title: Cytomegalovirus infection in heart transplant recipients is associated with impaired endothelial function.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medizinische Klinik und Poliklinik I, University Medical Center, Munich-Grosshadern, Germany.
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Petrakopoulou
authors.forename: Marion
authors.initials: M
authors.lastname: Kübrich
authors.forename: Sinan
authors.initials: S
authors.lastname: Pehlivanli
authors.forename: Bruno
authors.initials: B
authors.lastname: Meiser
authors.forename: Bruno
authors.initials: B
authors.lastname: Reichart
authors.forename: Wolfgang
authors.initials: W
authors.lastname: von Scheidt
authors.forename: Michael
authors.initials: M
authors.lastname: Weis
mesh_terms: D000328:Adult; D006328:Cardiac Catheterization; D017023:Coronary Angiography; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000503:physiopathology*; D003586:Cytomegalovirus Infections / Q000503:physiopathology* / Q000635:transmission; D018572:Disease-Free Survival; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005500:Follow-Up Studies; D006333:Heart Failure / Q000453:epidemiology; D016027:Heart Transplantation / Q000009:adverse effects; D006801:Humans; D015993:Life Tables; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D009204:Myocardial Revascularization / Q000706:statistics & numerical data; D011183:Postoperative Complications / Q000503:physiopathology*; D012086:Reoperation / Q000706:statistics & numerical data; D016019:Survival Analysis; D018084:Ultrasonography, Interventional; D014664:Vasodilation