Practical guidance on implementation of ESC recommendations on management of iron deficiency in chronic HF

Patients with chronic heart failure (CHF) often suffer from iron deficiency, which is associated with decreased exercise performance, impaired health-related quality of life and a worse prognosis, irrespective of the presence of anemia. In 2016, the European Society of Cardiology (ESC) published guidelines on the management of HF, which also formulated recommendations on the management of iron deficiency, a common and important co-morbidity. Iron deficiency is, however, still under-diagnosed and under-treated in clinical practice, possibly due to a lack of practical, easy-to-follow advice on how to diagnose and treat iron deficiency. Therefore, a working group now set out to compose practical guidance, relating to the procedures for screening, diagnosis and treatment of iron deficiency in patients with CHF.

2016 ESC Guidelines on management of iron deficiency in HF

• Iron status should be evaluated as part of the initial work-up of all newly diagnosed HF patients (class of recommendation I, level of evidence C).
• Ferritin and transferrin saturation (TSAT) are blood markers that can be used for diagnosis of iron deficiency.
• Treat iron deficiency based on a serum ferritin level<100μg/L, or 100–299μg/L when TSAT <20%. Ferritin and TSAT testing should be performed simultaneously and evaluated together.
• In patients who are both iron-deficient and anemic, it is important to investigate the underlying causes of reduced Hb levels.
• Current treatment options to correct iron deficiency in the general population are Intravenous (IV) or oral iron. In symptomatic patients with systolic HFrEF (LVEF >40%), iron deficiency is treated with IV ferric carboxymaltose (FCM) (class of recommendation IIa, level of evidence A).

Practical recommendations of the working group

• Iron status should also be evaluated in patients with existing CHF, independently of Hb level, particularly if they are symptomatic despite receiving optimal background HF medications.
• IV FCM should not be used in patients with Hb levels >15g/dL, as its efficacy is unknown in these patients.
• Contraindications for use of FCM include hypersensitivity for the active substance, to FCM or any of its excipients, known serious hypersensitivity to other parenteral iron products, the presence of anemia not attributed to iron deficiency, evidence of iron overload, or disturbances in the utilization of iron.
• Treatment with IV FCM should be used with caution in patients with acute or chronic infection and should be stopped in patients with ongoing bacteremia. Patients with known drug allergies, and those with atopic allergies, may be at an increased risk of hypersensitivity reaction. An increased risk of hypersensitivity reactions to parenteral iron complexes exists in patients with immune or inflammatory conditions.
• Determination of the initial iron need is calculated based on body weight and Hb levels (rather than ferritin or TSAT). The maximum recommended cumulative dose of FCM is 1000 mg iron (20mL FCM)/week.
• FCM can be administered in any health care setting where staff are trained and equipment is available to evaluate and treat a potential hypersensitivity reaction.
• IV FCM may be given as an injection or infusion. Administration is easily done as an undiluted slow bolus injection (100mg/min, or 15 min for a 1000 mg dose). If infused, FCM should not be over-diluted as this affects the stability of the drug. Patients should be observed for adverse effects for at least 30 min following each IV injection.
• It is recommended to re-evaluate iron status 3 months after administration of a correct dose of iron, and further iron repletion should be administered accordingly. If there is no response or Hb levels decrease, further investigation for other underlying causes should be considered as clinically indicated, particularly occult blood loss.
• Early re-evaluation of iron status (i.e. within 4 weeks of IV iron administration) should be avoided as ferritin levels increase markedly following IV iron administration, and cannot be used as an indicator of iron status during this time.
• After correction of iron deficiency, as part of routine follow-up consider re-evaluation of iron parameters (ferritin and TSAT) 1–2 times per year. Iron status should be re-evaluated if patients remain symptomatic despite receiving optimal background HF medications, or in the event that Hb levels decrease.

Other considerations

• There is a lack of clinical data supporting the efficacy of oral iron therapy in patients with CHF. Moreover, oral iron is often poorly tolerated in patients with CHF.
• There is no clinical evidence for IV FCM in patients with HFpEF (LVEF ≥50%) and limited clinical evidence in HFmrEF (LVEF 40–49%).

Several knowledge gaps relating to the role of IV iron therapy in HF patients remain. As a consequence, some of the practical recommendations are based on expert opinion of the working group instead. Ongoing trials will further address the effects of IV iron therapy in HF patients, including the impact of IV iron therapy on morbidity and mortality in systolic CHF patients with iron deficiency (FAIR-HF2 and IRONMAN studies) and the efficacy and safety of IV iron in patients with HFpEF or acute HF and iron deficiency (FAIR-HFpEF and AFFIRM-AHF studies).

Find this article online at Eur J Heart Fail.