On myocardial siderosis and left ventricular dysfunction in hemochromatosis

Carpenter, John-Paul; Grasso, A; Porter, John B.; Shah, Farrukh; Dooley, James; Pennell, Dudley J.

doi:10.1186/1532-429x-15-24

Cited by 34 publications

(28 citation statements)

References 43 publications

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“…However, when levels of ferritin are 41000 μg/l, myocardial siderosis increases markedly and it is present in 1/3 of patients. 64 Myocardial siderosis causes oxidative damage and resultant heart dysfunction. 65 It is believed that in conditions with iron excess, iron enters myocardial cells through L-type calcium channels (LTCC).…”

Section: Role Of Systemic Hepcidin In Heart Homeostasismentioning

confidence: 99%

Balance of cardiac and systemic hepcidin and its role in heart physiology and pathology

Vela

2018

Laboratory Investigation

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Hepcidin is the main regulator of iron metabolism in tissues. Its serum levels are mostly correlated with the levels of hepcidin expression from the liver, but local hepcidin can be important for the physiology of other organs as well. There is an increasing evidence that this is the case with cardiac hepcidin. This has been confirmed by studies with models of ischemic heart disease and other heart pathologies. In this review the discussion dissects the role of cardiac hepcidin in cellular homeostasis. This review is complemented with examination of the role of systemic hepcidin in heart disease and its use as a biochemical marker. The relationship between systemic vs local hepcidin in the heart is important because it can help us understand how the fine balance between the actions of two hepcidins affects heart function. Manipulating the axis systemic/cardiac hepcidin could serve as a new therapeutic strategy in heart diseases.

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Section: Role Of Systemic Hepcidin In Heart Homeostasismentioning

confidence: 99%

Balance of cardiac and systemic hepcidin and its role in heart physiology and pathology

Vela

2018

Laboratory Investigation

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“…As the disease progresses, iron accumulates in the remainder of the liver and also in the pancreas, where it deposits predominantly in acinar cells (Rahier et al, 1987). Later in the disease, iron loads in the myocardium of the heart (Carpenter et al, 2013). Clinical manifestations of hereditary hemochromatosis include hepatic fibrosis, cirrhosis, diabetes, and cardiomyopathy (Pietrangelo, 2010).…”

Section: Introductionmentioning

confidence: 99%

SLC39A14 Is Required for the Development of Hepatocellular Iron Overload in Murine Models of Hereditary Hemochromatosis

et al. 2015

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SUMMARY Nearly all forms of hereditary hemochromatosis are characterized by pathological iron accumulation in the liver, pancreas, and heart. These tissues preferentially load iron because they take up non-transferrin-bound iron (NTBI), which appears in the plasma during iron overload. Yet, how tissues take up NTBI is largely unknown. We report that ablation of Slc39a14, the gene coding for solute carrier SLC39A14 (also called ZIP14), in mice markedly reduced the uptake of plasma NTBI by the liver and pancreas. To test the role of SLC39A14 in tissue iron loading, we crossed Slc39a14−/− mice with Hfe−/− and Hfe2−/− mice, animal models of type 1 and type 2 (juvenile) hemochromatosis respectively. Slc39a14 deficiency in hemochromatotic mice greatly diminished iron loading of the liver and prevented iron deposition in hepatocytes and pancreatic acinar cells. The data suggest that inhibition of SLC39A14 may mitigate hepatic and pancreatic iron loading and associated pathologies in iron overload disorders.

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“…328 The application of noninvasive iron measurement technology needs to be evaluated in other iron-overload conditions after a report of its use in hereditary hemochromatosis. 329 Finally, a randomized controlled trial of long-term amlodipine treatment, which is a new strategy to prevent cardiac iron loading, is under way. This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit.…”

Section: Future Directionsmentioning

confidence: 99%

Cardiovascular Function and Treatment in β-Thalassemia Major

Pennell¹,

Udelson²,

Arai³

et al. 2013

Circulation

324

172

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This aim of this statement is to report an expert consensus on the diagnosis and treatment of cardiac dysfunction in β-thalassemia major (TM). This consensus statement does not cover other hemoglobinopathies, including thalassemia intermedia and sickle cell anemia, in which a different spectrum of cardiovascular complications is typical. There are considerable uncertainties in this field, with a few randomized controlled trials relating to treatment of chronic myocardial siderosis but none relating to treatment of acute heart failure. The principles of diagnosis and treatment of cardiac iron loading in TM are directly relevant to other iron-overload conditions, including in particular Diamond-Blackfan anemia, sideroblastic anemia, and hereditary hemochromatosis. Heart failure is the most common cause of death in TM and primarily results from cardiac iron accumulation. The diagnosis of ventricular dysfunction in TM patients differs from that in nonanemic patients because of the cardiovascular adaptation to chronic anemia in non–cardiac-loaded TM patients, which includes resting tachycardia, low blood pressure, enlarged end-diastolic volume, high ejection fraction, and high cardiac output. Chronic anemia also leads to background symptomatology such as dyspnea, which can mask the clinical diagnosis of cardiac dysfunction. Central to early identification of cardiac iron overload in TM is the estimation of cardiac iron by cardiac T2* magnetic resonance. Cardiac T2* <10 ms is the most important predictor of development of heart failure. Serum ferritin and liver iron concentration are not adequate surrogates for cardiac iron measurement. Assessment of cardiac function by noninvasive techniques can also be valuable clinically, but serial measurements to establish trends are usually required because interpretation of single absolute values is complicated by the abnormal cardiovascular hemodynamics in TM and measurement imprecision. Acute decompensated heart failure is a medical emergency and requires urgent consultation with a center with expertise in its management. The first principle of management of acute heart failure is control of cardiac toxicity related to free iron by urgent commencement of a continuous, uninterrupted infusion of high-dose intravenous deferoxamine, augmented by oral deferiprone. Considerable care is required to not exacerbate cardiovascular problems from overuse of diuretics or inotropes because of the unusual loading conditions in TM. The current knowledge on the efficacy of removal of cardiac iron by the 3 commercially available iron chelators is summarized for cardiac iron overload without overt cardiac dysfunction. Evidence from well-conducted randomized controlled trials shows superior efficacy of deferiprone versus deferoxamine, the superiority of combined deferiprone with deferoxamine versus deferoxamine alone, and the equivalence of deferasirox versus deferoxamine.

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On myocardial siderosis and left ventricular dysfunction in hemochromatosis

Cited by 34 publications

References 43 publications

Balance of cardiac and systemic hepcidin and its role in heart physiology and pathology

Balance of cardiac and systemic hepcidin and its role in heart physiology and pathology

SLC39A14 Is Required for the Development of Hepatocellular Iron Overload in Murine Models of Hereditary Hemochromatosis

Cardiovascular Function and Treatment in β-Thalassemia Major

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