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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary hemochromatosis (HHC) is one of the most common inherited disorders in the Caucasian population. Diagnosis usually made after an elevation in ferritin and serum transferrin saturation is noted, often accompanied by asymptomatic hepatomegaly. Diagnosis is confirmed by genetic testing or liver biopsy. Damage to organs is due to excessive intestinal iron, which is transported to and then deposited in the liver parenchyma, and the heart, skin, and endocrine organs, causing skin pigmentation, development of cirrhosis and hepatic carcinoma, diabetes and endocrine failure, and heart failure. Bony changes can be manifested by arthritis, often in non-weight-bearing joints. The treatment of HHC is phlebotomy, which depletes iron stores. When diagnosis is made before organ damage occurs, treatment can prevent manifestations of the disease. Skin pigmentation and some cardiac damage may reverse on depletion of iron stores, but liver and endocrine damage is rarely reversible. Arthropathy is also not reversible, and often continues to progress even with effective treatment. When hemochromatosis is diagnosed, all first degree relatives of the patient should undergo genetic testing. With early detection and treatment this can be a manageable chronic disease. If undetected, it is potentially fatal.
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PMID:Hereditary hemochromatosis: diagnosis and treatment in primary care. 1054 25

Thalassaemia is a group of genetic diseases where haemoglobin synthesis is impaired. This chronic anaemia leads to increased dietary iron absorption, which develops into iron overload pathology. Treatment through regular transfusions increases oxygen capacity but also provides iron through the red cells' haemoglobin. An essential treatment, in parallel with transfusions, is the use of chelating agents to remove the excess iron deposited in tissues. These deposits are found in the liver, spleen, heart, and pancreas and are associated with cardiac failure and diabetes. The deposits in these tissues of patients have been isolated as haemosiderin. Thalassaemia patients are particularly at risk of free radical induced damage. Thus, the present study has investigated, as a model system, human cells in vitro in the Comet assay in the presence of free radicals. This assay measures DNA damage, particularly DNA strand breakage. The effects of iron overload on cells oxidatively stressed with hydrogen peroxide (H(2)O(2)) have been determined as well as the effect of the chelating agent, deferoxamine. Iron overload was simulated with ferric (FeCl(3)) and ferrous chloride (FeCl(2)), ferrous sulphate (FeSO(4)) and haemosiderins. Both human lymphocytes from a male and a female donor and human adenocarcinoma colonic cells showed an increase in DNA damage in the Comet assay after treatment with H(2)O(2). Ferric chloride produced an increase in DNA damage in human colonic cells, but little or no damage in human lymphocytes. Ferrous chloride also produced weak DNA damage in human lymphocytes, but ferrous sulphate produced a dose-related response. Deferoxamine produced no DNA damage. When H(2)O(2) was combined with FeCl(3), FeCl(2), or FeSO(4), the DNA damage produced was as least as great as or slightly greater than with H(2)O(2) alone. When deferoxamine was combined with H(2)O(2) and FeSO(4) there was a consistent decrease in response. There was little or no decrease in response when deferoxamine was combined with H(2)O(2) and FeCl(3) or FeCl(2), but at high (100-300microm) doses there were changes in the appearance of cellular DNA from Comet tails to dense centres surrounded by a diffuse area. This was probably as a consequence of chelation processes. Haemosiderin produced no damage. The three fractions of haemosiderin examined were of three different densities and from a Thai patient where the oxyhydroxide phase is the ferrihydrite. The colour change was similar to that for FeCl(3), but the level of the ferric ion in the haemosiderin was possibly too low in the sample to produce a response. The next stage is to examine peripheral lymphocytes from thalassaemic patients, with and without chelation therapy, whose cells may be more sensitive to simulated iron overload and to lower levels of haemosiderin. Teratogenesis Carcinog. Mutagen. 20:11-26, 2000.
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PMID:Effects of iron salts and haemosiderin from a thalassaemia patient on oxygen radical damage as measured in the comet assay. 1060 74

Acute iron poisoning and chronic iron overload are well-known causes of myocardial failure. Although the exact mechanism is not known, excess iron-catalyzed free radical generation is conjectured to play a role in damaging the myocardium and altering cardiac function. We report here on the effects of acute and chronic iron-loading on the total iron concentration, glutathione peroxidase activity, and cytotoxic aldehyde production in the heart of a murine model (n = 35). Light microscopic examination for the presence of ferrous and ferric iron was undertaken following histochemical staining for these species. In addition, examination of representative samples by transmission electron microscopy was performed. Our findings show that iron-loading can result in significant increases in total iron concentrations, alterations to glutathione peroxidase activity, and increases in cytotoxic aldehyde concentrations in the hearts of mice. Furthermore, we observe that iron-loading can significantly alter and damage various cellular constituents (e.g., mitochondria, lysosomes, sarcoplasmic reticulum) and this may have bearing on the mechanism of iron-induced heart failure.
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PMID:A biochemical, histochemical, and electron microscopic study on the effects of iron-loading on the hearts of mice. 1061 16

Experimental and clinical studies have suggested an increased production of reactive oxygen species (ROS) in the failing myocardium. The present study aimed to obtain direct evidence for increased ROS and to determine the contribution of superoxide anion (*O(2)(-)), H(2)O(2), and hydroxy radical (*OH) in failing myocardial tissue. Heart failure was produced in adult mongrel dogs by rapid ventricular pacing at 240 bpm for 4 weeks. To assess the production of ROS directly, freeze-clamped myocardial tissue homogenates were reacted with the nitroxide radical, 4-hydroxy-2,2,6, 6,-tetramethyl-piperidine-N-oxyl, and its spin signals were detected by electron spin resonance spectroscopy. The rate of electron spin resonance signal decay, proportional to *OH level, was significantly increased in heart failure, which was inhibited by the addition of dimethylthiourea (*OH scavenger) into the reaction mixture. Increased *OH in the failing heart was abolished to the same extent in the presence of desferrioxamine (iron chelator), catalase (H(2)O(2) scavenger), and 4,5-dihydroxy-1,3-benzene disulfonic acid (Tiron; LaMotte) (*O(2)(-) scavenger), indicating that *OH originated from H(2)O(2) and *O(2)(-). Further, *O(2)(-) produced in normal myocardium in the presence of antimycin A (mitochondrial complex III inhibitor) could reproduce the increase of H(2)O(2) and *OH seen in the failing tissue. There was a significant positive relation between myocardial ROS level and left ventricular contractile dysfunction. In conclusion, in the failing myocardium, *OH was produced as a reactive product of *O(2)(-) and H(2)O(2), which might play an important role in left ventricular failure.
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PMID:Direct evidence for increased hydroxyl radicals originating from superoxide in the failing myocardium. 1066 4

Patients with beta-thalassaemia major frequently suffer from hypersiderosis which leads to hemochromatosis of major organs such as the heart and liver. Little information exists about the ultrastructural pathology of the human heart in beta-thalassaemia patients. Five Cypriot patients with elevated blood ferritin and intractable heart failure were investigated. Cardiac biopsies from these patients were studied by light and electron microscopy, as well as by X-ray microanalysis. Ultrastructural examination revealed the presence of disrupted myocytes showing loss of myofibers, dense nuclei, and a variable number of pleomorphic electron dense granules. These cytoplasmic granules or siderosomes consisted of iron-containing particles as confirmed by X-ray microanalysis. It is likely that the ultrastructural changes observed in myocytes of patients with beta-thalassaemia are largely due to iron deposition.
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PMID:Ultrastructural pathology of the heart in patients with beta-thalassaemia major. 1080 52

Although the mechanism of myocardial failure following acute iron poisoning is not known, excess iron-catalyzed free radical generation is conjectured to play a role. The effects of time (0 to 360 minutes) on total iron concentrations, glutathione peroxidase activity, and cytotoxic aldehyde production in heart of mice (B6D2F1, n = 65) were first investigated following acute iron-loading (20 mg iron dextran i.p./mouse). In a subsequent experiment, the effects of dose (0 to 80 mg iron dextran i.p./mouse, n = 75) on the aforementioned parameters were investigated. Our results show that the concentrations of cytotoxic aldehydes: (1) significantly differ over-time, with corresponding increases in total concentrations of iron (r = 0.93, p < 0.001); and (2) increase parallel to the total dose of iron administered (r = 0.95, p < 0.001). Furthermore, dose-and time-dependent alterations to glutathione peroxidase activity are observed, which is most likely due to an acute up-regulation of the enzyme as an endogenous protective response to increased free radical activity in the heart subsequent to iron-loading. While no single mechanism is likely to account for the complex pathophysiology of acute iron-induced heart failure, our results shown that iron-loading can result in significant free radical generation, as quantified by cytotoxic aldehydes, in heart tissue of mice. This is the first report on the effects of time and dose on cytotoxic aldehyde generation and glutathione peroxidase activity in heart of mice following acute iron-loading.
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PMID:Cytotoxic aldehyde generation in heart following acute iron-loading. 1083 29

An association between moderate anemia and poor perinatal outcomes has been found through epidemiologic studies, although available evidence cannot establish this relation as causal. Anemia may not be a direct cause of poor pregnancy outcomes, except in the case of maternal mortality resulting directly from severe anemia due to hypoxia and heart failure. Preventing or treating anemia, whether moderate or severe, is desirable. Because iron deficiency is a common cause of maternal anemia, iron supplementation is a common practice to reduce the incidence of maternal anemia. Nevertheless, the effectiveness of large-scale supplementation programs needs to be improved operationally and, where multiple micronutrient deficiencies are common, supplementation beyond iron and folate can be considered. High hemoglobin concentrations are often mistaken as adequate iron status; however, high hemoglobin is independent of iron status and is often associated with poor health outcomes. Very high hemoglobin concentrations cause high blood viscosity, which results in both compromised oxygen delivery to tissues and cerebrovascular complications. Epidemiologic studies have also found an association between high maternal hemoglobin concentrations and an increased risk of poor pregnancy outcomes. Evidence does not suggest that this association is causal; it could be better attributed to hypertensive disorders of pregnancy and to preeclampsia. The pathophysiologic mechanism of these conditions during pregnancy can produce higher hemoglobin concentrations because of reduced normal plasma expansion and cause fetal stress because of reduced placental-fetal perfusion. Accordingly, higher than normal hemoglobin concentrations should be regarded as an indicator of possible pregnancy complications, not necessarily as a sign of adequate iron nutrition, because iron supplementation does not increase hemoglobin higher than the optimal concentration needed for oxygen delivery.
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PMID:Significance of an abnormally low or high hemoglobin concentration during pregnancy: special consideration of iron nutrition. 1087 93

Juvenile hemochromatosis is a rare genetic disorder that causes iron overload. Clinical complications, which include liver cirrhosis, heart failure, hypogonadotropic hypogonadism and diabetes, appear earlier and are more severe than in HFE-related hemochromatosis. This disorder, therefore, requires an aggressive therapeutic approach to achieve iron depletion. We report here the case of a young Italian female with juvenile hemochromatosis who was unable to tolerate frequent phlebotomy because of coexistent ss-thalassemia trait. The patient was successfully iron-depleted by combining phlebotomy with recombinant human erythropoietin.
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PMID:Juvenile hemochromatosis associated with B-thalassemia treated by phlebotomy and recombinant human erythropoietin. 1094 34

Clinical complications of transfusional iron overload are still common in patients with thalassaemia major (TM) and it is not clear how best to monitor body iron stores during long-term follow-up to anticipate tissue damage. In this study, we have reviewed a group of 32 patients who underwent liver biopsy between 1984 and 1986. We developed a method of assessing the trend in serum ferritin (TSF) during long-term monitoring and compared this with mean serum ferritin (MSF) and initial liver iron (LI) concentration to determine whether, individually or in combination, they were accurate in predicting clinical outcome. LI levels were low (< 7 mg/g), medium (7-15 mg/g) and high (> 15 mg/g dry weight) in 15, 7 and 10 patients respectively. MSF was low (< 1500 microg/l), medium (1500-2500 microg/l) and high (> 2500 microg/l) in 10, 14 and 8 patients. TSF was low, medium and high risk in 9, 9 and 11 out of 29 evaluable patients. During a median follow-up of 13.6 years (range 2.3-14.8 years) after biopsy, nine patients died and an additional three patients developed heart failure. Hypothyroidism developed in five, hypoparathyroidism in four, and diabetes mellitus in seven patients. Cirrhosis developed in four of 10 evaluable patients. The clinical end-point of death or cardiac failure was significantly associated with increasing iron load using all three means of assessment. Although numbers were insufficient for statistical analysis, MSF or TSF were more closely associated with complications of iron overload than LI. There was no clear additional value in combining LI with MSF or TSF. The data show that quantitation of liver iron from a single liver biopsy has little value in long-term monitoring of iron stores. Most complications can be avoided if ferritin levels can be brought down to <1500 microg/l.
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PMID:Hepatic iron concentration combined with long-term monitoring of serum ferritin to predict complications of iron overload in thalassaemia major. 1105 91

Secondary and infiltrative cardiomyopathies are the least common forms of cardiomyopathy and often are the most difficult to treat. In all cases, efforts should be made to establish a specific diagnosis because the removal or avoidance of the causative agent (eg, alcohol, cocaine, persistent tachycardia) holds the best promise for reversal of ventricular dysfunction. Patients who present with a dilated cardiomyopathy (DCM) should be treated with standard heart failure therapy. However, the "standard" is changing and clinicians need to take heed of results of recent trials establishing the role of beta-blockers, aldosterone, and angiotensin receptor antagonists in addition to the regimen of digoxin, diuretics and angiotensin-converting enzyme (ACE) inhibitors. In contrast, patients who present with a more infiltrative clinical picture often manifest more diastolic dysfunction and need strict volume control to maintain euvolemia. For patients with biopsy-proven myocarditis, immunosuppressive therapy generally should be considered in an effort to maintain and potentially improve ventricular function. Patients with sarcoid heart disease have shown the greatest response to high-dose corticosteroids. Patients with hemochromatosis related cardiomyopathy should be treated with iron chelation therapy and phlebotomy. The role of cardiac transplantation is limited, as most of the secondary and infiltrative causes of cardiomyopathy are associated with an adverse posttransplant outcome. Other surgical options, such as left ventricular assist devices, may offer hope to patients who would otherwise be ineligible for cardiac transplantation. On the horizon, biventricular pacing and treatments targeted at cytokines and hormonal receptors hold the promise of improving symptoms and prolonging survival by counteracting the deleterious effects of these secondary mediators.
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PMID:Secondary and Infiltrative Cardiomyopathies. 1109 42


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