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Chagas' disease, caused by Trypanosoma cruzi, is an important cause of myocarditis and chronic cardiomyopathy and is accompanied by microvascular spasm and myocardial ischemia. We reported previously that infection of cultured endothelial cells with T. cruzi increased the synthesis of biologically active endothlein-1 (ET-1). In the present study, we examined the role of ET-1 in the cardiovascular system of CD1 mice infected with the Brazil strain of T. cruzi and C57BL/6 mice infected with the Tulahuen strain during acute infection. In the myocardium of infected mice myonecrosis and multiple pseudocysts were observed. There was also an intense vasculitis of the aorta, coronary artery, smaller myocardial vessels and the endocardial endothelium. Immunohistochemistry studies employing anti-ET-1 antibody revealed increased expression of ET-1 that was most intense in the endocardial and vascular endothelium. Elevated levels of mRNA for preproET-1, endothelin converting enzyme and ET-1 were observed in the same myocardial samples. Plasma ET-1 levels were significantly elevated in infected CD1 mice 10-15 days post infection. These observations suggest that increased levels of ET-1 are a consequence of the initial invasion of the cardiovascular system and provide a mechanism for infection-associated myocardial dysfunction.

Background: The normal pericardial sac accommodates a 250-350 gram heart and 15-50 ml of pericardial fluid. Cardiac enlargement and/or increases in fluid must be accompanied by an increase in pericardial volume and a concomitant expansion of the pericardial sac. The mechanism of such expansion has been debated, but theoretical considerations include fibroblastic proliferation with new connective tissue deposition versus remodeling of the pre-existent connective tissue., Design: Nineteen pericardia were obtained from consecutive adult autopsies. Total pericardial fluid was measured; the absolute value of pericardial fluid volume and cardiac weight were added to create a total score. Representative pericardial tissue was stained with hematoxylin-eosin (H&E), Masson's trichrome, and Verhoeff's elastin stain (EVG). An additional archival case with the pericardium from a 900-g heart with 1,000-ml of fluid was also included., Results: None of the sections showed histologic evidence of fibroblastic proliferation. Parameters indicative of collagen stretching or damage were evaluated. The greatest correlative factor in identifying an enlarged pericardium was the average of four measurements of the greatest distance between elastic fibers surrounding obliquely oriented collagen layers. Five of six cases with a cardiac score > 450 showed an average measurement of less than 15 microns, and 10 of 14 cases with a cardiac score < or = 450 showed an average measurement of > 15 microns = 0.0498). Histologic and ultrastructural evidence of collagen damage was identified in the pericardium from the 900-g heart with the 1,000-ml effusion., Conclusions: We propose that collagen stretching and slippage of obliquely oriented collagen layers contribute to the increased surface area needed to accommodate larger volumes. When these limits are exceeded, collagen damage ensues.

Cardiac papillary fibroelastomas are benign endocardial papillomas. They may arise from atrial or ventricular endocardium but most commonly are located in cardiac valves. Their papillary structure, with loose, friable projections, results in a high tendency for embolism. Tumor fragments often embolize to the coronary, systemic, or cerebral arterial systems. Thus, acute myocardial infarction, cerebrovascular accident, or peripheral arterial occlusion have resulted from these tumors. Retinal artery embolism is a rare complication of papillary fibroelastoma, and only five such patients have been reported in the English-language literature. We describe a 64-year-old woman who presented with transient painless loss of vision and was found to have a large papillary fibroelastoma on the right coronary cusp of the aortic valve by transesophageal echocardiography. The tumor was successfully removed at surgery., (Copyright © 1997 Elsevier Science Inc. All rights reserved.)

Cystinosis is a lysosomal storage disease classically associated with renal failure, photophobia, and hypothyroidism. Multi-organ dysfunction tends to develop over time, a factor of increasing significance as patient survival improves. Herein, we describe a male patient with cystinosis who developed a restrictive cardiomyopathy associated with myocardial cystine deposition and an ap-proximately 1000-fold elevation in myocardial cystine levels. Renal failure necessitated a kidney transplant at age 12. At age 31, the patient was diagnosed with progressive cardiac failure poorly responsive to aggressive antifailure therapy and risk factor modification. The patient died at age 33 in hypovolemic shock due to a ruptured pseudoaneurysm at an old renal transplant site., (Copyright © 1997 Elsevier Science Inc. All rights reserved.)

Chagas' disease, due to a chronic and persistent infection with the parasite Trypanosoma cruzi, is the cause of one of the most prevalent forms of congestive cardiomyopathy in South and Central America. In common with other congestive cardiomyopathies due to acquired and hereditary etiologies seen worldwide, chagasic cardiomyopathy is characterized by cardiomegaly, ventricular chamber remodeling, myocellular necrosis, and multifocal areas of interstitial and replacement fibrosis. The microscopic presence of the parasite in the late stages of the disease is rare. This review examines some of the evidence for the role of a dysfunctional microvasculature as a pathophysiological mechanism for myocardial damage in chagasic cardiomyopathy. Perturbations of the interstitial connective tissue matrix in Chagas' disease also are described in regard to the remodeling characteristic of the affected ventricle. Similar abnormalities of the microvasculature and matrix have been reported in other congestive cardiomyopathies, thereby suggesting that common pathophysiologic mechanisms may lead to ventricular damage even when the initiating etiologic agent is different. Preventive treatment or palliation of Chagas' cardiomyopathy and other congestive cardiomyopathies may result from a better understanding of these secondary pathogenetic events.

We report an autopsy case of disseminated tuberculosis and a coexisting, extremely rare parasitic zoonosis: pentastomiasis. The parasite was incidentally found in the pericardial sac and epicardium, associated with tuberculous pericarditis, in a 43-year-old woman from Georgia with presumptive Acquired Immunodeficiency Syndrome (AIDS). The cuticle was the only remaining intact structure of the parasite. The internal organs had undergone autolysis, but recognizable features were apparent. Gross and microscopic findings were highly suggestive of pentastomid species. The ultrastructure of the cuticle was consistent with a pentastomid arthropod. This is one of the few cases of visceral pentastomiasis reported in North America, and the first known example of heart involvement. The association of the parasitic infection and tuberculous pericarditis makes the case even more unusual.

To evaluate possible occult myocardial disease in patients with ventricular arrhythmias of unknown origin, over 11 years right ventricular endomyocardial biopsies (EMB) were performed on 80 consecutive such patients (29 Females, 51 Males; median age 42 years). Seventy-one (89%) had ventricular tachycardia or fibrillation, 7 (9%) had complex ventricular arrhythmias, and 2 (3%) had premature ventricular beats. None showed clinical evidence of congestive heart failure or significant coronary artery or valvular disease. Endomyocardial biopsies revealed pathologic changes in 70 out of 80 patients (88%). Of the 70 affected, 39 (56%) had nonspecific changes consistent with cardiomyopathy (e.g., myofiber hypertrophy, interstitial and perivascular fibrosis, and vascular sclerosis); 6 (9%) had active myocarditis (Myo); 7 (10%) had borderline Myo; 7 (10%) had small vessel disease; 6 (9%) had changes consistent with arrhythmogenic cardiomyopathy; 2 (3%) had amyloidosis; 2 (3%) had microfibrillar cardiomyopathy, and one (1.0%) showed intravascular organizing thrombus. Thus, EMB reveals a variety of abnormalities in the majority of patients presenting with ventricular arrhythmias without clinical evidence of structural heart disease.

naturally occurring hypertrophic cardiomyopathy (HCM) was diagnosed in 55 purebred pigs 6 to 12 months of age. Ten (18%) of the pigs died suddenly during auction or shipment or were found dead by their keepers. The other 45 pigs failed to meet the criteria for brediing stock. Forty-six purebred and 64 hybrid pigs were studied for control. Heart weights were significantly heavier (p < 0.001) in the pigs with HCM (473.5 ± 31.8 g; heart weight [HW]/body weight [BW] ratio 4.6 ± 0.7) than in the purebred (334.4 ± 29.7 g; HW/BW 3.4 ± 0.3) and hybrid (344.3 ± 28.9 g; HW/BW 3.4 ± 0.1) pigs without HCM. The ventricular septum (VS) in the 55 pigs with HCM was significantly thicker (26.0 ± 3.1 mm; p < 0.001) than in the purebred (19.6 ± 2.6 mm) and hybrid (14.1 ± 0.5 mm) pigs without HCM. The left ventricular free wall (LV) was significantly thicker (p < 0.001) in the pigs with HCM (20.0 ± 2.7 mm) than in the purebred (18.1 ± 2.1 mm) and hybrid (15.6 ± 0.3 mm) pigs without HCM. Asymmetric septal hypertrophy was evident because the ratio of VS to LV was significantly greater (p < 0.001) in the pigs with HCM (1.3 ± 0.2) than in the purebred (1.0 ± 0.2) and hybrid (0.9 ± 0.01) pigs without HCM. The anterior portion of the VS appeared to bulge into and impinge upon the left ventricular outflow tract, in which a fibrotic endocardial plaque was often seen. Histologic features included marked muscle cell disorganization in the VS, LV, right ventricular free wall. Abnormal intramural coronary arteries and myocardial fibrosis were seen in most pigs with HCM. Silver impregnation stains showed that there were marked increases in perimysial coils, pericellular weaves, and cell-to-cell struts. Matrix disorientation was evident in the hearts with HCM. Quantitation revealed that the collagen protein in the hearts with HCM (23.8 ± 2.8 μg/mg protein) was significantly higher (p < 0.001) than in the hearts of purebred (15.7 ± 1.8 μg/mg protein) and hybrid (13.9 ± 4.2 μg/m pprotein) pigs without HCM. Total muscle protein in the hearts of the purebred pigs with (51.6 ± 3.3 mg) and without (51.9 ± 3.0 mg) HCM was not different; however, in hearts with HCM (51.6 ± 3.3 mg) it was significantly higher (p < 0.001) than in those of hybrid pigs (47.6 ± 4.4 mg) without HCM. There was 47% to 52% more stainable collagen in the heart with HCM (44.7 ± 5.2 μg collagen/mg protein) than in the purebred (30.3 ± 4.0 μg collagen/mg protein) and hybrid (28.3 ± 8.1 μg collagen/mg protein) hearts without HCM. Gross and histologic features and connective tissue abnormalities in the pigs with HCM were strikingly similar to those in humans, cats, and dogs with HCM. Thus we conclude that spontaneous porcine HCM presents a new and important model for the cardiovascular investigator., (Copyright © 1994. Published by Elsevier Inc.)

Microfibrils-small, ubiquitous components of the extracellular matrix in many tissues-generally have not been recognized as causing infiltrative heart disease, except in a group of cardiac transplant patients treated with cyclosporin. Microfibrils are often associated with elastic tissue and contain the glycoprotein fibrillin, the P component of amyloid, and bound fibronectin. A genetically determined abnormality of fibrillin caused by point mutations of fibrillin genes recently was reported as the cause of Marfan's syndrome. However, to date, no abnormalities of increased fibrillin tissue deposition have been observed. In the last two years, while examining right ventricular endomyocardial biopsies, in four patients we noted abnormal histology distinct from the usual type of congestive cardiomyopathy but with a strong resemblance to amyloidosis. The patients presented with unexplained ventricular tachycardia (N = 3) and/or congestive heart failure (N = 2). Biopsies revealed subendocardial, interstitial, and perivascular hyaline eosinophilic fibrillar material that did not stain with Congo red. Electron microscopy revealed that this material was organized into bundles of tangled microfibrils composed of twisted and tubular structures measuring up to 17 nm wide, which did not resemble amyloid or cyclosporin-associated microfibrils. Immunoelectron microscopy of the index case, using monoclonal antibody to fibrillin, specifically identified these structures as fibrillin microfibrils; fibronectin also was bound to the interstitial microfibrils. We believe that the subendocardial and interstitial deposition of microfibrils in these four symptomatic patients may represent a new type of infiltrative cardiomyopathy, similar to but distinct from cardiac amyloidosis. We do not know yet if this disorder is genetic or acquired, or if the prognosis is better than that of cardiac amyloidosis. However, atypical cases of primary cardiac amyloidosis should be reevaluated in light of these findings., (Copyright © 1992. Published by Elsevier Inc.)