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(Circulation. 2004;110:II-207 – II-212.)
© 2004 American Heart Association, Inc.

Cardiac Transplantation and Surgery for Congestive Heart Failure

Cytomegalovirus Infection in Heart Transplant Recipients Is Associated With Impaired Endothelial Function

Paraskevi Petrakopoulou, MD; Marion Kübrich, MD; Sinan Pehlivanli, MD; Bruno Meiser, MD; Bruno Reichart, MD; Wolfgang von Scheidt, MD; Michael Weis, MD

From Medizinische Klinik und Poliklinik I (P.P., M.K., M.W.) and Herzchirurgische Klinik (B.M., B.R.), University Medical Center, Munich-Grosshadern, Germany; Ludwig-Maximilians University of Munich, Munich, Germany; Medizinische Klinik I, Klinikum Augsburg (S.P., W.v.S.), Augsburg, Germany.

Correspondence to Michael Weis, MD; Medizinische Klinik I, University Hospital Munich-Grosshadern, 81377 Munich, Germany. E-mail Michael.Weis{at}med.uni-muenchen.de

Background— Cardiac allograft vasculopathy (CAV) is initiated by allograft endothelial injury. We hypothesized that a major mechanism by which cytomegalovirus (CMV) could contribute to CAV is by dysregulation of the endothelial vasomotor response.

Methods— Coronary endothelial vasomotor function was determined in 183 consecutive patients (24±33 months after transplantation), and was correlated with recipient and donor CMV serological status before transplantation and with documented CMV infection episodes (CMVpp65Ag+). Serial endothelial function measurements were performed in a subgroup of 53 transplant recipients (1 month and 12 months after transplantation). The composite endpoint of cardiovascular related events and death during a follow-up of 66±41 months was analyzed based on the CMV serological status before transplantation.

Results— The medium event-free time for CMV-negative recipients of CMV-positive hearts was 8.1 years compared with 13.3 years for the other groups (P<0.05). Distal epicardial but not microvascular endothelial function was significantly impaired in CMV seronegative recipients of seropositive donor hearts (n=48) compared with all other groups (P<0.01 versus seronegative recipient/seronegative donor; P<0.05 versus seropositive recipient/seronegative donor; P<0.05 versus seropositive recipient/seropositive donor). Distal epicardial endothelial dysfunction was more pronounced in heart transplant recipients with a history of documented CMV infection compared with patients without any documented CMV infection (P<0.01). In a longitudinal subgroup analysis, distal epicardial and microcirculatory endothelial vasomotor response deteriorated significantly in recipients with documented CMV infection (P<0.05 versus baseline) but not in patients without previous CMV infection.

Conclusion— Documented CMV infection episodes in heart transplant recipients are associated with impaired coronary endothelial function. CMV-negative recipients of CMV-positive donor hearts have an impaired distal epicardial endothelial function and an increased incidence of cardiovascular-related events and death during follow-up. CMV infection may contribute to allograft failure by accelerating coronary endothelial dysfunction.

Key Words: inflammation • endothelium • nitric oxide • coronary vasomotor function