Kuchynka P, Palecek T, Nemecek E, Kovarnik T, Horak J, Vitkova I and Linhart A

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1 Is improvement of the left ventricular systolic function in patients with new-onset dilated cardiomyopathy related to the presence of virus or inflammation in endomyocardial biopsy? Kuchynka P, Palecek T, Nemecek E, Kovarnik T, Horak J, Vitkova I and Linhart A Department of Cardiovascular Medicine, General University Hospital, 1 st Faculty of Medicine, Charles University, Prague, Czech Republic Authors have no conflicts of interest

2 Viral Persistence and Prognosis patients (36 ± 18 years) - clinically susp. myocarditis tested by PCR - 31 (26%) viral genome + Caforio et al. Eur Heart J 2007;28:

3 Viral Persistence and Prognosis Kühl et al. Circulation 2005;112:

4 Viral Persistence and Prognosis patients (42 ± 15 years) - clinically susp. myocarditis - 79 (44%) PCR virus + Kindermann et al. Circulation 2008;118:

5 Viral Persistence and Prognosis Bock et al. N Engl J Med 2010;362:

6 Inflammation and Prognosis patients (42 ± 15 years) - clinically susp. myocarditis - 91 (50%) IH + Kindermann et al. Circulation 2008;118:

7 Inflammation and Prognosis patients (36 ± 18 years) - 85 active myocarditis - 89 borderline myocarditis lymfocytic myocarditis - 5 giant cell myocarditis - 7 other types Caforio et al. Eur Heart J 2007;28:

8 Aim of the Study To evaluate the significance of viral persistence and inflammation in endomyocardial biopsy in patients with new-onset unexplained DCM

9 Study Design Endomyocardial biopsy 110 subjects (53 ± 11 years, 34 women) with new-onset unexplained DCM - history of heart failure symptoms < 12 months - LVEF < 40% persisting after at least 2 weeks of conventional heart failure therapy

10 The Criteria of Unexplained DCM The absence of following: significant coronary artery disease moderate-to-severe primary valvulopathy significant congenital heart disease tachyarrhythmias; permanent pacemaker uncorrected metabolic or endocrine disorder history of alcohol or drug abuse history of cardiotoxic therapy family history of DCM

11 EMB Assessment Immunohistochemistry myocardial inflammation (Leucocytes > 14mm 2 and/or moderate/severe HLA-DR positivity) PCR Borrelia burgdorferi (Bb) PCR cardiotropic viruses: - herpetic viruses (HSV, EBV, CMV, HHV-6) - enteroviruses - parvovirus B-19 - adenovirus

12 Baseline Characteristics Heart Failure Symptoms + ECG Duration of symptoms 2,3 ± 2,0 months NYHA (I/II/III/IV) 0/12/50/48 Sinus rhythm 98 (89%) Atrial fibrillation 12 (11%) LBBB 21 (19%) RBBB 3 (3%) ST-T changes 46 (42%)

13 Baseline Characteristics Echocardiography LVEDD (mm) 68 ± 7 LVESD (mm) 58 ± 8 LVEF (%) 28 ± 7 LAV (ml) 101 ± 35 RV (mm) 37 ± 6 TAPSE (mm) 18 ± 4 PASP (mmhg) 42 ± 10 MR (1-4+) 34/61/13/2

14 EMB Results - I Immunohistochemistry + 35 (32%) Virus or Borrelia burgdorferi + 70 (64%) Virus + 56 (51%) Negative EMB 32 (29%)

15 EMB Results - II Borrelia burgdorferi 22 (20%) Parvovirus B of 88 (19%) > 500 ge/μg DNA 5 (29%) HHV-6 16 (15%) Enterovirus 8 (7%) HSV-1 4 (4%) CMV 3 (3%) Adenovirus 0 (0%)

16 EMB Results - III % 13 12% 22 20% 32 29% PCR virus + Immunohistochemistry - PCR virus + Immunohistochemistry + PCR virus - Immunohistochemistry + PCR virus - Immunohistochemistry - 0

17 Virus + / Immunohistochemistry ± Patients (27 patients with follow-up 6 months) Baseline 6 months F-U p LVEDD 65 ± 7 62 ± 7 LVESD 56 ± 7 50 ± 9 EF 29 ± 7 43 ± 10 LAV 101 ± ± 34 MR 1,6 ± 0,7 1,4 ± 0,6 TAPSE 18 ± 4 21 ± 4 NS PASP 41 ± ± 12 NS

18 Virus+ / Immunohistochemistry- Patients (14 patients with follow-up 6 months) Baseline 6 months F-U p LVEDD 63 ± 5 61 ± 4 NS LVESD 54 ± 6 48 ± 8 EF 29 ± 7 43 ± 12 LAV 108 ± ± 31 NS MR 2,0 ± 0,7 1,6 ± 0,7 TAPSE 17 ± 3 21 ± 3 PASP 45 ± ± 12 NS

19 Virus+ / Immunohistochemistry+ Patients (13 patients with follow-up 6 months) Baseline 6 months F-U p LVEDD 62 ± 9 59 ± 6 LVESD 59 ± 6 51 ± 9 EF 28 ± 6 42 ± 8 LAV 96 ± ± 36 NS MR 1,3 ± 0,5 1,2 ± 0,5 NS TAPSE 19 ± 5 20 ± 5 NS PASP 36 ± 7 35 ± 12 NS

20 EMB negative Patients (27 patients with follow-up 6 months) Baseline 6 months F-U p LVEDD 70 ± 7 65 ± 8 LVESD 59 ± 8 54 ± 9 EF 29 ± 8 40 ± 12 LAV 109 ± ± 21 MR 1,6 ± 0,7 1,4 ± 0,6 TAPSE 17 ± 4 21 ± 5 PASP 42 ± ± 6

21 EF % EMB+ vs. EMB- Patients (only conventional heart failure therapy) p=ns p 43±10 p 40 ±7 EMB positive patients n= ±7 29±7 EMB negative patients n= Baseline 6 M Baseline 6 M

22 Conclusions - I Microbial agent and/or inflammation are present in most patients with new-onset unexplained DCM (high prevalence of inflammatory cardiomyopathy). Conventional heart failure therapy is associated with similar improvement of LV EF in patients with new-onset DCM regardless the presence or absence of viral agent.

23 Conclusions - II Our findings of similar improvement in LV systolic function in both (EMB positive and EMB negative) groups treated only by conventional heart failure therapy might be explained either due to: 1) low impact of viral persistence on prognosis of affected subjects 2) or by underdiagnosing of inflammatory DCM by current techniques.

24 Thank you very much for your attention!

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