Recent Advances in Molecular Diagnostics and Treatment of Heart Muscle Diseases

Abstract

<p align="justify"> <span style="font-family:Verdana;">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</span><span> </span><span style="font-family:Verdana;">information allow</span><span style="font-family:Verdana;">s</span><span style="font-family:Verdana;"> 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</span><span> </span><span style="font-family:Verdana;">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</span><span> </span><span style="font-family:Verdana;">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</span><span> </span><span style="font-family:Verdana;">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.</span><span> </span><span style="font-family:Verdana;">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.</span> </p

Myocarditis—Personalized Medicine by Expanded Endomyocardial Biopsy Diagnostics

“…Invasive removal of a sufficient number of tissue samples by EMB is always necessary when an exact diagnosis cannot be obtained by other clinical methods and is influencing the following treatment [26] [58]. The use of LV EMB to investigate cardiomyopathies is currently discouraged because it is considered riskier than and as contributive as RV biopsy.…”

“…Additionally, with varying degrees of frequency distinct genotypes of erythroviruses including parvovirus B19 (B19V), human herpesvirus type 6 (HHV6A/B) and its chromosomally integrated form (ciHHV6 A/B), HIV, cytomegalovirus (CMV), herpes simplex type 2 virus, Epstein-Barr virus (EBV) and hepatitis C virus, among many others, have been identified in cardiac tissues [26]- [29].…”

“…As the pathophysiological changes of infectious and non-infectious myocarditis occur at a cellular and subcellular level, confirmation of a specific pathogen or inflammation requires a direct examination of myocardial tissue, which can be obtained without problems by means of a biopsy [26] [44]. In terms of therapeutic considerations it needs to be taken into account that a positive treatment effect will occur only if treatable causes such as viral infections, inflammatory processes, or cardiodepressive autoantibodies are present and the myocardium still has regenerative potential [4].…”

“…Storage disorders such as amyloidosis [26] [59], iron deposits, glycogen and others can be excluded or specified by additional staining, e.g., immunohistochemical differentiation of amyloid subtypes and optional electron microscopical analyses. The EMB diagnosis of myocarditis was based on histomorphological criteria according to the Dallas classification [26] [60].…”

“…Routine immunohistochemical diagnostics are based on the application of antibody-supported detection of inflammatory infiltrates (lymphocytes, macrophages, memory cells, B-cells ) and enhanced expression of tissue activation marker like adhesion molecules (HLA, ICAM, VCAM) or fibrotic proteins like collagens on cryofixed tissue section, following quantitative digital imaging analysis [26] [61] [62].…”