Antimyocardial Antibodies Research Articles

Value of morphological and laboratory markers in predicting the effectiveness of cryoballoon pulmonary vein isolation in atrial fibrillation

Aim. To determine the clinical, morphological, and biochemical pre­dictors of substrate-specific, non-vein-dependent atrial fibrillation (AF) by morphological and immunological examinations in patients with recurrent AF after pulmonary vein (PV) isolation.Material and methods. The study included 100 people (58 men and 42 women) with paroxysmal (n=89) and persistent (n=11) AF with a mean age of 58,2±9,4 years. After the primary operation, 15 people withdrew from the study due to refusal of reintervention, and 1 person withdrew due to suppuration of loop recorder bed and its explantation. A total of 100 patients underwent primary cryoballoon PV isolation with myocardial biopsy from the interventricular and interatrial septa, while 60 patients had subsequent hematoxylin-eosin and Van Gieson stains. Also, 100 patients were simultaneously implanted with ECG loop recorders for AF monitoring and blood was taken (before the intervention) for subsequent analysis of inflammation markers and antimyocardial antibodies. Patients underwent clinical observation during the year (visits after 3, 6, 12 months). Patients with relapses were referred for repeat electrophysiological examination and segmental ablation if PV ruptures were detected. After repeated intervention, the follow-up period was extended for a year with the same schedule of visits. According Two groups of patients were formed: without relapses (vein-dependent AF, group I) and with relapses (non-vein-dependent AF, group II), despite the achieved PV isolation as a result of 1 or 2 operations.Results. An analysis of morphological changes showed that an increase in AF recurrence risk by an average of 6,14 times (95% confidence interval: 1,14-47,6 (p=0,0462)) is associated with stage 2 interventricular septal fibrosis. Lymphocyte infiltration of the interventricular septum was associated with higher AF recurrence by an average of 9 times (95% confidence interval: 0,89-95,37) (p=0,0519).Among the laboratory parameters, a significantly higher concentration of the N-terminal pro-brain natriuretic peptide and a significantly lower concentration of antimyocardial antibodies were found in the group of patients with recurrent AF after LV isolation (p=0,0101).Conclusion. Inflammatory myocardium changes are an important link in the pathogenesis of AF and are associated with its recurrence.

Диагностические маркеры поражения сердца у пациентов со среднетяжелой формой новой коронавирусной инфекции

The results of numerous randomized clinical trials indicate the relationship of a new coronavirus infection (NCI) with the development of acute myocardial injury (AMI). Of great importance in the defeat of the heart belongs to the change in the cytokine and chemokine status, which determines the inflammatory potential. The aim of this work was a comprehensive assessment of clinical and laboratory indicators of the state of the heart in a new coronavirus infection and the determination of immunopathogenetic mechanisms of myocardial damage. 180 patients hospitalized with a diagnosis of «coronavirus infection COVID-19, virus identified (U07.1), moderate form» were examined. Risk factors, levels of cytokines and chemokines (IFN-α, IL-6, IL-17, MIP-1b), markers of cardiac damage/dysfunction (troponin I and FAFA, NTproBNP), and antimyocardial IgG antibodies were assessed. Statistical processing was carried out using the Microsoft Office package (Microsoft Excel), as well as the statistical package STATISTICA 9.0. The Shapiro-Wilk W test was used to check the normality of the distribution. Differences were considered significant at p ≤ 0.05, unreliable at p ≥ 0.05. It has been established that in the acute period, 45% of patients have an increase in troponin I values. They also have significantly higher levels of IL-6, IL-17 and MIP-1b against the background of inhibition of IFN-α production. In the acute period, a third of patients have antimyocardial antibodies, which are detected significantly more often and in higher titers in patients with AMI. The presence of a direct correlation between the level of antimyocardial antibodies and an increase in the amount of CRP, MIP-1b and IL-17 was established. The most significant risk factors for the development of myocardial damage in NCI are the presence of a burdened history of cardiovascular diseases, an increased body mass index, and diabetes mellitus. Thus, high levels of CRP, MIP-1b IL-17, antimyocardial antibodies, with a continuing deficiency without a tendency to restore the level of IFN-α, in the presence of the above risk factors, are diagnostically significant markers of AMI in patients with moderate NCI.

Значение инфекции в развитии фетальных нарушений сердечного ритма

Objective. To assess the impact of infection on the development of fetal arrhythmias. Patients and methods. The study included 84 pregnant women who were divided into two groups: the study group, which consisted of 44 patients aged 20–42 years (Me 31 ± 0.93 years) with fetal arrhythmia and/or minor heart defects at 21–41 weeks’ gestation (Me 37.41 ± 0.58 weeks), and the comparison group, which enrolled 40 pregnant women without fetal heart defects and with normal fetal heart rate to determine the significance of serological markers of myocarditis. Results. Significant titers of non-specific anti-myocardial antibodies to vascular smooth muscle and endothelium were detected in 14 (31.8%) and 7 (15.9%) fetuses, respectively. “Conditionally positive” titers for anti-smooth muscle antibodies were detected in 3 (6.8%) fetuses and for anti-endothelial cell antibodies in 4 (9%) fetuses. There was no significant increase in specific anti-heart antibody titers in both groups. Conclusion. Hypoxia should be considered as a trigger for fetal arrhythmias. The infectious and inflammatory processes are one of the links in the pathogenesis of fetal arrhythmias. Key words: fetal arrhythmia, intrauterine infection, minor heart defects

TWO MUTATIONS CONCOMITANCE IN FEMALE PATIENT WITH ARRHYTHMIC TYPE OF NONCOMPACTION MYOCARDIUM SYNDROME

Non-compaction myocardium syndrome of the left ventricle (NCM) is relatively new diagnosis. There is no consensual approach to classification, diagnostics, as treatment and management of patients with NCM till recently. Predictive value of the observed genetic mutations is not studied good enough too. Aim. The article is focused on a clinical case of female patient with NCM and lifethreatening ventricular rhythm disorders, revealed two independent mutations in genes coding sarcomere proteins of myocardium. Material and methods. Clinical and instrumental study, except standard methods, included serological diagnostics of myocarditis, defining a genome of cardiotropic viruses in blood, and MSCT of the heart; genetic study included sequencing on the platform Ion Torrent of the coding sequences and attached inthrone regions on 16 genes, which mutations might lead to NCM. Results. In current study we performed clinical, instrumental and genetic investigation of 59-year old female patient with NCM and sustained VT paroxysms of unknown duration that had been being registered since her 47 age, with frequent VE (up to 24 thousands per day). Ventricular dysrhythmias did not resolve regardless two interventions on RFA of the focus of arrhythmia and drug treatment. At the age 56 cardioverter-defibrillator was implanted, and during 3 years of follow-up there were 13 relevant shocks. There were high titers of antimyocardial antibodies. Differential diagnostics was about myocarditis, ACRV and NCM. Genetic test revealed two mutations heterozygous: p.Q1233* gene MYBPC3 and p.R237W in gene MYH7. These genes’ mutations are common findings in NCM. If two mutations found, it is a factor of higher risk of SCD and progradient course of the disease. Conclusion. Genetic changes (mutations) that influence morphology of myocardium proteins, determine primary cardiomyopathies. However, the velocity of a disease course and real conditions of a patient do determine non-genetic factors as well, including sex, age, comorbidities, infectious or immune myocarditis, range and effectiveness of treatment.

Prevalence of electrocardiographic abnormalities in patients with myasthenia gravis.

Myasthenia gravis (MG) is an immunological disorder of the neuromuscular junction, characterized by easy fatigability and weakness of the skeletal muscles. However, it has sometimes been reported that heart diseases including cardiomyopathies leading to sudden death have been observed in patients with MG. We studied the prevalence of electrocardiographic (ECG) abnormalities and heart disease in patients newly diagnosed with MG who had not received immunotherapy. Fifty-three patients with MG were enrolled in our study. We reviewed the ECG recordings of all patients on admission, and assessed the prevalence of ECG abnormalities and heart diseases associated with MG. Thirty-three (62.2%) patients had ECG abnormalities, including early repolarization (15 patients), negative T waves (9 patients), left ventricular hypertrophy (5 patients), and prolonged QTc (4 patients). A higher frequency of early repolarization was observed in patients with MG compared to healthy subjects. ECG abnormalities in patients with MG were more prevalent in our series than in the general population. This may be because of the increasing incidence of MG in the elderly. However, we also observed that younger patients developed severe heart disease, indicating the possibility of other mechanisms, such as the presence of antimyocardial antibodies. Clinicians should be aware of the complications of heart disease in patients with MG, especially during the perioperative period for thymectomy or thymomectomy.

Myocarditis in yound athletes

Aim. Development of informative differential diagnostic criteria of inflammatory myocardial involvement in young athletes. Methods. A total of 163 athletes (swimmers, football players and sailing athletes) aged 9 to 24 years (mean age 14.74±0,23 years, SD=3.03) were examined. Complete clinical and functional examination was performed. Remodeling of the left ventricle was studied in accordance with R. Devereux (1992) and B. Maron (2005) echocardiographic criteria. Myocardial morphometry results were compared with immunobiochemical markers of myocardial damage and titer of antimyocardial antibodies to the endothelium, cardiac conduction system, cardiomyocytes, and smooth muscle. Results. In 10 out of 40 athletes with echocardiographic signs of pathological remodeling of the left ventricle, the indicators of myocardial damage used as immunobiochemical screening tests, were increased, high titers of antimyocardial antibodies (more than 1:160), arrhythmias, sever conduction disorders, and high concentrations of infectious risk factors were revealed, allowing to diagnose subacute myocarditis. Conclusion. Subacute myocarditis should be excluded in athletes with echocardiographic signs of left ventricular myocardial remodeling and a high concentration of «infectious» risk factors based on immunobiochemical markers of myocardial damage and antimyocardial antibodies titer.

The diagnostic value of speckle-tracking echocardiography in myocarditis and dilated cardiomyopathy

The purpose of the investigation – to study the diagnostic opportunities of Speckle-Tracking Echocardiography (STE) in patients with Inflammatory Cardiomyopathy (ICM) and Dilated Cardiomyopathy (DCM). Materials and methods: We examined 27 patients: 14 – with ICM (1st group) and 13 – with DCM (2nd group), the average age was (36,1±3,2) and (37,6±2,8) years respectively. By the use of STE we studied the parameters of myocardial deformation, which were: the absolute values of Longitudinal Global Systolic Strain (LGSS), Circumferential Global Systolic Strain (CGSS), Radial Global Systolic Strain (RGSS), Velocity of LGSS (VLGSS), Velocity of CGSS (VCGSS) and Velocity of RGSS (VRGSS). In all patients were also performed the detection of serum antibody titers to the Myocardium (ATm) and the level of myocardium induced Blasttransformation Lymphocyte Activity (BTLAm). Both groups were comparable by the values of end systolic, end diastiolic volume, ejection fraction of the left ventricle (LV), which were measured by the use of 2D echocardiography and heart rate according to the ECG. Results: In the 1st group in comparison with the 2nd we detected the higher values of LGSS - (9,4±1,2) and (5,1±1,1) % (P<0,01), CGSS - (9,2±1,4) and (5,5±1,1) % (P<0,05), VCGSS - (0,65±0,08) and (0,42±0,06) s-1 (P<0,02) respectively. These findings provide the evidence of more pronounced impairment of LV contractile function in DCM than in ICM. The negative correlation was found in the 1st group between LGSS, CGSS, VCGSS and BTLAm - r=-0,47, (P<0,05); r=-0,37, (P<0,05); r=-0,38, (P<0,05) respectively and also between LGSS, CGSS, VLGSS and ATm titers - r=-0,42, (P<0,05); r=-0,57, (P<0,02); r=-0,41, (P<0,05) respectively. In the 2nd group we found correlation of STE parameters only with ATm titers, thus we observed the negative correlation between ATm titers and RGSS - r=-0,53, (P<0,02) as also with VRGSS r=-0,44, (P<0,05). These data may suggest the influence of both cellular and humoral autoimmune reactions on the impairment of the LV systolic function in ICM and only the humoral mechanisms in DCM that resulted in more pronounced myocardial damage associated with pathologic effects of ATm. Conclusion: The use of STE may be helpful for the assessment of LV contractile function in patients with inflammatory and dilated cardiomyopathy, we defined that DCM was characterized by more significant LV systolic dysfunction in comparison with ICM. We suggest the negative influence of both ATm and activated lymphocytes on the LV systolic function in ICM and only the antimyocardial antibodies in DCM.

Contribution of Acquired Factors to the Pathogenesis of Dilated Cardiomyopathy - The Cause of Dilated Cardiomyopathy: Genetic or Acquired? (Acquired-Side) -

Although genetic abnormalities play a pivotal role in the development of dilated cardiomyopathy (DCM), acquired infection and autoimmune abnormalities, or both, appear to be predominant underlying disorders. Of these, viral infection causes target organ damage via perforin produced by suppressor T cells. Thereafter, various antigens released from damaged myocytes are presented on the major histocompatibility complex II, which is expressed in antigen-presenting cells, resulting in activation of both cellular (Th1) and humoral (Th2) immunity. Various antimyocardial antibodies are detected in the serum of patients with DCM and recent findings suggest that at least some of them are directly related to the pathophysiology of DCM. An autoantibody targeting the β1-adrenergic receptor is related to the persistent myocardial damage resulting in DCM and provides the substrate for fatal ventricular arrhythmias. An antibody for the muscarinic M2 receptor is related to atrial fibrillation, an antibody targeting Na-K-ATPase is closely related to sudden cardiac death from fatal ventricular arrhythmias, and an autoantibody for troponin I increases the L-type calcium current and is related to myocardial damage. On the other hand, genetic factors are also involved in susceptibility to viral infection and aberrations of acquired immunity, including antigen presentation and autoantibody production. In conclusion, acquired factors are predominant causes of DCM, although the 2 predisposing factors are also linked to genetic abnormalities.

Presence of Circulating Anti-Myosin Antibodies in Endomyocardial Fibrosis

BackgroundEndomyocardial Fibrosis (EMF) is a tropical restrictive cardiomyopathy of unknown etiology with high prevalence in Sub-Saharan Africa, for which it is unclear whether the primary target of injury is the endocardial endothelium, the subendocardial fibroblast, the coronary microcirculation or the myocyte. In an attempt to explore the possibility of endocardial lesions being a result of an immune response against the myocyte we assessed the presence and frequency of circulating anti-myocardial antibodies in EMF patients.Methodology/Principal FindingsEMF classification, assessment of severity and staging was based on echocardiography. We used sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) of myocardial proteins followed by western blotting to screen serum samples for antiheart antibodies G and M classes. The degree of serum reactivity was correlated with the severity and activity of EMF. We studied 56 EMF patients and 10 healthy controls. IgG reactivity against myocardial proteins was stronger and more frequent in patients with EMF when compared to controls (30/56; 53.6% vs. 1/10; 10%, respectively). IgM reactivity was weak in both groups, although higher in EMF patients (11/56; 19.6%) when compared to controls (n = 0). EMF patients showed greater frequency and reactivity of IgG antibodies against myocardial proteins of molecular weights 35 kD, 42 kD and 70 kD (p values <0.01, <0.01 and <0.05 respectively).ConclusionsThe presence of antibodies against myocardial proteins was demonstrated in a subset of EMF patients. These immune markers seem to be related with activity and might provide an adjunct tool for diagnosis and classification of EMF, therefore improving its management by identifying patients who may benefit from immunosuppressive therapy. Further research is needed to clarify the role of autoimmunity in the pathogenesis of EMF.

Autoimmune Mechanisms Underlying Dilated Cardiomyopathy

Autoimmune abnormalities, as well as viral infection and genetic abnormalities, appear to be major predisposing factors for dilated cardiomyopathy (DCM). Abnormalities of cell-mediated immunity are mainly involved in the onset of cardiomyopathy secondary to myocarditis. However, various antimyocardial antibodies are detected in the serum of patients with DCM. The appearance of these antibodies was considered to be an epiphenomenon associated with myocyte injury resulting from myocarditis, but recent findings have suggested that at least some of them are directly related to the pathophysiology of DCM. In particular, an autoantibody targeting the beta1-adrenergic receptor that exhibits an agonist-like effect is related to the persistent myocardial damage resulting in DCM and provides substrates for fatal ventricular arrhythmias. In addition, an antibody for the muscarinic M2 receptor is related to atrial fibrillation, an antibody targeting Na-K-ATPase is closely related to sudden cardiac death as a result of fatal ventricular arrhythmias, and an autoantibody for troponin I increases the L-type calcium current and is related to the myocardial damage. Based on these findings, immunoadsorption therapy was developed to remove such autoantibodies in patients with refractory heart failure as a result of DCM.

Efficacy of intravenous immunoglobulin in chronic idiopathic pericarditis: report of four cases

Human intravenous immunoglobulins (hIVIgs) are used in two broad categories of diseases: immunodeficiency and autoimmunity. Among the immune-mediated diseases hIVIgs are of benefit in idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and dermatomyositis. Chronic idiopathic pericarditis (CIP) is a chronic disease of unknown origin characterized by recurrent episodes of pericardial inflammation. The cause of the recurrence is unknown, although in some cases it may be traced to a viral infection and to the presence of antimyocardial antibodies. Since a viral infection can induce an autoimmune process through a mechanism of molecular mimicry, and since the optimal therapy for prevention of the recurrences has not been established, we reasoned that treatment with hIVIgs could be beneficial in our patients unresponsive to previous immunosuppressive therapies. We describe four patients affected by CIP treated with monthly high-dose hIVIgs (0.4 g/kg daily for 5 consecutive days) for five times followed by administration every 2 months. Three of the four patients could permanently discontinue steroid therapy and are still in remission after years of follow-up. Our experience suggests that hIVIgs therapy may be a useful and safe treatment for CIP in steroid-dependent patients.

Modulatory effects on myocardial physiology induced by an anti- Trypanosoma cruzi monoclonal antibody involve recognition of major antigenic epitopes from β 1-adrenergic and M 2-muscarinic cholinergic receptors without requiring receptor cross-linking

It has been proposed that anti-myocardial antibodies (Ab) against neurotransmitter (NT) receptors are involved in the immunopathology of chronic Chagas' heart disease. We demonstrated that an anti- Trypanosoma cruzi monoclonal Ab (mAb), CAK20.12, binds to murine cardiac β-adrenergic and muscarinic acetyl choline (mACh) receptors eliciting abnormal physiological responses on normal heart. No cross-linking requirement for mAb actions was demonstrated using Fab fragment derived from CAK20.12. mAb binding to synthetic peptides from the second extracellular loop of both β 1-adrenergic and mACh receptors, demonstrated by ELISA, identified the region of NT receptors involved. Cross-reactivity between these peptides and T. cruzi antigen was confirmed by binding inhibition assays. These results support the existence of cross-reactivity due to molecular mimicry between a parasite antigen and the major antigenic epitopes present on both β 1-adrenergic and M 2-ACh receptors. Its possible relationship with cardiac dysfunction during chronic stage of Chagas' disease is also discussed.

Pleural Effusions Following Cardiac Injury and Coronary Artery Bypass Graft Surgery

This article discusses the pleural effusions that occur with the post-cardiac injury (Dressler's) syndrome (PCIS) and those that occur after coronary artery bypass graft (CABG) surgery. The PCIS can occur after any type of cardiac injury and is thought to be due to anti-myocardial antibodies. The primary symptoms are fever and chest pain, and pericarditis is frequently present. Pleural effusions are common with PCIS. The primary treatment for PCIS is a nonsteroidal anti-inflammatory agent or corticosteroids. Following CABG surgery, most patients will have a small unilateral left-sided pleural effusion, and approximately 10% of patients will have a larger effusion. These large effusions can be separated into early effusions occurring within the first 30 days of surgery that are bloody exudates with a high percentage of eosinophils, and late effusions occurring more than 30 days after surgery that are clear yellow lymphocytic exudates. The primary symptom of a patient with a pleural effusion post-CABG surgery is dyspnea; chest pain and fever are uncommon. Most patients with large pleural effusions postCABG surgery are managed successfully with one to three therapeutic thoracenteses.

Use of indirect immunofluorescence and Western blotting to assess the role of circulating antimyocardial antibodies in dogs with dilated cardiomyopathy

The presence of circulating anti-heart IgG and IgM autoantibodies was assessed by indirect immunofluorescence and by probing Western blot transfers of normal canine myocardial proteins separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis with samples of sera from dogs with dilated cardiomyopathy (n=27) and from healthy control dogs (n=20). No difference was demonstrated between the two groups using either method. Sera taken from the affected dogs at three monthly intervals throughout the course of the disease showed no change at all in the pattern of reactivity. The results of this study suggest that indirect immunofluorescence and the probing of Western blot transfers of a crude preparation of normal canine myocardium with canine sera will demonstrate too many apparent autoantigens for the technique to identify unique, disease-associated autoantibodies.

Incidental myocarditis with intravenous drug abuse: The pathology, immunopathology, and potential implications for human immunodeficiency virus-associated myocarditis

Human immunodeficiency virus (HIV)-associated myocarditis is well reported. Many of these patients are also intravenous (IV) drug abusers. This study examined sudden death victims from the Office of the Chief Medical Examiner, State of Maryland, for active myocarditis. A group of HIV-negative drug abusers is compared with a group of HIV-negative victims without any known risk factors for the acquired immunodeficiency syndrome. Using modified Dallas criteria combined with an avidin-biotin-labeled immunoperoxidase procedure, the cases were classified as active, borderline, or absent myocarditis. Serologic analysis for circulating antimyocardial antibody was performed along with phenotypic analysis of the infiltrate. Of the 15 IV drug abuse cases examined, none were positive for HIV (enzyme-linked immunosorbent assay and Western blot). With IV drug abuse as the primary risk factor, five cases demonstrated active myocarditis, while five others had borderline myocarditis. Only one of 10 low-risk patients had a lymphocytic infiltrate consistent with borderline myocarditis. Drug abuse-related myocarditis was associated with cardiac pathology resulting in sudden death in only one case. Antimyocardial antibodies were positive in four of the 15 IV drug abuse cases, including patients with active, borderline, and absent myocarditis. The phenotypic expression of the lymphocytic infiltrates was similar to the findings reported for idiopathic and HIV-related myocarditis (Am J Pathol 137:1365–1371, 1990). Toxicology studies did not implicate any particular drug of abuse, but the increased frequency of myocarditis observed may reflect complications of cocaine or the combined effects of opiates and cocaine. Intravenous drug abuse is an independent risk factor for myocarditis and must be taken into consideration in studies of HIV-associated myocarditis.

Immunology of Cardiac Tumors

Whereas abundant literature is available on mechanisms imposed by neoplastic diseases on the immune system, only few details are known about immunological parameters of autoreactive mechanisms directed against the heart. This report will focus on cardiac autoreactivity in patients with endomyocardial types of cardiac tumors (e.g. atrial myxomas), Hodgkin's disease, and with neoplastic pericardial effusion. In patients with atrial myxomas antimyolemmal antibodies were significantly increased when compared to non-cardiac controls. Antisarcolemmal antibodies were positive in 100% of trivalent immunoglobulin binding. Antiendothelial antibodies of the IgG type could be found in 86% of patients with atrial myxoma. Circulating immune complexes were present in 6 out of 7 patients. In 107 patients with Hodgkin's disease without pericarditis the presence of antimyolemmal antibodies was lower than in healthy controls. The incidence of antimyolemmal antibodies in 10 patients with pericarditis lymphogranulomatosa was 10%, whereas in postradiation pericarditis 8 of 15 patients demonstrated antimyolemmal antibodies. Antiendothelial antibodies were positive in 7 out of 15 patients. The number of patient lymphocytes available for functional assays is yet too small to permit further conclusions on cellular autoreactive mechanisms in Hodgkin's disease. Antimyocardial antibodies were found both in the serum and in the effusions at least in lower titers in all patients. With regard to in-vitro analysis it can not be excluded that a balance between protective and cytolytic antibodies keeps a normal mean of antibody-mediated cytolysis. Analysing the first line of defense, the natural killer cell activity was found significantly increased in neoplastic pericardial effusions, whereas peripheral blood and pericardial effusion showed no lymphocytotoxicity with isolated myocardial cells.

Morphological and immunological findings in heart biopsies of patients with suspected or treated myocarditis

From 1975 to 1985 at the Massachusetts General Hospital, 245 biopsies were performed in 170 patients to rule out clinically suspected myocarditis or for follow-up study of previously diagnosed myocarditis. Direct and indirect immunofluorescence studies were conducted on 193 specimens. Three-fourths of the biopsies did not show evidence of myocarditis. Endomyocardial biopsy specimens from patients with active myocarditis most frequently contained C3 whereas serum samples from patients with resolving myocarditis most often contained antimyocardial antibodies. In general, immunological findings correlated closely with the status of disease activity in these patients, including four who had had multiple relapses and immunosuppressive therapy. Our study confirms the presence of a humoral immunological mechanism, either primary or secondary, in myocarditis and indicates that immunological studies are a valuable adjunct to morphological examination.

Cardiac sarcoidosis--clinical and immunoserologic studies

Twenty-seven patients with bronchopulmonary or generalised sarcoidosis were classified with a clinical score as certain, probable, possible or no cardiac sarcoidosis. Certain cardiac involvement was assumed only when endomyocardial biopsy or necropsy showed a granuloma of the heart (N = I); it was probable (N = 14) when a resting or an exercise-induced defect in the thallium scan was found and severe arrhythmia (Lown III-V), A–V block (2nd or 3rd degree), cardiomegaly, pericardial effusion or segmental wall motion abnormality was detected in addition; it was considered possible (N = 7) when only one of the above-mentioned criteria (rhythm disturbances, cardiomegaly/pericardial effusion, exercise-induced defect in the thallium scan) was positive. With thallium-201 scintigraphy a defect at rest was found in nine, on exercise in six, at rest and on exercise in six, and no defects were found in six cases. Determination of antimyocardial antibodies with adult human and rat cardiocytes and with cryostat sections, and of circulating immune complexes, showed differences from non-cardiac controls but not from patients with sarcoidosis and a negative score for cardiac manifestations. Antimyolemmal antibodies of the IgG class were found in all patients, and of the IgM class in 30–50% of all patients irrespective of cardiac involvement. Only complement fixation to the myolemma was cardiospecific. Cytolytic serum activity, NK cell activity, antibody-dependent (ADCC) and -independent lymphocytotoxicity against vital heart cells could not be detected in any group of patients.

Characterization of circulating immune complexes in heart disease.

Circulating immune complexes (CIC) were characterized for the content in IgG, IgA, IgM, C3 and C4 in patients with heart disease. The levels of IgG, IgM and C4 in PEG-precipitates of patients' sera were significantly higher than those found in controls, and the precipitation profile was similar to that of rheumatoid arthritis patients. Differences were observed in the composition of CIC: IgM was highest in association with myocarditis, and C3 predominated in cases of valvular disease. Complex-bound C4 was significantly higher in patients with myocardial infarction which developed pericarditis either early or late in the evolution of the disorder. Antimyocardial antibodies could be detected in sera and in corresponding PEG-precipitates. The bulk of the data suggests that CIC might play a pathogenetic role in various heart diseases.

Postcoronary pain and the postmyocardial infarction syndrome.

Since non-specific chest pain, which is a common feature after myocardial infarction, may be due to a mild form of Dressler's (postmyocardial infarction) syndrome 80 patients were studied after confirmed myocardial infarction. Two patients had clinical features of classical Dressler's syndrome with high erythrocyte sedimentation rates and strongly positive results for antimyocardial antibodies. Twenty three patients had non-specific chest pain; none had clinical features of Dressler's syndrome. There was no difference in the erythrocyte sedimentation rate between this group and the remainder who had no pain. Equal numbers in each group had weakly positive test results for antimyocardial antibodies; none had a strongly positive result. Thus there appears to be no evidence for a mild form of Dressler's syndrome, and the erythrocyte sedimentation rate and weakly positive results for antimyocardial antibodies are of no diagnostic value in Dressler's syndrome.