Guidelines for autopsy investigation of sudden cardiac death.

Although sudden cardiac death is one of the most important mode of death in Western Countries, pathologists and public health physicians have not given this problem the attention it deserves. New methods of preventing potentially fatal arrhythmias have been developed and the accurate diagnosis of the causes of sudden cardiac death is now of particular importance. Pathologists are responsible for determining the precise cause of sudden death but there is considerable variation in the way in which they approach this increasingly complex task. The Association for European Cardiovascular Pathology developed these Guidelines, which represent the minimum standard that is required in the routine autopsy practice for the adequate assessment of sudden cardiac death, including not only a protocol for heart examination and histological sampling, but also for toxicology and molecular investigation. Our recommendations apply to University Medical Centres, Regional and District Hospitals and all types of Forensic Medicine Institutes. If a uniform method of investigation is adopted throughout the European Union, this will lead to improvements in standards of practice, allow meaningful comparisons between different communities and regions and, most importantly, permit future trends in the patterns of disease causing sudden death to be monitored.

C4d-the witness of humoral rejection.

OBJECTIVE: Acute antibody-mediated (humoral) rejection is a major cause of morbidity, graft loss, and mortality among heart transplant patients. Herein we have presented our experience using C4d to characterize humoral rejection. MATERIALS AND METHODS: All nonformalin-fixed cardiac graft biopsies (protocol or emergency) received between May 2007 and May 2008 were examined by immunofluorescence for C4d. RESULTS: One hundred twelve endomyocardial biopsies from 25 transplanted patients included 20 males and 5 females of ages ranging from 3 to 71 years. The number of biopsies per subject varied from 1 to 11; the timespan between transplantation and the diagnostic biopsies ranged from days to 8 years. Thirteen biopsies showed acute humoral rejection (intramyocardial capillaries positive for C4d); 31, acute cellular rejection (grades 1R, 2R); 7, both humoral and cellular rejection; and 1, acute humoral rejection and allograft vasculopathy. Some of the positive biopsies belonged to the same person, and some to transplanted individuals with signs and symptoms suggestive of rejection, while others did not. The persistence of humoral rejection, despite the disappearance of a cellular component, correlated with slower clinicoechocardiographic improvement. CONCLUSIONS: C4d positivity is a morphologic sign of humoral rejection. It may hasten the appearance and/or worsening of allograft vasculopathy independent of patient age or posttransplantation time.

Morphologic Study of Homograft Valves before and after Cryopreservation and after Short-Term Implantation in Patients.

Cryopreserved heart valve homografts have been implanted in patients for the past 15 years, but controversies still exist on the survival of donor cells, matrix maintenance, and possible rejection by the host. Therefore a full morphologic study (histology, immunohistochemistry, transmission electron microscopy, and cuprolinic blue-TEM for glycosaminoglycans [GAG]) of short-term implanted uninfected grafts was done using unimplanted valves as the reference. Unimplanted tissues consisted of 5 fresh and 11 cryopreserved valves. Eight implants were recovered at reoperation [4] or autopsy [4], 4 from the right and 4 from the left ventricular outflow tract. The implantation time was 2 hours to 30 days. For unimplanted valves we found a partial preservation of the endothelium, the presence of dendritic Langerhans cells (Lc) and macrophages, and no significant damage to fibroblasts, collagen framework, and GAG pattern, except when the tissues had been ischemic for a long time. Explanted cusps exhibited (i) early disappearance of endothelium and Lc; (ii) nonspecific low-grade inflammatory cell infiltration, mostly of monocytoid type; (iii) viable degree of devitalization of fibroblasts with persistence of viable cells in some areas in most cusps; and (iv) fair preservation of collagen framework and GAGs. It is likely that, in view of the good graft preservation at implantation, humoral rejection is responsible for the earlier destruction of the endothelium and dendritic cells and the delayed devitalization of the fibroblasts and that preservation of the collagen framework and other intercellular matrix components (glycosaminoglycans) should guarantee longterm graft function.