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Transcriptomic Biomarkers for the Accurate Diagnosis of Myocarditis
Study Questions:
Does the transcriptome obtained from an endomyocardial biopsy yield clinically relevant and accurate molecular signatures for diagnosis of lymphocytic myocarditis?
Methods:
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. Validation with real-time reverse-transcription polymerase chain reaction (RT-PCR) was performed in a randomly selected subset of patients.
Results:
The investigators identified 9,878 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, 46-100) and 100% specificity (95% confidence interval, 66-100), 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 RT-PCR analysis further reduced this subset to a highly robust molecular signature of 13 genes, which still performed with 100% accuracy.
Conclusions:
The authors concluded that transcriptomic biomarkers from a single endomyocardial biopsy can improve the clinical detection of patients with inflammatory diseases of the heart.
Perspective:
This study suggests that both the transcriptomic biomarker derived from prediction analysis of microarrays analysis and the parsimonious molecular signature that resulted from multiple classification algorithms and testing for biological plausibility performed highly accurately and should be clinically valuable tools for the detection of myocarditis. Although the more comprehensive biomarker of 62 genes performed with slightly higher accuracy, the 13-gene molecular signature is more practical for clinical application. The transcriptomic approach, coupled with the use of highly specific imaging techniques, might enhance diagnostic accuracy of myocarditis, but requires further independent validation in larger cohorts.
Keywords: Transcriptome, Inflammation, Biomarkers, Cardiomyopathies, Biopsy, Heart Failure, Myocarditis
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