Donate Help Contact The AHA Sign In Home
American Heart Association
Circulation
Search: search_blue_button Advanced Search
Circulation. 2008;118:238-246
Published online before print June 30, 2008, doi: 10.1161/CIRCULATIONAHA.107.756544
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
118/3/238    most recent
CIRCULATIONAHA.107.756544v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Heidecker, B.
Right arrow Articles by Hare, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Heidecker, B.
Right arrow Articles by Hare, J. M.
Related Collections
Right arrow Clinical genetics
Right arrow Other heart failure
Right arrow Congestive
Right arrow Gene expression
Right arrow Genomics
Right arrow Heart failure - basic studies
Right arrow Physiological and pathological control of gene expression
Right arrow Gene therapy
Right arrow Genetics of cardiovascular disease

(Circulation. 2008;118:238-246.)
© 2008 American Heart Association, Inc.


Heart Failure

Transcriptomic Biomarkers for Individual Risk Assessment in New-Onset Heart Failure

Bettina Heidecker, MD; Edward K. Kasper, MD; Ilan S. Wittstein, MD; Hunter C. Champion, MD, PhD; Elayne Breton, RN; Stuart D. Russell, MD; Michelle M. Kittleson, MD, PhD; Kenneth L. Baughman, MD; Joshua M. Hare, MD

From the University of Miami (B.H., J.M.H.), Miller School of Medicine, Miami, Fla; The Johns Hopkins Hospital (E.K.K., I.S.W., H.C.C., E.B., S.D.R.), Baltimore, Md; University of California, Los Angeles (M.M.K.); and Brigham and Women’s Hospital (K.L.B.), Boston, Mass.

Correspondence to Joshua M. Hare, MD, Miller School of Medicine, University of Miami Division of Cardiology, CRB, 1120 NW 14th St, Suite 1124, Miami, FL 33136. E-mail jhare{at}med.miami.edu

Received December 3, 2007; accepted April 28, 2008.

Background— Prediction of prognosis remains a major unmet need in new-onset heart failure (HF). Although several clinical tests are in use, none accurately distinguish between patients with poor versus excellent survival. We hypothesized that a transcriptomic signature, generated from a single endomyocardial biopsy, could serve as a novel prognostic biomarker in HF.

Methods and Results— Endomyocardial biopsy samples and clinical data were collected from all patients presenting with new-onset HF from 1997 to 2006. Among a total of 350 endomyocardial biopsy samples, 180 were identified as idiopathic dilated cardiomyopathy. Patients with phenotypic extremes in survival were selected: good prognosis (event-free survival for at least 5 years; n=25) and poor prognosis (events [death, requirement for left ventricular assist device, or cardiac transplant] within the first 2 years of presentation with HF symptoms; n=18). We used human U133 Plus 2.0 microarrays (Affymetrix) and analyzed the data with significance analysis of microarrays and prediction analysis of microarrays. We identified 46 overexpressed genes in patients with good versus poor prognosis, of which 45 genes were selected by prediction analysis of microarrays for prediction of prognosis in a train set (n=29) with subsequent validation in test sets (n=14 each). The biomarker performed with 74% sensitivity (95% CI 69% to 79%) and 90% specificity (95% CI 87% to 93%) after 50 random partitions.

Conclusions— These findings suggest the potential of transcriptomic biomarkers to predict prognosis in patients with new-onset HF from a single endomyocardial biopsy sample. In addition, our findings offer potential novel therapeutic targets for HF and cardiomyopathy.


 

CLINICAL PERSPECTIVE




This article has been cited by other articles:


Home page
CirculationHome page
R. Sarwar and S. A. Cook
Genomic Analysis of Left Ventricular Remodeling
Circulation, August 4, 2009; 120(5): 437 - 444.
[Full Text] [PDF]


Home page
Brief BioinformHome page
F. Azuaje, Y. Devaux, and D. Wagner
Computational biology for cardiovascular biomarker discovery
Brief Bioinform, July 1, 2009; 10(4): 367 - 377.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
K. B. Margulies, D. P. Bednarik, and D. L. Dries
Genomics, transcriptional profiling, and heart failure.
J. Am. Coll. Cardiol., May 12, 2009; 53(19): 1752 - 1759.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
S. J. Matkovich, D. J. Van Booven, K. A. Youker, G. Torre-Amione, A. Diwan, W. H. Eschenbacher, L. E. Dorn, M. A. Watson, K. B. Margulies, and G. W. Dorn II
Reciprocal Regulation of Myocardial microRNAs and Messenger RNA in Human Cardiomyopathy and Reversal of the microRNA Signature by Biomechanical Support
Circulation, March 10, 2009; 119(9): 1263 - 1271.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
W.H. W. Tang and G. S. Francis
The Year in Heart Failure
J. Am. Coll. Cardiol., November 11, 2008; 52(20): 1671 - 1678.
[Full Text] [PDF]


Home page
CirculationHome page
G. W. Dorn II and S. J. Matkovich
Put Your Chips on Transcriptomics
Circulation, July 15, 2008; 118(3): 216 - 218.
[Full Text] [PDF]