Myocarditis: Etiology, Pathogenesis, and Their Implications in Clinical Practice

Brociek, Emil; Tymińska, Agata; Giordani, Andrea Silvio; Caforio, Alida L.P.; Wojnicz, Romuald; Grabowski, Marcin; Ozierański, Krzysztof

doi:10.3390/biology12060874

Cited by 9 publications

(6 citation statements)

References 192 publications

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“…In adolescent males, however, myocarditis can have a mild outward clinical appearance yet result in severe cardiac fibrosis (scarring), with permanent damage to the heart muscle [274,275]. Such damage can eventually lead to congestive heart failure and death many years later [276]. The registrational trials were insufficient for detecting these long-range hazards, most of which only became evident after 2.5 years of follow-up observation and over a billion mRNA injections.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 mRNA Vaccines: Lessons Learned from the Registrational Trials and Global Vaccination Campaign

Mead,

Seneff,

Wolfinger

et al. 2024

Cureus

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Our understanding of COVID-19 vaccinations and their impact on health and mortality has evolved substantially since the first vaccine rollouts. Published reports from the original randomized phase 3 trials concluded that the COVID-19 mRNA vaccines could greatly reduce COVID-19 symptoms. In the interim, problems with the methods, execution, and reporting of these pivotal trials have emerged. Re-analysis of the Pfizer trial data identified statistically significant increases in serious adverse events (SAEs) in the vaccine group. Numerous SAEs were identified following the Emergency Use Authorization (EUA), including death, cancer, cardiac events, and various autoimmune, hematological, reproductive, and neurological disorders. Furthermore, these products never underwent adequate safety and toxicological testing in accordance with previously established scientific standards. Among the other major topics addressed in this narrative review are the published analyses of serious harms to humans, quality control issues and process-related impurities, mechanisms underlying adverse events (AEs), the immunologic basis for vaccine inefficacy, and concerning mortality trends based on the registrational trial data. The risk-benefit imbalance substantiated by the evidence to date contraindicates further booster injections and suggests that, at a minimum, the mRNA injections should be removed from the childhood immunization program until proper safety and toxicological studies are conducted. Federal agency approval of the COVID-19 mRNA vaccines on a blanket-coverage population-wide basis had no support from an honest assessment of all relevant registrational data and commensurate consideration of risks versus benefits. Given the extensive, well-documented SAEs and unacceptably high harm-to-reward ratio, we urge governments to endorse a global moratorium on the modified mRNA products until all relevant questions pertaining to causality, residual DNA, and aberrant protein production are answered.

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Section: Discussionmentioning

confidence: 99%

COVID-19 mRNA Vaccines: Lessons Learned from the Registrational Trials and Global Vaccination Campaign

Mead,

Seneff,

Wolfinger

et al. 2024

Cureus

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“…Additionally, international studies have also highlighted the antifibrotic and anti-inflammatory effects of the S/V, particularly relevant in the context of AM [4,15,23].…”

Section: Discussionmentioning

confidence: 99%

Вибір Блокатора Ренін-Ангіотензин-Альдостеронової Системи Для Лікування Серцевої Недостатності При Гострому Міокардиті

Nesukay,

Kovalenko,

Cherniuk

et al. 2024

UJC

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The aim – to evaluate the effectiveness of sacubitril/valsartan and enalapril in heart failure treatment in patients with acute severe myocarditis with reduced left ventricular ejection fraction based on dynamic analysis of the heart structural and functional changes.Materials and methods. The study is based on the results of examinations of 90 patients with a severe course of acute myocarditis (AM) with reduced ejection fraction (EF) of the left ventricle (LV) – ≤40 %. The patients were divided into two groups: the 1st group included 48 patients who were treated with an angiotensin-converting enzyme (ACE) inhibitor – enalapril as part of heart failure (HF) therapy; the 2nd group included 42 patients with AM who received the sacubitril/valsartan combination instead of enalapril in the complex therapy of HF. All patients underwent a 6-minute walk test, echocardiography (EchoCG) with the speckle-tracking method, and cardiac magnetic resonance imaging (CMR). Examinations were carried out three times: in the 1st month from the onset of AM symptoms before the appointment of drug therapy, after 6 and 12 months of observation. Part of the patients from the 1st group, namely 25 patients (52.1 %) in whom the use of ACE inhibitors proved to be ineffective after six months, was transferred to the combination of sacubitril/valsartan (group 1A).Results and discussion. After six months of treatment, compared to the 1st group, the patients of the 2nd group were distinguished by better indicators of the structural and functional state of the heart, which characterise the contractility and volume of the LV – the values of LV EF and LV longitudinal global systolic strain (LGSS) were higher by 13,7 and 26.2 % respectively, LV end-diastolic volume index (EDVi) was 13.2% lower, as well as a 21.7 % lower number of LV segments in which delayed contrast was detected on cardiac MRI. After six months of taking the sacubitril/valsartan combination in 1A group patients, an improvement in the structural and functional state of the heart was also achieved: the values of LVEF and LGSS increased by 19.2 % and 27.9 %, respectively, and LV EDVi decreased by 19.0 %; the number of LV segments in which delayed enhancement was determined on cardiac MRI decreased by 30.7 %. With the help of regression analysis, it was established the presence of a set of factors that determine the priority of prescribing the sacubitril/valsartan combination as initial therapy in patients with severe myocarditis: presence of reduced LVEF – ≤40 %; pronounced decrease in longitudinal and circular global LV strain – ≤8.5 and ≤9.0 %, respectively; pronounced dilatation of the LV – EDVi ≥102 ml/m2; presence of III or higher HF functional class; presence of delayed enhancement in ≥ 5,0 LV segments according to cardiac MRI data.Conclusions. In patients with a severe course of myocarditis, the sacubitril/valsartan combination prescribed as initial therapy showed higher effectiveness compared to ACE inhibitors in terms of improving contractility and reducing LV dilatation, as well as improving the functional class of heart failure. A complex of factors has been established that prove the expediency of prescribing the sacubitril/valsartan combination as initial therapy for heart failure in patients with acute myocarditis.

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“…Acute myocarditis can be induced by a multitude of infectious agents, primarily viruses, though bacteria and parasites may also play a role. Geographic variability in the etiology of myocarditis is observed in relation to demographic factors, with viral etiologies prevailing in developed countries, while Central and South America exhibit a higher incidence of Chagas disease, caused by the protozoan Trypanosoma Cruzi [ 15 ]. Historically, enteroviruses and adenoviruses were recognized as the predominant etiological agents of viral myocarditis.…”

Section: Etiology: Infectious Versus Non-infectious Myocarditismentioning

confidence: 99%

“… A schematic résumé of possible myocarditis etiologies; adapted from Brociek et al [ 15 ] and from Tschöpe et al [ 16 ]. The list is not exhaustive.…”

Section: Figurementioning

confidence: 99%

The Role of the Immune System in Pathobiology and Therapy of Myocarditis: A Review

Vicenzetto,

Giordani,

Menghi

et al. 2024

Biomedicines

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The role of the immune system in myocarditis onset and progression involves a range of complex cellular and molecular pathways. Both innate and adaptive immunity contribute to myocarditis pathogenesis, regardless of its infectious or non-infectious nature and across different histological and clinical subtypes. The heterogeneity of myocarditis etiologies and molecular effectors is one of the determinants of its clinical variability, manifesting as a spectrum of disease phenotype and progression. This spectrum ranges from a fulminant presentation with spontaneous recovery to a slowly progressing, refractory heart failure with ventricular dysfunction, to arrhythmic storm and sudden cardiac death. In this review, we first examine the updated definition and classification of myocarditis at clinical, biomolecular and histopathological levels. We then discuss recent insights on the role of specific immune cell populations in myocarditis pathogenesis, with particular emphasis on established or potential therapeutic applications. Besides the well-known immunosuppressive agents, whose efficacy has been already demonstrated in human clinical trials, we discuss the immunomodulatory effects of other drugs commonly used in clinical practice for myocarditis management. The immunological complexity of myocarditis, while presenting a challenge to simplistic understanding, also represents an opportunity for the development of different therapeutic approaches with promising results.

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Myocarditis: Etiology, Pathogenesis, and Their Implications in Clinical Practice

Cited by 9 publications

References 192 publications

COVID-19 mRNA Vaccines: Lessons Learned from the Registrational Trials and Global Vaccination Campaign

COVID-19 mRNA Vaccines: Lessons Learned from the Registrational Trials and Global Vaccination Campaign

Вибір Блокатора Ренін-Ангіотензин-Альдостеронової Системи Для Лікування Серцевої Недостатності При Гострому Міокардиті

The Role of the Immune System in Pathobiology and Therapy of Myocarditis: A Review

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