IMAGE: A Comparison of AlloMap Molecular Testing and Traditional Biopsy-based Surveillance for Heart Transplant Rejection

Inclusion Criteria:

   1. Heart transplant recipients who are > 6 months to 5 years (> 6-60 months)
   post-transplant.

   2. Age ≥ 18 years.

   3. Stable outpatient being seen for routine monitoring of rejection. Stability is defined
   as absence of prior or current evidence of either severe cardiac allograft
   vasculopathy (CAV) or antibody-mediated rejection (AMR) with associated hemodynamic
   compromise.

      1. Severe CAV is defined as either

         - > 50% left main stenosis;

         - ≥ 50% stenosis in ≥ 2 primary vessels (proximal 1/3 or middle 1/3 of the LAD
         or LCx, RCA to takeoff of PDA in right-dominant coronary circulations) or

         - Isolated branch stenoses of > 50% in all 3 systems (diagonal branches,
         obtuse marginal branches, distal 1/3 of LAD or LCx, PDA, PLB, and RCA to
         takeoff of PDA in non-dominant systems).

      2. AMR with associated hemodynamic compromise is defined as AMR (defined according
      to local criteria) with either

         - A left ventricular ejection fraction (LVEF) ≤ 30% or at least 25% lower than
         the baseline value,

         - A cardiac index < 2 l/min/m2, or

         - The use of inotropic agents to support circulation.

   4. Left ventricular ejection fraction ≥ 45% by Echocardiography, Multiple Gated
   Acquisition (MUGA) scan, or ventriculography at study entry (baseline / enrollment
   study).

Exclusion Criteria:

   1. Patients < 7 calendar months after heart transplantation.

   2. Any clinical signs of declining graft function:

      1. Symptoms of Congestive Heart Failure (CHF) at the enrollment visit.

      2. Signs of decompensated heart failure, including the development of a new S3
      gallop at the enrollment visit.

      3. Elevated right heart pressures with diminished cardiac index < 2.2 L/min/m2 that
      is new compared to a previous measurement within 6 months.

      4. Decrease in LVEF as measured by echocardiography: ≥ 25% compared to prior
      measurement within 6 months.

   3. Rejection therapy for biopsy-proven ISHLT Grade 3A or higher during the preceding 2
   months.

   4. Major changes in immunosuppression therapy within previous 30 days (e.g.,
   discontinuation of calcineurin inhibitors, switch from mycophenolate mofetil to
   sirolimus or vice versa).

   5. Unable to give written informed consent.

   6. Patient receiving hematopoietic growth factors (e.g., Neupogen, Epogen) currently or
   during the previous 30 days.

   7. Patients receiving ≥ 20 mg/day of prednisone equivalent corticosteroids at the time of
   enrollment.

   8. Patient enrolled in a trial requiring routine surveillance endomyocardial biopsies.

   9. Patient received transfusion within preceding 4 weeks.

10. Patients with end-stage renal disease requiring some form of renal replacement therapy
   (hemodialysis or peritoneal dialysis).

11. Pregnancy at the time of enrollment.