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Controversies in myocarditis

  • Viral persistence is clinically and prognostically relevant: Pro, presented by H P Schultheiss (Berlin, DE) - Slides
  • Viral persistence is clinically and prognostically relevant: Contra, presented by S Heymans (Maastricht, NL) - Slides, Rebuttal Slides
  • Endomyocardial biopsy is the diagnostic gold standard: Pro, presented by L Cooper (Rochester, US) - Slides, Rebuttal Slides
  • Endomyocardial biopsy is the diagnostic gold standard: Contra, presented by J Schulz-Menger (Berlin, DE)
Myocardial Disease

The first part of the ‘pro and contra’ session addressed the question whether viral persistence is clinically and prognostic relevant.

In the first part (pro) presented by Prof. Schultheiss (Berlin, Germany), data with regard to prevalence of cardiotropic viruses associated with mycarditis and dilated cardiomypathy were discussed. It was shown that not only CVB3 and adenoviral persistence are negative prognostic factors in those patients, but in addition PVB 19 in a substantial amount of patients. As the pathogenetic role of PVB 19 in heart muscle diseases so far is not completely understood and under discussion, Prof. Schultheiss was able to show that viral load alone is not important, but transcriptional activity of this virus makes the difference. He proposes first, that infection of endothelial cells with PVB 19 occurs in the bone marrow. Secondly, genetic predisposition in a given patient is responsible for the type of the immune response, which includes adequate activation of regulatory factors such as reg T-cells or micro RNA’s.

In the contra part given by Prof. Heymans (Maastricht, Netherlands) the speaker points out that the prognostic relevance of viral persistence in myocardial diseases is not a question with regard to the virus but depends on the degree of heart failure, as the failing heart is more prone for viral reactivation. Secondly, he was able to show that for example PVB 19 is present not only in patients with mycarditis and DCM, but in addition in other forms of heart disease and in normal hearts with low copy numbers. He reported, that the immunogenetic background is responsible in patients with acute mycarditis and not the virus per se and that the evolvement of DCM after viral infection is unclear as clinical evidence, for that hypothesis is lacking.

In the rebuttal Prof. Schultheiss points out, that: 

  1. treatment leads to viral clearance with improvement of EF in cases of CVB3 and ADV infections,
  2. mechanisms of viral reactivation in PVB 19 infections are under investigation,
  3. an intact immune system is responsible for viral clearance and
  4. that effective treatment of PVB 19 positive cases may depend on active replication of that virus.

 Prof. Heymans points out, that so far the percentage of patients with active replication of PVB 19 is not known and that on the other hand IvIg therapy in PVB 19 related DCM improves cardiac function. He concluded that the failing heart is an immune diseased heart.

Both speakers summarized that gene factors, status of the immune system, viral positivity and activity in addition to structural and metabolic features in a given patient are responsible for the extend of heart failure. The second part of the ‘pro and contra’ session addressed the question whether endomyocardial biopsy is the diagnostic gold standard.

In the first part (pro), Prof. Cooper (Rochester, USA) pointed out that in all cases where EMB is performed, a clinical usefull, prognostic and therapeutic relevant information should be the aim, keeping the costs and the safety of the patient in mind. As it is known that especially in giant cell, myocarditis and some forms of granulomatous myocardial diseases outcome is poor, EMB can add data which are relevant for the treatment and outcome for the patients. As it was shown recently, that myocardial inflammation detected by immunohistochemistry has a poor outcome, too, EMB is helpful on those cases, where myocardial inflammation to a higher extend is suspected.

In the rebuttal Prof. Schulz-Menger (Berlin, Germany) informed that cardiac MRI after defining different criteria for the diagnosis of myocardial inflammatory diseases is able to detect inflammation with high sensitivity and specificity, thus helping to differentiate forms of myocardial inflammation, oedema and fibrosis and is therefore able to provide prognostic relevant information for the patients.

Both speakers summarized, that 1) in addition to clinical scenarios defined EMB is of special importance in giant cell and fulminant myocarditis, in granulomatous myocarditis and viral induced forms, and patients after therapy should be followed in registries. MRI as non-invasive tool with regard to the diagnosis of mycarditis is sensitive, and is also helpful to follow patients after biopsy and treatment, and may be used to diagnose patients with normal ejection fraction. EMB and MRI are not exclusive of one another but should used in combination to provide as much information as needed, to reach a definitive diagnosis in a given patient.




Controversies in myocarditis

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.