Abstract
AimsIron 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 ResultsAmong 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.ConclusionIron 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 Registrationwww.ClinicalTrials.gov, identifier NCT02078947.
Highlights
In patients with heart failure (HF) and reduced ejection fraction (HFrEF), iron deficiency (ID) is a known predictor of adverse outcomes (Jankowska et al, 2010; Klip et al, 2013)
Inclusion criteria were (i) signs and symptoms of HF using the New York Heart Association classes II or III, (ii) left ventricular (LV) ejection fraction ≥ 50%, (iii) diastolic dysfunction defined as E/e > 15 or E/e > 8 + N-terminal pro-B-type natriuretic peptide (NTproBNP) > 220 pg/mL (Paulus et al, 2007), (iv) sedentary lifestyle, and (v) optimal medical treatment and clinically stable for ≥ 6 weeks
We concluded that in patients with HF with preserved ejection fraction (HFpEF), (i) ID is a very frequent comorbidity, (ii) iron parameters relate to diastolic function and aerobic exercise capacity only in patients with ID, (iii) patient phenotyping is significantly impacted by including ID, and (iv) a phenogroup of younger women with HFpEF has a high prevalence of ID but a few other comorbidities
Summary
In patients with heart failure (HF) and reduced ejection fraction (HFrEF), iron deficiency (ID) is a known predictor of adverse outcomes (Jankowska et al, 2010; Klip et al, 2013). Less is known about the influence of iron status on functional status and myocardial performance in HF with preserved ejection fraction (HFpEF). HFpEF accounts for half of the HF hospital admissions, and its pathophysiology is characterized by both cardiac (e.g., diastolic dysfunction) and non-cardiac (e.g., skeletal myopathy) abnormalities causing exercise intolerance (Shimiaie et al, 2015; Gevaert et al, 2019; Pugliese et al, 2019). Observational data show a strong relationship between ID and a reduced aerobic exercise capacity, measured as peak oxygen uptake (peak V O2), in patients with HFpEF (Beale et al, 2019). A relationship of ID to either exercise capacity or left ventricular (LV) stiffness could not be found in a small study of patients with HFpEF (Kasner et al, 2013)
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