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Be part of the knowledge.™Relationship between various definitions of iron deficiency and outcomes in HF
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Introduction and methods
Background
There are many definitions of iron deficiency (ID) for patients with HF. International guidelines define ID in HF as serum ferritin<100 ng/mL or TSAT <20% if ferritin is 100-299 ng/mL [1,2]. However, observational studies have suggested that serum iron concentration and TSAT might be more strongly associated with prognosis compared to serum ferritin [3-7].
Aim of the study
This study investigated the effect of different definitions of ID on its prevalence and associations with outcomes in patients with chronic HF.
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Methods
The study population consisted of patients with HF who were referred to a regional HF clinic. 4422 patients had all required iron indices and were included in the analysis (n=1429 with HFrEF, n=820 with HFmrEF, n=1,832 with HFpEF, n=341 with HF and high NT-proBNP ≥125 ng/L, but missing information on LVEF).
The study investigated four different categorical variables for ID: 1) international guideline criteria (ferritin<100 ng/mL or TSAT <20% if ferritin 100-299 ng/mL), 2) ferritin <100 ng/mL, 3) TSAT <20%, and 4) serum iron ≤13 mmol/L.
Patients were followed up clinically and by electronic records for a medium of 49 months (25th and 75th percentile: 18-89).
Main results
Prevalence of ID
- The prevalence of ID among patients with chronic HF was high and ranged from 44% to 68% depending on the definition of ID.
- Irrespective of the ID definition, ID was more common in women, those with more severe symptoms, and those who did not have HFrEF.
- 3011 (68%) patients met guideline criteria for ID. 2506 (83%) of them had ferritin <100 ng/mL and 1079 (36%) of them had a TSAT >20%.
- 1543 (35%) patients had anemia.
Relationship between different ID definitions and mortality
- There was no association between guideline criteria for ID and mortality.
- TSAT <20% (vs. ≥20%) and serum iron ≤13 µmol/L (vs. >13 µmol/L) were independently associated with greater all-cause mortality in multivariable analyses (HR 1.27; 95% CI 1.14-1.43, P<0.001, and HR 1.37, 95% CI 1.22-1.54, P<0.001, respectively). There was no significant association between these variables and CV mortality in the multivariable model.
- Ferritin <100 ng/mL was associated with lower CV mortality in multivariable analyses (HR 0.83, 95% CI 0.71-0.96, P=0.02).
- Ferritin <300 ng/mL was associated with both lower all-cause mortality (HR 0.69, 95% CI 0.58-0.81, P<0.001) and CV mortality (HR 0.78, 95% CI 0.61-0.99, P=0.048) in the multivariable model.
- There were no significant interactions in the adjusted models between the different ID criteria and HF phenotypes for all-cause mortality or CV mortality.
Conclusion
ID is common in patients with chronic HF. There was no significant association between the current guideline definition of ID and mortality. Serum ferritin <100 ng/mL was associated with lower mortality. On the other hand, TSAT<20% and serum iron ≤13 µmol/L were independently associated with all-cause mortality, with no interaction between HF phenotypes.
‘Clinical trial data should be analyzed to determine the criteria for ID that best identify patients with HF likely to benefit from iron replacement.’ according to the authors of the article.
References
1. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2021;42(36):3599–3726.
2. YC W, Mariell J, Biykem B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure. J Am Coll Cardiol. 2017;70(6):776–803.
3. Grote Beverborg N, Klip IjT, Meijers WC, et al. Definition of iron deficiency based on the gold standard of bone marrow iron staining in heart failure patients. Circ Heart Fail. 2018;11(2):e004519.
4. Okonko DO, Mandal AKJ, Missouris CG, Poole-Wilson PA. Disordered iron homeostasis in chronic heart failure: Prevalence, predictors, and relation to anemia, exercise capacity, and survival. J Am Coll Cardiol. 2011;58(12):1241–1251.
5. Moliner P, Jankowska EA, van Veldhuisen DJ, et al. Clinical correlates and prognostic impact of impaired iron storage versus impaired iron transport in an international cohort of 1821 patients with chronic heart failure. Int J Cardiol. 2017;243:360–366.
6. Cleland JGF, Zhang J, Pellicori P, et al. Prevalence and outcomes of anemia and hematinic deficiencies in patients with chronic heart failure. JAMA Cardiol. 2016;1(5):539–547.
7. Graham FJ, Masini G, Pellicori P, et al. Natural history and prognostic significance of iron deficiency and anaemia in ambulatory patients with chronic heart failure. Eur J Heart Fail. Published online May 28, 2021. https://doi.org/10.1002/ejhf.2251
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