Acute Lymphocytic Myocarditis Research Articles

Dramatic Improvement of Acute Fulminant Lymphocytic Myocarditis with Short-course Intravenous Pulse Corticosteroids: A Case Study

We report a 31-year-old patient with acute fulminant myocarditis, resulting in cardiogenic shock that necessitated mechanical circulatory support, who improved dramatically after treatment with intravenous (IV) pulse steroids. A coordinated multidisciplinary team was the key secret in the cure of this critical patient. In this case study, we focus on the role of IV pulse steroids in the treatment of fulminant lymphocytic myocarditis.

Acute lymphocytic myocarditis presenting as complete heart block in an adult: a case report

BackgroundComplete heart block (CHB) as a first presentation of acute viral myocarditis is a rare occurrence associated with increased morbidity and mortality. In such cases, an endomyocardial biopsy is recommended to make a clear histological diagnosis aiding to differentiate from other possible conditions such as sarcoiditic myocarditis, giant cell myocarditis, and eosinophilic myocarditis. Insertion of a permanent pacemaker may be considered on a case-to-case basis.Case presentationA previously healthy 21-year-old female presented to the emergency department after having suffered two episodes of syncope on a background of a few days’ history of myalgias, chills, and rigors. Electrocardiogram showed high-grade Mobitz II block with intermittent periods of CHB. A bedside echocardiogram upon admission demonstrated normal biventricular systolic function. Given the patient’s unstable haemodynamic status and lack of obvious reversible causes for the CHB, a permanent dual-chamber pacemaker was inserted urgently. Initial blood investigations indicated an ongoing inflammatory process highlighting the possibility of myocarditis as a cause of the CHB. Therefore, a troponin level was taken and was noted to be elevated confirming the suspicion of myocarditis. The left ventricular ejection fraction (LVEF) decreased over the following days to approximately 20%, clinically resulting in pulmonary oedema and acute shortness of breath. The patient required aggressive intravenous diuresis and anti-heart failure medication. An endomyocardial biopsy (EMB) confirmed the diagnosis of lymphocytic myocarditis. The patient’s condition improved secondary to an improvement in LVEF and resolution of the heart block. A cardiac magnetic resonance (CMR) imaging performed 6 weeks from admission reported an improved LVEF of 51% with no late gadolinium enhancement (LGE). Based on the reassuring CMR findings and the resolution of CHB on follow-up pacemaker checks, it was deemed safe to explant the pacemaker.ConclusionsAcute myocarditis may be complicated with high-degree AV block and cardiogenic shock necessitating close observation in a critical care unit. A permanent pacemaker may provide atrio-ventricular synchrony which helps stabilise the patient’s condition and protect from a prolonged period of heart block. Early myocardial fibrosis on EMB and degree of LGE on CMR are indicators of persistent atrioventricular block. Guideline-directed treatment of heart failure is essential.

P369 AUTOIMMUNE LYMPHOCYTIC MYOCARDITIS: ONE SIZE DOES NOT FIT ALL

Abstract Fulminant myocarditis (MF) is an acute onset, rapidly progressive and potentially fatal inflammatory cardiomyopathy which could manifests with cardiogenic shock and incessant arrhythmias. There is often a need for aminic or mechanical support to the circulation in the acute phase, waiting to obtain a histological diagnosis as quickly as possible to establish a specific therapy. Mortality in the acute phases is high, with a worse prognosis than in other forms of presentation of myocarditis, even in the long term. We report the case of a 45–year–old Asian woman suffering from autoimmune hypothyroidism, who had been reporting atypical chest pain for about 3 days, associated with fever, asthenia, and vomiting. On admission, the patient was in cardiogenic shock; an echocardiogram revealed biventricular dysfunction. Pulmonary embolism and acute coronary syndrome were excluded. Blood tests showed a significant troponin rise, neutrophilic leukocytosis, and hypertransaminasemia. Anti heart antibodies (AHA) were negative. Amine support with dobutamine and norepinephrine was then started. The first EKG showed an advanced atrioventricular block with a ventricular escape with the need for emergency temporary PM placement. Right heart catheterization showed pressures in the pulmonary circulation at the upper limits with average resistance and reduced cardiac index. An endomyocardial biopsy (EMB) was performed, subsequently complicated by cardiac tamponade due to lead displacement, treated with urgent pericardiocentesis. At the end of the procedure, the appearance of incoming episodes of complete BAV was highlighted, for which ICD implantation was performed. The biopsy showed virus–negative diffuse acute lymphocytic myocarditis. Cortisone therapy was therefore started, with immediate benefit, until the aminic support was suspended. A follow–up echocardiogram showed a complete recovery of normal biventricular function. In MF, early diagnosis, and the possibility of establishing specific therapy are crucial to reduce mortality. EMB is the only method that allows you to make an etiological diagnosis and exclude a possible infectious genesis. The patient‘s prognosis, in fact, in addition to supportive therapy, depends on the possibility of establishing a targeted treatment as soon as possible, which in virus–negative autoimmune forms consists of an immunosuppressive therapy modulated on the patient‘s histological type and clinic.

Abstract 15244: Rapid Recognition and Implementation of Mechanical Circulatory Support in Rare Fulminant Lymphocytic Myocarditis

Case Presentation: A 65 year-old woman with heart failure, nonischemic cardiomyopathy, atrial fibrillation, hypertension, prior stroke presented with chest pain and shortness of breath for three days. She was ill-appearing, hypotensive and tachypneic, with troponins reaching greater than 125,000 ng/L. Initial ECG demonstrated sinus rhythm with inferior ST elevations and lateral T wave inversions, however emergent catheterization revealed angiographically normal coronary arteries. Repeat 2D echocardiography showed sharp decline to ejection fraction (EF) 5-10%. Patient subsequently developed cardiogenic shock and despite inotropes, vasopressors and intra-aortic balloon pump, she suffered ventricular fibrillation arrest requiring defibrillation. This prompted escalation with emergent veno-arterial extracorporeal membrane oxygenation. Endomyocardial biopsy findings taken at that time were consistent with lymphocytic myocarditis with negative viral panel. Her hospital course was also complicated by acute renal injury, respiratory failure requiring intubation, metabolic acidosis and shock liver. With treatment with high dose steroids and mechanical circulatory support, the patient's severely diminished EF improved to 20% and she is undergoing placement of a left ventricular assist device. Discussion: Fulminant lymphocytic myocarditis is a rare disease that has clinically and pathologically distinct features from subacute or acute lymphocytic myocarditis particularly in its timeline of onset and features of hemodynamic compromise. It most frequently affects young and pediatric individuals and can result in significant mortality and morbidity. This case with an older patient with severe fulminant lymphocytic myocarditis confirmed on biopsy highlights: 1) the importance of early recognition affecting survival outcome, 2) golden standard for diagnosis with endomyocardial biopsy and immunohistochemical analysis for subtype-specific evidence-based treatment, and 3) integrated medical and surgical management, including mechanical circulatory support as an essential life-saving tool.

Inflammatory infiltration of the cardiac conduction system in acute lymphocytic myocarditis.

A 53-year-old man with prior history of bone marrow transplant after acute myeloblastic leukaemia was admitted in the acute cardiac care unit due to suspected acute myocarditis. At admission, his electrocardiogram (ECG) showed right bundle branch block and left anterior fascicular block (Panel A). Previously, he had been assessed regularly in a dedicated cardio-oncology clinic, with normal ECG and transthoracic echocardiography (see Supplementary material online, Videos S1 and S2). Despite high-dose pulses of methylprednisolone, he developed both complete atrio-ventricular (AV) block and progressive left ventricular systolic dysfunction (see Supplementary material online, Videos S3 and S4), leading to cardiogenic shock requiring temporary transvenous pacing and mechanical circulatory support with VA-ECMO. However, he died on day 9 due to multiorgan failure. Gross examination of the heart (Panel B) was normal, but histopathology and immunohistochemistry showed significant infiltration of the ventricular myocardium (Panel C), AV node (Panel D) left anterior fascicle (Panel E), and right bundle branch (Panel F) by mononuclear CD3 + T cells, consistent with the diagnosis of lymphocytic myocarditis. High-definition images S1-S8 are included in the Supplementary material online.

Clinical characteristics and outcome of biopsy-proven myocarditis in children – Results of the German prospective multicentre registry “MYKKE”

BackgroundHeart failure (HF) due to myocarditis might not respond in the same way to standard therapy as HF due to other aetiologies. The aim of this study was to investigate the value of endomyocardial biopsies (EMB) for clinical decision-making and its relation to the outcome of paediatric patients with myocarditis. MethodsClinical and EMB data of children with myocarditis collected for the MYKKE-registry between 2013 and 2020 from 23 centres were analysed. EMB studies included histology, immunohistology, and molecular pathology. The occurrence of major adverse cardiac events (MACE) including mechanical circulatory support (MCS), heart transplantation, and/or death was defined as a combined endpoint. ResultsMyocarditis was diagnosed in 209/260 patients: 64% healing/chronic lymphocytic myocarditis, 23% acute lymphocytic myocarditis (AM), 14% healed myocarditis, no giant cell myocarditis. The median age was 12.8 (1.4–15.9) years. Time from symptom-onset to EMB was 11.0 (4.0–29.0) days. Children with AM and high amounts of mononuclear cell infiltrates were significantly younger with signs of HF compared to those with healing/chronic or healed myocarditis. Myocardial viral DNA/RNA detection had no significant effect on outcome. The worst event-free survival was seen in patients with healing/chronic myocarditis (24%), followed by acute (31%) and healed myocarditis (58%, p = 0.294). A weaning rate of 64% from MCS was found in AM. ConclusionsEMB provides important information on the type and stage of myocardial inflammation and supports further decision-making. Children with fulminant clinical presentation, high amounts of mononuclear cell infiltrates or healing/chronic inflammation and young age have the highest risk for MACE.

The role of endomyocardial biopsy in suspected myocarditis in the contemporary era: a 10-year National Transplant Centre experience

BackgroundDiagnostic endomyocardial biopsy (EMB) in patients with suspected myocarditis helps to direct therapy and guide prognosis. This study aimed to investigate the correlation between the 2007 clinical guideline indications for EMB and the presence of a diagnostic biopsy result and associated outcomes in patients with suspected myocarditis in a national quaternary referral center in a contemporary cohort. MethodsAll cases of suspected myocarditis referred to the National Cardiac Transplant Centre who underwent EMB between 2009 and 2019 were identified retrospectively through pathology records. Outcomes including subsequent need for inotrope and/or mechanical circulatory support (MCS), heart transplantation and in-hospital mortality were recorded. ResultsIn total, 25 (68% male, mean age of 45 ± 15 years) EMBs were performed for this indication across this time period, 64% (n = 16) of which demonstrated diagnostic results, the majority (75%, n = 12) identifying acute lymphocytic myocarditis, 13% (n = 2) giant cell, one patient (6.3%) eosinophilic and one (6.3%) an immune checkpoint inhibitor myocarditis. The majority of those with histologically confirmed myocarditis had a Class I or IIa guideline indication for EMB (n = 12, 75%). The remaining 4 patients (25%), either met Class IIb criteria (n = 2) or would not have been accounted for in this guideline. The majority of patients requiring inotropes and/or MCS (n = 9/11), and/or heart transplant (n = 3/4), or who later died (n = 4/5) were in the diagnostic biopsy group. ConclusionsIn this 10-year National referral sample, 75% of patients with histologically confirmed myocarditis had a Class I or IIa indication for EMB, reinforcing the usefulness of traditional guidelines in this contemporary era. However, 25% of patients with a subsequent confirmed histological diagnosis had either none or a less well-established indication for EMB, highlighting the need for clinical suspicion outside of accepted clinical scenarios.

Clinical Characteristics and Outcome of Biopsy-Proven Myocarditis in Children – Results of the German Prospective Multicentre Registry 'MYKKE'

Background: Heart failure (HF) due to myocarditis might not respond in the same way to standard therapy as HF due to other aetiologies. The aim of this study was to investigate the value of endomyocardial biopsies (EMB) for clinical decision-making and its relation to the outcome of paediatric patients with myocarditis. Methods: Clinical and EMB data of children with myocarditis collected for the MYKKE-registry between 2013 and 2020 from 23 centres were analysed. EMB studies included histology, immunohistology, and molecular pathology. The occurrence of major adverse cardiac events (MACE) including mechanical circulatory support (MCS), heart transplantation, and/or death was defined as a combined endpoint. Results: Myocarditis was diagnosed in 209/260 patients: 64% healing/chronic lymphocytic myocarditis, 23% acute lymphocytic myocarditis (AM), 14% healed myocarditis, no giant cell myocarditis. The median age was 12.8 (1.4-15.9) years. Time from symptom-onset to EMB was 11.0 (4.0-29.0) days. Children with AM and high amounts of mononuclear cell infiltrates were significantly younger with signs of HF compared to those with healing/chronic or healed myocarditis. Myocardial viral DNA/RNA detection had no significant effect on outcome. The worst event-free survival was seen in patients with healing/chronic myocarditis (24%), followed by acute (31%) and healed myocarditis (58%, p=0.294). A weaning rate of 64% from MCS was found in AM. Conclusions: EMB provides important information on the type and stage of myocardial inflammation and supports further decision-making. Children with fulminant clinical presentation, high amounts of mononuclear cell infiltrates or healing/chronic inflammation and young age have the highest risk for MACE.

Case report of severe PCR-confirmed COVID-19 myocarditis in a European patient manifesting in mid January 2020.

BackgroundViral genesis is the most common cause of myocarditis. COVID-19-associated myocarditis seems to be a notable extrapulmonary manifestation, which may result in the need for a different treatment. There has been no positive polymerase chain reaction (PCR) testing of SARS-CoV-2 in heart specimens, thus far.Case summaryA 48-year-old male patient presented with fever, dyspnoea, and haemoptysis. Laboratory findings showed highly elevated inflammatory and cardiac damage markers. Thoracic computed tomography (CT) revealed bilateral, patchy peripheral ground-glass opacities with a crazy-paving pattern, focal consolidations, and mild pleural effusions. Cardiac imaging with echocardiography and magnetic resonance imaging (MRI) detected a reduced biventricular function. MRI additionally showed myocardial oedema and late gadolinium enhancement. Lung and heart biopsies were performed, revealing alveolitis with necrosis and acute lymphocytic myocarditis. Testing for usual cardiotropic viruses was negative, and no aspects of vasculitis or granuloma could be found. Due to fulfilling the criteria, the patient was diagnosed with rheumatic vasculitis. Treatment with cyclophosphamide and steroids was initiated. Later, the patient reported a history of travel to Tyrol in mid January. Consequently, PCR testing for SARS-CoV-2 was performed, which was positive in the heart specimen. Immunosuppressive treatment was discontinued. During a follow-up visit at the end of April, the patient’s recovery was stable.DiscussionIn COVID-19 infections, myocardial inflammation can be present as an extrapulmonary manifestation. Positive PCR testing confirms myocardial invasion of the virus. Imaging and laboratory studies correlate with the histopathological findings, and thus should be performed in COVID-19 patients who are suspicious for myocarditis. Supportive treatment with steroids may be useful in these patients.

A Review of the Extrapulmonary Manifestations of the 2019 Novel Coronavirus Disease (COVID-19)

Background: Since the onset of the 2019 novel coronavirus disease (COVID-19), many reports have presented the disease as a respiratory disease, thereby limiting diagnosis to presentations with respiratory symptoms. This review critically analyzes and consolidates published literature describing extrapulmonary features of COVID-19. Methods: Recently published full-text literature on the extrapulmonary manifestations of COVID-19 was reviewed. The studies reviewed focused on the cardiovascular, gastrointestinal, nervous, hematopoietic, genitourinary, and musculoskeletal systems; and ocular, otorhinolaryngological, and cutaneous symptoms. Results: A total of 28 original articles were selected and analyzed. The most common extrapulmonary manifestations were acute cardiac injury (7.2-19.7%), arrhythmia (16.7%), and shock (8.7%) in the cardiovascular system; anorexia (83.8%), liver abnormality (14.8-37.2%), diarrhea (3.8-29.3%), abdominal pain (0.4-12.0%), nausea (9.5%), and vomiting (0.8-5.0%) in the gastrointestinal system; acute cerebrovascular disease and loss of consciousness (36.4%) in the nervous system; lymphopenia (40.0%-64.0), leukocytosis (14.3-23.4%), anemia (15.0%), thrombocytopenia (7.0%), elevated D-dimer (42.0%), and prolonged prothrombin time (2.1-6.0%) in the hematopoietic system; and proteinuria (43.9-62.7%), hematuria (26.7%), elevated urea (27.1%) and creatinine (18.6%), and acute kidney injury (3.6-5.1%) in the urinary system. Others include sore throat (28.6%), erythematous rash (15.9%), arthralgia/myalgia (14.8%), widespread urticaria (3.4%), and singular reports of acute myopericarditis, acute lymphocytic myocarditis, meningitis, viral encephalitis, testicular pain, anosmia, and acute conjunctivitis. Conclusion: COVID-19 affects every organ-system and can cause extrapulmonary symptoms with or without respiratory symptoms. A high index of suspicion is required to help healthcare providers achieve early diagnosis, prompt treatment, and reduce the chances of spreading the disease within the community.

Viral presence-guided immunomodulation in lymphocytic myocarditis: an update.

Latest statements from European and American societies recommend to rule out viral presence in endomyocardial biopsy (EMB) via polymerase chain reaction (PCR) analysis before starting immunosuppression or immunomodulation in acute lymphocytic myocarditis presenting with life‐threatening scenarios. However, recommendations in myocarditis are mostly based on heterogeneous studies enrolling patients with inflammatory cardiomyopathies and established heart failure rather than acute myocarditis. Thus, definitive evidence of a survival benefit from immunomodulation guided by viral presence is currently lacking. Finally, distinguishing innocent bystanders from causative agents among EMB‐detected viruses remain challenging and a major goal to achieve in the near future. Therefore, considerable divergence remains between official recommendations and clinical practice, including the possibility of starting immunosuppressive therapy empirically, without knowing viral PCR results. This review systematically discusses the unsolved issues of immunomodulation guided by viral presence in acute lymphocytic myocarditis, namely (i) virus epidemiology and prognosis, (ii) variability of viral presence rates, (iii) the role of potential viral bystander findings, and (iv) the main results of immunosuppression controlled trials in lymphocytic myocarditis. Furthermore, a practical approach for the critical use of viral presence analysis in guiding immunomodulation is provided, highlighting its importance before starting immunosuppression or immunomodulation. Future, multicentre studies are needed to address specific scenarios such as fulminant lymphocytic myocarditis and a virus‐tailored management as for parvovirus B19.

Transradial left ventricular endomyocardial biopsy feasibility, safety and clinical usefulness: Initial experience of a tertiary university center

Introduction and objectivesOver the last decade, several studies have suggested that left ventricular endomyocardial biopsy is safer and has a higher diagnostic yield than transvenous right ventricular biopsy. In addition, recent publications indicate that the transradial approach is a feasible and safe alternative to the transfemoral approach for sampling the left ventricle. We report our initial experience with transradial endomyocardial biopsy with regards to feasibility, safety and usefulness. MethodsSingle-center registry of consecutive patients undergoing intended transradial left endomyocardial biopsy. Clinical and technical data were collected prospectively, with a particular focus on success rate and complications. ResultsTwenty-seven patients were screened for left ventricle biopsy. Twenty (25) were selected for an intended transradial approach (mean age 51±18 years old, 22 male). Success rate was 100% with no crossover to femoral approach. There were no major complications. Two patients experienced mild radial spasm. One of them also had a run of non-sustained ventricular tachycardia.Indication for biopsy was either myocarditis or cardiomyopathy of unknown etiology. The final diagnosis was acute lymphocytic myocarditis in five patients, chronic myocarditis in one patient, amyloid light-chain amyloidosis in four patients and transthyretin amyloidosis in six patients. Myocarditis was ruled out in eight patients and amyloidosis in one patient. ConclusionsTransradial left ventricle endomyocardial biopsy is a very safe and feasible method of sampling the myocardium for histopathological analysis, with a good diagnostic yield and clinically meaningful results in properly selected patients.

Persistent left ventricular dysfunction after acute lymphocytic myocarditis: Frequency and predictors.

BackgroundPersistent left ventricular (LV) systolic dysfunction in patients with acute lymphocytic myocarditis (LM) is widely unexplored.ObjectivesTo assess the frequency and predictors of persistent LV dysfunction in patients with LM and reduced LVEF at admission.Methods and resultsWe retrospectively evaluated 89 consecutive patients with histologically-proven acute myocarditis enrolled at three Italian referral hospitals. A subgroup of 48 patients with LM, baseline systolic impairment and an available echocardiographic assessment at 12 months (6–18) from discharge constituted the study population. The primary study end-point was persistent LV dysfunction, defined as LVEF <50% at 1-year, and was observed in 27/48 patients (56.3%). Higher LV end-diastolic diameter at admission (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.04–1.43, p = 0.002), non-fulminant presentation (OR 8.46, 95% CI 1.28–55.75, p = 0.013) and presence of a poor lymphocytic infiltrate (OR 12.40, 95% CI 1.23–124.97, p = 0.010) emerged as independent predictors of persistent LV dysfunction at multivariate analysis (area under the curve 0.91, 95% CI 0.82–0.99). Pre-discharge LVEF was lower in patients with persistent LV dysfunction compared to the others (32%±8 vs. 53%±8, p <0.001), and this single variable showed the best accuracy in predicting the study end-point (area under the curve 0.95, 95% CI 0.89–1.00).ConclusionsMore than half of patients presenting with acute LM and LVEF <50% who survive the acute phase show persistent LV dysfunction after 1-year from hospital discharge. Features of subacute inflammatory process and of established myocardial damage at initial hospitalization emerged as predictors of this end-point.

Acute Steroid Responsive Lymphocytic Myocarditis Confirmed by Multimodal Imaging and Histopathology

Acute Steroid Responsive Lymphocytic Myocarditis Confirmed by Multimodal Imaging and Histopathology

A Case of Acute Myocarditis During Treatment With Anti-PD-1 Antibody Nivolumab in a Melanoma Patient

A 69-year-old woman presented to our hospital with general malaise and tachycardia. She had been treated with an immune checkpoint inhibitor nivolumab (anti-PD-1 antibody) for advanced melanoma of the right eye with liver and bone metastasis. Electrocardiogram showed ST-segment elevation in inferior leads in association with elevated myocardial biomarkers (creatine kinase 728 IU/L, creatine kinase MB isozyme 487 IU/L, and cardiac troponin T 1.60 ng/dL). Echocardiography showed diffuse, moderate hypokinesis of the left ventricle. Emergent coronary angiography revealed normal epicardial coronary arteries and we suspected acute myocarditis as an underlying disease. Left ventricular function was gradually deteriorated with the development of pulmonary congestion, and we started prednisolone at 100 mg/day. Thereafter, the levels of cardiac enzymes declined and left ventricular ejection fraction was gradually improved from 30% to 48%. Myocardial biopsy performed before the treatment with prednisolone demonstrated infiltration of lymphocytes that were CD8 positive and CD4 negative. Real-time PCR and immunohistochemical analysis of biopsied samples for cardiotropic viruses were negative. Immune checkpoint inhibitors are now used for the treatment of advanced melanoma and lung cancers, being known to cause immune-related adverse effects such as thyroiditis, pneumonitis, and pancreatitis. To the best of our knowledge, this is the first reported case of acute lymphocytic myocarditis related to nivolumab treatment.

How Long Should We Wait for Recovery from Acute Fulminant Myocarditis?

A 54-year-old diabetic man presented to the hospital with shock and bradycardia. His initial estimated left ventricular ejection fraction (LVEF) was 15% and the electrocardiogram showed a junctional escape rhythm with a wide QRS complex and no P wave. Intensive supportive therapy was initiated after inserting a pacemaker and starting extracorporeal membrane oxygenation. A myocardial biopsy confirmed acute lymphocytic myocarditis with extensive myocyte necrosis, and cardiac transplantation was planned. However, the patient survived without transplantation after vigorous hemodynamic support for 2 weeks. After discharge, he had limited activity for 4 months due to dyspnea caused by a reduced systolic heart function (LVEF, 21%) with a junctional escaped beat. His systolic function recovered markedly 6 months after stopping the hemodynamic support, with the presence of a P wave and narrowed QRS complex. (Korean J Med 2015;89:439-443)

Formation of the inflammasome in acute myocarditis

Acutemyocarditisisanin flammatorydisorderoftheheartmuscleinwhichtheseverityofinjurydependsbothonthenatureoftheoffendingagent(i.e.virus)andontheensuinginflammatoryresponse.Thede fini-tion excludes, however, the response to ischemic or toxic injury. Theheart, however, like other organs, may provide a stereotyped responsetoinjury.Followingischemicinjury,theformationoftheinfl ammasomein the heart promotes heart failure [1].Theinflammasome is a macro-molecular structure activated during injury that amplifies the responseby processing Interleukin-1β (IL-1β) and IL-18, and promotion of celldeath [2]. Viral infections may lead to either death of the virus and thecell (pyroptosis), or survival of both cell and virus with persistence ofthe infection through inhibition of the inflammasome (evasion) [3].Therearenoreportsoftheinflammasomeinacutemyocarditis.Wehy-pothesize that the viral infection or the ensuing cellular destructionleads to the formation of the inflammasome, providing an opportunityto explore inflammasome-related markers for diagnostic or prognosticpurposes. Furthermore at present day, there are no specific treatmentsfor acute myocarditis, and thus inhibitors of the inflammasome couldrepresent a new therapeutic approach.We studied samples obtainedthrough endomyocardialbiopsy in11patients with acute lymphocytic myocarditis (b4 weeks of symptomsonset) in Trieste, Italy. The diagnosis was based upon pathology exam-ination and clinical scenario (Table 1). As a comparison group westudied autopsy samples of 11 patients with acute myocarditis diag-nosed post mortem, and 5 control subjects who had died withoutacute myocarditis or other acute cardiac conditions.Weemployedimmunofluorescencestainingtodetectin flammasomeaggregatesusingantibodiesraisedagainstthescaffoldprotein,ApoptosisSpeck-like protein containing a caspase-1 recruiting domain (ASC), and/or the effector protein, caspase-1, as previously described [1].Tocharac-terizethetypeofcell,weusedadoublestainingtechniquewithantibod-ies against cardiac actin to identify cardiomyocytes, S100A4 to identifyfibroblasts, andCD31 forendothelialcells. To overcomefor the auto fluo-rescence of sarcomeric proteins, we used a solution of 1% Sudan black in70% ethanol for 5 min. Images of samples were acquired with an IX70microscope and cellSens Dimension di gital imaging software (Olympus,Central Valley, PA) using a 40× objective (400× magnification). Filtersets for each separate fluorescence-conjugated antibody were layeredtorenderacompositeimage.Theinflammasome “specks” were countedby cell type (cardiomyocyte, leukocytes, fibroblasts and endothelialcells) per high power field of view (40×). Data are presented as medianand interquartile range and non-parametric Mann–Whitney test wasused.Intracellularaggregates of ASC and/ or caspase-1 indicative of the for-mation of the inflammasome were seen in leukocytes, cardiomyocytes,fibroblasts and endothelial cells in heart biopsy samples of all 11 cases(100%), and in heart samples of 10 of 11 post-mortem cases (91%), andin none of the controls (0%, P b 0.002)(Fig. 1). ASC aggregates co-localized with caspase-1 aggregates in virtually all cases. The numberof inflammasomes was variable across cases ranging between 3 and 14specks in biopsies, and between 0 and 45 specks per field in autopsies,without statistically significant differences (data not shown). Some

Surgical Thrombectomy of Two Left Ventricular Thrombi in a Child With Acute Myocarditis

Myocarditis is a potentially life-threatening disease. Although ventricular thrombus formation in myocarditis is rare, it carries the risk of serious complications. We report on a 10-year-old previously healthy girl presenting with 2 large left ventricular thrombi in acute lymphocytic acute myocarditis. No coagulation disorder was found. Her clinical course and mobile thrombi characteristics prompted us to carry out an urgent surgical thrombectomy rather than primary anticoagulation therapy. The patient has recovered well without clinical signs of thromboembolism.

Surgical thrombectomy of two left ventricular thrombi in a child with acute myocarditis

Introduction: Left ventricular (LV) thrombus formation is a rare but serious complication in myocarditis. We report about an adipose 10-year-old previously healthy girl (body weight 58 kg, length 135 cm) presenting with two large left ventricular thrombi in acute lymphocytic myocarditis.

An unusual case of giant cell myocarditis missed in a Heartmate-2 left ventricle apical-wedge section: a case report and review of the literature

Herein we present a case of fulminant myocarditis in a woman previously treated for B-cell lymphoma. While the clinical context was suggestive of adriamycin-induced cardiomyopathy, the initial pathology of the Heartmate-2 apical core showed lymphocytic myocarditis. After 8 months of stability, the patient presented with progressive heart failure and recurrent ventricular arrhythmias. An endomyocardial biopsy revealed findings typical of giant cell myocarditis (GCM); poor response to immunosuppressive therapy and marked hemodynamic instability led to urgent transplantation. To our knowledge, this is the first reported case of GCM following an acute lymphocytic myocarditis and the second GCM case associated with B-cell lymphoma.