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Iron Deficiency Definitions in Heart Failure Across Ejection Fraction Phenotypes: Prevalence, Symptoms, and
Felix Lindberg1, Carin Corovic Cabrera1, Lina Benson1
1Department of Clinical Science and Education, Södersjukhuset, Karolinska Institute, Stockholm, Sweden.
Insights
Iron deficiency (ID) is common in heart failure (HF) and linked to worse quality of life. Defining ID using transferrin saturation (TSAT) <20% best identifies patients at higher risk for mortality and hospitalizations.
Area of Science:
- Cardiology
- Internal Medicine
- Nutritional Science
Background:
- Iron deficiency (ID) definition impacts prevalence, prognosis, and treatment benefits in heart failure (HF).
- Understanding the optimal ID definition is crucial for patient stratification and therapeutic interventions.
Purpose of the Study:
- To evaluate four distinct definitions of ID in heart failure with reduced, mildly reduced, and preserved ejection fraction (HFrEF, HFmrEF, HFpEF).
- To assess the association of each ID definition with health-related quality of life (HR-QoL), symptoms, and clinical outcomes.
Main Methods:
- Analysis of 20,673 patients from the Swedish HF Registry (2017-2023).
- ID was assessed using four criteria: current HF guidelines, IRONMAN trial criteria, transferrin saturation (TSAT) <20%, and ferritin <100 μg/L.
- Outcomes included mortality, hospitalizations, HR-QoL, and symptoms.
Main Results:
- ID prevalence varied by definition, highest in HFpEF.
- All definitions correlated with worse symptoms; TSAT <20% and IRONMAN criteria were linked to poorer HR-QoL.
- TSAT <20% and IRONMAN criteria demonstrated the strongest associations with adverse outcomes, including mortality and hospitalizations.
- TSAT <20% exhibited the greatest prognostic accuracy and discrimination, particularly in HFpEF.
Conclusions:
- Iron deficiency is highly prevalent across HF types and associated with adverse outcomes regardless of definition.
- Defining ID by TSAT <20% appears most effective for identifying high-risk patients for clinical trials.
- This definition offers robust associations with mortality and hospitalization, guiding better patient selection for interventions.
Background:
How iron deficiency (ID) is defined in heart failure (HF) may affect ID prevalence, associated prognosis, and achievable intravenous iron benefit.
Objectives:
This study assessed 4 definitions of ID in heart failure with reduced ejection fraction (HFrEF), heart failure with mildly reduced ejection fraction (HFmrEF), and heart failure with preserved ejection fraction (HFpEF) and evaluated prevalence, associated health-related quality of life (HR-QoL), symptoms, and cause-specific morbidity and mortality.
Methods:
Patients enrolled in the Swedish HF Registry from 2017 to 2023 were included. ID was defined as follows: 1) in current HF guidelines; 2) in the IRONMAN (Intravenous Iron Treatment in Patients With Heart Failure and Iron Deficiency) trial; 3) with transferrin saturation (TSAT) <20%; and 4) with a ferritin value <100 μg/L.
Results:
Of 20,673 patients (median age 74 years [Q1-Q3: 65-80 years]; 32% female), 49% fulfilled guideline ID criteria (HFrEF, 48%; HFmrEF, 48%; HFpEF, 54%), 53% fulfilled IRONMAN criteria (HFrEF, 52%; HFmrEF, 52%; HFpEF, 59%), 36% had TSAT <20% (HFrEF, 36%; HFmrEF, 34%; HFpEF, 41%), and 37% has a ferritin level <100 μg/L (HFrEF, 35%; HFmrEF, 37%; HFpEF, 42%). All definitions were independently associated with worse symptoms, and all except ferritin <100 μg/L were associated with worse HR-QoL. TSAT <20% and IRONMAN ID criteria were independently associated with a higher risk of all outcomes, including cardiovascular or all-cause death and HF or all-cause/cardiovascular/noncardiovascular hospitalizations. Guidelines-defined ID was independently associated only with outcomes containing HF hospitalizations or total all-cause hospitalizations, and ferritin <100 μg/L was associated with no outcome. TSAT <20% and IRONMAN ID criteria had stronger associations in HFpEF for outcomes containing HF hospitalization (P interaction < 0.05). TSAT <20% showed the greatest prognostic associations and discrimination.
Conclusions:
Irrespective of definition, ID was highly prevalent (highest in HFpEF) and independently associated with worse symptoms or HR-QoL. ID defined as TSAT <20% showed the strongest associations with outcomes, including mortality and HF or cardiovascular/noncardiovascular hospitalizations, likely representing the preferred definition with which to enroll a higher-risk group in trials.
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