2013 recommendation remains current. 9. IMPORTANT COMORBIDITIES IN HF 9.2. Anemia: Recommendations Recommendations for Anemia COR LOE Recommendations Comment/Rationale IIb B-R In patients with NYHA class II and III HF and iron deficiency (ferritin <100 ng/mL or 100 to 300 ng/mL if transferrin saturation is <20%), intravenous iron replacement might be reasonable to improve functional status and QoL.173,174 NEW: New evidence consistent with therapeutic benefit. See Online Data Supplement D. Routine baseline assessment of all patients with HF includes an evaluation for anemia in addition to other baseline laboratory measurements. Anemia is independently associated with HF disease severity, and iron deficiency appears to be uniquely associated with reduced exercise capacity. When iron deficiency is diagnosed and after full evaluation for cause, intravenous repletion of iron, especially in the setting of concomitant hepcidin deficiency in HF, may improve exercise capacity and QoL. Studies examining correction of iron deficiency in HF have demonstrated improvement in surrogate endpoints, such as QoL, NT- proBNP, and LVEF; however, controlled trials have been underpowered to detect reductions in hard clinical endpoints. The FAIR-HF (Ferric Carboxymaltose Assessment in Patients With Iron Deficiency and Chronic Heart Failure) trial173 demonstrated improvements in NYHA class and functional capacity over a short- term exposure. The CONFIRM-HF (Ferric Carboxymaltose Evaluation on Performance in Patients With Iron Deficiency in Combination with Chronic Heart Failure) included a larger cohort of patients (n=304) and demonstrated improvements in 6-minute walk test. A meta-analysis of 5 prospective controlled studies (631 patients) evaluated the effect of intravenous iron on deaths, hospitalizations, and other events in patients with HF and iron deficiency.175 Patients receiving intravenous iron experienced limited but statistically significant improvements in functional capacity and LVEF but no reduction in mortality rate. 