Original pre-clinical scienceDiverse morphologic manifestations of cardiac allograft vasculopathy: A pathologic study of 64 allograft hearts
Section snippets
Methods
To assure optimal preservation of tissue morphology we did not include autopsy cases in this study, but instead limited our investigation to explanted hearts from patients undergoing retransplantation. Archival records, tissue paraffin blocks and microscopic sections were retrieved from 64 patients who underwent retransplantation. The patients were divided into 3 groups: adult males (≥18 years of age); adult females; and children.
Demographic and clinical data were extracted from the medical
Results
A large number of patients transplanted at our institution had their initial transplantation or part of their follow-up at other institutions, so complete medical records were not readily available for this subgroup of patients. The study consisted of 64 patients, which included 45 adult males, 9 adult females and 10 pediatric patients (3 males and 7 females). The adult males were 18 to 70 years of age (mean 49 years), adult females were 19 to 62 years of age (mean 40 years), and the pediatric
Myocardial findings
In adult males, the mean heart weight was 405 g. In adult females the mean heart weight was 207 g. In the pediatric group the mean heart weight was 110 g. The heaviest adult male heart weighed 1,240 g, the heaviest adult female heart 376 g, and the heaviest pediatric heart 350 g. However, all of these weights are actually less than the total heart weights, because portions of the atria are usually missing from the explanted hearts, and at our institution fresh tissue is harvested from the apex
Vascular findings
In all hearts, at least one of the four major epicardial coronary arteries had gross luminal narrowing. Overall, 78% (169 of 216) of the microscopic slides of the epicardial coronary arteries examined showed circumferential lesions narrowing the lumens.
Greater than 75% narrowing in any of the major coronary arteries was seen in the LAD in 17%, the LCx in 27% and the RCA in 22% of hearts. In 2 hearts there was severe narrowing (85% and 90%) of the left main coronary artery. All hearts had
Discussion
CAV is the leading cause of late morbidity and mortality after heart transplantation. The pathogenesis of CAV is not completely understood. CAV is currently not entirely preventable or treatable. Mechanical interventions such as drug-eluting stents20 have shown at least temporary benefit; however, due to the diffuse nature of the epicardial and intramyocardial arterial lesions observed, stents are a sub-optimal treatment. Drug therapy, such as everolimus, should be more effective than
Disclosure statement
W-h.L., a visiting cardiovascular pathology fellow, and K.P., a UCLA medical student, contributed equally as first authors of this study. J.K. is currently affiliated with the Department of Medicine, Cedars–Sinai Health Institute, Los Angeles, California. The study was funded in part by the Piansky Family Trust, a generous endowment to the Department of Pathology and Laboratory Medicine at UCLA (to M.C.F.). The expert histologic laboratory skills of Lonhsheng Hong are acknowledged. None of the
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2022, American Journal of PathologyCitation Excerpt :That is, chronic graft injury is a far greater current clinical problem than is early graft loss due to acute rejection. In heart transplantation, cardiac allograft vasculopathy (CAV) is a form of pronounced coronary artery disease that occurs over time after transplant1 and remains the major source of transplant loss and recipient mortality.2,3 Moreover, it has become increasingly apparent over the past several years that the development of donor-specific antibodies (DSAs) is strongly associated with CAV and chronic allograft rejection in general through the process of antibody-mediated rejection (AMR).4,5