Potena Luciano, Holweg Cecile T J, Chin Clifford, Luikart Helen, Weisshaar Dana, Narasimhan Balasubramanian, Fearon William F, Lewis David B, Cooke John P, Mocarski Edward S, Valantine Hannah A
Division of Cardiovascular Medicine, Stanford University School of Medicine, CA, USA.
Transplantation. 2006 Aug 15;82(3):398-405. doi: 10.1097/01.tp.0000229039.87735.76.
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.
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).
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.
抗巨细胞病毒（CMV）预防措施可预防急性疾病，但其对亚临床感染和移植器官结局的影响尚不清楚。我们试图确定心脏移植后三个月进行的CMV预防是否能改善患者预后。
这项对66名心脏移植受者的前瞻性队列研究比较了积极的CMV预防措施（n = 21，CMV高效价免疫球蛋白[CMVIG]加四周静脉注射更昔洛韦，随后两个月口服缬更昔洛韦）与标准预防措施（n = 45，静脉注射更昔洛韦四周）。预防措施基于移植前供体（D）和受者（R）的CMV血清学检查：R-/D+接受积极预防；R+接受标准预防。观察指标包括：通过外周血多形核白细胞的DNA聚合酶链反应评估CMV感染、急性排斥反应以及通过血管内超声评估心脏移植血管病变（CAV）。所有患者均完成了一年的随访。结果：除四名患者（每组两名）外，所有患者的CMV感染均为亚临床感染。与标准预防组相比，接受积极治疗的患者CMV感染发生率较低（73±10%对94±4%；P = 0.038），且急性排斥反应分级≥3A的相对风险独立降低（相对风险[95%CI]=0.55[0.26 - 0.96]；P = 0.03）。积极预防的患者在冠状动脉管腔狭窄方面（管腔容积变化=-21±13%对-10±14%；P = 0.05）以及血管收缩方面（血管容积变化=-15±11%对-3±18%；P = 0.03），CAV的进展也较慢。
延长（缬）更昔洛韦加CMVIG可降低病毒水平、急性排斥反应和移植器官血管病变，提示慢性亚临床感染在影响心脏移植受者的最常见疾病的病理生理过程中发挥作用。
