As one in every two heart failure patients has iron deficiency, an appropriate and timely question asked during the meeting was: “should iron be at the heart of our concerns?”
This topic was addressed by Dr Carolyn Lam (National Heart Centre, Singapore) during a Vifor satellite symposium. Iron deficiency is frequently defined as a serum ferritin <100 μg/L (or 100–299 ng/ml, if transferrin saturation [TSAT] <20%); the usual iron deficit in a 35–70 kg heart failure patient with a haemoglobin 10–14 g/dl is 1,000 mg.
Iron deficiency is common irrespective of haemoglobin, sex, ethnicity, and even ejection fraction. In heart failure patients it adversely affects:
- functional status, including exercise capacity
- quality of life
Iron deficiency (but not anaemia) is associated with adverse prognosis. Myocardial iron content is decreased in advanced heart failure independently of anaemia, which impairs mitochondrial function as shown by diminished citric acid cycle enzyme activity.
The symposium considered why iron deficiency is so common. There are multiple causes, notably gastrointestinal blood loss, malabsorption and malnutrition, which all cause reduced iron stores (absolute iron deficiency). But “heart failure is a chronic inflammatory condition,” Dr Lam told the meeting, resulting in reduced iron mobilisation and functional iron deficiency.
Dr Lam reviewed a number of studies of intravenous (iv) iron replacement in heart failure patients with reduced ejection fraction (HFrEF) (left ventricular ejection fraction [LVEF] ≤ 40%, New York Heart Association [NYHA] Class II-IV) and also with iron deficiency.
- FAIR-HF1 (n=459), which showed improvements in the Patient Global Assessment (PGA) score, NYHA class and in the six-minute walk test (6MWT) with intravenous ferric carboxymaltose (FCM) compared to placebo.
- CONFIRM-HF trial2 (n=300), which showed significant improvements with FCM versus placebo in the 6MWT at 24 weeks (and secondary end points) in a similar patient population.
- EFFECT-HF3 (n=172) demonstrated in the primary analysis that treatment with iv FCM in patients with heart failure and iron deficiency improved iron stores and had a favourable effect on peak oxygen consumption (VO2) with FCM compared to standard of care.
These studies, Dr Lam explained, were in contrast to results from IRONOUT-HF4 (n=225), where oral iron replacement had no effect on exercise capacity in HFrEF patients with iron deficiency, as measured using change in VO2. This was a reflection of poor absorption, “ a high-dose oral iron minimally repleted iron stores”, said Dr Lam. The results of IRONOUT-HF suggest that there is currently no role for routine oral iron supplementation in patients with HFrEF and iron deficiency.
Current European Society of Cardiology guidelines5 recommend screening of iron status in all newly diagnosed patients with systolic heart failure and consideration of iv FCM in symptomatic patients with HFrEF and iron deficiency.
“Iron deficiency is clinically and prognostically important irrespective of anaemia. And correction of iron deficiency with iv FCM improves symptoms, quality of life, and exercise capacity,” Dr Lam summarised. “Studies have been initiated to evaluate the effect of iv iron on morbidity and mortality end points.”
You can find all of our reports from the ESC 2017 here.
1. Anker SD, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 2009;361:2436–48 https://doi.org/10.1056/NEJMoa0908355
2. Ponikowski P, et al. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. Eur Heart J 2015;36:657–68 https://doi.org/10.1093/eurheartj/ehu385
3. Van Veldhuissen DJ, et al. Effect of ferric carboxymaltose on exercise capacity in patients with chronic heart failure and iron deficiency. Circulation 2017;136: (published online 12 July 2017 https://doi.org/10.1161/CIRCULATIONAHA.117.027497)
4. Lewis GD, et al. Effect of oral iron repletion on exercise capacity in patients with heart failure with reduced ejection fraction and iron deficiency: The IRONOUT HF Randomized Clinical Trial. JAMA 2017;317(19):1958–66 https://doi.org/10.1001/jama.2017.5427
5. Ponikowski P, et al. 2016 European Society of Cardiology Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2016;37:2129–200 https://doi.org/10.1093/eurheartj/ehw128