Prognosis and possible presymptomatic manifestations of congestive cardiomyopathy (COCM)Supported in part by grant of Deutsche Forschungsgemeinschaft, SFB 30 Kardiologie Düsseldorf.

Kuhn, H.; Breithardt, Günter; Knieriem, H.-J.; Köhler, Erich; Lösse, B; Seipel, L; Loogen, F

doi:10.1136/pgmj.54.633.451

Cited by 88 publications

(29 citation statements)

References 15 publications

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“…28 That is, among cardiac hypertrophy, myocyte hypertrophy, and nuclear hypertrophy, only nuclear hypertrophy can distinguish the type of cardiac hypertrophy. At present, there is no morphological marker at the cellular level that distinguishes between normal and impaired systolic function of hypertrophic hearts; 28,29 that is, HCM and DCM cannot be distinguished solely by the histological findings of endomyocardial biopsies. Thus, a high incidence of marked nuclear hypertrophy of myocytes might be a special morphological feature of hypertrophic hearts with ventricular dilatation and systolic dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Nuclear Hypertrophy Reflects Increased Biosynthetic Activities in Myocytes of Human Hypertrophic Hearts

Koda

Takemura

Okada

et al. 2006

Circ J

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n response to various stresses, cardiac myocytes present phenotypic alterations of the cytoplasm, such as increased cell volume, increased fraction of subcellular organelles in contrast to decreased fractions of myofilaments, mitochondriosis, and intracytoplasmic vacuoles. 1,2 Nuclear structure is markedly altered as well. The nuclear change has been well characterized as "hypertrophied nucleus" by the morphological hallmarks of severe crenation of the nuclear membrane (bizarre shape) and widespread clumping of chromatin. [3][4][5] However, the significance of such dramatic alteration of the nuclear phenotype in hypertrophic hearts is largely unknown. We previously reported that hypertrophied nuclei in the myocytes of human hearts with dilated cardiomyopathy (DCM) were accompanied by increased activity of DNA repair/synthesis. 6 Scholz et al speculated that the nuclear abnormalities might be the primary event in the pathogenesis of DCM and that they might lead to a reduced transcriptional rate, which most probably was the cause of the lack of myofilaments and other degenerative changes. 7 However, the molecular biological alterations are largely unknown in the hypertrophied nucleus of various hypertrophic hearts. We hypothesize that such a nuclear phenotype change is associated with various molecular biological alterations occurring in myocyte nuclei of pathologic hearts, which may also be related to cardiac functional alterations. Thus, the major aim of the present study was to use endomyocardial biopsy specimens from hypertrophic hearts of various etiologies to examine linkages between the structural and molecular biological alterations of the hypertrophied nuclei of cardiac myocytes of human hypertrophic hearts. Methods Patients and Endomyocardial BiopsiesThis study was approved by the Institutional Research Committee. A total of 93 patients with hypertrophic hearts were studied (Table 1): DCM (n=23); postmyocarditis (n=13); hypertrophic cardiomyopathy (HCM, n=21); apical hypertrophic cardiomyopathy (APH, n=11); hypertensive heart disease (HHD, n=11); 14 nonhypertrophic hearts served as controls. There were 67 males and 26 females with a mean age of 58±13 years. Echocardiography, cardiac catheterization, and coronary angiography were performed and left ventricular (LV) endomyocardial biopsies were obtained. Measurements included by echocardiography, LV mass index (LVMI); interventricular septal thickness, and LV posterior wall thickness, and by cardiac catheterization, LV end-diastolic volume index, LV ejection fraction (LVEF), and LV end-diastolic pressure. Each endomyocardial biopsy was originally performed for differentiation between primary and secondary myocardial diseases. The Background The nucleus of the myocytes in human hypertrophic hearts is characterized by its bizarre shape and widespread clumping of chromatin. The functional significance has not been determined. Methods and ResultsLeft ventricular (LV) endomyocardial biopsies obtained from patients with dilated cardiomyopathy (DCM, n=23), postmy...

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Section: Discussionmentioning

confidence: 99%

Nuclear Hypertrophy Reflects Increased Biosynthetic Activities in Myocytes of Human Hypertrophic Hearts

Koda

Takemura

Okada

et al. 2006

Circ J

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“…was used by the individual pathologists and included acute myocarditis, borderline myocarditis, chronic myocarditis, focal myocarditis, myocarditis, and resolving myocarditis. One pathologist believed that patient 3 had inadequate tissue and three pathologists thought that staining was inadequate in patient 13. Figure 1 is a hematoxylin and eosin-stained slide from patient 7, in whom a diagnosis of definite myocarditis was made by three pathologists; all three agreed that a high lymphocyte count was present.…”

Section: Methodsmentioning

confidence: 99%

Interobserver variability in the pathologic interpretation of endomyocardial biopsy results.

Shanes¹,

Ghali²,

Billingham³

et al. 1987

Circulation

233

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Controversy exists over the role of endomyocardial biopsy in evaluating patients with dilated cardiomyopathy, particularly in detecting myocarditis and in assessing prognosis. Interobserver variability, if high, could explain conflicting reports. To assess this possibility, we submitted biopsy specimens from 16 patients with dilated cardiomyopathy to seven cardiac pathologists. The same slides were independently reviewed by each and assessed for fibrosis, hypertrophy, nuclear changes on a 0 to 3 + scale, mean lymphocyte count per high-power field, and myocarditis. The prevalance of significant fibrosis ranged from 25% to 69%, hypertrophy from 19% to 88%, nuclear changes from 31% to 94%, and abnormal lymphocyte count from 0 to 38%. One or more pathologists diagnosed definite or possible myocarditis in 11 of the 16 patients. Of these 11 patients, three pathologists agreed about three and two pathologists agreed about five. Myocarditis was diagnosed by a single pathologist in three cases. We conclude that interobserver variability is high in interpreting biopsy specimens from patients with dilated cardiomyopathy and that quantitative and standardized methods are needed to increase diagnostic consistency.

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“…Rather, in our own study and those of others, bundle-branch block gives the impression of being a marker of a slowly progressing degenerative disease affecting not only the conduction system but also the myocardium. [44][45][46] A slow increase in cumulative mortality over time would then be expected but would be detected only in large populations followed up for a long period of time.…”

Section: Mortalitymentioning

confidence: 99%

Bundle-Branch Block in a General Male Population

et al. 1998

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Background-Interest in bundle-branch block has focused primarily on its role as a predictor of mortality and coexisting cardiovascular diseases. Previous studies of prevalence, correlation to cardiovascular disease, and mortality have produced conflicting results. Methods and Results-We studied a random-sampled population of 855 men who were 50 years old in 1963 and followed them up for 30 years with repeated examinations. Men who developed bundle-branch block were studied with regard to cumulative incidence, relationship with cardiovascular disease/risk factors, and survival. The prevalence of bundle-branch block increases from 1% at age 50 years to 17% at age 80 years, resulting in a cumulative incidence of 18%. No significant relationship with ischemic heart disease or mortality was found. Men who would develop bundle-branch block had a bigger heart volume at age 50 years and developed diabetes mellitus and congestive heart disease during follow-up more often than control subjects. Conclusions-Bundle-branch block correlates strongly to age and is common in elderly men. Our results support the theory that bundle-branch block is a marker of a slowly progressing degenerative disease that also affects the myocardium.(Circulation. 1998;98:2494-2500.)

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Prognosis and possible presymptomatic manifestations of congestive cardiomyopathy (COCM)Supported in part by grant of Deutsche Forschungsgemeinschaft, SFB 30 Kardiologie Düsseldorf.

Cited by 88 publications

References 15 publications

Nuclear Hypertrophy Reflects Increased Biosynthetic Activities in Myocytes of Human Hypertrophic Hearts

Nuclear Hypertrophy Reflects Increased Biosynthetic Activities in Myocytes of Human Hypertrophic Hearts

Interobserver variability in the pathologic interpretation of endomyocardial biopsy results.

Bundle-Branch Block in a General Male Population

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