Etiology Of Idiopathic Dilated Cardiomyopathy Research Articles

Comparison of Immune Profiles in Fetal Hearts with Idiopathic Dilated Cardiomyopathy, Maternal Autoimmune-Associated Dilated Cardiomyopathy and the Normal Fetus.

The etiology of idiopathic dilated cardiomyopathy (iDCM) remains unknown. Immune therapies have improved outcome in fetuses with DCM born to mothers with autoimmune disease (aDCM). The purpose of this retrospective study was to compare the myocardial B and T cell profiles in fetuses and neonates with idiopathic DCM (iDCM) versus autoimmune-mediated DCM (aDCM) and to describe the normal cell maturation within the human fetal myocardium. Of 60 fetal autopsy cases identified from institutional databases, 10 had aDCM (18-38 weeks), 12 iDCM (19-37 weeks) and 38 had normal hearts (11-40 weeks). Paraffin-embedded myocardium sections were stained for all lymphocyte (CD45), B cells (CD20, CD79a), T cells (CD3, CD4, CD7, CD8) and monocyte (CD68) surface markers. Two independent, blinded cell counts were performed. Normal hearts expressed all B and T cell markers in a bimodal fashion, with peaks at 22 and 37 weeks of gestation. The aDCM cohort was most distinct from normal hearts, with less overall T cell markers [EST -9.1 (2.6) cells/mm(2), p = 0.001], CD4 [EST -2.0 (0.6), p = 0.001], CD3 [EST -3.9 (1.0), p < 0.001], CD7 [EST -3.0 (1.1), p = 0.01] overall B cell markers [EST -4.9 (1.8), p = 0.01] and CD79a counts [EST -2.3 (0.9), p = 0.01]. The iDCM group had less overall B cell markers [EST -4.0 (1.8), p = 0.03] and CD79a [EST -1.7 (0.9), p = 0.05], but no difference in T cell markers. Autoimmune-mediated DCM fetuses have less B and T cell markers, whereas iDCM fetuses have less B cell markers compared with normal fetal hearts. The fetal immune system may play a role in the normal development of the heart and evolution of dilated cardiomyopathy.

A Polymorphism at Position +874 in The IFN-γ Gene is Associated with Susceptibility for Dilated Cardiomyopathy

The etiology of idiopathic dilated cardiomyopathy (DCM) is largely unknown. One hypothesis is that immunological factors are responsible for disease development. Single nucleotide polymorphisms (SNP) at position +874 of the IFN-γ gene and at position -168 of the MHC2TA gene have previously been shown to associate with infl ammatory and autoimmune disorders. We analysed their possible infl uence on susceptibility and prognosis in patients with DCM. Genotypes were determined by real-time PCR in 442 patients and 425 controls. Genotype frequencies were found signifi cantly different between patients and controls for IFN-γ (p=0.029), but not for MHC2TA (p=0.26). In a logistic regression analysis, the high producing TT genotype of IFN-γ was signfi cantly more common in patients than controls (OR 1.55 [1.12-2.15], p=0.009). None of the polymorphisms had an infl uence on long-term outcome, 10-years mortality with a HR of 0.94 (p=0.74) and 0.85 (p=0.30), IFN-γ and MHC2TA, respectively. A 50% higher risk to develop DCM for individuals with the TT genotype of the IFN- gene is a new finding and emphasize the role of IFN- in DCM pathology.

Evaluation of viral infection in the myocardium of patients with idiopathic dilated cardiomyopathy

OBJECTIVESThe aim of this study was to evaluate the viral etiology of idiopathic dilated cardiomyopathy (DCM).BACKGROUNDThe demonstration of enteroviral genome in hearts with DCM has reinforced the importance of enteroviruses in the pathogenesis of DCM. However, there is uncertainty about the character and activity of enteroviruses detected in the myocardium. Recently, the association of hepatitis C virus or adenovirus with DCM has been reported.METHODSMyocardial specimens from 26 patients with idiopathic DCM, which were obtained at partial left ventriculectomy (PLV), were examined virologically. Strand-specific detection of enteroviral RNA was performed to differentiate active viral replication from latent persistence. Polymerase chain reaction was used to detect genomic sequences of hepatitis C virus, adenovirus, cytomegalovirus, influenza viruses, mumps virus, herpes simplex viruses, varicella-zoster virus and Epstein-Barr virus.RESULTSPlus-strand enteroviral RNA was detected in 9 (35%) of the 26 patients. Minus-strand enteroviral RNA was determined in seven (78%) of these nine plus-strand RNA-positive patients. Sequence analysis revealed that the enteroviruses detected were coxsackie B viruses, such as coxsackievirus B3 and B4. However, genetic material from other viruses was not detected. Six (86%) of seven minus-strand enteroviral RNA-positive patients died of cardiac insufficiency within the first six months after PLV.CONCLUSIONSCoxsackie B viruses were seen in hearts with idiopathic DCM. Active viral RNA replication appeared to be present in a significant proportion of these cases. Minus-strand coxsackieviral RNA in the myocardium can be a marker for poor clinical outcome after PLV. There was no evidence of persistent infection by other viruses in hearts with DCM.

No evidence for persistent enterovirus infection in patients with end-stage idiopathic dilated cardiomyopathy.

Persistence of enteroviruses in heart tissue has been implicated in the etiology of idiopathic dilated cardiomyopathy (IDC). Therefore, we determined the prevalence of enterovirus RNA in heart tissue from patients with end-stage IDC. During heart transplantation, 287 transmural biopsy specimens were aseptically collected from the explanted hearts of 38 patients with IDC and of 39 patients with cardiac failure of known cause. A nested polymerase chain reaction with general specificity for enteroviruses was used to screen for the presence of enterovirus RNA in the heart tissue samples. No enterovirus RNA was detected in any of the 287 heart biopsy specimens. These findings lead to a conclusion that enteroviruses do not persist in heart tissue from patients with end-stage IDC, nor with other heart diseases of known cause.

Prevalence and etiology of idiopathic dilated cardiomyopathy (summary of a National Heart, Lung, and Blood Institute Workshop)

Idiopathic dilated cardiomyopathy (IDC) is the primary indication for cardiac transplantation, with associated costs of approximately $177 million per year. Recognizing the economic implications of IDC, the increasing incidence, and the limited information on pathogenesis and prognosis, the National Heart, Lung, and Blood Institute convened a workshop on the Prevalence and Etiology of Idiopathic Dilated Cardiomyopathy on June 13 to 14, 1991. The difficulties of studying the disease were reviewed, including its relatively low prevalence, its potentially pluricausal nature, and the fact that it is often a diagnosis of exclusion. Still, it presents significant challenges to the cardiovascular scientific community, since the mechanism of myocardial damage and related etiologic and prognostic factors are virtually unknown. The development of more reliable measures of immune-mediated damage and noninvasive measures of impaired cardiac function present new research opportunities in this disorder. Standardized diagnostic criteria for use in observational and interventional trials were developed, and priorities for future research were proposed. Population-based registries and nested case-control studies, where feasible, are appropriate study designs for tracking incidence and prevalence, and for identifying risk factors, respectively. Interventional studies should focus on secondary prevention, through modifying immunemediated damage in clinically evident dilated cardiomyopathy, and through prevention of sudden death in patients with the disorder. Primary prevention trials must await the identification of modifiable risk factors and of appropriate and effective interventions.

Enzyme histochemistry of endomyocardial biopsies in idiopathic dilated cardiomyopathy.

The etiology of idiopathic dilated cardiomyopathy (DCM) is yet unknown; this study aimed at further differentiation of the disease by means of enzyme histochemistry. Endomyocardial biopsies from the left ventricle of 40 DCM patients and 5 control specimens had enzymes examined histochemically and semiquantitatively and analyzed according to staining intensities of nicotinamide adenine dinucleotide tetrazolium reductase (NADH-TR), succinate dehydrogenase, cytochrome c oxidase, lactate dehydrogenase and acid phosphatase (aPh). In DCM, the NADH-TR activity was elevated as compared to controls, indicating impaired mitochondrial oxidative phosphorylation. However, a concrete relation of enzyme histochemical intensity to anamnestic, hemodynamic or histomorphometric data could not be determined, except for the fact that the intensity of the lysosomal enzyme aPh was elevated in DCM patients with a relatively high left ventricular ejection fraction. The results demonstrate an interindependence of structural, hemodynamic and historical parameters as well as enzyme concentrations in DCM. Thus, a pathological change in the enzyme concentrations tested here cannot be responsible for the functional myocardial impairment in DCM.