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1.
Clin Exp Rheumatol ; 40(4): 834-837, 2021 Oct.
Article in English | MEDLINE | ID: mdl-35522541

ABSTRACT

Eosinophilic granulomatosis with polyangiitis (EGPA) is characterised by many features, including asthma, allergic rhinitis, peripheral and tissue eosinophilia, and vasculitis. Its pathophysiology is still unclear and we suggest that there are different phenotypes of EGPA, which may respond differently to available treatments. Within the most promising targeting biotherapy, benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, has proved both highly effective and safe. We report herewith a case of EGPA presenting a myocarditis relapse successfully treated with benralizumab.


Subject(s)
Churg-Strauss Syndrome , Granulomatosis with Polyangiitis , Myocarditis , Antibodies, Monoclonal, Humanized/therapeutic use , Churg-Strauss Syndrome/complications , Churg-Strauss Syndrome/drug therapy , Granulomatosis with Polyangiitis/complications , Granulomatosis with Polyangiitis/drug therapy , Humans , Myocarditis/drug therapy , Myocarditis/etiology
4.
J Immunother Cancer ; 10(4)2022 Apr.
Article in English | MEDLINE | ID: mdl-35383117

ABSTRACT

Immune-checkpoint inhibitors (ICI) have revolutionized cancer therapy but are associated with infrequent but lethal myocarditis, for which management remains uncertain. Abatacept, a CTLA-4 fusion protein targeting CD86 on antigen presenting cells and leading to global T-cell anergy, has been described as a potential treatment in individual reports. Yet, abatacept treatment dosage, schedule and optimal combination with other immunosuppressive therapies are unclear. We describe a 25-year-old man who developed pembrolizumab (anti-PD1)-induced myocarditis 14 days after first injection for thymoma treatment, which deteriorated into cardiogenic shock, with sustained ventricular arrhythmia, requiring urgent extracorporeal life support implantation, despite prompt initiation of corticosteroids and mycophenolate-mofetil. Using a strategy of serial measurement ensuring with a target of >80% CD86 receptor occupancy on circulating monocytes, abatacept dose was adjusted and combined with ruxolitinib and methylprednisolone. This strategy resulted in high-dose of abatacept: 60 mg/kg in three doses (20 mg/kg each) within the first 10 days, followed by two doses. Clinical improvement occurred within 7 days, with resolution of systolic cardiac dysfunction, and ventricular arrhythmias resulting in successful discharge from hospital. We reversed a case of nearly lethal ICI-myocarditis, using specific patient-dose adjusted abatacept, which may serve as basis for personalized treatment of patients with severe ICI-adverse events. Trial registration number: NCT04294771.


Subject(s)
Abatacept , Immune Checkpoint Inhibitors , Myocarditis , Pyrazoles , Abatacept/adverse effects , Abatacept/therapeutic use , Adult , Humans , Immune Checkpoint Inhibitors/adverse effects , Male , Myocarditis/chemically induced , Myocarditis/drug therapy , Nitriles , Pyrazoles/adverse effects , Pyrazoles/therapeutic use , Pyrimidines
5.
Int J Biochem Cell Biol ; 146: 106208, 2022 May.
Article in English | MEDLINE | ID: mdl-35381374

ABSTRACT

Viral myocarditis (VMC) is the main cause of sudden acute heart failure and cardiac death in adolescents; however, treatment for VMC is limited. Trehalose is a natural non-reductive disaccharide that protects against cardiovascular diseases by inducing autophagy. The protective effect of trehalose on VMC and the specific mechanism remains unclear. In this study, we established a VMC mouse model, treated with trehalose in vivo, and cultured B cells from VMC mice with trehalose in vitro to elucidate the effect of trehalose on B cells in acute VMC. Trehalose alleviated myocardial injury in VMC mice and increased the number of autophagosomes, LC3II/LC3I ratio, and expression level of LAMP2, whereas it decreased the expression of p62 in VMC-B cells. Bafilomycin A1 suppressed VMC-B cell autophagy induced by trehalose. At the mechanistic level, trehalose treatment significantly upregulated the phosphorylation of AMPK and ULK1 in VMC-B cells. Dorsomorphin and SBI-0206965 abolished the increased phosphorylation level and altered the expression levels of autophagy-related proteins. In conclusion, trehalose alleviates myocardial inflammatory damage of VMC by inducing B cell autophagy, mediated by the AMPK/ULK1 signalling pathway. Thus, trehalose may be a potentially useful molecule for alleviating myocardial injury in VMC.


Subject(s)
Coxsackievirus Infections , Myocarditis , AMP-Activated Protein Kinases/metabolism , Animals , Autophagy , Autophagy-Related Protein-1 Homolog , Coxsackievirus Infections/complications , Coxsackievirus Infections/drug therapy , Coxsackievirus Infections/metabolism , Mice , Mice, Inbred BALB C , Myocarditis/drug therapy , Trehalose/pharmacology , Trehalose/therapeutic use
6.
Immunotherapy ; 14(7): 511-520, 2022 May.
Article in English | MEDLINE | ID: mdl-35321560

ABSTRACT

Immune checkpoint inhibitors have been incorporated into the treatment of various malignancies. An increasing body of literature is reporting rare but potentially fatal adverse events associated with these agents. In this case series, the authors report the clinical features and outcomes of seven patients who received immune checkpoint inhibitors for different solid organ malignancies and developed a tetrad of immune-related myocarditis, myositis, myasthenia gravis and transaminitis. Herein the authors review the literature and describe the current diagnostic and management approach for this overlapping syndrome. The authors' series highlights the importance of a high index of clinical suspicion, prompt comprehensive investigations, early multidisciplinary team involvement and initiation of immunosuppressive therapy when immune-related adverse events are suspected.


Cancer immunotherapy is used in the treatment of different cancer types. Immunotherapy activates the immune system to detect and attack cancer cells, but side effects may arise from the immune system inadvertently attacking normal tissues and organs. The increased use of immunotherapy has led to an increase in the reporting of rare but potentially life-threatening treatment-related side effects. In this case series, the authors report the clinical features and outcomes of seven patients who developed inflammation of the heart, muscles, nerve and muscle junctions and liver following treatment with immunotherapy. The authors review the scientific literature and discuss the current understanding of and management approach to this rare syndrome. The authors' report highlights the importance of a high degree of clinical suspicion, prompt comprehensive testing to confirm diagnosis, early involvement of experts from different specialties and early initiation of treatment in the management of this unique syndrome.


Subject(s)
Myasthenia Gravis , Myocarditis , Myositis , Neoplasms , Humans , Immune Checkpoint Inhibitors/adverse effects , Myasthenia Gravis/chemically induced , Myocarditis/chemically induced , Myocarditis/diagnosis , Myocarditis/drug therapy , Myositis/chemically induced , Myositis/diagnosis , Neoplasms/drug therapy
7.
ESC Heart Fail ; 9(3): 2020-2026, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35322589

ABSTRACT

Immune checkpoint inhibitors (ICIs) have become a new hope for many patients with advanced cancer by blocking tumour immune evasion. However, with the widespread use of ICIs, immune-related adverse events (irAEs) have also been discovered and reported increasingly. Immune-related myocarditis, the most dangerous one of irAEs, still has high mortality in the context of the current treatment. We report the case of a 60-year-old female with fulminant myocarditis induced by ICIs, which caused her to experience frequent ventricular arrhythmias such as ventricular fibrillation and heart failure. She was successfully treated with current mainstream therapies for immune-related myocarditis and additional treatment of sacubitril-valsartan and dapagliflozin. The intriguing observation that the patient condition recovered relatively rapidly in this case shows a possible treatment inspiration, which may be helpful for treating ICIs-associated myocarditis and improving cancer patients' clinical prognosis.


Subject(s)
Myocarditis , Neoplasms , Aminobutyrates , Biphenyl Compounds , Female , Humans , Immune Checkpoint Inhibitors/adverse effects , Middle Aged , Myocarditis/chemically induced , Myocarditis/diagnosis , Myocarditis/drug therapy
8.
Oxid Med Cell Longev ; 2022: 1344946, 2022.
Article in English | MEDLINE | ID: mdl-35265259

ABSTRACT

Due to existing evidence regarding antioxidant and anti-inflammatory effects of Melissa officinalis extracts (MOEs), this study was aimed at investigating the potential of ethanolic MOE to prevent the development of myocarditis and its ability to ameliorate the severity of experimental autoimmune myocarditis (EAM) by investigating MOE effects on in vivo cardiac function, structure, morphology, and oxidative stress parameters. A total of 50 7-week-old male Dark Agouti rats were enrolled in the study and randomly allocated into the following groups: CTRL, nontreated healthy rats; EAM, nontreated rats with EAM; MOE50, MOE100, and MOE200, rats with EAM treated with either 50, 100, or 200 mg/kg of MOE for 3 weeks per os. Myocarditis was induced by immunization of the rats with porcine myocardial myosin (0.5 mg) emulsion on day 0. Cardiac function and dimensions of the left ventricle (LV) were assessed via echocardiography. Additionally, the blood pressure and heart rate were measured. On day 21, rats were sacrificed and the hearts were isolated for further histopathological analyses (H/E and Picrosirius red staining). The blood samples were collected to determine oxidative stress parameters. The EAM group characteristically showed greater LV wall thickness and lower ejection fraction (50.33 ± 7.94% vs. 84.81 ± 7.74%) and fractional shortening compared to CTRL (p < 0.05). MOE significantly improved echocardiographic parameters (EF in MOE200 81.44 ± 5.51%) and also reduced inflammatory infiltrate (by 88.46%; p < 0.001) and collagen content (by 76.39%; p < 0.001) in the heart tissues, especially in the MOE200 group compared to the EAM group. In addition, MOEs induced a significant decrease of prooxidants production (O2 -, H2O2, and TBARS) and improved antioxidant defense system via increase in GSH, SOD, and CAT compared to EAM, with medium and high dose being more effective than low dose (p < 0.05). The present study suggests that ethanolic MOEs, especially in a 200 mg/kg dose, improve cardiac function and myocardial architecture, possibly via oxidative stress mitigation, thus preventing heart remodeling, development of dilated cardiomyopathy, and subsequent heart failure connected with EAM. MOEs might be considered as a potentially helpful adjuvant therapy in patients with autoimmune myocarditis.


Subject(s)
Autoimmune Diseases/drug therapy , Melissa/chemistry , Myocarditis/drug therapy , Animals , Disease Models, Animal , Humans , Male , Rats
9.
BMJ Case Rep ; 15(3)2022 Mar 07.
Article in English | MEDLINE | ID: mdl-35256366

ABSTRACT

A woman in her 20s presented with chest pain, dyspnoea, arthralgia, muscle weakness and skin discolouration. She was diagnosed with dermatomyositis. During her admission, she developed pleuritic chest pain and shortness of breath accompanied by a significant troponin I rise. Her echocardiogram showed a hyperdynamic left ventricle with a trivial pericardial effusion; there were no regional wall motion abnormalities. Gadolinium-diethylenetriaminepantaacetic-enhanced cardiac MRI showed extensive myocarditis. She was started on corticosteroids and azathioprine which led to an improvement of symptoms and biochemical markers.


Subject(s)
Dermatomyositis , Myocarditis , Pericardial Effusion , Dermatomyositis/complications , Dermatomyositis/diagnosis , Dermatomyositis/drug therapy , Female , Gadolinium , Humans , Magnetic Resonance Imaging , Myocarditis/complications , Myocarditis/diagnosis , Myocarditis/drug therapy , Pericardial Effusion/complications
10.
J Psychiatr Pract ; 28(2): 170-175, 2022 Mar 03.
Article in English | MEDLINE | ID: mdl-35238829

ABSTRACT

BACKGROUND: Clozapine, an antipsychotic medication used to treat treatment-refractory schizophrenia, has been associated with various dangerous side effects, including myocarditis. However, there have been few published cases reporting on patients with clozapine-induced myocarditis confirmed by cardiac magnetic resonance imaging or the management, treatment, and follow-up of these patients. METHODS: This report describes 2 cases of patients with treatment-refractory schizophrenia evidencing transient clozapine-induced myocarditis. Detailed information including laboratory values, imaging results, and clinical notes were gathered. FINDINGS: The 2 cases demonstrated differing manifestations of clozapine-induced myocarditis. Both cases showed that such myocarditis can be transient and can be treated clinically with close observation without discontinuation of clozapine. IMPLICATIONS: These cases show that clozapine-induced myocarditis is transient at times and can self-resolve without discontinuation of clozapine. These observations may suggest a change in clinical practice so that, with close observation, we can avoid risking psychiatric decompensation in select patients with a history of treatment-resistant schizophrenia.


Subject(s)
Antipsychotic Agents , Clozapine , Drug-Related Side Effects and Adverse Reactions , Myocarditis , Antipsychotic Agents/adverse effects , Clozapine/adverse effects , Humans , Magnetic Resonance Imaging , Myocarditis/chemically induced , Myocarditis/drug therapy
11.
Viruses ; 14(2)2022 01 31.
Article in English | MEDLINE | ID: mdl-35215893

ABSTRACT

INTRODUCTION: This study investigated the spontaneous clinical course of patients with endomyocardial biopsy (EMB)-proven lymphocytic myocarditis and cardiac human herpesvirus 6 (HHV6) DNA presence, and the effectiveness of steroid-based intervention in HHV6-positive patients. RESULTS: 756 heart failure (HF) patients underwent an EMB procedure to determine the underlying cause of unexplained HF. Low levels of HHV6 DNA, detectable by nested PCR only, were found in 10.4% of the cases (n = 79) of which 62% (n = 49) showed myocardial inflammation. The spontaneous course of patients with EMB-proven HHV6 DNA-associated lymphocytic myocarditis (n = 26) showed significant improvements in the left ventricular ejection fraction (LVEF) and clinical symptoms, respectively, in 15/26 (60%) patients, 3-12 months after disease onset. EMB mRNA expression of components of the NLRP3 inflammasome pathway and protein analysis of cardiac remodeling markers, analyzed by real-time PCR and MALDI mass spectrometry, respectively, did not differ between HHV6-positive and -negative patients. In another cohort of patients with ongoing symptoms related to lymphocytic myocarditis associated with cardiac levels of HHV6-DNA copy numbers <500 copies/µg cardiac DNA, quantified by real-time PCR, the efficacy and safety of steroid-based immunosuppression for six months was investigated. Steroid-based immunosuppression improved the LVEF (≥5%) in 8/10 patients and reduced cardiac inflammation in 7/10 patients, without an increase in cardiac HHV6 DNA levels in follow-up EMBs. CONCLUSION: Low HHV6 DNA levels are frequently detected in the myocardium, independent of inflammation. In patients with lymphocytic myocarditis with low levels of HHV6 DNA, the spontaneous clinical improvement is nearby 60%. In selected symptomatic patients with cardiac HHV6 DNA copy numbers less than 500 copies/µg cardiac DNA and without signs of an active systemic HHV6 infection, steroid-based therapy was found to be effective and safe. This finding needs to be further confirmed in large, randomized trials.


Subject(s)
Herpesvirus 6, Human/physiology , Immunosuppressive Agents/administration & dosage , Myocarditis/drug therapy , Myocarditis/virology , Roseolovirus Infections/drug therapy , Roseolovirus Infections/virology , Steroids/administration & dosage , Adult , Aged , Biopsy , Cohort Studies , DNA, Viral/genetics , Female , Gene Dosage , Herpesvirus 6, Human/genetics , Herpesvirus 6, Human/isolation & purification , Humans , Male , Middle Aged , Myocarditis/immunology , Myocarditis/physiopathology , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/immunology , Roseolovirus Infections/immunology , Roseolovirus Infections/physiopathology , Stroke Volume
12.
Signal Transduct Target Ther ; 7(1): 57, 2022 02 23.
Article in English | MEDLINE | ID: mdl-35197452

ABSTRACT

The coronavirus disease 2019 (COVID-19) is a highly transmissible disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that poses a major threat to global public health. Although COVID-19 primarily affects the respiratory system, causing severe pneumonia and acute respiratory distress syndrome in severe cases, it can also result in multiple extrapulmonary complications. The pathogenesis of extrapulmonary damage in patients with COVID-19 is probably multifactorial, involving both the direct effects of SARS-CoV-2 and the indirect mechanisms associated with the host inflammatory response. Recognition of features and pathogenesis of extrapulmonary complications has clinical implications for identifying disease progression and designing therapeutic strategies. This review provides an overview of the extrapulmonary complications of COVID-19 from immunological and pathophysiologic perspectives and focuses on the pathogenesis and potential therapeutic targets for the management of COVID-19.


Subject(s)
Acute Kidney Injury/complications , COVID-19/complications , Cytokine Release Syndrome/complications , Disseminated Intravascular Coagulation/complications , Lymphopenia/complications , Myocarditis/complications , Pulmonary Embolism/complications , Acute Kidney Injury/drug therapy , Acute Kidney Injury/immunology , Acute Kidney Injury/virology , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/immunology , COVID-19/virology , Clinical Trials as Topic , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/immunology , Disseminated Intravascular Coagulation/virology , Endothelial Cells/drug effects , Endothelial Cells/immunology , Endothelial Cells/virology , Humans , Immunity, Innate/drug effects , Immunologic Factors/therapeutic use , Lymphopenia/drug therapy , Lymphopenia/immunology , Lymphopenia/virology , Myocarditis/drug therapy , Myocarditis/immunology , Myocarditis/virology , Pulmonary Embolism/drug therapy , Pulmonary Embolism/immunology , Pulmonary Embolism/virology , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/immunology , SARS-CoV-2/drug effects , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity
13.
ESC Heart Fail ; 9(2): 925-941, 2022 04.
Article in English | MEDLINE | ID: mdl-35178861

ABSTRACT

AIM: The acute phase of a coxsackievirus 3 (CVB3)-induced myocarditis involves direct toxic cardiac effects and the systemic activation of the immune system, including the cardiosplenic axis. Consequently, the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) inflammasome pathway is activated, which plays a role in disease pathogenesis and progression. The anti-inflammatory drug colchicine exerts its effects, in part, via reducing NLRP3 activity, and has been shown to improve several cardiac diseases, including acute coronary syndrome and pericarditis. The aim of the present study was to evaluate the potential of colchicine to improve experimental CVB3-induced myocarditis. METHODS AND RESULTS: C57BL6/j mice were intraperitoneally injected with 1 × 105 plaque forming units of CVB3. After 24 h, mice were treated with colchicine (5 µmol/kg body weight) or phosphate-buffered saline (PBS) via oral gavage (p.o.). Seven days post infection, cardiac function was haemodynamically characterized via conductance catheter measurements. Blood, the left ventricle (LV) and spleen were harvested for subsequent analyses. In vitro experiments on LV-derived fibroblasts (FB) and HL-1 cells were performed to further evaluate the anti-(fibro)inflammatory and anti-apoptotic effects of colchicine via gene expression analysis, Sirius Red assay, and flow cytometry. CVB3 + colchicine mice displayed improved LV function compared with CVB3 + PBS mice, paralleled by a 4.7-fold (P < 0.01) and 1.7-fold (P < 0.001) reduction in LV CVB3 gene expression and cardiac troponin-I levels in the serum, respectively. Evaluation of components of the NLRP3 inflammasome revealed an increased percentage of apoptosis-associated speck-like protein containing a CARD domain (ASC)-expressing, caspase-1-expressing, and interleukin-1ß-expressing cells in the myocardium and in the spleen of CVB3 + PBS vs. control mice, which was reduced in CVB3 + colchicine compared with CVB3 + PBS mice. This was accompanied by 1.4-fold (P < 0.0001), 1.7-fold (P < 0.0001), and 1.7-fold (P < 0.0001) lower numbers of cardiac dendritic cells, natural killer cells, and macrophages, respectively, in CVB3 + colchicine compared with CVB3 + PBS mice. A 1.9-fold (P < 0.05) and 4.6-fold (P < 0.001) reduced cardiac gene expression of the fibrotic markers, Col1a1 and lysyl oxidase, respectively, was detected in CVB3 + colchicine mice compared with CVB3 + PBS animals, and reflected by a 2.2-fold (P < 0.05) decreased Collagen I/III protein ratio. Colchicine further reduced Col3a1 mRNA and collagen protein expression in CVB3-infected FB and lowered apoptosis and viral progeny release in CVB3-infected HL-1 cells. In both CVB3 FB and HL-1 cells, colchicine down-regulated the NLRP3 inflammasome-related components ASC, caspase-1, and IL-1ß. CONCLUSIONS: Colchicine improves LV function in CVB3-induced myocarditis, involving a decrease in cardiac and splenic NLRP3 inflammasome activity, without exacerbation of CVB3 load.


Subject(s)
Inflammasomes , Myocarditis , Animals , Colchicine/pharmacology , Colchicine/therapeutic use , Disease Progression , Humans , Inflammasomes/metabolism , Inflammasomes/therapeutic use , Mice , Myocarditis/drug therapy , Myocarditis/prevention & control , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
14.
Zhongguo Zhong Yao Za Zhi ; 47(3): 829-835, 2022 Feb.
Article in Chinese | MEDLINE | ID: mdl-35178966

ABSTRACT

To evaluate the pharmacoeconomic value of Qidong Yixin Oral Liquid in the treatment of viral myocarditis(Qi-Yin deficiency syndrome) by supplementing Qi, nourishing the heart, calming the mind, and relieving palpitation, the present study performed the Meta-analysis based on the published papers on Qidong Yixin Oral Liquid by AMSTAR and carried out pharmacoeconomic evaluation using TreeAge Pro by the cost-effectiveness analysis. The results showed that the quality of the included papers was good. After four weeks of treatment, Qidong Yixin Oral Liquid combined with the conventional treatment regimen was superior to the conventional treatment in improving creatine kinase isoenzyme, and the difference was statistically significant. Furthermore, the treatment cost was also higher than that of conventional treatment, with an incremental cost-effectiveness ratio of CNY 95.89, accounting for 0.30% of per capita disposable income. The results of sensitivity analysis showed that the research results were robust. Therefore, based on the assumption that the per capita disposable income in 2020 was the threshold of patients' willingness to pay, it is more economical for patients with viral myocarditis to use Qidong Yixin Oral Liquid combined with conventional secondary prevention regimen than conventio-nal secondary prevention regimen alone. The economic evaluation of Qidong Yixin Oral Liquid in the treatment of viral myocarditis will help physicians and patients choose optimal treatment options, improve rational clinical medication, and provide references for the efficient allocation and utilization of medical resources in China.


Subject(s)
Drugs, Chinese Herbal , Myocarditis , Cost-Benefit Analysis , Drugs, Chinese Herbal/therapeutic use , Economics, Pharmaceutical , Humans , Myocarditis/drug therapy , Qi , Yin Deficiency/drug therapy
17.
Expert Rev Clin Pharmacol ; 15(1): 65-78, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35062840

ABSTRACT

INTRODUCTION: Pharmacovigilance studies have definitely established that clozapine can cause myocarditis. Two published reviews suggested that on rare occasions other antipsychotics may induce myocarditis. AREAS COVERED: This review explored myocarditis associated with antipsychotics other than clozapine by conducting a systematic search of the literature and critically analyzing the current data in VigiBase compared to the data on clozapine-associated myocarditis. VigiBase is the World Health Organization's global pharmacovigilance database that uses a statistical signal for associations with a logarithmic measure of disproportionality called the information component (IC). EXPERT OPINION: For quetiapine, VigiBase provided 106 reports of myocarditis and a significant statistical signal (IC = 1.8; IC025 = 1.5) which was confounded by 48% (51/106) with clozapine co-prescription. Combining the literature and VigiBase cases provided five probable myocarditis cases during quetiapine monotherapy (4 after overdose or rapid titration). For olanzapine, VigiBase provided 107 reports of myocarditis and a significant statistical signal (IC = 2.1; IC025 = 1.8) probably explained by 77% (82/107) using clozapine co-prescription. Combining the literature and VigiBase cases provided one probable myocarditis case during olanzapine monotherapy. Combining the literature and VigiBase provided another three probable cases during therapy with other antipsychotics during overdose or titration with a high dose.


Subject(s)
Antipsychotic Agents , Clozapine , Myocarditis , Antipsychotic Agents/adverse effects , Clozapine/adverse effects , Humans , Myocarditis/chemically induced , Myocarditis/drug therapy , Myocarditis/epidemiology , Olanzapine/adverse effects , Pharmacovigilance
18.
Nat Commun ; 13(1): 25, 2022 01 10.
Article in English | MEDLINE | ID: mdl-35013204

ABSTRACT

While multiple pharmacological drugs have been associated with myocarditis, temporal trends and overall mortality have not been reported. Here we report the spectrum and main features of 5108 reports of drug-induced myocarditis, in a worldwide pharmacovigilance analysis, comprising more than 21 million individual-case-safety reports from 1967 to 2020. Significant association between myocarditis and a suspected drug is assessed using disproportionality analyses, which use Bayesian information component estimates. Overall, we identify 62 drugs associated with myocarditis, 41 of which are categorized into 5 main pharmacological classes: antipsychotics (n = 3108 reports), salicylates (n = 340), antineoplastic-cytotoxics (n = 190), antineoplastic-immunotherapies (n = 538), and vaccines (n = 790). Thirty-eight (61.3%) drugs were not previously reported associated with myocarditis. Antipsychotic was the first (1979) and most reported class (n = 3018). In 2019, the two most reported classes were antipsychotics (54.7%) and immunotherapies (29.5%). Time-to-onset between treatment start and myocarditis is 15 [interquartile range: 10; 23] days. Subsequent mortality is 10.3% and differs between drug classes with immunotherapies the highest, 32.5% and salicylates the lowest, 2.6%. These elements highlight the diversity of presentations of myocarditis depending on drug class, and show the emerging role of antineoplastic drugs in the field of drug-induced myocarditis.


Subject(s)
Myocarditis/chemically induced , Myocarditis/drug therapy , Pharmaceutical Preparations , Pharmacovigilance , Systems Analysis , Adverse Drug Reaction Reporting Systems , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Antipsychotic Agents/adverse effects , Antipsychotic Agents/therapeutic use , Bayes Theorem , Cross-Sectional Studies , Data Management , Databases, Factual , Humans , Immunotherapy , Myocarditis/mortality , World Health Organization
19.
J Theor Biol ; 537: 111002, 2022 03 21.
Article in English | MEDLINE | ID: mdl-35007511

ABSTRACT

Autoimmune myocarditis is a rare, but frequently fatal, side effect of immune checkpoint inhibitors (ICIs), a class of cancer therapies. Despite extensive experimental work on the causes, development and progression of this disease, much still remains unknown about the importance of the different immunological pathways involved. We present a mathematical model of autoimmune myocarditis and the effects of ICIs on its development and progression to either resolution or chronic inflammation. From this, we gain a better understanding of the role of immune cells, cytokines and other components of the immune system in driving the cardiotoxicity of ICIs. We parameterise the model using existing data from the literature, and show that qualitative model behaviour is consistent with disease characteristics seen in patients in an ICI-free context. The bifurcation structures of the model show how the presence of ICIs increases the risk of developing autoimmune myocarditis. This predictive modelling approach is a first step towards determining treatment regimens that balance the benefits of treating cancer with the risk of developing autoimmune myocarditis.


Subject(s)
Myocarditis , Neoplasms , Cardiotoxicity/drug therapy , Cardiotoxicity/etiology , Humans , Immune Checkpoint Inhibitors , Models, Theoretical , Myocarditis/chemically induced , Myocarditis/complications , Myocarditis/drug therapy , Neoplasms/complications , Neoplasms/drug therapy
20.
Front Immunol ; 12: 799077, 2021.
Article in English | MEDLINE | ID: mdl-34975911

ABSTRACT

Immune checkpoint inhibitor (ICI)-associated immune-related adverse events (irAEs) are becoming important safety issues worthy of attention despite the exciting therapeutic prospects. The growing development of new ICIs also brings new cases of irAEs, raising more challenges to clinicians. Cardiac injury is rare but life-threatening among diverse organ injuries, and effective interventions are critical for patients. Here, we report a novel programmed cell death protein-1 (PD-1) inhibitor tislelizumab-associated severe myocarditis and myositis accompanied by liver and kidney damage in a ureteral urothelial cancer patient, who was firstly treated by cardiologists because of cardiac symptoms. Due to the lack of experience about ICI-associated irAEs, an initial low-dose (0.5 mg/kg/day) and short-term methylprednisolone therapy was used and found to be ineffective and risky to the patient; then, steroid therapy was modulated to a higher dose (1.5 mg/kg/day) with prolonged time course, and improvement of patient symptoms and laboratory markers were observed quickly and persistently. The patient did not show adverse events under this steroid dosage. This case reports a rare tislelizumab-related myocarditis and multiple organ injuries, which provides valuable experience to cardiologists like us. Early recognition of ICI-associated myocarditis and sufficient dosage and time course of glucocorticoid therapy are critical for severe cases. High-quality clinical evidence about the precise diagnosis and therapy in ICI-associated myocarditis and other organ injuries are necessary to guide our clinical works.


Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Glucocorticoids/administration & dosage , Immune Checkpoint Inhibitors/adverse effects , Methylprednisolone/administration & dosage , Myocarditis/drug therapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Ureteral Neoplasms/drug therapy , Acute Kidney Injury/chemically induced , Acute Kidney Injury/diagnosis , Acute Kidney Injury/drug therapy , Aged , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/etiology , Drug Administration Schedule , Glucocorticoids/adverse effects , Humans , Male , Methylprednisolone/adverse effects , Myocarditis/chemically induced , Myocarditis/diagnosis , Myositis/chemically induced , Myositis/diagnosis , Myositis/drug therapy , Programmed Cell Death 1 Receptor/immunology , Severity of Illness Index , Time Factors , Treatment Outcome , Ureteral Neoplasms/immunology , Ureteral Neoplasms/pathology
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