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
Abstract
:1. Introduction
2. Patients and Methods
2.1. Patients
2.2. Analysis of Myocardial Morphology and Inflammation
2.3. Nucleic Acid Isolation, Reverse Transcription (RT) and nPCR for cDNA
2.4. Preamplification and Gene-Expression Analysis
2.5. Statistics
3. Results
3.1. Distinctive Myocardial Gene-Expression Profiles Which Serve to Identify IGCM
3.2. Application of IGCM-Specific Gene Profiling across the Entire Cohort of Patients with Acute Cardiac Decompensation
3.3. Immunohistologic Analysis of Intramyocardial Infiltration in GCM Patients
3.4. Correlation of Immunohistochemical Markers with Deregulated Genes
3.5. EMB-Based Diagnosis Out of The Entire Study Group
3.6. Clinical and Hemodynamic Outcome of IGCM Patients at Follow-Up after Immunosuppressive Treatment
4. Discussion
5. Conclusions
6. Limitations
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
CCL20 | chemokine (C-C motif) ligand 20 |
CCR5 | chemokine receptor 5 |
CCR6 | chemokine receptor 6 |
CPT1 | carnitine palmitoyltransferase I |
DCM | dilated cardiomyopathy |
DCMi | inflammatory DCM |
EMB | endomyocardial biopsy |
EOM | eosinophilic myocarditis |
EvG | elastic van Gieson stain |
GCs | giant cells |
IGCM | idiopathic giant cell myocarditis |
IVSD | intraventricular septum diameter |
LVEDD | left ventricular end-diastolic diameter |
LVEF | left ventricular ejection fraction |
LVPW | left ventricular posterior wall |
NYHA | New York Heart Association Classification |
RT-qPCR | reverse transcription-quantitative polymerase chain reaction |
TAPSE | tricuspid annular plane systolic excursion |
TLR8 | toll-like receptor 8 |
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n | 23 |
---|---|
Age (years) | 48.5 ± 12.9 |
LVEF (%) | 51.5 ± 15.4 |
LVEDD (mm) | 55.5 ± 9.3 |
TAPSE (mm) | 23 ± 4.1 |
IVSD (mm) | 11.8 ± 3.1 |
LVPW (mm) | 11.2 ± 2.8 |
Patient Data | Entire Cohort |
---|---|
n | 427 |
Age (years) | 47.03 ± 15.69 |
LVEF (%) | 38.54 ± 17.89 |
LVEDD (mm) | 54.51 ± 8.75 |
TAPSE (mm) | 22.40 ± 5.93 |
IVSD (mm) | 11.31 ± 2.80 |
LVPW (mm) | 10.84 ± 2.40 |
NYHA I/II/III/VI (n) | 0/0/250/177 |
Suspected clinical diagnoses (No., n): | |
- AMC | 180 |
- IGCM | 30 |
- DCMi | 100 |
- EOM | 11 |
- cardiac sarcoidosis | 20 |
- unexplained acute heart failure | 86 |
Patient Data | IGCM (By Histology) | IGCM (By Gene Profiling) |
---|---|---|
Immunohistology | ||
- CD3+ lymphocytes infiltration/mm2 | 312.4 ± 297.3 | 125.8 ± 196.3 * |
- LFA-1+ lymphocytes infiltration/mm2 | 462.6 ± 413.8 | 183.4 ± 215.0 * |
- CD45R0+ T memory cell infiltration/mm2 | 533.3 ± 349.6 | 114.9 ± 502.3 * |
- perforin+ cell infiltration/mm2 | 16.23 ± 26.00 | 14.14 ± 32.23 |
- Mac-1+ macrophages infiltration/mm2 | 428.8 ± 344.0 | 181.1 ± 227.1 * |
Patient Data | IGCM (By Histology) At baseline | IGCM (By Histology) After therapy | IGCM (By Gene Profiling) At baseline | IGCM (By Gene Profiling) After therapy |
---|---|---|---|---|
n | 17 | 17 | 23 | 23 |
LVEF (%) | 19.0 ± 14.22 * | 47.25 ± 12.27 | 31.3 ± 15.0 * | 49.9 ± 12.4 |
LVEDD (mm) | 56.23 ± 5.23 | 55.62 ± 8.43 | 56.43 ± 7.28 | 55.93 ± 4.29 |
TAPSE (mm) | 20.48 ± 5.13 | 21.23 ± 5.34 | 21.96 ± 7.53 | 21.81 ± 6.33 |
IVSD (mm) | 10.98 ± 3.15 | 10.42 ± 4.21 | 11.12 ± 3.15 | 11.02 ± 4.12 |
LVPW (mm) | 10.14 ± 2.41 | 10.05 ± 2.24 | 10.25 ± 2.16 | 10.58 ± 2.07 |
NYHA I/II/III/VI | 0/0/6/11 | 0/11/6/0 | 0/0/11/12 | 0/18/5/0 |
Immunohistologic Analysis | ||||
CD3+ T lymphocytes infiltration/mm2 | 397.3.4 ± 305.3 ** | 23.57 ± 19.23 | 169.1 ± 111.5 ** | 15.72 ± 17.94 |
LFA-1+ lymphocytes infiltration/mm2 | 612.6 ± 405.5 ** | 40.91 ± 21.00 | 190.8 ± 119.6 * | 23.77 ± 20.69 |
CD45R0+ T memory cells/mm2 | 584.5 ± 340.5 * | 63.95 ± 59.47 | 208.1 ± 158.3 | 33.99 ± 25.62 |
perforin+ cytotoxic cells/mm2 | 21.70 ± 28.42 | 0.97 ± 0.72 | 39.22 ± 48.64 | 2.17 ± 4.73 |
Mac-1+ macrophages infiltration/mm2 | 569.3 ± 311.5 ** | 59.44 ± 18.92 | 200.5 ± 111.3 ** | 40.10 ± 26.42 |
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Escher, F.; Pietsch, H.; Aleshcheva, G.; Wenzel, P.; Fruhwald, F.; Stumpf, C.; Westermann, D.; Bauersachs, J.; Enseleit, F.; Ruschitzka, F.; et al. 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. J. Clin. Med. 2020, 9, 2689. https://doi.org/10.3390/jcm9092689
Escher F, Pietsch H, Aleshcheva G, Wenzel P, Fruhwald F, Stumpf C, Westermann D, Bauersachs J, Enseleit F, Ruschitzka F, et al. 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. Journal of Clinical Medicine. 2020; 9(9):2689. https://doi.org/10.3390/jcm9092689
Chicago/Turabian StyleEscher, Felicitas, Heiko Pietsch, Ganna Aleshcheva, Philip Wenzel, Friedrich Fruhwald, Christian Stumpf, Dirk Westermann, Johann Bauersachs, Frank Enseleit, Frank Ruschitzka, and et al. 2020. "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" Journal of Clinical Medicine 9, no. 9: 2689. https://doi.org/10.3390/jcm9092689