Iron Deficiency Impacts Diastolic Function, Aerobic Exercise Capacity, and Patient Phenotyping in Heart Failure With Preserved Ejection Fraction: A Subanalysis of the OptimEx-Clin Study

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.

Exercise training response according to baseline ferrokinetics in heart failure with preserved ejection fraction: A substudy of the TRAINING‐HF trial

“…Accordingly, a prior study showed that in subjects with unexplained dyspnea, ID was associated with lower functional capacity, peripheral oxygen extraction, and biventricular contractile reserve 23 . Furthermore, regarding patients with HFpEF, previous observational studies 6,8,9 using cross‐sectional approaches have found that ID was consistently associated with reduced exercise capacity.…”

“…In heart failure (HF), iron deficiency (ID) is a highly prevalent and multifactorial condition, [1][2][3][4][5][6][7][8][9][10] and it is associated with impaired functional capacity 6,8,9,11 and poor prognosis 3,5,10 irrespective of left ventricular ejection fraction (LVEF). Although intravenous iron replacement in patients with HF with reduced ejection fraction (HFrEF) resulted in exercise capacity and quality of life improvement and risk hospitalization for worsening HF reduction, [12][13][14] there is limited and inconclusive evidence regarding the effects of iron replacement in patients with preserved ejection fraction (HFpEF).…”

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“…Un estudio retrospectivo de un solo centro encontró que la FCM EV en pacientes con ICFEp mejoró el estado funcional y la función cardíaca. (96) Se espera que los ensayos con las formulaciones clásicas y nuevas en curso nos den más evidencia sobre sus efectos en esta población. (97,98)…”

Imaging of heart disease in women: review and case presentation

“…AI could also be beneficial in patients with HFpEF. In a subgroup of predominantly female HFpEF patients with few risk factors for the condition, ML techniques identified an iron overload state, thus providing the means to assess pathophysiological pathways for HFpEF in women [ 222 ].…”