La myocardite : une toxicité rare mais grave sous immunothérapie. / [Myocarditis: Uncommon but severe toxicity of immune checkpoint inhibitors].

Traditional cancer therapies, such as treatment with anthracyclines and chest radiation, are known to induce cardiovascular complications. Currently, the increase of cancer therapies will involve new mechanisms such as cancer immunotherapies, also called immune checkpoint inhibitors (PD-1, PD-L1 and CTLA-4 inhibitors). These treatments have shown long-term remissions in subgroup of cancers, including melanomas, non-small-cell lung cancer, urothelial carcinoma, renal cell carcinoma, squamous cell carcinoma of the head and neck and colorectal cancer. Although these treatments will change the natural course of these cancers, they may sometimes induce cardiovascular complications, which has been reported as about 1 % in the literature. Currently, the physicians must keep in mind one uncommon but severe cardiac complication: auto-immune myocarditis. The clinical presentation may include various symptoms like chest pain, heart failure or rhythm disorders. In this situation, a baseline cardiologic check-up before starting cancer immunotherapy may be very helpful. Cardiac biomarkers (troponin and brain natriuretic peptide) and 12-lead resting electrocardiogram must be promptly performed when myocarditis is suspected. A cardiologist's opinion must be requested in emergency to discuss both a transthoracic echocardiography and the appropriate treatment (stopping immunotherapy, adding immunosuppressive treatment such as corticoids) and the monitoring in an intensive care unit. Cardiac MRI and endomyocardial biopsies may help to approach the final diagnosis. In this situation, other cancer therapies may be discussed.

Complications ischémiques de l'artérite à cellules géantes. / [Giant cell arteritis: Ischemic complications].

GCA ischemic complications occur generally in patients with a yet undiagnosed or uncontrolled disease. When disease control is fair, ischemic complications may be due mostly to atheromatosis. Ophtalmic complications are most frequent and are dominated by anterior ischemic optic neuropathy. Vasculitic strokes occur essentially in the vertebrobasilar arterial territory. Overt vasculitic coronary disease is exceptional. The diagnosis of upper and lower limbs ischemic complications benefit from advances in echography (halo sign) and positron emission tomography imaging. Treatment relies on corticosteroids (initially 1mg/kg prednisone or more, preceded by intravenous methylprednisolone gigadoses if necessary), the control of cardiovascular risk factors and antiplatelet drugs; heparin may be indicated for threatening limbs ischemia.

Cardiac troponin I autoantibody induces myocardial dysfunction by PTEN signaling activation.

BACKGROUND: The objective of the current study was to study the molecular mechanism(s) underlying cardiac troponin I autoantibody (cTnIAAb) binding to cardiomyocyte and resultant myocardial damage/dysfunction. METHODS: cTnIAAb was purified from serum of 10 acute myocardial infarction (AMI) patients with left ventricular remodeling. Recombinant human cTnI was used to generate three mouse-derived monoclonal anti-cTnI antibodies (cTnImAb1, cTnImAb2, and cTnImAb3). The target proteins in cardiac myocyte membrane bound to cTnImAb and effect of cTnIAAb and cTnImAb on apoptosis and myocardial function were determined. FINDINGS: We found that cTnIAAb/cTnImAb1 directly bound to the cardiomyocyte membraneα-Enolase (ENO1) and triggered cell apoptosis via increased expression of ENO1 and Bax, decreased expression of Bcl2, subsequently activating Caspase8, Caspase 3, phosphatase and tensin homolog (PTEN) while inhibiting Akt activity. This cTnIAAb-ENO1-PTEN-Akt signaling axis contributed to increased myocardial apoptosis, myocardial collagen deposition, and impaired systolic dysfunction. INTERPRETATION: Results obtained in this study indicate that cTnIAAb is involved in the process of ventricular remodeling after myocardial injury. FUND: The National Natural Science Foundation of China (Grant#: 81260026).

CaMKII Activity in the Inflammatory Response of Cardiac Diseases.

Inflammation is a physiological process by which the body responds to external insults and stress conditions, and it is characterized by the production of pro-inflammatory mediators such as cytokines. The acute inflammatory response is solved by removing the threat. Conversely, a chronic inflammatory state is established due to a prolonged inflammatory response and may lead to tissue damage. Based on the evidence of a reciprocal regulation between inflammation process and calcium unbalance, here we described the involvement of a calcium sensor in cardiac diseases with inflammatory drift. Indeed, the Ca2+/calmodulin-dependent protein kinase II (CaMKII) is activated in several diseases with an inflammatory component, such as myocardial infarction, ischemia/reperfusion injury, pressure overload/hypertrophy, and arrhythmic syndromes, in which it actively regulates pro-inflammatory signaling, among which includes nuclear factor kappa-B (NF-κB), thus contributing to pathological cardiac remodeling. Thus, CaMKII may represent a key target to modulate the severity of the inflammatory-driven degeneration.

Myopericarditis as a presentation of eosinophilic granulomatosus with polyangiitis (EGPA).

A 60-year-old woman was admitted to the hospital with worsening dyspnoea, cough and chest pain. This was on a background of weight loss, decreased appetite, mononeuritis multiplex, chronic eosinophilia and a single episode of a non-blanching rash. Investigations demonstrated a raised troponin and ischaemic changes on ECG, and she was therefore initially treated for a presumed myocardial infarction. However, her symptoms failed to improve with treatment for the acute coronary syndrome. A coronary angiogram revealed no significant flow-limiting disease, and further investigations yielded confirmation of raised eosinophils and a positive perinuclear antineutrophil cytoplasmic antibody test. An echocardiogram demonstrated a pericardial effusion, and subsequent cardiac magnetic resonance features were compatible with myopericarditis. In light of these findings, the patient was diagnosed with eosinophilic granulomatous with polyangiitis and commenced on high-dose intravenous methylprednisolone and cyclophosphamide. She made an excellent recovery and remains in remission on azathioprine and a tapering dose of corticosteroids.

Rapid Disappearance of Intraventricular Mobile Structures with Steroids in Eosinophilic Granulomatosis with Polyangiitis.

Endomyocarditis in Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare complication, commonly involving an apical mass compatible with a thrombus. However, no previous report has discussed mobile structures detected by echocardiography in a patient with EGPA. A 53-year-old man with asthma presented with low-grade fever, consciousness disturbance, and vomiting. Magnetic resonance imaging showed multiple acute infarctions in the bilateral cerebrum and cerebellum. Remarkable eosinophilia was observed, and transthoracic echocardiography showed multiple mobile structures originating from the left ventricular septum. The day after admission, he developed left partial hemianopia and intracranial hemorrhage was identified in his right occipital lobe. Skin biopsy showed infiltration of eosinophils in the arterial wall, and we diagnosed EGPA. Myocardial biopsy was performed from the right ventricular wall, and eosinophilic infiltration into the endocardium and myocardium was observed. Endomyocarditis secondary to EGPA was confirmed, and steroid therapy was immediately initiated. Ten days after steroid therapy, the mobile structures in the left ventricle disappeared completely. He suffered no recurrence of stroke with continued steroid therapy. Mobile structures in the left ventricle in patients with active EGPA could be treated conservatively with steroid therapy.

The spectrum of myocarditis: from pathology to the clinics.

Myocarditis is an inflammatory disease of the myocardium, which may occur in isolation or as part of systemic infectious/immune/autoimmune conditions, characterized by vast aetiologic, clinical and histopathologic heterogeneity. The broad spectrum of myocarditis can be categorized according to the prevalent histopathologic pattern including lymphocytic, lympho-histiocytic, eosinophilic and neutrophilic forms, giant cell myocarditis and myocarditis with granulomata. Diverse histopathologic substrates generally reflect different aetiologies and pathogenetic mechanisms and may be critical to clinical decision-making. Active vasculitis, when present, completes the inflammatory spectrum. Unfortunately, the correlation of histopathologic patterns, clinical presentation and disease course in myocarditis is still largely unresolved, due to limited availability of bioptic samples at specific stages of disease and impracticality of serial sampling. We here review the elements supporting an aetiology-driven diagnostic work-up in myocarditis, emphasizing the importance of integrating pathologic studies with clinical features and information derived from multimodality imaging. Furthermore, we explore myocardial inflammation in genetic cardiomyopathies, its role in driving clinical variability and the potential of transcriptomic and proteomic analysis in our understanding of these complex interrelations.

Fatal influenza myocarditis with incessant ventricular tachycardia.

Influenza myocarditis is an underappreciated and severe complication of influenza infection, estimated to be present in about 10% of all influenza cases. We present a case of a woman who precipitously died of fulminant influenza myocarditis and then review the historical data, literature and expert recommendations for suspecting and managing influenza myocarditis.

Pembrolizumab plus pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma (KEYNOTE-183): a randomised, open-label, phase 3 trial.

BACKGROUND: Pomalidomide and dexamethasone is a standard of care for patients with multiple myeloma in whom bortezomib and lenalidomide treatment has failed. KEYNOTE-183 assessed efficacy and safety of pomalidomide and dexamethasone with or without pembrolizumab in patients with relapsed or refractory multiple myeloma. Here, we present the findings of an unplanned, ad-hoc interim analysis at the request of the US Food and Drug Administration (FDA). METHODS: KEYNOTE-183 was a randomised, open-label, phase 3 trial done at 97 medical centres across 11 countries (Australia, Canada, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Spain, and USA). Patients aged at least 18 years with multiple myeloma, an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, previously treated with at least two lines of therapy (excluding pomalidomide) and refractory to the last line were randomly assigned 1:1 to the pembrolizumab plus pomalidomide and dexamethasone group or the pomalidomide and dexamethasone group via an interactive voice response or integrated web response system. Patients received oral pomalidomide 4 mg daily on days 1-21 and oral low-dose dexamethasone 40 mg on days 1, 8, 15, and 22 in 28-day cycles, with or without intravenous pembrolizumab 200 mg every 3 weeks. The dual primary endpoints were progression-free survival and overall survival. Efficacy was assessed in all randomly assigned patients and safety was assessed in patients who received at least one dose of study treatment. The trial is registered at ClinicalTrials.gov, number NCT02576977, and it is closed for accrual. FINDINGS: Between Jan 18, 2016, and June 7, 2017, 249 patients were randomly assigned to either the pembrolizumab plus pomalidomide and dexamethasone group (n=125) or the pomalidomide and dexamethasone group (n=124). On July 3, 2017, the FDA established that risks associated with the triple combination outweighed benefits and halted the study. Median follow-up was 8·1 months (IQR 4·5-10·9). Median progression-free survival was 5·6 months (95% CI 3·7-7·5) in the pembrolizumab plus pomalidomide and dexamethasone group versus 8·4 months (5·9-not reached) in the pomalidomide and dexamethasone group; progression-free survival estimates at 6 months were 48% (95% CI 37-58) versus 60% (49-69) at 6 months (hazard ratio [HR] 1·53; 95% CI 1·05-2·22; p=0·98). Median overall survival was not reached (95% CI 12·9-not reached) versus 15·2 months (12·7-not reached; HR 1·61; 95% CI 0·91-2·85; p=0·95); overall survival estimates at 6 months were 82% (95% CI 74-88) versus 90% (82-95). Serious adverse events occurred in 75 (63%) of 120 patients in the pembrolizumab plus pomalidomide and dexamethasone group versus 56 (46%) of 121 patients in the pomalidomide and dexamethasone group. Four (3%) treatment-related deaths occurred in the pembrolizumab plus pomalidomide and dexamethasone group (one each of unknown cause, neutropenic sepsis, myocarditis, and Stevens-Johnson syndrome); myocarditis and Stevens-Johnson syndrome were considered related to pembrolizumab. No treatment-related deaths were reported in the pomalidomide and dexamethasone group. INTERPRETATION: The results from this unplanned, FDA-requested, interim analysis showed that the benefit-risk profile of pembrolizumab plus pomalidomide and dexamethasone is unfavourable for patients with relapsed or refractory multiple myeloma. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co (Kenilworth, NJ, USA).

Sepsis causes right ventricular myocardial inflammation independent of pulmonary hypertension in a porcine sepsis model.

INTRODUCTION: Right ventricular (RV) myocardial dysfunction is a common feature in septic shock. It can worsen outcome, but the etiology is poorly understood. Pulmonary artery hypertension (PAH) plays a part in the pathogenesis of the right heart dysfunction in sepsis but its importance is unknown. In pigs, PAH in sepsis is substantial and the translational value of porcine sepsis models therefore questioned. We hypothesized that porcine sepsis causes a myocardial inflammatory response which leads to myocardial dysfunction independent of PAH. MATERIALS AND METHODS: Sepsis was induced by Escherichia coli-infusion in 10 pigs resulting in PAH and increased right ventricular pressure (RVP). The same degree of RVP was achieved by external pulmonary artery banding (PAB) in a consecutive series of 6 animals. RESULTS: Sepsis, but not PAB, led to increase in endothelial damage marker PAI-1 and cytokines TNF and IL-6 (all p<0.05) in plasma. In myocardium, TNF and IL-6 were significantly elevated in sepsis, TNF in both ventricles and IL-6 mostly in RV, while IL-1ß, IL-18 and C5a were significantly higher in RV compared to LV after PAB (all p<0.05). Myocardial mRNA levels of IL-1ß, IL-6, IL-18, IP-10, E-selectin and PAI-1 were significantly elevated in RV and LV during sepsis compared to PAB, while Caspase-1 was decreased in septic compared to PAB animals (all p<0.05). Cathepsin L activity was increased in RV by PAB, while sepsis inhibited this response. Escherichia coli-induced sepsis caused myocardial inflammation independent of PAH. CONCLUSION: Prominent PAH should therefore not exclude porcine sepsis models to further our understanding of human sepsis.

Clozapine-Related Myocarditis and Rechallenge: A Case Series and Clinical Review.

PURPOSE/BACKGROUND: That clozapine is the only agent with an indication for treatment-resistant schizophrenia presents real challenges if clozapine-related myocarditis (CIM) occurs. Clinicians have chosen to rechallenge with a second trial of clozapine in the face of CIM. However, there is very limited literature of this topic. METHODS/PROCEDURES: Three cases who underwent clozapine rechallenge after CIM are reviewed and discussed in the context of existing literature and current recommendations. FINDINGS/RESULTS: We present 3 young male patients with schizophrenia and schizoaffective disorder who developed CIM during a first clozapine trial, stopped treatment, and subsequently underwent a second clozapine trial. In all cases, the rechallenge was discontinued owing to suspected CIM. A review of the literature includes reports of both successful and unsuccessful clozapine rechallenges after CIM and suggests certain risk factors. Clozapine rechallenge after CIM may be undertaken, as now occurs on occasion with agranulocytosis, although rates of success may be lower. Any such undertaking calls for education, careful monitoring, cautious titration, and a multidisciplinary approach. The balance of risk versus benefits must be considered, and strategies may include a drug holiday, more frequent monitoring upon reinitiation, and slower titration. IMPLICATIONS/CONCLUSIONS: Pressure to undertake a rechallenge reflects clozapine's unique role in treatment-resistant schizophrenia and absence of other comparable options. However, it is not without risk, and more research is needed to understand those at increased risk, as well as established strategies that diminish this.

Nivolumab-induced Myocarditis Successfully Treated with Corticosteroid Therapy: A Case Report and Review of the Literature.

A 62-year-old man presented to our hospital for the further evaluation and treatment of his back pain, general fatigue, and dyspnea, which had developed 4 days after the 29th administration of nivolumab to treat his lung cancer. Based on his clinical history, elevated serum cardiac enzyme values, and cardiac magnetic resonance (CMR) imaging and myocardial biopsy findings, he was diagnosed with myocarditis induced by nivolumab. Corticosteroid therapy improved his condition, and CMR performed on hospital day 11 also showed remarkable improvement. Although nivolumab-induced myocarditis is rare, cardiologists should consider it when encountering patients treated with such a drug for malignant disease.

Human pulmonary dirofilariasis with secondary myocarditis.

Dirofilariasis is a little-known zoonosis, with dogs and cats as definitive hosts. It is caused by nematodes and transmitted by mosquito bites. We report the case of a 67-year-old man with a consumptive syndrome with two subpleural pulmonary opacities. A transthoracic lung biopsy revealed a Dirofilaria worm. Myocardial nuclear magnetic resonance (NMR) demonstrated dilated cardiomyopathy after myocarditis related to dirofilariasis. Human infection is rare and occurs accidentally. The most common radiological alteration is a mainly subpleural coin lesion. Dirofilariasis is a neglected emergent disease and knowledge about it is important for differential diagnoses from neoplastic pulmonary nodules.

First case report of inducible heart block in Lyme disease and an update of Lyme carditis.

BACKGROUND: Lyme disease (LD), is the most common vector-borne illness in the US and Europe, with predominantly cutaneous, articular, cardiac and neuro-psychiatric manifestations. LD affects all layers of the heart and every part of the conducting system. Carditis is a less common manifestation of LD. Heart block (HB) as the initial and sole manifestation of LD is rare. Inducible HB has never been reported in LD. We report a case of heart block (HB) inducible with exercise and reversible with rest. CASE PRESENTATION: A 37-year-old male presented to the emergency department after experiencing two episodes of syncope while at work. He presented, with a heart rate of 57 bpm, and the ECG showed sinus bradycardia with first degree AV block. The PR interval was 480 ms (NL 120-200 ms). Physical exam was unremarkable. The cardiologist's initial impression was vaso-vagal attack. He developed high degree AV block during a stress test for the initial work up, which resolved on cessation of exercise. A similar episode while walking in the hallway, resolved at rest. The high degree AV block appeared inducible with exercise and reversible with rest. His Lyme serology was strongly positive. He was treated with ceftriaxone and doxycycline. After completing treatment, the patient had a normal ECG and returned to work without limitations, doing manual labor. CONCLUSIONS: Manifestations of Lyme carditis (LC) vary from asymptomatic and symptomatic electrocardiographic changes and heart block (HB) reversible with treatment, to sudden death. HB as the sole and initial presentation of LC is rare. There have been no reports of inducible HB in LD. Here we present a case of inducible and reversible high degree HB in a case of LC and an update of literature. Exercise and stress testing should be avoided in suspected cases of LC until resolution of carditis. Lyme carditis should be suspected in individuals with cardiac manifestations in an endemic area, particularly in the younger patients with no other etiology evident.

The Causes of Canine Myocarditis and Myocardial Fibrosis Are Elusive by Targeted Molecular Testing: Retrospective Analysis and Literature Review.

Myocarditis can cause death or permanent heart damage. As epidemiologic and etiopathologic data for canine myocarditis are lacking, we performed a retrospective study using nucleic acid extracted from archived (2007 to 2015) tissues from myocarditis cases and control dogs without myocardial lesions. Heart tissue from pediatric/juvenile and adult dogs was tested with a comprehensive panel of conventional and real-time polymerase chain reaction (PCR) assays targeting recognized agents of canine myocarditis based on a literature review and informed by the comparative epidemiology of human myocarditis. The PCR screen, which included canine parvovirus 2 (CPV-2), canine distemper virus, canine herpesvirus, Borrelia spp, West Nile virus, adenovirus, parainfluenza virus, pneumovirus, respiratory coronavirus, influenza virus, Bartonella spp, Rickettsia spp, Mycoplasma spp, and Neospora caninum, did not detect agents in 35 of 66 cases (53%; 95% confidence interval [CI], 41%-65%) and was frequently negative in adults (21/26); by comparison, agents were not detected in 27 of 57 controls (47%; 95% CI, 35%-60%). Canine distemper virus, herpesvirus, adenovirus, coronavirus, parainfluenza virus, Mycoplasma haemocanis, and N. caninum were occasionally detected in both cases and controls; thus, PCR detection was not considered to indicate causation. We previously reported that CPV-2 continues to be associated with myocarditis in young dogs despite widespread vaccination; in adults, CPV-2 was detected in 2 of 26 cases and 4 of 22 controls. As several agents were similarly detected in cases and controls, it is unclear if these are cardiopathogenic, incidental, or latent. West Nile virus was detected at the analytic limit in 1 adult case. We did not detect Borrelia spp, Bartonella spp, Rickettsia spp, or influenza A virus in the myocarditis cases. These data demonstrate the limitations of current targeted diagnostic tests and the need for additional research to identify unknown agents and develop testing strategies for canine myocarditis.

Fulminant myocarditis associated with severe fever with thrombocytopenia syndrome: a case report.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral infectious disease with high mortality. It causes multiple organ dysfunction; however, myocarditis has never been reported as a complication with SFTS. CASE PRESENTATION: A 62-year-old previously healthy woman developed fever, fatigue, diarrhea, and a mild consciousness disorder. She visited a local clinic, and laboratory data showed leukocytopenia, thrombocytopenia, and elevation of the aspartate aminotransferase level. She was transferred to Kagoshima University Hospital and diagnosed as having SFTS by real-time reverse transcription polymerase chain reaction. Subsequently, her blood pressure gradually decreased despite fluid resuscitation and vasopressor administration. Based on elevated toroponin I levels in serum, a transient diffuse left ventricular hypokinesis and wall thickening in echocardiography, diffuse ST elevation in electrocardiography, and exclusion of other heart diseases, she was diagnosed as having fulminant myocarditis. After hemodynamic support with inotropic agents, she recovered near normal cardiac function. She was discharged to home on day 28. CONCLUSIONS: We report the first case of fulminant myocarditis associated with SFTS.

Pericardial Disease, Myocardial Disease, and Great Vessel Abnormalities in Horses.

Pericardial, myocardial, and great vessel diseases are relatively rare in horses. The clinical signs are often nonspecific and vague, or related to the underlying cause. Physical examination usually reveals tachycardia, fever, venous distension or jugular pulsation, a weak or bounding arterial pulse, ventral edema, and abnormal cardiac auscultation such as arrhythmia, murmur, or muffled heart sounds. The prognosis depends on the underlying cause and the disease progression, and ranges from full recovery to poor prognosis for survival. This article focuses on the etiology, diagnosis, prognosis, and treatment of pericarditis, pericardial mass lesions, myocarditis, cardiomyopathy, and great vessel aneurysm or rupture.

Clinical Overlap Between Myopericarditis and Stress Induced Cardiomyopathy: A Diagnostic and Therapeutic Challenge.

BACKGROUND Stress induced cardiomyopathy (SIC) is characterized by non-obstructive coronary arteries and characteristic ventricular apical ballooning. The exact pathogenesis of SIC is not well recognized. We present an unusual case of SIC that mimicked acute myopericarditis and discuss the effect of this masquerading presentation of SIC in recognizing pathophysiological association between myopericarditis and SIC and limitations of current diagnostic criteria. CASE REPORT A 47-year-old female presented with flu-like illness and pleuritic chest pain. An electrocardiogram (ECG) showed diffuse PR depressions and ST elevations, troponin 5 ng/mL, hemoglobin 14.2 mg/dL, leukocytosis (white blood cell count of 15.1×103/uL) and erythrocyte sedimentation rate (ESR) of 22.4 mm/hour. Echocardiogram showed reduced ejection fraction (EF) with apical ballooning. Catheterization showed non-obstructive coronary disease. The patient was given colchicine and ibuprofen for 1 day with symptom resolution over the next 2 days and repeat echocardiogram with preserved EF. Troponin trended down to 3.24 ng/mL and 0.44 ng/mL, 6 hours apart. ECG showed resolution of PR depressions and subsequent T wave inversions in 1, AVl, V1-V6 by day 3. The diagnosis of myopericarditis was favored by viral prodrome, fever, pleuritic pain, pericardial rub, ECG findings, and elevated ESR. History of emotional stress, characteristic ballooning of left ventricle apex with rapid resolution favored SIC. CONCLUSIONS This case showed that SIC and myocarditis need not be mutually exclusive and differentiating clinically between these 2 entities can be difficult. Alternatively, SIC can accompany other cardiac conditions like myocardial infarction, pericarditis, and myocarditis making diagnosis and management challenging. Clinicians need to be cautious while making this differentiation as duration and type of therapy may be significantly different. SIC can be considered a variant of regional inflammatory myocarditis wherein pericarditis may result secondary to extension of myocardial inflammation to overlying pericardium. The current Mayo Clinic criteria for diagnosis of SIC appears to be outdated, not accounting for such atypical presentations, and therefore needs to be revised.

ADAR1p150 Forms a Complex with Dicer to Promote miRNA-222 Activity and Regulate PTEN Expression in CVB3-Induced Viral Myocarditis.

Adenosine deaminases acting on RNA (ADAR) are enzymes that regulate RNA metabolism through post-transcriptional mechanisms. ADAR1 is involved in a variety of pathological conditions including inflammation, cancer, and the host defense against viral infections. However, the role of ADAR1p150 in vascular disease remains unclear. In this study, we examined the expression of ADAR1p150 and its role in viral myocarditis (VMC) in a mouse model. VMC mouse cardiomyocytes showed significantly higher expression of ADAR1p150 compared to the control samples. Coimmunoprecipitation verified that ADAR1p150 forms a complex with Dicer in VMC. miRNA-222, which is involved in many cardiac diseases, is highly expressed in cardiomyocytes in VMC. In addition, the expression of miRNA-222 was promoted by ADAR1p150/Dicer. Among the target genes of miRNA-222, the expression of phosphatase-and-tensin (PTEN) protein was significantly reduced in VMC. By using a bioinformatics tool, we found a potential binding site of miRNA-222 on the PTEN gene's 3'-UTR, suggesting that miRNA-222 might play a regulatory role. In cultured cells, miR-222 suppressed PTEN expression. Our findings suggest that ADAR1p150 plays a key role in complexing with Dicer and promoting the expression of miRNA-222, the latter of which suppresses the expression of the target gene PTEN during VMC. Our work reveals a previously unknown role of ADAR1p150 in gene expression in VMC.