Are Current Blood Iron Levels Appropriate for Use in Patients With Heart Failure?

The chemical symbol for iron is Fe, which stems from the Latin word for iron, Ferrum. Therefore, it is easy to see the connection on how ferritin is the protein responsible for iron storage and release in the body and transferrin is the protein responsible for transporting that iron.

Appropriate levels of both indicate sufficient iron levels in the blood, levels that often drop when an individual develops heart failure (HF), resulting in iron deficiency (ID). Despite previous clinical trial results showing a benefit to iron therapy in these patients, the designated levels of ferritin and transferrin—less than 100 ng/mL and saturation below 20%—that trigger its need could be inaccurate, according to research from JACC: Basic to Translational Science.

“Because serum markers of systemic iron, such as ferritin and TSAT [serum transferrin saturation], do not accurately reflect the status of iron in cardiomyocytes, reliable markers of cellular and mitochondrial iron may enable clinicians to differentiate HF patients who do not need IV [intravenous] iron and, on the contrary, may benefit from cellular and mitochondrial iron chelators,” the study authors noted.

Currently, they are based on limits first used to diagnose ID in patients with chronic kidney disease. A possible result is the unnecessary administration of iron therapy, especially IV iron, to patients with HF who do not need it, which carries with it dangerous risks. For example, reactive oxygen species production can lead to buildup of free radicals in cells, which can cause cell damage and apoptosis.

“[Because] cellular iron levels in myocardial tissue appear to be dysregulated in HF,” according to the study authors, “the definition of ID in HF based on a ferritin level <100 ng/mL or TSAT <20% appears lenient and potentially inclusive of patients without ID who do not need any form of iron supplementation and particularly not the IV form.”

Going forward, suggestions on firming up guidelines for the use of iron therapy in patients with HF include the following:

• Delineating whether myocardial iron levels change because of a pathologic or protective response from myocytes
• Investigating the use of iron chelation therapy
• Determining the long-term safety of IV iron
• Exploring dietary iron restriction

Reference

Ghafourian K, Shapiro JS, Goodman L, Ardehali H. Iron and heart failure: diagnosis, therapies, and future directions. JACC Basic Transl Sci. 2020;5(3):300-313. doi: 10.1016/j.jacbts.2019.08.009.