Immunomodulating Therapies in Acute Myocarditis and Recurrent/Acute Pericarditis

Abstract

The field of inflammatory disease of the heart or “cardio-immunology” is rapidly evolving due to the wider use of non-invasive diagnostic tools able to detect and monitor myocardial inflammation. In acute myocarditis, recent data on the use of immunomodulating therapies have been reported both in the setting of systemic autoimmune disorders and in the setting of isolated forms, especially in patients with specific histology (e.g., eosinophilic myocarditis) or with an arrhythmicburden. A role for immunosuppressive therapies has been also shown in severe cases of coronavirus disease 2019 (COVID-19), a condition that can be associated with cardiac injury and acute myocarditis. Furthermore, ongoing clinical trials are assessing the role of high dosage methylprednisolone in the context of acute myocarditis complicated by heart failure or fulminant presentation or the role of anakinra to treat patients with acute myocarditis excluding patients with hemodynamically unstable conditions. In addition, the explosion of immune-mediated therapies in oncology has introduced new pathophysiological entities, such as immune-checkpoint inhibitor-associated myocarditis and new basic research models to understand the interaction between the cardiac and immune systems. Here we provide a broad overview of evolving areas in cardio-immunology. We summarize the use of new imaging tools in combination with endomyocardial biopsy and laboratory parameters such as high sensitivity troponin to monitor the response to immunomodulating therapies based on recent evidence and clinical experience. Concerning pericarditis, the normal composition of pericardial fluid has been recently elucidated, allowing to assess the actual presence of inflammation; indeed, normal pericardial fluid is rich in nucleated cells, protein, albumin, LDH, at levels consistent with inflammatory exudates in other biological fluids. Importantly, recent findings showed how innate immunity plays a pivotal role in the pathogenesis of recurrent pericarditis with raised C-reactive protein, with inflammasome and IL-1 overproduction as drivers for systemic inflammatory response. In the era of tailored medicine, anti-IL-1 agents such as anakinra and rilonacept have been demonstrated highly effective in patients with recurrent pericarditis associated with an inflammatory phenotype.

Innate Immunity in Cardiovascular Diseases – Identification of Novel Molecular Players and Targets

“…Conduction of such studies is challenging indeed and requires multicentric cooperation between experienced centers, but given the often young age of affected patients and possible life-saving impact the effort appears warranted. For further in-depth discussion regarding design and key problems of immunomodulating treatment trials in human cardiomyopathies we may refer the reader to a recent review [27].…”

“…In view of possible therapeutic relevance, it appears recommendable to further evaluate the hypothesis of independent immunologic risk in major SCN5A variant-carrier cohorts [25]. For further in-depth discussion of recent approaches towards the potential of immunomodulating therapies in human cardiomyopathies we may refer the reader to a recent review covering the field from classical inflammatory cardiomyopathies to immunecheckpoint inhibitor-associated and SARS-CoV-2-associated myocardial inflammation [27].…”

Innate Immunity in Cardiovascular Diseases – Identification of Novel Molecular Players and Targets

“…Conduction of such studies is challenging indeed and requires multicentric cooperation between experienced centers, but given the often young age of affected patients and possible life-saving impact the effort appears warranted. For an in-depth discussion regarding design and key problems of immunomodulating treatment trials in human cardiomyopathies we may refer the reader to a comprehensive recent review [27].…”

“…In view of possible therapeutic relevance, it appears recommendable to further evaluate the hypothesis of independent immunologic risk in major SCN5A variant-carrier cohorts [23]. For further in-depth discussion of recent approaches towards the potential of immunomodulating therapies in human cardiomyopathies we may refer the reader to a recent review covering the field from classical inflammatory cardiomyopathies to immunecheckpoint inhibitor-associated and SARS-CoV-2-associated myocardial inflammation [27].…”

Recent highlights on myocarditis, cardiovascular complications of COVID-19, and cardiomyopathies from the International Journal of Cardiology: Heart & Vasculature

“…While two randomized controlled trials are assessing the efficacy and safety of methylprednisolone (MYocarditis THerapy with Steroids [MYTHS], NCT05150704) and the anti-interleukin-1 drug anakinra (Anakinra Versus Placebo for the Treatment of Acute MyocarditIS [ARAMIS], NCT03018834) in patients with acute myocarditis, the role of immunosuppression is consolidated in eosinophilic, giant cell and sarcoidotic myocarditis [12] , [13] . An updated review in this Journal dealing with the current therapeutic options for cardiac sarcoidosis [14] showed that even if steroids remain the first-line treatment, the use of non-steroidal disease-modifying antirheumatic agents like methotrexate and infliximab is increasing, allowing a reduction in the maintenance steroid dose.…”