Abstract
Aims: The diagnostic approach to idiopathic giant-cell myocarditis (IGCM) is based on identifying various patterns of inflammatory cell infiltration and multinucleated giant cells (GCs) in histologic sections taken from endomyocardial biopsies (EMBs). The sampling error for detecting focally located GCs by histopathology is high, however. The aim of this study was to demonstrate the feasibility of gene profiling as a new diagnostic method in clinical practice, namely in a large cohort of patients suffering from acute cardiac decompensation. Methods and Results: In this retrospective multicenter study, EMBs taken from n = 427 patients with clinically acute cardiac decompensation and suspected acute myocarditis were screened (mean age: 47.03 ± 15.69 years). In each patient, the EMBs were analyzed on the basis of histology, immunohistology, molecular virology, and gene-expression profiling. Out of the total of n = 427 patient samples examined, GCs could be detected in 26 cases (6.1%) by histology. An established myocardial gene profile consisting of 27 genes was revealed; this was narrowed down to a specified profile of five genes (CPT1, CCL20, CCR5, CCR6, TLR8) which serve to identify histologically proven IGCM with high specificity in 25 of the 26 patients (96.2%). Once this newly established profiling approach was applied to the remaining patient samples, an additional n = 31 patients (7.3%) could be identified as having IGCM without any histologic proof of myocardial GCs. In a subgroup analysis, patients diagnosed with IGCM using this gene profiling respond in a similar fashion to immunosuppressive therapy as patients diagnosed with IGCM by conventional histology alone. Conclusions: Myocardial gene-expression profiling is a promising new method in clinical practice, one which can predict IGCM even in the absence of any direct histologic proof of GCs in EMB sections. Gene profiling is of great clinical relevance in terms of (a) overcoming the sampling error associated with purely histologic examinations and (b) monitoring the effectiveness of therapy.
Highlights
Cardiac inflammatory processes involving giant cells comprise a diverse group of disorders [1,2,3,4] Idiopathic giant-cell myocarditis (IGCM) is regarded as a distinct clinical and pathological entity having an exclusively cardiac manifestation
The main findings of this study are: (1) Of a selected panel of 27 genes previously identified to be regulated in patients with idiopathic giant-cell myocarditis (IGCM), five genes (CPT1, CCL20, chemokine receptor 5 (CCR5), chemokine receptor 6 (CCR6), toll-like receptor 8 (TLR8)) are highly specific for patients with IGCM compared with controls; (2) Our study suggests that by using this panel of five genes, 54.3% of all IGCM cases would have been missed by using conventional histologic examination alone; (3) Patients diagnosed with IGCM using this gene profile panel respond in a similar fashion to immunosuppressive therapy as patients diagnosed with IGCM by conventional histology alone, supporting the clinical utility of gene profiling in patients presenting with unexplained acute heart failure
Myocardial gene-expression profiling to diagnose IGCM was applied in clinical practice for the first time, namely within a large cohort of patients suffering from unexplained acute cardiac decompensation
Summary
Cardiac inflammatory processes involving giant cells comprise a diverse group of disorders [1,2,3,4] Idiopathic giant-cell myocarditis (IGCM) is regarded as a distinct clinical and pathological entity having an exclusively cardiac manifestation. This rapidly progressive disease is associated with myocyte necrosis and poor cardiac outcome [5,6]. Published studies have shown [10,11] that myocardial gene-expression profiling defines a distinct gene expression pattern which serves to indicate the presence of IGCM even without any histologic detection of GCs. Generally
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
