Quantitation of cytomegalovirus infection-associated histologic findings in endomyocardial biopsies of heart allografts.

To investigate whether histologic changes in heart allografts may be associated with cytomegalovirus infection, 46 heart transplant recipients were monitored for cytomegalovirus. Altogether, 762 endomyocardial biopsy specimens were analyzed. The histologic changes were semiquantitatively scored from mild to severe, and special attention was paid to inflammatory infiltrates and vascular changes. Cytomegalovirus infection occurred in 27 of 46 patients, shown by cytomegalovirus-antigenemia test. The endomyocardial biopsy findings were investigated in relation to cytomegalovirus-antigenemia. In the acute phase of cytomegalovirus infection during antigenemia, an inflammatory infiltrate, subendothelial lymphocytosis, was a characteristic finding in the endomyocardial biopsy specimens. An intense arteriolar endothelial cell proliferation and thickening of intima occurred. Long-term histologic findings with two years follow-up revealed a cytomegalovirus-associated enhanced vascular intimal thickening that narrowed the lumen of small intramyocardial arterioles. Acute rejection episodes were diagnosed in 15 of 27 patients with cytomegalovirus and in 9 of 19 patients free of cytomegalovirus. The inflammatory infiltrate of acute rejection was more peripheral to the vessels and did not obscure the findings characteristic to cytomegalovirus infection. The arteriolar endothelial proliferation and intimal thickening were significantly more prominent in cytomegalovirus infection than in biopsy specimens from patients with rejection only. In long-term follow-up, arteriolar endothelial proliferation declined, but the intimal thickness persisted and increased. The increase was significantly higher in patients with cytomegalovirus than in patients with rejection. In conclusion, an inflammatory response in vessel walls with alterations of small intramyocardial arterioles leading to narrowing of the vascular lumen of the graft was associated with cytomegalovirus infection in heart transplant patients.