Biomedical subjects
Publications and source records attributed to W C Roberts.
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Heterograft porcine valves have gained wide acceptance in replacement of diseased cardiac valves, and their clinical performance in adults has been very satisfactory over follow-up periods of up to 8 years. Valve replacement in children is relatively infrequent and experience with porcine xenografts is necessarily small. Our combined experience at three university hospitals has been with 25 children, 17 months to 16 years of age, who have been followed for 10 to 54 months (mean follow-up 33 months). Porcine valves were used to replace the aortic valve in nine, the mitral valve in seven, both valves in two, the tricuspid valve in two, and the pulmonary valve in five patients. Severe bioprosthetic valve dysfunction has occurred in five (20%) of these patients so far and necessitated replacement because of severe stenosis in mitral (two) or aortic (three) valve prostheses at 18 to 45 months after implantation; one postoperative death occurred among the five reoperations. Pathological examination showed extensive fragmentation of collagen with focal heavy calcification and degeneration. In addition we have encountered deterioration and calcification of two porcine valves in 23 valved conduits followed for 12 to 70 months (mean 43 months), requiring removal and replacement of the valves 65 and 67 months after implantation. This experience indicates a disquietingly high incidence of relatively early failure of porcine xenograft valves in children. This is significantly higher than the failure rate observed in adult patients. The failure rate is not consistently related to the small size of an implanted valve which becomes relatively narrow with the growth of the patient, leading to excessive turbulence and trauma to the prosthesis. Other factors, including increased turnover of calcium and accelerated rejection in growing children, may contribute to these failures and should be examined in order to improve long-term results. A satisfactory performance would make heterografts the ideal valvular prosthesis in children, since anticoagulation is avoided.
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The hospital autopsy rate in the United States dropped from 41 per cent in 1964 to 22 per cent in 1975. This reduction is attributable to a declining interest for many reasons by clinicians, surgeons, pathologists, families of the deceased and hospital administrators and hospital accreditors. Various advances in medicine and surgery in recent years have not replaced the value of the autopsy; indeed they have increased the potential information to be gained from it. For interest in autopsies to be revived among physicians and surgeons, pathologists must provide more expert information from the autopsy. To provide the type of information sought from autopsies by physicians and surgeons, the training of pathologists must be altered so that there can be more specialization in anatomic pathology and more subspecialization in the various organ systems, as in internal medicine. In addition, the means of communication between anatomic pathologists and clinicians needs altering so that important clinical questions are recognized by pathologists, and the answers sought and promptly, understandably and diplomatically communicated to physicians and surgeons. Moreover, the large body of information obtained in recent years from autopsies alone needs to be better recognized by clinicians so that they may better understand the value of these examinations.
Sudden death is a recognized complication in symptomatic patients with hypertrophic cardiomyopathy. However, its occurrence in patients with no or transient previous cardiac symptoms presents a particularly challenging diagnostic and therapeutic dilemma. Therefore, 26 patients with hypertrophic cardiomyopathy whose death was the first definitive manifestation of cardiac disease were evaluated. Their ages ranged from 8 to 49 years (mean 18) and 23 were less than 25 years of age; 19 were male and 7 female. Of the 26 patients, 13 died during or immediately after moderate or severe physical exertion. Of 12 patients with previous cardiac catheterization, 6 had no or a small left ventricular outflow tract gradient under basal conditions and 6 had an outflow gradient of 50 mm Hg or greater. Left ventricular end-diastolic pressure was elevated in nine patients, and the ventricular septum was moderately to severely thickened (17 mm or more) in all patients. The electrocardiogram was abnormal in all 19 patients studied before death. Thus, sudden death may be the first definitive manifestation of cardiac disease in some patients with hypertrophic cardiomyopathy. Although the effects of patient selection in this study group cannot be excluded, sudden death was common in children and young adults and was often related to physical exertion; each patient showed a distinctly abnormal electrocardiogram and moderate to severe ventricular septal thickening.
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Histologically proven infection of the heart by Candida organisms occurred in 17 (10%) of 168 cancer patients with candidiasis studied at necropsy. All 17 patients were among the 85 patients with disseminated Candida infection; none of the 83 patients with localized candidiasis had involvement of the heart. Abscesses in the myocardium were present by histologic examination in all 17 patients and in 8 were evident on gross inspection as well. The mural endocardium was also affected in 5 patients from direct extension of a myocardial abscess. The valves were uninvolved. Pericardial infection was detected in 2 patients. The 17 patients with cardiac Candida infection had a higher frequency of positive premortem blood and cerebrospinal fluid cultures and of presence of Candida in the heart's blood than did the 68 patients with disseminated candidiasis but without involvement of the heart. Symptoms or signs of cardiac dysfunction resulting from the cardiac Candida infection were not readily detected in any patient. The clinical and pathologic features of cardiac candidiasis in cancer patients are distinct from those observed in Candida endocarditis.
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Necropsy findings are described in eight Newfoundland dogs from the same colony with discrete subaortic stenosis. Infective endocarditis involving the aortic valve occurred in four dogs and in each it proved fatal. Damage to the aortic valve cusps by the jet of blood ejected through the discretely narrowed left ventricular outflow tract predisposes to the development of infective endocarditis in both dogs and human beings with discrete subaortic stenosis. Severe abnormality of the intramural coronary arteries in the ventricular septum, which also occurs in patients with hypertrophic cardiomyopathy, was present in all eight dogs. Myocardial fiber disorganization and asymmetric septal hypertrophy, two other findings observed in patients with hypertrophic cardiomyopathy, were absent in each of the eight Newfoundland dogs with discrete subaortic stenosis.
Eight families were identified in which premature cardiac death due to hypertrophic cardiomyopathy occurred with unusual frequency. A total of 69 first degree relatives in the eight families were studied; 41 relatives had evidence of hypertrophic cardiomyopathy and 31 (75 per cent) died of their heart disease. Eighteen of these 31 patients were less than 25 years of age at the time of death. Death was sudden and unexpected in 23 of the 31 patients; in 15 of these 23 patients sudden death was the initial manifestation of cardiac disease. The remaining eight patients (seven were from two families) died after a chronic cardiac illness characterized by congestive heart failure, atrial fibrillation or thromboembolic events. Hence, premature cardiac death occurs frequently in certain families with hypertrophic cardiomyopathy. Such deaths are usually sudden, often occur in previously asymptomatic subjects and are common in children and young adults. These findings suggest that some families may manifest an unusually virulent expression of hypertrophic cardiomyopathy. Although this study cannot establish the precise prevalence with which "malignant" hypertrophic cardiomyopathy occurs, such families appear to be uncommon.
Scanning and transmission electron microscopic studies were made of (1) 12 glutaraldehyde-treated porcine valvular heterografts that had been implanted in patients for 2 days to 76 months; (2) 3 unimplanted commercially processed porcine aortic valves; and (3) 1 unprocessed porcine aortic valve. Comparison of unprocessed porcine valves and unimplanted commercially processed valves showed loss of endothelium and acid mucopolysaccharides during preimplantation processing. Short-term (less than 2 months) changes after implantation consisted of insudation of plasma proteins, penetration of erythrocytes into surface crevices, formation of a thin surface layer of fibrin, and deposition of macrophages, giant cells and a few platelets. Longer-term (more than 2 months) changes were proportional to the time interval after implantation and consisted of progressive disruption of collagen, erosion of the valve surfaces, formation of aggregates of platelets and accumulation of lipid. The surfaces of the leaflets did not become covered with endothelium or with a fibrous sheath. Calcific deposits were found in one valve and bacterial organisms in another. Thus, progressive breakdown of collagen appears to be a critical factor in determining the long-term durability of glutaraldehyde-treated porcine valvular heterografts.
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