UMLS:C0018801 - FACTA Search

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

GH exerts direct effects on myocardial growth and function. Evidence from laboratory models shows that GH (or IGF-I) induces mRNA expression for specific contractile proteins and myocyte hypertrophy. Furthermore, GH increases the force of contraction and determines myosin phenoconversion toward the low ATPase activity V3 isoform. These data provide plausible explanations for the cardiac abnormalities observed in clinical settings of excessive or defective GH production. In acromegaly, the functional consequences of GH excess initially prevail (hyperkinetic syndrome), followed by alterations of cardiac function when myocardial hypertrophy develops. This involves both ventricles and is purposeless because it occurs without increased wall stress. Hypertrophy also entails proliferation of the myocardial fibrous tissue that leads to interstitial remodeling. The functional consequence is an impaired ventricular relaxation that causes a diastolic dysfunction, followed by impairment of systolic function. In untreated disease, cardiac performance slowly but inexorably deteriorates and heart failure eventually develops. Several lines of evidence support the specificity of heart disease in acromegaly. Particularly demonstrative are the recent studies in which GH production was suppressed by octreotide, with a consequent significant regression of hypertrophy and improvement of cardiac dysfunction. It is not yet established whether full recovery of normal cardiac morphology and function is possible after correction of GH excess. The point is not a minor one since the possibility to revert, albeit partially, myocardial fibrosis is of great relevance to the control of cardiac hypertrophy in general. GHD leads to a reduced mass of both ventricles and to impaired cardiac performance with low heart rate (hypokinetic syndrome). These alterations are particularly evident during physical exercise and might provide an important contribution to the reduced exercise capacity of GHD patients, in addition to the reduced muscle mass and strength. The data also support a role of GH in the maintenance of a normal cardiac structure and performance. The hypokinetic syndrome is well documented in young patients in whom GHD began very early in their childhood. In contrast, the data in adult-onset GHD are less consistent. This suggests that the consequences of GHD are more relevant if the disorder starts during early heart development. As observed with other abnormalities associated with GHD, cardiac dysfunction is also susceptible to marked improvement by hrGH. This observation lends further support to the proposal to treat these patients with replacement therapy.
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PMID:Growth hormone and the heart. 784 68

Our own previous ultrastructural studies in human hearts with dilated cardiomyopathy and heart failure showed sarcomeric and cytoskeletal disarrangement. On the basis of these findings we tested the hypothesis that in cardiomyopathic failing hearts not only the sarcomere structure but also the organization and the amount of numerous contractile proteins are disturbed. Titin was included in this study because it is the elastic "third" filament of the sarcomere and also plays an important role as template for myosin and actin filaments in sarcomerogenesis. Human cardiac tissue obtained at the time of transplantation surgery was investigated using immunohistochemistry with monoclonal antibodies against titin, myosin, actin, tropomyosin, and troponin T. Additionally, isolated myocytes from rat or pig heart were used for the standardization of the localization pattern. In normal tissue, myosin and the thin filament complex showed a regular cross striation that was wider in myosin staining than for actin, troponin T, and tropomyosin corresponding with the different width of the A and I bands in the sarcomere. Titin localization in normal human and animal myocardium showed a regular cross striation pattern. In diseased cardiac tissue titin fluorescence intensity was reduced and frequently disorganization or almost complete loss of titin from many myocytes were present. Severe abnormalities of contractile proteins consisting of disarrangement or lack of filaments were also observed. Double staining procedures showed that in the same myocyte defects of the contractile apparatus were accompanied by a simultaneous reduction of titin indicating that the "third" sarcomeric filament system is involved in heart failure. Abnormalities of titin expression may be especially important because titin significantly influences sarcomeric elastic behaviour and is necessary as template for the organization of newly synthesized myosin and actin filaments. The loss of titin may contribute to the altered compliance in failing hearts. It is concluded that disorganization and loss of titin, myosin, and the thin filament complex are severe in the failing human heart because of dilated cardiomyopathy and that these changes may represent several of the most important components of the structural correlate of reduced cardiac function.
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PMID:Altered expression of titin and contractile proteins in failing human myocardium. 786 90

The advent of molecular biology techniques has profoundly changed pathophysiological concepts of myocardial hypertrophy and overload-induced heart failure. Heart failure is a consequence of the limits and imperfection of biological adaptation to mechanical overload. Factors including fibrosis, senescence, ischemia, inflammation, catabolism and hormonal response may contribute to myocardial dysfunction. In humans changes in the genes coding for myosin are observed only in the atrial myocardium, in association with diastolic left ventricular function. In most animal species, alteration in proteins involved in intracellular calcium movement and autonomic nervous dysfunction are responsible for both reduction of Vmax and arrhythmias associated with myocardial hypertrophy. Moreover, myocardial fibrosis is a major determinant of enhanced left ventricular stiffness and arrhythmogenicity.
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PMID:[Physiopathology of cardiac insufficiency. Biological factors of adaptation and disadaptation of the heart to chronic mechanical overload]. 787 7

Diabetic cardiomyopathy as a distinct entity was first recognized by Rubler et al. in diabetics with congestive heart failure (CHF), who had no evidence of coronary atherosclerosis. The Framingham study showed a 2.4-fold increased incidence of CHF in diabetic men and a 5.1-fold increase in diabetic women over 18 years. Pathological studies show left ventricular hypertrophy and fibrosis with varying degrees of small vessel disease, the functional significance of which is uncertain. Hypertension was recognized as an important cofactor in the development of fatal congestive heart failure in diabetics. On cardiac catheterization, in patients symptomatic of heart failure, either congestive or restrictive patterns have been observed. In contrast, asymptomatic diabetics had decreased left ventricular compliance but normal systolic function on hemodynamic study. Noninvasive studies show alterations in systolic and especially diastolic function, particularly in diabetics with microvascular complications and/or coexistent hypertension. Using load-independent measures of contractility, however, systolic function was generally found to be normal in asymptomatic normotensive diabetics. Experimental studies have focused on the mildly diabetic dog and the severely diabetic rat. Decreased left ventricular compliance and increased interstitial connective tissue were observed in chronically diabetic dogs. In contrast, ventricular myocardium from diabetic rats exhibits a reversible decrease in the speed of contraction, prolongation of contraction, and a delay in relaxation. These mechanical changes are associated with a decreased myosin ATPase, a shift in myosin isoenzyme distribution, alterations in a variety of Ca2+ fluxes, and changes in responses to alpha- and beta-adrenergic and cholinergic stimulation. These biochemical changes may be secondary to alterations in carbohydrate, lipid, and adenine nucleotide metabolism in the diabetic heart.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diabetic cardiomyopathy. 808 30

Hypertrophic cardiomyopathy is a heterogeneous disease with autosomal dominant Mendelian inheritance. In 1989, the 1st locus for hypertrophic cardiomyopathy was mapped to cardiac myosin genes located on chromosome 14q1. Soon, several mutations that cosegregated with inheritance of the disease were identified in the beta-myosin heavy chain gene, or MHY7. More than 30 missense mutations and 1 deletion mutation in the beta-myosin heavy chain gene have since been described. Recently, expression of both the mutant beta-myosin heavy chain mRNA and the mutant protein has been shown in the cardiac and skeletal muscles of individuals with hypertrophic cardiomyopathy. Characterization of the clinical features of beta-myosin heavy chain mutations has shown that certain mutations, such as Arg403Gln and Arg719Trp mutations, are associated with high rate of sudden cardiac death. In addition to the beta-myosin heavy chain gene, 3 new loci for hypertrophic cardiomyopathy have recently been described, but the candidate genes have not yet been identified. Dilated cardiomyopathy can be inherited as an autosomal dominant, autosomal recessive, and X-linked disease. The familial form of dilated cardiomyopathy comprises approximately 20% of the cases of idiopathic cardiomyopathy. Echocardiographic abnormalities such as left ventricular enlargement are present in 10% of asymptomatic relatives. No gene for familial dilated cardiomyopathy has been identified, but linkage studies using polymorphic, short-tandem repeat markers are ongoing. Dilated cardiomyopathy is a common manifestation of Duchenne/Becker muscular dystrophy. Heart failure is a common cause of death in the affected individuals. The gene responsible for this disease is the dystrophin gene located on X chromosome. There have been reports in these patients of several dystrophin-gene deletion mutations, which result in a decrease in the expression of the dystrophin protein in the cardiac and skeletal tissues. X-linked cardiomyopathy, in which the disease is restricted to the heart, has also been linked to the dystrophin gene. Myotonic dystrophy is an autosomal dominant disease that commonly involves the myocardium and the conduction tissue, resulting in conduction defects and heart failure. Sudden cardiac death is the most common cause of mortality in patients with myotonic dystrophy. Recently, the myotonin protein kinase gene located on chromosome 19 was identified as the gene responsible for this disease. Expansion of the number of trinucleotide repeats in the myotonin protein kinase gene results in myotonic dystrophy. Mutations in mitochondrial DNA have been associated with hypertrophic and dilated cardiomyopathy. The inheritance of mitochondrial cardiomyopathy is maternal and the disease is associated with certain systemic disorders.
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PMID:Molecular basis of hypertrophic and dilated cardiomyopathy. 818 May 12

We report 4 adult patients with thyrotoxicosis accompanied by irreversible low-output heart failure. Each patient showed elevated plasma levels of thyroid hormone and prolonged low-output heart failure even after thyroid function returned to normal. Specimens of the right ventricular myocardium stained with anti-beta myosin heavy-chain MAb showed a normal staining pattern with a predominance of the beta-form. Our observations suggest that thyrotoxicosis may be one possible cause of irreversible cardiomyopathy.
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PMID:Irreversible cardiomyopathy due to thyrotoxicosis. 818 12

The mechanisms of actions of thyroid hormone in various tissues are largely viewed as cell nucleus-mediated. However, several actions of this hormone are definitively extranuclear, and these include effects on the activities of Ca(2+)-adenosine triphosphatases (ATPases) of myocardial sarcolemma and, apparently, sarcoplasmic reticulum in animal models. Both effects would serve to reduce cytoplasmic (sarcoplasmic) [Ca2+]. Sarcoplasmic reticulum uptake of Ca2+ from sarcoplasm is mediated by Ca(2+)-ATPase and is deficient in end-stage heart failure; thyroid hormone can enhance sarcoplasmic reticulum Ca(2+)-ATPase activity acutely via an extranuclear mechanism or indirectly via the myosin-associated Ca(2+)-ATPase gene. Such actions would serve to improve myocardial relaxation, thus improvement in diastolic dysfunction, and may be cardioprotective if excessive levels of sarcoplasmic [Ca2+] develop during reperfusion of previously ischemic tissue. Action of thyroid hormone on sarcolemmal Ca(2+)-ATPase activity will enhance Ca2+ efflux, and a recently described effect of the hormone on myocardial Na+ inactivation current may serve to increase or reduce sarcoplasmic [Ca2+], depending upon the vector of Na+/Ca2+ exchange. This article reviews acute effects of thyroid hormone on the heart that are extranuclear in mechanism.
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PMID:Acute cellular actions of thyroid hormone and myocardial function. 833 93

Changes of ischemic myocardium following coronary occlusion, including active and passive functions, and adaptive changes of non-ischemic surviving myocardium have been summarized under the term "left ventricular remodeling" post myocardial infarction. An increase in left ventricular volume may be a consequence, and associated with an adverse prognosis. Although left ventricular dilatation may increase stroke volume and, thus, be compensatory at first, in about one-fifth of patients it ultimately results in progressive dysfunction and heart failure. Major determinants of this process are time, infarct size, infarct location, global left ventricular function assessed 4 days after infarction by radionuclide ejection fraction and right heart catheter (stroke volume), and morphology of the infarct-associated coronary artery. The surviving myocardium hypertrophies and may also dilate structurally. Depression of left ventricular ejection fraction chronically after the infarct is due to deterioration of wall motion of chamber segments initially classified normal by radionuclide analysis. Biochemical changes may also occur, including reduction of phosphocreatine, prolongation of time to peak Cai2+, and changes in myosin isoforms. Systemic or local humoral factors may be involved in these changes, however, clear evidence is still lacking. Perfusion of surviving myocardium may be altered under various conditions due to morphologic and functional changes of coronary vasculature. Successful prevention of heart failure and death by angiotensin converting enzyme inhibitors in asymptomatic patients with left ventricular dysfunction post-myocardial infarction has supported the pathophysiologic concepts of remodeling.
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PMID:Ventricular remodeling after myocardial infarction. Experimental and clinical studies. 835 28

In an attempt to elucidate the effects of two major risk factors of heart failure in humans, high blood pressure and coronary artery disease, renal hypertension and coronary artery constriction were induced singularly and in combination in rats, and the functional, structural, and biochemical alterations of the myocardium were examined 12-13 wk later. Renal hypertension (RH), coronary narrowing (CN), and their association (NH) resulted in left ventricular failure demonstrated by a significant increase in left ventricular end-diastolic pressure, a decrease in +dP/dt and -dP/dt, and a reduction in stroke volume and cardiac output. Measurements of ventricular loading documented that RH was characterized by elevations in systolic and diastolic wall stress of 42 and 160%, respectively. Corresponding changes with NH were 80 and 315%. CN was accompanied by an augmentation of diastolic wall stress only (280%). The abnormalities in mural stress were coupled with reductions in systolic and diastolic wall thickness-to-chamber radius ratios of 39 and 29% after CN. These anatomic parameters were preserved with RH, whereas the systolic wall thickness-to-chamber radius ratio was reduced 31% with NH. Structurally, multiple foci of replacement fibrosis were found with each intervention. The sites of tissue injury and their volume percent in the myocardium were comparable with CN and RH but were significantly more numerous and occupied a larger fraction of the ventricular wall in the presence of NH. Biochemically, the calcium dose-response curve of myofibrillar Mg2+ adenosinetriphosphatase (ATPase) activity did not vary with CN, RH, and NH. In contrast, a marked decrease in Ca2+ myosin ATPase activity was found in NH rats in association with a shift in myosin isoenzymes from V1 to V3. In conclusion, multiple physiological, morphological, and biochemical factors may participate in the generation of the abnormalities in ventricular loading with hypertension and/or coronary artery stenosis.
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PMID:Effects of hypertension and coronary constriction on cardiac function, morphology, and contractile proteins in rats. 836 72

Familial hypertrophic cardiomyopathy (FHCM) is a heterogeneous disease with an autosomal dominant Mendelian inheritance and variable penetrance. Several mutations in the beta-myosin heavy chain (beta MHC) gene, the first gene identified for this disease, have been described that co-segregate with the inheritance of the disease. All the mutations in the beta MHC gene encode for the globular head of the myosin protein except for the deletion mutation which encodes for the carboxy-terminus (rod) of the protein. The clinical features associated with some of the mutations in the beta MHC gene have been characterized. A missense mutation in exon 13 of the beta MHC gene, is associated with a higher incidence of sudden cardiac death and severe form of the disease, while some others are associated with a more benign form of the disease. Recently, three other loci, on chromosomes 1q3, 11q11 and 15q2, for FHCM have been identified and research is ongoing to identify the candidate genes. Cardiac involvement in Duchenne/Becker muscular dystrophy (DMD), and myotonic dystrophy is common. Heart failure due to dilated cardiomyopathy and sudden cardiac death are the common causes of death in these disorders. The genes responsible for DMD and myotonic dystrophy are dystrophin and myotonin protein kinase genes located on chromosomes X and 19 respectively. The disease in DMD is due to deletion mutations in the dystrophin gene, while myotonic dystrophy is due to expansion of the GCT trinucleotide repeats in the myotonin-protein kinase gene. Familial dilated cardiomyopathy comprises 20% of cases of idiopathic dilated cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular genetics of cardiomyopathies. 837 3

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