Spectrum and diagnosis of myocardial rejection

Right ventricular endomyocardial biopsy has become the mainstay for the diagnosis of acute cardiac rejection. The intelligent inerpretation of endomyocardial biopsy specimens requires knowledge of the artifacts inherent to the procedure as well as specific rejection and nonrejection pathology. Myocardial contraction bands, artifactual tissue spreading, and prior biopsy site changes should not be misinterpreted as evidence of myocyte damage, interstitial edema, or rejection, respectively. The Billingham criteria for acute cardiac rejection (mild, moderate, and severe) are still the most widely utilized, although other schemes for rejection have also shown clinical usefulness. Additionally, there is increasing evidence that some patients may develop a vascular or humoral rejection that may be more difficult to diagnose by endomyocardial biopsy without utilization of special techniques--for example, immunofluorescence. Nonrejection pathology frequently seen post-transplantation includes ischemia or catecholamine effect, interstitial fibrosis, myocardial calcification, cyclosporine-associated endocardial infiltrates (Quilty effect), myocyte hypertrophy, and infections (CMV, toxoplasmosis). Coronary artery disease continues to be the most significant threat to long-term survival. The spectrum of pathologic changes in the vessels range from mild intimal thickening to severe concentric intimal fibrosis involving extramural, as well as intramural, coronaries to lesions virtually identical to native atherosclerosis. Patients with diffuse narrowing involving large and small intramyocardial vessels appear to be at greater risk for myocardial infarction, death, or retransplantation than patients with other types of coronary pathology. Although important, these large vessel changes are rarely identified by endomyocardial biopsy.