MYOCARDITIS AND BIOMARKERS Dr C. Guenancia Service de Cardiologie CHU Dijon
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Myocarditis: background Caforio et al. European Heart Journal (2013) 34, 2636 2648
Myocarditis: background Caforio et al. European Heart Journal (2013) 34, 2636 2648
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
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
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, 2636 2648
Serology / PCR Caforio et al. European Heart Journal (2013) 34, 2636 2648
Viral serology Not recommended in clinical practice Poor correlation to EMB viral detection Sensitivity 9% Specificity 77% Mahfoud et al. EHJ 32, 897-903 (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)
Inflammatory biomarkers Caforio et al. European Heart Journal (2013) 34, 2636 2648
Inflammatory biomarkers Heinz-Peter Schultheiss et al. Eur Heart J 2011;32:2616-2625 Published on behalf of the European Society of Cardiology. All rights reserved. The Author 2011. For permissions please email: journals.permissions@oup.com
Inflammatory biomarkers CRP, Erythrocyte Sedimentation Rate Non specific Also increased in acute pericarditis
Inflammatory biomarkers CRP, Erythrocyte Sedimentation Rate Non specific Also increased in acute pericarditis Endomyocardial SDF-1 Zuern et al. Clin Res Cardiol (2015) 104:1033 1043
Inflammatory biomarkers Serum IL 10 levels in fulminant acute myocarditis: only independent predictor of heart-assist device application Izumi et al. Herz (2012) 37: 627-631
Cardiac injury biomarkers Caforio et al. European Heart Journal (2013) 34, 2636 2648
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) 30:1354-1359 Smith et al. Circulation (1997) 95:163-168
Cardiac injury biomarkers Acute Myocarditis diagnosis Troponin Hs AUC: 0.878, p = 0.002 Hs-TNT>50 pg/ml Sensitivity 83% Specificity 80% Copeptin NT-proBNP Proadrenomedullin Ukena et al. Clin Res Cardiol (2014) 103:743-751
Cardiac injury biomarkers Acute Myocarditis Prognosis
Anti Heart Antibodies Caforio et al. European Heart Journal (2013) 34, 2636 2648
Anti-heart antibodies Caforio et al. European Heart Journal (2013) 34, 2636 2648
mirs Caforio et al. European Heart Journal (2013) 34, 2636 2648
MicroRNAs Small non-coding RNAs 20-24 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
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) 36:2909-2919
MicroRNAs Corsten et al. EHJ (2015) 36:2909-2919
MicroRNAs Van den Hoogen et al. Current Genomics (2015) 16: 88-94
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: 258-264 Prognostic assessment: SDF-1 Nt-proBNP mirs: Therapeutic trials?