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Biomedicines
Special Issues
Advances in Myocarditis: Molecular and Immune Mechanisms, Diagnosis and Treatment
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Advances in Myocarditis: Molecular and Immune Mechanisms, Diagnosis and Treatment

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 July 2024) | Viewed by 6243

Special Issue Editor

Dr. Gaetano Thiene

E-Mail Website
Guest Editor
Department of Cardiac, Thoracic, Vascular Sciences and Public Health, Medical School, University of Padua, 35121 Padova, Italy
Interests: cardiovascular disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Myocarditis is an inflammatory disease of the heart muscle, both infective and immune in origin. Nowadays, with the advent of endomyocardial biopsy, molecular investigation is also feasible in humans to gain an insight into cell biology and pathogenetic mechanisms for improving diagnosis, therapy and prevention. Moreover, new perspectives are emerging in terms of clinical, non-invasive diagnosis through Cardiac Magnetic Resonance (CMR) and treatment to favor the spontaneous resolution of fulminant myocarditis, by putting the heart temporarily at rest with Extra Corporeal Membrane Oxygenation (ECMO).

Contributions on the following topics are welcome:

  • CMR as a novel means of non-invasive clinical diagnosis.
  • Molecular diagnosis of viral infections and possible anti-viral therapy.
  • ECMO to overcome fulminant-onset myocarditis.
  • Advances in therapy for both viral and immune myocarditis.
  • The role and types of implantable defibrillator to prevent arrhythmic sudden death.
  • The pathogenetic mechanisms of viral myocarditis as a cause of cardiomyocyte death, evolving towards dilated cardiomyopathy.
  • The role of endomyocardial biopsy in establishing the histotype of myocarditis, with inherent therapeutic and prognostic implications.
  • Vaccinations to prevent viral myocarditis in children.
  • COVID myocarditis: immune reaction to vaccination or a settlement of the coronavirus within the myocardium?
  • New drug therapy.
  • Telling the story of myocarditis, from the invention of the microscope to polymerase chain reaction (PCR).
  • Are rheumatic and chagas myocarditis still a big global problem?
  • Overall, the role of the immune system in myocarditis.

Dr. Gaetano Thiene
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cardiac magnetic resonance (CMR)
  • endomyocardial biopsy
  • extra corporeal membrane oxygenation (ECMO)
  • immune system
  • molecular pathology
  • myocarditis
  • viruses

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Published Papers (5 papers)

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Research

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15 pages, 10762 KiB  
Article
Lymphocytic Myocarditis in Children with Parvovirus B19 Infection: Pathological and Molecular Insights
by Lisann Pelzl, Sabrina Mantino, Martina Sauter, Tatiana Manuylova, Ulrich Vogel and Karin Klingel
Biomedicines 2024, 12(8), 1909; https://doi.org/10.3390/biomedicines12081909 - 20 Aug 2024
Viewed by 445
Abstract
Background: This study aims to evaluate the role of parvovirus B19 (B19V) in the pathogenesis of myocarditis in a paediatric population, including post-mortem samples from two children. Methods: From 2004 to 2023, endomyocardial biopsies (EMBs) from children under 16 years of age were [...] Read more.
Background: This study aims to evaluate the role of parvovirus B19 (B19V) in the pathogenesis of myocarditis in a paediatric population, including post-mortem samples from two children. Methods: From 2004 to 2023, endomyocardial biopsies (EMBs) from children under 16 years of age were analyzed using histology, immunohistochemistry, and molecular pathology. A total of 306 children with acute and 1060 children with chronic lymphocytic myocarditis were identified. Results: B19V infection was more frequent in acute myocarditis than in chronic myocarditis (43% vs. 14%), with higher viral loads in acute cases regardless of age. The most prominent cardiac CD3+ T cell infiltration was noted in children < 2 years, correlating with high cardiac B19V loads. In two male infants who died from B19V infection, B19V DNA was localized in the endothelial cells of multiple organs using in situ hybridization. Virus replication was found in the endothelial cells of small cardiac arterioles and venules but not in capillaries. B19V DNA/mRNA was also detected in immune cells, especially in the spleen and lymph nodes, revealing virus replication in B lymphocytes. Conclusions: B19V can induce severe lymphocytic myocarditis, especially in young children. The simultaneous histopathological and molecular assessment of EMBs is important for early diagnosis of viral myocarditis, preventing severe disease, and ensuring appropriate therapy. Full article
(This article belongs to the Special Issue Advances in Myocarditis: Molecular and Immune Mechanisms, Diagnosis and Treatment)
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18 pages, 1688 KiB  
Article
RhoA/ROCK Pathway Is Upregulated in Experimental Autoimmune Myocarditis and Is Inhibited by Simvastatin at the Stage of Myosin Light Chain Phosphorylation
by Monika Skrzypiec-Spring, Maciej Kaczorowski, Alina Rak-Pasikowska, Agnieszka Sapa-Wojciechowska, Krzysztof Kujawa, Agnieszka Żuryń, Iwona Bil-Lula, Agnieszka Hałoń and Adam Szeląg
Biomedicines 2024, 12(3), 596; https://doi.org/10.3390/biomedicines12030596 - 7 Mar 2024
Viewed by 1021
Abstract
Many studies have proven the involvement of the RhoA/ROCK pathway in autoimmune and cardiovascular diseases and the beneficial effects of its downregulation. Here, we examined whether the effect of simvastatin on experimental autoimmune myocarditis (EAM) may be through targeting the Ras homolog family [...] Read more.
Many studies have proven the involvement of the RhoA/ROCK pathway in autoimmune and cardiovascular diseases and the beneficial effects of its downregulation. Here, we examined whether the effect of simvastatin on experimental autoimmune myocarditis (EAM) may be through targeting the Ras homolog family member A/Rho-associated coiled-coil containing kinases (RhoA/ROCK) pathway and whether previously shown downregulation of metalloproteinase 9 (MMP-9) could be associated with MLC phosphorylation. Two doses of simvastatin were administered to experimental rats with autoimmune myocarditis by gastric gavage for 3 weeks, at the stage of development of the inflammatory process. Immunohistochemical staining for RhoA and ROCK1 was evaluated semi-quantitatively with H-score. The RhoA staining showed no significant differences in expression between the groups, but the ROCK1 expression was significantly upregulated in the hearts of the EAM group and was not downregulated by simvastatin. The Western blotting analysis of the last downstream product of the RhoA/ROCK axis, phosphorylated myosin light chain (phospho-MYL9), revealed that protein content increased in EAM hearts and it was prevented by the highest dose of simvastatin. Our findings suggest that the RhoA/ROCK pathway is upregulated in EAM, and simvastatin in EAM settings inhibits the RhoA/ROCK pathway at the stage of phosphorylation of myosin light chains and provides a new insight into the molecular pathology of autoimmune myocarditis. Full article
(This article belongs to the Special Issue Advances in Myocarditis: Molecular and Immune Mechanisms, Diagnosis and Treatment)
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Review

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16 pages, 1601 KiB  
Review
Immunomodulating and Immunosuppressive Therapy for Virus-Negative Immune-Mediated Myocarditis
by Andrea Frustaci, Claudio Letizia, Maria Alfarano, Giulia Marchionni, Romina Verardo and Cristina Chimenti
Biomedicines 2024, 12(7), 1565; https://doi.org/10.3390/biomedicines12071565 - 15 Jul 2024
Viewed by 683
Abstract
Myocarditis is an inflammatory disease of the myocardium caused by infectious and noninfectious agents. Clinical manifestations range from mildly symptomatic forms to acute heart failure, cardiogenic shock, life-threatening arrhythmias and sudden death. Myocarditis is still a challenging diagnosis because of its wide variability [...] Read more.
Myocarditis is an inflammatory disease of the myocardium caused by infectious and noninfectious agents. Clinical manifestations range from mildly symptomatic forms to acute heart failure, cardiogenic shock, life-threatening arrhythmias and sudden death. Myocarditis is still a challenging diagnosis because of its wide variability in clinical presentation and unpredictable course. Moreover, a standardized, specific treatment in not yet available. Immunosuppressive treatment for virus-negative lymphocytic myocarditis is still controversial. Conversely, immunosuppression is well established in sarcoidosis, eosinophilic, giant-cell, drug hypersensitivity, and trauma-related myocarditis as well as lymphocytic myocarditis associated with connective tissue diseases or with the rejection of a transplanted heart. Recently, immunosuppressive therapy has been also recognized as an effective treatment in virus-negative inflammatory cardiomyopathy. The aim of this review is to underline the role of immunomodulating and immunosuppressive therapies in patients with immune-mediated myocarditis and illustrate the different treatment strategies depending on the etiology. An endomyocardial biopsy remains the gold standard for the diagnosis of myocarditis as well as for a tailored treatment. Full article
(This article belongs to the Special Issue Advances in Myocarditis: Molecular and Immune Mechanisms, Diagnosis and Treatment)
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22 pages, 15855 KiB  
Review
Storytelling of Myocarditis
by Gaetano Thiene
Biomedicines 2024, 12(4), 832; https://doi.org/10.3390/biomedicines12040832 - 9 Apr 2024
Viewed by 1115
Abstract
In 1900, Fiedler first reported autopsy cases with peculiar inflammation of the myocardium, which he named interstitial myocarditis. He postulated an isolated cardiac inflammation of the myocardium in the absence of multiorgan involvement and with a poor prognosis due to invisible microorganisms, which [...] Read more.
In 1900, Fiedler first reported autopsy cases with peculiar inflammation of the myocardium, which he named interstitial myocarditis. He postulated an isolated cardiac inflammation of the myocardium in the absence of multiorgan involvement and with a poor prognosis due to invisible microorganisms, which years later would have been identified as viruses. The revision of original histologic sections by Schmorl showed cases with lymphocytes and others with giant-cell inflammatory histotypes. The in vivo diagnosis of myocarditis became possible thanks to right cardiac catheterization with endomyocardial biopsy (EMB). The gold standard for diagnosis was achieved with the employment of immunohistochemistry and molecular investigation by Polymerase Chain Reaction (PCR), which allows for the detection of viruses as causal agents. Both RNA and DNA were revealed to be cardiotropic, with a common receptor (CAR). A protease, coded by coxsackie virus, disrupts the cytoskeleton and accounts for cell death. Unfortunately, vaccination, despite having been revealed to be effective in animal experiments, has not yet entered the clinical field for prevention. Cardiac Magnetic Resonance turned out to be a revolutionary tool for in vivo diagnosis through the detection of edema (inflammatory exudate). Myocarditis may be fulminant in terms of clinical presentation but not necessarily fatal. The application of ExtraCorporeal Membrane Oxygenation (ECMO) allows for relieving the overloaded native heart. Full article
(This article belongs to the Special Issue Advances in Myocarditis: Molecular and Immune Mechanisms, Diagnosis and Treatment)
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18 pages, 2757 KiB  
Review
Eosinophilic Myocarditis: From Bench to Bedside
by Francesco Piccirillo, Sara Mastroberardino, Vincenzo Nafisio, Matteo Fiorentino, Andrea Segreti, Annunziata Nusca, Gian Paolo Ussia and Francesco Grigioni
Biomedicines 2024, 12(3), 656; https://doi.org/10.3390/biomedicines12030656 - 14 Mar 2024
Viewed by 2243
Abstract
Myocarditis is a polymorphic and potentially life-threatening disease characterized by a large variability in clinical presentation and prognosis. Within the broad spectrum of etiology, eosinophilic myocarditis represents a rare condition characterized by eosinophilic infiltration of the myocardium, usually associated with peripheral eosinophilia. Albeit [...] Read more.
Myocarditis is a polymorphic and potentially life-threatening disease characterized by a large variability in clinical presentation and prognosis. Within the broad spectrum of etiology, eosinophilic myocarditis represents a rare condition characterized by eosinophilic infiltration of the myocardium, usually associated with peripheral eosinophilia. Albeit uncommon, eosinophilic myocarditis could be potentially life-threatening, ranging from mild asymptomatic disease to multifocal widespread infiltrates associated with myocardial necrosis, thrombotic complications, and endomyocardial fibrosis. Moreover, it could progress to dilated cardiomyopathy, resulting in a poor prognosis. The leading causes of eosinophilic myocarditis are hypersensitivity reactions, eosinophilic granulomatosis with polyangiitis, cancer, hyper-eosinophilic syndrome variants, and infections. A thorough evaluation and accurate diagnosis are crucial to identifying the underlying cause and defining the appropriate therapeutic strategy. On these bases, this comprehensive review aims to summarize the current knowledge on eosinophilic myocarditis, providing a schematic and practical approach to diagnosing, evaluating, and treating eosinophilic myocarditis. Full article
(This article belongs to the Special Issue Advances in Myocarditis: Molecular and Immune Mechanisms, Diagnosis and Treatment)
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