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Myocardial fibrosis in endomyocardial biopsy specimens: do different bioptomes affect estimation?

Estimation of fibrosis in endomyocardial biopsy specimens (EMB) is integral to their assessment; typically, EMB fibrosis is assessed qualitatively. We quantitated percent fibrosis in 697 paraffin-embedded, Masson's trichrome stained EMB taken from 6 sites along the right ventricular septum and from 1 site in the left ventricular free wall, utilizing Caves-Schultz (C-S) and Cordis (C) bioptomes and a scalpel in 34 formaldehyde-fixed autopsy hearts, 22 of which were anatomically normal (AN) and 7 of which were idiopathically dilated. Total tissue area and area of fibrosis were quantitated by computer-based image analysis. The mean total areas as obtained by the C-S and C bioptomes and scalpel were 0.0535 cm2 (+/- 0.028), 0.0338 cm2 (+/- 0.020), and 0.4370 cm2 (+/- 0.144), respectively. The C-S and C bioptomes and the scalpel from all hearts yielded percent fibrosis of 10.6, 12.3, and 5.4, respectively. The AN hearts had percents of 9.3, 11.8, and 4.5, while the ID hearts had 11.0, 13.7, and 7.3% fibrosis, respectively, by each sampling method. A consistent pattern was observed: the larger the piece of endomyocardium, i.e., scalpel greater than CS greater than C, the lesser the quantitated percent fibrosis. Thus, beyond allowing for biological variability in the degree of endomyocardial fibrosis, the impact of EMB size and the biotome type must be accommodated in qualitative surgical reports pertaining to myopathic hearts.

Adult↗

Correlations of fibrosis in endomyocardial biopsies from patients with aortic valve disease.

The amount of fibrosis in endomyocardial biopsies from 55 patients with aortic stenosis and 42 patients with aortic regurgitaion was measured. Sixty per cent of the patients with aortic stenosis had some degree of fibrosis; the degree of fibrosis correlated strongly with ejection fraction, peak systolic gradient, symptoms of cardiac failure, and mortality. In patients with aortic regurgitation, fibrosis was found in 40 per cent and was never severe. A correlation was found with symptoms of cardiac failure and mortality at follow-up, but not with ejection fraction or degree of regurgitation.

Adult↗

Endocardectomy for the surgical treatment of endocardial fibrosis of the left ventricle.

Two patients with endomyocardial fibrosis of the left ventricle were treated by endocardectomy plus mitral valve replacement. In both cases the results of surgery were satisfactory. No consequences related to eosinophilia, which was present before operation in one of them, were noted. The poor prognosis of this progressive disease and the inefficiency of medical treatment compared with the good surgical results already reported from various centres encourage early operation for all patients with endomyocardial fibrosis who have symptoms. Because of the pathophysiology of the disease, endocardectomy should be attempted in all cases and anti-coagulant treatment continued for life.

Adult↗

Noncardiovascular findings associated with heart disease in the idiopathic hypereosinophilic syndrome.

Heart disease characterized by endomyocardial fibrosis is one of the major causes of morbidity and mortality in the idiopathic hypereosinophilic syndrome. From our series of 50 patients with idiopathic hypereosinophilia, we defined the noncardiovascular characteristics that distinguish patients at risk of developing endomyocardial fibrosis from those who remain free of heart disease. These groups did not differ with respect to the extent of eosinophilia or the duration of disease. Patients with clinically overt heart disease were more likely (p less than 0.05) to be male and HLA-Bw44 positive and have splenomegaly, thrombocytopenia, elevated serum levels of vitamin B12, and hypogranular or vacuolated eosinophils and abnormal early myeloid precursors in the peripheral blood. These idiopathic hypereosinophilic patients with heart disease were also more likely to have fibrosis and decreased megakaryocytes in the bone marrow. In contrast, those who remained free of heart disease tended to be female and have angioedema, hypergammaglobulinemia, elevated serum levels of immunoglobulin E (IgE), and circulating immune complexes. Therefore, in the idiopathic hypereosinophilic syndrome, male patients with a myeloproliferative type disorder and the HLA-Bw44 haplotype were at a much increased risk for the development of endomyocardial fibrosis. However, those patients with a hypersensitivity-like illness and angioedema who were female did not develop heart disease. Appreciation of this relative degree of risk for the major complication of the idiopathic hypereosinophilic syndrome should prove useful in the early identification and appropriate treatment of patients in whom endomyocardial fibrosis might develop.

Adult↗

Endomyocardial firbrosis and Löffler's endocarditis parietalis fibroplastica.

The morphological features of endomyocardial fibrosis and Löffler's endocarditis are described. Sixteen cases of the chronic stage of Löffler's endocarditis were compared with pathological material of thirty-two patients with endomyocardial fibrosis. No morphological differences were noted. It is suggested that endomyocardial fibrosis and LOffler's endocarditis are part of the same disease spectrum, the origin of which can be traced back to the presence of eosinophils in the myocardium.

Endocarditis↗

Arterial lesions associated with medial disorganization and fibrosis in endomyocardial biopsies from human cardiac allografts.

We describe distinctive arterial lesions in endomyocardial biopsies from patients with human cardiac allografts. The lesions affected principally the media of small arteries and consisted of misorientation of smooth muscle cells and fibrosis. This remodelling was most prevalent in the subadventitial zone, but sometimes extended to involve the full thickness of the media. In the most extreme cases medial smooth muscle cells ran parallel to the long axis of the vessel and were segregated into small bundles and single cells separated by collagen which merged with the adventitial fibrosis. The intima was always normal. Abnormal arteries were present in 16% of 603 consecutive biopsies from 44 patients, and 39% of lesions occurred in 16% of patients. No lesions were found in endomyocardial biopsies from 25 non-transplanted patients, nor in mucosal biopsies from both transplanted and non-transplanted patients, confirming that the appearances were not due to biopsy artefact. There was early arterial remodelling in biopsies within two weeks of transplantation and none of the stages resembled vascular rejection. Fifty per cent of biopsies from some patients contained arterial lesions, suggesting that in susceptible patients they are common.

Adult↗

Fibrosis-induced reduction of endomyocardium in the rat after isoproterenol treatment.

Isoproterenol treatment leads to endomyocardial fibrosis with muscle fibers encircled by fibrillar collagen. This study was undertaken in the rat to determine if muscle encased in collagen would subsequently become either necrotic or atrophic. For this purpose, we monitored the fibrillar nature of myocardial collagen, its alignment with muscle, and the morphology of the endomyocardium, together with the response in diastolic and systolic myocardial stiffness, immediately on completion (10 days) and 30 days after a course of subcutaneous isoproterenol (500 micrograms/kg/day). We found 1) left ventricular hypertrophy at 10 and 30 days with an increase in collagen volume fraction (p less than 0.01) that consisted of a meshwork of thick and thin collagen fibers that encircled endomyocardial muscle, 2) a variable reduction in endocardial muscle fiber diameter at 30 days with the greatest thinning seen in muscle encircled by fibrous tissue, and 3) an elevation (p less than 0.01) in the slope of the diastolic stress-strain relation at 10 and 30 days. The developed systolic stress-strain relation, which was elevated at 10 days (p less than 0.01), declined (p less than 0.05) with the reduction in endomyocardial muscle mass. Thus, endomyocardial muscle, encircled by fibrillar collagen, will atrophy over time, and this leads to a reduction in active stiffness. These findings may, in part, explain why progressive ventricular dysfunction accompanies chronic myocardial disease with endomyocardial fibrosis.

Animals↗

[Endomyocardiopathy and eosinophilia (author's transl)].

Clinical, laboratory, and necropsy findings in a male patient with marked eosinophilia and fatal cardiac failure are reported. Necropsy revealed an obliteration of the left ventricle caused by endomyocardial fibrosis, left ventricle hypertrophy, and white thrombus. There was also found endomyocardial fibrosis and hypertrophy of the right ventricle. Pathogenesis and treatment of endomyocardiopathies are discussed.

Cardiac Catheterization↗

Epidemiology and etiology of cardiomyopathy in Africa.

BACKGROUND: Cardiomyopathy, an often irreversible form of heart muscle disease that is associated with a dismal outcome, is endemic in Africa. The primary objective of this review was to summarize the current state of knowledge on the epidemiology and etiology of cardiomyopathy in people living in Africa and to identify new avenues for research. METHODS AND RESULTS: We searched MEDLINE (January 1, 1966, through February 12, 2005) and reference lists of articles for relevant references. Unlike other parts of the world in which cardiomyopathy is rare, dilated cardiomyopathy is a major cause of heart failure throughout Africa. Similarly, peripartum cardiomyopathy is ubiquitous on the continent, with an incidence ranging from 1 in 100 to 1 in 1000 deliveries. There is an apparent marked regional variation in the pathogenesis of dilated cardiomyopathy and peripartum cardiomyopathy, underlining the heterogeneity of causative factors in these conditions. By contrast, endomyocardial fibrosis is restricted to the tropical regions of East, Central, and West Africa. Although the pathogenesis of endomyocardial fibrosis is not fully understood, it seems that the conditioning factors are geography and diet, the triggering factor may be an as yet unidentified infective agent, and the perpetuating factor is eosinophilia. Although epidemiological studies are lacking, hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy seem to have characteristics similar to those of other populations elsewhere in the world. CONCLUSIONS: There is a need for large-scale epidemiological studies of the incidence, prevalence, determinants, and outcome of cardiomyopathy in Africa to inform strategies for the treatment and prevention of heart muscle disease on the continent.

Africa↗

Visceral organ involvement is infrequent in oral submucous fibrosis (OSF).

Associated visceral organ involvement evidence by systemic fibrosis has not been explored in oral submucous fibrosis (OSF). The investigations in this aspect were limited to loco-regional sites of naso/oropharynx and oesophagus. The study of whether the oral fibrosis is part of a systemic spectrum of disease involving multiple organs is an interesting pursuit. With this intention the patients diagnosed on clinical and histological grounds for OSF were concurrently tested by biophysical means for the presence of endomyocardial fibrosis (EMF), pancreatic (PF) and retroperitoneal fibrosis (RPF), which are endemic to the area studied. Twenty-five (n = 25) cases of OSF who visited the Department of Oral pathology & Microbiology. Govt. Dental College, Trivandrum, India for symptomatic relief of their illness comprised the study group. Ten (n = 10) age and sex matched healthy volunteers comprised the control. All the subjects have had undergone cardiologic and gastrointestinal investigations to rule out the possibility of concurrent EMF and PF. The patients were all of Indian ethnic extraction and mostly (> 90%) were from low socio economic classes. The mean age of the patients was 54.16 +/- 14.6 years, including 18 females and 7 males (F:M = 2.57:1). The severity of fibrosis was unrelated to the age of patients (P > 0.05). All the patients were chewers of areca quid (12%)/tobacco (88%). In addition to quid chewing 3/25 (12%) patients smoked 'bidi' and 6/25 (24%) consumed home brewed liquor (arrack/toddy) which contain about 40-50% ethanol. Statistically no relationship was observed between the clinical stages of OSF and severity of epithelial dysplasia in this study (P > 0.05). Out of the 25 patients, 5 (20%) showed sclerotic aortic value which may be an age related finding. Also 7 (28%) patients were found to be hypertensive and interstitial lung disease was present in 2 (8%). The possibility of EMF in one female patient who showed thickened RV apical endocardium was ruled out by cardiac catheterisation. Thus none of the patients showed evidence of endomyocardial fibrosis. The pancreas was found to be hyperchoic in 8(32 1/4) by ultra sonography. Liver was found to be hyperchoic in 6 (24%). Fat stain in stool samples was found to be positive in 13(58%). The hyperchogenecity of pancreas may be due to alcoholism or an underlying endocrine pancreatic insufficiency like diabetes and not due to pancreatic fibrosis. The positivity of fat stain could be due to fatty liver/alcoholism. Thus the study fails to reveal any evidence of pancreatic fibrosis in the group. The lack of any evidence of an associated visceral organ fibrosis in OSF made it prudent to believe that this is a loco-regional disease, initiated by local factors and propagated under their influence without systemic involvement.

Age Distribution↗

[Mitral valve insufficiency secondary to endocardial fibrosis associated with distomatosis].

A new case of assumed parasitic cardiac disease is reported once more; a 67 year old woman with a trematode injection presenting with mitral incompetence and left ventricular failure. Biventricular endomyocardial fibrosis predominating at the apex was diagnosed at angiography and confirmed at surgery. Mitral incompetence was related to retraction of the papillary muscles which were surrounded by fibrosis, the rest of the mitral apparatus being normal. There was no indication for endocardectomy and so, mitral valve replacement alone was performed. There are few previous reports of parasitic cardiac disease: one case of left ventricular endomyocardial fibrosis, one case of biventricular fibroplastic parietal endocarditis and one case of cardiomyopathy. This report emphasises the need for cardiac examination in patients with parasitic diseases.

Aged↗

Clinical spectrum and endomyocardial biopsy findings in eosinophilic heart disease.

Fourteen cases of heart disease with hypereosinophilia were analyzed employing conventional cardiologic methods, including echocardiography, cardiac catheterization, and endomyocardial biopsy. The cases were divided into four types: Acute carditic (endocarditis, myocarditis, pericarditis; five cases); ventricular dilation (three cases); restrictive (three cases); electric disturbance (three cases). Biopsy revealed significant changes in all cases. In one case of the ventricular dilation type, endomyocardial fibrosis with myocardial degeneration was seen, and in another case mural thrombus formation was shown to be present. In three cases of the restrictive type, endomyocardial fibrosis (EMF) was observed. In two cases of the electric disturbance type, minor right ventricular myocardial degeneration was observed. In two of the three cases of the carditic type and in three of eight cases in other categories, postmyocarditic changes were observed. The course of the disease compared with the type of disorder revealed a short course in the carditic type and a longer course, ranging from 2 to 24 years, with one exception, in the other types. It is also confirmed that the various histopathologic changes can be related to particular clinical presentations. We have shown that the basic changes in eosinophilic heart disease are not restricted to the endomyocardium and that they occur in various parts of the heart causing more widespread manifestations. The more comprehensive term "eosinophilic heart disease" is a preferable description.

Adolescent↗

Endomyocardial biopsy.

Endomyocardial biopsy is an accepted, useful invasive tool for the analysis of human endomyocardium at the cellular and subcellular levels. It is applicable in the evaluation of specific diseases including cardiac allograft rejection, myocarditis, anthracycline cardiotoxicity, and infiltrative cardiomyopathies. The procedure can be performed in a cardiac catheterization room on an outpatient basis. The technique is quite safe when performed by trained cardiologists. Left ventricular biopsies are also safe but require systemic heparinization to prevent thromboembolization. The clinical indications for performing an endomyocardial biopsy include routine followup and suspected rejection of cardiac allograft, suspected myocarditis, monitoring or diagnosis of suspected anthracycline cardiotoxicity, and suspected secondary cardiomyopathies. Left ventricular endomyocardial biopsy is indicated for diseases that predominantly involve the left side of the heart, including left heart irradiation, cardiac fibroelastosis in infants, endomyocardial fibrosis, and scleroderma heart disease, and when right ventricular biopsy is unsuccessful. Endomyocardial biopsy is increasingly being used for research in the areas of tissue biochemistry, primary and valvular cardiomyopathies, immunology, beta receptor enzymology, drug interactions, and myocardial fibrosis. Endomyocardial biopsy has not been shown to be clinically useful in the evaluation of primary, dilated, hypertrophic, or alcoholic cardiomyopathies. These disease processes all lack pathognomomic microscopic abnormalities, and subclassification has neither been successful nor therapeutically useful. In addition, this technique is limited in diagnosing any cardiac abnormality that is not diffuse, inasmuch as only a few samples of the endomyocardial layer are obtained for evaluation. Therefore, a negative biopsy result is not 100 percent specific in excluding certain diseases. A further limitation of this technique is the need for an experienced cardiac pathologist who is well versed in interpretation of biopsy specimens. Finally, there should be a sufficiently large case load to train and to maintain skilled practitioners so that the procedure can be performed with little risk. The role of endomyocardial biopsy will continue to expand as research continues to find more uses for the technique and as more clinicians become skilled in its use.

Antibiotics, Antineoplastic↗