MYOCARDITIS AND BIOMARKERS. Dr C. Guenancia Service de Cardiologie CHU Dijon

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1 MYOCARDITIS AND BIOMARKERS Dr C. Guenancia Service de Cardiologie CHU Dijon

Déclaration de Relations Professionnelles Disclosure Statement of Financial

une affiliation ou des intérêts financiers ou intérêts de tout ordre avec

des octrois de recherche d'ʹune société commerciale : I currently have, or

interests of any order with a company or I receive compensation or fees or

2 Déclaration de Relations Professionnelles Disclosure Statement of Financial Interest J'ʹai actuellement, ou j'ʹai eu au cours des deux dernières années, une affiliation ou des intérêts financiers ou intérêts de tout ordre avec une société commerciale ou je reçois une rémunération ou des redevances ou des octrois de recherche d'ʹune société commerciale : I currently have, or have had over the last two years, an affiliation or financial interests or interests of any order with a company or I receive compensation or fees or research grants with a commercial company : Affiliation/Financial Relationship None

3 Myocarditis: background Caforio et al. European Heart Journal (2013) 34,

4 Myocarditis: background Caforio et al. European Heart Journal (2013) 34,

5 Myocarditis: background Myocarditis: Tricky diagnosis Multiples causes No specific biomarker Availability of MRI Risk of Endomyocardial Biopsy (EMB) Need of new biomarkers : Earlier diagnosis Improved prognostic stratification Treatment guidance

6 Biomarkers Biomarker = biological marker Any substance, structure, or process that can be measured in the body or its products and influence or predict the incidence of outcome or disease WHO 2001 Blood +++ Non invasive Easy to obtain Tissular

7 Biomarkers and myocarditis ESC Working Group on Myocardial and Pericardial Diseases position statement Troponins, eythrocyte sedimentation rate, reactive C protein levels should be assessed in all patients Routine viral serology testing is not recommended Serum samples should be assessed, if possible, for cardiac autoantibodies, if one (or more) of the published test is available according to specific centre experience Caforio et al. European Heart Journal (2013) 34,

8 Serology / PCR Caforio et al. European Heart Journal (2013) 34,

9 Viral serology Not recommended in clinical practice Poor correlation to EMB viral detection Sensitivity 9% Specificity 77% Mahfoud et al. EHJ 32, (2011) Because : The determination of a viral infection by serology is only feasible at the time of symptom onset High prevalence of involved viruses in the general population Frequent reactivations of previous infections (no IgM or IgA)

10 Inflammatory biomarkers Caforio et al. European Heart Journal (2013) 34,

European Society of Cardiology. All rights reserved.

11 Inflammatory biomarkers Heinz-Peter Schultheiss et al. Eur Heart J 2011;32: Published on behalf of the European Society of Cardiology. All rights reserved. The Author For permissions please journals.permissions@oup.com

12 Inflammatory biomarkers CRP, Erythrocyte Sedimentation Rate Non specific Also increased in acute pericarditis

13 Inflammatory biomarkers CRP, Erythrocyte Sedimentation Rate Non specific Also increased in acute pericarditis Endomyocardial SDF-1 Zuern et al. Clin Res Cardiol (2015) 104:

14 Inflammatory biomarkers Serum IL 10 levels in fulminant acute myocarditis: only independent predictor of heart-assist device application Izumi et al. Herz (2012) 37:

15 Cardiac injury biomarkers Caforio et al. European Heart Journal (2013) 34,

16 Cardiac injury biomarkers Troponin A negative troponin does not eliminate the diagnostic of myocarditis! ctnt : 26 + / 49 (53%) 94% specificity, 53% sensitivity ctni : 18/53 (34%) 89% specificity, 34% sensitivity Lauer et al. JACC (1997) 30: Smith et al. Circulation (1997) 95:

17 Cardiac injury biomarkers Acute Myocarditis diagnosis Troponin Hs AUC: 0.878, p = Hs-TNT>50 pg/ml Sensitivity 83% Specificity 80% Copeptin NT-proBNP Proadrenomedullin Ukena et al. Clin Res Cardiol (2014) 103:

18 Cardiac injury biomarkers Acute Myocarditis Prognosis

19 Anti Heart Antibodies Caforio et al. European Heart Journal (2013) 34,

20 Anti-heart antibodies Caforio et al. European Heart Journal (2013) 34,

21 mirs Caforio et al. European Heart Journal (2013) 34,

22 MicroRNAs Small non-coding RNAs nucleotides Post-transcriptional protein expression regulation by binding messenger RNAs Involved in Cardiac biology Cell proliferation and apoptosis Regulation of immune responses The expression of certain mirnas changes during cardiac disease and heart failure interesting targets in the potential treatment of cardiovascular diseases, such as myocarditis

23 MicroRNAs Increased cardiac expression of of mir Cluster 221/222 in a model of viral myocarditis (Coxsackie B3 virus) Protective role Potentiel therapeutic target Combination with immune modulating therapies? Corsten et al. EHJ (2015) 36:

24 MicroRNAs Corsten et al. EHJ (2015) 36:

25 MicroRNAs Van den Hoogen et al. Current Genomics (2015) 16: 88-94

26 Conclusion Myocarditis: Complex pathophysiology Multiples etiologies and clinical presentations à No turnkey biomarker! Hs Troponin promising for diagnostic Coupled to MRI? Sramko et al. AJC (2013) 111: Prognostic assessment: SDF-1 Nt-proBNP mirs: Therapeutic trials?

P. Messner Pellenc, C. Robert

P. Messner Pellenc, C. Robert Déclaration de Relations Professionnelles Disclosure Statement of Financial Interest J'ai actuellement, ou j'ai eu au cours des deux dernières années, une affiliation ou des