BACKGROUND Iron deficiency may impair aerobic performance. This study aimed to determine whether treatment with intravenous iron (ferric carboxymaltose) would improve symptoms in patients who had heart failure, reduced left ventricular ejection fraction, and iron deficiency, either with or without anemia. METHODS We enrolled 459 patients with chronic heart failure of New York Heart Association (NYHA) functional class II or III, a left ventricular ejection fraction of 40% or less (for patients with NYHA class II) or 45% or less (for NYHA class III), iron deficiency (ferritin level <100 μg per liter or between 100 and 299 μg per liter, if the transferrin saturation was <20%), and a hemoglobin level of 95 to 135 g per liter. Patients were randomly assigned, in a 2:1 ratio, to receive 200 mg of intravenous iron (ferric carboxymaltose) or saline (placebo). The primary end points were the self-reported Patient Global Assessment and NYHA functional class, both at week 24. Secondary end points included the distance walked in 6 minutes and the health-related quality of life. RESULTS Among the patients receiving ferric carboxymaltose, 50% reported being much or moderately improved, as compared with 28% of patients receiving placebo, according to the Patient Global Assessment (odds ratio for improvement, 2.51; 95% confidence interval [CI], 1.75 to 3.61). Among the patients assigned to ferric carboxymaltose, 47% had an NYHA functional class I or II at week 24, as compared with 30% of patients assigned to placebo (odds ratio for improvement by one class, 2.40; 95% CI, 1.55 to 3.71). Results were similar in patients with anemia and those without anemia. Significant improvements were seen with ferric carboxymaltose in the distance on the 6-minute walk test and quality-of-life assessments. The rates of death, adverse events, and serious adverse events were similar in the two study groups. CONCLUSIONS Treatment with intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency, with or without anemia, improves symptoms, functional capacity, and quality of life; the side-effect profile is acceptable. (ClinicalTrials.gov number, NCT00520780.

Iron deficiency is common in patients with chronic HF, relates to disease severity, and is a strong and independent predictor of outcome. In this study, ID appears to have greater predictive power than anemia.

In patients with systolic CHF, ID is common and constitutes a strong, independent predictor of unfavourable outcome. Iron supplementation may be considered as a therapeutic approach in these patients to improve prognosis.

Intravenous iron loading improved exercise capacity and symptoms in patients with CHF and evidence of abnormal iron metabolism. Benefits were more evident in anemic patients. (Effect of Intravenous Ferrous Sucrose on Exercise Capacity in Chronic Heart Failure; http://www.clinicaltrials.gov/ct/show/NCT00125996; NCT00125996).

Background-In patients with chronic heart failure (CHF) and preserved exercise tolerance, the value of cardiopulmonary exercise testing for risk stratification is not known. Elevated slope of ventilatory response to exercise (V E/V CO 2 ) predicts poor prognosis in advanced CHF. Derangement of cardiopulmonary reflexes may trigger exercise hyperpnea. We assessed the relationship between cardiopulmonary reflexes and V E/V CO 2 and investigated the prognostic value of V E/V CO 2 in CHF patients with preserved exercise tolerance. Methods and Results-Among 344 consecutive CHF patients, we identified 123 with preserved exercise capacity, defined as a peak oxygen consumption (peak V O 2 ) Ն18 mL · kg Ϫ1 · min Ϫ1 (age 56 years; left ventricular ejection fraction 28%; peak V O 2 23.5 mL · kg Ϫ1 · min Ϫ1 ). Hypoxic and hypercapnic chemosensitivity (nϭ38), heart rate variability (nϭ34), baroreflex sensitivity (nϭ20), and ergoreflex activity (nϭ20) were also assessed. We identified 40 patients (33%) with high V E/V CO 2 (ie, Ͼ34.0). During follow-up (49Ϯ22 months, Ͼ3 years in all survivors), 34 patients died (3-year survival 81%). High V E/V CO 2 (hazard ratio 4.3, PϽ0.0001) but not peak V O 2 (Pϭ0.7) predicted mortality. In patients with high V E/V CO 2 , 3-year survival was 57%, compared with 93% in patients with normal V E/V CO 2 (PϽ0.0001). Patients with high V E/V CO 2 demonstrated impaired reflex control, as evidenced by augmented peripheral (Pϭ0.01) and central (Pϭ0.0006) chemosensitivity, depressed low-frequency component of heart rate variability (PϽ0.0001) and baroreflex sensitivity (Pϭ0.03), and overactive ergoreceptors (Pϭ0.003) compared with patients with normal V E/V CO 2 . Conclusions-In CHF patients with preserved exercise capacity, enhanced ventilatory response to exercise is a simple marker of a widespread derangement of cardiovascular reflex control; it predicts poor prognosis, which peak V O 2 does not. (Circulation. 2001;103:967-972.)