title: Acute rejection and cardiac allograft vascular disease is reduced by suppression of subclinical cytomegalovirus infection.
abstract: BACKGROUND
  Anticytomegalovirus (CMV) prophylaxis prevents the acute disease but its impact on subclinical infection and allograft outcome is unknown. We sought to determine whether CMV prophylaxis administered for three months after heart transplant would improve patient outcomes.
  
  
  METHODS
  This prospective cohort study of 66 heart transplant recipients compared aggressive CMV prophylaxis (n = 21, CMV hyperimmune globulin [CMVIG] plus four weeks of intravenous ganciclovir followed by two months of valganciclovir); with standard prophylaxis (n = 45, intravenous ganciclovir for four weeks). Prophylaxis was based on pretransplant donor (D) and recipient (R) CMV serology: R-/D+ received aggressive prophylaxis; R+ received standard prophylaxis. Outcome measures were: CMV infection assessed by DNA-polymerase chain reaction on peripheral blood polymorphonuclear leukocytes, acute rejection, and cardiac allograft vascular disease (CAV) assessed by intravascular ultrasound. All patients completed one year of follow-up. RESULTS.: CMV infection was subclinical in all but four patients (two in each group). Aggressively treated patients had a lower incidence of CMV infection (73 +/- 10% vs. 94 +/- 4%; P = 0.038), and an independent reduced relative risk for acute rejection graded > or =3A (relative risk [95% CI] = 0.55 [0.26-0.96]; P = 0.03), as compared with the standard prophylaxis group. Aggressively prophylaxed patients also showed a slower progression of CAV, in terms of coronary artery lumen loss (lumen volume change=-21 +/- 13% vs. -10+/-14%; P = 0.05); and vessel shrinkage (vessel volume change = -15 +/- 11% vs. -3 +/- 18%; P = 0.03).
  
  
  CONCLUSIONS
  Prolonged (val)ganciclovir plus CMVIG reduces viral levels, acute rejection, and allograft vascular disease, suggesting a role for chronic subclinical infection in the pathophysiology of the most common diseases affecting heart transplant recipients.
authors.affiliation: Division of Cardiovascular Medicine, Stanford University School of Medicine, CA, USA.
authors.forename: Luciano
authors.initials: L
authors.lastname: Potena
authors.forename: Cecile T J
authors.initials: CT
authors.lastname: Holweg
authors.forename: Clifford
authors.initials: C
authors.lastname: Chin
authors.forename: Helen
authors.initials: H
authors.lastname: Luikart
authors.forename: Dana
authors.initials: D
authors.lastname: Weisshaar
authors.forename: Balasubramanian
authors.initials: B
authors.lastname: Narasimhan
authors.forename: William F
authors.initials: WF
authors.lastname: Fearon
authors.forename: David B
authors.initials: DB
authors.lastname: Lewis
authors.forename: John P
authors.initials: JP
authors.lastname: Cooke
authors.forename: Edward S
authors.initials: ES
authors.lastname: Mocarski
authors.forename: Hannah A
authors.initials: HA
authors.lastname: Valantine
mesh_terms: D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000276:immunology* / Q000601:surgery* / Q000821:virology; D015331:Cohort Studies; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control* / Q000821:virology*; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D008875:Middle Aged; D018146:Muromegalovirus / Q000502:physiology*; D012307:Risk Factors; D013997:Time Factors; D014184:Transplantation, Homologous / Q000276:immunology