Successful Treatment of Iron-Overload Cardiomyopathy in Hereditary Hemochromatosis With Deferoxamine and Deferiprone

Tauchenová, Lydie; Křížová, Barbora; Kubánek, Miloš; Fraňková, Soňa; Melenovský, Vojtěch; Tintěra, Jaroslav; Kautznerová, Dana; Malušková, Jana; Jirsa, M; Kautzner, Josef

doi:10.1016/j.cjca.2016.07.589

Cited by 19 publications

(14 citation statements)

References 5 publications

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“…The rationale for iron chelation as a neuroprotectant relies primarily on the idea that chelation removes free iron present in the blood and enhances iron elimination in the urine. After gaining access to other body compartments, DFO could also act by chelating free extracellular and cytosolic iron, whereas its effect on blood TSAT or blood total iron levels is modest (Tauchenová et al, 2016). In fact, DFO was shown to have an extremely slow removal rate of iron from Tf (Abergel and Raymond, 2008).…”

Section: The Ferroptotic Component Of Stroke-induced Neurodegenerationmentioning

confidence: 99%

Deciphering the Iron Side of Stroke: Neurodegeneration at the Crossroads Between Iron Dyshomeostasis, Excitotoxicity, and Ferroptosis

DeGregorio-Rocasolano

2019

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In general, iron represents a double-edged sword in metabolism in most tissues, especially in the brain. Although the high metabolic demands of brain cells require iron as a redox-active metal for ATP-producing enzymes, the brain is highly vulnerable to the devastating consequences of excessive iron-induced oxidative stress and, as recently found, to ferroptosis as well. The blood–brain barrier (BBB) protects the brain from fluctuations in systemic iron. Under pathological conditions, especially in acute brain pathologies such as stroke, the BBB is disrupted, and iron pools from the blood gain sudden access to the brain parenchyma, which is crucial in mediating stroke-induced neurodegeneration. Each brain cell type reacts with changes in their expression of proteins involved in iron uptake, efflux, storage, and mobilization to preserve its internal iron homeostasis, with specific organelles such as mitochondria showing specialized responses. However, during ischemia, neurons are challenged with excess extracellular glutamate in the presence of high levels of extracellular iron; this causes glutamate receptor overactivation that boosts neuronal iron uptake and a subsequent overproduction of membrane peroxides. This glutamate-driven neuronal death can be attenuated by iron-chelating compounds or free radical scavenger molecules. Moreover, vascular wall rupture in hemorrhagic stroke results in the accumulation and lysis of iron-rich red blood cells at the brain parenchyma and the subsequent presence of hemoglobin and heme iron at the extracellular milieu, thereby contributing to iron-induced lipid peroxidation and cell death. This review summarizes recent progresses made in understanding the ferroptosis component underlying both ischemic and hemorrhagic stroke subtypes.

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Section: The Ferroptotic Component Of Stroke-induced Neurodegenerationmentioning

confidence: 99%

Deciphering the Iron Side of Stroke: Neurodegeneration at the Crossroads Between Iron Dyshomeostasis, Excitotoxicity, and Ferroptosis

DeGregorio-Rocasolano

2019

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“…8,9,21 Genetic testing enables clinicians to detect the disease at an early stage and, consequently, to start treatment early enough to stop alterations in different organs, including the heart. 9,15,[22][23][24][25] Echocardiography is a well-known noninvasive method for revealing cardiac abnormalities. Two-dimensional speckle tracking echocardiography (2D STE) is a valuable tool used to evaluate global and regional function of the left ventricle (LV) and appears to be more precise and accurate than traditional echocardiography for detecting subtle myocardial abnormalities.…”

Section: Backg Rou N Dmentioning

confidence: 99%

“…Myocardial iron loading of the heart is well known as a possible complication in the late stages of HH in terms of both diastolic and systolic function, and it is responsible for approximately 1/3 of the deaths that occur due to the natural course of HH . Genetic testing enables clinicians to detect the disease at an early stage and, consequently, to start treatment early enough to stop alterations in different organs, including the heart …”

Section: Introductionmentioning

confidence: 99%

Can two‐dimensional speckle tracking echocardiography be useful for left ventricular assessment in the early stages of hereditary haemochromatosis?

Rozwadowska

Daniłowicz‐Szymanowicz

Fijałkowski

et al. 2018

Echocardiography

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Background Hereditary haemochromatosis (HH) is a common inherited disease. Abnormally increased intestinal iron absorption and accelerated recycling of iron by macrophages lead to progressive body iron accumulation and the generation of oxidative stress. In the late stages, iron overload can lead to dysfunction of the left ventricle (LV). It is believed that two‐dimensional speckle tracking echocardiography (2D STE) can evaluate LV dysfunction more accurately than conventional echocardiography. This accurate evaluation seems to be clinically important in the early stages of HH before substantial damage of the LV. Evaluation of this assessment was the purpose of this paper. Methods We prospectively enrolled 24 patients with early diagnosed HH and without any history of cardiovascular diseases; 23 healthy age‐ and sex‐matched volunteers constituted the control group. Standard echocardiographic parameters and LV rotation and strain parameters were assessed and compared between the groups. Results All echocardiographic parameters were within normal ranges, and there were no differences between the groups. 2D STE revealed significantly worse basal and apical rotation, twist and torsion values in HH patients. The peak systolic longitudinal strain was decreased in HH patients, even though the LV ejection fraction (LVEF) was normal. There were weak correlations between the iron turnover and 2D STE parameters. Conclusions 2D STE seems to be more sensitive than traditional echocardiography for detecting LV abnormalities in HH patients who are diagnosed early. The results of this study may be clinically useful, but their relevance and therapeutic implications remain to be confirmed by further studies.

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“…Although venesection is the treatment of choice in hemochromatosis, other iron depletion therapies have also been tested in HH patients [118,119] . Another iron depletion therapy involves the application of iron chelation therapy to facilitate iron mobilisation and excretion.…”

Section: Diagnosis and Treatment Of Hcc In Hh Patientsmentioning

confidence: 99%

“…Another iron depletion therapy involves the application of iron chelation therapy to facilitate iron mobilisation and excretion. The iron chelating drugs desferioxamine, deferiprone and deferasirox have been tested in HH patients [118,119] . A phase I/II clinical trial for deferasirox has shown it to reduce iron burden in HH patients homozygous for the C282Y mutation [118] .…”

Section: Diagnosis and Treatment Of Hcc In Hh Patientsmentioning

confidence: 99%

Association between hereditary hemochromatosis and hepatocellular carcinoma: a comprehensive review

Jayachandran¹,

Shrestha²,

Bridle³

et al. 2020

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Hepatocellular carcinoma (HCC) is a significant global health problem with high morbidity and mortality. Its incidence is increasing exponentially worldwide with a close overlap between annual incidence and death rates. Even though significant advances have been made in HCC treatment, fewer than 20% of patients with HCC are suitable for potentially curative treatment. Hereditary hemochromatosis (HH) is an important genetic risk factor for HCC. HH is an autosomal recessive disorder of iron metabolism, characterised by elevated iron deposition in most organs including the liver, leading to progressive organ dysfunction. HCC is a complication of HH, nearly always occurring in patients with cirrhosis and contributes to increased mortality rates. Identifying the susceptibility of development of HCC in HH patients has gained much traction. This review summarises the current knowledge with regard to the association of HH and HCC in order to encourage further research. In this review, we focus particularly on HFE gene-related HH. Herein, we highlight and discuss emerging clinical research which addresses the prevalence of HCC in HH patients and the coincidence of HH with other risk factors for HCC development. We also focus on the therapeutic tools in the management of HCC associated with HH.

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Successful Treatment of Iron-Overload Cardiomyopathy in Hereditary Hemochromatosis With Deferoxamine and Deferiprone

Cited by 19 publications

References 5 publications

Deciphering the Iron Side of Stroke: Neurodegeneration at the Crossroads Between Iron Dyshomeostasis, Excitotoxicity, and Ferroptosis

Deciphering the Iron Side of Stroke: Neurodegeneration at the Crossroads Between Iron Dyshomeostasis, Excitotoxicity, and Ferroptosis

Can two‐dimensional speckle tracking echocardiography be useful for left ventricular assessment in the early stages of hereditary haemochromatosis?

Association between hereditary hemochromatosis and hepatocellular carcinoma: a comprehensive review

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