Author + information
- Received July 11, 2019
- Revision received August 29, 2019
- Accepted August 29, 2019
- Published online March 23, 2020.
- Kambiz Ghafourian, MD, MPH,
- Jason S. Shapiro, PhD,
- Lauren Goodman and
- Hossein Ardehali, MD, PhD∗ ()
- ↵∗Address for correspondence:
Dr. Hossein Ardehali, Feinberg Cardiovascular and Renal Research Institute, Northwestern University, SQBRC 8-521, 303 East Superior Avenue, Chicago, Illinois 60611.
• Intravenous iron supplementation provides symptomatic relief in patients with heart failure and concomitant iron deficiency.
• The current definition of iron deficiency based on ferritin <100 ng/ml or transferrin saturation <20% may not accurately reflect the levels of iron within tissue and cells. Therefore, intravenous iron may be administered to heart failure patients who do not require iron supplementation.
• Intravenous administration of iron bypasses essential regulatory mechanisms and can cause endothelial damage via the production of reactive oxygen species.
• Although iron should be given to patients with heart failure and iron deficiency, sufficient consideration should be given to the route of administration and the potential for adverse effects, especially in non–iron deficient patients.
• Further research must be conducted to determine whether changes in the cellular and subcellular distribution of iron in patients with heart failure are compensatory and beneficial or maladaptive and potentiates disease.
To date, 3 clinical trials have shown symptomatic benefit from the use of intravenous (IV) iron in patients with heart failure (HF) with low serum iron. This has led to recommendations in support of the use of IV iron in this population. However, the systemic and cellular mechanisms of iron homeostasis in cardiomyocyte health and disease are distinct, complex, and poorly understood. Iron metabolism in HF appears dysregulated, but it is still unclear whether the changes are maladaptive and pathologic or compensatory and protective for the cardiomyocytes. The serum markers of iron deficiency in HF do not accurately reflect cellular and mitochondrial iron levels, and the current definition based on the ferritin and transferrin saturation values is broad and inclusive of patients who do not need IV iron. This is particularly relevant in view of the potential risks that are associated with the use of IV iron. Reliable markers of cellular iron status may differentiate subgroups of HF patients who would benefit from cellular and mitochondrial iron chelation rather than IV iron.
Supported by NIH R01 HL127646-01A1, NIH R01 HL140973-01, and NIH R01 HL138982-01A1. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received July 11, 2019.
- Revision received August 29, 2019.
- Accepted August 29, 2019.
- 2020 The Authors
- Systemic Iron Regulation
- Cellular Iron Regulation in the Heart
- Dysregulation of Iron Metabolism in Heart Disease: Excess or Deficiency?
- Iron Supplementation in HF
- Intravenous Iron Supplementation in HF: Clinical Trials
- Side Effects of IV Iron: Cause for Concern
- Is Oral Iron Effective in HF?
- Iron Chelation in Cardiovascular Disease