Active lymphocytic myocarditis treated with murine OKT3 monoclonal antibody in a patient presenting with intractable ventricular tachycardia

This report describes the case of a 33-year-old woman with biopsy-proven, active lymphocytic myocarditis manifested by intractable ventricular tachycardia, nonspecific intraventricular block, and myocardial dysfunction. We treated hersuccessfully with OKT3 monoclonal antibody and antiarrhythmic agents. Immunosuppression is not recommended in patients with infectious or postinfectious myocarditis. However, it may have an important role in autoimmune myocarditis. In the few reports in the medical literature that we were able to find, OKT3 monoclonal antibody was administered early in the setting of acute, fulminant autoimmune myocarditis. Our patient received OKT3 therapy in a later phase of the disease, when inflammatory infiltrates were accompanied by extensive fibrosis and severe damage of cardiomyocytes. Our patient had concomitant Helicobacter pylori infection and a strong positive family history of gastric cancer, a disease often associated with H. pylori. We discuss the possibility of a causal relationship between H. pylori infection and autoimmune myocarditis.     

Fatal acute pulmonary hypertension caused by pulmonary tumour thrombotic microangiopathy

Chronic active Epstein-Barr virus (CAEBV) infection is characterized by chronic or recurrent infectious mononucleosis-like symptoms and the prognosis of CAEBV infection is quite poor. The incidence of myocarditis as a complication of EBV infection is not so high and it is unusual that heart failure appears as the initial symptom. However, it is very important to detect and treat chronic active myocarditis in the early phase of CAEBV infection because chronic active myocarditis disorganizes and decreases cardiomyocytes, resulting in the progression to heart failure. We report a case of a 45-year-old man with CAEBV infection for 5 years. Echocardiography revealed moderate left ventricular systolic dysfunction with mild pericardial effusion. Endomyocardial biopsies demonstrated massive lymphocytic infiltration with adjacent myocytolysis and necrosis of cardiomyocytes suggesting active myocarditis. Immunohistological analysis of biopsies revealed that the infiltrating cells were mainly T lymphocytes. And some of the infiltrating cells showed a positive signal for the EBV-encoded small nuclear RNA by in situ hybridization. Positron emission tomography using (18)F-fluoro-2-deoxyglucose ((18)F-FDG) performed revealed increased uptake of (18)F-FDG of whole left ventricular wall with mild heterogeneity.     

Complete atrioventricular block persisting after regression of infectious myocarditis

Atrioventricular block is usually transient during the course of infectious myocarditis. We report the case of a patient presenting with complete infra-hisian atrioventricular block occurring in the setting of infectious myocarditis and in whom a pacemaker should be finally implanted. Borderline serologies for picornavirus were present 6 weeks later. Complete atrioventricular block persisted during the two years of follow-up despite otherwise complete regression of the myocarditis. We then discuss the main features of conduction disturbances complicating infectious myocarditis, including a list as complete as possible of all the causal agents possibly involved.     

Endocardial fibroelastosis: Myocardial and vascular alterations associated with viral-like nuclear particles

Although clinical, immunologic, and experimental evidence exists implicating in utero viral infection of the myocardium in the development of primary endocardial fibroelastosis, the infectious etiology of this condition remains somewhat controversial. To date, specific features of viral myocarditis and morphological demonstration of viral particles have not been described in EFE. The present case is the first in which extensive light microscopic and ultrastructural analysis of the myocardium revealed abnormalities consistent with a primary viral myocarditis associated with typical EFE. These alterations consisted of chronic myocardial inflammation, extensive interstitial fibrosis, severe degenerative changes in myocardial cells, and a marked proliferation of endothelial cells in large and small intramyocardial vessels leading to vascular occlusions. In support of the infectious etiology of this disease, similar features were noted in skeletal muscle. Most interestingly, viral-like particles were observed in many myocardial and endothelial nuclei. Although we are not absolutely certain of the viral nature of these particles, their appearance suggests viral associated material. We propose that the presence of these particles in this case in association with the other morphological alterations is support for the viral etiology of EFE. The prominent vascular occlusion observed in the myocardium may be an important clue to the pathogenesis of fibroelastosis as either a primary or secondary disease.     

Listerial myocarditis in cardiac transplantation

Clinical signs of heart failure developed in two cardiac transplant recipients and were interpreted initially as graft rejection. Morphologic examination of explanted hearts revealed myocarditis with abscess formation and necrosis consistent with a bacterial process; Listeria monocytogenes was isolated from myocardial tissue in the first case and from blood in both. The first patient also developed signs of meningoencephalitis, but the second had no signs of infection outside the heart. Antimicrobial therapy and retransplantation were successful in eradicating listeriosis. The differential diagnosis of heart failure in cardiac transplant recipients includes infectious myocarditis due to L. monocytogenes.     

Subacute myocarditis as a manifestation of acquired immunodeficiency syndrome

A case of acquired immunodeficiency syndrome associated with myocarditis is reported. The myocarditis was peculiar in that it heralded the syndrome and followed a subacute course. It was most probably of infectious origin, although no pathogen has positively been identified; it may have been caused by a cytomegalovirus or even by the human immunodeficiency virus itself on a background of genetic predisposition. This case shows that while cardiologists are concerned with cardiac disorders occurring during AIDS, they must also consider the possibility of AIDS when confronted with a myocarditis.     

Ictero-haemorrhagic leptospirosis with a cardiac presentation in a patient returning from an endemic zone

On returning from a tropical area, the occurrence of rapidly evolving cardiogenic shock in an infectious context should quickly suggest the diagnosis, for which specific treatment can affect the outcome. The dramatic case of a young female presenting with ictero-haemorrhagic leptospirosis diagnosed post-mortem, demonstrated this pathology with the unusual association of complete atrio-ventricular block and myocarditis in a haemorrhagic context.     

Likely tuberculous myocarditis mimicking an acute coronary syndrome

Acute systemic infections may involve the heart, mostly represented by myocarditis and pericarditis. We report the case of a likely myopericarditis in an adult, leading to the diagnosis of tuberculosis infection. The clinical presentation was an acute coronary syndrome with elevated troponin Ic. An alternative diagnosis of myopericarditis was considered. Chest X-ray depicted a miliary pattern and a CT-scan demonstrated bilateral micronodules with a "tree-in-bud" pattern associated with parenchymal consolidations in the apical segment of the left upper lobe, suggesting infectious bronchiolitis. As the direct microscopic examination of the bronchial expectoration revealed the presence of Koch's bacterium, a diagnosis of a tuberculous myocarditis was likely. The clinical, electrocardiographic and CT-scan findings are shown; cardiac effects associated with tuberculosis are discussed.     

Idiopathic dilated cardiomyopathy: a persistent viral infection or an organ-specific autoimmune disease? The trial of 2 major pathogenetic hypotheses]

Aetiology and pathogenesis of idiopathic dilated cardiomyopathy (DCM) are uncertain. The two major pathogenetic hypotheses are: 1) autoimmunity; 2) persistent viral infection. Indirect evidence for virus association comes from the finding of raised titres of antibody to coxsackievirus in DCM, but infectious virus has never been isolated in myocardium from DCM patients. Bowles et al. using the slot-blotting technique reported that enteroviral RNA was commonly detectable in the myocardium of patients with myocarditis (53%) and with DCM (52%). Other groups using this as well as more refined hybridization techniques have failed to confirm such a high prevalence. Detection of enteroviral genomic RNA in cardiac tissue does not, however, imply active infection or pathogenicity. Thus the mechanisms of chronic myocardial damage in the absence of whole competent infectious virus remain uncertain. The other major pathogenetic hypothesis in DCM involves autoimmune mediated damage to myocytes. Circulating organ specific autoantibodies have been reported in a quarter of a group of patients with idiopathic DCM. This suggests that there may be autoimmune mechanisms operating at least in this subset of patients, but the exact relation of these antibodies to the pathogenesis and prognosis needs to be defined. The abnormal expression of major histocompatibility complex class II antigens on cardiac microvascular endothelium in endomyocardial biopsy tissue from DCM patients, and the reported association with HLA-DR4 phenotype lend further support to the autoimmune hypothesis. The viral and the autoimmune hypothesis in chronic myocarditis and in DCM are not mutually exclusive. In experimentally murine virus-induced myocarditis infectious virus can no longer be recovered from the myocardium after two weeks, although nucleic acid sequences of the viral genome are still detectable. The development of chronic inflammation takes place only in mice with a predisposing genetic background. Chronic myocyte damage is associated with the production of circulating heart-specific autoantibodies and autoreactive lymphocytes. In this animal model chronic myocarditis appears to be a virus-triggered or precipitated autoimmune disease, rather than a persistent viral infection with tissue damage due to active virus synthesis and replication. A similar transition from acute myocarditis into DCM may occur in man.     

Infectious myocarditis: the role of the cardiac vasculature

Infectious myocarditis is the result of an immune response to a microbial infection of the heart. The blood vessels of the heart, both the intramyocardial microvasculature and the large epicardial coronary arteries, play an important role in the pathogenesis of infectious myocarditis. First of all, in addition to cardiomyocytes, endothelial cells of the cardiac (micro)vasculature are direct targets for infection. Moreover, through the expression of adhesion molecules and antigen presenting Major Histocompatibility Complex molecules, the blood vessels assist in shaping the cellular immune response in infectious myocarditis. In addition, damage and dysfunction of the cardiac (micro)vasculature are associated with thrombus formation as well as aberrant regulation of vascular tone including coronary vasospasm. These in turn can cause cardiac perfusion abnormalities and even myocardial infarction. In this review, we will discuss the role of the cardiac (micro)vasculature in the pathogenesis of infectious myocarditis.     

Antibody-mediated immune enhancement in coxsackievirus B3 myocarditis

The aim of the present study was to explore the contribution of antibody-mediated immune enhancement in coxsackievirus B3(CB3) infection. Murine macrophage-like P388D1 cells were exposed to various concentrations of anti-CB3 immunoglobulin G (anti-CB3 IgG) or the Fab fragment of anti-CB3 IgG, and were infected with CB3 in Experiment I. High concentrations of anti-CB3 IgG showed a virus-neutralizing activity; however, a subneutralizing antibody concentration of IgG significantly enhanced virus replication. This infectious enhancement was blocked not only by the pretreatment of heat-aggregated gamma-globulin but by a specific Fc receptor (Fc gamma III/II receptor) antibody treatment. In contrast, the Fab fragment of anti-CB3 IgG did not enhance CB3 infection, but showed a rational neutralizing activity to CB3. These findings suggest the presence of Fc receptor mediated enhancement of CB3 infection in vitro. In Experiment II, C(3)H/He mice were inoculated with various amounts of an amyocarditic variant of CB3 followed 15 days later by myocarditic CB3. By this rechallenge, myocarditis was not induced in the mice with high neutralizing antibody titers. There was an inverse relationship between preexisting neutralizing antibody titers and the severity of myocarditis. The severity of myocarditis and myocardial CB3 titers, however, were markedly enhanced in the mice with a subneutralizing level of immunity compared to those with no immunity. The distribution of myocardial Fc receptor-bearing cells and serum macrophage inflammatory protein-2 levels paralleled the severity of myocarditis. By another virus rechallenge in Experiment III, enhanced infection of CB3 was not observed in vivo. These findings suggest that antibody-mediated immune enhancement might be involved in the pathogenesis of CB3 myocarditis.     

Myocarditis and Raw Meat Consumption: Strange Bedfellows!

Trichinellosis is a parasitic infection that is associated with the consumption of raw meat. The specific genotype Trichinella nativa has been found in raw bear meat. The most common genotype that has been linked with myocarditis is T spiralis. We present a case of T nativa myocarditis secondary to consumption of raw bear meat. The clinical manifestations as well as therapy of this specific genotype is outlined.     

Fulminant Cytomegalovirus Myocarditis in an Immunocompetent Host: Resolution with Oral Valganciclovir

We report a case of fulminant myocarditis after a primary cytomegalovirus infection, in a previously healthy 72-year-old woman. The infection underwent clinical and immunologic resolution consequent to treatment with oral valganciclovir. In an immunocompetent host, the primary cytomegalovirus infection is usually asymptomatic or manifests itself as a heterophile-negative mononucleosis-like syndrome. Cytomegalovirus myocarditis is uncommon in immunocompetent patients. After presenting our case, we review the literature on cytomegalovirus myocarditis in immunocompetent individuals.     

Acute cardiac insufficiency and toxoplasmosis

The authors report the case of a 21-year old, non-immunocompromised girl who presented with severe acute heart failure associated with Toxoplasma infection. The outcome was favourable: cure without sequelae was obtained in a few months with a symptomatic and specific treatment consisting of spiramycin and methylprednisolone. This case is interesting for several reasons. The occurrence of such an acute heart disease is extremely rare in patients with toxoplasmic myocarditis, and so is the presence of a septal focus suspected on the basis of a predominantly septal hypokinesia at echocardiography and of enzymatic changes. The development of an acute heart failure should suggest a diagnosis of toxoplasmic myocarditis, which is rare but important since a specific treatment is available.     

A case report of Creutzfeldt-Jakob disease associated with myocarditis

We have encountered a case of Creutzfeldt-Jakob disease associated with myocarditis. A 77 year-old woman was admitted to a hospital with complaints of rapidly progressive visual disturbance, myoclonus and dementia. Electroencephalogram revealed a periodic synchronous discharge and Creutzfeldt-Jakob disease was suspected. Then she moved to our hospital, because acute myocarditis was combined with ST-T changes on electrocardiogram, and generalized hypokinetic motion of the left ventricle on echocardiogram. The abnormal findings in electrocardiography and echocardiography were transient. Blood levels of enzymes derived from the myocardium were slightly elevated. We could not find a distinct increase in the titer of neutralizing antibody to various viruses. In this case, the cause of myocarditis may have been associated with the infectious agent of Creutzfeldt-Jakob disease. This report might be the first one with a case of Creutzfeldt-Jakob disease complicated with myocarditis.     

Acute Myocarditis after COVID-19 vaccination: A case report

IntroductionThe etiology of myocarditis often remains undetermined. A large variety of infectious agents, systemic diseases, drugs, and toxins can cause the disease. We report the case of a 19-year-old man who developed myocarditis three days after Pfizer-BioNTech COVID-19 booster vaccination.Case reportA 19-year-old man, presenting with troponin-positive acute chest pain, was referred to our department. He had received the Pfizer-BioNTech COVID-19 vaccine three days prior to his admission. The diagnosis of acute myocarditis was confirmed by cardiovascular magnetic resonance imaging. Patient hemodynamic status remained stable during hospitalization. The left ventricular ejection fraction was preserved during hospital stay and at one-month follow-up. We found no evidence for another infectious or autoimmune etiology.ConclusionAlthough imputability of the vaccine cannot be formally established on the basis of this case report, the findings raise the possibility of an association between mRNA COVID-19 vaccination and acute myocarditis.     

Coxsackie Myocarditis Complicating Treatment of Hodgkin's Lymphoma

Summary: A fatal case of Coxsackie 64 myocarditis complicating treatment of Hodgkin's lymphoma in an adult is reported. The virus was isolated from the myocardium obtained at autopsy and light microscopy confirmed a myocarditis with involvement of the conduction system. Electron-microscopy showed dense mitochondrial inclusions. Coxsackie myocarditis rarely results in death of affected adults. It is postulated in this case that the treatment of the Hodgkin's lymphoma resulted in B lymphocyte depletion, allowing a more virulent infection to occur with resultant fatal myocarditis.     

Cytomegalovirus myocarditis in an immunocompetent patient

Viral infections can lead to myocardial inflammation, resulting in acute myocarditis. Acute myocarditis is mostly self-limiting, but it can lead to severe dilated cardiomyopathy and rarely to acute cardiac tamponade. We report a rare case of myocarditis in a young immunocompentent male patient due to a recent cytomegalovirus (CMV) infection. The clinical presentation was an influenza-like syndrome, classical for a CMV infection, in combination with mild chest pain. Further exploration showed inflammation-compatible perimyocardial images on magnetic resonance imaging (MRI). Following the symptomatic perimyocardial inflammation, the patient developed an acute asymptomatic self-limiting CMV hepatitis, a rare combination. Moreover, there was a remarkable evolution of both clinical signs with first increasing cardiac enzymes due to myocarditis and later on development of acute hepatitis. In this case report, we present the typical MRI images of myocarditis and discuss the CMV cardiac effects as well as the combination of CMV myocarditis and hepatitis.     

Echocardiography in acute infectious myocarditis

Two cases of acute infectious myocarditis are reported, of which one was fatal. Echocardiographic features included normal left ventricular size with diffuse asynergy of the wall movements, increased right ventricular size, an echocardiographic pattern of thickened posterior pericardium, and also mural thrombus of the left ventricle in the fatal case. These echocardiographic changes were totally reversible in the nonfatal case. Hence, because of acute fulminant myocarditis, the left ventricle may be noncompliant, with poor systolic function leading to pulmonic edema and even death.