Relationship between various definitions of iron deficiency and outcomes in HF
Criteria for Iron Deficiency in Patients With Heart Failure
Introduction and methods
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.
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).
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.
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.