Randomized Pilot Trial of Gene Expression Profiling Versus Heart Biopsy in the First Year After Heart Transplant

Abstract

Background-The endomyocardial biopsy (EMB) is considered the gold standard in rejection surveillance post cardiac transplant, but is invasive, with risk of complications. A previous trial suggested that the gene expression profiling (GEP) blood test was noninferior to EMB between 6 and 60 months post transplant. As most rejections occur in the first 6 months, we conducted a single-center randomized trial of GEP versus EMB starting at 55 days post transplant (when GEP is valid). Methods and Results-Sixty heart transplant patients meeting inclusion criteria were randomized beginning at 55 days post transplant to either GEP or EMB arms. A positive GEP ≥30 between 2 and 6 months, or ≥34 after 6 months, prompted a follow-up biopsy. The primary end point included a composite of death/retransplant, rejection with hemodynamic compromise or graft dysfunction at 18 months post transplant. A coprimary end point included change in first-year maximal intimal thickness by intravascular ultrasound, a recognized surrogate for long-term outcome. Corticosteroid weaning was assessed in both the groups. The composite end point was similar between the GEP and EMB groups (10% versus 17%; log-rank P=0.44). The coprimary end point of first-year intravascular ultrasound change demonstrated no difference in mean maximal intimal thickness (0.35±0.36 versus 0.36±0.26 mm; P=0.944). Steroid weaning was successful in both the groups (91% versus 95%). Conclusions-In this pilot study, GEP starting at 55 days post transplant seems comparable with EMB for rejection surveillance in selected heart transplant patients and does not result in increased adverse outcomes. GEP also seems useful to guide corticosteroid weaning. Larger randomized trials are required to confirm these findings. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00962377.

Clinical usefulness of gene-expression profile to rule out acute rejection after heart transplantation: CARGO II

“…The IMAGE 3 and E-IMAGE 24 studies have demonstrated that the number of surveillance biopsies was safely reduced while the clinical outcomes of patients managed with GEP surveillance were non-inferior to outcomes in patients managed with the biopsy strategy.…”

Acute cellular rejection later than one year after heart transplantation: A single‐center retrospective study at Skåne University Hospital in Lund 1988‐2010

“…We suggest these “high‐risk” patients should include, but not be limited to, sex‐mismatched recipients and those with first‐year ACR, as indicated by our findings. Patients who do not qualify as “high risk” could instead be considered for novel noninvasive genomic surveillance for ACR such as gene expression profiling (GEP; AlloMap ® : CareDx, Brisbane, CA, USA), which has shown able to reliably rule out severe ACR in asymptomatic “low‐risk” patients later than 6 months post‐HT, and possibly even earlier than that …”

The AlloMap™ genomic biomarker story: 10 years after

“…While the IMAGE study design decision allowed/necessitated the redefinition of rejection, it also motivated the Early‐IMAGE (E‐IMAGE) study that confirmed the early CARGO study results of AlloMap use in the period between day 56 and 180 post‐heart transplantation …”

“…E-IMAGE also confirmed early observations by the CARGO investigators of the safety of immunosuppression (prednisone) weaning using AlloMap as guidance in the period between day 56 and 180 postheart transplantation. 28…”