Frequency, extent, and distribution of endomyocardial adipose tissue: Morphometric analysis of endomyocardial biopsy specimens from 241 patients.

Features of endomyocardial biopsy specimens (EMB) have been analyzed extensively; however, the frequency, distribution, and associations of adipose tissue in EMB taken from patients with failing hearts have received less attention. We analyzed morphologically and morphometrically EMB from 241 patients (159 male, 82 female, mean age 46.6 years, range 18-76) for whom six diagnostic clinicopathologic categories (including normality) were separately defined. The mean surface area of EMB, mean area of quantifiable adipose tissue, and percentage area attributable to fat were determined by computer-based morphometry to be 6.5 mm(2), 0.4 mm(2), and 6.5%, respectively. The mean number of biopsy pieces, number of pieces with fat, and percentage of pieces with fat were 4.1, 1.1, and 28.9%, respectively. Patients with arrhythmogenic right ventricular dysplasia had greater percentage area attributable to fat (19.8% vs. 8.9%; p < 0.0027) and greater number of pieces with adipose tissue (2.9 vs. 1.0, p < 0.0001) than did patients in diagnostic categories with the next most fatty EMB. There were no differences between males and females in EMB surface area fat or percentage of pieces with fat. Older patients (above the mean age) had greater adipose tissue in EMB (percentage area attributable to fat) than did younger patients (8.1% vs. 4.8%; p < 0.01). Body mass index (kg/m(2)) did not correlate with percentage EMB tissue area attributable to fat. Larger EMBs (above the mean area) were neither more frequently nor more involved by fat than were smaller biopsy specimens (6.4% vs 6.6% fat, respectively). Typically, adipose tissue in EMB percolated widely through the myocardium, and the mean number of EMB pieces did not influence the likelihood of finding fat deposits. Fat was intimately associated with blood vessels and was frequently associated with small areas of interstitial and replacement fibrosis. The high frequency of adipose tissue in EMB and the relatively large area constituted by fat in some EMB supports autopsy observations that focal and widespread fatty infiltration of the right ventricular endomyocardium is to be expected and reflected in EMB sampling. Excessive myocardial fat may play a pathogenic role in cardiomyopathy.

Insensitivity of right ventricular endomyocardial biopsy in the diagnosis of myocarditis.

The clinical suspicion of myocarditis relies strongly on endomyocardial biopsy for confirmation, yet the sensitivity of the procedure in this setting has not been clearly defined. Biopsy sensitivity was determined in 14 hearts with histologically proved myocarditis studied ex vivo, including 12 autopsy hearts and 2 native hearts explanted at cardiac transplantation. With use of the Stanford and Cordis bioptomes, endoymocardial biopsy was performed near the apex on the right side of the ventricular septum (four to five samples/bioptome per patient) and repeated in the nonapical portion of the septum from the moderator band to the subpulmonary infundibulum (additional three to five samples/bioptome per patient). In a casewise assessment, 43% to 57% of the endomyocardial samples were diagnostic for myocarditis, as calculated separately for each bioptome in each region of sampling (apical/nonapical). Both apical and nonapical sensitivity improved to 64% when the findings of the two bioptomes were combined (eight to nine samples/patient in each region). By collectively analyzing all available samples for each patient, 11 (79%) of 14 cases could be diagnosed, but this required a mean of 17.2 samples/patient, a number clinically unrealistic. The exclusion of four cases of fungal myocarditis from analysis did not significantly alter the results. In transmural ventricular sections, none of four patients with sudden death had inflammatory disease confined to the conduction system. In conclusion, despite six to eight negative biopsy samples/patient with suspected myocarditis, repeat biopsy may still be warranted.

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.

Familial aortic dissection in absence of ascending aortic aneurysms: a lethal syndrome associated with precocious systemic hypertension.

The interaction of elevated blood pressure and aortic metabolism in the genesis of aortic dissection is uncharacterized. A kindred with fatal familial aortic dissection in association with precocious systemic hypertension and in absence of a definable connective tissue syndrome has undergone genealogical, clinical, pathological, and biochemical evaluation. Six family members spanning three generations have died of acute dissection. Five men died at a mean age of 28 years (range 22-34), while the proband's paternal grandmother died at 62 years of age. All were hypertensive. A constellation of subtle clinical features points toward deficient integrity of connective tissues; however, major hallmarks of known connective tissue syndromes including aortic root ectasia or aneurysms are absent. Studies of cultured dermal and aortae fibroblasts of two of the proband's brothers mitigate against Ehlers-Danlos IV syndrome. This family's susceptibility to aortic dissection reflects the synergistic liability of coexistent elevated blood pressure and metabolic abnormalities in the genesis of aortic degeneration.

Duplex pulsed Doppler echocardiography in mitral regurgitation.

The accuracy of duplex pulsed Doppler echocardiography (d-PDE) for detecting mitral regurgitation was evaluated in 35 patients undergoing d-PDE, cardiac auscultation, and left ventriculography. With three transducer positions, the overall d-PDE sensitivity was 95%, specificity was 100%, positive predictive value was 100%, negative predictive value was 94%, and diagnostic accuracy was 97% compared with ventriculography. This technique was superior to auscultation (sensitivity 74%, specificity 94%, positive predictive value 93%, negative predictive value 75%, diagnostic accuracy 83%). No false-positive d-PDE results occurred, but discordant false-negative results occurred frequently among the three transducer positions. If discordant negative results are considered to be false negative, then d-PDE is both sensitive and specific when mitral regurgitation is defined as systolic spectral broadening in any one transducer position.

Immunohistochemical characterization of lymphocytes in uninflamed ventricular myocardium. Implications for myocarditis.

Evaluation of endomyocardial biopsy specimens for lymphocytic myocarditis requires accurate identification of lymphocytes, a task at times difficult considering that other myocardial interstitial cells mimic lymphocyte morphology. To wit, the number of mononuclear cells present in normal (uninflamed) myocardium has remained in doubt. We studied the myocardium from hearts that were obtained at autopsy and transvenous endomyocardial biopsy specimens with monoclonal antibodies and immunohistochemical stains to determine the normal numbers and distribution of lymphocytes in uninflamed hearts. In the ventricular myocardium of hearts obtained at autopsy, total immunohistochemically marked lymphocytes averaged 3.6/sq mm, with most being T-cell marker-positive. The ratio of T-helper to T-suppressor-cytotoxic (OKT-4:OKT-8) cells was 1.44. The number of myocardial lymphocytes demonstrated by immunohistochemical staining correlated well with, but was consistently less than, the number obtained by quantitative light microscopic studies on unmarked samples. Thus, the immunohistochemical technique allows for objective enumeration of cells and provides avenues for quantitation of lymphocyte subpopulations in inflamed hearts.

Quantitative evaluation of inflammation in biopsy specimens from idiopathically failing or irritable hearts: experience in 80 pediatric and adult patients.

The histologic criteria for the diagnosis of myocarditis on an endomyocardial biopsy specimen are troubled by varying institutional criteria and interobserver differences. A comprehensive approach to tissue evaluation including quantitative assessment of mononuclear cell populations enhances the accuracy and the specificity of the morphologic diagnosis. Future efforts to characterize the infiltrating cell lines in inflammatory conditions of the heart will aid in the ultimate refinement of therapeutic efficacy.