557 C ardiac allograft rejection is experienced by 20% to 50% of patients at least once during the first year after cardiac transplantation, with the highest incidence of acute cellular rejection occurring in the first 6 months. 1 Endomyocardial biopsy (EMB) is currently acknowledged as the gold standard in monitoring rejection status post cardiac transplantation. 2 However, EMB has potential for serious complications and is invasive and resource-intensive. Clinical Perspective on p 564 Immediate complications of EMB can include access site hematoma, transient arrhythmias, right bundle branch block, occult pulmonary embolism, and cardiac tamponade secondary to myocardial perforation. 3 Longer-term compli- cations include chronic tricuspid regurgitation (sometimes requiring valve replacement) and more rarely, coronary artery to right ventricular fistula. 4 Deaths as a direct conse- quence of EMB, although rare, have even been reported. 5 Alternative noninvasive methods of rejection surveil- lance have been pursued. These noninvasive methods have included echocardiography, cardiac magnetic resonance and molecular imaging, specific electrophysiological markers, and peripheral blood analysis. 6 These noninvasive tests are based on either detection of myocardial injury (myocardial edema) or upregulation of the immune system. However, none of these tests have demonstrated sufficient reliabil- ity to replace the EMB. Peripheral blood analysis seems the most promising and specific, and is the only noninva- sive surveillance method recommended in the most recent International Society for Heart and Lung Transplantation (ISHLT) guidelines. 1 Gene expression profiling (GEP) with the AlloMap blood test (CareDx Inc, Brisbane, CA) is based on the analysis of peripheral blood mononuclear cell RNA with a multigene algorithm that uses 20 genes (11 informative and 9 controls) as a means of detecting rejection. The 11 informative genes Original Article © 2015 American Heart Association, Inc. Circ Heart Fail is available at http://circheartfailure.ahajournals.org DOI: 10.1161/CIRCHEARTFAILURE.114.001658 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. (Circ Heart Fail. 2015;8:557-564. DOI: 10.1161/CIRCHEARTFAILURE.114.001658.) Key Words: cardiac transplantation ■ gene-expression profiling ■ graft rejection Received July 25, 2014; accepted February 13, 2015. From the Advanced Heart Disease Section, Cedars-Sinai Heart Institute, Los Angeles, CA. Correspondence to Jon Kobashigawa, MD, Cedars-Sinai Heart Institute, 127 S. San Vicente Blvd, Los Angeles, CA 90048. E-mail Kobashigawaj@cshs.org Randomized Pilot Trial of Gene Expression Profiling Versus Heart Biopsy in the First Year After Heart Transplant Early Invasive Monitoring Attenuation Through Gene Expression Trial Jon Kobashigawa, MD; Jignesh Patel, MD, PhD; Babak Azarbal, MD; Michelle Kittleson, MD, PhD; David Chang, MD; Lawrence Czer, MD; Tiffany Daun, RN; Minh Luu, MBBS; Alfredo Trento, MD; Richard Cheng, MD; Fardad Esmailian, MD