Evaluation of Myocardial Gene Expression Profiling for Superior Diagnosis of Idiopathic Giant-Cell Myocarditis and Clinical Feasibility in a Large Cohort of Patients with Acute Cardiac Decompensation.

Autor: Escher F; Institute of Cardiac Diagnostics and Therapy, IKDT GmbH, 12203 Berlin, Germany.; Department of Cardiology, Charité-University Medicine Berlin, Campus Virchow-Klinikum, 13353 Berlin, Germany.; German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany., Pietsch H; Institute of Cardiac Diagnostics and Therapy, IKDT GmbH, 12203 Berlin, Germany.; Department of Cardiology, Charité-University Medicine Berlin, Campus Virchow-Klinikum, 13353 Berlin, Germany.; German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany., Aleshcheva G; Institute of Cardiac Diagnostics and Therapy, IKDT GmbH, 12203 Berlin, Germany., Wenzel P; University Medical Center Mainz, Department of Cardiology and Center for Thrombosis and Haemostasis, 55131 Mainz, Germany., Fruhwald F; Department of Internal Medicine, Division of Cardiology, Medical University Graz, 8036 Graz, Austria., Stumpf C; Department of Cardiology, Klinikum Bayreuth GmbH, Medical Clinic II, 95445 Bayreuth, Germany., Westermann D; University Heart Center Hamburg, Department of Internal Medicine and Interventional Cardiology, 20251 Hamburg, Germany., Bauersachs J; Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany., Enseleit F; Department of Cardiology, University Hospital Zurich, 8091 Zurich, Switzerland., Ruschitzka F; Department of Cardiology, University Hospital Zurich, 8091 Zurich, Switzerland., Nägele H; Department for Cardiac Insufficiency and Device Therapy, Albertinen-Hospital, 22457 Hamburg, Germany., Laugwitz KL; Department of Cardiology, Klinikum rechts der Isar, 81675 Munich, Germany., Haake H; Department of Cardiology, Electrophysiology and Intensive Care Medicine, Kliniken Maria Hilf GmbH, 41063 Monchengladbach, Germany., Frey N; Department of Internal Medicine III-Cardiology, Angiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, 24105 Kiel, Germany., Brachmann J; Department of Internal Medicine, Division of Cardiology, Clinical Center Coburg, 96450 Coburg, Germany., Huber K; 3rd Medical Department with Cardiology, Wilhelminenhospital Vienna, 1160 Vienna, Austria., Braun-Dullaeus RC; Department of Cardiology und Angiology, University Magdeburg, 39106 Magdeburg, Germany., Bergmann MW; Cardiologicum Hamburg Wandsbek, 22041 Hamburg, Germany., Strotmann J; Department of Cardiology, Städtisches Krankenhaus Kiel GmbH, 24116 Kiel, Germany., Grönefeld G; Department of Cardiology, Asklepios Klinik Barmbek, 22307 Hamburg, Germany., Krülls-Münch J; Department of Cardiology and Angiology, Carl-Thiem-Klinikum Cottbus gGmbH, 03048 Cottbus, Germany., Westenfeld R; Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany., Skurk C; German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany.; Department of Cardiology Charité-University Medicine Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany., Landmesser U; German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany.; Department of Cardiology Charité-University Medicine Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany., Pieske B; Department of Cardiology, Charité-University Medicine Berlin, Campus Virchow-Klinikum, 13353 Berlin, Germany.; German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany., Gross UM; Institute of Cardiac Diagnostics and Therapy, IKDT GmbH, 12203 Berlin, Germany., Morawietz L; Institute of Cardiac Diagnostics and Therapy, IKDT GmbH, 12203 Berlin, Germany., Schultheiss HP; Institute of Cardiac Diagnostics and Therapy, IKDT GmbH, 12203 Berlin, Germany.
Jazyk: angličtina
Zdroj: Journal of clinical medicine [J Clin Med] 2020 Aug 19; Vol. 9 (9). Date of Electronic Publication: 2020 Aug 19.
DOI: 10.3390/jcm9092689
Abstrakt: 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.
Competing Interests: None declared.
Databáze: MEDLINE