Subacute Myocarditis Research Articles

Sports behaviour and adherence to sports and exercise recommendations in patients with myocarditis

AimIn the clinical setting of acute myocarditis, existing guidelines recommend refraining from moderate-intensity to high-intensity sports for 3–6 months, yet the extent to which these recommendations are implemented by clinicians...

MYOCARDITIS: VIRUS OR DESMOSOME?

Abstract Patient Profile Female, 56 yo, arterial hypertension, FH of autoimmune diseases, no history of sudden death. Medical History: • At the age of 46: Hospitalized for chest pain. Coronary angiography: negative. Diagnosis: myocardial ischemia with normal coronary arteries. • 2018: Hospitalized again for angina. ECG showed low voltages, flat T–waves in the inf–lat. leads. Coronary angiography: negative. Biopsy Mild hypertrophy and cytoplasmic vacuolization, minimal increase in interstitial fibrosis, no necrosis or inflammatory infiltrates. Mild nonspecific cardiomyopathy. Viral DNA test positive for HHV–6. Serology: HHV–6 in blood (neg), IgG HHV–6 (pos), IgM (neg). Diagnosis: myocarditis due to HHV–6. • San Camillo Cardiomyopathy Center: Echocardiogram: basal ant–lat. hypokinesia, EF 60%. Therapy: Bisoprolol 3.75 mg, Ramipril 5 mg, Ranolazine 1000 mg. MRI: basal transmural ant–lat. and subepicardial lateral LGE. Oedema and hypokinesia coexists. Subacute myocarditis. MRI at 1 year: mild left ventricular dilation, EF 60%, meso–subepicardial LGE in the ant–lat and inf mid–basal regions without oedema. Serial Holter ECGs: frequent polymorphic ventricular ectopics, couplets, and runs. CPET: normal exercise capacity, pVO2 19.4 (ml/min)/kg (90%). Genetic testing VUS in DSC, probably pathogenic, and VUS in ABCC9, PKP2, DSP (2 mutations) with uncertain clinical significance. • In 2022: Readmitted for angina. Elevated Troponin levels. Coro CT angiography: negative. MRI: EF 45%, akinesia of the apex and apical lat. wall; diffuse LGE and edema. Pericardial effusion. Patient refused biopsy. Discharged after recovery (EF 52%) with the diagnosis of recurrent myocarditis. Empagliflozin added. • Follow up. ECG: progression of repolarization abnormalities (TWI in V1–V3 + inf.–lat. leads). Biopsy: fibroadipose replacement, no necrosis or inflammatory infiltrates. Chronic myocarditis and sequels. Viral tests: negative. CPET and stress echo: VO2peak 20.7 (ml/kg)/min (88%), normal work capacity. Very rare monomorphic PVCs. EF 50%, preserved contractile reserve. Conclusions Diagnosis of left dominant arrhythmogenic cardiomyopathy with a typical pattern for hot phases of myocardial inflammation. The first episode could have been triggered by a viral infection on a predisposing genetic substrate. Nadolol 40 mg x2 was introduced. The possibility of ICD implantation was discussed, and patient refused. A six–month follow–up was planned. Family screening results were negative.

Sustained Myocarditis following Messenger RNA Vaccination against Coronavirus Disease 2019: Relation to Neutralizing Antibody and Amelioration by Low-Dose Booster Vaccination

We recently reported that sub-acute myocarditis occurred following the initial two doses of messenger RNA-based vaccination against coronavirus disease 2019 (0.3 mL Comirnaty®) in elderly Japanese patients with cardiac dysfunction. The present retrospective study of 76 patients revealed that myocarditis following the initial doses persisted for 12 months, was associated with low levels of neutralizing antibodies, and was ameliorated by reducing the third vaccine dose. Low neutralizing antibody levels (<220 U/mL) after the initial doses were an independent predictor of persistent clinical events, defined as death or marked changes in brain natriuretic peptide levels. When the third dose was reduced (0.1 mL), changes in brain natriuretic peptide levels were significantly smaller (p = 0.02, n = 25), no deaths occurred due to heart failure, and neutralizing antibody levels increased 41-fold (p < 0.001) compared with the initial doses. Reduced booster doses could facilitate the worldwide distribution of messenger RNA vaccines.

Abstract 10745: Return to Play After Covid-19 Infection: Cardiac Imaging Findings in Youth

Introduction: SARS CoV2 has been associated with acute and subacute myocarditis. Screening after COVID-19 has been recommended prior to returning to physical activity. The yield of such investigations, particularly in youth, remains unknown. Methods: Retrospective chart review was performed of patients evaluated in a cardiology clinic for return to play (RTP) after COVID-19 between 01/20 - 06/21. Iteratively updated guidance for testing was provided to ambulatory providers. Patients with MIS-C were excluded. We reviewed demographics, clinical evaluation, and cardiac imaging. Results: Of 429 patients (age 16.3 ± 2.7 [range 8-21] yrs, 44% male) evaluated including 9 with pre-existing heart disease, 318 underwent echocardiograms and 23 also had cardiac MRI. Cardiac MRI was performed for abnormal screening ECG or echocardiogram or cardiovascular symptoms. New echocardiographic abnormalities were detected in 69 patients: 4 were possibly related to COVID-19 infection, 3 were new structural heart disease (2 anomalous coronary, 1 bicuspid aortic valve), and 62 were normal variants or trivial findings. New ventricular dysfunction (right or left, qualitative dysfunction or LV ejection fraction [EF] &lt;55%) was noted in 11 patients (LV EF mean 52.7 ± 2.6%, minimum 46%). Eight underwent cardiac MRI confirming trivial to no ventricular dysfunction and none of the 23 MRIs demonstrated late gadolinium enhancement or met Lake Louise criteria for myocarditis. All patients without new diagnoses of structural heart disease were ultimately deemed safe to return to previous levels of physical activity. Conclusions: Cardiovascular evaluation for RTP of youth after COVID-19 demonstrated mild transient abnormalities and incidental findings, but no diagnoses of myocarditis. These data suggest early concerns about subclinical myocarditis may have been overestimated. Future studies should consider the costs and benefits of current society algorithms for such evaluations.

Comprehensive Cardiac Magnetic Resonance to Detect Subacute Myocarditis.

(1) Background: Compared to acute myocarditis in the initial phase, detection of subacute myocarditis with cardiac magnetic resonance (CMR) parameters can be challenging due to a lower degree of myocardial inflammation compared to the acute phase. (2) Objectives: To systematically evaluate non-invasive CMR imaging parameters in acute and subacute myocarditis. (3) Methods: 48 patients (age 37 (IQR 28–55) years; 52% female) with clinically suspected myocarditis were consecutively included. Patients with onset of symptoms ≤2 weeks prior to 1.5T CMR were assigned to the acute group (n = 25, 52%), patients with symptom duration >2 to 6 weeks were assigned to the subacute group (n = 23, 48%). CMR protocol comprised morphology, function, 3D-strain, late gadolinium enhancement (LGE) imaging and mapping (T1, ECV, T2). (4) Results: Highest diagnostic performance in the detection of subacute myocarditis was achieved by ECV evaluation either as single parameter or in combination with T1 mapping (applying a segmental or global increase of native T1 > 1015 ms and ECV > 28%), sensitivity 96% and accuracy 91%. Compared to subacute myocarditis, acute myocarditis demonstrated higher prevalence and extent of LGE (AUC 0.76) and increased T2 (AUC 0.66). (5) Conclusions: A comprehensive CMR approach allows reliable diagnosis of clinically suspected subacute myocarditis. Thereby, ECV alone or in combination with native T1 mapping indicated the best performance for diagnosing subacute myocarditis. Acute vs. subacute myocarditis is difficult to discriminate by CMR alone, due to chronological connection and overlap of pathologic findings.

A clinical case of inflammatory cardiomyopathy due to subacute viral myocarditis associated with the novel coronavirus infection in an ambulance worker (issues of diagnosis and examination of the relationship between disease and occupation

Medical workers are a group at increased risk of infection with the SARS-CoV-2 virus when providing medical care in modern conditions. The novel coronavirus infection can be considered as an occupational disease in medical workers if the infection occurred while performing their professional duties. One of the most important complications of the new coronavirus infection is the lesion of the cardiovascular system. The presented clinical case reflects one of the possible serious complications of the coronavirus infection that developed in a medical worker against the background of chronic autoimmune pathology, i.e. severe myocarditis with pulmonary embolism, which led to the formation of inflammatory cardiomyopathy with congestive heart failure. The article presents the principles and results of a medical examination conducted in order to establish a causal relationship between the disease and professional activity.

A clinical case of inflammatory cardiomyopathy due to experienced subacute viral myocarditis associated with the new coronavirus infection COVID-19 of occupational genesis

A clinical case of inflammatory cardiomyopathy due to experienced subacute viral myocarditis associated with the new coronavirus infection COVID-19 of occupational genesis

Кардиальные и вегетативные проявления long-COVID у детей

Approximately 5–15% of children develop post-COVID-19 syndrome after SARS-CoV-2 infection, which manifests itself with various pathological symptoms for more than 12 weeks. Cardiovascular symptoms range from serious myocardial inflammation, manifestations of essential hypertension to signs of autonomic dysfunction with a tendency to hypersympathicotonia, which negatively affects the quality of life of children. We report a case of subacute myocarditis in a patient with long-COVID after a low-symptomatic acute disease. This case illustrates high clinical significance of timely diagnosis of long-COVID using gadolinium-enhanced magnetic resonance imaging, which was performed in our country for the first time in pediatric practice. We developed criteria for early diagnosis of autonomic dysfunction specific for children and adolescents. We also developed treatment recommendations, including behavioral therapy, drug, and non-drug treatments. Key words: long-COVID, autonomic dysfunction, hypersympathicotonia, myocarditis, behavioral therapy, non-drug treatment

Association of ECG parameters with late gadolinium enhancement and outcome in patients with clinical suspicion of acute or subacute myocarditis referred for CMR imaging.

BackgroundRisk stratification of myocarditis is challenging due to variable clinical presentations. Cardiovascular magnetic resonance (CMR) is the primary non-invasive imaging modality to investigate myocarditis while electrocardiograms (ECG) are routinely included in the clinical work-up. The association of ECG parameters with CMR tissue characterisation and their prognostic value were investigated in patients with clinically suspected myocarditis.Methods and resultsConsecutive patients with suspected myocarditis who underwent CMR and ECG were analysed. Major adverse cardiovascular event (MACE) included all-cause death, hospitalisation for heart failure, heart transplantation, documented sustained ventricular arrhythmia, or recurrent myocarditis. A total of 587 patients were followed for a median of 3.9 years. A wide QRS-T angle, low voltage and fragmented QRS were significantly associated with late gadolinium enhancement. Further, a wide QRS-T angle, low voltage and prolonged QTc duration were associated with MACE in the univariable analysis. In a multivariable model, late gadolinium enhancement (HR: 1.90, 95%CI: 1.17–3.10; p = 0.010) and the ECG parameters of a low QRS voltage (HR: 1.86, 95%CI: 1.01–3.42; p = 0.046) and QRS-T-angle (HR: 1.01, 95%CI: 1.00–1.01; p = 0.029) remained independently associated with outcome. The cumulative incidence of MACE was incrementally higher when findings of both CMR and ECG were abnormal (p<0.001).ConclusionIn patients with clinically suspected myocarditis, abnormal ECG parameters are associated with abnormal tissue characteristics detected by CMR. Further, ECG and CMR findings have independent prognostic implications for morbidity and mortality. Integrating both exams into clinical decision-making may play a role in risk stratification in this heterogeneous patient population.

P872 A case of transient atrioventricular block: the role of cardiac magnetic resonance imaging

Abstract A 42-year old man with no relevant past medical history presented to the emergency department for recurrent transient loss of consciousness in the last 12 hours. 3 weeks earlier he had flu-like symptoms which spontaneously resolved. Physical examination revealed altered mental state, heart rate 30 beats per minute, respiratory rate 30 cycles per minute, blood pressure 70/40mmHg and basal lung rales on pulmonary auscultation. Blood gas analysis revealed hyperlactacidemia with hypocapnia. Electrocardiogram showed third-degree atrioventricular block. Atropine was administrated (total dose 3mg) with no rate response. Transcutaneous pacing was initiated followed by a temporary transvenous pacemaker, removed after 72 hours. Transthoracic echocardiogram revealed compromised left ventricular systolic function (ejection fraction by Simpson’s method 45%) due to septal dyskinesia and reduced global longitudinal strain (-11%). Blood analysis revealed erythrocyte sedimentation rate 20mm/hr, C-reactive protein 2.43mg/dL and negative high-sensitivity troponin T (9.44ng/L). Rheumatologic screening was negative. Coronary computed tomography angiography revealed normal epicardial coronaries. Cardiac magnetic resonance imaging (CMRI) performed 7 days after admission revealed preserved left ventricular systolic function (ejection fraction 51%). Late gadolinium enhancement showed scared myocardium in the medium and basal segments of the interventricular septum, compatible with subacute myocarditis. Due to the history of recurrent syncope, a permanent pacemaker was inserted. The patient was discharged the day after. No further syncope occurred. In last pacemaker follow-up, 9 months after presentation, patient had 0% auricular and ventricular pacing and 100% sensing over the previous 6 months. Discussion Transient atrioventricular block is a well-known complication of myocarditis when there is involvement of the conduction system by the inflammatory reaction. However, in rare cases it can persist or recur. CMRI plays an important role in these cases. Gadolinium-enhanced CMRI can be used to access the extent of inflammation and cellular edema and delayed-enhanced CMRI can also be used to quantify scarring which has important prognostic value. CMRI can also play a crucial role in excluding infiltrative disorders with conduction system involvement. Also, in these patients, the transient aspect of atrioventricular block poses a challenge when deciding about permanent pacemaker insertion. Abstract P872 Figure. Magnetic Ressonance IVS

A Subtle Subacute Myocarditis in a Middle-aged Amateur Athlete

A Subtle Subacute Myocarditis in a Middle-aged Amateur Athlete

MYOCARDITIS WITH OUTCOME IN DILATED CARDIOMYOPATHY COMPLICATED BY REFRACTORY HEART FAILURE AND REQUIRING HEART TRANSPLANTATION

The article describes the clinical case of subacute myocarditis in a child with an outcome in dilated cardiomyopathy, complicated with congestive heart failure. Difficulties in diagnosing the disease that manifested with cardiac arrhythmia are discussed. The main signs suggesting postmiocardic cardiomyopathy included a reduced deflection voltage and frequent ventricular extrasystoles with episodes of the ventricular tachycardia in the onset of the disease, left ventricular dilatation, a significant decrease in ejection fraction, increased activity of natriuretic peptide, findings of perfusion scintigraphy and magnetic resonance imaging. Medical therapy and implantation of a cardioverter defibrillator were ineffective. The child repeatedly suffered from syncopal conditions with circulatory arrest, which required resuscitation. Due to the ineffectiveness of drug therapy conducted in the leading federal centres, considering cardiac transplantation abroad was recommended.

Auxiliary diagnostic potential of ventricle geometry and late gadolinium enhancement in left ventricular non-compaction; non-randomized case control study

BackgroundThere are still ambiguities existing in regard to left ventricular non-compaction (LVNC) diagnostic imaging. The aim of our study was to analyze diagnostic potential of late gadolinium enhancement (LGE) and ventricle geometry in patients with LVNC and controls.MethodsData on cardiac magnetic resonance imaging (CMR) studies for LVNC were reassessed from the hospital’s database (3.75 years; n=1975 exams). Matching sample of controls included cases with no structural heart disease, hypertrophic or dilative cardiomyopathy, arrhythmogenic right ventricular dysplasia or subacute myocarditis. Eccentricity of the left ventricle was measured at end diastole in the region with pronounced NC and maximal to minimal ratio (MaxMinEDDR) was calculated.ResultsStudy included 255 patients referred for CMR, 100 (39.2%) with LVNC (prevalence in the studied period 5.01%) and 155 (60.8%) controls. Existing LGE had sensitivity of 52.5% (95%-CI:42.3–62.5), specificity of 80.4% (95%-CI:73.2–86.5) for LVNC, area under curve (AUC) 0.664 (95%-CI:0.603–0.722);p<0.001. MaxMinEDDR>1.10 had sensitivity of 95.0% (95%-CI:88.7–98.4), specificity of 82.6% (95%-CI: 75.7–88.2) for LVNC, AUC 0.917 (95%-CI:0.876–0.948); p<0.001. LGE correlated with Max-Min-EDD-R (Rho=0.130; p=0.038) and there was significant difference in ROC analysis ΔAUC0.244 (95%-CI:0.175–0.314); p<0.001. LGE also correlated negatively with stroke volume and systolic function (both p<0.05, respectively).ConclusionsLGE was found to be frequently expressed in patients with LVNC, but without sufficient power to be used as a discriminative diagnostic parameter. Both LGE and eccentricity of the left ventricle were found to be relatively solid diagnostic landmarks of complex infrastructural and functional changes within the failing heart.

Subacute Myocarditis Associated with Bocavirus Infection in an 8-Week-Old Infant.

Subacute Myocarditis Associated with Bocavirus Infection in an 8-Week-Old Infant.

Pathological study of an outbreak of hydropericardium syndrome in Giriraja chicken

Hydropericardium syndrome was recorded in Giriraja chicken of 7 weeks old in Vaduvur village of Thanjavur district during the month of March 2014. The clinical signs recorded were dullness, depression with 32.73% morbidity and 94.44% mortality. On postmortem examination, pericardial sac revealed 5 ml of straw coloured clear fluid. The liver was enlarged, pale with whitish foci. Lungs revealed congestion with oedema. Kidneys were pale with accentuation of renal tubules. Spleen was congested. Cytological examination of liver revealed micro to macro vacuolar changes in the cytoplasm of hepatocytes. On histopathological examination, the liver showed diffuse severe hepatosis with intranuclear eosinophilic and basophilic inclusion bodies. Heart revealed subacute myocarditis with mild fatty changes in myocardial fibres. Kidneys revealed tubular nephrosis. Based on clinical signs, cytological and pathomorphological examination, the disease outbreak in Giriraja chicken farm was diagnosed as hydropericardium syndrome.

Coronary Artery Dilatation in Viral Myocarditis Mimics Coronary Artery Findings in Kawasaki Disease.

Coronary artery (CA) dilatations are typical to Kawasaki disease (KD) in the pediatric population. CA involvement is a useful feature to help establish the diagnosis of KD. Since myocarditis is omnipresent in the acute phase of KD, we sought to investigate whether viral myocarditis may cause CA dilatation. This retrospective study reviewed 14 consecutive patients diagnosed with acute myocarditis at CHU Sainte-Justine, Montreal. KD diagnosis was excluded for all patients. All echocardiography studies were reviewed by an independent experienced echocardiographer for CA size and myocardial function parameters. CA involvement was classified under three categories: definite dilatation (Z-score ≥2.5 in one or more CA), occult dilatation (Z-score variation ≥2 points for the same CA on two different echocardiograms, but maximum Z-score always <2.5), and no dilatation otherwise. Demographics, laboratory values, microbial etiology testing, and diagnostic studies were collected from medical records. Mean age at presentation was 1.67±3.22years, where 11/14 (78%) presented with acute and three with subacute myocarditis. Five (36%) patients had normal CA measurements, six (43%) had occult dilatation, and three (21%) had definite dilatation. Maximal CA Z-score was within the first 8days of presentation. Patients with viral myocarditis can present CA dilatation during the acute phase of the illness. This finding should be taken into account when KD diagnosis is being based on the CA involvement as the two illnesses may present with similar features.

Myocarditis in yound athletes

Aim. Development of informative differential diagnostic criteria of inflammatory myocardial involvement in young athletes. Methods. A total of 163 athletes (swimmers, football players and sailing athletes) aged 9 to 24 years (mean age 14.74±0,23 years, SD=3.03) were examined. Complete clinical and functional examination was performed. Remodeling of the left ventricle was studied in accordance with R. Devereux (1992) and B. Maron (2005) echocardiographic criteria. Myocardial morphometry results were compared with immunobiochemical markers of myocardial damage and titer of antimyocardial antibodies to the endothelium, cardiac conduction system, cardiomyocytes, and smooth muscle. Results. In 10 out of 40 athletes with echocardiographic signs of pathological remodeling of the left ventricle, the indicators of myocardial damage used as immunobiochemical screening tests, were increased, high titers of antimyocardial antibodies (more than 1:160), arrhythmias, sever conduction disorders, and high concentrations of infectious risk factors were revealed, allowing to diagnose subacute myocarditis. Conclusion. Subacute myocarditis should be excluded in athletes with echocardiographic signs of left ventricular myocardial remodeling and a high concentration of «infectious» risk factors based on immunobiochemical markers of myocardial damage and antimyocardial antibodies titer.

MYOCARDIAL BIOPSY IN GENERAL CARE CLINIC: PATIENTS SELECTION, THE RESULTS, SIGNIFICANCE FOR TREATMENT STRATEGY

Aim. To analyze the results of first 50 endomyocardial biopsies (EMB) in general care clinic, to clarify the selection criteria and procedure role in management decision in patients with various noncoronarogenic diseases of myocardium. Material and methods. Totally 50 patients included, who had been underwent EMB during 2007-2014 (31 men, mean age 44,3±13,5). Investigation included the level of anticardiac antibodies (n=49), DNA of herpes group viruses and parvovirus B19 by PCR in blood (n=40) and myocardium (n=49), scintigraphy of myocardium (n=20), MDCT (n=21), MRI (n=17), coronary arteriography (n=22), genetician consultation (n=15). EMB of the right ventricle was done using biopsy forceps STANDARD 5.5 F 104 FEMORAL (Cordis). The materials were coloured with hematoxyline-eosine, picrofucsine by Van Hison, Schiff reactives, Pearls, red congo. The study was approved by the Ethics Comitteeof FMSMU. Results. Indications for EMB were set for 3 groups of patients: 1. With dilated cardiomyopathy (DCMP) as a syndrome, including the probability of acute/ subacute myocarditis (n=7), allergic myocarditis (n=1), myocarditis with myocardial infarction (n=1), vasculitis (n=3), possible myocarditis in long-lasting course of DCMP (n=9), in patients with non-compact myocardium, myodystrophy of Emeri-Dreyfus and possible arrhythmogenic dysplasia of the right ventricle (n=7). 2. With "idiopathic" rhythm and conduction disorders (n=18), including high probability of myocarditis (n=13), vasculitis (n=2), necessity for differentiation of myocarditis and genetic cardiomyopathies (n=3). 3. With the syndrome of primary myocardial hypertrophy (n=3). EMB was informative in all patients, myocarditis found in 82,6%. Conclusion. The criteria for high diagnostic value of EMB is nosological way of selection. In addition to current scenarios it is aimfull to perform EMB if clinically significant ischemia with non-changed coronary arteries, with suspected myocarditis in patients with genetic cardiomyopathies, inborn defects, CHD and other established heart diseases. The EMB results define the tactics of medication and surgical treatment.

Streptomyces lavendulaeProtease Inhibitor: Purification, Gene Overexpression, and 3-Dimensional Structure

Protease inhibitorstrypsin (STI1, Streptomyces trypsin inhibitor 1) has been identified, purified by ammonium sulfate precipitation and Sephadex G-100 gel filtration. SDS-PAGE of protease inhibitor showed molecular weight of approximately 10 KDa. PCR product (~1615 bp) ofsti1gene was cloned in expression vectorpACYC177/ET3dand transformed inEscherichia coliJM109.Protease inhibitorstrypsin was purified and used as antivirus against Coxsackievirus B3 (CVB3). CVB3 is one of the major causative agents of chronic, subacute, acute, and fulminant myocarditis as well as pancreatitis and aseptic meningitis. It has been reported that more than 50% of human myocarditis is associated with CVB3 infection.

Adiponectin promotes coxsackievirus B3 myocarditis by suppression of acute anti-viral immune responses

Adiponectin (APN) is an immunomodulatory adipocytokine that improves outcome in patients with virus-negative inflammatory cardiomyopathy and mice with autoimmune myocarditis. Here, we investigated whether APN modulates cardiac inflammation and injury in coxsackievirus B3 (CVB3) myocarditis. Myocarditis was induced by CVB3 infection of APN-KO and WT mice. APN reconstitution was performed by adenoviral gene transfer. Expression analyses were performed by qRT-PCR and immunoblot. Cardiac histology was analyzed by H&E-stain and immunohistochemistry. APN-KO mice exhibited diminished subacute myocarditis with reduced viral load, attenuated inflammatory infiltrates determined by NKp46, F4/80 and CD3/CD4/CD8 expression and reduced IFNβ, IFNγ, TNFα, IL-1β and IL-12 levels. Moreover, myocardial injury assessed by necrotic lesions and troponin I release was attenuated resulting in preserved left ventricular function. Those changes were reversed by APN reconstitution. APN had no influence on adhesion, uptake or replication of CVB3 in cardiac myocytes. In acute CVB3 myocarditis, cardiac viral load did not differ between APN-KO and WT mice. However, APN-KO mice displayed an enhanced acute immune response, i.e. increased expression of myocardial CD14, IFNβ, IFNγ, IL-12, and TNFα resulting in increased cardiac infiltration with pro-inflammatory M1 macrophages and activated NK cells. Up-regulation of cardiac CD14 expression, type I and II IFNs and inflammatory cell accumulation in APN-KO mice was inhibited by APN reconstitution. Our observations indicate that APN promotes CVB3 myocarditis by suppression of toll-like receptor-dependent innate immune responses, polarization of anti-inflammatory M2 macrophages and reduction of number and activation of NK cells resulting in attenuated acute anti-viral immune responses.