P2425Effects of intravenous iron therapy on chemoreflex sensitivity and sleep disordered breathing in chronic heart failure

Abstract

Background: Intravenous iron therapy has been reported to improve clinical conditions in chronic heart failure (CHF) patients. The mechanisms underlying such an improvement are complex and yet not completely understood. Altered chemoreflex sensitivity and presence of sleep disordered breathing may both characterize the pathophysiology of CHF, could be reciprocally interrelated and might be worsened by anemia and iron deficiency. We hypothesized that intravenous iron therapy would favorably affect chemoreflex sensing in CHF by improving a deranged iron metabolism and hemoglobin concentration. Methods: We performed a double‐blind randomized controlled (ferric carboxymaltose: placebo=2:1) study investigating the effects of intravenous iron therapy on chemoreflex sensitivity and sleep disordered breathing in anemic, irondeficient CHF patients with left ventricular ejection fraction ≤45%. Anemia was defined as Hb<13 g/dL in men and <12 g/dL in women; iron deficiency as ferritin <100 mcg/L or ferritin <300 mcg/L if transferrin saturation was <20%. Central chemoreflex sensitivity was assessed as the slope of the relationship between minute ventilation and the partial pressure for end‐tidal CO2 during a 4‐minute rebreathing of a mixture of 7% CO2 in oxygen. Breathing pattern during sleep was assessed by cardiorespiratory monitoring during the night. Examinations were performed before and one month after intravenous iron therapy targeted to replenish iron stores according to the Ganzoni's formula modified to account for the differences of Hb reference values between genders. Results: Out of 70 patients enrolled, 58 completed the study (age 71±10, 21% women, mean hemoglobin 11.3±1.0 g/dL), 38 randomized to i.v. ferric carboxymaltose and 20 to i.v. placebo. Clinical characteristics, blood tests and echocardiography of the two study groups did not differ at baseline, this being the case also for chemoreflex sensitivity and burden of sleep breathing disorders. Intra‐ venous iron was associated with reduction of central chemoreflex sensitivity (from 4.6±6.5 to 2.9±2.9 L/min/mmHg, p<0.05), with no changes under placebo (from 4.4±4.6 to 4.6±3.9 L/min/mmHg). After therapy, apnea‐hypopnea index and oxygen desaturation index during nighttime were lower in the active arm group than in the placebo group (12±12 vs 19±12 /h and 13±12 vs 21±12 respectively, p<0.05). In the whole population, the changes in oxygen desaturation index were inversely correlated with hemoglobin changes (R2=0.17, p<0.05). NYHA class improved only in the active treatment group (61% of patients in NYHA >2 at baseline vs 26% after treatment, p<0.05) but not in the placebo group. Conclusions: Intravenous iron therapy may improve central chemoreflex sensitivity and sleep disordered breathing in CHF. Such effect of intravenous iron therapy may explain part of its favorable impact on quality of life in CHF reported in previous studies.