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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The life expectancy of patients with thalassemia major has significantly increased in recent years, as reported by several groups in different countries. However, complications are still frequent and affect the patients' quality of life. In a recent study from the United Kingdom, it was found that 50% of the patients had died before age 35. At that age, 65% of the patients from an Italian long-term study were still alive. Heart disease is responsible for more than half of the deaths. The prevalence of complications in Italian patients born after 1970 includes heart failure in 7%, hypogonadism in 55%, hypothyroidism in 11%, and diabetes in 6%. Similar data were reported in patients from the United States. In the Italian study, lower ferritin levels were associated with a lower probability of experiencing heart failure and with prolonged survival. Osteoporosis and osteopenia are common and affect virtually all patients. Hepatitis C virus antibodies are present in 85% of multitransfused Italian patients, 23% of patients in the United Kingdom, 35% in the United States, 34% in France, and 21% in India. Hepatocellular carcinoma can complicate the course of hepatitis. A survey of Italian centers has identified 23 such cases in patients with a thalassemia syndrome. In conclusion, rates of survival and complication-free survival continue to improve, due to better treatment strategies. New complications are appearing in long-term survivors. Iron overload of the heart remains the main cause of morbidity and mortality.
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PMID:Survival and complications in thalassemia. 1633 50

Recent results from independent studies suggest that deferiprone is more cardioprotective than deferoxamine. Patients on long-term treatment with deferiprone have a better myocardial magnetic resonance imaging pattern and less chance to develop a new cardiac disease or worsen an existing one. Most of these observations are retrospective and require confirmation from randomized controlled trials. Other new observations regard the effects of combining the two chelators. Most results indicate an additional effect on iron excretion and a significant reduction of the time required to mitigate severe iron overload and to reverse clinical heart disease. Again, these data require confirmation, as they were mostly obtained on individual cases or small groups of patients treated with a wide range of combinations of the two chelators, but the univocity of results is impressive. After many years of controversy, deferiprone is emerging as a useful oral iron chelator that enhances the chances for the patient to have optimal treatment. Well-designed and -conducted studies will help in answering the questions still open.
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PMID:Deferiprone: New insight. 1633 62

Magnetic resonance T2* values of the myocardium are directly related to tissue iron levels. Minor effects from myocardial oxygenation and fibrosis are overwhelmed by the highly dominant iron effect in clinically relevant levels of myocardial iron overload. Myocardial T2* values less than 20 ms indicate iron overload, and this is considered severe when T2* is less than 10 ms. Decreasing myocardial T2* levels are associated with systolic and diastolic ventricular dysfunction. Most recorded cases of heart failure in thalassemia to date have occurred in patients with very low T2* values (in the severe range). Exceptions to this have occurred in patients with other causes of heart failure such as concomitant congenital heart disease. In patients presenting with heart failure who undergo aggressive chelation with continuous intravenous deferoxamine, longitudinal studies show that myocardial T2* increases, and this is accompanied by increases in ejection fraction and relief of heart failure. In cross-sectional studies, the myocardial T2* and ejection fraction of patients on deferiprone was superior to that of patients on deferoxamine. Randomized controlled prospective trials comparing these two drugs for their action in clearing myocardial iron, as measured by myocardial T2*, are under way and should report in 2005/2006. These trials will clarify the role of different chelators in the management of myocardial iron overload and may be valuable in reducing the toll of death in thalassemia from heart failure.
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PMID:T2* magnetic resonance and myocardial iron in thalassemia. 1633 85

Iron cardiomyopathy remains the leading cause of death in patients with thalassemia major. Magnetic resonance imaging (MRI) is ideally suited for monitoring thalassemia patients because it can detect cardiac and liver iron burdens as well as accurately measure left ventricular dimensions and function. However, patients with thalassemia have unique physiology that alters their normative data. In this article, we review the physiology and pathophysiology of thalassemic heart disease as well as the use of MRI to monitor it. Despite regular transfusions, thalassemia major patients have larger ventricular volumes, higher cardiac outputs, and lower total vascular resistances than published data for healthy control subjects; these hemodynamic findings are consistent with chronic anemia. Cardiac iron overload increases the relative risk of further dilation, arrhythmias, and decreased systolic function. However, many patients are asymptomatic despite heavy cardiac burdens. We explore possible mechanisms behind cardiac iron-function relationships and relate these mechanisms to clinical observations.
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PMID:Physiology and pathophysiology of iron cardiomyopathy in thalassemia. 1633 87

Two hundred and seventy-three patients with thalassaemia major (TM) were followed in the Ferrara Thalassaemia Centre over a thirty-year period. Forty-two patients had insulin dependent diabetes mellitus (IDDM). The first case was diagnosed in 1973. The incidence of IDDM peaked in 1986 (3.9%), and it was 0.7% at the time of the study (March 1998). The prevalence of IDDM increased progressively over time, reaching 14.2% in 1998. Mean age at diagnosis of IDDM was 18.2 -/+ 3.6 years and this also rose significantly during the study period (p<0.01). Hypogonadism was present in 91% of patients with IDDM, hypothyroidism in 68%, hypoparathyroidism in 21%, and cardiopathy in 69%, all significantly more prevalent than in patients without IDDM. These complications appeared with the same frequency before and after the diagnosis of IDDM. Survival of patients with and without IDDM was similar and no difference in the primary cause of death was found between the two groups. Main risk factors associated with IDDM were poor compliance with desferioxamine (DFO) treatment (p<0.05%), advanced age at the start of intensive chelation therapy (p<0.001), liver cirrhosis or severe fibrosis (p<0.0001, odds ratio 9.5, CI 95% 2.8-32.6). Prevalence of impaired glucose tolerance (IGT) was highest in 1981, 1984, and 1985 when the incidence of IDDM was increasing; in 1995 the prevalence of IGT in patients aged 16-20 years was lower in comparison with that observed in 1975 (17% vs. 59%, p<0.01). Risk factors associated with IGT were: male sex (p<0.05), poor compliance with DFO therapy (p<0.05) and liver iron concentration 4 times above the normal value. In conclusion, our longitudinal study confirms that the incidence of IDDM and prevalence of IGT have been decreasing over the course of the last decade, appearing at a more advanced age, although some differences have not reached statistical significance. Iron overload and liver disease were the main associated risk factors, while positive family history for diabetes did not influence glucose metabolism in our patients.
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PMID:Diabetes mellitus and impaired glucose tolerance in thalassaemia major: incidence, prevalence, risk factors and survival in patients followed in the Ferrara Center. 1646 13

Heart disease is the leading cause of mortality and one of the main causes of morbidity in beta-thalassemia. The clinical spectrum of the thalassemia syndrome ranges from the severe, transfusion--dependent thalassemia major and the asymptomatic carrier state. Thalassemia intermedia represents a milder form and is usually transfusion-independent. Two main factors determine cardiac disease in this form. One is the high output state that results from chronic tissue hypoxia and from hypoxia-induced compensatory reactions. The other is the vascular involvement that leads to an increased pulmonary vascular resistance and an increased systemic vascular stiffness. Valvular abnormalities and iron overload also contribute to a less extent. As a result, both right and left ventricles have to maintain a high cardiac output level through a stiff vascular bed. Right heart involvement with age-related pulmonary hypertension followed by congestive heart failure dominates the clinical picture. Although the left heart is also affected, systolic left ventricular function is usually preserved but this may also be decompensated under conditions characterized by excessive cardiac work load.
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PMID:Heart disease in thalassemia intermedia: a review of the underlying pathophysiology. 1748 90

Thalassemia is anemia of variable severity, arising from mutations of genes encoding the hemoglobin alpha and beta chains. Severe thalassemia is associated with iron overload, tissue lesions, and high risk for cardiovascular complications, and iron-mediated cardiomyopathy is the main cause of death in this condition. Thalassemia major (TM) patients exhibit cardiovascular abnormalities consistent with chronic anemia; these include enlargement of the ventricular chambers, increased cardiac output, and reduced total vascular resistance. Cardiac iron overload in TM patients due to long-term transfusion can cause further chamber dilation, decreased contractility, and arrhythmia. Paradoxically, many such patients remain asymptomatic until decompensation occurs. For decades, magnetic resonance imaging and echocardiography have been performed to detect advanced cardiac dysfunction; however, reliable evaluation tools for the early detection of cardiac abnormalities are currently in demand. This article reviews the mechanisms underlying the development of heart disease in thalassemia and strategies for therapeutic intervention in TM patients with congestive heart failure.
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PMID:Mechanisms of and obstacles to iron cardiomyopathy in thalassemia. 1850 36

Although the presence of nontransferrin bound plasma iron (NTBI) in transfusional iron overload is well documented, knowledge about its clinical significance is limited. We assessed NTBI levels in a large and homogeneous series of thalassemia patients on regular transfusion and chelation and explored the hypothesis that NTBI levels may be associated with relevant clinical outcomes: in particular, heart disease. Among 174 patients with thalassemia major and intermedia, we showed the presence NTBI in 145 of 174 or 83.3% of cases. NTBI levels correlated with transferrin saturation, age, and ALT, and not with serum ferritin or liver iron concentrations. At a multiple regression analysis, transferrin saturation and heart disease but not age was independent predictors of NTBI. Patients with heart disease had NTBI levels significantly higher than those without. All patients with heart disease had transferrin saturation above 70%, and all were NTBI positive. Conversely, none of the patients without NTBI and/or with transferrin saturation less than 70% had preclinical or clinical heart disease. To our knowledge, this is the first documentation of a link between the presence of NTBI in thalassemic patients with transfusional iron overload and heart disease. Further investigation from these preliminary findings may clarify whether NTBI assessment may have a role in evaluating the risks and optimizing treatment for transfusion-dependent patients.
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PMID:High nontransferrin bound iron levels and heart disease in thalassemia major. 1900 28

Thalassemia major is a rare inherited anemia, and affected children require blood transfusions every 2-4 weeks to survive. Repeated blood transfusions lead to a build-up of toxic levels of iron in the body, causing organ damage and premature death, primarily due to iron-induced heart disease. Deferiprone is one of a few drugs that are routinely used in medicine for the treatment of iron overload in thalassemic patients. This drug is usually administered daily at high doses (50-100 mg/kg) with a very low toxicity. Agranulocytosis is the most serious side effect of deferiprone, with a reported incidence of 0.6 per 100 patient-years. We document an illustrated case report of necrotizing gingivostomatitis, an oral manifestation of agranulocytosis secondary to deferiprone use involving the gingiva and palatal mucosa of a thalassemia major patient. Various causes of precipitation of agranulocytosis in these patients and a possible relationship of necrotizing gingivostomatitis with deferiprone are highlighted in this case report.
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PMID:Necrotizing stomatitis: a possible periodontal manifestation of deferiprone-induced agranulocytosis. 1977 31

Beta-thalassemia is an inherited hemoglobin disorder resulting in chronic hemolytic anemia that typically requires life-long transfusion therapy. Although traditionally prevalent in the Mediterranean basin, Middle East, North India, and Southeast Asia, immigration of those populations to North America and Western Europe has rendered beta-thalassemia a global health problem. Cardiac complications represent the primary cause of mortality and one of the major causes of morbidity in those patients. Heart disease is mainly expressed by a particular cardiomyopathy that progressively leads to heart failure and death. The beta-thalassemia cardiomyopathy is mainly characterized by 2 distinct phenotypes, a dilated phenotype, with left ventricular dilatation and impaired contractility and a restrictive phenotype, with restrictive left ventricular filling, pulmonary hypertension, and right heart failure. The pathophysiology of the disorder is multifactorial, with a central role of myocardial iron overload and the significant contribution of immunoinflammatory mechanisms. Patients' management is demanding and requires a multidisciplinary approach, preferably in specialized centers.
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PMID:Beta-thalassemia cardiomyopathy: history, present considerations, and future perspectives. 2048 95


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