Recent Advances in Molecular Diagnostics and Treatment of Heart Muscle Diseases

Abstract

Cardiomyopathies are acute or chronic disorders of myocardium. Diagnostic characterization of disease entities demands endomyocardial biopsy analyses with histological, immunohistochemical and molecular biological tissue evaluations to establish a final diagnosis. Only such biopsy-based information allows so far a specific treatment of distinct cardiomyopathy subgroups. In order to reduce sampling error, tissue specimens have to be obtained and analyzed to get clinically relevant data for specific treatment options. Specific gene expression and microRNA (miRNAs) profiles as well as genetic markers add additional valuable information which not only reduce the sampling error but also improve patient management. Advantages of such biomarkers result from their general expression within the entire altered myocardium. Thus, obtained information does not depend on small tissue areas reached by biopsy. This very fact allows prediction of a myocardial infection even in virus-negative areas adjoining positive biopsy specimen. The combination of multiple deregulated miRNAs or genes into one disease specific diagnostic profile demands the integration of new profiling technologies in the routine workflows of cardiological laboratories. In future, multiplex approaches allowing rapid and absolutely reliable identification of inflammatory or virally-induced myocardial diseases will replace singleplex methods such as direct detection of viral genomes in one single biopsy. miRNAs are stable biomarkers which are not only detectable in tissue samples but also in body fluids. Consequently, the determination of distinct miRNA patterns in e.g. peripheral blood samples will provide a systemic diagnostic approach for the characterization of distinct cardiomyopathies by means of non-invasive methods. This will reduce the number of undiagnosed patients who have to undergo endomyocardial biopsy for final confirmation of their myocardial complaints. The resulting molecular diagnostics will pave the way from biopsy focused interpretation to systemic analysis of cardiomyopathies. To reach this goal, the set-up of modern diagnostics harks back to the broad portfolio of high-end analytical techniques and tools.