Myocarditis Presenting Research Articles

Immunosuppressive Therapy and Risk Stratification of Patients With Myocarditis Presenting With Ventricular Arrhythmias

This study sought to investigate the effects of immunosuppression on arrhythmic myocarditis. The effects of immunosuppressive therapy (IST) on ventricular arrhythmia (VA) have not been reported in patients with immune-mediated biopsy-proven myocarditis. Furthermore, myocarditis arrhythmic risk is still unpredictable. We enrolled 255 patients with biopsy-proven virus-negative myocarditis and VA (major: ventricular fibrillation, ventricular tachycardia; minor: nonsustained ventricular tachycardia, Lown grade≥2 premature ventral complexes) at presentation. Serum cardiac autoantibodies (antiheart antibodies, anti-intercalated disk autoantibodies [AIDA]) were detected by a standardized indirect immunofluorescence technique. Whenever accepted and noncontraindicated, IST was started. Control individuals (IST-) were chosen after 1:1 matching to IST+ patients by age, sex, ethnicity, left ventricular ejection fraction, VA type, and treatment. A total of 58 matched patient couples (age 42 ± 13 years; 67% male) were analyzed in the main study cohort. IST duration was 12 ± 1months. By the 24-month prospective follow-up, major VA occurred in 6 IST+ versus 10 IST- patients (p=0.42), with no episodes following IST termination. As compared to IST- patients, IST+ patients showed a significant reduction in minor VA burden, as well as improvement in clinical, laboratory, and imaging findings (all p<0.05). Major VA onset and positive AIDA status were independently associated with major VA at follow-up (hazard ratio [HR]: 14.2; 95% confidence interval [CI]: 2.9 to 68.7 and HR: 8.0; 95%CI: 2.6 to 25.2, respectively; both p<0.001). Furthermore, in the whole study population (N=255), IST was independently associated with protection from major VA (HR: 0.3; 95%CI: 0.2 to 0.7; p=0.01) at 38 ± 21months of follow-up. In patients with immune-mediated virus-negative myocarditis presenting with VA, IST is associated with positive effects on minor VA and nonarrhythmic endpoints. Short-term effects are limited on major VA, which were independently associated with major VA onset and positive AIDA.

Use of SARS-CoV-2-infected deceased organ donors: Should we always "just say no?"

In the context of a rapidly evolving pandemic, multiple organizations have released guidelines stating that all organs from potential deceased donors with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection should be deferred, including from otherwise medically eligible donors found to have mild or asymptomatic SARS‐CoV‐2 discovered on routine donor screening. In this article, we critically examine the available data on the risk of transmission of SARS‐CoV‐2 through organ transplantation. The isolation of SARS‐CoV‐2 from nonlung clinical specimens, the detection of SARS‐CoV‐2 in autopsy specimens, previous experience with the related coronaviruses SARS‐CoV and MERS‐CoV, and the vast experience with other common RNA respiratory viruses are all addressed. Taken together, these data provide little evidence to suggest the presence of intact transmissible SARS‐CoV in organs that can potentially be transplanted, specifically liver and heart. Other considerations including ethical, financial, societal, and logistical concerns are also addressed. We conclude that, for selected patients with high waitlist mortality, transplant programs should consider accepting heart or liver transplants from deceased donors with SARS‐CoV‐2 infection.

Clinical presentation, cardiovascular findings, etiology, and outcome of myocarditis in dogs: 64 cases with presumptive antemortem diagnosis (26 confirmed postmortem) and 137 cases with postmortem diagnosis only (2004–2017)

IntroductionThis study describes presentation, cardiovascular abnormalities, etiology, and outcome of canine myocarditis in geographic areas not endemic for Trypanosoma or Leishmania. AnimalsSixty-four (presumed antemortem diagnosis) and 137 (postmortem diagnosis only) client-owned dogs at two tertiary care facilities were included. Materials and methodsMedical records of dogs with clinical or histopathological diagnosis of myocarditis were reviewed retrospectively. ResultsCommon examination findings in dogs with a presumed antemortem diagnosis included fever (21%) and heart murmur (19%). Median cardiac troponin I was 12.2 ng/mL (range: 0.2–808.0 ng/mL), and troponin exceeded 1.0 ng/mL in 26 of 29 (90%) dogs. Ventricular ectopy was the most common arrhythmia (54%), whereas decreased left ventricular systolic function was the most common echocardiographic abnormality (56%). An infectious etiology was diagnosed in 35 of 64 (55%) dogs. Confirmed infectious etiologies included bacterial sepsis (n = 9) or extension of endocarditis (3), toxoplasmosis or neosporosis (3), parvovirus (2), and one case each of bartonellosis, trypanosomiasis, leptospirosis, and dirofilariasis. Median survival time was 4 days (range: 0–828 days) for all dogs vs. 82 days for dogs who survived at least 2 weeks after diagnosis. Presence of pericardial effusion or azotemia was a significant predictor of non-survival. The most common inflammatory infiltrate on histopathology was neutrophilic (47%), and 20 of 137 (14.5%) dogs had concurrent bacterial endocarditis on postmortem. ConclusionsBacterial infection was the most common confirmed etiology of myocarditis in this study. Prognosis for canine myocarditis is guarded and similar to that reported for infective endocarditis. Criteria for the antemortem diagnosis of canine myocarditis are suggested.

Acute Myocarditis After Black Widow Spider Bite: A Case Report.

The black widow spider (BWS) is a venomous spider whose bite can cause various clinical conditions that range from local damage to serious systemic complications, including death. Cases of myocarditis following a BWS bite are rare but they can be fatal on occasion. However, the prognostic significance of the bite and presentation of myocarditis is unknown. Our case involved a 50-year-old man who presented with myocarditis after being bitten by a BWS and subsequently admitted to the intensive care unit for cardiac monitoring. During the hospital stay, he showed worsening signs on both the electrocardiographic and echocardiographic evaluations despite therapeutic success. Subsequent cardiac magnetic resonance and coronary angiography investigations showed no significant alterations; blood and instrumental test results slowly improved, and the patient was discharged home after 12 days of hospitalization without complications. This case illustrates that acute myocarditis, although an infrequent complication of BWS bite, has the potential to be lethal. The correct diagnosis, which is not always easy to formulate, is important to identify those patients who can benefit from careful monitoring and specific therapies aimed at reducing the risk of life.

Impact of ventricular arrhythmias on outcomes in children with myocarditis.

Children affected with acute myocarditis may progress rapidly into profound ventricular dysfunction and ventricular arrhythmias. The objective of this study is to assess the impact of ventricular arrhythmias on in-hospital mortality and the use of mechanical circulatory support in patients with myocarditis. Pediatric patients (age 0-18years) admitted with myocarditis were identified from the National Inpatient Sample dataset for the years 2002-2015. A total of 12,489 patients with myocarditis were identified. Of them, 1627 patients were with ventricular arrhythmias and 10,862 patients without ventricular arrhythmias. Mortality was higher in those with ventricular arrhythmias (19.5% vs. 2.8%, OR = 8.47; 95% CI 7.16-10.04; p < 0.001). The median length of stay and the median cost of hospitalization were higher in the ventricular arrhythmias group (9days vs. 4days, p < 0.001 and $121,826 vs. $37,658, p < 0.001, respectively). There was a substantial increase in the utilization of extracorporeal membrane oxygenation (ECMO) in patients with ventricular arrhythmias (25.4% vs. 2.7%, OR = 12.40; 95% CI 10.55-14.57; p < 0.001). The use of ventricular assist devices (VADs) was higher in patients with ventricular arrhythmias (4.5% vs. 1.3%, OR = 3.76; 95% CI 2.82-5.01; p < 0.001). An improvement in discharge survival was observed over the years of study in both VA and non-VA groups; associated with this decline in mortality, there was a rising trend of ECMO utilization.Conclusion: Development of ventricular arrhythmia in children with myocarditis is a strong predictor for mortality and ECMO utilization. What is Known: • The clinical presentation of pediatric myocarditis varies from no symptoms of myocardial dysfunction to a rapidly progressing severe congestive heart failure. • Little is known about the predictors of mortality in children with suspected myocarditis. What is New: • Development of ventricular arrhythmia in children with myocarditis is a strong predictor for mortality and ECMO utilization. • Improvement in discharge survival was observed over the years of study; associated with this decline in mortality, there was a rising trend of ECMO utilization.

Fulminant Bacterial Myocarditis Presenting as Myocardial Infarction

A previously healthy man presented with inferior myocardial infarction and recent upper respiratory tract infection. Bacteremia was detected and treated; however, the patient developed refractory polymorphic ventricular tachycardia storm and shock. Clinical autopsy revealed the diagnosis of isolated bacterial myocarditis. (Level of Difficulty: Beginner.)

Immune-Related Myocarditis Presenting as Shortness of Breath and Complete Heart Block in an Urothelial Cancer Patient Receiving Pembrolizumab: A Case Report

Pembrolizumab is an immune-checkpoint inhibitor (ICI) drug approved for the treatment of patients who have locally advanced or metastatic urothelial cancer and are not eligible for cisplatin-containing therapy. However, like other antiPD-1s, pembrolizumab can cause immune- related adverse events (irAEs), some of which can be serious enough to warrant emergency care 3-7. Pembrolizumab-related cardiac irAEs, owing to the increased morbidity and mortality associated with them, can present a special challenge in the emergency department. Most documented cardiac irAEs occurred in patients receiving anti-PD-1s in combination with other agents or in patients with pre-existing heart conditions and were easily resolved with steroid treatment8. Herein, we describe a case with unclear symptom presentation in a patient with no previous cardiac history receiving only 1 dose of pembrolizumab. Knowledge gained from this case and others will help elucidate the early- and late-onset toxic effects associated with pembrolizumab and inform the development of effective algorithms for the identification and management of these effects, thereby optimizing the safety of pembrolizumab and other immunotherapy agents in the Emergency Department.

Isolated intraventricular conduction delay in fulminant myocarditis: A case report

Introduction: Fulminant myocarditis is uncommon. Making the diagnosis in the emergency department is difficult due to the nonspecific clinical presentation and electrocardiogram results. Case presentation: A 58-year-old Chinese woman presented to an emergency department with dizziness and malaise for 2 days. She was hypotensive and afebrile. Initial electrocardiogram showed isolated nonspecific intraventricular conduction delay. Despite resuscitation, she rapidly deteriorated in the emergency department and eventually succumbed. Autopsy and histological examination of heart muscle found acute inflammatory cell infiltration and multifocal necrosis, suggestive of acute fulminant myocarditis. Discussion: There is a wide range of differential diagnosis of nonspecific intraventricular conduction delay. Clinical presentation of mycoarditis is also often non-specific. Rapid and accurate recognition of the condition is essential to save life. Conclusion: Fulminant myocarditis presenting with cardiogenic shock and isolated intraventricular conduction delay on electrocardiogram poses a diagnostic challenge as illustrated in this case report.

PRESENTATION AND LONG TERM OUTCOMES OF IMMUNE CHECKPOINT INHIBITOR RELATED MYOCARDITIS

Cancer treatment in the past decade has rapidly changed with the introduction of immune checkpoint inhibitors (ICIs). Myocarditis is a rare but potentially deadly complication of ICI treatment. We aim to describe presentation and long-term outcomes of ICI related myocarditis in comparison to a

Idiopathic Eosinophilic Myocarditis Presenting with Features of an Acute Coronary Syndrome

SummaryA 62-year-old female was admitted with severe left-sided chest pain, nausea and pre-syncope. She had widespread T wave inversion on ECG and elevated troponins and was suspected to have an acute coronary syndrome event. Invasive coronary angiogram revealed normal coronary anatomy with no flow-limiting lesions. Echocardiography and cardiac MRI revealed impaired left ventricular (LV) systolic impairment, a mobile LV apical thrombus and a moderate global pericardial effusion with no significant compromise. Full blood count analysis indicated the patient to have significant eosinophilia, and the patient was diagnosed with idiopathic eosinophilic myocarditis. She was commenced on Prednisolone and Apixaban, and eosinophil levels returned to normal after 10 days of steroids. Over the course of 3 months, the patient had a complete recovery of her LV function and resolution of the LV thrombus. This case highlights a rare, reversible case of idiopathic eosinophilic myocarditis which may present similar to acute coronary syndrome.

Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis

BackgroundThere is a need for improved methods for detection and risk stratification of myocarditis associated with immune checkpoint inhibitors (ICIs). Global longitudinal strain (GLS) is a sensitive marker of cardiac toxicity among patients receiving standard chemotherapy. There are no data on the use of GLS in ICI myocarditis. ObjectivesThis study sought to evaluate the role of GLS and assess its association with cardiac events among patients with ICI myocarditis. MethodsThis study retrospectively compared echocardiographic GLS by speckle tracking at presentation with ICI myocarditis (cases, n = 101) to that from patients receiving an ICI who did not develop myocarditis (control subjects, n = 92). Where available, GLS was also measured pre-ICI in both groups. Major adverse cardiac events (MACE) were defined as a composite of cardiogenic shock, arrest, complete heart block, and cardiac death. ResultsCases and control subjects were similar in age, sex, and cancer type. At presentation with myocarditis, 61 cases (60%) had a normal ejection fraction (EF). Pre-ICI, GLS was similar between cases and control subjects (20.3 ± 2.6% vs. 20.6 ± 2.0%; p = 0.60). There was no change in GLS among control subjects on an ICI without myocarditis (pre-ICI vs. on ICI, 20.6 ± 2.0% vs. 20.5 ± 1.9%; p = 0.41); in contrast, among cases, GLS decreased to 14.1 ± 2.8% (p < 0.001). The GLS at presentation with myocarditis was lower among cases presenting with either a reduced (12.3 ± 2.7%) or preserved EF (15.3 ± 2.0%; p < 0.001). Over a median follow-up of 162 days, 51 (51%) experienced MACE. The risk of MACE was higher with a lower GLS among patients with either a reduced or preserved EF. After adjustment for EF, each percent reduction in GLS was associated with a 1.5-fold increase in MACE among patients with a reduced EF (hazard ratio: 1.5; 95% confidence interval: 1.2 to 1.8) and a 4.4-fold increase with a preserved EF (hazard ratio: 4.4; 95% confidence interval: 2.4 to 7.8). ConclusionsGLS decreases with ICI myocarditis and, compared with control subjects, was lower among cases presenting with either a preserved or reduced EF. Lower GLS was strongly associated with MACE in ICI myocarditis presenting with either a preserved or reduced EF.

Acute enterovirus infections significantly alter host cellular DNA methylation status

Acute infections with enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) usually cause Hand, foot and mouth disease (HFMD) among infants and young children with several large outbreaks worldwide. Unfortunately, the molecular mechanisms underlying enterovirus infections remain largely unknown. In this study, we analyzed the genome-wide DNA methylation patterns of host cells in response to EV71 and CVA16 infections using the Illumina Infinium HumanMethylation450 BeadChip. Of over 480,000 loci studied, significant differential methylation was observed between EV71 infected-cells and control cells at 3957 CpG sites, out of which 2478 were hypermethylated and 1479 were hypomethylated, whereas CVA16 infection resulted in methylation level changes of 5194 CpG sites with 4288 hypermethylated and 906 hypomethylated. These differential methylated loci displayed a wide range of genomic distributions in chromosomes, inside and surrounding areas (shores and shelves) of CpG islands, as well as functional gene regions including promoter, gene body and 3’UTR. Based on methylation alterations, 1189 genes were identified to be potentially co-associated with the replication processes of two enteroviruses. GO function annotation and enrichment analysis of 1189 common differentially methylated genes reflected a broad spectrum of biological regulatory events during viral infection. KEGG pathway analysis indicated the involvement of diverse signaling pathways including viral myocarditis, Notch signaling and antigen processing and presentation. Our present study provides a novel insight into enterovirus-host interaction network at epigenetic profile, thus contributing to improved understanding of HFMD pathogenesis.

Scrub typhus in patients with acute febrile illness: a 5-year study from India.

Scrub typhus was once thought to be a disease of rural origin and was confined to specific pockets in South Asia. Early diagnosis and treatment is extremely important as it is associated with high mortality if left untreated. To delineate the clinical and molecular epidemiology of scrub typhus in patients presenting with acute febrile illness from various parts of India. During the study period of 5 years (October 2013 to October 2018), a total of 1742 patients with acute febrile illness <15 days were enrolled after taking informed consent. Patients were diagnosed using IgM Enzyme-linked immunosorbent assay (ELISA) based on the pre-determined region specific cut offs. Patients with positive IgM ELISA were also subjected to IgM Immunofluorescence assay and nested polymerase chain reaction (PCR) assay. The demographic and relevant clinical details of the patients were documented and analyzed. A total of 210 (12.1%) patients were diagnosed with scrub typhus. Of these, nested PCR was positive in only 85 patients. Sequencing and phylogenetic analysis showed that the predominant circulating genotypes were Gilliam and Karp. On multivariate analysis, acute respiratory distress syndrome, myocarditis, encephalitis/encephalopathy, jaundice and splenomegaly were significantly more common in those patients who were diagnosed with scrub typhus. A total of 14 patients diagnosed with scrub typhus succumbed to the illness. Patients with fever, headache, pulmonary manifestations, CNS manifestations, myocarditis, transaminitis or thrombocytopenia presenting in the monsoon and post-monsoon season should be evaluated for scrub typhus irrespective of the geographical location in India.

The Added Value of Cardiac Magnetic Resonance in Muscular Dystrophies.

Muscular dystrophies (MD) represent a heterogeneous group of rare genetic diseases that often lead to significant weakness due to progressive muscle degeneration. In many forms of MD, cardiac manifestations including heart failure, atrial and ventricular arrhythmias and conduction abnormalities can occur and may be a predominant feature of the disease. Cardiac magnetic resonance (CMR) can assess cardiac anatomy, global and regional ventricular function, volumes and mass as well as presence of myocardial inflammation, infiltration or fibrosis. The role for cardiac MRI has been well-established in a wide range of muscular dystrophies related cardiomyopathies. CMR is a more sensitive technique than echocardiography for early diagnosis of cardiac involvement. It has also great potential to improve the prediction of long-term outcome, particularly the development of heart failure and arrhythmic events; however it still has to be validated by longitudinal studies including large populations. This review will outline the utility of CMR in patients with muscular dystrophies for assessment of myocardial involvement, risk stratification, and in guiding therapeutic management.

LGE-MRI in the Assessment of Left-ventricular Remodelling in Myocarditis.

Background: The exact morbidity of myocarditis is unknown, as the treatment is generally delayed in virtue of misdiagnosis or missed diagnosis.Aim: The aim of this study was to identify prognostic factors of left-ventricular remodeling on CMRI performed in patients with pathological proven myocarditis.Methods: Sixty-two cases with various presentations of myocarditis (39 cases with heart failure; 23 cases with arrhythmias) were selected. All patients, who underwent coronary angiography, endomyocardial biopsy, were divided into positive-remodeling and negative-remodelling groups to analyse LGE and cardiac cine parameters at presentation and subsequent to 3 months.Results: Comparison of two subgroups in CMRI is as follows: positive LGE (65.6% vs. 86.7%; p<0.05), LVEF (41.3±14.8% vs. 37.6±10.1%; p=0.62), (25.7±2.0% vs. 24.0±2.5%; p=0.81), (44.5±3.9mm vs. 46.3±5.4mm; p=0.76), (129.1±8.5ml vs. 135.3±12.2ml; p=0.26), (74.8±7.3ml vs. 79.1±10.0ml; p=0.55), (52.0±5.7g vs. 49.6±6.5g; p=0.71), (34.9±3.5ml vs. 32.4±6.2ml; p=0.68), (3.8±0.7L/min vs. 3.1±0.5L/min; p=0.64), (2.9±0.6L/min*m2 vs. 2.7±0.5L/min*m2; p=0.79).Conclusion: LGE-MRI is rewarding as an independent predictor in left-ventricular positive and negative remodelling of myocarditis.

Assessment of Different Presentations of Myocarditis in Pediatric Intensive Care Units: (A Multi-Center study in Al-Sharqia Governorate).

Assessment of Different Presentations of Myocarditis in Pediatric Intensive Care Units: (A Multi-Center study in Al-Sharqia Governorate).

P5560Assessing etiology in a cohort of patients with myocarditis presenting with complex ventricular arrhythmias: can the percutaneous endomyocardial biopsy help?

Abstract Background Myocarditis represents a common but often under-diagnosed disease, with a wide range of clinical presentations; diagnosis is often presumptive and a clear etiology leading to a specific therapeutic approach is usually not identified. Purpose To describe and assess disease etiology in a cohort of myocarditis patients (pts) with arrhythmic presentation undergoing an invasive diagnostic work-up. Methods All pts with myocarditis presenting with ventricular arrhythmias undergoing an electro-anatomical mapping (EAM) guided endo-myocardial biopsy (EMB) at our institution were enrolled. All enrolled pts also underwent cardiac magnetic resonance imaging (MRI) and an electrophysiological study (EPS). Demographics, arrhythmic presentation, MRI data, arrhythmic inducibility at EPS, EAM and EMB biopsy data were retrieved and analyzed. Molecular biology testing for cardio-tropic virus genome as well as leukocyte immunohistochemical typization were routinely performed on all EMB samples. Results Twenty-six pts were enrolled (85% male, 39±6 y.o.). Clinical presentation was an organized ventricular arrhythmia in 16 (62%) pts (n=3 non-sustained ventricular arrhythmia; n=9 sustained ventricular arrhythmia; n=4 ventricular fibrillation) while frequent (&gt;10.000) premature ventricular complexes (PVCs) in the remaining 10 (38%) pts. MRI showed a late gadolinium enhancement (LGE) pattern consistent with myocarditis in all pts (35% left LGE; 65% right LGE). At the EPS, 10 (38%) pts showed inducibility for SVTs and underwent an intra-cardiac defibrillator (ICD) implant, while 4 (16%) more were implanted for secondary arrhythmic prevention. EAM was performed in 18 (70%), 6 (22%) and 2 (8%) pts in the right, left and in both ventricle respectively; in all cases, abnormal myocardial voltages were retrieved in the area showing LGE at MRI. Extensive myocardial scarring was detected in 7 (27%) pts. All EMB were performed without peri-procedural complications; inflammatory infiltrate and substrate alteration consistent with myocarditis were retrieved in 100% of the bioptic samples. Viral genome was identified in 13 (50%) samples (n=5 Human Herpes Virus 6; n=2 Parvovirus B 19; n=3 Adenovirus; n=1 Ebstein Barr Virus; n=1 Cytomegalovirus; n=1 Rhinovirus) and specific human immunoglobulin treatment was undergone by a single pt; eosinophilic infiltration was found in 2 (8%) patients; lymphocite invasion and auto-antibodies consistent with auto-immune myocarditis were detected in 2 (8%) patients and appropriate immunosuppressive therapy was started, while a myocardial band contraction pattern typical of toxic myocarditis was found in a single (4%) patient [Figure 1]. Different Myocarditis Etiology Rates Conclusion In our myocarditis cohort, EMB confirmed viruses to represented the first myocarditis etiological agent. Despite an invasive work-out, 31% of the cohort etiology still remains unclear.

COXSACKIE B2 VIRUS: FROM A SOCCER GAME TO FULMINANT MYOCARDITIS

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: The presentation of viral myocarditis ranges from no symptoms to devastating illness.1 This is an unfortunate case of Coxsackie B2 virus induced Fulminant Myocarditis (FM); which despite aggressive medical and mechanical circulatory support progressed to fatality. CASE PRESENTATION: A 20-year-old male patient was transferred to our hospital with respiratory failure and shock. He presented to his local hospital with dyspnea, fever, myalgias and arthralgias that started after an indoor soccer game two weeks earlier. Prior to admission he was treated with inhalers, steroids and antibiotics without improvement. The TTE showed an LVEF 30% and Chest CT Scan showed bilateral consolidations and multiple nodules surrounded by ground glass opacities. Mechanical ventilation, vasopressors and inotropes were initiated prior to transferring him to our hospital. Upon arrival he required paralysis and pronation to improve his hypoxia. He was started on broad spectrum antimicrobials. However, the initial infectious workup was negative. Further workup obtained due to persistent fever revealed portal vein thrombosis which was treated with heparin. Hypercoagulability, malignancy and rheumatology tests were unrevealing. Expanded infectious workup was most notable for positive Coxsackie B2 serology with titers that increased 4-fold during hospitalization to 1:320, consistent with viral myocarditis. TEE showed persistent LV dysfunction, global LV wall motion abnormalities, increased septal wall thickness, severe mitral regurgitation and moderate tricuspid regurgitation. After receiving diuretics, vasopressors and inotropes he improved and was extubated. He subsequently decompensated requiring reintubation and resumption of inotropes. ECMO was initiated with biventricular assist device support. Heart transplant was considered but his hospital course was complicated by severe deconditioning and went on to develop GI bleeds, acute renal failure, fungemia, pulmonary abscess status post decortication and contained pulmonary artery rupture. On ICU day #97, his illness was deemed not survivable and his family withdrew care. DISCUSSION: Coxsackie B serotypes are among the more common causes of viral myocarditis, which may evolve into FM.2 FM is defined as 2-4 weeks of acute illness, followed by cardiogenic shock, needing hemodynamic support; and myocardial inflammatory infiltrates on histology. FM has a dramatic and progressive clinical course, with a severely impaired LVEF.3 It often requires prolonged hemodynamic support and referral for heart transplant.4 In general, in-hospital outcomes are poor; with increased morbidity and up to 32% reported mortality.5 CONCLUSIONS: Coxsackie B induced Fulminant Myocarditis portends increased morbidity and mortality, even after aggressive medical and mechanical circulatory support. Reference #1: Kindermann et al. J Am Coll Cardiol. 2012;59:779–92. Reference #2: Mehta et al. Case Reports in Infectious Diseases. 2018;ID 4258296:1-4. Reference #3: Ammirati et al. Circulation. 2017;136:529-45. DISCLOSURES: No relevant relationships by Stefanie DiGiandomenico, source=Web Response No relevant relationships by Tirsa Ferrer Marrero, source=Web Response No relevant relationships by Javeria Haque, source=Web Response No relevant relationships by Christopher Roberts, source=Web Response No relevant relationships by Gabriel Ryan, source=Web Response no disclosure on file for Jonathon Truwit; No relevant relationships by Krista Tuomela, source=Web Response No relevant relationships by Jane Wainaina, source=Web Response

2422Outcome of histologically-proven fulminant versus acute non-fulminant myocarditis with left ventricular systolic dysfunction. Evidence from the International Registry on Acute Myocarditis

Abstract Background Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular (LV) dysfunction requiring inotropes and/or mechanical circulatory support. Based on a retrospective single-center study published in 2000, patients with FM were considered to have better outcomes than those affected by acute non-fulminant myocarditis (NFM) presenting with LV systolic dysfunction (LVSD). Recently, this tenet was challenged, though substantial disagreement still exists. Purpose Aim of the present study is to provide additional evidence on the outcome of FM and to ascertain if patient stratification based on the main histologic subtypes can provide additional prognostic information. Methods Two hundred and twenty patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms &lt;30 days) presenting with LVSD were included in a retrospective, international registry comprising 16 tertiary hospitals in the United States, Europe, and Japan. The primary endpoint was the occurrence of cardiac death or heart transplant (HTx) within 60 days from admission and at long-term follow-up. Results Patients with FM (N=165) had significantly higher rates of cardiac death and HTx compared with those with NFM (N=55), both at 60 days (28.0% vs. 1.8%, p=0.0001) and at 7-year follow up (47.7% vs. 10.4%, p&lt;0.0001; Figure). At Cox-multivariate analysis, the histologic subtype emerged as a further variable affecting outcome in FM patients, with giant cell myocarditis having a significantly worse prognosis compared with eosinophilic and lymphocytic myocarditis both at 60 days (62.5% vs. 26.3% vs. 21.0%) and at 3 years (81.3% vs. 39.9% vs. 37.3%, overall p&lt;0.0001). In a sub-analysis including only adults with lymphocytic myocarditis, the main endpoints occurred more frequently in FM compared with NFM both at 60 days (19.5% vs. 0%, p=0.005) and up to 7 years (41.4% vs. 3.1%, p=0.0004). Outcome of FM vs NFM Conclusions The results of this international registry confirm that patients with FM have higher rates of cardiac death and HTx both in the short and long-term compared with patients with NFM. Furthermore, we provide evidence that the histologic subtype of FM carries independent prognostic value, highlighting the need for timely endomyocardial biopsy in this condition. Acknowledgement/Funding None

P6450Plasminogen activator inhibitor type-1 (PAI-1) expression relates to the presence of myocardial inflammation in patients with nonischemic cardiomyopathy

Abstract Background Plasminogen activator inhibitor type-1 (PAI-1) is an important inhibitor of the fibrinolytic pathway and an acute phase reactant in response to inflammatory cytokines, resulting in thrombosis, arteriosclerosis, and tissue fibrosis. It has been identified as a potential biomarker for coronary artery disease and metabolic syndrom. However, so far, nothing is known about its importance in nonischemic cardiomyopathy. Aims To analyzed PAI-1 expression in patients with different forms of cardiomyopathies and evaluate possible influence of PAI-1-dependent pathomechanisms in patients with intramyocardial inflammation. Methods and results In this study, endomyocardial biopsies (EMBs) from 309 patients (mean age 48.0±13.9 years) with different forms of cardiomyopathies were enrolled, including 123 patients with dilated cardiomyopathy (DCM) (mean LVEF 28.01±9.06%) and 186 patients with EMB-proven virus-negative inflammatory cardiomyopathy (DCMi) (mean LVEF 31.76±14.14%). 10 patients (mean LVEF 60.50±4.76%) without viral or inflammation in EMB served as controls. Hemodynamic parameters were measured by catheterization and echocardiography. EMBs were performed at first admission after exclusion of ischemic of valvular heart disease. In EMBs PAI-1 was assessed by immunohistology including digital imaging analysis. PAI-1 expression was significantly higher in patients with DCMi in contrast to DCM patients and controls (0.517±2.20 vs. 0.187±0.598 vs. 0.023±0.032% Area Fraction; p=0.0002). PAI-expression correlates significantly with lymphocytic infiltrates (for CD3 r=0.56, p&lt;0.0001, and LFA-1 r=0.59, p&lt;0.0001). This was found to be independent of hemodynamic parameters, and age. Conclusion Myocardial inflammation is associated with a significant increase in PAI-1 expression in DCMi independently of the hemodynamic conditions. This new pathophysiological axis could be a potiential therapeutic target in future treatment stategies in DCMi.