Prophylaxis versus preemptive anti-cytomegalovirus approach for prevention of allograft vasculopathy in heart transplant recipients

J Heart Lung Transplant. 2009 May;28(5):461-7. doi: 10.1016/j.healun.2009.02.009.

Abstract

Background: Cytomegalovirus (CMV) infection may influence the development of cardiac allograft vasculopathy (CAV). Prophylactic or preemptive administration of anti-CMV agents effectively prevents acute CMV manifestations. However, studies comparing allograft-related outcomes between these anti-CMV approaches are lacking. Herein we report a longitudinal observational study comparing CAV development between prophylactic and preemptive approaches.

Methods: The 1-year change in maximal intimal thickening (MIT) assessed by intravascular ultrasound at 1 and 12 months after heart transplantation (the major surrogate for late survival) was compared in groups of patients routinely assigned to a preemptive strategy (from November 2004 to October 2005; n = 21) or receiving valganciclovir prophylaxis (from November 2005 to October 2006; n = 19). CMV infection was monitored with pp65 antigenemia.

Results: The 1-year increase in MIT was significantly lower in patients receiving prophylaxis compared with those managed preemptively (0.15 +/- 0.17 vs 0.31 +/- 0.20 mm; p = 0.01). Prophylaxed recipients presented less frequently with MIT change > or =0.3 mm (p = 0.03) and > or =0.5 mm (p = 0.10) than those managed preemptively. Prophylaxis was also associated with later onset of CMV infection (p = 0.01), lower peak CMV detection (p < 0.01) and reduced incidence of CMV disease/syndrome (p = 0.04). After adjusting for metabolic risk factors and other possible confounders, prophylaxis remained independently associated with lower risk for MIT change > or =0.3 mm (odds ratio = 0.09, 95% confidence interval 0.01 to 0.93; p = 0.04).

Conclusions: Universal prophylaxis was associated with delayed onset of CMV infection, lower viral burden, reduced CMV disease/syndrome and less intimal thickening, as compared with a preemptive anti-CMV approach. Randomized studies are required to confirm the potential benefits of prophylaxis vs a preemptive approach in heart transplant recipients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Cohort Studies
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / etiology
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / prevention & control*
  • Coronary Stenosis / diagnostic imaging
  • Coronary Stenosis / etiology
  • Coronary Stenosis / mortality
  • Coronary Stenosis / prevention & control
  • Cytomegalovirus Infections / complications*
  • Cytomegalovirus Infections / diagnostic imaging
  • Cytomegalovirus Infections / drug therapy*
  • Cytomegalovirus Infections / mortality
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Ganciclovir / adverse effects
  • Ganciclovir / therapeutic use*
  • Heart Transplantation*
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use
  • Infusions, Intravenous
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Phosphoproteins / blood
  • Postoperative Complications / diagnostic imaging
  • Postoperative Complications / etiology
  • Postoperative Complications / mortality
  • Postoperative Complications / prevention & control*
  • Prospective Studies
  • Risk Factors
  • Survival Analysis
  • Ultrasonography, Interventional
  • Viral Load
  • Viral Matrix Proteins / blood

Substances

  • Antiviral Agents
  • Immunosuppressive Agents
  • Phosphoproteins
  • Viral Matrix Proteins
  • cytomegalovirus matrix protein 65kDa
  • Ganciclovir