Interferon beta-1b therapy in chronic viral dilated cardiomyopathy--is there a role for specific therapy?

BACKGROUND: Myocardial biopsy can be used for the detection of viral genome in dilated cardiomyopathy (DCM). Pilot studies have previously reported beneficial effects on clinical outcome and safety of an antiviral therapy using interferon beta-1b in chronic viral DCM. METHODS AND RESULTS: Myocardial biopsies were taken from patients with DCM. Using polymerase chain reaction and Southern Blot analysis, viral genome could be detected in 49% of patients. In 42 patients with viral infection, off-label use with interferon beta-1b was initiated. A further 68 patients formed the control group. The outcome was evaluated after follow-up with echocardiography, exercise electrocardiogram, and New York Heart Association class. A total of 81 men and 29 women with a median left ventricular ejection fraction of 34% were included. The follow-up period was 36 months. In 33 (79%) patients with interferon beta-1b treatment, minor adverse reactions occurred, but no major adverse events were reported. No significant benefit for interferon beta-1b treatment on clinical outcome could be detected during follow-up. CONCLUSIONS: Off-label use with interferon beta-1b in patients with viral DCM is feasible and safe under routine clinical practice. Concerning the herein evaluated clinical outcome parameters, promising results from pilot studies could not be confirmed. High prevalence of parvovirus B19 (92%) might influence the results.

Myocardial inflammation and non-ischaemic heart failure: is there a role for C-reactive protein?

Whereas C-reactive protein (CRP) is acknowledged as a cardiovascular risk marker, there is ongoing discussion about its role as a risk factor. Previous studies focused on the effects of CRP on ischaemic heart failure and atherosclerosis. In this study we investigated distribution of CRP, the Terminal Complement Complex (C5b-9) and macrophages (CD68) in the myocardium of patients suffering from non-ischaemic heart failure and their implication on clinical parameters. Endomyocardial biopsies were taken from 66 patients suffering from dilated cardiomyopathy (DCM). Biopsies were analysed by immunohistochemical and immunofluorescent staining for CRP, C5b-9 and CD68. Viral DNA/RNA for adenovirus, enterovirus, parvovirus B19 and human herpes virus 6 was detected by PCR and Southern blot analysis. Myocardial biopsy findings were correlated with plasma level of hsCRP and NT-proBNP as well as echocardiography, exercise test and NYHA class. In 18 (27%) patients, a positive staining for CRP and in 57 (86%) patients a positive staining for C5b-9 was detected. All patients showed myocardial infiltration with macrophages with an average of 39 cells/mm(2). CRP, C5b-9 and CD68 co-localised within the myocardium. No correlation was observed for inflammatory proteins and plasma level of hsCRP, NT-proBNP and clinical parameters. CRP is frequently present in the myocardium of patients suffering from DCM and co-localises with C5b-9 and macrophages. CRP may contribute to myocardial damage in DCM via activation of the complement system and chemotaxis of macrophages.

Prognostic role of myocardial tumor necrosis factor-alpha and terminal complement complex expression in patients with dilated cardiomyopathy.

BACKGROUND: In patients with dilated cardiomyopathy (DCM), elevated plasma levels of tumor necrosis factor-alpha (TNF-alpha) are associated with poor prognosis. The terminal complement complex (C5b-9) stimulates myocardial TNF-alpha expression. AIMS: To investigate whether myocardial TNF-alpha and C5b-9 expression correlate with clinical outcome in DCM. METHODS AND RESULTS: 71 patients with DCM underwent myocardial biopsy. Biopsies were analyzed for TNF-alpha, C5b-9, markers of inflammation and for viral genome. Patients were divided into three groups according to biopsy results: group A: no TNF-alpha and no C5b-9; group B: TNF-alpha or C5b-9; and group C: TNF-alpha and C5b-9. NYHA classification, ECG and echocardiography were documented. Patients received conventional treatment of heart failure and, in a few cases, additional treatment with interferon beta(1b) (virus positive) or prednisolone (inflammatory DCM). There were 13 patients (18%) in group A, 19 patients (27%) in group B, and 39 patients (55%) in group C. All groups had a similar and significant improvement in NYHA classification and echocardiographic parameters. TNF-alpha and C5b-9 did not significantly correlate with the presence of viral genome or with markers of inflammation. CONCLUSION: TNF-alpha and C5b-9 are widely distributed in the myocardium of DCM patients. Neither of the antigens correlates with clinical outcome. Myocardial TNF-alpha may not be a useful prognostic marker in DCM.

Myocardial biopsy findings and gadolinium enhanced cardiovascular magnetic resonance in dilated cardiomyopathy.

BACKGROUND: In some patients suffering from dilated cardiomyopathy (DCM) magnetic resonance imaging (MRI) shows late gadolinium enhancement with variable distribution. Myocardial biopsies in DCM reveal a chronic myocardial inflammatory process in almost 50% and myocardial persistence of adenoviral or enteroviral genome in about 15% of the patients. AIMS: We prospectively investigated whether the pattern of late gadolinium enhancement correlates with myocardial biopsy findings. METHODS AND RESULTS: 42 patients with DCM and 42 control subjects underwent contrast MRI. In the DCM group, endomyocardial biopsies were performed and evaluated for inflammation and viral genome. None of the control subjects showed late gadolinium enhancement whereas in 29 DCM patients (69%) gadolinium enhancement was detectable (p<0.001). 21 of the DCM patients (50%) showed midwall septal enhancement, 7 patients (17%) showed a patchy distribution of hyperenhancement and 1 patient (2%) showed enhancement typical for ischemic heart disease. In myocardial biopsy analysis, 2 patients (5%) showed persistence of viral genome, 18 patients (43%) showed inflammation and in 22 patients (52%) neither virus nor inflammation was detected. The pattern of late gadolinium enhancement and myocardial biopsy findings were not significantly correlated (p = 0.854). CONCLUSION: MRI as a non-invasive technique cannot replace myocardial biopsy for the differential diagnosis of DCM.

Myocardial biopsy based classification and treatment in patients with dilated cardiomyopathy.

BACKGROUND: We investigated whether myocardial biopsy analysis for inflammation and viruses correlates with outcome in dilated cardiomyopathy. METHODS: Myocardial biopsies of 82 patients were analyzed for HLAI, HLAII, CD54, CD2, CD68 and entero-/adenovirus. Ejection fraction was determined by left ventriculography. NYHA classification, electrocardiogram (ECG) and echocardiography were analyzed at first admission and for follow up. Patients were attributed to three groups: (A) no inflammation/no virus (B) inflammation/no virus (C) virus with/without inflammation. Patients not responding to conventional treatment of heart failure received interferon beta1b (group C) or prednisolone (group B). Median follow up was 7 months (group A), 11 months (group B) and 14.5 months (group C). RESULTS: Thirty nine patients (48%) belonged to group A, 33 patients (40%) to group B, 10 patients (12%) to group C. Only enterovirus was detected. Ejection fraction at admission was worse for group B compared to group A (p=0.003). Groups A and B improved for echocardiography and NYHA (p< or =0.001). Group C improved for echocardiography only (p=0.031). Group B showed a better outcome for echocardiography (p=0.014) and NYHA (p=0.023) than group A. CONCLUSIONS: Inflammatory cardiomyopathy shows the best outcome. Antiinflammatory or antiviral treatment may be an option in patients not responding to conventional therapy.