Persistence of interstitial inflammation after episodes of cardiac rejection associated with systemic infection

To determine whether systemic infection has an effect on cardiac allografts, we compared heart transplant biopsy specimens showing acute cardiac rejection in patients with and without associated systemic infection.

Systemic infection was defined as positive bacterial, viral, or fungal cultures with systemic symptoms such as sepsis, fever, or malaise. Patients were identified by chart review to verify the presence or absence of infection and the cardiac biopsy specimens were examined for evidence of rejection. Eight patients (eight episodes of treated acute rejection) with evidence of systemic infection and 11 patients (14 episodes of treated acute rejection) without evidence of systemic infection were identified.

Patients with rejection and infection showed persistent interstitial inflammation longer than patients with only rejection and was most often represented by International Society for Heart and Lung Transplantation rejection grade 1B. Days to resolution or last biopsy was 20 to 602 days (mean 196 days) for patients with rejection and infection versus 15 to 133 days (mean 60 days) for patients with rejection alone. Results of two-tailed, unpaired t-test comparing the number of days of persistent inflammatory infiltrates in the patients with and without infection were statistically significant (p = 0.0192).

Heart transplant recipients with treated acute rejection and systemic infection more frequently have persistent interstitial inflammatory infiltrates than do heart cardiac transplant recipients with treated acute rejection and no associated infection. No impact of acute rejection or associated infection on the incidence of allograft coronary artery disease was apparent. Although further evaluation of these findings is necessary, we speculate that heart transplant recipients with systemic infection and acute rejection have greater immunologic activity leading to persistent interstitial inflammation and may possibly be associated with a higher incidence of chronic rejection.