Should I routinely screen my patients with heart failure for iron deficiency?

Even in the absence of anemia, screening for iron deficiency (ID) has been recommended in patients with heart failure (HF) with reduced ejection fraction (HFrEF) by some European and Australia-New Zealand cardiology societies. 1

In contrast, the 2017 American College of Cardiology/American Heart Association/Heart Failure Society of America guidelines do not mention routine screening for ID in such patients but instead state (under “Anemia”) that in patients with NYHA class II and III HF and ID (ferritin < 100 ng/mL or 100 to 300 ng/mL plus transferrin saturation <20%), IV iron replacement “might be reasonable” to improve functional status and quality of life (IIb-weak recommendation).2

As these guidelines are primarily based on data derived from patients with HFrEF, whether patients with HF with preserved (eg, >45%) ejection fraction (HFpEF) should undergo routine screening for ID is even less clear due to conflicting data based on limited small studies 3,4

What is known is that up to 50% or more of patients with HF with or without anemia may have ID. 5 Although most studies involving ID and HF have involved patients with HFrEF, similarly high prevalence of ID in HFpEF has been reported. 6,7

A 2016 meta-analysis involving patients with HFrEF and ID found that IV iron therapy alleviates HF symptoms and improves outcomes, exercise capacity and quality of life irrespective of concomitant anemia; all-cause and cardiovascular mortality rates were not significantly impacted, however.8  

Fortunately, larger trials in the setting of acute and chronic systolic HF are underway (Affirm-AHF, 9 IRONMAN 10).  Stay tuned!

Bonus Pearl: Did you know that iron deficiency directly affects human cardiomyocyte function by impairing mitochondrial respiration  and reducing its contractility and relaxation?11

References

  1. Silverberg DS, Wexler D, Schwartz D. Is correction of iron deficiency a new addition to the treatment of the heart failure? Int J Mol Sci 2015;16:14056-74. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490538/
  2. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure. Circulation 2017;136:e137-e161. https://www.ahajournals.org/doi/pdf/10.1161/CIR.0000000000000509
  3. Kasner M, Aleksandrov AS, Westermann D, et al. Functional iron deficiency and diastolic function in heart failure with preserved ejection fraction. International J of Cardiol 2013;168:12:4652-57. https://www.ncbi.nlm.nih.gov/pubmed/23968714
  4. Enjuanes C, Klip IT, Bruguera J, et al. Iron deficiency and health-related quality of life in chronic heart failure: results from a multicenter European study. Int J Cardiol 2014;174:268-275. https://www.ncbi.nlm.nih.gov/pubmed/24768464
  5. Drodz M, Jankowska EA, Banasiak W, et al. Iron therapy in patients with heart failure and iron deficiency: review of iron preparations for practitioners. Am J Cardiovasc Drugs 2017;17:183-201. https://www.ncbi.nlm.nih.gov/pubmed/28039585
  6. Bekfani T, Pellicori P, Morris D, et al. Iron deficiency in patients with heart failure with preserved ejection fraction and its association with reduced exercise capacity, muscle strength and quality of life. Clin Res Cardiol 2018, July 26. Doi: 10. 1007/s00392-018-1344-x. https://www.ncbi.nlm.nih.gov/pubmed/30051186
  7. Nunez J, Dominguez E, Ramon JM, et al. Iron deficiency and functional capacity in patients with advanced heart failure with preserved ejection fraction. International J Cardiol 2016;207:365-67. https://www.internationaljournalofcardiology.com/article/S0167-5273(16)30185-1/abstract
  8. Jankowska EA, Tkaczynszyn M, Suchocki T, et al. Effects of intravenous iron therapy in iron-deficient patients with systolic heart failure: a meta-analysis of randomized controlled trials. Eur J Heart Failure 2016;18:786-95. https://www.ncbi.nlm.nih.gov/pubmed/26821594
  9. https://clinicaltrials.gov/ct2/show/NCT02937454
  10. https://clinicaltrials.gov/ct2/show/NCT02642562
  11. Hoes MF, Beverborg NG, Kijlstra JD, et al. Iron deficiency impairs contractility of human cardiomyoctyes through decreased mitochondrial function. Eur J Heart Failure 2018;20:910-19. https://www.ncbi.nlm.nih.gov/pubmed/29484788  

 

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Should I routinely screen my patients with heart failure for iron deficiency?

How much blood is needed in the GI tract to cause melena?

Melena, characterized by black tarry stools, can occur with as little as 50 cc of blood in the stomach. How do we know this? We need to go back to clinical experiments involving oral administration of citrated blood in human subjects back in 1930’s and 40’s. 1-3 One study was performed on a group of “healthy medical students” who drank their own blood!3

Melena suggests an upper GI bleeding source where there is more time for enzymatic breakdown to transform blood to melena. Although gastric acid may also contribute to its formation, it does not appear to be a pre-requisite to melena as blood inserted into the small bowel or cecum can also produce melenic stools if it stays there long enough. Melena is dependent primarily on the length of transit time of blood in the GI tract, such that very rapid movement of 1 liter of blood from upper GI tract may lead to bright red blood per rectum, not melena, within 4 hours.2,4

Don’t get melena confused with other causes of dark stools such as oral iron supplementation and bismuth-containing medications (eg, Peptobismol®). In addition to its tarry texture, melena also has a characteristic pungent odor.

References

  1. Schiff L, Stevens R, Shaprio N, et al. Observations on the oral administration of citrated blood in man. Am J Med Sci 1942;203:409-12.
  2. Srygley FD, Gerardo CJ, Tran T, et al. Does this patient have a severe upper gastrointestinal bleed. JAMA 2012;307:1072-79. https://jamanetwork.com/journals/jama/article-abstract/1105075?redirect=true
  3. Daniel WA, Egan S. The quantity of blood required to produce a tarry stool. JAMA 1939;113:2232.
  4. Wilson ID. Hematemesis, melena, and hematochezia. In: Walker HK, Hall WD, Hurst JW, eds. Clinical Methods: The history, physical, and laboratory examinations. 3rd edition. Boston: Butterworths:1990. Chapter 85. Available from: https://www.ncbi.nlm.nih.gov/books/NBK411/

 

Contributed in part by Brad Lander, MD, Mass General Hospital, Boston, MA.

How much blood is needed in the GI tract to cause melena?