Positive Pretransplantation Cytomegalovirus Serology Is a Risk Factor for Cardiac Allograft Vasculopathy in Children

Abstract

Background-Cytomegalovirus (CMV) infection has been implicated as a cause of posttransplantation coronary artery disease in adults. The purpose of this retrospective observational study was to evaluate the effect of CMV on outcome after heart transplantation in children. Methods and Results-Risk factors tested were recipient age, sex, and pretransplantation CMV serology; use of anti-CMV prophylaxis; posttransplantation evidence of CMV infection; and donor CMV serology. Transplantations were stratified traditionally according to CMV risk as low risk (recipient negative/donor negative), intermediate risk (recipient positive), and high risk (recipient negative/donor positive). Primary outcome measures were (1) development of coronary artery vasculopathy, (2) mortality (or graft loss) that occurred outside the early postoperative period, and (3) death (or graft loss) due to vasculopathy. Analysis was by proportional hazards modeling. A total of 165 children underwent heart transplantation, with a mean age at transplantation of 7.8 (SD 5.6) years. Thirty-two children had laboratory evidence of CMV infection after transplantation, but only 6 developed CMV disease or syndrome. Traditional CMV risk stratification correlated well with CMV infection but did not predict mortality, coronary artery disease, or coronary death. In contrast, positive recipient CMV was the only independent predictor of all 3 outcome measures: coronary artery disease (hazard ratioϭ3.6), all-cause mortality (partial hazard ratioϭ4.1), and coronary death (hazard ratioϭ4.6). Conclusions-In children, pretransplantation recipient CMV status is a more powerful predictor for the development of clinically significant vasculopathy and subsequent death than traditional risk stratification. This phenomenon warrants further investigation.

Endothelial Dysfunction and Cytomegalovirus Replication in Pediatric Heart Transplantation

“…17 Pretransplantation CMV seropositivity (and consequent lack of aggressive prophylaxis) appears to be associated with coronary lumen loss. 18 This is consistent with our previous work on CMV and graft vasculopathy in children 3 and with our current findings in which viral DNA was documented in patients CMV IgG positive before transplantation. That subclinical CMV infection may have a systemic endothelial effect is further illustrated by our finding that 11 of the 12 children with posttransplantation CMV replication did not go on to develop overt CMV disease yet showed reduced systemic endothelial function.…”

“…However, studies have highlighted the relationship between CMV and allograft vasculopathy in adults 1,2,13 and, more recently, in children. 3 One of the hallmarks of allograft vasculopathy is endothelial dysfunction. 5 Although the mechanisms by which CMV may cause vasculopathy are unknown, it is likely that dysfunction of the endothelium is important.…”

“…1,2 We have shown CMV serology to be an important factor in allograft vasculopathy of pediatric recipients. 3 Coronary endothelial dysfunction is associated with CMV infection 4 and the later development of transplant vasculopathy. 5 Recent work has shown that lowlevel systemic CMV infection is common after transplantation, 6 although infection of the heart itself is rare.…”

Diagnosis and management of coronary allograft vasculopathy in children and adolescents

“…According to their findings, within the 4 different patterns of infarct-atypical LGE-CMR, only the diffuse form was significantly higher patients early post transplantation, but they could not establish a definite reason for the findings [116] . Hussain et al [117] , have taken this technique further showing that high resolution late gadolinium enhancement (LGE) can be used to show vessel wall disease in CAV with good correlation with IVUS Figure 10. LGE scores correlated well with the maximal intimal thickness and mean intimal index [Pearson coefficient 0.80 (P < 0.001) and 0.92 (P < 0.001), respectively]. An enhancement diameter > 7.5 mm gave promising sensitivity and specificity values of 86% and 93%, respectively, for the detection of significant CAV.…”

Cytomegalovirus Infection and Cardiac Allograft Vasculopathy in Children

“…3,9 In the current issue of Circulation, Hussain and colleagues investigate the role of pretransplantation CMV serostatus and posttransplantation CMV infection on CAD in a pediatric heart transplantation population. 10 A total of 165 children were studied retrospectively with the primary outcome measures of development of graft CAD, mortality or graft loss beyond 6 months from transplantation, and death or graft loss caused by CAD. Of these children, 32 developed laboratory evidence of CMV infection, but only 6 developed CMV disease or syndrome.…”