Outcomes AlloMap Registry: the Long-term Management and Outcomes of Heart Transplant Recipients With AlloMap Testing

The standard of care in adult heart transplant recipients has been to perform periodic
endomyocardial biopsies for surveillance for rejection. Because of the risks and discomforts
associated with the biopsy procedure, a non-invasive test (AlloMap) based on gene-expression
profiling of peripheral blood was developed and introduced in 2005 to identify heart
transplant recipients who have a low probability of rejection at the time of protocol
surveillance testing. The schedule of AlloMap surveillance testing has been derived from the
customary timing of surveillance biopsies: e.g. at 1 to 2 month intervals for patients who
are 6 and 12 post-transplantation, and at 3, 4 or 6 months after the first year
post-transplantation.

In the large multicenter IMAGE (Invasive Monitoring Attenuation by Gene Expression Profiling)
602 patients in the United States who had undergone cardiac transplantation at least 6 months
prior were randomized 1:1 to either surveillance with routine biopsy or AlloMap testing.
Patients in both groups were also monitored with echocardiography. A primary outcome event
was defined as an episode of rejection with hemodynamic compromise, graft dysfunction due to
other causes, death or retransplantation. Over a median follow-up period of 19 months, 297
patients who were monitored with AlloMap and 305 patients who underwent routine biopsies had
similar 2-year cumulative rates of events (14.5% and 15.3%, respectively; hazard ratio with
gene-expression profiling, 1.04; 95% confidence interval, 0.67 to 1.68).

This Outcomes AlloMap Registry (OAR) study is designed to collect similar clinical outcomes
information as studied in IMAGE, in a larger cohort of patients (approximately 2000) followed
for up to 5 years. At each routine clinic visit, key clinical features such as rejection
surveillance management schedules, testing results (e.g. blood levels of immunosuppressive
agents), and AlloMap scores will be collected. This larger and longer term follow-up dataset
is intended to enable further elucidation, through analyses techniques such as multivariate
Cox proportional hazards models, of the surveillance management features which may be
associated or contribute to the most favorable long term outcomes of the heart recipients.

Inclusion Criteria:

- New and existing heart transplant recipients ≥ 2 months (≥ 55 days) post-transplant
receiving post-transplant care at the enrolling centers for interim surveillance
monitoring that includes AlloMap testing