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

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

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

BACKGROUND: Myocardial reflectivity is abnormally increased in patients with thalassemia major under transfusion treatment, probably due to myocardial iron deposits and/or secondary structural changes. Such increased reflectivity has been detected by both qualitative and subjective analysis of two-dimensional echocardiographic (2-D echo) images and quantitative assessment of integrated backscatter amplitude with noncommercially available ultrasound prototypes. The purpose of this study was to assess the acoustic properties of myocardium in patients with beta-thalassemia major and iron overload by means of quantitative computerized offline textural analysis of conventionally recorded 2-D echo images, and to compare textural data with other qualitative (visual assessment) and quantitative (ultrasound backscatter analysis) approaches for myocardial ultrasound tissue characterization simultaneously applied to these patients. METHODS AND RESULTS: Thirty-five young patients with thalassemia major, without clinical signs of cardiac failure, and 20 age and sex matched normal controls were studied by echocardiography. Each patient was receiving blood transfusion every 2-3 weeks. Two-dimensional echo images, obtained with a commercially available echocardiograph using the parasternal long-axis view, were digitized off line and analyzed by first and second order texture algorithms applied to regions of interest in the myocardium (septal and posterior wall). The mean gray level value was higher in thalassemic patients than in controls on both the septum (110 +/- 25 vs 57 +/- 13, arbitrary units on a 0-255 scale; P < 0.01) and posterior wall (91 +/- 25 vs 67 +/- 18; P < 0.01). Among second order statistical parameters, contrast and angular second moment significantly (P < 0.01) differentiated septal and posterior walls of patients and controls. In thalassemic patients, no consistent correlation was found between wall texture parameters and hematologic (years of transfusions and chelation, number of transfusions), 2-D echo (posterior wall thickness, left ventricular end-diastolic diameter), and Doppler (transmitral E/A waves ratio) parameters. Myocardial walls with visually assessed increased echo reflectivity showed a trend toward higher values of mean gray level when compared with myocardial segments with qualitatively assessed normal reflectivity (septum: 121 +/- 26 vs 106 +/- 24; posterior wall: 105 +/- 23 vs 87 +/- 23). Although radiofrequency integrated backscatter has been demonstrated to be capable of identifying thalassemic patients, no significant correlation was found between mean gray level (by texture analysis) and radiofrequency data (septum: r = 0.03; posterior wall: r = 0.09; P = NS for both). CONCLUSIONS: Myocardial walls affected by hemochromatosis show ultrasound image texture alterations that may be quantified with digital image analysis techniques and appear mostly unrelated to hematologic and conventional, as well as radiofrequency-based, echocardiographic parameters. These changes in quantitatively evaluated echo reflectivity are present even before the development of clinical and echocardiographic signs of cardiac dysfunction. (ECHOCARDIOGRAPHY, Volume 13, January 1996)
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PMID:Quantitative Texture Analysis in Two-Dimensional Echocardiography: Application to the Diagnosis of Myocardial Hemochromatosis. 1144 99

Patients with beta thalassemia major present with severe anemia and need continuous transfusion therapy. The consequent iron overload leads to hemochromatosis. Initial cardiac involvement can be present in thalassemic patients without clinical manifestations of heart failure. The purpose of this study was to assess the contractile reserve of the left ventricle in patients with normal baseline two-dimensional (2-D) echocardiographic findings using low dose dobutamine echocardiography. The underlying hypothesis was that, at an early stage, structural impairment of the myocardial wall due to myocardial iron deposits and/or secondary fibrotic changes could be so subtle so as not to impair resting systolic function, but is severe enough to blunt or even exhaust the contractile response to inotropic stimulation. Twenty-four consecutive patients (13 men and 11 women; ages 18 +/- 3.8 years) with beta thalassemia major undergoing evaluation for bone marrow transplantation entered the study. By selection, all were asymptomatic, without clinical signs of cardiac failure, and had normal regional and global systolic function at baseline echocardiographic study. A control group of 16 age and sex matched subjects was also studied. All underwent baseline, 2-D, and Doppler study, as well as dobutamine stress (up to 5 &mgr;g/kg per min) 2-D echocardiographic study. Patients and controls showed comparable values of indexes of global (ejection fraction: 0.64 +/- 0.06 vs 0.65 +/- 0.05, P = NS) and regional (systolic thickening of posterior wall: 90 +/- 34 vs 91 +/- 34%, P = NS) function at baseline. Left ventricular diastolic filling was evaluated with Doppler echocardiography. Peak flow velocity in early diastole was increased in thalassemic patients compared to controls (114 +/- 16 vs 96 +/- 18 cm/sec, P < 0.01), and flow velocity deceleration time was reduced (139 +/- 17 vs 157 +/- 20 msec, P < 0.01). At peak dobutamine, thalassemic patients showed a blunted contractile response compared to controls for indexes of both global (ejection fraction: 0.62 +/- 0.06 vs 0.69 +/- 0.05, P < 0.01) and regional (% systolic thickening of posterior wall: 91 +/- 36 vs 130 +/- 39%, P < 0.01) function. When individual patient analysis was performed, echocardiographic parameters were beyond the 95% confidence limits obtained from normal controls in 5 (21%) of the 24 study patients by one or more Doppler diastolic indexes, in 6 (25%) by indexes of contractile reserve, and in 11 (46%) by one of either diastolic function or contractile reserve indexes. These data demonstrate that the "iron heart" of asymptomatic thalassemic patients is a weak heart. Even if the regional and global systolic functions are similar to normals under resting conditions, the application of an inotropic challenge unmasks the weakness of these hearts, which can be identified at an earlier stage of their natural history through the blunted contractile response following the infusion of low dose dobutamine. The information on contractile reserve is not redundant, but rather incremental and in addition to that provided by Doppler echocardiographic indexes, which may be abnormal in these patients. (ECHOCARDIOGRAPHY, Volume 13, September 1996)
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PMID:Reduced Left Ventricular Contractile Reserve Identified by Low Dose Dobutamine Echocardiography as an Early Marker of Cardiac Involvement in Asymptomatic Patients with Thalassemia Major. 1144 56

Hemochromatosis is a genetic disease of iron overload due to intestinal hyperabsorption of iron. It is one of the most prevalent autosomal recessive diseases in Caucasian populations. Hemochromatosis causes severe visceral and metabolic complications at adulthood, which include cirrhosis, diabetes, arthropathy and cardiac failure. A major breakthrough has been the discovery, in 1996, of the HFE gene which is strongly associated with the phenotypic expression of the disease. This discovery has, very quickly, provided a powerful genetic blood test which permits, in most cases, to establish the diagnosis in a non invasive way (i.e. without a liver biopsy). Hemochromatosis can be cured by repeated venesections provided the diagnosis has been detected sufficiently early. Moreover, an efficient preventive strategy can be applied to family members and should now be proposed to the general population. Finally, the identification of the HFE gene has paved the way for the identification of new iron overload entities.
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PMID:Hemochromatosis at the intersection of classical medicine and molecular biology. 1155 26

Heart failure due to chronic iron overload is a leading cause of cardiovascular mortality in the second and third decades of life worldwide, but its mechanism is not known. Deficiencies of selenium have been shown to result in damage to the myocardium and to the development of various cardiomyopathies. In the current investigation, the dose-dependent effects of chronic iron toxicosis on heart tissue concentrations of selenium and the protective antioxidant enzyme glutathione peroxidase (GPx) were investigated in a murine model of iron-overload cardiomyopathy (n = 20). Significant dose-dependent decreases in heart tissue selenium concentrations (r = -0.95, p < 0.001) and selenium-dependent GPx activity (r = -0.93, p < 0.001) were observed in chronically iron-loaded mice in comparison with placebo controls. These results suggest that dietary supplementation with selenium may be beneficial in the clinical management of disorders of iron metabolism.
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PMID:Decreasing effects of iron toxicosis on selenium and glutathione peroxidase activity. 1185 44

Iron deposition in the heart occurs in beta-thalassaemia major and contributes to cardiac dysfunction. Eighteen patients with beta-thalassaemia major were assessed clinically and had non-invasive investigations. They were young (15.5 +/- 3.6 years). Two patients had clinical heart failure. Doppler echocardiography demonstrated higher transmitral peak flow velocity in early and late diastole compared with controls (e: p<0.05, a: p<0.01). Transtricuspid peak late diastolic flow velocity was higher in patients (p<0.005). Isovolumic relaxation time was shortened (p<0.001). Pulmonary venous flow velocity was higher in diastole than systole (S: 0.51 +/- 0.11 m/s, D: 0.62 +/- 0.08 m/s). Reversal of pulmonary venous flow during atrial systole was seen in eight patients. These diastolic filling abnormalities did not significantly change with blood transfusion. Left ventricular ejection fraction was normal in patients. Two patients had cardiomegaly on chest X-ray. In beta-thalassaemia with iron overload, there is a restrictive pattern of diastolic dysfunction. This is not altered by recent blood transfusion. Left ventricular function remains relatively intact.
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PMID:Non-invasive cardiac assessment in beta-thalassaemia major. 1213 42

Juvenile hemochromatosis or type 2 hemochromatosis is a rare inherited recessive disease, which leads to severe iron overload earlier in life than HFE-related hemochromatosis. Increased transferrin saturation and serum ferritin as well as parenchymal iron deposition and liver fibrosis may be observed in childhood. Clinical symptoms of hypogonadism and cardiac disease develop before the age of 30. The disease is usually progressive and if untreated may become fatal because of heart failure. The type 2 hemochromatosis locus maps to chromosome 1q21, but the gene has not yet been isolated. The severity and the early expression of juvenile hemochromatosis suggest that the gene product has a crucial role in the regulation of iron homeostasis.
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PMID:Juvenile hemochromatosis. 1238 99

Effective management of iron overload in thalassaemia requires monitoring both for iron toxicity and the effects of excessive chelation. Careful monitoring together with adherence to established regimens using desferrioxamine (DFO) results in a 78% survival rate at 40 years of age at UCLH, with steadily improving survival as progressive cohorts receive chelation earlier in life. By contrast, survival is considerably below this in non-specialist centres. The prognostic significance of the measures being used in monitoring should be known so that decisions about chelation management are evidence-based. Serum ferritin measurement, although easy to perform frequently, is subject to variability and falsely high or falsely low values in relation to body iron are frequently obtained. However, there is evidence that persistently high ferritin values above 2500 microg/l have poor prognostic significance in patients treated with DFO. Liver iron predicts total body iron in a more predictable way than serum ferritin in thalassaemia. Liver iron concentrations of 15 mg/g dry weight appear to predict those patients who develop heart failure in subjects treated with DFO. The prognostic significance of this measurement or indeed other measurements of iron overload in patients treated with other chelation regimens is not known. Recent advances with MRI imaging have aroused interest in its use for monitoring patients with thalassaemia. A recent publication suggests a relationship between left ventricular ejection fraction and cardiac T2*, the value of which shortens with increasing iron concentrations in the liver and hence by inference in the heart. The prognostic value of this technique has not yet been demonstrated in prospective studies and hence changes in therapy based on this measurement alone should be considered with caution at this time. The value of monitoring to decrease morbidity from iron overload is also discussed, particularly with reference to the estimation of iron deposition in the pituitary.
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PMID:Monitoring chelation therapy to achieve optimal outcome in the treatment of thalassaemia. 1240 11


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