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

We report the clinical, biochemical, and genetic characteristics of 13 hemochromatosis patients from Saguenay-Lac-Saint-Jean in whom the first symptoms appeared before age 30. Although the mean age at onset of the first symptoms was 21. 5 years, their mean age at diagnosis was 23.8 years; the diagnosis was particularly delayed among women. Seventy-seven percent of the patients had hypogonadotrophic hypogonadism and 69% heart failure and/or cardiac arrhythmias. Genetic analysis of the HFE gene revealed heterozygosity for the C282Y mutation in 2 patients and for the S65C mutation in 2 others and homozygosity for the H63D mutation in 1 patient. The remaining 8 patients had no identified mutation in the HFE gene, although sequencing of all seven codons and intron-exon junctions was performed (5 patients). All 13 patients fulfill the clinical criteria of juvenile hemochromatosis and represent the largest cluster thus far reported.
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PMID:Clinical and molecular aspects of juvenile hemochromatosis in Saguenay-Lac-Saint-Jean (Quebec, canada). 1077 71

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

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

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

Most patients diagnosed with secondary hemochromatosis have had repeated blood transfusions. Cardiac failure accounts for approximately one-third of the deaths associated with hemochromatosis. Liver dysfunction or hormonal disorders such as diabetes generally precede cardiac failure. A 23-year-old woman with hemochromatosis had, despite significant left ventricular dysfunction, liver function within the normal range on biochemical evaluation. She was treated for congestive heart failure and given desferoxamine intravenously. She did not have primary hemochromatosis, and had not received multiple blood transfusions or iron supplement. As a child the patient had been diagnosed with congenital non-spherocytic hemolytic anemia not requiring transfusion; thus, this is a unique case of secondary hemochromatosis.
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PMID:Cardiac dysfunction because of secondary hemochromatosis caused by congenital non-spherocytic hemolytic anemia. 1121 22

Iron-overload cardiomyopathy is a restrictive cardiomyopathy that manifests itself as systolic or diastolic dysfunction secondary to increased deposition of iron in the heart and occurs with common genetic disorders such as primary hemochromatosis and beta-thalassemia major. Although the exact mechanism of iron-induced heart failure remains to be elucidated, the toxicity of iron in biological systems is believed to be attributed to its ability to catalyze the generation of oxygen-free radicals. In the current investigation, the dose-dependent effects of chronic iron-loading on heart tissue concentrations of iron, glutathione peroxidase (GPx) activity, free-radical production, and cardiac dysfunction were investigated in a murine model of iron-overload cardiomyopathy. It was shown that chronic iron-overload results in dose-dependent (a) increases in myocardial iron burden, (b) decreases in the protective antioxidant enzyme GPx activity, (c) increased free-radical production, and (d) increased mortality. These findings show that the mechanism of iron-induced heart dysfunction involves in part free radical-mediated processes.
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PMID:Iron-overload cardiomyopathy: evidence for a free radical--mediated mechanism of injury and dysfunction in a murine model. 1123 11

The energy needed by cardiac muscle to maintain proper function is supplied by adenosine Ariphosphate primarily (ATP) production through breakdown of fatty acids. Metabolic cardiomyopathies can be caused by disturbances in metabolism, for example diabetes mellitus, hypertrophy and heart failure or alcoholic cardiomyopathy. Deficiency in enzymes of the mitochondrial beta-oxidation show a varying degree of cardiac manifestation. Aberrations of mitochondrial DNA lead to a wide variety of cardiac disorders, without any obvious correlation between genotype and phenotype. A completely different pathogenetic model comprises cardiac manifestation of systemic metabolic diseases caused by deficiencies of various enzymes in a variety of metabolic pathways. Examples of these disorders are glycogen storage diseases (e.g. glycogenosis type II and III), lysosomal storage diseases (e.g. Niemann-Pick disease, Gaucher disease, I-cell disease, various types of mucopolysaccharidoses, GM1 gangliosidosis, galactosialidosis, carbohydrate-deficient glycoprotein syndromes and Sandhoff's disease). There are some systemic diseases which can also affect the heart, for example triosephosphate isomerase deficiency, hereditary haemochromatosis, CD 36 defect or propionic acidaemia.
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PMID:Metabolic cardiomyopathies. 1129 85

During the last decades efforts regarding dietary iron supply focused mostly on the prevention of deficiencies, especially during growth and pregnancy. Correspondingly, homeostatic mechanisms increase intestinal iron absorption in iron deficiency, but its downregulation at high intake levels seems insufficient to prevent accumulation of high iron stores at high intake. There is no regulated iron excretion in overload. Excess of pharmaceutical iron may cause toxicity and therapeutic doses may cause gastrointestinal side effects. Chronic iron excess, e.g. in primary and secondary hemochromatosis, may lead to hepatic fibrosis, diabetes mellitus and cardiac failure. Chronic intake of 50-100 mg Fe/day of highly bioavailable iron with home-brewed beer in sub-Saharan Africans lead to cirrhosis and diabetes. Applying a safety factor of 2 would lead to an upper safe level of 25-50 mg Fe/day for this endpoint of conventional iron toxicity. However, beyond this kind of damage iron is known to catalyze the generation of hydroxyl radicals from superoxide anions and to increase oxidative stress which, in turn, increases free iron concentration. This self-amplifying process may cause damage to lipid membranes and proteins, which relates radical generation and organ damage after ischemia-reperfusion events to available free iron in clinical and experimental settings. Correspondingly, epidemiological studies as well as observations in heterozygotes for hereditary hemochromatosis suggest that the risk of atherosclerosis and acute myocardial infarction is related to body iron stores, though there is conflicting epidemiological evidence as well. The most recent and best controlled studies, however, support the hypothesis that iron stores are related to cardiovascular risk. Iron-amplified oxidative stress may also increase DNA damage, oxidative activation of precancerogens and support tumor cell growth. This is supported by experimental, clinical and epidemiological observations. Due to these mechanisms high iron stores may present a health hazard. Though this has not been finally proven, available evidence strongly recommends not to increase iron intake beyond physiological requirements. To avoid iron deficiency symptoms, on the other hand, care must be taken to meet recommended daily intake.
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PMID:Safety aspects of iron in food. 1142

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


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