Fulminant Lymphocytic Myocarditis Research Articles

Multisystemic Inflammation Influences Prognosis in Fulminant Lymphocytic Myocarditis.

Multisystem inflammatory syndrome (MIS) is a hyperinflammatory shock associated with cardiac dysfunction and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, there are no reports on using MIS criteria, such as multisystemic inflammation (MSI) in fulminant myocarditis, without SARS-CoV-2 infection. This study investigated the differences in clinical characteristics and course between patients with fulminant lymphocytic myocarditis (FLM) plus MSI and those without MSI.Methods and Results: This multicenter retrospective cohort study included 273 patients with FLM registered in the JROAD-DPC database between April 2014 and March 2017. We evaluated the presence of MSI using criteria modified from previously reported MIS criteria and compared the characteristics and risk of mortality or heart transplantation between FLM patients with MSI and without MSI. Of the 273 patients with FLM, 107 (39%) were diagnosed with MSI. The MSI group was younger (44 vs. 57 years; P<0.0001) and had more females (50% vs. 36%; P=0.0236), a higher incidence of pericardial effusion (58% vs. 40%; P=0.0073), and a lower 90-day mortality rate (19% vs. 33%; P=0.0185) than the non-MSI group. The risk of mortality at 90 days was lower in FLM patients aged <50 years with MSI aged <50 years than in those without MSI (P=0.0463). These results suggest that MSI may influence the prognosis of FLM, especially in patients aged <50 years.

(1136) - Fulminant Lymphocytic Myocarditis with Acute Biventricular Failure: The Role of Mechanical Circulatory Support

(1136) - Fulminant Lymphocytic Myocarditis with Acute Biventricular Failure: The Role of Mechanical Circulatory Support

Fulminant Myocarditis Associated With Parvovirus B19 and Epstein-Barr Virus Coinfection

Abstract Parvovirus B19 (PVB19) and Epstein-Barr virus (EBV) commonly cause infection worldwide, with most persons infected during childhood. Their disease courses are usually mild and brief; however, PVB19 and EBV have been implicated as etiologies of viral myocarditis. We report a case of PVB19 and EBV coinfection associated with fulminant lymphocytic myocarditis. We address the implications of the case, including the differential diagnosis, immunomodulatory treatment considerations, and evidence for the pathologic roles of PVB19, EBV, and coinfection in myocarditis. Although the pathogenic roles of PVB19 or EBV alone in myocarditis are not well established, coinfection of PVB19 and EBV may unlock their pathogenic roles causing fulminant myocarditis. Treatment with steroids and intravenous immunoglobulin G in a patient with rapid clinical deterioration despite the presence of active infection on endomyocardial biopsy by polymerase chain reaction can result in a safe and quick recovery of fulminant viral myocarditis. Early and aggressive intervention, including both mechanical circulatory support and immunomodulatory therapy, may be key to improved outcomes in cases of fulminant myocarditis.

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.

Fulminant Lymphocytic Myocarditis During Pregnancy Treated With Temporary Mechanical Circulatory Supports and Aggressive Immunosuppression.

Fulminant Lymphocytic Myocarditis During Pregnancy Treated With Temporary Mechanical Circulatory Supports and Aggressive Immunosuppression.

Fulminant Giant Cell Myocarditis vs. Lymphocytic Myocarditis: A Comparison of Their Clinical Characteristics, Treatments, and Outcomes.

Objectives: Fulminant myocarditis (FM) is a rapidly progressive and frequently fatal form of myocarditis that has been difficult to classify. This study aims to compare the clinical characteristics, treatments and outcomes in patients with fulminant giant cell myocarditis (FGCM) and fulminant lymphocytic myocarditis (FLM).Methods and Results: In our retrospective study, nine patients with FGCM (mean age 47.9 ± 7.5 years, six female) and 7 FLM (mean age 42.1 ± 12.3 years, four female) patients confirmed by histology in the last 11 years were included. Most patients with FGCM and FLM were NYHA functional class IV (56 vs. 100%, p = 0.132). Patients with FGCM had significantly lower levels of high-sensitivity C-reactive protein [hs-CRP, 4.4 (2.0–10.2) mg/L vs. 13.6 (12.6–14.6) mg/L, P = 0.004, data shown as the median with IQR], creatine kinase-myoglobin [CK-MB, 1.4 (1.0–3.2) ng/ml vs. 14.6 (3.0–64.9) ng/ml, P = 0.025, median with IQR], and alanine aminotransferase [ALT, 38.0 (25.0–61.5) IU/L vs. 997.0 (50.0–3,080.0) IU/L, P = 0.030, median with IQR] and greater right ventricular end-diastolic diameter (RVEDD) [2.9 ± 0.3 cm vs. 2.4 ± 0.6 cm, P = 0.034, mean ± SD] than those with FLM. No differences were observed in the use of intra-aortic balloon pump (44 vs. 43%, p = 1.000) and extracorporeal membrane oxygenation (11 vs. 43%, p = 0.262) between the two groups. The long-term survival rate was significantly lower in FGCM group compared with FLM group (0 vs. 71.4%, p = 0.022). A multivariate cox regression analysis showed the level of hs-CRP (hazard ratio = 0.871, 95% confidence interval: 0.761–0.996, P = 0.043) was an independent prognostic factor for FM patients. Furthermore, the level of hs-CRP had a good ability to discriminate between patients with FGCM and FLM (AUC = 0.94, 95% confidence interval: 0.4213–0.9964).Conclusions: The inflammatory response and myocardial damage in the patients with FGCM were milder than those with FLM. Patients with FGCM had distinctly poorer prognoses compared with those with FLM. Our results suggest that hs-CRP could be a promising prognostic biomarker and a hs-CRP level of 11.71 mg/L is an appropriate cutoff point for the differentiating diagnosis between patients with FGCM and FLM.

Fulminant myocarditis parvovirus B19 related in a young woman

We present the case of a 18-year-old female with fulminant lymphocytic myocarditis caused by Parvovirus B19 (PVB19), successfully treated using temporary LVAD. In the literature there is no consensus on the surgical strategy. While some surgeons prefer to use a single device supporting only the LV, others prefer to start immediately with a biventricular supporting. At pre-procedural ultrasound evaluation, her anatomical features were not suitable for a percutaneous device such as the Impella. Thus, a temporary paracorporeal continuous flow LVAD was inserted. The heart recovery allowed LVAD removal 9 days after the implant.

Fulminant Lymphocytic Myocarditis Possibly Secondary to Rhinovirus Infection in an Adolescent Female

Introduction Rhinovirus is responsible for a large number of upper respiratory tract infections annually. While viral infection is a well-known cause of dilated cardiomyopathy (DCM), rhinovirus-associated myocarditis is not well understood. This is a case of a young woman who suffered cardiogenic shock due to fulminant lymphocytic myocarditis and diagnostic testing noting the presence of rhinovirus, suggesting potential causation. Case Description During late autumn, a healthy 19 year old woman noted 1 week of progressive exertional dyspnea associated with a non-productive cough and epigastric pain. She was diagnosed with a new-onset DCM at a community hospital and transferred to our tertiary center for further management. Urgent echocardiography demonstrated severe biventricular systolic dysfunction and chamber dilation but normal wall thickness. Severe tricuspid valve insufficiency was present secondary to torn chordea tendinae causing a flail septal leaflet Cardiac magnetic resonance imaging revealed diffuse biventricular sub-endocardial delayed enhancement concerning for fulminant myocarditis. Viral respiratory testing was positive for rhinovirus alone. Other laboratory diagnostic data was unremarkable. Cardiac catheterization was conducted, demonstrating the absence of coronary artery disease, but severely impaired cardiac output with an index of 1.65 L/min/m2 and moderately elevated left sided filling pressures. An endomyocardial biopsy confirmed lymphocytic myocarditis with extensive necrosis and fibrosis and CD68 positivity indicating macrophage predominate infiltrate. On the night of hospital day 3, hemodynamic instability was noted with an accelerating frequency of ventricular ectopy. Dobutmaine was started and the initiation of temporary mechanical support was attempted with Impella, However, this was aborted due to catheter occlusion of a small diameter femoral artery given her small stature. Therefore, central VA ECMO was placed. An expedited heart transplant evaluation was begun which she received 8 days later. Gross pathology of the explanted heart confirmed the diagnosis, with a mixed T-cell and B-cell lymphocytic infiltrate. Several months post-transplant, she is thriving. In the absence of other compelling causes of DCM, rhinovirus remains a possible culprit. Viral myocarditis is typically characterized by direct myocyte damage causing necrosis and host immune system upregulation leading to molecular mimicry. However, rhinovirus direct cardiac toxicity has not been identified. To date, two other reported cases of unexplained DCM in a 4 and 27 year-old showed the presence of rhinovirus on nasal swab however, myocardial biopsy was not performed. Conclusion This case presents a missed opportunity for confirming the link between rhinovirus and DCM. Confirmatory viral PCR on biopsy tissue should become a practice standard in any suspected cases and as a standard investigation in cases with unclear etiology.

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.

2421Immunosuppressive therapy and prognosis in biopsy-proven fulminant lymphocytic myocarditis requiring veno-arterial extracorporeal membranous oxygenation support

Abstract Background Fulminant myocarditis is one of the fatal diseases for which effective management has not yet been established. Immunosuppressive therapy (IST) using corticosteroid has been actively applied to giant cell or eosinophilic myocarditis, there is no consensus on the efficacy of lymphocytic myocarditis, which is suspected of involving viral infection. Actually, IST for lymphocytic myocarditis is not recommended in the European Society of Cardiology guidelines, but in the Japanese Circulation Society guidelines, it is approved for use in refractory cases in the absence of curative therapy for myocarditis established. Purpose The purpose of this study was to explore the potential efficacy of immunosuppressive therapy on acute phase in fulminant lymphocytic myocarditis (FLM) requiring veno-arterial extracorporeal membranous oxygenation (VA-ECMO) support. Method We conducted CHANGE-PUMP study that was retrospectively enrolled 99 patients with fulminant myocarditis required VA-ECMO support in the Tokai area (central part of Japan) for the past 20 years. Lymphocytic myocarditis was defined by pathological category. Patients were divided into two groups depending on whether IST using corticosteroid was performed in the clinical course. Results: Sixty-six patients were pathologically diagnosed as fulminant myocarditis by endomyocardial biopsy, of which only 49 patients were FLM. IST were indicated in 8 (16%) out of 49 patients of FLM (IST group; n=8, non-IST group; n=41). Kaplan-Meier survival analysis showed a lower survival rate in the IST group than in the non-IST group (p=0.073). However, in all cases, based on our guidelines, IST was initiated after becoming refractory to MCS treatment. Immunosupressive therapy and prognosis Conclusion In the retrospective analysis, biopsy-proven FLM patients with IST required VA-ECMO support had low survival rates. However, the timing of IST introduction was late and concerned. In the present era when advanced mechanical support appears and the survival rate of fulminant myocarditis is expected to improve, a multicenter prospective study is needed to establish an indication of IST in the acute phase of fulminant myocarditis.

Fulminant Lymphocytic Myocarditis

ABSTRACT Fulminant lymphocytic myocarditis is rare, and affects approximately 200 people per year in the US. It is most frequently diagnosed in males between the ages of 20 and 40 years. Most patie...

Immunosuppressive treatment in fulminant myocarditis and gene expression pattern associated with, but no histological confirmation of giant cell myocarditis.

A healthy woman with acute onset of pulmonary oedema and severely depressed left ventricular function underwent endomyocardial biopsy under the clinical suspicion of fulminant myocarditis. While awaiting the results of biopsy, the situation deteriorated to Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) and extracorporeal membrane oxygenation was implanted. Finally, immunohistochemistry in biopsy specimen corresponded to fulminant lymphocytic myocarditis, although active myocarditis was excluded. Furthermore, gene expression profiling identified giant cell myocarditis although multinuclear cells were absent. This prompted the start of immunosuppression with cortisone and cyclosporine. The patient fully recovered.

Myocarditis and ARVC/D: Variants or mimics?

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a disease characterized by fibrofatty replacement of the right ventricular (RV) myocardium, which is generally considered to be based on variations in desmosomal genes. However, its pathogenesis is not completely clear since myocarditis and high-intensity athletics have both been postulated to contribute to the onset and progression of the disease pattern. We observed a 21-year-old woman who presented with fulminant lymphocytic myocarditis and subsequently fulfilled the diagnostic criteria for ARVC/D by imaging and electrocardiographic characteristics after complete resolution of left ventricular (LV) abnormalities associated with myocarditis. None of the known common mutations associated with ARVC/D were identified in this patient. This report supports the hypothesis of a common pathophysiology of ARVC/D associated with desmosomal dysfunction, which can be based on genetic predisposition or acquired injury.

Anti-thymocyte Globulin as an Adjunct to Treatment of Fulminant Lymphocytic Myocarditis

There is much debate over the role of immunosuppression in the treatment of acute and fulminant myocarditis. The low incidence of the condition prevents large numbers of cases for study, and treatment protocols vary greatly between institutions. In this study we add our experience with anti-thymocyte globulin as an adjunct to standard medical therapy for 5 patients presenting with cardiogenic shock due to fulminant myocarditis. All cases were associated with rapid and dramatic improvement in hemodynamic and electrophysiologic abnormalities, returning patients to NYHA Class I and cardiac function to normal or near normal by discharge.

91: T-Lymphocyte Cytolytic Therapy as Treatment of Fulminant Lymphocytic Myocarditis Is Associated with Rapid Improvement in Hemodynamic and Cardiac Rhythm Abnormalities

91: T-Lymphocyte Cytolytic Therapy as Treatment of Fulminant Lymphocytic Myocarditis Is Associated with Rapid Improvement in Hemodynamic and Cardiac Rhythm Abnormalities

Incessant ventricular tachycardia in fulminant lymphocytic myocarditis: Evidence for origin in the Purkinje system and successful treatment with ablation

Q v Q v ntroduction ulminant myocarditis is characterized by an acute critical llness at presentation but excellent long-term survival if the atient survives the acute episode. In pediatric patients ith acute heart failure secondary to acute lymphocytic yocarditis, freedom from death or transplantation was 9% during follow-up. Although ventricular arrhythmia on nitial presentation occurred in a minority of these patients, entricular arrhythmia was the only significant independent redictor of mortality in one series. The mechanism of entricular arrhythmias in acute myocarditis is unknown, nd investigation is hampered by the rapidly changing subtrate. Similarly, treatment can be challenging because drug herapy is not always effective.

The role of right ventricular endomyocardial biopsy for idiopathic giant cell myocarditis

Background: Idiopathic giant cell myocarditis (GCM) is an uncommon cause of cardiac failure distinguished clinically from lymphocytic myocarditis by rapidly progressive heart failure, arrhythmias, and heart block. Unlike fulminant lymphocytic myocarditis, patients with fulminant cardiac failure caused by GCM may respond to certain immunosuppressive agents; however, right ventricular endomyocardial biopsy (EMB) is infrequently used to establish the diagnosis partly because the sensitivity of EMB for GCM is unknown. The purpose of this study was to estimate the sensitivity of right ventricular EMB for GCM in a referral population. Methods and Results: Twenty subjects (of 63 total) in the Multicenter Giant Cell Myocarditis Registry underwent both right ventricular EMB and heart pathology (HRTP) evaluation from apical wedge, explantation, or autopsy. The false-negative rate of right ventricular EMB was defined as the ratio of negative EMB to positive HRTP results. Ten of the 20 subjects were women. The mean age was 38 years (range, 16-53 years). Twelve (60%) subjects had a positive EMB and positive HRTP confirming GCM. Three (15%) had a negative EMB and positive HRTP for GCM. Five had a positive EMB and negative HRTP evaluation for GCM. The resulting sensitivity of EMB for GCM was 80% (12/15) with a positive predictive value of 71%. Assuming the 5 subjects with a positive EMB and negative HRTP are true positives, the sensitivity improves to 85% (17/20). Predictors of negative HRTP after positive EMB were time from symptom onset to HRTP (P.006) and time from EMB to HRTP (P.03). Conclusions: The sensitivity of right ventricular EMB is high in patients with GCM who have early disease presentation and a fulminant clinical course. Although these results may not apply to individuals with less aggressive disease, EMB may be used selectively to distinguish fulminant heart failure caused by GCM from other causes in which the prognosis may differ.

Mechanical bridge to recovery in fulminant myocarditis

A patient with acute fulminant lymphocytic myocarditis and cardiogenic shock was successfully treated by mechanical offloading of the left ventricle. A nonpulsatile left-heart bypass was undertaken with an implantable centrifugal blood pump. Careful weaning resulted in device removal on the seventh day. Left and right ventricular function is sustained at 7 months. Widespread application of this method depends on the availability of an inexpensive user friendly blood pump, appropriate weaning protocols and emerging strategies to promote sustainabile myocardial recovery.