Iron deficiency in heart failure with reduced ejection fraction
The case
A 75-year-old man with heart failure with reduced ejection fraction (35%) takes maximally tolerated doses of bisoprolol 10 mg daily, empagliflozin 10 mg daily, spironolactone 25 mg daily and sacubitril-valsartan 97/103 mg twice daily. He presents with 3 months of fatigue and worsening exertional dyspnoea. He has no history of gastrointestinal bleeding. Examination shows only mild bibasal crepitations. Haemoglobin is 105 g/L (130–180), ferritin 80 micrograms/L (30–400), transferrin saturation 18% (15–45%) and eGFR is stable at 55 mL/min/1.73 m². Echocardiogram shows no interval change. What is the most appropriate single pharmacological intervention?
Options
- AGive intravenous ferric carboxymaltose
- BAdd dapagliflozin as additional therapy
- CIncrease spironolactone to 50 mg
- DSwitch to metoprolol succinate daily
- EStart low-dose digoxin for symptoms
Think it through before you read on. Which single option is best, and why are the other four wrong?
Show the answer and explanation
Answer
A. Give intravenous ferric carboxymaltose
Why this is the right answer
This man is already on all four pillars of heart failure treatment: a beta-blocker, an SGLT2 inhibitor, a mineralocorticoid receptor antagonist and an angiotensin receptor-neprilysin inhibitor. All are at maximal tolerated doses. There is no room to add or increase these drugs.
The question then asks what else is treatable. His iron studies show iron deficiency by heart failure criteria: ferritin below 100 micrograms/L, or ferritin 100–299 micrograms/L with transferrin saturation below 20% [VERIFY]. Note that these cut-offs are higher than the general population definition, because inflammation in heart failure raises ferritin.
Iron deficiency in heart failure worsens symptoms and exercise capacity even without anaemia. Trials such as FAIR-HF and AFFIRM-AHF showed that intravenous iron improves symptoms, quality of life and reduces heart failure admissions. Oral iron does not work well in this setting because absorption is poor.
The Australian heart failure guideline (NHFA/CSANZ, 2018) recommends intravenous iron for symptomatic HFrEF with iron deficiency [VERIFY]. Ferric carboxymaltose is the formulation with the strongest evidence.
Because he has no bleeding history and a normal examination, iron replacement is reasonable now. If there were red flags for gastrointestinal blood loss, investigation of the cause would come first.
Why the other options are wrong
- B
He already takes empagliflozin; a second SGLT2 inhibitor adds nothing.
- C
Increasing spironolactone risks hyperkalaemia with an eGFR of 55, and 25 mg is the usual maintenance dose.
- D
Bisoprolol and metoprolol succinate have equivalent evidence; switching gives no benefit.
- E
Digoxin reduces admissions modestly but has no mortality benefit and is risky in an older man with reduced kidney function; a reversible cause should be treated first.
High-yield takeaway
In HFrEF, iron deficiency is ferritin under 100, or 100–299 with TSAT under 20%, and the treatment is intravenous iron, not tablets.
Reference: NHFA/CSANZ Guidelines for the Prevention, Detection and Management of Heart Failure in Australia (2018)
Common questions
Why is the ferritin cut-off higher in heart failure?
Ferritin rises with inflammation, and heart failure is an inflammatory state, so a ferritin under 100 can still mean the iron stores are empty.
Can oral iron be used instead?
It is not recommended for iron deficiency in heart failure. Absorption is poor, and the trials that showed benefit used intravenous iron.
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