Performance of gene-expression profiling test score variability to predict future clinical events in heart transplant recipients

BMC Cardiovascular Disorders

Johan Vanhaecke⁷  James P. Yee³  Emir Deljkich³  Lane Eubank³  David Hiller³  Pascal Leprince^1,11  Mario Deng⁶  Daniel Hoefer^1,12  Roberto Fiocchi^1,13  Michal Zakliczyński^1,14  Jayan Parameshwar⁹  Heather Ross²  Christoph Bara^1,10  Paul Mohacsi⁴  Andreas Zuckermann⁸  Uwe Schulz¹  Jörg Stypmann^1,15  Maria G. Crespo-Leiro⁵ 

[1]Ruhr University of Bochum, Bad Oeynhausen, Germany

[2]Toronto General Hospital, Toronto, Canada

[3]CareDx, Brisbane, USA

[4]University Hospital Bern, Bern, Switzerland

[5]Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS. Universidade da Coruña (UDC), Coruña, Spain

[6]David Geffen School of Medicine, University of California, Los Angeles, USA

[7]Department of Cardiology, Herestraat 49, Leuven, 3000, Belgium

[8]Medical University of Vienna, Vienna, Austria

[9]Papworth Hospital, Papworth Everard, Cambridge, UK

[10]Hannover Medical School, Hannover, Germany

[11]Groupe Hospitalier Pitié-Salpêtrière, Paris, France

[12]Innsbruck Medical University, Innsbruck, Austria

[13]Ospedali Riuniti di Bergamo, Bergamo, Italy

[14]Silesian Center for Heart Disease, Zabrze, Poland

[15]University Hospital Muenster, Muenster, Germany

关键词: Gene expression profiling score;    AlloMap score variability;    Acute cellular rejection;    Surveillance of cardiac recipients;    AlloMap;    Gene expression profiling;    Heart transplant;   

Others  :  1229137
DOI  :  10.1186/s12872-015-0106-1

 received in 2015-07-02, accepted in 2015-09-21,  发布年份 2015

【 摘 要 】

Background

A single non-invasive gene expression profiling (GEP) test (AlloMap®) is often used to discriminate if a heart transplant recipient is at a low risk of acute cellular rejection at time of testing. In a randomized trial, use of the test (a GEP score from 0–40) has been shown to be non-inferior to a routine endomyocardial biopsy for surveillance after heart transplantation in selected low-risk patients with respect to clinical outcomes. Recently, it was suggested that the within-patient variability of consecutive GEP scores may be used to independently predict future clinical events; however, future studies were recommended. Here we performed an analysis of an independent patient population to determine the prognostic utility of within-patient variability of GEP scores in predicting future clinical events.

Methods

We defined the GEP score variability as the standard deviation of four GEP scores collected ≥315 days post-transplantation. Of the 737 patients from the Cardiac Allograft Rejection Gene Expression Observational (CARGO) II trial, 36 were assigned to the composite event group (death, re-transplantation or graft failure ≥315 days post-transplantation and within 3 years of the final GEP test) and 55 were assigned to the control group (non-event patients). In this case-controlled study, the performance of GEP score variability to predict future events was evaluated by the area under the receiver operator characteristics curve (AUC ROC). The negative predictive values (NPV) and positive predictive values (PPV) including 95 % confidence intervals (CI) of GEP score variability were calculated.

Results

The estimated prevalence of events was 17 %. Events occurred at a median of 391 (inter-quartile range 376) days after the final GEP test. The GEP variability AUC ROC for the prediction of a composite event was 0.72 (95 % CI 0.6-0.8). The NPV for GEP score variability of 0.6 was 97 % (95 % CI 91.4-100.0); the PPV for GEP score variability of 1.5 was 35.4 % (95 % CI 13.5-75.8).

Conclusion

In heart transplant recipients, a GEP score variability may be used to predict the probability that a composite event will occur within 3 years after the last GEP score.

Trial registration

Clinicaltrials.gov identifier NCT00761787

【 授权许可】

   
2015 Crespo-Leiro et al.

【 图 表 】

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