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Iron Deficiency Impacts Diastolic Function, Aerobic Exercise Capacity, and Patient Phenotyping in Heart Failure With
Andreas B Gevaert1,2, Stephan Mueller3,4, Ephraim B Winzer5
1Research Group Cardiovascular Diseases, GENCOR (Genetics, Pharmacology & Physiopathology of Heart, Blood, Vessels and Skeleton) Department, University of Antwerp, Antwerp, Belgium.
Insights
Iron deficiency in heart failure with preserved ejection fraction (HFpEF) is common and linked to worse diastolic function and exercise capacity. Addressing iron status is crucial for accurate HFpEF patient phenotyping.
Area of Science:
- Cardiology
- Internal Medicine
- Exercise Physiology
Background:
- Iron deficiency (ID) negatively impacts prognosis and exercise capacity in heart failure with reduced ejection fraction (HFrEF).
- Data on iron status in heart failure with preserved ejection fraction (HFpEF) is limited.
- HFpEF affects a significant patient population, often with comorbidities impacting quality of life.
Purpose of the Study:
- To investigate the association between iron status, diastolic dysfunction, and aerobic exercise capacity in patients with HFpEF.
- To determine the contribution of iron status to the phenotyping of HFpEF patients.
- To explore potential therapeutic targets related to iron metabolism in HFpEF.
Main Methods:
- Analysis of baseline iron status (iron, ferritin, transferrin saturation) in 169 HFpEF patients from the OptimEx-Clin trial.
- Assessment of exercise capacity (peak oxygen uptake) and diastolic function (E/e').
- Multivariable regression models and machine learning for patient phenotyping.
Main Results:
- Iron deficiency was prevalent in 60% of HFpEF patients, more common in women.
- Diastolic function and peak oxygen uptake were independently related to iron parameters in patients with HFpEF and ID.
- Machine learning identified a phenogroup with high ID prevalence (86%), predominantly female, and fewer HFpEF risk factors.
Conclusions:
- Iron parameters are independently associated with impaired diastolic function and reduced aerobic capacity in HFpEF patients with ID.
- Including iron status in phenotyping analyses significantly influences the classification and understanding of HFpEF patient subgroups.
- These findings highlight the importance of assessing and potentially treating iron deficiency in HFpEF management.
Aims:
Iron deficiency (ID) is linked to reduced aerobic exercise capacity and poor prognosis in patients with heart failure (HF) with reduced ejection fraction (HFrEF); however, data for HF with preserved ejection fraction (HFpEF) is scarce. We assessed the relationship between iron status and diastolic dysfunction as well as aerobic exercise capacity in HFpEF, and the contribution of iron status to patient phenotyping.
Methods And Results:
Among 180 patients with HFpEF (66% women; median age, 71 years) recruited for the Optimizing Exercise Training in Prevention and Treatment of Diastolic HF (OptimEx-Clin) trial, baseline iron status, including iron, ferritin, and transferrin saturation, was analyzed (n = 169) in addition to exercise capacity (peak oxygen uptake [peak V̇O2]) and diastolic function (E/e'). ID was present in 60% of patients and was more common in women. In multivariable linear regression models, we found that diastolic function and peak V̇O2 were independently related to iron parameters; however, these relationships were present only in patients with HFpEF and ID [E/e' and iron: β-0.19 (95% confidence interval -0.32, -0.07), p = 0.003; E/e' and transferrin saturation: β-0.16 (-0.28, -0.04), p = 0.011; peak V̇O2 and iron: β 3.76 (1.08, 6.44), p = 0.007; peak V̇O2 and transferrin saturation: β 3.58 (0.99, 6.16), p = 0.007]. Applying machine learning, patients were classified into three phenogroups. One phenogroup was predominantly characterized by the female sex and few HFpEF risk factors but a high prevalence of ID (86%, p < 0.001 vs. other phenogroups). When excluding ID from the phenotyping analysis, results were negatively influenced.
Conclusion:
Iron parameters are independently associated with impaired diastolic function and low aerobic capacity in patients with HFpEF and ID. Patient phenotyping in HFpEF is influenced by including ID.
Clinical Trial Registration:
www.ClinicalTrials.gov, identifier NCT02078947.
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