Cardiac allograft vasculopathy (CAV) is the major cause of long-term graft failure in heart transplant recipients. Although several immune-mediated and metabolic risk factors have been implicated in the pathogenesis of CAV, no effective therapy is currently available to treat established CAV and prevent its adverse outcomes. Therefore, the main clinical strategy is based on prevention and treatment of factors known to trigger its development. Although the mechanism is vague, cytomegalovirus (CMV) infection is believed to play a key role in CAV progression.

Two strategies involving administration of specific anti-CMV agents are recommended for prevention of CMV infection/disease: universal prophylaxis and preemptive therapy. The pros and cons of the two strategies are still debated, in the absence of randomized studies addressing graft-related outcomes and viral mechanisms of graft damage, and without any clear evidence of superiority of either approach.

The investigators conceived this randomized prospective project to compare the effect of preemptive anti-CMV strategy with universal anti-CMV prophylaxis on CMV infection and on one-year increase in coronary intimal thickening. Patients will be additionally randomized to receive either mycophenolate mofetil or everolimus, in light of the possible anti-CMV properties of everolimus.

Inclusion Criteria:

• Age ≥ 18y
• Heart or heart-kidney combined transplant
• Positive CMV serology at the time of transplant
• Glomerular filtration rate ≥ 20 ml/min/1.73m2 with MDRD at randomization.
• Written informed consent

Exclusion Criteria:

• Panel Reactive Antibody ≥50%
• Less than 1000/mmc neutrophils at the time of randomization
• Less than 30,000/mmc platelets at the time of randomization
• Clinical significant infection in the 2 weeks prior to transplant
• Glomerular filtration rate < 20 ml/min/1.73m2 estimated with MDRD formula at the time of randomization or hemodialysis treatment
• Intolerance towards valganciclovir, everolimus, mycophenolate or cyc-losporine
• Known contraindication to statin use
• Negative CMV serology at the time of transplant
• HIV positive testing
• Severe comorbidities that, based on investigator's judgment, contraindicate study drugs or procedures
• Potentially childbearing women who refuse to use contraceptives
• Participation to an interventional study in the 2 preceding weeks
• Unwillingness or inability to follow study procedure and to sign written in-formed consent