min, p<0.05) and VO2/workload slope was steeper (Δ0.67±1.7 L/min/W, p<0.01). CONCLUSIONS Intravenous ferric carboxymaltose improves the hypercapnic ventilatory response and sleep-related breathing disorders in patients with heart failure, anemia and iron deficiency. These newly described findings, along with improved oxygen delivery to exercising muscles, likely contribute to the favorable effects of ferric carboxymaltose in anemic patients with heart failure. This article is protected by copyright. All rights reserved.