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PubMedDate not supplied

Diagnostic accuracy of antimyosin scintigraphy in suspected myocarditis.

BACKGROUND: Radiolabeled antibody specific for cardiac myosin administered intravenously has been used to define noninvasively regions of myocardial necrosis. Inflammatory heart disorders such as myocarditis and heart transplant rejection demonstrate diffuse and often faint myocardial uptake of antimyosin antibody. This study was undertaken to evaluate the reproducibility and diagnostic accuracy of antimyosin antibody imaging for the detection of patients with suspected myocarditis. METHODS AND RESULTS: Fifty antimyosin scans, performed consecutively in patients with suspected myocarditis, were evaluated by one independent observer and two panels of observers. Antimyosin scan interpretations were compared with endomyocardial biopsy results and also with serial changes in left ventricular function. An independent observer (A) and a panel of five observers (A through E) interpreted the antimyosin scans as positive or negative on the basis of both planar images and tomographic reconstructions. Three of the five observers (A through C) again interpreted the scans but based interpretation only on planar images. Blinded random sequence evaluation of antimyosin scans based on the planar and tomographic interpretations revealed moderate agreement between the independent observer (A) and the group of observers (A through E) (kappa = 0.58). There was also moderate agreement between interpretations based on planar images alone and interpretations based on both planar and tomographic images (kappa [A through E]/[A through C] = 0.57; kappa [A through C]/A = 0.48). Comparison of antimyosin scan results with histologic evidence of myocarditis in endomyocardial biopsy specimens demonstrated that all scan results obtained from the individual or the panels of observers had a very high sensitivity (91% to 100%) and a high negative predictive value (93% to 100%). The specificity (31% to 44%) and positive predictive value (28% to 33%) were less impressive. We also compared the scan and biopsy results with the composite clinical standard of significant left ventricular functional improvement. Endomyocardial biopsy demonstrated poor sensitivity (35%) compared with antimyosin scans (82% to 94%) but had superior specificity (endomyocardial biopsy, 79%; antimyosin scan, 25% to 42%). The specificity of interpretations based on planar and tomographic interpretations (38% to 42%) was better than the planar images alone (25%). If reversible left ventricular dysfunction is considered clinical evidence of myocarditis, this study suggests that a negative endomyocardial biopsy significantly misses the presence of the disease. On the other hand, a negative antimyosin scan almost invariably excludes myocarditis. CONCLUSIONS: This study demonstrates a high degree of interobserver reproducibility of antimyosin interpretation. Comparison of the scintigraphic results with histologic and clinical standards indicates a high sensitivity of antimyosin scans for the detection of myocarditis. The antimyosin scan is also not likely to miss clinically or pathologically diagnosed myocarditis, in contrast to the endomyocardial biopsy, which missed clinically validated myocarditis 65% of time. The combination of high sensitivity and negative predictive value suggests that antimyosin scintigraphy may be an effective screening procedure for obviating biopsies in patients with suspected myocarditis.

Anti-Inflammatory Agents↗
PubMed2006

Coronary flow reserve and heart failure in experimental coxsackievirus myocarditis. A transthoracic Doppler echocardiography study.

The objective of this study was to apply transthoracic Doppler echocardiography (TTDE) in mice to study coronary flow reserve (CFR), an index of coronary microvascular function, in mild and severe forms of experimental viral myocarditis. Regarding methodology, BALB/c mice were infected with cardiotropic coxsackieviruses causing either a mild (Nancy strain) or a severe (Woodruff strain) myocarditis. Left ventricular dimensions, fractional shortening, and CFR (ratio of left coronary artery flow velocity during maximal adenosine-induced vasodilatation to rest) were measured by TTDE before infection and again 1 or 2 wk after infection. As a result, the resting flow velocity did not change after infection. In contrast, CFR reduced significantly 1 wk after infection with either virus variant [from 2.5 (SD 0.3) to 1.4 (SD 0.1) in severe and from 2.4 (SD 0.4) to 2.1 (SD 0.3) in mild myocarditis], being significantly lower in the severe than mild myocarditis. CFR remained low in severe myocarditis 2 wk after infection. Fractional shortening decreased to the same levels 1 wk after infection with either virus variant [from 0.54 (SD 0.02) to 0.43 (SD 0.03) in severe and from 0.51 (SD 0.03) to 0.44 (SD 0.02) in mild myocarditis, P < 0.05]. However, 2 wk after infection, mice with severe myocarditis had enlarged left ventricles and lower fractional shortening [0.31 (SD 0.03)] than mice with mild myocarditis [0.47 (SD 0.02), P < 0.01]. In conclusion, CFR measured with TTDE is reduced in coxsackievirus myocarditis in mice. Low CFR is associated with progressive heart failure, indicating that dysfunction of coronary microcirculation is a determinant of poor outcome in viral myocarditis.

Animals↗
PubMed1990

Peripartum myocarditis and cardiomyopathy.

The clinical and pathologic features of 18 consecutive patients with peripartum cardiomyopathy at The Johns Hopkins Hospital were examined in an attempt to define the incidence of myocarditis and to determine its response to immunosuppressive agents. In addition to routine studies, patients were evaluated with echocardiography, nuclear ventriculography, right heart catheterization, and myocardial biopsy. Fourteen of the 18 patients (78%) showed evidence of myocarditis. Of these, 10 were treated with immunosuppressive therapy. Nine of the 10 treated patients with myocarditis had subjective and objective improvement. Follow-up endomyocardial biopsies in these patients showed resolution or substantial improvement in myocarditis. Four patients with myocarditis not treated with immunosuppressives also improved. All patients improving spontaneously presented with congestive heart failure within 1 month of delivery and improved dramatically within days of presentation. Four of the 18 patients showed no evidence of myocarditis. Of these, two improved, and two deteriorated (both requiring cardiac transplantation). None of these four patients were treated with immunosuppressive therapy. We conclude that in patients with peripartum cardiomyopathy, 1) the etiology remains unclear although myocarditis was present in 78% of those with this condition, 2) resolution of myocarditis is associated with significant improvement in left ventricular function, 3) myocarditis may resolve spontaneously without detectable loss of cardiac function, and 4) immunosuppressive therapy in patients with myocarditis and persistent left ventricular dysfunction may improve left ventricular function and prognosis.

Adult↗
PubMed2004

Animal models for autoimmune myocarditis and autoimmune thyroiditis.

This chapter describes four murine models of autoimmune diseases: two related to autoimmune myocarditis and two related to autoimmune thyroiditis. The first model, Coxsackie virus B3 (CB3)-induced myocarditis, results in the development of acute myocarditis in susceptible as well as resistant mouse strains, whereas chronic myocarditis develops only in genetically susceptible mice. CB3-induced myocarditis closely resembles the course of human myocarditis, which is believed to be initiated by viral infection. Mouse cardiac myosin heavy chain has been identified as the major antigen associated with the late chronic phase of viral myocarditis. The second model is cardiac myosin-induced experimental autoimmune myocarditis (EAM) and, in a modification, cardiac alpha-myosin heavy chain peptide-induced myocarditis. In the EAM model, cardiac myosin or the relevant peptide in Freund's complete adjuvant (FCA) is injected subcutaneously into mice. The immune response, the histological changes, and the genetic susceptibility seen in EAM are similar to those of CB3-induced myocarditis. The third model is experimental autoimmune thyroiditis (EAT). EAT can be induced in genetically susceptible strains of mice by immunization with mouse thyroglobulin in FCA or lipopolysaccharide. Mice susceptible to EAT have the H-2A(k), H-2A(s), or H-2A(q) alleles. We describe here a standard technique for the induction of EAT; it was developed in our laboratory and is widely used as a model for studying Hashimoto's thyroiditis. The fourth model presented in this chapter is that of spontaneous autoimmune thyroiditis in NOD.H2h4 mice. These mice express the H-2A(k) allele on an NOD genetic background and develop spontaneous thyroiditis, which is exacerbated with dietary iodine.

Amino Acid Sequence↗
PubMed1996

Recognition and optimum management of myocarditis.

Myocarditis is a poorly understood condition and its prevalence is largely underestimated. A significant proportion of cases may be subclinical and chronic, leading to dilated cardiomyopathy, which represents the first cause of heart transplantation worldwide. Although inflammation of the myocardium can be associated with various causes, particularly viruses, myocarditis is usually idiopathic. Present evidence suggests that some 'idiopathic' and chronic 'postviral' myocarditis cases may be autoimmune, whereas others with acute self-limited disease or with persisting pathogenic virus by molecular methods may represent viral myocarditis. The major obstacle in identifying a specific therapy in myocarditis lies in the difficulty of a thorough clinical characterisation of individual patients in relation to viral and autoimmune involvement. This also explains the inconclusive results of trials of immunosuppressive drugs in myocarditis/dilated cardiomyopathy. Diagnosis is based upon endomyocardial biopsy. Management of myocarditis requires avoidance of agents that exacerbate myocarditis or depress myocardial function, and conventional therapy for heart failure (diuretics, ACE inhibitors and, if indicated, digoxin) and arrhythmias. Although at present the use of immunosuppressive therapy cannot be recommended on a routine basis, the recent Myocarditis Treatment Trial, where an aetiologically heterogeneous patient population was treated without significant adverse effects, provides some rationale for applying the same immunosuppression protocol to selected patients, e.g. those with active biopsy-proven myocarditis, unresponsive to conventional therapy, prior to transplantation, and those with idiopathic giant cell myocarditis.

Aging↗
PubMed2005

Evaluation of cardiac lesions and risk factors associated with myocarditis and dilated cardiomyopathy in southern sea otters (Enhydra lutris nereis).

OBJECTIVE: To describe cardiac lesions and identify risk factors associated with myocarditis and dilated cardiomyopathy (DCM) in beach-cast southern sea otters. ANIMALS: Free-ranging southern sea otters. PROCEDURE: Sea otters were necropsied at the Marine Wildlife Veterinary Care and Research Center from 1998 through 2001. Microscopic and gross necropsy findings were used to classify sea otters as myocarditis or DCM case otters or control otters. Univariate, multivariate, and spatial analytical techniques were used to evaluate associations among myocarditis; DCM; common sea otter pathogens; and potential infectious, toxic, and nutritional causes. RESULTS: Clusters of sea otters with myocarditis and DCM were identified in the southern aspect of the sea otter range from May to November 2000. Risk factors for myocarditis included age, good body condition, and exposure to domoic acid and Sarcocystis neurona. Myocarditis associated with domoic acid occurred predominantly in the southern part of the range, whereas myocarditis associated with S. neurona occurred in the northern part of the range. Age and suspected previous exposure to domoic acid were identified as major risk factors for DCM. A sample of otters with DCM had significantly lower concentrations of myocardial L-carnitine than control and myocarditis case otters. CONCLUSIONS AND CLINICAL RELEVANCE: Cardiac disease is an important cause of death in southern sea otters. Domoic acid toxicosis and infection with S. neurona are likely to be 2 important causes of myocarditis in sea otters. Domoic acid-induced myocarditis appears to progress to DCM, and depletion of myocardial L-carnitine may play a key role in this pathogenesis.

Animals↗
PubMed2000

[Diagnosis and course of myocarditis: a survey in the medical clinics of Zurich University Hospital 1980 to 1998].

The clinical picture of myocarditis/myopericarditis is of importance in differential diagnosis, especially in younger patients with suspected myocardial infarction. Myocarditis/myopericarditis commonly presents with chest pain, and the diagnosis is usually established on clinical grounds. However, endomyocardial biopsy is necessary to confirm the diagnosis. We evaluated the characteristics of acute myocarditis over the years 1980-1998 in 54 patients of the Department of Medicine of the University Hospital, Zurich. Two to 6 patients per year were hospitalised with this diagnosis. In most cases the diagnosis was established by a combination of criteria, such as a preceding infection of the upper respiratory tract, thoracic pain, ST segment elevations in different precordial leads followed by T wave inversions, arrhythmias, elevation of cardiac enzymes, reversible hypokinesia by echocardiography and normal coronary arteries. At least 3 of 5 criteria were requested. In a first step we analysed retrospectively all patients with acute myocarditis/myopericarditis in the years 1980-1993. Among 30 cases of acute myocarditis/myopericarditis the following causes could be identified: one influenza B, one Toxoplasma gondii infection, 2 Epstein-Barr infections and one bacterial myocarditis with gram-negative rods. The aetiology of the other 25 cases remained unknown. The majority of myocarditis/myopericarditis healed without complications. One patient with Epstein-Barr myocarditis and one with Toxoplasma gondii infection died. Two patients developed dilated cardiomyopathy. In a second phase we analysed prospectively all cases with acute myocarditis/myopericarditis over the period 1994-1998: 24 patients with acute myocarditis/myopericarditis were hospitalised. At that time coronary angiography and endomyocardial biopsies were performed more frequently. We found 2 patients with giant cell myocarditis and 2 with Toxoplasma gondii infection and HIV, all of whom died. In addition, there were 2 patients with eosinophilic myocarditis, one with Lyme carditis, one with Epstein-Barr myocarditis, one with myopericarditis after Campylobacter enteritis and one histologically proven myocarditis after pneumonia with Haemophilus influenzae. The aetiology of the remaining 13 cases with myocarditis/myopericarditis could not be established. Three patients with probable viral myocarditis developed cardiogenic shock requiring intraaortic balloon pump, and fully recovered. The patient with Lyme carditis manifested with total atrioventricular block and was treated with a temporary pacemaker. One patient with lymphocytic myocarditis required heart transplantation because of terminal heart failure and one female patient with histologically proven diffuse lympho-monocytic myocarditis died of cardiogenic shock. All the other cases healed without complications. Serologies are of little diagnostic value and should be restricted to serologies with therapeutic implications. We believe that the apparent increase in myocarditis/myopericarditis in recent years is a result of better diagnostic tools, such as more specific cardiac enzyme tests, coronary angiography and endomyocardial biopsies. In most cases the therapy remains symptomatic. In elected, severe cases steroids and other immunosuppressive drugs are sometimes used.

Acute Disease↗
PubMed2002

Clinicopathological correlates can predict acute myocarditis in patients with recent-onset heart failure: preliminary data.

BACKGROUND: The aim of this study was to verify whether or not the clinical profile could be helpful in diagnosing myocarditis in patients with recent-onset (< 6 months) heart failure, suspected myocarditis and a biopsy-proven diagnosis. METHODS: From March 1998 to December 2000, 118 patients underwent a complete clinical, hemodynamic, echocardiographic and laboratory examination and a diagnostic endomyocardial biopsy in our Department; among them, 28 patients were admitted with clinically suspected myocarditis; in 9, the diagnosis was confirmed by the histopathologic findings. RESULTS: At the time of presentation, patients with biopsy-proven myocarditis showed early in-hospital admission (median 6 vs 69 days) with fever, a higher sinus rate and a significantly lower systolic blood pressure. Left ventricular dilation was observed in the non-myocarditis group only (left ventricular end-diastolic diameter 65.0 +/- 8.9 vs 52.6 +/- 5.8 mm); right ventricular function, as assessed by evaluation of the tricuspid annulus plane systolic excursion (TAPSE) and the right ventricular ejection fraction (RVEF) were found to be significantly lower in the myocarditis group (TAPSE 14.2 +/- 3.6 vs 20.3 +/- 7.0 mm; RVEF 21.3 +/- 11.1 vs 30.3 +/- 11.5%). Only patients with biopsy-proven myocarditis had an increase in serum creatine kinase and inflammatory markers (erythrocyte sedimentation rate and white blood cell count). Three cases had a clinical presentation of fulminant myocarditis showing marked increases in the serum levels of creatine kinase and inflammatory markers, and severely compromised right ventricular function and cardiac index. CONCLUSIONS: At univariate analysis, an early onset, fever, tachycardia, hypotension, a reduced right ventricular function, increased creatine kinase, erythrocyte sedimentation rate and white blood cell count were predictive of myocarditis. In patients with recent-onset heart failure, the clinical, laboratory and echocardiographic profiles can suggest, but not prove, a diagnosis of myocarditis.

Acute Disease↗
PubMed2004

Fatal myocarditis: morphologic and clinical features.

BACKGROUND: Autopsy studies report a frequency of myocarditis ranging from 0.11 to 5.5% in the general population, reaching almost 50% in selected groups. Myocarditis is often undiagnosed and the incidence of fatal course myocarditis has never been evaluated. The aim of our study was to assess the frequency of fatal course myocarditis in a consecutive series of autopsies and to describe the clinical, histological and morphologic features of the disease. METHODS: From January 1, 1995 to January 31, 1996, 2560 autopsies were performed, and 143 cases of active myocarditis were diagnosed (5.6%). RESULTS: In 39 cases (1.5%; 12 males; 4/39 aged < or = 35 years) active myocarditis was identified as the final cause of death. Only in 1 case was myocarditis suspected ante-mortem. The histological pattern was lymphocytic in 64% of cases. A mixed inflammatory infiltration was found in 33% and a granulomatous infiltration in 3%. In 49% of cases myocarditis was localized in both ventricles and the interventricular septum. The clinical presentation of myocarditis was heart failure in 18/39 patients (46%), cardiac arrest in 4/39 patients (10%) and syncope and chest pain in 1/39 patient (3%). The mean creatine phosphokinase levels were 890 +/- 2742 IU/I (assessed in 11/39 patients, 28%) but they were increased only in 7/39 (18%). ECG (performed in 29/39 patients, 74%) showed sinus rhythm in 16/39 patients (55%, > 100 b/min in 41%), atrioventricular or interventricular conduction defects in 10/39 patients (34%) and a pathological Q wave in 4/39 patients (14%). At echocardiography (performed in 7/39 patients, 18%), right and/or left ventricular dysfunction was found to be present in 5 cases (71%) and a pericardial effusion in 4 cases (57%). CONCLUSIONS: Myocarditis is underdiagnosed ante-mortem. A high index of clinical suspicion is mandatory for prompt diagnosis and treatment of this fatal disease seen also in the young.

Adolescent↗
PubMed1990

Genetic control of mouse cytomegalovirus-induced myocarditis.

Mouse cytomegalovirus (MCMV) infection of mice induced myocarditis, characterized by a mononuclear cell infiltrate with associated necrosis of myofibres. Myocarditis was observed in parallel with viral inclusion-bearing cells in the heart during the acute phase of the infection. Myocarditis also persisted after the acute phase when viral antigens were no longer detectable by immunoperoxidase histochemistry and infectious virus could not be cultivated from various organs. The influence of host genetic factors on the development of cytomegalovirus-induced myocarditis was investigated using H-2 congenic and recombinant inbred mouse strains. Analysis of congenic variants with C57BL/10 and BALB/c backgrounds and the A/J strain revealed that genes linked to the H-2 complex influenced susceptibility to peak levels of MCMV-induced myocarditis seen 7 and 10 days post-infection. In addition, non-H-2 genes of the BALB/c background were important in determining the severity of myocarditis. Analysis of the strain distribution pattern of the CXB recombinant inbred series did not disclose the identity of the BALB/c non-H-2-linked allele conferring susceptibility to MCMV-induced myocarditis. The level of myocarditis seen in the F1 hybrid between the high-responder BALB/c and low-responder C57BL/6 strains suggested dominant inheritance. The amount of viral replication in the major target organs did not correlate with the severity of myocarditis. In conclusion, at least two genes, one mapping to the H-2 complex and another non-H-2-linked gene, influenced the development of myocarditis in MCMV-infected mice.

Animals↗
PubMed1997

Ten-year experience with endomyocardial biopsy in myocarditis presenting with congestive heart failure: frequency, pathologic characteristics, treatment and follow-up.

The present study summarizes our ten-year (1985-1995) experience with endomyocardial biopsy (EMB) in patients with idiopathic congestive heart failure (CHF), with specific reference to frequency of myocarditis, treatment policy, relative benefits, and follow-up. Of the 601 patients who constituted our series, 38 were clinically suspected of having myocarditis on the bases of a very recent onset of congestive heart failure and/or of arrhythmias and/or of conduction disturbances, and of a close-to-recent history of flu-like febrile illness. Corresponding EMBs showed myocarditis in 16 of the 38 cases (42.1%). A further 10 EMBs, from patients with a recent onset of congestive heart failure without prior infection episodes, showed myocarditis. Therefore, biopsy-proven myocarditis occurred in 26 of the 601 patients (4.3%). Of the 26 cases, 21 were lymphocytic, 1 was necrotizing granulomatous, 1 was eosinophilic and occurred in a patient who later developed overt zoonosis, 1 had some giant cells within endocardial inflammatory infiltrates, and 2 were borderline forms. In active myocarditis, inflammatory cells mostly constituted of T-lymphocytes (CD45RO+) with sparse macrophages (CD68+) and a few B cells (CD20+). B-lymphocytes and macrophages, along with activated T-lymphocytes, all expressed MHC class II HLA DR molecules, which were also expressed "de novo" by activated endothelial calls of capillaries and of small intramural vessels. HLA DR revealed itself as a very useful marker for the detection of activated inflammatory and endothelial cells. We also noted an increase in the number of perivascular and interstitial mast cells. Ultrastructural study was helpful for the characterization of myocyte damage and of interactions between inflammatory cells and myocytes. In 4 cases (1 of whom was later revealed as HIV positive, and subsequently died of AIDS), we found microreticulotubular structures in endothelial cells of small vessel and capillaries; in 7 cases, there were myocyte changes similar to those described in polymyositis; in 1 case, we observed subplasmalemmal buddings, but no viral particles; in 6 cases, there was extensive myocyte damage with myofibrillar lysis and focal adipous metaplasia; the remaining 6 cases showed myocyte damage of differing extent and severity; in the borderline forms, such damage coexisted with interstitial fibrosis. One of the 21 lymphocytic myocardites was not treated because during hospital screening the patient proved to be HIV positive; of the remaining 20 active myocardites, 11 were treated with a 6-month tapered steroid and azathioprine protocol (one was treated for 24 months), while 9 were not treated. The corresponding follow-up was: 6 deaths (congestive heart failure), 2 cardiac transplants and 3 survivals (1 with pace-maker) in the treated group, and 3 deaths (2 of congestive heart failure and 1 of sudden death), 1 cardiac transplant and 5 survivals (1 on the waiting list for transplantation) in the non-treated group. One of the 2 patients with borderline myocarditis died of congestive heart failure, and 1 is alive. Of the 22 patients with clinical diagnosis of myocarditis and negative biopsy, 7 died of congestive heart failure (2 on the waiting list for transplantation), 4 underwent cardiac transplantation, and 11 are alive (1 is awaiting transplantation). Of the 20 patients currently alive, 1 was originally in NYHA class III, 15 were in class II and 4 were in class I. Of the 20 overall patients who died, 12 were originally in NYHA class IV, 6 in class III, 2 in class II; of the 8 patients who underwent transplantation, 6 were originally in NYHA class IV and 2 in class III. Our overall experience shows that the frequency of myocarditis diagnosed according to Dallas criteria is high in patients with clinical diagnosis of myocarditis, while it is extremely low in dilated cardiomyopathy patients. This finding suggests that, although non-specific, recent onset of symptoms and prior febrile infe

Adolescent↗
PubMed2005

Therapy for pediatric myocarditis.

Pediatric myocarditis is most often associated with the acute or subacute onset of congestive heart failure in a previously healthy child. Myocarditis presenting with acute, severe symptomatology, termed fulminant myocarditis, has a high rate of recovery. Aggressive supportive care is indicated in fulminant myocarditis, including mechanical circulatory support. For subacute heart failure, supportive care remains the mainstay of therapy for myocarditis. A number of uncontrolled pediatric studies using both immunosuppressive therapy and/or immunomodulating therapy with intravenous gamma globulin have suggested these therapies are safe and useful in treating pediatric myocarditis. However, translating these results into recommended, routine therapy for pediatric myocarditis is complicated by the high rate of spontaneous improvement of myocarditis with supportive care, and the lack of demonstrable benefit for immunosuppressive and immunomodulating therapies in blinded, randomized, placebo-controlled trials in adult myocarditis. Heart transplantation remains the final therapeutic option for children with myocarditis and intractable severe heart failure.

Journal Article↗
PubMed2004

Inhibition of coxsackie B3 virus induced myocarditis in mice by 2-(3,4-dichlorophenoxy)-5-nitrobenzonitrile.

Myocarditis is a common cause of dilated cardiomyopathy, one of the most important single causes of heart transplantation. Coxsackie B viruses (CBV) are considered to be the principal etiological agents of viral myocarditis and direct virus-induced damage to the heart tissue has been suggested to be the main mechanism underlying myocarditis in the murine model [Horwitz et al. 2000 Nat Med 6:693-697]. We demonstrate that 2-(3,4-dichloro-phenoxy)-5-nitrobenzonitrile (DNB), a compound that was earlier shown to exhibit broad-spectrum anti-picornavirus activity is also markedly active against CBV replication in primary human myocard fibroblast. To challenge the hypothesis of [Horwitz et al. 2000 Nat Med 6:693-697] we assessed whether DNB is able to prevent the development of CBV-induced myocarditis in a murine model. Subcutaneous (s.c.) administration of DNB at 250 mg/kg/day, at multiple injection sites (m.i.s.), for a period of seven consecutive days (starting at 1 day before infection) to 4-week old C3H-mice resulted in a (i) 62% reduction in the number of myocarditis foci as compared to the untreated control animals (p = 1.7 x 10(-10)) and (ii) a concomitant reduction in viral titers in the heart. These findings indicate that selective inhibition of the replication of CBV may have a beneficial effect on the development of viral myocarditis and confirms that direct viral induced damage is the main mechanism underlying CBV-induced myocarditis. Early diagnosis of virus-induced myocarditis will likely be mandatory for an antiviral drug treatment regimen to achieve its greatest clinical benefit.

Animals↗
PubMed1997

Feasibility of diagnosing chronic myocarditis by endomyocardial biopsy.

In studies of all the layers of autopsied hearts from patients with chronic myocarditis, local clusters of lymphocytes are frequently noted, in contrast with hearts obtained from patients with acute myocarditis. Myocardial biopsy specimens, however are no larger than about 2mm x 3mm. With this in mind, the present study was undertaken to determine whether chronic myocarditis can be diagnosed by endomyocardial biopsy. Specimens were obtained from seven patients in whom chronic myocarditis was confirmed by the clinical course and by autopsy findings. In H&E stained specimens, sites corresponding to the biopsy sites in both ventricles (right ventricular free wall, right ventricular side of the ventricular septum, left ventricular lateral wall) were selected at random (five sites each from the right and left ventricles in each patient) and examined under a light microscope. A mean of 5 or more lymphocytes per visual field (by light microscopy at 400-fold magnification), a proposed quantitative diagnostic criterion of myocarditis, was noted in the right ventricle in three patients (5 lymphocytes in two patients and 6 in one patient) and in the left ventricle in one patient (5 lymphocytes). Also, when the presence of lymphocyte clusters, considered to be a characteristic feature of chronic myocarditis, was determined, clusters of 20 or more lymphocytes per visual field were found in the same patients as those mentioned above, namely, in three patients (42.8%) in the right ventricle, as mentioned above, and in one patient (14.3%) in the left ventricle. At the sites of these lymphocyte clusters. findings such as degenerative changes of the myocardial cells and interstitial fibrosis were also associated, making possible a diagnosis of myocarditis. Therefore, in chronic myocarditis, even if five specimens are obtained by right ventricular biopsy, in approximately one half of patients the diagnosis of chronic myocarditis will be missed because of sampling errors.

Adolescent↗
PubMed1998

[Antimyosin scintigraphy for diagnosis and follow-up of patients with clinically suspected myocarditis].

Antimyosin-scintigraphy is believed to have a high specificity but a low sensitivity for the diagnosis of myocarditis when histological analysis of endomyocardial biopsy is used as the reference method. However, the histological evaluation itself seems to have a low sensitivity for the diagnosis of myocarditis. Therefore, immunohistological techniques have been developed for the detection of lymphocytic infiltrates and increased expression of HLA antigens in the myocardium. The present study compares the results of antimyosin-scintigraphy with histological and immunohistological analysis of the endomyocardial biopsy. 65 patients with clinically suspected myocarditis underwent antimyosin-scintigraphy and histological and immunohistological analysis of the endomyocardial biopsy. Myocarditis could be diagnosed histologically in only 9/36 (25%) patients with a positive antimyosin scan but additional immunohistological analysis revealed lymphocytic infiltrates in 31 (86%) of these patients. In 29 patients with a normal antimyosin scan, histological analysis showed evidence of myocarditis in 3 (10%) patients; additional immunohistological evaluation disclosed lymphocytic infiltrates in 17 (59%) patients. With immunohistological analysis of the endomyocardial biopsy as the reference method, antimyosin-scintigraphy has a high sensitivity but a lower specificity for the diagnosis of myocarditis. Detection of autoantibodies against human cardiac myosin in patients with myocarditis is associated with a significantly lower incidence of positive antimyosin scans in these patients. Antimyosin-scintigraphy was repeated after six months in 14 patients with myocarditis. Histological and immunohistological evaluation of the endomyocardial biopsy now showed persistent myocarditis in 3/8 patients with a positive antimyosin scan and in 5/6 patients with a normal antimyosin scan.

Adult↗
PubMed1993

Effects of cyclosporine, prednisolone and aspirin on rat autoimmune giant cell myocarditis.

OBJECTIVES: Preventive effects of cyclosporine, prednisolone and aspirin on autoimmune giant cell myocarditis in rats were investigated. BACKGROUND: The therapeutic efficacy of immunosuppressants for human myocarditis is controversial. Although harmful effects of immunosuppressive therapy on experimental viral myocarditis have been reported, the effects on autoimmune myocarditis have not been investigated. Recently, a novel experimental autoimmune myocarditis model characterized by congestive heart failure and multinucleated giant cell has been established. Using this model, the preventive effects of cyclosporine, prednisolone and aspirin on autoimmune myocarditis were investigated. METHODS: Lewis rats were immunized with cardiac myosin in complete Freund's adjuvant on days 0 and 7. In experiment 1, four groups of seven rats each were established. Rats in each group received for 21 days intraperitoneal injections of either 1) phosphate-buffered saline solution, 1 ml/day (control); 2) cyclosporine, 20 mg/kg body weight per day (cyclosporine 20); 3) prednisolone, 4 mg/kg per day; or 4) aspirin, 15 mg/kg per day. In experiment 2, two additional groups (five rats each) received for 21 days an injection of cyclosporine, 1 or 5 mg/kg per day (cyclosporine 1 and cyclosporine 5, respectively). All rats were killed on day 21, when histopathologic studies were performed and the titers of antimyosin antibodies were measured. RESULTS: The rats in the control, prednisolone and aspirin groups became ill and immobile in week 3. In comparison, rats in the cyclosporine 5 and 20 groups were still active until death was induced. Heart weight/body weight, lung weight/body weight and liver weight/body weight ratios in the rats in the cyclosporine 5 and cyclosporine 20 groups were significantly lower than those in the control group, and no differences were detectable among rats in the control, prednisolone and aspirin groups. The rats in the latter three groups and the cyclosporine 1 groups showed severe myocarditis with multinucleated giant cells. However, myocarditis was effectively prevented in the rats in the cyclosporine 5 and 20 groups. The histologic scores in each group were 2.91 in the control group, 2.14 in the prednisolone group, 2.91 in the aspirin group and 0.02, 2.58 and 0.07, respectively, in the cyclosporine 20, 1 and 5 groups. Production of antimyosin antibodies was remarkably suppressed in rats in the cyclosporine 5 and 20 groups in comparison with values in all other groups. CONCLUSIONS: Autoimmune myocarditis is preventable by cyclosporine but not by prednisolone or aspirin in usual dosages.

Animals↗
PubMed2004

Serum levels of interleukin-10 on admission as a prognostic predictor of human fulminant myocarditis.

OBJECTIVES: We assessed the significance of serum cytokine levels in patients with fulminant myocarditis. BACKGROUND: Although many investigations have demonstrated the crucial role of cytokines in the development of myocarditis, it remains uncertain whether serum levels of cytokines enable one to predict the prognosis of human myocarditis, especially concerning cardiogenic shock (CS) requiring a mechanical cardiopulmonary support system (MCSS). METHODS: We studied 22 consecutive patients with fulminant myocarditis and compared them with 15 patients with acute myocardial infarction (AMI) requiring MCSS. The patients with myocarditis were classified into three groups: eight patients with CS requiring MCSS on admission (group 1); six patients who unexpectedly lapsed into CS requiring MCSS more than two days after catecholamine had been initiated (group 2); and eight patients without MCSS (group 3). Furthermore, 14 patients with myocarditis requiring MCSS were divided into a fatal group (n = 5) and a survival group (n = 9). Biochemical markers, including serum cytokine levels and hemodynamic variables on admission, were analyzed. RESULTS: Serum levels of interleukin (IL)-10 and tumor necrosis factor-alpha, but not other cytokines, were significantly higher in myocarditis than in AMI. Only serum levels of IL-10 were significantly higher in group 1 and 2 than in group 3 (49.1 +/- 37.5/20.7 +/- 17.6 pg/ml vs. 2.4 +/- 1.1 pg/ml; p = 0.0008/0.0012). Serum IL-10 levels were also significantly higher in the fatal group than in the survival group with myocarditis (74.0 +/- 27.0 pg/ml vs. 16.4 +/- 8.8 pg/ml; p = 0.003). CONCLUSIONS: Serum IL-10 levels on admission enabled one to predict subsequent CS requiring MCSS and mortality of fulminant myocarditis patients.

Adolescent↗
PubMed2001

Myocarditis in patients with clinical presentation of myocardial infarction and normal coronary angiograms.

OBJECTIVES: The aim of this study was to assess the diagnosis of myocarditis in patients presenting with acute myocardial infarction (MI) and normal coronary angiograms. BACKGROUND: Most often in these patients, the etiologic diagnosis remains unclear once they are found to have normal coronary arteries. The diagnosis of myocarditis mimicking MI is clinically relevant, because numerous arguments suggest a relation between myocarditis and dilated cardiomyopathy. Myocardial indium-111 (111In)-antimyosin antibody (AMA)/rest thallium-201 (201Tl) imaging allows noninvasive detection of myocarditis. METHODS: Forty-five patients admitted to three intensive care units for suspicion of acute MI, with normal coronary angiograms, were investigated. Indium-111-AMA planar images and then a dual-isotope rest AMA/201Tl tomographic study were performed. Six-month echocardiographic follow-up was obtained in 80% of the patients with initial left ventricular (LV) wall motion abnormalities. RESULTS: In eight patients, AMA and 201Tl scintigraphy were negative. In two patients, a matched 201Tl defect and focal AMA uptake suggested acute MI (due to prolonged vasospasm or spontaneously reperfused coronary occlusion). In 17 patients, diffuse AMA uptake over the whole LV suggested diffuse myocarditis. In 18 patients, focal AMA uptake with a normal 201Tl scan suggested diffuse but heterogeneous, or focal myocarditis. Complete functional recovery was observed in 81% of the patients with a pattern of myocarditis. CONCLUSIONS: Among 45 patients presenting with acute MI and normal coronary angiograms, 38% had diffuse myocarditis and 40% had a scintigraphic pattern of heterogeneous or focal myocarditis. Short-term follow-up showed complete LV functional recovery in 81% of these patients.

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