Clinical Features and Outcomes of Delayed-onset Primary Cytomegalovirus Disease in Cardiac Transplant Recipients

Background: Cytomegalovirus (CMV)-seronegative recipients of cardiac allografts from CMV-seropositive donors (CMV D⁺/R^-) are at highest risk of CMV disease after transplantation. This study was conducted to investigate the incidence, clinical features, risk factors and outcome of delayed-onset primary CMV disease in cardiac recipients who received anti-CMV prophylaxis. Methods: This study enrolled all CMV D⁺/R^- cardiac recipients during the period from 2000 to 2004. The medical records of patients were reviewed to assess clinical variables and outcomes. The data were analyzed using descriptive statistics and survival analysis. Results: During the 5-year study period, a total of 31 cardiac recipients had CMV D⁺/R^- serostatus (mean age ± SD: 49.2 ± 13.7 years; 74% male). All patients received oral ganciclovir (n = 6) or valganciclovir (n = 25) prophylaxis for a median duration of 95 days (interquartile range: 90 to 100). No breakthrough CMV disease was observed. However, 9 (29%) patients developed delayed-onset primary CMV disease (3 with CMV syndrome, 6 with gastrointestinal disease) during the period from 120 to 444 days after transplantation. No demographic or clinical variable was significantly associated with delayed-onset primary CMV disease. However, acute rejection with a severity of Grade ≥2 showed a trend toward association with CMV disease (hazards ratio: 2.46; 95% confidence interval: 0.66 to 9.2; p = 0.18). During the mean (±SD) follow-up period of 2.9 (±1.68) years, 3 patients died. CMV disease was not associated with all-cause mortality. Conclusions: In the contemporary era of anti-viral prophylaxis, delayed-onset primary CMV disease remains a common complication among CMV D⁺/R^- cardiac recipients. This finding warrants a better strategy for CMV prevention.