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Prognostic value of three iron deficiency definitions in patients with advanced heart failure
Charikleia Papadopoulou1,2, Johannes Reinhold1,3, Nicolai Grüner-Hegge1
1Royal Papworth Hospital, Cambridge, UK.
Insights
Iron deficiency in advanced heart failure impacts prognosis. Definitions based on serum iron or transferrin saturation predict adverse outcomes, unlike the guideline definition, highlighting the importance of precise iron deficiency assessment.
Area of Science:
- Cardiology
- Hematology
- Clinical Medicine
Background:
- Iron deficiency (ID) is prevalent in advanced heart failure (HF).
- Uncertainty exists regarding the optimal definition of ID and its prognostic implications in HF patients.
- Accurate ID assessment is crucial for managing advanced HF and guiding treatment decisions.
Purpose of the Study:
- To evaluate three distinct definitions of iron deficiency.
- To assess the association between these ID definitions and clinical outcomes in patients with advanced heart failure.
- To determine the most reliable definition of ID for predicting prognosis in heart transplant candidates.
Main Methods:
- A cohort of 801 patients referred for heart transplantation was analyzed.
- Iron deficiency was defined using three criteria: guideline definition (ferritin and transferrin saturation), serum iron concentration, and transferrin saturation.
- The primary outcome was a composite of mortality, urgent transplantation, or mechanical circulatory support.
Main Results:
- The prevalence of iron deficiency ranged from 39% to 55% based on the definition used.
- ID defined by serum iron (HR 1.532) or transferrin saturation (HR 1.595) independently predicted adverse outcomes.
- The guideline definition of ID did not show a significant association with the primary outcome (HR 1.085).
Conclusions:
- Iron deficiency, specifically when defined by serum iron or transferrin saturation, is linked to poorer prognosis in advanced heart failure.
- The current guideline definition for iron deficiency may not accurately capture the risk in these patients.
- These findings underscore the need for refined diagnostic criteria for iron deficiency in advanced heart failure management.
Aims:
There is uncertainty about the definition of iron deficiency (ID) and the association between ID and prognosis in patients with advanced heart failure. We evaluated three definitions of ID in patients referred for heart transplantation.
Methods And Results:
Consecutive patients assessed for heart transplantation at a single UK centre between January 2010 and May 2022 were included. ID was defined as (1) serum ferritin concentration of <100 ng/ml, or 100-299 ng/ml with transferrin saturation <20% (guideline definition), (2) serum iron concentration ≤13 μmol/L, or (3) transferrin saturation <20%. The primary outcome measure was a composite of all-cause mortality, urgent heart transplantation or need for mechanical circulatory support. Overall, 801 patients were included, and the prevalence of ID was 39-55% depending on the definition used. ID, defined by either serum iron or transferrin saturation, was an independent predictor of the primary outcome measure (hazard ratio [HR] 1.532, 95% confidence interval [CI] 1.264-1.944, and HR 1.595, 95% CI 1.323-2.033, respectively), but the same association was not seen with the guideline definition of ID (HR 1.085, 95% CI 0.8827-1.333). These findings were robust in multivariable Cox regression analysis. ID, by all definitions, was associated with lower 6-min walk distance, lower peak oxygen consumption, higher intra-cardiac filling pressures and lower cardiac output.
Conclusions:
Iron deficiency, when defined by serum iron concentration or transferrin saturation, was associated with increased frequency of adverse clinical outcomes in patients with advanced heart failure. The same association was not seen with guideline definition of ID.
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