Iron and Heart Failure

Ghafourian, Kambiz; Shapiro, Jason S.; Goodman, Lauren; Ardehali, Hossein

doi:10.1016/j.jacbts.2019.08.009

Cited by 69 publications

(62 citation statements)

References 81 publications

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“…These patients may well have elevated levels of both BNP and NTBI. [ 1 , 4 , 5 ] Of interest, we found an independent association of NTBI concentration with the combination of higher levels of both d-ROM and BNP. This result indicates a possible role for NTBI as an antioxidant in physiological conditions without iron or cardiac overload.…”

Section: Discussionmentioning

confidence: 66%

Analytical evaluation of serum non–transferrin-bound iron and its relationships with oxidative stress and cardiac load in the general population

et al. 2021

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Excessive iron accumulation provokes toxic effects, especially in the cardiovascular system. Under iron overload, labile free non–transferrin-bound iron (NTBI) can induce cardiovascular damage with increased oxidative stress. However, the significance of NTBI in individuals without iron overload and overt cardiovascular disease has not been investigated. We aimed to examine the distribution of serum NTBI and its relationship with oxidative stress and cardiac load under physiological conditions in the general population. We enrolled individuals undergoing an annual health check-up and measured serum NTBI and derivatives of reactive oxygen metabolites (d-ROM), an oxidative stress marker. In addition, we evaluated serum levels of B-type natriuretic peptide (BNP) to examine cardiac load. We excluded patients with anemia, renal dysfunction, cancer, active inflammatory disease, or a history of cardiovascular disease. A total of 1244 individuals (57.8 ± 11.8 years) were enrolled, all of whom had detectable serum NTBI. d-ROM and BNP showed significant trends across NTBI quartiles. Multivariable regression analysis revealed that serum iron and low-density lipoprotein cholesterol were positively associated with NTBI but that age, d-ROM, and BNP showed an inverse association with this measure. In logistic regression analysis, NTBI was independently associated with a combination of higher levels of both d-ROM and BNP than the upper quartiles after adjustment for possible confounding factors. Serum NTBI concentration is detectable in the general population and shows significant inverse associations with oxidative stress and cardiac load. These findings indicate that serum NTBI in physiological conditions does not necessarily reflect increased oxidative stress, in contrast to the implications of higher levels in states of iron overload or pathological conditions.

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Section: Discussionmentioning

confidence: 66%

Analytical evaluation of serum non–transferrin-bound iron and its relationships with oxidative stress and cardiac load in the general population

et al. 2021

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“…Iron deficiency is a common condition affecting approximately 50% of patients with heart failure ( Lavoie, 2020 ). Clinical trials have demonstrated the symptomatic benefit of treating iron-deficient heart failure patients with intravenous iron supplementation ( Anker et al, 2009 ; Ghafourian et al, 2020 ). However, heart failure patients may have underlying myocardial iron overload ( Ghafourian et al, 2020 ; Sawicki et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

“…Clinical trials have demonstrated the symptomatic benefit of treating iron-deficient heart failure patients with intravenous iron supplementation ( Anker et al, 2009 ; Ghafourian et al, 2020 ). However, heart failure patients may have underlying myocardial iron overload ( Ghafourian et al, 2020 ; Sawicki et al, 2015 ). In addition, a high-iron diet caused severe cardiac dysfunction in cardiomyocyte-specific FTH1-deficient mice ( Fang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Iron derived from autophagy-mediated ferritin degradation induces cardiomyocyte death and heart failure in mice

Ito

Omiya

Rusu

et al. 2021

eLife

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Heart failure is a major public health problem, and abnormal iron metabolism is common in patients with heart failure. Although iron is necessary for metabolic homeostasis, it induces a programmed necrosis. Iron release from ferritin storage is through nuclear receptor coactivator 4 (NCOA4)-mediated autophagic degradation, known as ferritinophagy. However, the role of ferritinophagy in the stressed heart remains unclear. Deletion of Ncoa4 in mouse hearts reduced left ventricular chamber size and improved cardiac function along with the attenuation of the upregulation of ferritinophagy-mediated ferritin degradation 4 weeks after pressure overload. Free ferrous iron overload and increased lipid peroxidation were suppressed in NCOA4-deficient hearts. A potent inhibitor of lipid peroxidation, ferrostatin-1, significantly mitigated the development of pressure overload-induced dilated cardiomyopathy in wild-type mice. Thus, the activation of ferritinophagy results in the development of heart failure, whereas inhibition of this process protects the heart against hemodynamic stress.

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“…Treatment with ferric carboxymaltose (FCM) has consistently been shown to improve surrogates of functional capacity and quality of life in patients with HF and reduced ejection fraction 4–6 . However, the mechanisms underlying such benefits remain controversial 7,8 . Different in vitro studies showed detrimental effects of ID on mitochondrial function among myoblasts and cardiomyocytes 9,10 .…”

Section: Introductionmentioning

confidence: 99%

Short‐term changes in left and right systolic function following ferric carboxymaltose: a substudy of the Myocardial‐IRON trial

et al. 2020

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Aims The mechanisms underlying the beneficial effect of ferric carboxymaltose (FCM) in patients with heart failure (HF) and iron deficiency (ID) have not been completely characterized. The Myocardial-IRON trial was a double-blind, randomized trial that evaluated myocardial iron repletion following FCM vs. placebo in 53 patients with HF and ID. In this post hoc analysis, we evaluated whether treatment with FCM was associated with cardiac magnetic resonance changes in left and right ventricular function (LVEF and RVEF, respectively) at different points of systolic dysfunction. Methods and results We included patients from the Myocardial-IRON trial with left and right ventricular systolic dysfunction (LVSD and RVSD, respectively) at enrolment. Linear mixed regression models were used to evaluate changes at 7 and 30 days on LVEF and RVEF at cardiac magnetic resonance. At enrolment, 27 (50.9%) and 38 (71.7%) patients had LVEF < 40% (LVSD 1) or <45% (LVSD 2), respectively, and 10 (18.9%) and 17 (32.1%) patients had RVEF < 45% (RVSD 1) or <51% in women and <52% in men (RVSD 2) , respectively. Treatment with FCM was associated with a significant improvement in LVEF at 30 days (LVSD 1 : Δ2.3%, P < 0.001; LVSD 2 : Δ4.1, P = 0.014). FCM was also associated with a significant and early improvement in RVEF at 7 days (RVSD 1 : Δ6.9%, P = 0.003; RVSD 2 : Δ3.2%, P = 0.003) that persisted at 30 days (RVSD 1 : Δ8.1%, P < 0.001; RVSD 2 : Δ4.7%, P < 0.001). Conclusions In patients with HF and systolic dysfunction with ID, FCM was associated with short-term improvement in LVEF and, especially, in RVEF.

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Iron and Heart Failure

Cited by 69 publications

References 81 publications

Analytical evaluation of serum non–transferrin-bound iron and its relationships with oxidative stress and cardiac load in the general population

Analytical evaluation of serum non–transferrin-bound iron and its relationships with oxidative stress and cardiac load in the general population

Iron derived from autophagy-mediated ferritin degradation induces cardiomyocyte death and heart failure in mice

Short‐term changes in left and right systolic function following ferric carboxymaltose: a substudy of the Myocardial‐IRON trial

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