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on March 12, 2007

Circulation. 2007
Published online before print March 12, 2007, doi: 10.1161/CIRCULATIONAHA.106.627570
A more recent version of this article appeared on April 3, 2007
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*Cytomegalovirus Infections
*Heart Transplantation
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Right arrow CV surgery: transplantation, ventricular assistance, cardiomyopathy
Right arrow Pediatric and congenital heart disease, including cardiovascular surgery

Submitted on April 21, 2006
Accepted on December 21, 2006

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

Tarique Hussain MBBCh, MA, MRCPCH*, Michael Burch MBChB, MD, FRCPCH, Matthew J. Fenton MBBS, BSc, MRCPCH, Pauline M. Whitmore RGN, RSCN, Philip Rees MBBCh, BSc, FRCPCH, Martin Elliott MBBS, MD, FRCS, and Paul Aurora MBBS, BSc, MSc, MRCPCH

From Paediatric Cardiology, Great Ormond Street Hospital, London, United Kingdom.

* To whom correspondence should be addressed. E-mail: tarique{at}doctors.org.uk.

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 ratio=3.6), all-cause mortality (partial hazard ratio=4.1), and coronary death (hazard ratio=4.6).

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.


Key words: coronary disease • pediatrics • transplantation • viruses




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