Controversies in myocarditis

Transcription

1 Controversies in myocarditis Virus persistence is relevant: contra Prof.dr. Stephane Heymans Dep. Cardiology, CARIM/Maastricht University

2 (Parvo)virus persistence marks the failing heart Chicken or the egg?

3 Virus persistence 6 months after acute myocarditis relates to heart failure Kuhl et al. Circulation Sep 27;112(13):

4 Contra: (PVB19)-virus persistence is present in different forms of HF PVB19 and other viruses present in different forms of HF, not only in DCM Stewart et al, Circ HF, 2011, p71 Lotze et al, J Med Virol, 2010, p1449 Giacca M. (Trieste, personal communication). But: Proper controls normal hearts- are lacking. Information on viral load unclear.

5 Viral load (copies/µgdna) But (Parvo)virus load is higher in the the failing compared to normal heart 78 % * 75 % 76 % * * 78 % Normal hearts DCM Isch HD Valvular HD n= 49 n= 109 n= 28 n= 21 Data submitted for publication * P<0.01 in diseased vs. normal hearts

6 Viral load (copies/µgdna) Contra: PVB19 is present in different forms of HF 78 % * 75 % 76 % * * 78 % Normal hearts DCM Isch HD Valvular HD n= 49 n= 109 n= 28 n= 21 Data submitted for publication * P<0.01 in diseased vs. normal hearts

7 Contra 1. (PVB19) Virus persistence occurs in different forms of heart failure

8 Similar pattern in virus persistence in myocarditis vs. cardiomyopathy Acute myocarditis (n=20) Idiopathic cardiomyopathy (n=215) Virus negatief PVB19 Virus negatief PVB19 EV + EBV HH6 + EBV EV EBV PVB19 + EBV PVB19 + HHV6 HHV6 PVB19 + EBV PVB19 + HHV6 + EV PVB19 + EV PVB19 + EV + EBV PVB19 + HHV6

9 What is viral myocarditis.?

10 Cough of the heart myocarditis and heart failure ParvovirusB19 Coxsackievirus Herpesvirus (EBV, HHV6) > 70 % of population infected Δ Immuno-genetic background Δ External factors Co-infection viruses Fatigue < 1 % of population myocarditis Inflammation +++ Cadiac necrosis

11 Herpes viruses adverse inflammation and injury Herpes simplex virus Δ Immunogenetic background Some persons are susceptible External factors Other viruses Illness Fatigue

12 And: PVB19 can trigger myocarditis Exaggerated inflammatory response Against common cough viruses Herpesvirus, parvovirus, enterovirus, + Virus in the heart Adverse inflammation Heart Failure

13 Contra 1. (PVB19) Virus persistence occurs in different forms of heart failure 2. Immuno-genetic background and not the virus per se is central

14 Yes, viruses can trigger myocarditis BUT?? Myocarditis evolve in DCM due to virus persistence??

15 ?? Myocarditis evolve in DCM due to virus persistence?? Contra: DCM is a multifactorial disease, and myocarditis = DCM Contra: lack of pre-clinical evidence for PVB19 persistence triggering HF development at long term

16 Idiopathic dilated cardiomyopathy Gene factors Metabolic Δ Structural Δ DCM Inflammatory Δ Virus persistence

17 Contra 1. (PVB19) Virus persistence occurs in different forms of heart failure 2. Immuno-genetic background and not the virus per se is central in myocarditis 3. Lack of (Pre)clinical evidence for virus persistence induced chronic HF

18 Failing heart is an immune-diseased heart allowing PVB19 reactivation?

19 Viral load (copies/µgdna) Failing heart is a immune-diseased heart allowing PVB19 reactivation * * * Normal hearts DCM Isch HD Valvular HD

20 Failing heart is a immune-diseased heart allowing PVB19 reactivation Diseased heart Virus reactivation Δ Immunebackground Further injury???

21 PVB19 reactivation causing further injury? Viral infection in the heart increased in cardiac transplants (Moulik, JACC, 2010, p582) Independent predictor of graft loss and coronary vasculopathy But not significant for PVB19.

22 Contra 1. (PVB19) Virus persistence occurs in different forms of heart failure 2. Immuno-genetic background and not the virus per se is central in myocarditis 3. Lack of (Pre)clinical evidence for virus persistence induced chronic HF

23 Conclusion Yes!! Viruses induce acute myocarditis.. But pending on immunogenetic background Virus persistence relates to different forms of chronic heart failure PVB19 reactivation in diseased >< normal hearts. PVB19 reactivation further injury??? Need for pre-clinical studies Need for clinical studies, such as IV Ig in PVB19- cardiomyopathy

24

25 Thank you! Maastricht University, CHFR, CARIM B. Schroen M. Corsten P. Carai M. de Vrie A. Papageorgiou R. Dennert R. Van Leeuwen W. Verhesen de Windt L. Stassen F. de Winther M. Lutgens E. Santaris Pharma - S. Kauppinen - M. Lindow Amsterdam, AMC Y. Pinto E. Creemers Trieste, ICGEB Giacca M. Serena Zacchigna Hannover Medical School T. Thum Cambridge E. Vigoroto KULeuven, J. Staessen P. Carmeliet 2005 B B B B