Transcriptomic biomarkers for the accurate diagnosis of myocarditis

Bettina Heidecker, Michelle M. Kittleson, Edward K. Kasper, Ilan S. Wittstein, Hunter C. Champion, Stuart D. Russell, Ralph H. Hruban, E. Rene Rodriguez, Kenneth L. Baughman, Joshua Hare

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Background-: Lymphocytic myocarditis is a clinically important condition that is difficult to diagnose and distinguish. We hypothesized that the transcriptome obtained from an endomyocardial biopsy would yield clinically relevant and accurate molecular signatures. Methods and results-: Microarray analysis was performed on samples from patients with histologically proven lymphocytic myocarditis (n=16) and idiopathic dilated cardiomyopathy (n=32) to develop accurate diagnostic transcriptome-based biomarkers using multiple classification algorithms. We identified 9878 differentially expressed genes in lymphocytic myocarditis versus idiopathic dilated cardiomyopathy (fold change >1.2; false discovery rate <5%) from which a transcriptome-based biomarker containing 62 genes was identified that distinguished myocarditis with 100% sensitivity (95% confidence interval, 46 to 100) and 100% specificity (95% confidence interval, 66 to 100) and was generalizable to a broad range of secondary cardiomyopathies associated with inflammation (n=27), ischemic cardiomyopathy (n=8), and the normal heart (n=11). Multiple classification algorithms and quantitative real-time reverse-transcription polymerase chain reaction analysis further reduced this subset to a highly robust molecular signature of 13 genes, which still performed with 100% accuracy. CONCLUSIONS-: Together, these findings demonstrate that transcriptomic biomarkers from a single endomyocardial biopsy can improve the clinical detection of patients with inflammatory diseases of the heart. This approach advances the clinical management and treatment of cardiac disorders with highly variable outcome.

Original languageEnglish
Pages (from-to)1174-1184
Number of pages11
JournalCirculation
Volume123
Issue number11
DOIs
StatePublished - Mar 22 2011

Fingerprint

Myocarditis
Biomarkers
Transcriptome
Dilated Cardiomyopathy
Cardiomyopathies
Confidence Intervals
Genes
Biopsy
Microarray Analysis
Reverse Transcription
Heart Diseases
Inflammation
Polymerase Chain Reaction
Therapeutics

Keywords

  • biomarker
  • gene expression
  • gene microarray
  • heart failure
  • myocarditis

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Heidecker, B., Kittleson, M. M., Kasper, E. K., Wittstein, I. S., Champion, H. C., Russell, S. D., ... Hare, J. (2011). Transcriptomic biomarkers for the accurate diagnosis of myocarditis. Circulation, 123(11), 1174-1184. https://doi.org/10.1161/CIRCULATIONAHA.110.002857

Transcriptomic biomarkers for the accurate diagnosis of myocarditis. / Heidecker, Bettina; Kittleson, Michelle M.; Kasper, Edward K.; Wittstein, Ilan S.; Champion, Hunter C.; Russell, Stuart D.; Hruban, Ralph H.; Rodriguez, E. Rene; Baughman, Kenneth L.; Hare, Joshua.

In: Circulation, Vol. 123, No. 11, 22.03.2011, p. 1174-1184.

Research output: Contribution to journalArticle

Heidecker, B, Kittleson, MM, Kasper, EK, Wittstein, IS, Champion, HC, Russell, SD, Hruban, RH, Rodriguez, ER, Baughman, KL & Hare, J 2011, 'Transcriptomic biomarkers for the accurate diagnosis of myocarditis', Circulation, vol. 123, no. 11, pp. 1174-1184. https://doi.org/10.1161/CIRCULATIONAHA.110.002857
Heidecker B, Kittleson MM, Kasper EK, Wittstein IS, Champion HC, Russell SD et al. Transcriptomic biomarkers for the accurate diagnosis of myocarditis. Circulation. 2011 Mar 22;123(11):1174-1184. https://doi.org/10.1161/CIRCULATIONAHA.110.002857
Heidecker, Bettina ; Kittleson, Michelle M. ; Kasper, Edward K. ; Wittstein, Ilan S. ; Champion, Hunter C. ; Russell, Stuart D. ; Hruban, Ralph H. ; Rodriguez, E. Rene ; Baughman, Kenneth L. ; Hare, Joshua. / Transcriptomic biomarkers for the accurate diagnosis of myocarditis. In: Circulation. 2011 ; Vol. 123, No. 11. pp. 1174-1184.
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