Lymphocytic Myocarditis Research Articles

Long-Term Outcomes of Dilated Cardiomyopathy Diagnosed During Childhood

Background— Existing studies of childhood dilated cardiomyopathy deal mainly with early survival. This population-based study examines long-term outcomes for children with dilated cardiomyopathy. Methods and Results— The diagnosis of dilated cardiomyopathy was based on clinical, echocardiographic, and pathological findings. The primary study end point included time to the combined outcome of death or cardiac transplantation. There were 175 patients 0 to <10 years of age at the time of diagnosis. Survival free from death or transplantation was 74% (95% confidence interval, 67–80) 1 year after diagnosis, 62% (95% confidence interval, 55–69) at 10 years, and 56% (95% confidence interval, 46–65) at 20 years. In multivariable analysis, age at diagnosis <4 weeks or >5 years, familial cardiomyopathy, and lower baseline left ventricular fractional shortening Z score were associated with increased risk of death or transplantation, as was lower left ventricular fractional shortening Z score during follow-up. At 15 years after diagnosis, echocardiographic normalization had occurred in 69% of surviving study subjects. Normalization was related to higher baseline left ventricular fractional shortening Z score, higher left ventricular fractional shortening Z score during follow-up, and greater improvement in left ventricular fractional shortening Z score. Children with lymphocytic myocarditis had better survival and a higher rate of echocardiographic normalization. At the latest follow-up, 100 of 104 of survivors (96%) were free of cardiac symptoms, and 83 (80%) were no longer receiving pharmacotherapy. Conclusions— Death or transplantation occurred in 26% of patients with childhood dilated cardiomyopathy within 1 year of diagnosis and ~1% per year thereafter. Risk factors for death or transplantation include age at diagnosis, familial cardiomyopathy, and severity of left ventricular dysfunction. The majority of surviving subjects are well and free of cardiac medication.

Role of Left Ventricular Biopsy in the Management of Heart Disease

More than 50 years after the first description of transvenous endomyocardial heart biopsy (EMB),1 the role of EMB remains controversial. EMB is often essential for the diagnosis of allograft rejection and specific forms of native myocardial disease, including amyloidosis and giant cell myocarditis,2 yet expert consensus for the utility of EMB in more common scenarios is lacking. For example, a 2013 position statement from the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases recommends heart biopsy be performed for all cases of suspected myocarditis, including most acute and chronic dilated cardiomyopathy.3 In contrast, the “2013 ACCF/AHA Guideline for the Management of Heart Failure” recommends that “endomyocardial biopsy should not be performed in the routine evaluation of patients with heart failure.” (class of recommendation III).4 The European Society of Cardiology Working Group and the American College of Cardiology Foundation/American Heart Association recommendations are both based on expert opinion (level of evidence C). Article see p 1531 Most authorities in the field agree on the unique ability of EMB to diagnose specific viral heart infections and distinguish prognostically valuable histological patterns such as sarcoidosis or lymphocytic myocarditis.5,6 Lymphocytic myocarditis is a histological biomarker that predicts both successful bridging to recovery after left ventricular (LV) assist device placement in adults7 …

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.

Outcome of Patients Having Heart Transplantation for Lymphocytic Myocarditis

Heart transplantation (HT) for myocarditis has been controversial because of earlier reports of a poor prognosis after the procedure. We sought to determine whether lymphocytic myocarditis (LM) at the time of HT affects cardiac allograft rejection and survival after HT compared with other patients without LM in the current era of HT. We retrospectively reviewed 759 consecutive patients who underwent de novo HT at Columbia University Medical Center between 2000 and 2010 and compared prognosis after HT of the patients with pathologically proven LM in their explanted hearts with that of age- and gender-matched patients with idiopathic dilated cardiomyopathy (IDC group; n = 96) and with ischemic cardiomyopathy (IC group; n = 64). Thirty-two patients (4.2%) had LM in the explanted hearts pathologically. Among the 3 groups, no statistically significant difference was observed in the number of biopsy-diagnosed acute cellular rejection (ACR; International Society for Heart & Lung Transportation grade ≥2R) events during the first year after HT. In contrast, the frequency of biopsy-diagnosed ACR in subsequent years was greater in the LM group (n = 8, 3.8%) than in IC group (n = 3, 0.5%, p = 0.006), although no different from that of patients with IDC. The frequency of antibody-mediated rejection and posttransplant survival did not differ among the 3 groups. In conclusion, patients with pre-HT LM have an increased frequency of late ACR after HT compared with patients with IC. Nevertheless, survival of LM patients after HT is comparable to that of patients transplanted for IDC or IC.

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.

First therapeutic use of Artesunate in treatment of human herpesvirus 6B myocarditis in a child

BackgroundHuman herpesvirus 6 (HHV-6) is an important cause of fulminant or acute viral myocarditis. However, insufficiency of standard antiviral treatment against HHV-6 is an emerging problem. ObjectivesTo describe the case of child with HHV-6 myocarditis who was treated by unloading with a left ventricular assist device and Artesunate. Study designCase report supported by histological and viral diagnoses via a combination of histology/immunohistochemistry and polymerase chain reaction techniques performed on cardiac tissues before and after treatment. ResultsFollowing therapeutic intervention, the clinical status and heart function improved. Endomyocardial biopsies revealed decreased levels of HHV-6B DNA in the myocardium and the disappearance of histological findings in support of lymphocytic myocarditis. Left ventricular assist device could be explanted. No adverse effects of Artesunate were noted. ConclusionsIn addition to existing heart failure treatments, Artesunate can be considered as an effective candidate for clinical use in cases of HHV-6B associated myocarditis.

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.

Fatal Toxoplasmosis in a Vinaceous Amazon Parrot (Amazona vinacea)

Toxoplasmosis was diagnosed in a vinaceous Amazon parrot based on histopathology and immunohistochemistry. The bird was prostrate on the bottom of the cage and died. Necropsy revealed edema and congestion of the lungs, cloudy air sacs, and mild hepatomegaly. Histopathology revealed severe pulmonary congestion and edema and interstitial mononuclear cell inflammation associated with many cysts containing bradyzoites of Toxoplasma gondii scattered throughout. The heart had mild multifocal lymphocytic myocarditis and free tachyzoites in the muscle fibers, and the kidneys had mild interstitial nephritis and a few cysts containing bradyzoites of T. gondii. Immunohistochemistry was negative for Sarcocystis falcatula and Neospora caninum and confirmed the protozoa as T. gondii. This is the first description of T. gondii in an endangered species ofa Brazilian psittacine.

Immunosuppressive therapy in virus-negative inflammatory cardiomyopathy

While there is general agreement on the favorable impact of immunosuppression in eosinophilic, granulomatous, giant cell and lymphocytic myocarditis and with inflammatory myocardial disease associated with connective tissue disorders or with rejection of a transplanted heart, its therapeutic role in the treatment of lymphocytic inflammatory cardiomyopathy (ICM) is still debated. Previous retrospective studies reported a relevant (≥ 10% left ventricular ejection fraction) clinical benefit in 90% of patients with virus-negative ICM and no cardiac impairment in 85% of patients with virus-positive ICM following immunosuppression. Some studies identified cardiomyocyte HLA up-regulation as an additional indicator of ICM susceptibility to immunosuppressive therapy. Recently in a single-center randomized prospective double-blind trial using a combination of prednisone (1mg/kg per day for 4 weeks followed by 0.33mg/kg per day for 5 months) and azathioprine (2mg/kg per day for 6 months) in addition to supportive treatment in 85 virus-negative ICM patients, a significant improvement of left ventricular ejection fraction and a significant reduction of left ventricular dimensions in 88% of 43 treated patients was reported when compared to 42 patients receiving placebo who showed a cardiac impairment initially in 83% of cases (TIMIC study). These data confirm the efficacy of immunosuppression in virus-negative ICM. The lack of response in 12% of cases suggests that the missing response might be due to the presence of viruses which were not screened for or to mechanisms of damage and inflammation not susceptible to immunosuppression. The recovery of cardiac function in responders to immunosuppression was associated with the inhibition of cardiomyocyte death, an increase of cell proliferation and with newly synthesized contractile material.

Giant cell myocarditis

Giant cell myocarditis (GCM) usually presents as acute dilated cardiomyopathy that does not improve with guideline-based treatments. Ventricular tachycardia and heart block occur in a substantial number of patients. Diagnosis by endomyocardial biopsy can allow for the addition of immunosuppressive therapy and timely use of mechanical circulatory support when indicated. Recent studies suggest that the ventricular arrhythmias in GCM may be mediated by a cytokine-induced change in desmosomal protein expression. Genomic and proteomic studies suggest that the regulation of inflammatory pathways differs in GCM from lymphocytic myocarditis. Transplantation remains an effective therapy despite a 20-25% risk of GCM recurrence in the allograft. Recurrence in the native heart occurs up to 8years after initial diagnosis. The long-term management of GCM patients, who initially recover, is not known and highlights the need for continuing multicenter collaborative clinical investigations.

Endomyocardial Biopsy (EMB) Has Diagnostic and Clinical Utility in Acute Onset Cardiomyopathy

Endomyocardial Biopsy (EMB) Has Diagnostic and Clinical Utility in Acute Onset Cardiomyopathy

C6 Not all IRIS's are equal: a case of sudden death

BackgroundMyocarditis is a well-recognised complication of HIV infection but is seldom observed in clinical practice in the UK. Additionally, myocarditis has been associated with sudden unexplained death in the general...

Electronic Control Devices

The use of deadly force by law enforcement personnel is a hot-button issue in contemporary society. Their responsibility is to handle life-threatening situations while, as much as possible, avoiding fatalities or serious injuries of suspects, bystanders, or themselves. In these settings, the use of lethal weapons must be weighed against reactions to circumstances that do not pose an imminent threat of a fatal outcome. Moreover, use of intense physical restraint instead of lethal weapons in less ominous situations is not without risk either, in that fatal events due to asphyxia have occurred as an unintended consequence of this nonlethal control strategy. In addition, the decision whether deployment of a lethal weapon, as opposed to physical restraint, is the proper action in a specific confrontation often must be made quickly, leaving little time for assessing options. Article see p 2417 The development of electronic control devices (ECDs), or stun guns, emerged as an alternative strategy, allegedly effective for controlling a threatening confrontation without resorting to needless serious injuries or fatalities. In principle, the ECD is more forgiving of errors of judgment than a firearm. The ECD is designed to deliver a painful and physically disabling electric shock, temporarily incapacitating a threatening individual. Although a significant number of deaths in association with, or following the use of, ECDs have been cited in a lay publication,1 peer-reviewed literature on the topic has been limited to several case reports, largely in the form of letters to the editors of journals.2 However, associations or correlations, in the absence of extremely strong population-based hazard ratios,3 are inadequate to support a scientific conclusion of causation, without additional information supporting the likelihood of a direct causal relation in an individual case. Data limited to a few case reports make it difficult to provide informed statements …

Myocardites aiguës

Myocarditis is defined as inflammation of the myocardium accompanied by myocellular necrosis. Acute myocarditis must be considered in patients who present with recent-onset of cardiac failure or arrhythmia. Fulminant myocarditis is a distinct entity characterized by sudden onset of severe congestive heart failure or cardiogenic shock, usually following a flu-like illness, parvovirus B19, human herpesvirus 6, coxsackievirus and adenovirus being the most frequently viruses responsible for the disease. Treatment of myocarditis remains largely supportive, since immunosuppression has not been proven to be beneficial for acute lymphocytic myocarditis. Trials of antiviral therapies, or immunostimulants such as interferons, suggest a potential therapeutic role but require further investigation. Lastly, early recognition of patients rapidly progressing to refractory cardiac failure and their immediate transfer to a medical-surgical center experienced in mechanical circulatory support is warranted. In this setting, ECMO should be the first-line mechanical assistance. For highly unstable patients, a Mobile Cardiac Assistance Unit, that rapidly travels to primary care hospitals with a portable ECMO system and hooks it up before refractory multiorgan failure takes hold, is the preferred option.

Poster #105 MONOZYGOTIC TWINS DISCORDANT FOR BIPOLAR DISORDER SHOW FUNCTIONAL DNA METHYLATION CHANGES IN WHOLE BLOOD AND BRAIN

To evaluate the prognosis of leftventricular (LV) aneurysms with normal global function caused bymyocarditis.LV aneurysms may result fromidiopathic or viral myocarditis. The prognosis of inflammatory LVaneurysms when associated with a normal cardiac function isunknown.Among 353 patients with a histologicdiagnosis of myocarditis, 12 (3.3%) had single or multiple localized, LV aneurysms (length, 10.6 ± 3.1 mm; width, 7.4 ± 4.2 mm) withnormal cardiac function. Presenting symptoms were ventriculartachycardia (VT) in nine patients and unexplained chest pain in three. All patients underwent laboratory tests and noninvasive and invasivecardiac examinations, including biventricular endomyocardialbiopsy.In all patients, LV endomyocardialbiopsy specimen showed a lymphocytic myocarditis with focal intensemyocytolysis or damage of intramural vessels, whereas right ventricularbiopsy was diagnostic for myocarditis only in three. Serologic studysuggested a viral infection in 3 patients and an immunologic disorderin 2, although it was negative in 7. Treatment included antiarrhythmicsin 9 patients with VT, β-blockers in 1 with chest pain, andimmunosuppression (prednisone and azathioprine for 5 months) in 4 withactive myocarditis (2 with chest pain and 2 with VT). Atintermediate-term follow-up (mean, 53 months; range, 12 to 120 months),LV function was persistently normal in all patients, with an LVaneurysm occlusion being observed in two patients. All patients wereasymptomatic, with no VT recurrence or major clinical events. Nonerequired implantable electrical devices or a surgicalintervention.LV aneurysms with normalglobal function caused by myocarditis are an uncommon benign entity inwhich major therapeutic regimens are usuallyunnecessary.

Serological diagnostics of myocardium diseases based on multivariate analysis of cardiotrophic autoantibodies’ profiles

We analyzed profiles of IgG autoantibodies to 16 cardiac specific proteins and their main immunogenic region B-epitopes, in the groups of already verified cardiac pathology: acute and chronic lymphocytic myocarditis, ST elevation myocardial infarction, postinfarction remodeling of myocardium, dilated cardiomyopathy and in healthy controls along with patients, suffered from gastritis (to evaluate immune response against cross-reactive B-epitopes). AAB specific patterns allowed us to distinguish cases among themselves by means of multiparametrical canonical discriminant analysis in approximately 95% of cases. Positive predictive value in the group of MYO reached 95%, in the STEMI—89%, in the PIR—99%, in the DCM—99%, in the group of gastritis—88%. Principal component analysis of mentioned cardiac pathologies extended current clinical knowledge of their immunopathogenesis. Obtained data markedly proved a usability of serum AAB profiling for non invasive screening, differential diagnostics and working hypothesis composition.

Abstract 18051: High Prevalence of Active Myocarditis in Patients with Takotsubo Cardiomyopathy: A Magnetic Resonance-endomyocardial Biopsy Study

Background: Tako-tsubo cardiomyopathy (TTC) was recently classified as a cardiomyopathy with distinct clinical and angiographic features, but mechanisms of cardiac dysfunction and histological substrate are still largely unclear. We evaluated cardiac magnetic resonance (CMR) and endomyocardial biopsy (EMB) findings in patients with TTC. Methods: Twenty consecutive patients (19 F, 58±12 years) with clinical and angiographic features of TTC underwent CMR with edema (STIR images) and delayed enhancement (DE) studies. Of these, 15 patients also underwent EMB. Myocardial samples obtained from apical akinetic left ventricular segments were processed for histology, immunohistochemistry and polymerase chain reaction (PCR) for cardiotropic viruses. Results: All patients presented acute chest pain with ST-segment elevation in anterior leads and evidence of myocardial necrosis. Symptoms were precipitated by emotional stress in 12 (60%) cases. At CMR DE was observed in 11 patients (55%) in all cases with a subepicardial or midventricular pattern; edema was observed in 10 (50%) patients, associated with DE in 8 cases. Neither DE nor edema was observed in 7 patients. In 11 patients (73%) EMB showed an active lymphocytic myocarditis with evidence of activated T lymphocytes. In 4 patients (27%) contraction band necrosis was observed. PCR identified parvovirus B19 viral genome in 3 patients with myocarditis. Among patients with a histological diagnosis of myocarditis CMR showed DE in 10 and edema in 8 cases. One patient with myocarditis had neither DE nor edema at CMR. Patients with contraction-band necrosis showed no DE or edema at CMR. Three myocarditis virus-negative patients failing to recovery after 6 weeks from clinical presentation, received prednisone and azathioprine for 8 weeks with significant improvement of left ventricular contractility. Conclusions: Acute myocarditis represents a frequent substrate of TTC. CMR may help to identify myocardial inflammation in TTC patients. Immunohistochemical and virological diagnosis through EMB may affect both treatment and prognosis. Further studies are needed to clarify the prevalence of acute myocarditis among TTC patients and the possible association between emotional stress and viral infection.

Altered Desmosomal Proteins in Granulomatous Myocarditis and Potential Pathogenic Links to Arrhythmogenic Right Ventricular Cardiomyopathy

Immunoreactive signal for the desmosomal protein plakoglobin (γ-catenin) is reduced at cardiac intercalated disks in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), a highly arrhythmogenic condition caused by mutations in genes encoding desmosomal proteins. Previously, we observed a false-positive case in which plakoglobin signal was reduced in a patient initially believed to have ARVC but who actually had cardiac sarcoidosis. Sarcoidosis can masquerade clinically as ARVC but has not been previously associated with altered desmosomal proteins. We observed marked reduction in immunoreactive signal for plakoglobin at cardiac myocyte junctions in patients with sarcoidosis and giant cell myocarditis, both highly arrhythmogenic forms of myocarditis associated with granulomatous inflammation. In contrast, plakoglobin signal was not depressed in lymphocytic (nongranulomatous) myocarditis. To determine whether cytokines might promote dislocation of plakoglobin from desmosomes, we incubated cultures of neonatal rat ventricular myocytes with selected inflammatory mediators. Brief exposure to low concentrations of interleukin (IL)-17, tumor necrosis factor-α (TNF-α), and IL-6 (cytokines implicated in granulomatous myocarditis) caused translocation of plakoglobin from cell-cell junctions to intracellular sites, whereas other potent cytokines implicated in nongranulomatous myocarditis had no effect, even at much higher concentrations. We also observed myocardial expression of IL-17 and TNF-α and elevated levels of serum inflammatory mediators, including IL-6R, IL-8, monocyte chemoattractant protein 1, and macrophage inflammatory protein 1β, in patients with ARVC (all P<0.0001 compared with controls). The results suggest novel disease mechanisms involving desmosomal proteins in granulomatous myocarditis and implicate cytokines, perhaps derived in part from the myocardium, in disruption of desmosomal proteins and arrhythmogenesis in ARVC.

When Should High-Grade Heart Block Trigger a Search for a Treatable Cardiomyopathy?

High-degree heart block is an uncommon manifestation of acute myocarditis in adults. The rate of heart block requiring a pacemaker in biopsy-proven acute lymphocytic myocarditis generally is low but has been reported in up to 8.3% of cases.1 Important exceptions include cardiac sarcoidosis and giant cell myocarditis (GCM), 2 uncommon and idiopathic disorders for which early immunosuppression may improve clinical outcomes. High-degree heart block occurs in the course of biopsy-proven cardiac sarcoidosis in 23% to 30% of cases (Table).2 In GCM, second- or third-degree heart block requiring a pacemaker occurs in 25% of cases.3 View this table: Table. Prevalence of Various Cardiac Findings in Cardiac Sarcoidosis During the Course of Disease Article see p 303 This relatively high rate of heart block reflects the severity of the clinical course of cardiac sarcoidosis and GCM, which have a higher rate of death and heart transplantation than lymphocytic myocarditis.1,4 Unlike acute lymphocytic myocarditis, for which immunosuppression usually is not beneficial,5 GCM or cardiac sarcoidosis may improve with certain combinations of immunosuppressive drugs. In the case of acute GCM, cyclosporine combined with corticosteroids and usually a T-cell lytic agent like muromonab-CD3 improves transplant-free survival.6 Uncontrolled case series also suggested that left ventricular (LV) dysfunction due to cardiac sarcoidosis may improve with corticosteroid therapy.7 Because GCM and cardiac sarcoidosis are rare disorders, endomyocardial biopsy is not routinely recommended to detect them in the setting of complete heart block unless cardiomyopathy is present.8 Although a recommendation class was not assigned to …