Diagnostic transcriptomic biomarkers in inflammatory cardiomyopathies

Abstract

Molecular signatures that function as very sensitive diagnostic biomarker for myocarditis, heart disease and disorders thereof, are identified.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]The present application claims the priority of U.S. provisional patent application No. 61 / 183,306 filed Jun. 2, 2009, which is incorporated herein by reference in its entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH[0002]This invention was made with U.S. government support under grant numbers U54-HL081028 (Specialized Center for Cell Based Therapy) and R01s HL084275, AG025017, HL065455, and HL094849, which were awarded by the National Institutes of Health. The U.S. government may have certain rights in the invention,FIELD OF THE INVENTION[0003]This invention relates to biomarkers of heart disease, myocarditis, novel drug therapeutic targets, compositions and methods of predicting, diagnosing and treating heart diseases and related disorders thereof. More specifically, the invention concerns methods and compositions based on unique molecular signatures associated with various aspects of cardiac diseases and disorders.BACKGROUND[00...

AI Technical Summary

Problems solved by technology

Myocarditis can be difficult to diagnose requiring multiple endomyocardial biopsies (EMBs).

Even with multiple biopsies, consensus among pathologists has been difficult to attain.

In a previous decision analysis investigating the value of EMBs to improve clinical outcome with specific therapy, histological inaccuracy was a major limiting factor for efficacy of treatment.

In addition, the important subtypes of myocarditis have highly distinct outcomes, require markedly different therapeutic strategies, and can be difficult to distinguish based on standard histopathology.

The screening may be done, for example, either because the compound is designed to have a pharmacological effect on certain cell types, or because a compound designed to have effects elsewhere may have unintended side effects.

However, none of them were able to detect KRT78 in any of the samples.

Distinction of inflammatory as compared to non-inflammatory cardiomyopathies by standard histology has, prior to this study, represented a major diagnostic challenge.

Moreover, delineating between different inflammatory cardiomyopathies with highly variable clinical courses has been, prior to this study, an even more challenging task.

Inflammatory disorders of the heart have been, prior to this study, notoriously difficult to diagnose due to the patchy nature of the inflammation.

Interestingly, classification of peripartum cardiomyopathy was less accurate, most likely because of multiple factors interacting in this type of disease, ranging from nonspecific changes such as replacement fibrosis to lymphocytic infiltration.

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