Gene-expression profiling for rejection surveillance after cardiac transplantation.
BACKGROUND
Endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardiac transplant. However, this procedure is uncomfortable, and there are risks associated with it. Gene-expression profiling of peripheral-blood specimens has been shown to correlate with the results of an endomyocardial biopsy.


METHODS
We randomly assigned 602 patients who had undergone cardiac transplantation 6 months to 5 years previously to be monitored for rejection with the use of gene-expression profiling or with the use of routine endomyocardial biopsies, in addition to clinical and echocardiographic assessment of graft function. We performed a noninferiority comparison of the two approaches with respect to the composite primary outcome of rejection with hemodynamic compromise, graft dysfunction due to other causes, death, or retransplantation.


RESULTS
During a median follow-up period of 19 months, patients who were monitored with gene-expression profiling and those who underwent routine biopsies had similar 2-year cumulative rates of the composite primary outcome (14.5% and 15.3%, respectively; hazard ratio with gene-expression profiling, 1.04; 95% confidence interval, 0.67 to 1.68). The 2-year rates of death from any cause were also similar in the two groups (6.3% and 5.5%, respectively; P=0.82). Patients who were monitored with the use of gene-expression profiling underwent fewer biopsies per person-year of follow-up than did patients who were monitored with the use of endomyocardial biopsies (0.5 vs. 3.0, P<0.001).


CONCLUSIONS
Among selected patients who had received a cardiac transplant more than 6 months previously and who were at a low risk for rejection, a strategy of monitoring for rejection that involved gene-expression profiling, as compared with routine biopsies, was not associated with an increased risk of serious adverse outcomes and resulted in the performance of significantly fewer biopsies. (ClinicalTrials.gov number, NCT00351559.)
Pham
Michael X
MX
Stanford University Medical Center, Stanford, California, USA.
Teuteberg
Jeffrey J
JJ
Kfoury
Abdallah G
AG
Starling
Randall C
RC
Deng
Mario C
MC
Cappola
Thomas P
TP
Kao
Andrew
A
Anderson
Allen S
AS
Cotts
William G
WG
Ewald
Gregory A
GA
Baran
David A
DA
Bogaev
Roberta C
RC
Elashoff
Barbara
B
Baron
Helen
H
Yee
James
J
Valantine
Hannah A
HA
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy / Q000009:adverse effects / Q000706:statistics & numerical data; D016001:Confidence Intervals; D004699:Endocardium / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006084:Graft Rejection / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D016027:Heart Transplantation / Q000401:mortality; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D012086:Reoperation; D015996:Survival Rate; D055815:Young Adult