Alcoholic cardiomyopathy : The result of dosage and individual predisposition.

The individual amount of alcohol consumed acutely or chronically decides on harm or benefit to a person's health. Available data suggest that one to two drinks in men and one drink in women will benefit the cardiovascular system over time, one drink being 17.6 ml 100 % alcohol. Moderate drinking can reduce the incidence and mortality of coronary artery disease, heart failure, diabetes, ischemic and hemorrhagic stroke. More than this amount can lead to alcoholic cardiomyopathy, which is defined as alcohol toxicity to the heart muscle itself by ethanol and its metabolites. Historical examples of interest are the Munich beer heart and the Tübingen wine heart. Associated with chronic alcohol abuse but having different etiologies are beriberi heart disease (vitamin B1 deficiency) and cardiac cirrhosis as hyperdynamic cardiomyopathies, arsenic poising in the Manchester beer epidemic, and cobalt intoxication in Quebec beer drinker's disease. Chronic heavy alcohol abuse will also increase blood pressure and cause a downregulation of the immune system that could lead to increased susceptibility to infections, which in turn could add to the development of heart failure. Myocardial tissue analysis resembles idiopathic cardiomyopathy or chronic myocarditis. In the diagnostic work-up of alcoholic cardiomyopathy, the confirmation of alcohol abuse by carbohydrate deficient transferrin (CDT) and increased liver enzymes, and the involvement of the heart by markers of heart failure (e.g., NT-proBNP) and of necrosis (e.g., troponins or CKMb) is mandatory. Treatment of alcoholic cardiomyopathy consists of alcohol abstinence and heart failure medication.

[Anti-heat shock protein 70 (anti - Hsp 70) antibodies in alcohol use disorder patients]. / Przeciwciala przeciw bialku wstrzasu termicznego 70 kDa (anty- Hsp 70) u osób z zespolem zaleznosci alkoholowej.

The expression of the most important chaperone protein - Hsp70 and autoimmunity directed against it is a risk factor of cardiovascular diseases, increased in subjects with alcohol use disorder (AUD). The aim of the study was to evaluate the level of anti-Hsp 70 protein antibodies (anti-Hsp 70) in sera of AUD patients during abstinence period. Material and methods. The study included 54 subjects with AUD diagnosed basing on DSM IV criteria. In the studied group clinimetric evaluation was performed, plasma lipids, basic transketolase activity in erythrocytes (TK), thiamine pyrophosphate (TPP) activation of transketolase and the level of anti-Hsp 70 antibodies were evaluated as well. Results. In AUD subjects anti-Hsp 70 level was decreased during abstinence period. During first month of abstinency it correlated negatively with total cholesterol concentration (rS=-0.8857, p=0.0188) and the percentage of TPP stimulation (rS=-0.5960, p<0.05), and during 6 months of abstinence with HDL cholesterol (rS=-0.6848, p=0.0289). After 1 year of abstinence anti-Hsp 70 correlated positively with basic TK activity (rS=0.9550, p=0.0008). Sex is an independent factor influencing anti-Hsp 70 level in AUD subjects (B=60.9469, p=0.0435). In multiple regression model including results of clinimetric evaluation and its effect on the level of anti-Hsp 70 antibodies in AUD patients during 1 month of abstinency anti-Hsp 70 correlated with TWEAK scale score (BETA=-1.4543, p=0.0144) and AUDIT score (BETA-=1.2255, p=0.0224). In 2-6 months of abstinency anti-Hsp 70 correlated with TWEAK score (BETA=1.1110, p=0.0418). After 1 year of abstinency anti-Hsp 70 correlated with AUDIT score (BETA=-1.2161, p=0.0210). Conclusion. The autoimmune reaction against Hsp 70 is decreased during abstinency in AUD patients. Its relation with plasma lipids and thiamine deficiency may lead to increased risk of cardiovascular disorders. TWEAK and AUDIT scoring seem to be most useful for clinimetric evaluation in the context of the role of anti-Hsp 70 antibodies.

Autoantibodies against human ventricular myosin in sera of patients with acute and chronic myocarditis.

OBJECTIVES: The present study investigated the presence of antimyosin autoantibodies in sera of patients with myocarditis and in three control groups: healthy blood donors, patients with alcoholic cardiomyopathy and patients with other cardiac diseases. BACKGROUND: An increasing body of evidence indicates that in the course of myocarditis, autoimmunologic mechanisms may play a pathogenetic role. Animal studies with Coxsackie B3 virus-induced murine myocarditis could demonstrate the appearance of circulating autoantibodies against cardiac myosin. METHODS: Sera were analyzed by enzyme-linked immunosorbent assay (ELISA) and Western blot with human left ventricular myosin as antigen. RESULTS: Seventeen (42%) of 40 serum samples from patients with myocarditis showed antibody-binding against myosin, whereas only 1 (2.5%) of 39 samples from healthy blood donors and 9 (21%) of 43 samples from patients with other cardiac diseases showed autoantibodies against myosin (p < 0.05 vs. myocarditis). In sera from patients with alcoholic cardiomyopathy (n = 12), no antibodies against human ventricular myosin could be detected. In Western blots, the antimyosin antibodies in patients with myocarditis bound to the myosin heavy chain. Using protein-A sepharose chromatography, it could be shown that the antimyosin autoantibodies are of the immunoglobulin G (IgG) type. In ELISA, the antimyosin autoantibodies bind equally to myosin prepared from either cardiac or skeletal muscle, respectively. CONCLUSIONS: These results demonstrate the presence of autoantibodies against human ventricular myosin in patients with myocarditis. The prevalence of these autoantibodies is significantly higher in patients with myocarditis than in patients with other cardiac diseases. No organ specificity of the autoantibodies could be detected.

Anti-beta-receptor antibodies in human dilated cardiomyopathy and correlation with HLA-DR antigens.

The mechanisms responsible for the decline in the density of beta-adrenoceptors in the failing myocardium have not been adequately defined. It is a possibility that the nature of the process leading to heart failure may determine, in large part, the pathogenesis of this decline. Sera of some patients with dilated cardiomyopathy contain antibodies directed against the beta-adrenoceptor, as judged by ligand binding inhibition, immunoprecipitation and immunoblotting assays. Because deranged immune function is thought to play a role in dilated cardiomyopathy, immunogenetic markers of the propensity to develop anti-beta-receptor antibodies were sought. The prevalence of HLA-DR4 was significantly higher in dilated cardiomyopathy patients (40 vs 24% in 511 normal subjects, pc less than 0.001). In contrast, no association was found between HLA phenotypes and alcoholic cardiomyopathy. Furthermore, 72% (13 of 18) of the HLA-DR4 dilated cardiomyopathy patients had anti-beta-receptor antibodies compared to 22% (7 of 33) HLA-DR4-negative patients; in the latter, presence of antibody was linked to the HLA-DR1 phenotype. Conversely, 67% (15 of 23) of the antibody-positive patients were typed as HLA-DR4 compared to only 10% of the antibody-negative patients. Interestingly, none of the 23 antibody-positive patients were typed as HLA-DR3 while 37% of the antibody-negative did. Only 25% of alcoholic cardiomyopathy patients had anti-beta-receptor antibodies and no preponderant HLA association could be demonstrated. These results suggest that the presence of anti-beta-receptor antibodies in patients with idiopathic dilated cardiomyopathy may be under the control of the major histocompatibility locus.

Diagnostic relevance of humoral and cytotoxic immune reactions in primary and secondary dilated cardiomyopathy.

Circulating muscle-specific antimyolemmal antibodies (AMLAs) were found in 18 of 61 patients with secondary dilated cardiomyopathy (DC). All 18 patients had clinical or histologic evidence of previous perimyocarditis. AMLAs were found both in patients' serum samples and bound to the sarcolemmal sheath of the autologous myocardial biopsy specimen. Only AMLAs in postmyocardiac DC induced cytolysis of vital cardiocytes in the presence of complement, whereas hepatocytes remained unaffected. Titers of AMLAs correlated with the degree of cardiocytolysis. In contrast, antiinterfibrillary antibodies were found in 49% patients with primary DC (n = 79) and in 61% of patients (n = 30) with alcoholic DC. The incidence of antifibrillary antibodies of the antimyosin type was 23 and 24%, respectively. Incidence of both antibodies increased according to the severity assessed by New York Heart Association functional classes. Circulating immune complexes assayed by a new Clq-solid phase fluorometric assay were present in 30% of patients with postmyocarditic DC only. Lymphocyte-mediated cytotoxicity against heterologous cardiac target cells (K-cell activity) was measured in 33% of patients each with primary and secondary alcoholic DC but not postmyocarditic DC. There were no blocking factors in primary but were some in alcoholic heart disease.

Alcoholic cardiomyopathy versus chronic myocarditis--immunohistological investigations with LCA, CD3, CD68 and tenascin.

Dilated cardiomyopathy (DCM) is a disorder of unknown aetiology characterized by the left ventricular cavity enlargement and wall thinning associated with reduced left ventricular wall motion. DCM in chronic alcoholics is supposed to be caused by alcohol induced myocardial damage (alcoholic cardiomyopathy). Nevertheless, cardiotropic viruses, such as enteroviruses have long been suspected as causative agents for at least some forms of DCM. In the present study, 13 cases of DCM in chronic alcoholics were investigated with qualification and quantification of infiltrating leucocytes using immunohistological antibodies against leucocyte common antigen (LCA), T-lymphocytes (CD3) and macrophages (CD68). In addition, the expression of tenascin, playing a role in the initiation of fibrotic changes, was examined. All antigens were known to be possibly enhanced in cases of chronic myocarditis. Using these immunohistological techniques, 2 out of 13 cases had evidence for chronic inflammatory myocardial alterations in the sense of lymphocytic infiltrates (>2.0 CD3 T-lymphocytes/visual field at 400 x (HPF); >7 CD3 T-lymphocytes per mm(2)). These cases were diagnosed as having inflammatory cardiomyopathy. The other cases without myocardial inflammation were diagnosed as idiopathic/alcoholic DCM.

[Antigens A and B of the HLA system in dilated cardiomyopathies related to alcohol]. / Etude des antigènes A et B du système HLA dans les myocardiopathies dilatées liées à l'alcool.

It has been hypothesized that dilated cardiomyopathy (DCM) is of dysimmune origin. Conventional immunological studies have provided no evidence that a primary disregulation of immune mechanisms is involved. In the present study, the possibility of an individual predisposition to DCM resting on a preferential distribution of HLA system antigens has been investigated. Typing of the HLA system antigens A and B was performed in a group of 38 DCM patients who were heavy drinkers. The results were compared with those obtained in: (a) 57 alcoholic patients without cardiopathy, and (b) a population of 306 healthy subjects. All subjects were caucasians. Compared with alcoholic patients without cardiac disease, DCM patients had a prevalence of B8 allele. The relative risk of developing DCM was 2.83 in the presence of the B8 antigen. This result suggests a genetic predisposition to DCM: the B8 allele, prevalent among our patients, is associated with the phenotype of numerous autoimmune diseases. This study therefore supports the theory that DCM is of dysimmune origin, but this must be confirmed by further investigations conducted on a larger number of cases.

[Specific immunologic diagnosis of alcoholic myocardial dystrophy]. / Spetsificheskaia immunologicheskaia diagnostika alkogol'noi miokardiodistrofii.

The paper deals with the results of specific anticardiac antibody determination in 124 patients with alcoholic damage to the myocardium (Stages I-III chronic alcoholism), 36 healthy subjects, and 33 patients with various cardiovascular diseases. It was established that specific antibodies were present in the sera from patients with alcoholic myocardial dystrophy, but absent in healthy subjects and almost completely absent in patients with cardiac diseases of other etiology. This enables the authors to recommend that specific anticardiac antibodies be identified to detect alcoholic myocardial damage. The procedure proposed provides a high diagnostic accuracy (89.2%), has no contraindications, requires no special preparation of the patient for the examination, therefore may be used both in the in- and outpatient settings.

[The viral and immunological characteristics of cardiomyopathies and myocarditis]. / Virusoimmunologicheskaia kharakteristika kardiomiopatii i miokarditov.

As many as 97 patients with myocardial lesions: congestive and hypertrophic cardiomyopathy (CMP), postmyocarditis CMP (PM CMP), myocarditis (MC), alcoholic heart injury (AHI), coronary heart disease (CHD), vegetodysovarian myocardiodystrophy were examined by means of a complex of the virological tests (for Coxsackie B, Epstein-Barr and hepatitis B viruses) and immunoassays (for antibodies to different components of the myocardium, leukocyte migration inhibition test, antibody-dependent cellular cytotoxicity test, measurements of T and B lymphocytes and their subpopulations, and so forth). Virus infection was shown to be of a role for the onset of acute MC (usually reversible) and congestive CMP. At the same time the autoimmune mechanisms of the lesions were conclusively ascertained in MC associated with heart failure and in PM CMP. In patients with congestive CMP and AHI coupled with heart failure, antibodies to nerve fibers of the myocardium could be demonstrated in the presence of T-lymphocyte deficiency and high titers of antibodies to Epstein-Barr virus. This does not allow excluding myocardial denervation leading to refractory heart failure. Some immunological parameters made use of in the study provide an opportunity of an objective evaluation of the effect glucocorticoid treatment produces on patients suffering from MC and PM CMP.

Anticardiolipin antibodies associated with alcoholic cardiomyopathy.

Anticardiolipin antibodies are associated with arterial and venous thrombosis, and repetitive miscarriages. The involvement of the heart has been described frequently and can evolve into cardiomyopathy. It has been known for some decades that chronic alcoholism can lead to alcoholic cardiomyopathy (ACM). The objective of this study was to evaluate whether anticardiolipin antibodies represent a worse prognosis for patients with ACM. The authors present a case of a chronic alcoholic patient (30 y of alcoholism) who died at 44 y of age, and who was considered positive for anticardiolipin antibodies. The patient developed deep vein thrombosis, and peripheral arterial and pulmonary embolism. The presence of another risk factor seems to represent a worse prognosis for patients with ACM.

Immunologic investigation in cardiomyopathies.

A group of 6 patients with congestive cardiomyopathy were investigated from the immunologic pint of view. Changes of serum immunoglobulins with increase of IgA and IgM were observed in all the patients. The immunofluorescence test in myocardial fragments, taken by transparietal biopsy from the six patients, confirmed the presence of IgA and IgG in two cases. A pathogenic immunologic mechanism is discussed in cardiomyopathies and especially in the alcoholic one.

Immunological results in myocardial diseases.

Immunological studies have shown new diagnostically important changes in alcoholic and viral myocarditis, as well as in congestive cardiomyopathy. Increased heart size correlated with the degree of congestive heart failure, as well as with negative immunofluorescence and an increased IgA concentration in the serum. These findings may serve as a diagnostic aid in patients with myocardial disease due to alcohol abuse. Viral heart disease is characterized by a variety of symptoms and nuclear antibodies (IgM) can be of help in the differential diagnosis. Heart muscle tissue of patients with congestive cardiomyopathy preferentially binds IgG and IgA. In addition to the other changes these findings are of diagnostic importance. It seems likely that results similar to those obtained for humoral antibodies in congestive cardiomyopathy will apply in the correlation of the haemodynamic status of the patients. The pathophysiological implication of these findings is not clear at present, but the evolution of congestive cardiomyopathy appears to be associated with binding of immunoglobulin to the myocardium, as well as with humoral antiheart antibodies.

[The clinical significance of cellular immunity factors in patients with myocardiodystrophies]. / Klinicheskoe znachenie nekotorykh faktorov kletochnogo immuniteta u bol'nykh miokardiodistrofiiami.

Different changes of cellular immunological homeostasis were found in an investigation of 70 patients with myocardial dystrophy of various origin. Patients with alcohol lesions of the heart and tonsillogenous myocardial dystrophy showed T- and B-lymphopenia. Persons with dysmetabolic myocardial dystrophy showed a partial inhibition of E-rosette formation. The functional activity of T-lymphocytes evaluated by the reaction of blast transformation of leucocytes was intact in patients with myocardial infarction.

Circulating antibodies to cardiac protein-acetaldehyde adducts in alcoholic heart muscle disease.

1. Serum samples from patients with alcoholic heart muscle disease and from control subjects with and without heart disease who did not drink to excess were screened by Western immunoblotting for antibodies to acetaldehyde-modified cardiac cytosolic proteins. 2. Two of the 64 control samples (from subjects with and without heart disease who were not drinking and from subjects with alcoholic liver disease) had detectable (IgG) antibody to acetaldehyde-modified cardiac proteins. 3. By contrast, 7 of 21 (33%) patients with alcoholic heart muscle disease had antibodies against cyanoborohydride-stabilized, acetaldehyde-modified human cardiac cytosolic protein antigens (P < 0.001). 4. Antibodies were of IgG class in six patients and IgA class in five. The molecular sizes of the protein antigens observed ranged from 58 to 120 kDa. 5. These results suggest that a proportion of patients with alcoholic heart muscle disease develop immunogenic cardiac protein-acetaldehyde adducts. The presence of antibodies to these adducts may be a marker for the diagnosis of this heart disease, or possibly for its pathogenesis.

[Peripheral T-lymphocyte subpopulations in primary and alcoholic dilated cardiomyopathy]. / Etude des sous-populations lymphocytaires T périphériques au cours des myocardiopathies dilatées primitives et alcooliques.

In order to test the hypothesis of the role of a suppressor/cytotoxic T lymphocyte deficit in the pathogenesis of dilated cardiomyopathies (DCM), 20 patients (11 alcoholic-A; 9 primary-P) were compared with 24 normal controls (N) and 10 patients with chronic cardiac failure (CCF). The percentage of OKT 3, a global assessment of the T lymphocytes, did not differ significantly between the groups. The percentage of OKT 4 (helper T lymphocytes) was significantly lower in DCM (43 +/- 8.1 p. 100) compared to N (51.92 +/- 8.1 p. 100), p less than 0.001. The percentage of OKT 4 was also lower in CCF (45.3 +/- 3.91 p. 100) compared to N (p less than 0.05). There was a very significant decrease in the percentage of OKT 8 (suppressor/cytotoxic T lymphocytes) in DCM (17.23 +/- 4.78 p. 100) compared to N (26.42 +/- 5.72 p. 100) (p less than 10(-8)). A reduction of OKT 8 was also observed in CCF compared to N (p less than 0.05). The ratio of OKT 4/OKT 8 was significantly higher in DCM (2.7 +/- 0.97) compared to N (2.08 +/- 0.6) (p less than 0.05). This difference was not observed in CCF (2.19 +/- 0.48). There were no differences between DCM A and P. These results indicate that chronic cardiac failure is associated with an equal reduction in the percentage of OKT 4 and OKT 8 lymphocytes. Dilated cardiomyopathy is associated with a large reduction in the OKT 4 and especially in the of OKT 8 with a statistically significant increase in the OKT 4/OKT 8 ratio. Although chronic cardiac failure seems to affect lymphocytes, these results are compatible with a deficit of suppressor/cytotoxic T lymphocytes in dilated cardiomyopathies.