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

During a review of all cases of heart disease, including hypertensive cardiac failure, seen in Botswana during a period of sixteen months by one Specialist Physician observer, the importance of Idiopathic Cardiomyopathy as the commonest cause of cardiac failure clearly emerged. The aetiology of this condition and its relationship to hypertension and other factors causing an increased load on the myocardium are discussed. Viral myocarditis is presented as a separate entity, possibly playing a part in causation.
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PMID:Idiopathic cardiomyopathy in Botswana. 44 85

The aetiology of dilated cardiomyopathy is unknown by definition. Viral myocarditis is often viewed as an early stage in the progression of the disease leading to cardiomyopathy and heart failure in humans. The chronic inflammatory process is manifested histologically as a sparse, diffuse lymphocytic infiltration of the myocardium, classified as borderline or ongoing myocarditis according to the Dallas classification. Because of limitations of light microscopy, chronic myocarditis remains an enigmatic condition to diagnose and to treat. In contrast to routine histological staining procedures, immunohistochemical methods enable better identification and quantification of infiltrating cells and also provide further evidence that the activated immunological process within the myocardium is ongoing. In 176 patients with clinically suspected dilated cardiomyopathy, borderline myocarditis was diagnosed in only 14 cases (8%) histologically. However, using immunohistological analysis of endomyocardial biopsies, pathologically increased lymphocytic infiltration was revealed in 67 biopsy specimens (38%), and activated lymphocytes or activated macrophages in all analysed inflamed cardiac tissues. All positive biopsies showed an activated vascular endothelium, demonstrated by the enhanced expression of different adhesion molecules. Various cytokines were locally released from activated inflammatory cells. This may cause a cytokine-rich micro-environment which could be responsible for the enhanced expression of adhesion molecules and thereby contribute to the inflammatory traffic of immune cells into inflamed myocardial areas. These observations underline the hypothesis that the immune process is still active in a group of patients with clinically suspected dilated cardiomyopathy, causing progression of the disease.
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PMID:Immunohistochemistry in dilated cardiomyopathy. 868 73

Viral myocarditis is an important cause of heart failure and dilated cardiomyopathy. T lymphocytes are implicated in myocardial damage in murine models of coxsackievirus B3 (CVB3) myocarditis. We used knockout mice lacking CD4 (CD4(-/-)), CD8 (CD8(-/-)), both coreceptors (CD4(-/-)CD8(-/-)), or the T-cell receptor beta chain (TCRbeta(-/-)) to address the contribution of T-cell subpopulations to host susceptibility to CVB3 myocarditis. Severity of disease was magnified in CD8(-/-) mice but attenuated in CD4(-/-) mice, consistent with a pathogenic role for CD4(+) lymphocytes. Elimination of both CD4 and CD8 molecules from T lymphocytes by genetic knockout better protected mice from myocarditis, demonstrating that both CD4(+) and CD8(+) T cells contribute to host susceptibility. The same benefit occurred in TCRbeta(-/-) mice, with prolonged survival and minimal myocardial disease observed after CVB3 infection. Elevated interferon-gamma and decreased tumor necrosis factor-alpha expression are associated with attenuated myocardial damage in CD4(-/-)CD8(-/-) mice. These results show that the presence of TCRalphabeta(+) T cells enhances host susceptibility to myocarditis. The severity of myocardial damage and associated mortality are dependent on the predominant T-cell type available to respond to CVB3 infection. One mechanism by which CD4(+) and CD8(+) T-cell subsets influence the pathogenesis of myocarditis may involve specific cytokine expression patterns.
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PMID:Susceptibility to myocarditis is dependent on the response of alphabeta T lymphocytes to coxsackieviral infection. 1048 59

Myocarditis is the most common cause of heart failure in children. We investigated viral etiology of myocarditis/dilated cardiomyopathy (DCM) in children and correlated molecular findings with pathologic and clinical data. Polymerase chain reaction (PCR) or reverse transcription (RT)-PCR were used to analyze 59 endomyocardial biopsies from 48 consecutive young (<18 yrs) patients (pts) with clinical and histologic diagnosis of myocarditis and DCM, employing primers designed to amplify specific sequences of various DNA and RNA viruses. Nucleic acids were successfully extracted in 41 pts and viral genomes were found in 20 (49%): 12 out of 26 pts (46%) with myocarditis, 6 out of 13 (46%) pts with DCM, and both patients with endocardial fibroelastosis. Enteroviruses were more common in DCM (72%), whereas adenoviruses and enteroviruses shared the same rate (36%) in myocarditis. The mumps virus genome was detected in the two pts with endocardial fibroelastosis. More diffuse inflammatory infiltrates and myocyte damage as well as more impaired left ventricular end diastolic volume and shortening fraction were noted in viral positive cases. PCR positive pts had a worse outcome, resulting in transplantation or death. Three out of 8 pts with viral myocarditis who underwent cardiac transplantation had recurrent PCR-proven graft viral infection. Viral myocarditis/DCM appeared to be a more severe disease than nonviral forms. Enteroviruses were more common in DCM, whereas adenoviruses were as frequent as enteroviruses in myocarditis. Persistence of viral infection was associated with disease deterioration. Viral myocarditis relapsed after transplantation.
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PMID:Molecular diagnosis of myocarditis and dilated cardiomyopathy in children: clinicopathologic features and prognostic implications. 1245 37

It is generally well accepted that one third of patients with viral myocarditis experience a complete recovery of normal cardiac function, one third improve clinically but show residual cardiac dysfunction, and one third experience chronic heart failure and die or require heart transplantation. It is hoped that a better understanding of the underlying cause and pathogenesis of this disease will increase the number of patients who experience a complete recovery. New advances in both the diagnosis and treatment of viral myocarditis continue to enter clinical practice at a rapid pace, and it is likely that a genomic approach to the diagnostic evaluation and treatment of this disease will become possible in the near future. Viral myocarditis, however, will remain a significant diagnosticand therapeutic challenge to both physicians and scientists alike.
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PMID:A formidable challenge: the diagnosis and treatment of viral myocarditis in children. 1284 11

Matrix metalloproteinases (MMP), a family of proteases, are involved in the degradation of extracellular matrix proteins and hence in the determination of interstitial architecture. In the heart, MMPs have been found to play a significant role in the development of myocardial remodeling and congestive heart failure. Tissue inhibitors of matrix metalloproteinases (TIMPs) represent a family of proteins which are known to regulate the expression and activity of MMPs. TIMPs are endogenous physiological inhibitors of MMPs and their concomitant downregulation in heart failure suggests the existence of a critical balance between MMPs and TIMPs in the normal maintenance of myocardial interstitial homeostasis. In addition, cytokines regulate expression of both MMPs and TIMPs besides eliciting a direct effect on myocardial cell function. Therefore, myocardial inflammation may also contribute to the development of cardiac remodeling along with other stimuli like mechanical stress and humoral factors. Viral myocarditis, a predisposing factor for dilated cardiomyopathy, is a condition in which extent of intramyocardial inflammation is thought to determine the progression of disease. Inflammatory events in the heart following viral infection are speculated to be responsible for the transition of myocarditis to dilated cardiomyopathy. In viral myocarditis and other inflammatory heart diseases, the inflammatory cells and their battery of cytokines may also alter the myocardial MMP-TIMP system and eventually lead to dilation of the heart and ventricular dysfunction. The objective of this review is to present an overall picture of the inflammatory phase in viral myocarditis and discuss the possible interactions between inflammation and myocardial MMP profiles which may lead to the evolution of dilated cardiomyopathy.
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PMID:Myocardial remodeling in viral heart disease: possible interactions between inflammatory mediators and MMP-TIMP system. 1473 65

Viral myocarditis is an important cause of heart failure and cardiomyopathy. Immunosenescence, characterized by a dramatic reduction in immune responsiveness, can increase susceptibility to cardiopathology from viral infections. The T-cell receptor (TCR) Vbeta 8.1 peptide, a 16-mer peptide, has shown immuno-regulating and immunostimulating effects in viral-induced immunodeficiency. In our study, 18-mo-old C57Bl/6 female mice were treated twice with TCR Vbeta8.1 peptide and 10 d before sacrifice were injected ip with coxsackievirus B3. Cardiac histopathology was assessed for lesion severity. Splenocyte cyto-kine production (interleukin-2, -4, -6, interferon-gamma) and heart viral titers were determined. Our data suggest that immunosenescence suppressed both T helper (Th1) and Th2 cytokine production and that treatment with TCR Vbeta8.1 peptide induced cytokine stimulation close to levels seen in young mice. Nontreated aged mice developed some degree of myocarditis (75% mild and 25% severe), whereas only 35% of the peptide-treated aged group developed cardiopathology, with 25% being mild and 10% severe. Heart tissue from nontreated aged mice infected with coxsackievirus had a higher viral titer than hearts of aged mice equally infected but treated with the peptide. In conclusion, TCR Vbeta8.1 peptide induced immunoregulation, and inhibited or reduced coxsackievirus B3-induced cardiopathology in aged mice.
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PMID:T-cell receptor vbeta8.1 peptide reduces coxsackievirus-induced cardiopathology in aged mice. 1573 82

Viral myocarditis is a frequent and often unrecognised cause of post-inflammatory cardiomyopathy. The role of viral persistence and heart-specific autoimmunity in the development of myocarditis and heart failure is still controversial. This review updates the current view on the immunological mechanisms of disease development and addresses the current and future role of immunomodulation and immunosuppression as treatment options for defined subgroups of patients with myocarditis or dilated cardiomyopathy.
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PMID:Myocarditis: the immunologist's view on pathogenesis and treatment. 1610 25

Viral myocarditis can present as dramatic heart failure in the young, and chronic indolent cardiomyopathy in the older adult. The outcome of the disease is still poor, associated with high mortality during long-term follow-up. Enteroviral myocarditis serves as an excellent model to understand virus and host interactions. The virus enters the target cells via collaborating receptors, and this process triggers an inflammatory response in the host. The immune reaction is a two-edged sword, with appropriate activation of the immune system capable of clearing the virus, but excessive activation leads to a chronic inflammatory process that triggers the remodeling of the heart and consequent clinical heart failure. Through genetic dissection strategies, we have identified that the acquired immune system is activated through the T cell receptor and signaling amplification systems, such as the tyrosine kinase p56lck, phosphatase CD45 and downstream ERK1/2, and the family of cytokines. This signaling system not only promotes inflammatory cell clonal expansion but paradoxically also promotes viral proliferation. The innate immune system is now recognized as playing an ever-expanding role in coordinating the host immune response through the Toll-like receptors, triggering downstream signaling adaptors such as MyD88, IRAK, and TRIF/IRFs. These lead to activation of cytokines or interferons, depending on the balance of the signal contributions. The ongoing research in this area should help us to understand the immune response of the heart to viral infection, while identifying potential targets for therapy.
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PMID:Recent insights into the role of host innate and acquired immunity responses. 1632 61

Myocarditis is an inflammatory heart muscle disease, resulting from various etiologies, both noninfectious and infectious, which may be associated or not with cardiac dysfunction. Its course is unpredictable: it may spontaneously resolve or evolve into dilated cardiomyopathy and heart failure. A possible connection between myocarditis and dilated cardiomyopathy has long been postulated, but the intimate mechanisms linking these two conditions are still poorly understood. Viral myocarditis could induce a dilated cardiomyopathy through viral persistence and/or by triggering an autoimmune process. Understanding the mechanisms underlying the relationship between myocarditis and dilated cardiomyopathy will help in identifying an effective strategy of treatment aimed to stop and prevent cardiac damage. Specifically, we need to (a) evaluate the potential role of autoantibodies in disease prevention and progression, and understand their importance as markers of disease progression; (b) clarify the role of immunoregulation in exacerbating the disease.
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PMID:Myocarditis and dilated cardiomyopathy: possible connections and treatments. 1854 64


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