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

The histopathology, ultrastructure, and clinicopathologic correlations in six patients with cardiac failure and iron encrustation of lung elastic tissue were examined at autopsy. Transmission electron microscopy (TEM) and energy dispersive x-ray analysis were applied to two cases. Of the group, five patients had cardiac failure due to systemic hypertension (4 patients), valvular disease (4 patients), or coronary atherosclerosis (4 patients). Biventricular failure in one patient was associated with sleep apnea. Both iron and calcium, identified by histochemical stains, impregnated degenerated alveolar and vascular elastic fibers and were associated with a foreign body reaction and focal interstitial fibrosis. Energy dispersive x-ray analysis and TEM demonstrated iron and calcium on the microfibrillar portion of elastin. Morphometry indicated vascular changes of pulmonary venous hypertension. The authors concluded that mineral deposition probably represents nonspecific precipitation of metallic ions on altered elastic fibers in patients with cardiac failure. "Mineralizing elastosis" potentially contributes to lung restriction and, occasionally, can be a source of diagnostic confusion.
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PMID:Mineralizing pulmonary elastosis in chronic cardiac failure. "Endogenous pneumoconiosis" revisited. 827 51

Accumulation of Fe in the myocardium in circumstances of transferrin saturation is associated with heart failure in Fe-loaded patients. To characterize the underlying causes of this phenomenon, we measured the flux as well as the speciation of Fe in normal and Fe-loaded cultures of rat myocardiocytes. Fe loading with low-molecular-weight Fe (ferric ammonium citrate) promoted a dose- and time-dependent increase in the rate of uptake of non-transferrin-bound Fe (NTBI) that was positively correlated (R = 0.9, p < 0.005) with cellular iron content. At concentrations sufficient to produce this up-regulation, membrane integrity was unaffected but the rate of spontaneous beating of the cells was decreased by 60%. The enhanced rate of NTBI uptake in Fe-loaded cells reverted to control rates after treatment with therapeutic concentrations of Fe chelators deferoxamine, 1,2-dimethyl-3-hydroxypyrid-4-one and 1,2-diethyl-3-hydroxypyrid-4-one under conditions where approximately 80% of the cellular Fe was removed by chelation. Fe loading of cultured myocytes also induced shifts in Fe speciation. Thus the ratio of Fe bound in hemosiderin-like precipitates to ferritin-bound Fe increased twofold, from a range of 0.84 to 1.44 in control cells to 1.96 to 3.3 in iron-loaded cells. This increased ratio was similar to that measured in the heart and liver of a thalassemic patient who underwent a double transplant for the failure of both organs, even though the Fe content of the heart (mean, 5.8 mg Fe/gm dry weight) was much less than that of the liver (28.1 mg/gm dry weight). These results suggest that increased rates of uptake of NTBI may exacerbate iron loading of the heart and contribute to iron-mediated cardiotoxicity, whereas the clinical benefits of chelation therapy may be enhanced by the down-regulation of NTBI uptake.
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PMID:Effects of iron loading on uptake, speciation, and chelation of iron in cultured myocardial cells. 832 Apr 86

Haemochromatosis is an inherited disorder of iron metabolism characterized by a general iron over loading. Without diagnosis and early treatment, it is a serious and potentially fatal disease by cardiac failure or hepatocellular carcinoma in particular. Gene prevalence was estimated at 0.06 in Brittany, so that haemochromatosis may be the most common genetic disease in this area. The biochemical defect of the disease is unknown; only one fact is well established: the iron absorption through duodenal mucosa is excessive. However we don't know if it is a primary event. The gene is also unknown but in 1975 it was located on the short arm of chromosome 6, closely linked to the HLA class I region, less than 1 cM from HLA-A. None of the genes coding for the known iron proteins could be the haemochromatosis gene because of their chromosomal localization. In order to locate this gene with precision, we have used a reverse genetic approach now called positional cloning. Characterization of new polymorphic markers and linkage disequilibrium analysis, have led us to locate the gene within a 350 kb region around HLA-A. We have then searched for all the structural genes in this region. Seven new genes have been so identified and located with precision. A structural analysis of these genes was undertaken to find an eventual abnormality in patients.
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PMID:[Molecular genetics of hemochromatosis]. 835 73

In patients with thalassemia major iron overload leads to symptoms of cardiac failure and it is the most frequent cause of death. A sub group of asymptomatic thalassemic patients (Th Pts) who underwent bone marrow transplantation (BMT) and who presented persistently high serum ferritin level and heavy haemosiderosis were subjected to cardiological study to evaluate possible iron-related cardiac disease. We report here preliminary results obtained from the Echocardiographic studies carried out at baseline and at eight months follow-up in a group of ex-thalassemic after transplant who underwent phlebotomy in the attempt to reduce the iron overload.
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PMID:Echocardiographic study in ex-thalassemic patients with iron overload, preliminary observations during phlebotomy therapy. 837 47

Dilated cardiomyopathy is a frequent and serious complication of idiopathic hemochromatosis. The mechanism by which disordered iron metabolism induces heart failure is not entirely understood, but myocardial dysfunction appears to be intimately related to the deposition of iron in myocytes. Cardiac function characteristically worsens or improves in proportion to the degree of iron accumulation in cardiac myocytes. The authors report the case of a 47-year-old man with idiopathic hemochromatosis and cirrhosis who developed symptoms of congestive heart failure and was found to have dilated cardiomyopathy 7 months after receiving a liver transplant. An initial endomyocardial heart biopsy demonstrated severe iron deposition in myocytes. The patient's heart failure worsened in the next 3 years and he eventually required a heart transplant. Examination of the explanted heart revealed dilated cardiomyopathy, but the previously demonstrated iron deposits in the cardiac myocytes were depleted. This "uncoupling" of cardiac function and cardiac iron load suggests that a threshold may be reached at which point the metabolic and ultrastructural derangements of iron deposition are no longer reversible, even with the removal of the inciting agent. Furthermore, displacement of myocyte iron stores after liver transplantation implicates altered hepatic iron metabolism as a primary or contributing mechanism in the pathophysiology of idiopathic hemochromatosis.
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PMID:Progressive hemochromatotic cardiomyopathy despite reversal of iron deposition after liver transplantation. 842 14

Progressive tissue iron deposition from multiple blood transfusions is common in beta-thalassaemia and pulmonary iron deposition may result in parenchymal damage. The objectives of this study were to: 1) determine the predominant pulmonary dysfunction in patients with thalassaemia major; and 2) demonstrate that parenchymal disease, if present, is at the level of the alveolocapillary membrane. Fourteen thalassaemia major patients (13 nonsmokers) receiving regular blood transfusion and without any history of chronic respiratory disease were recruited. Pulmonary function tests and echocardiography were performed before the scheduled transfusions. Three patients with the most restricted lung function were selected for high resolution computerized tomography (CT) of the lungs. One patient had an obstructive pattern with a forced expiratory volume in one second as percentage of forced vital capacity (FEV1/FVC) of 71%. Four patients demonstrated a restrictive pattern, as defined by total lung capacity (TLC) less than 80% predicted with normal FEV1/FVC%. Twelve patients had pulmonary transfer factors for carbon monoxide (TL,CO) below 80% pred, even after correction for the anaemia, indicating parenchymal disease. Eight of these 12 patients had alveolocapillary membrane defect, as demonstrated by a gas transfer factor of the pulmonary membrane (Tm) less than 80% pred. Mean resting arterial oxygen saturation was 95 +/- 2 (range 92-98) %. Eleven patients had oxygen desaturation of 5% or more during exercise on a bicycle ergometer, consistent with interstitial lung disease. There was no clinical or echocardiographic evidence of heart failure. Percentage predicted TLC was inversely correlated with age (r = -0.547; p = 0.043). Both percentage predicted TLC and TL,CO were not correlated with iron burden or desferoxamine ratio. High resolution CT in the three selected patients showed no evidence of pulmonary fibrosis. We conclude that thalassaemia major patients have a predominant restrictive lung dysfunction with pulmonary parenchymal disease and alveolocapillary membrane block. The restrictive and interstitial lung disease could not be accounted for by iron loading or pulmonary fibrosis in our patients.
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PMID:Lungs in thalassaemia major patients receiving regular transfusion. 883 48

Approximately 1.5 million persons in the United States are affected by iron overload diseases, which are primarily caused by hereditary hemochromatosis--the most common genetic disorder in the United States. Hereditary hemochromatosis is characterized by increased iron absorption in the gastrointestinal tract, which may cause lifelong excessive iron absorption and accumulation and serious health effects, including arthritis, cirrhosis, diabetes, impotence, heart failure, and death. Hereditary hemochromatosis is an autosomal recessive disease; the estimated prevalence of the homozygous genotype is 1:200 - 1:250 persons, and 10% of persons are carriers. Although the disease was previously believed to affect primarily white males of northern European descent, recent data indicate hereditary hemochromatosis also occurs among blacks. Moreover, iron overload diseases are underdiagnosed among whites and may not be considered in other racial/ethnic groups (e.g., Hispanics) even when compatible symptoms and clinical findings are present. As part of a joint demonstration project during August-October 1995 to determine the overall prevalence of iron overload, CDC reviewed data from a health-maintenance organization (HMO) in San Diego, California; the prevalence among Hispanics appeared similar to that for non-Hispanic whites. This report presents the preliminary findings of an analysis of the prevalence of iron overload among Hispanics and compares these findings with nationally representative data from the Third National Health and Nutrition Examination Survey (NHANES III). These findings indicate that the prevalence of possible iron overload among Hispanic clients of the HMO based on initial screening was consistent with the nationwide prevalence of possible iron overload based on a single screening test for Hispanics of Mexican descent and non-Hispanic whites.
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PMID:Iron overload disorders among Hispanics--San Diego, California, 1995. 900 7

We reviewed clinical data, autopsy reports, and microscopic slides on 10 patients with sleep apnea/obesity hypoventilation syndrome (SA/OHS) to define the cardiopulmonary pathological features and establish clinicopathologic correlations. Ten obese (>136 kg) patients without SA/OHS were studied as controls. Patients with SA/OHS exhibited biventricular cardiac failure and pulmonary hypertension with a higher prevalence of moderate/severe pulmonary hemosiderosis (8 v 0 patients), alveolar hemorrhage (7 v 4 patients), capillary proliferation (4 v 0 patients), iron encrustation of elastica (1 v 0 patients) and medial hypertrophy of muscular pulmonary arteries (11.9 +/- 2.4 v 9.7 +/- 1.6%) (P < .05). In two patients capillary proliferation resembled capillary hemangiomatosis. Mean right ventricular thickness was higher in the SA/OHS group (0.71 +/- 0.17 v 0.42 +/- 0.1 cm) (P < .01). Four patients with SA/OHS and three controls had moderate/severe myocardial fibrosis. Biventricular cardiac failure caused death in seven patients with SA/OHS. Hypoxia is probably the most important cause of pulmonary hypertension, arterial muscularization, and right ventricular hypertrophy in SA/ OHS. Left ventricular failure in some SA/OHS patients may be the result of hypertensive cardiac disease. In others, the etiology of left ventricular failure was not determined morphologically, suggesting functional abnormalities related to obesity and/or apneic episodes.
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PMID:Cardiopulmonary pathology in patients with sleep apnea/obesity hypoventilation syndrome. 938 47

Haemochromatosis is the most common genetic disease in individuals of Northern European origin. This disorder of iron metabolism, for which the molecular basis remains poorly understood, is characterized by an excessive absorption of dietary iron through the duodenal mucosa. Progressive iron loading of parenchymal organs results in the mid-life onset of clinical complications, and patients may succumb to cardiac failure and/or hepato-carcinoma. But patients who undergo early diagnosis and phlebotomy treatment before the development of organ damage have a normal life expectancy. The haemochromatosis gene was recently isolated and encodes a HLA class I related protein. A missense mutation (C282Y) in the homozygous configuration was observed in more than 92% of the patients. So diagnosis and genetic counselling are getting modified by this direct genotyping test.
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PMID:[Genetic hemochromatosis]. 923 20

Chronic mild liver enzyme abnormalities are attributable to hereditary hemochromatosis in at least 3% of cases. Hemochromatosis formerly was diagnosed late with diabetes and hepatic and cardiac failure. Only recently have the autosomal recessive inheritance and subtle early presentations been understood. However, patients still wait many years and see many physicians before receiving a correct diagnosis. Increased serum transferrin saturation is currently the best test for detection of those likely to accumulate iron. Serum ferritin identifies those requiring treatment. When liver biopsy (controversial in asymptomatic individuals) is indicated, chemical measurement of liver iron content is helpful and therapeutic phlebotomy is the only effective treatment. Caucasian-type hemochromatosis (prevalence of 0.005) is associated with genetic abnormalities in HLA-H but also occurs in other ethnic groups. Those of African descent may have a different but also heritable iron-loading disease. Caucasian-type and to a lesser extent African iron loading are detectable early by laboratory testing. Early treatment restores normal expectations of length and quality of life in the Caucasian disease. Long-term treatment data are not yet available in African iron loading. Laboratory-initiated screening programs using unsaturated iron-binding capacity can eliminate symptomatic hemochromatosis.
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PMID:Mild liver enzyme abnormalities: eliminating hemochromatosis as cause. 926 5


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