Viral presence‐guided immunomodulation in lymphocytic myocarditis: an update

Abstract

Latest statements from European and American societies recommend to rule out viral presence in endomyocardial biopsy (EMB) via polymerase chain reaction (PCR) analysis before starting immunosuppression or immunomodulation in acute lymphocytic myocarditis presenting with life-threatening scenarios. However, recommendations in myocarditis are mostly based on heterogeneous studies enrolling patients with inflammatory cardiomyopathies and established heart failure rather than acute myocarditis. Thus, definitive evidence of a survival benefit from immunomodulation guided by viral presence is currently lacking. Finally, distinguishing innocent bystanders from causative agents among EMB-detected viruses remain challenging and a major goal to achieve in the near future. Therefore, considerable divergence remains between official recommendations and clinical practice, including the possibility of starting immunosuppressive therapy empirically, without knowing viral PCR results. This review systematically discusses the unsolved issues of immunomodulation guided by viral presence in acute lymphocytic myocarditis, namely (i) virus epidemiology and prognosis, (ii) variability of viral presence rates, (iii) the role of potential viral bystander findings, and (iv) the main results of immunosuppression controlled trials in lymphocytic myocarditis. Furthermore, a practical approach for the critical use of viral presence analysis in guiding immunomodulation is provided, highlighting its importance before starting immunosuppression or immunomodulation. Future, multicentre studies are needed to address specific scenarios such as fulminant lymphocytic myocarditis and a virus-tailored management as for parvovirus B19.

Clinically Suspected Myocarditis in the Course of Severe Acute Respiratory Syndrome Novel Coronavirus-2 Infection: Fact or Fiction?

“…To reach an etiological diagnosis of infectious myocarditis, molecular investigations (polymerase chain reaction (PCR) or in-situ hybridization) on myocardial tissue for common cardiotropic viruses should be performed [2] . Molecular analysis with PCR for viral presence in the myocardium should require investigation of both EMB specimens and blood samples, as this technique is the gold standard to rule out the possibility of false positives [3] .…”

Exploring the possible link between myocarditis and mRNA COVID-19 vaccines

“…Similarly, subjects are discouraged from receiving the second dose of the vaccine in case they develop myocarditis following the first dose, especially young patients. Finally, caution is recommended for vaccine administration in young patients with immune-mediated diseases or under chronic immunosuppression [15] as the cost-effectiveness analysis of vaccination in these settings requires careful evaluation in the nearest future.…”

Myocarditis: Which Role for Genetics?

“…Although genome sequences of more than 27 viruses have been detected in hearts with myocarditis, only the pathogenic mechanism of enteroviruses has been well studied in animal models. This pathogenic mechanism implies the internalization through a transmembrane Coxsackievirus and adenovirus receptor and the induction of a rapid cytolysis with subsequent cardiac inflammation [6][7][8][9][10]. Mechanisms of viral entry, replication, cellular injury, and death from other nonenteroviruses remain poorly understood and are still a matter of investigation [10].…”