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

Insufficient angiogenesis is one of the causes leading to tissue ischemia and dysfunction. In heart failure, there is increasing evidence showing decreased capillary density in the left ventricle (LV) myocardium, although the detailed mechanisms contributing to it are not clear. The goal of this study was to investigate the role of thyroid hormone receptors (TRs) in the coronary microvascular rarefaction under pathological cardiac hypertrophy. The LV from hypertrophied/failing hearts induced by ascending aortic constriction (AAC) exhibited severe microvascular rarefaction, and this phenomenon was restored by chronic T(3) administration. Coronary endothelial cells (ECs) isolated from AAC hearts expressed lower TRbeta mRNA than control ECs, and chronic T(3) administration restored TRbeta mRNA expression level in AAC hearts to the control level. Among different TR subtype-specific knockout mice, TRbeta knockout and TRalpha/TRbeta double-knockout mice both exhibited significantly less capillary density in LV compared with wild-type mice. In vitro, coronary ECs isolated from TRbeta knockout mice lacked the ability to form capillary networks. In addition, we identified that kinase insert domain protein receptor/fetal liver kinase-1 (vascular endothelial growth factor-2 receptor) was one of the angiogenic mediators controlled by T(3) administration in the AAC heart. These data suggest that TRbeta in the coronary ECs regulates capillary density during cardiac development, and down-regulation of TRbeta results in coronary microvascular rarefaction during pathological hypertrophy.
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PMID:Thyroid hormone receptor-beta is associated with coronary angiogenesis during pathological cardiac hypertrophy. 1907 85

Recent studies in various rodent models of pathologic ventricular hypertrophy report the re-expression of deiodinase type 3 (D3) in cardiomyocytes. D3 inactivates thyroid hormone (T3) and is mainly expressed in tissues during development. The stimulation of D3 activity in ventricular hypertrophy and subsequent heart failure is associated with severe impairment of cardiac T3 signaling. Hypoxia-induced signaling appears to drive D3 expression in the hypertrophic cardiomyocyte, but other signaling cascades implicated in hypertrophy are also capable of stimulating transcription of the DIO3 gene. Many cardiac genes are transcriptionally regulated by T3 and impairment of T3 signaling will not only reduce energy turnover, but also lead to changes in gene expression that contribute to contractile dysfunction in pathologic remodeling. Whether stimulation of D3 activity and the ensuing local T3-deficiency is an adaptive response of the stressed heart or part of the pathologic signaling network leading to heart failure, remains to be established.
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PMID:Cardiomyocyte-specific inactivation of thyroid hormone in pathologic ventricular hypertrophy: an adaptative response or part of the problem? 1910 95

Thyroid hormone exerts a large number of influences on the cardiovascular system. Increased thyroid hormone action increases the force and speed of systolic contraction and the speed of diastolic relaxation and these are largely beneficial effects. Furthermore, thyroid hormone has marked electrophysiological effects increasing heart rate and the propensity for atrial fibrillation and these effects are largely mal-adaptive. In addition, thyroid hormone markedly increases cardiac angiogenesis and decreases vascular tone. These multiple thyroid hormone effects are largely mediated by the action of nuclear based thyroid hormone receptors (TR) the thyroid hormone receptor alpha and beta. TRalpha is the predominant isoform in the heart. Rapid nongenomic thyroid hormone effects also occur, which can be clearly demonstrated in ex-vivo experiments. Some of the most marked thyroid hormone effects in cardiac myocytes involve influences on calcium flux, with thyroid hormone promoting expression of the gene encoding the calcium pump of the sarcoplasmic reticulum (SERCa2). In contrast, in hypothyroid animals phospholamban levels, which inhibit the SERCa2 pump, are increased. In addition, marked effects are exerted on the calcium channel of the sarcoplasmic reticulum the ryanodine channel. Related to myofibrillar proteins, myosin heavy chain alpha is increased by T3 and MHC beta is decreased. Complex and interesting interactions occur between cardiac hypertrophy induced by excess thyroid hormone action and cardiac hypertrophy occurring with heart failure. The thyroid hormone mediated cardiac hypertrophy in its initial phases presents a physiological hypertrophy with increases in SERCa2 levels and decreased expression of MHC beta. In contrast, pressure overload induced heart failure leads to a "pathological" cardiac hypertrophy which is largely mediated by activation of the calcineurin system and the MAPkinases signaling system. Recent evidence indicates that heart failure can lead to a downregulation of the thyroid hormone signaling system in the heart. In the failing heart, decreases of thyroid hormone receptor levels occur. In addition, serum levels of T4 and T3 are decreased with heart failure in the frame of the non-thyroidal illness syndrome. The decrease in T3 serves as an indicator for a bad prognosis in the heart failure patient being linked to increased mortality. In animal models, it can be shown that in pressure overload-induced cardiac hypertrophy a decrease of thyroid hormone receptor levels occurs. Cardiac function can be improved by increasing expression of thyroid hormone receptors mediated by adeno-associated virus based gene transfer. The failing heart may develop a "hypothyroid" status contributing to diminished cardiac contractile function.
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PMID:Cardiac hypertrophy and thyroid hormone signaling. 1912 27

This article provides information and a commentary on trials relevant to the pathophysiology, prevention, and treatment of heart failure presented at the Heart Failure Society of America and the American Heart Association meetings in 2008. Unpublished reports should be considered as preliminary, as analyses may change in the final publication. (i) SADHART-CHF showed no difference in outcome for heart failure patients with depression treated with sertraline compared with placebo. (ii) A controlled release carvedilol formulation showed similar LV haemodynamic effects to the standard carvedilol formulation in the COMPARE study. (iii) A post hoc analysis of the MOMENTUM study suggested that patients with less severe heart failure may be more likely to benefit from a continuous aortic flow augmentation device. (iv) A thyroid hormone analogue was poorly tolerated in patients with heart failure. (v) HF-ACTION showed that exercise training is safe and offers modest clinical benefits in patients with heart failure. (vi) Irbesartan failed to improve outcomes in patients with preserved ejection fraction in the I-PRESERVE study. (vii) A phase II study of beta-interferon administration in patients with dilated cardiomyopathy showed encouraging results. (viii) The BACH study showed that mid-regional pro-adrenomedullin was more accurate than BNP or NT-proBNP at predicting outcome at 90 days in patients with acute heart failure. (ix) A secondary analysis from ATHENA showed a reduction in cardiovascular hospitalizations and strokes for patients with atrial fibrillation receiving dronedarone compared with placebo.
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PMID:Clinical trials update from the Heart Failure Society of America and the American Heart Association meetings in 2008: SADHART-CHF, COMPARE, MOMENTUM, thyroid hormone analogue study, HF-ACTION, I-PRESERVE, beta-interferon study, BACH, and ATHENA. 1916 21

Within the short period from 1802 to 1840 four physicians from four different countries (Flajani in Italy, Parry in England, Graves in Ireland and Basedow in Germany) independently described a hitherto unknown disease, the hallmark of which were tachycardia and enlargement of the thyroid. Three of the physicians also noted exophthalmos. In sequence, the disease was attributed to primary cardiac disease, then to increased sympathetic nerve discharge, and finally to thyroid hyper-function. The latter concept failed to explain the exophthalmos, which cannot be reproduced by over-dosage of thyroid hormone. Explanations for the exophthalmos went from cardiac failure (causing swelling of the thyroid and retro-orbital tissues), to sympathetic nerve discharge, to over-secretion of TSH, to production within the pituitary of TSH fragments with exophthalmogenic properties, and finally to shared auto-antigens of thyroidal and retroorbital tissue. The latter theory is favoured today, after it had been recognized that thyroid hyperfunction in Graves' disease was due to auto-antibodies to the thyroidal TSH receptor; such receptors were postulated also to be present in retroorbital tissue. Thus, each generation of scientists explained the pathogenesis of exophthalmos with the methods and concepts available to medical research at any given time. Although big advances have been made, future research may be good for some unexpected surprises.
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PMID:Thyroid eye disease: a historical perspective. 1983 79

The heart is subjected to chronic mechanical unloading during prolonged spaceflight and microgravity. The heart in patients with end-stage heart failure is also unloaded in prolonged duration after left ventricular assist devices (LVAD) are implanted. Heterotopic heart transplantation in rats is an established model of chronic cardiac unloading, and has been used to investigate the effects of chronic cardiac unloading on the heart. Observations that have been found using this experimental model are as follow. Chronic cardiac unloading induces time-dependent depressions of Ca2+ handling and myocyte contractility, which are associated with the shift of myosin heavy chain (MHC) isozymes and altered expressions of Ca2+ cycling-related proteins. Treatment with the physiological treatment dose of thyroid hormone restores the expression levels of Ca2+ cycling-related proteins, Ca2+ handling, and contractile function of cardiac myocytes in chronically unloaded hearts. Although future studies are required to determine precise mechanisms of the beneficial effects of thyroid hormone on chronically unloaded hearts, these observations may have clinical implications in the future for chronic cardiac unloading in the space industry as well as in the treatment of patients with end-stage heart failure supported by LVAD.
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PMID:Thyroid hormone and chronically unloaded hearts. 1987 60

Thyroid dysfunction, however mild, can significantly affect the cardiovascular (CV) system. The effects of thyroid hormones may be viewed as genomic and non-genomic, with the former occurring over a longer time scale and both affecting structural and functional proteins in CV tissue. As the interplay between thyroid function and the CV system becomes elucidated, particularly in the context of a system biology approach, the heart failure phenotype is better understood. Symptomatology is related to disturbance in inotropic and chronotropic function. Moreover, biochemical changes reflected by thyroid function testing with the non-thyroidal illness syndrome can prognosticate and guide therapy in heart failure. In addition, empiric treatment with thyroid hormone analogues or T3 represent emergent and highly controversial interventions.
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PMID:Thyroid hormones and the cardiovascular system: pathophysiology and interventions. 1991 24

Cardiac hypertrophy is a significant independent risk factor for increased mortality, comprising of maladaptive changes in cellular, molecular and metabolic processes that ultimately lead to heart failure. However, cardiac hypertrophy represents a continuum from physiological to compensatory to pathological hypertrophy, so that treatment modalities aimed to shift hypertrophy towards the physiological phenotype would represent an attractive therapeutic strategy. Many of the physiological changes caused by thyroid hormone (TH) treatment may provide direct benefit to the failing heart. Recent experimental studies have shown that TH rapidly activates pro-survival PKB/Akt-mTOR signaling pathways, thus providing cytoprotection and increasing synthesis of normal contractile proteins and metabolic enzymes. TH induces a normal physiological phenotype by binding to nuclear TH receptors that regulate expression of specific genes which promote cell survival and enhance contractile function. Physiological cardiac growth occurs with a coordinated angiogenic response that normalizes myocardial perfusion during hypertrophy, and recent studies support a significant role for TH and its endothelial cell surface integrin receptors and nuclear receptors in neovascularization during TH-induced hypertrophy. The present review examines these molecular mechanisms and intracellular signaling pathways activated in thyroid hormone-induced cardiac hypertrophy that support its therapeutic potential in the treatment of heart disease.
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PMID:Signaling mechanisms in thyroid hormone-induced cardiac hypertrophy. 2000 76

Excessive thyroid hormone induces cardiac hypertrophy and promotes heart failure in patients with hyperthyroidism, but the mechanism remains elusive. Rats were orally administered with levothyroxine (100 microg/kg, T(4)) for 4 weeks to induce hyperthyroidism. The calculated stroke volume decreased and the shortening amplitude-frequency relationship in unloaded contraction of isolated cardiomyocytes was negative in T(4)-treated rats. Apoptotic rates increased and DNA laddering was also detectable in T(4)-treated rat hearts. By contrast, in primary cultured cardiomyocytes, T(3) induced dose-dependent hypertrophy but did not affect the apoptotic rate. Angiotensin II further increased the apoptotic rate of T(3)-induced hypertrophied cardiomyocytes. The apoptotic rate was dependent on the extent of cardiomyocyte hypertrophy. These results suggest that cardiac contractility is enhanced during the early stage of hyperthyroidism, but decreased during the late stage of hyperthyroidism. The hypertrophied cardiomyocytes were also susceptible to apoptotic stimulation by angiotensin II. Depressed cardiac contractility and enhanced apoptosis may lead to heart failure in hypertrophied myocardium.
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PMID:Excessive thyroxine enhances susceptibility to apoptosis and decreases contractility of cardiomyocytes. 2012 86

A 56-year-old woman with Graves' disease presented with the complaints of diarrhea and palpitations. Physical examination and laboratory data revealed hypothermia and signs of mild hyperthyroidism, heart failure, hepatic dysfunction with jaundice, hypoglycemia, and lactic acidosis. The patient was diagnosed as having developed the complication of thyroid storm in the absence of marked elevation of the thyroid hormone levels, because of the potential hepatic and cardiac dysfunctions caused by heavy alcohol drinking. A year later, after successful treatment, the patient remains well without any clinical evidence of heart failure or hepatic dysfunction. Thyroid storm associated with lactic acidosis and hypothermia is a serious condition and has rarely been reported. Prompt treatment is essential even if the serum thyroid hormone levels are not markedly elevated. We present a report about this patient, as her life could eventually be saved.
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PMID:A patient with Graves' disease who survived despite developing thyroid storm and lactic acidosis. 2073 31


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