Organ-specific cardiac autoanfibodies in dilated cardiomyopathy: Frequency and clinical correlates in Polish patients

Organ- and disease-specific cardiac autoantibodies are foundin a third of dilated cardiomyopathy patients from the U.K.and Italy and represent markers of autoimmune involvement. Therole of autoimmunity may vary in dilated cardiomyopathy patientsfrom different countries due to differences in genetic susceptibilityto autoimmune diseases. The aim of this study was to assessthe frequency of organ-specific cardiac autoantibodies detectedby immunofluorescence in a consecutive series of patients withdilated cardiomyopathy and in disease and normal control subjectsfrom Poland The study groups included 79 patients with idiopathic(WHO criteria) dilated cardiomyopathy, 55 patients with othercardiac disease and 60 normal subjects. Cardiac antibody testswere performed by indirect immunofluorescence on human heart,skeletal muscle was used to identify cross-reacting antibodies.The frequency of organ-specific cardiac autoantibodies was higherin patients with dilated cardiomyopathy (21/79, 27%) than incontrols with other cardiac disease (1/55, 2% P<0·001)or in normal subjects (7/60, 12% P<0·02). Conversely,cross-reactive antibodies were detected in similar proportionsin patients with dilated cardiomyopathy (5/79, 6%), diseasecontrols (7/55, 13%) and normal subjects (6/60, 10%, P=ns).The organ-specific antibody was more common in patients withdilated cardiomyopathy with insidious onset of disease (17/34,50%) compared to those who did not exhibit this feature (4/45,9%, P<0·0001) Organ- and disease-specific cardiacautoantibodies were found in 27% of Polish patients with dilatedcardiomyopathy at diagnosis; this is evidence for autoimmuneinvolvement in a subset of patients from our country, as seenin a previously reported series of Western European origin.The association of antibody status with insidious onset of symptomsis in keeping with the long latency period observed in otherautoimmune disorders.     

Organ-specific cardiac autoantibodies in dilated cardiomyopathy: Frequency and clinical correlates in Polish patients

Organ- and disease-specific cardiac autoantibodies are foundin a third of dilated cardiomyopathy patients from the U.K.and Italy and represent markers of autoimmune involvement. Therole of autoimmunity may vary in dilated cardiomyopathy patientsfrom different countries due to differences in genetic susceptibilityto autoimmune diseases. The aim of this study was to assessthe frequency of organ-specific cardiac autoantibodies detectedby immunofluorescence in a consecutive series of patients withdilated cardiomyopathy and in disease and normal control subjectsfrom Poland The study groups included 79 patients with idiopathic(WHO criteria) dilated cardiomyopathy, 55 patients with othercardiac disease and 60 normal subjects. Cardiac antibody testswere performed by indirect immunofluorescence on human heart,skeletal muscle was used to identify cross-reacting antibodies.The frequency of organ-specific cardiac autoantibodies was higherin patients with dilated cardiomyopathy (21/79, 27%) than incontrols with other cardiac disease (1/55, 2% P<0.001) orin normal subjects (7/60, 12% P<0.02). Conversely, cross-reactiveantibodies were detected in similar proportions in patientswith dilated cardiomyopathy (5/79, 6%), disease controls (7/55,13%) and normal subjects (6/60, 10%, P=ns). The organ-specificantibody was more common in patients with dilated cardiomyopathywith insidious onset of disease (17/34, 50%) compared to thosewho did not exhibit this feature (4/45, 9%, P<0.0001) Organ-and disease-specific cardiac autoantibodies were found in 27%of Polish patients with dilated cardiomyopathy at diagnosis;this is evidence for autoimmune involvement in a subset of patientsfrom our country, as seen in a previously reported series ofWestern European origin. The association of antibody statuswith insidious onset of symptoms is in keeping with the longlatency period observed in other autoimmune disorders.     

Right ventricular dilated cardiomyopathy associated with primary biliary cirrhosis.

A case of right ventricular dilated cardiomyopathy associated with primary biliary cirrhosis is described. The patient was a middle aged woman, who initially complained of fatigue and itching. The diagnosis of primary biliary cirrhosis was made based on clinical, biochemical and histological evidence of the disease. Seven years later severe right-sided heart failure developed. The diagnosis of right ventricular dilated cardiomyopathy was made based on echocardiographic and angiographic evidence of a globally dilated and poorly contracting right ventricle. Left ventricular function was within normal limits. Autoimmune serology screening at this time revealed the presence of organ-specific cardiac antibody (titre 1/20) and of antinuclear antibody (titre 1/80) by indirect immunofluorescence. There were no findings of mitochondrial antibody or other non-organ specific or organ-specific antibodies. Overall, this assessment demonstrates autoimmunity in both hepatic and heart muscle disease in a patient with primary biliary cirrhosis and right ventricular dilated cardiomyopathy.     

Cardiac and skeletal muscle abnormalities in cardiomyopathy: comparison of patients with ventricular tachycardia or congestive heart failure

Results of cardiac muscle and skeletal muscle biopsies were compared in 22 patients with cardiomyopathy; 11 patients presented with symptoms secondary to ventricular tachycardia (Group 1) and 11 had symptoms of severe congestive heart failure (Group 2). No patient had structural or ischemic cardiac disease. In Group 1 patients, hemodynamic abnormalities were subtle, but invasive study demonstrated dilated cardiomyopathy in two patients and restrictive cardiomyopathy in nine. In Group 2, eight patients had dilated cardiomyopathy and three had restrictive cardiomyopathy. Cardiac biopsy results were abnormal in all 22 patients and the abnormalities were similar for the two groups. Cardiac histologic study revealed a spectrum of abnormalities including fibrosis, dilated sarcoplasmic reticulum, increased numbers of intercalated discs and mitochondrial abnormalities. Histologic abnormalities of skeletal muscle were similar in each group, consisting of endomysial fibrosis and increased lipid deposits. Slightly more than half of the Group 1 and Group 2 patients also had a low concentration of skeletal muscle long chain acylcarnitine. These data demonstrate that abnormalities of both cardiac and skeletal muscle are common in patients with cardiomyopathy; abnormalities are similar whether initial symptoms are due to ventricular tachycardia or congestive heart failure. It is suggested that these patients with cardiomyopathy may have a generalized myopathy.     

Autoimmune myocarditis and dilated cardiomyopathy: focus on cardiac autoantibodies

Criteria of organ-specific autoimmunity are fulfilled in a subset of patients with myocarditis/dilated cardiomyopathy (DCM). In particular, circulating heart-reactive autoantibodies are found in patients and symptom-free relatives. These autoantibodies are directed against multiple antigens, some of which are expressed in the heart (organ-specific), others in heart and some skeletal muscle fibres (partially-heart specific) or in heart and skeletal muscle (muscle-specific). Distinct autoantibodies have different frequency in disease and normal controls. Different techniques detect one or more antibodies, thus they cannot be used interchangeably for screening. It is unknown whether the same patients produce more antibodies or different patient groups develop autoimmunity to distinct antigens. IgG antibodies, shown to be cardiac and disease-specific for myocarditis/DCM, can be used as autoimmune markers for identifying patients in whom immunosuppression may be beneficial and relatives at risk. Some autoantibodies may also have a functional role, but further work is needed.     

Serial electrocardiographic changes in idiopathic dilated cardiomyopathy confirmed at necropsy

Serial electrocardiographic changes in necropsy-proven idiopathic dilated cardiomyopathy are evaluated and a method of predicting heart weight using QRS amplitudes is described. In 34 patients with multiple electrocardiograms (mean 3/patient) progressive prolongation of PR interval (0.18 +/- 0.03 to 0.21 +/- 0.03, p less than 0.001) and QRS duration (0.10 +/- 0.02 to 0.13 +/- 0.03, p less than 0.0001) was noted. Progressive conduction abnormalities were common (82%). QTc interval and QRS- and T-wave axes did not change. In 50 patients with electrocardiograms within 60 days of death, total 12-lead QRS and V1 through V6 QRS amplitude correlated better with heart weight (r = 0.51, p less than 0.0001 and r = 0.55, p less than 0.0001) than the Estes-Romhilt score did. The mean total 12-lead QRS amplitude was 138 mm with a mean of 106 for V1 through V6. In 31 patients cardiac mass index was calculated and showed significant correlation with 12-lead and V1 through V6 QRS amplitudes (r = 0.68, p less than 0.0001 and r = 0.75, p less than 0.0001, respectively). The QRS amplitudes remained constant during the illness. By using total 12-lead QRS or frontal plane QRS amplitude, heart weight can be predicted as early as 2 years before death. Use of body surface area and QRS amplitude criteria increases the accuracy of heart weight prediction. Thus, progressive electrocardiographic changes are common in patients with idiopathic dilated cardiomyopathy and QRS amplitude criteria are more accurate in the prediction of left ventricular hypertrophy than standard criteria.     

Left ventricular flow propagation during early filling is related to wall relaxation: a color M-mode Doppler analysis.

OBJECTIVES. This study was designed to evaluate the relation between the velocity of flow propagation and left ventricular relaxation by using color M-mode Doppler echocardiography to analyze flow propagation in the left ventricle. BACKGROUND. Noninvasive attempts to identify alterations in left ventricular relaxation have been hampered because both the relaxation rate and left atrial filling pressure are the determinants of peak early velocity and filling rate. METHODS. Color M-mode velocity data were transferred to a microcomputer and compared with conventional pulsed Doppler data to assess the ability of color M-mode echocardiography to analyze velocity field properties. The velocity of flow propagation was measured as the slope of the flow wave front during early filling in normal subjects (n = 29) and in patients with disease that alters relaxation (dilated cardiomyopathy [n = 31], ischemic cardiomyopathy [n = 8], hypertrophic cardiomyopathy [n = 5], systemic hypertension [n = 22] and aortic valve disease [n = 25]). In nine patients with end-stage dilated cardiomyopathy, echocardiographic and left heart catheterization data were obtained at baseline and during intracoronary dobutamine infusion. RESULTS. Color M-mode and pulsed Doppler echocardiographic data were highly correlated (n = 217, r = 0.94, p less than 0.0001, velocity range 0.2 to 1.5 m/s). The velocity of flow propagation was lower in patients than in normal subjects (0.46 +/- 0.15 vs. 0.84 +/- 0.11 m/s, p less than 0.0001). The decrease was significant in all disease forms with or without left ventricular dilation. The velocity of flow propagation was related to peak early velocity in normal subjects (p less than 0.001) but not in patients. It varied inversely with the isovolumetric relaxation time constant during dobutamine infusion and the two variables were highly correlated (p less than 0.0001). CONCLUSIONS. The velocity of flow propagation during early filling seems to be highly dependent on the left ventricular relaxation rate and could be an important tool in studying diastolic function.     

Autoantibodies against beta-adrenoceptors in human idiopathic dilated cardiomyopathy

Although it is recognized that the number of cardiac beta-adrenoceptors is reduced in human dilated cardiomyopathy, the mechanisms involved have not been defined. We examined the possible role of altered humoral immunity by comparing the effect of sera from patients with idiopathic dilated cardiomyopathy (n = 20), ischemic or valvular heart disease (n = 28), or controls with no known cardiac disease (n = 18) on the binding of radioligands to cardiac beta-receptors. The ability of sera from cardiomyopathic patients to inhibit the binding of [3H]dihydroalprenolol to rat cardiac membranes was significantly higher than that of the other two patient groups (40 +/- 5% at 50-fold serum dilution compared to 14 +/- 3% for the ischemic/valvular heart disease group, and 14 +/- 4% for the normal control group, p less than 0.001). A similar inhibition was exerted by IgG from cardiomyopathic patients. Only the number, not the affinity, of the beta-receptors was decreased by cardiomyopathic sera. This decrease could be prevented by preincubating the sera with anti-human IgG, indicating the presence of autoantibodies. Furthermore, the sera were ineffective against cardiac alpha 1-adrenoceptors and considerably less effective against lung beta 2-receptors. In addition to ligand binding inhibition, sera from cardiomyopathic patients could immunoprecipitate beta-adrenoceptors quantitatively from solubilized cardiac membranes. Positive sera inhibited significantly isoproterenol-stimulated adenylate cyclase with no effect on basal or NaF-stimulated activities. These results document the presence in sera from patients with idiopathic dilated cardiomyopathy of autoantibodies directed against the cardiac beta 1-adrenoceptor which may play an important role in the regulation of inotropic responsiveness to beta-agonists.     

Pulmonary function and respiratory muscle strength in chronic heart failure: comparison between ischaemic and idiopathic dilated cardiomyopathy.

OBJECTIVE: To compare pulmonary function and respiratory muscle strength in patients with ischaemic and idiopathic dilated cardiomyopathy, well matched for indices of heart failure. METHODS: The study involved 30 patients with ischaemic cardiomyopathy and 30 with idiopathic dilated cardiomyopathy. The groups were well matched for age, weight, and clinical severity of cardiac dysfunction as assessed by ejection fraction and the New York Heart Association functional class. There were more smokers in the ischaemic group (p < 0.05), but indices of pulmonary function were comparable. RESULTS: Mean (SD) maximum static inspiratory pressure was lower in dilated cardiomyopathy than in ischaemic cardiomyopathy (73 (20) v 84 (22) cm H2O, p < 0.05), as was the maximum static expiratory pressure (90 (20) v 104 (21) cm H2O, p < 0.05). CONCLUSIONS: For a given degree of cardiac dysfunction, the respiratory muscles are weaker in patients with idiopathic dilated cardiomyopathy than in those with ischaemic cardiomyopathy.     

Identification of alpha- and beta-cardiac myosin heavy chain isoforms as major autoantigens in dilated cardiomyopathy.

BACKGROUND. Immunization with cardiac myosin induces experimental autoimmune heart disease in genetically predisposed mice. These mice produce heart-specific autoantibodies, some of which are directed against the cardiac myosin isoform. METHODS AND RESULTS. We have reported the presence of circulating heart-specific autoantibodies in 26% of patients with idiopathic dilated cardiomyopathy (DCM) using indirect immunofluorescence. To identify the autoantigen(s) recognized by heart-specific autoantibodies in human disease, we tested, by Western blotting, sera from 26 DCM patients, 14 of whom were cardiac antibody-positive and 12 antibody-negative, as well as sera from 12 patients with cardiac failure from ischemic or valvular heart disease and from 13 normal subjects who were cardiac antibody-negative. Crude myofibrillar proteins and myosin preparations extracted from human atrial or ventricular specimens were used as antigens. Sodium dodecyl sulfate polyacrylamide gel electrophoresis was performed. The proteins were electrophoretically transferred to nitrocellulose sheets. The paper strips were incubated in sera from patients or controls at 1:100 dilution; the reaction was revealed with a peroxidase-labeled second antibody against human immunoglobulin. Twelve of the 14 DCM sera (86%) containing heart-specific antibodies reacted with both the alpha- (atrial specific) and beta- (ventricular and slow skeletal) myosin heavy chain isoforms; none of the 13 normal sera (p = 0.0001) and one of the 24 heart failure-negative control sera (4%, p = 0.0001) contained antibodies against myosin heavy chain. CONCLUSIONS. These findings indicate that alpha- and beta-cardiac myosin heavy chain isoforms as in the murine model of autoimmune heart disease are major autoantigens in patients with idiopathic DCM.     

The measurement of enzyme activities in endomyocardial biopsies from patients with congestive (dilated) cardiomyopathy and specific heart muscle disease

50 patients with heart muscle disease have been investigated using routine invasive and non-invasive techniques, including endomyocardial biopsy. Enzyme activities in myocardial tissue obtained by biopsy have been measured in dilated cardiomyopathy and heart muscle disease and compared. Significant differences in enzyme activity have been found between dilated cardiomyopathy and alcoholic heart muscle disease when the groups are defined by detailed drinking histories. CPK (p less than 0.002), MDH (p less than 0.001), LDH (p less than 0.001) and alpha HBD (p less than 0.001). The changes in the enzyme levels may be an adaptive response to alcohol although serial study did not show a fall in enzyme activities after 3-6 months abstinence. Preliminary data furthermore indicates an association of the alpha HBD/LDH and LDH/CPK enzyme activity ratios and ejection fraction. This data supports the diagnosis of a specific heart muscle disease in response to alcohol excess.     

Defective myocardial carnitine metabolism in congestive heart failure secondary to dilated cardiomyopathy and to coronary, hypertensive and valvular heart diseases

Reduced myocardial carnitine concentrations in the explanted heart and elevated plasma levels have been found in patients undergoing heart transplant for end-stage congestive heart failure (CHF). To evaluate a possible loss of myocardial carnitine in less severe stages of CHF, total myocardial carnitine levels were compared in right ventricular endomyocardial biopsies from 28 patients with mild, moderate and severe dilated cardiomyopathy, 8 patients with CHF of different origin and 13 normal control subjects. If possible, free myocardial carnitine and free and total plasma carnitine were also determined. For the first time, myocardial carnitine levels have been measured in endomyocardial biopsies from 13 normal human hearts (control values: 9.9 +/- 0.8 nmol/mg noncollagen protein). In comparison with these control values, total myocardial carnitine was significantly reduced in patients with dilated cardiomyopathy (6.1 +/- 0.5 nmol/mg noncollagen protein, p less than 0.0001), and CHF of other origins (6.6 +/- 1.1 nmol/mg noncollagen protein, p less than 0.02). Free myocardial carnitine concentrations in dilated cardiomyopathy (4.6 +/- 0.4 nmol/mg noncollagen protein) and CHF of different origin (4.4 +/- 0.5 nmol/mg noncollagen protein) were also significantly different from control values (control values: 9.7 +/- 0.7 nmol/mg noncollagen protein, p less than 0.0001 and p less than 0.005 for both groups). The loss of free and total myocardial carnitine was comparable in dilated cardiomyopathy and CHF due to other diseases. In contrast, plasma free and total carnitine levels in the CHF patients were significantly elevated (67 +/- 5.5 mumol/liter, control values 41 +/- 3.7 mumol/liter, p less than 0.005). Alterations in myocardial carnitine metabolism represent nonspecific biochemical markers in CHF with yet unknown consequences for myocardial function.     

Circulating cardiac autoantibodies in dilated cardiomyopathy and myocarditis: pathogenetic and clinical significance

Dilated cardiomyopathy (DCM) is a relevant cause of heart failure and a common indication for heart transplantation. It may be idiopathic, familial/genetic, viral, autoimmune or immune-mediated associated with a viral infection. Myocarditis is an inflammatory disease of the myocardium; it may be idiopathic, infectious or autoimmune and may heal or lead to DCM. Thus, in a patient subset, myocarditis and DCM are thought to represent the acute and chronic stages of an organ-specific autoimmune disease of the myocardium. In keeping with this hypothesis, autoimmune features in patients with myocarditis/DCM include: familial aggregation; a weak association with HLA-DR4; abnormal expression of HLA class II on cardiac endothelium on endomyocardial biopsy; and detection of organ- and disease-specific cardiac autoantibodies of the IgG class in the sera of affected patients and symptom-free relatives. The cardiac autoantibodies detected by immunofluorescence are directed against multiple antigens. Two of these, first identified using immunoblotting and confirmed by ELISA, are the atrial-specific alpha- and the ventricular and skeletal muscle beta-heavy chain isoform. The alpha-myosin isoform fulfils the expected criteria for organ-specific autoimmunity, in that immunization with cardiac, but not skeletal myosin reproduces, in susceptible mouse strains, the human disease phenotype of myocarditis/DCM; in addition, alpha-myosin is entirely cardiac-specific. Additional antigenic targets of heart-reactive autoantibodies include unknown sarcolemmal proteins, mitochondrial enzymes, beta-adrenergic and muscarinic receptors. For some of these antibodies, there is in vitro evidence for a functional role. The organ-specific cardiac autoantibodies detected by immunofluorescence in symptom-free relatives were associated with echocardiographic features suggestive of early disease. Mid-term follow-up suggests that these antibodies are predictive markers of progression to DCM among symptom-free relatives with or without abnormal echocardiographic findings.     

Acute Systemic and Regional Hemodynamic Effects of Alpha1-Adrenoceptor Blockade in Conscious Spontaneously Hypertensive Rats

The acute hemodynamic effect of the selective alpha₁,-antagonist,2-[4-(n-butyryl)-homopiperazine-l-yl]-4-amino-6,7–dimethoxy-quinazoline (bunazosin; E-643), was studied by the microsphere technique in 62 conscious spontaneously hypertensive rats. We found that (a) a large fall in total peripheral resistance with a moderate increase in cardiac output accounted for the moderate decrease in arterial pressure; (b) the heart rate did not change; (c) the skeletal muscle, brain, heart, and gastrointestinal tract sensitively dilated, and kidney less sensitively dilated, their resistance vessels, with little change in their blood flow.     

Familial dilated cardiomyopathy: evidence for genetic and phenotypic heterogeneity. Heart Muscle Disease Study Group.

OBJECTIVES: This study was performed to evaluate the characteristics, mode of inheritance and etiology of familial dilated cardiomyopathy (FDC). BACKGROUND: A genetic form of disease transmission has been identified in a relevant proportion of patients with dilated cardiomyopathy (DCM). Variable clinical characteristics and patterns of inheritance, and an increased frequency of cardiac antibodies have been reported. An analysis of FDC may improve the understanding of the disease and the management of patients. METHODS: Of 350 consecutive patients with idiopathic DCM, 281 relatives from 60 families were examined. Family studies included clinical examination, electrocardiography, echocardiography and blood sampling. Of the 60 DCM index patients examined, 39 were attributable to FDC and 21 were due to sporadic DCM. Clinical features, histology, mode of inheritance and autoimmune serology were examined, molecular genetic studies were undertaken and the difference between familial and sporadic forms was analyzed. RESULTS: Only a younger age (p = 0.0005) and a higher ejection fraction (p = 0.03) could clinically distinguish FDC patients from those with sporadic DCM. However, a number of distinct subtypes of FDC were identified: 1) autosomal dominant, the most frequent form (56%); 2) autosomal recessive (16%), characterized by worse prognosis; 3) X-linked FDC (10%), with different mutations of the dystrophin gene; 4) a novel form of autosomal dominant DCM with subclinical skeletal muscle disease (7.7%); 5) FDC with conduction defects (2.6%), and 6) rare unclassifiable forms (7.7%). The forms with skeletal muscle involvement were characterized by a restrictive filling pattern; the forms with isolated cardiomyopathy had an increased frequency of organ-specific cardiac autoantibodies. Histologic signs of myocarditis were frequent and nonspecific. CONCLUSIONS: Familial dilated cardiomyopathy is frequent, cannot be predicted on a clinical or morphologic basis and requires family screening for identification. The phenotypic heterogeneity, different patterns of transmission, different frequencies of cardiac autoantibodies and the initial molecular genetic data indicate that multiple genes and pathogenetic mechanisms can lead to FDC.     

Resting heart rate and cardiac function in dilated cardiomyopathy

We hypothesized that, within the normal range of resting heart rate, heart rate and left ventricular ejection fraction would be inversely correlated and heart rate and left ventricular filling would be correlated in patients with dilated cardiomyopathy and not correlated in patients with normal cardiac function. At rest, heart rate, left ventricular ejection fraction, and three measures of diastolic filling (time to peak filling rate, peak filling rate, and first half filling fraction) were recorded using radionuclide ventriculography in subjects with no cardiac disease, patients with idiopathic dilated cardiomyopathy, and patients with dilated cardiomyopathy associated with ischemic heart disease. Heart rate had significant inverse correlations with left ventricular ejection fraction (r=-0.55, P=0.0007) and time to peak filling rate (r=-0.47, P=0.005) and a positive correlation with peak filling rate (r=0.73, P<0.0001) in patients with idiopathic dilated cardiomyopathy; heart rate was correlated only weakly with these measures in the absence of cardiac disease and essentially was not correlated in dilated cardiomyopathy due to ischemic heart disease. The change in resting heart rate with left ventricular ejection fraction and time to peak filling rate were significantly (P<0.05) different between patients with no cardiac disease and those with idiopathic dilated cardiomyopathy. Thus, resting heart rate correlated significantly with left ventricular ejection fraction and diastolic filling in patients with idiopathic dilated cardiomyopathy.     

Reduced heart lipid peroxidation precedes cardiac dilatation in turkeys with naturally occurring cardiomyopathy

STUDY OBJECTIVE--The aim of the study was to determine if reduced heart lipid peroxidation in 1-2 month old turkeys with furazolidone induced dilated cardiomyopathy is drug related and model dependent, a non-specific characteristic of the dilated turkey heart, or if alterations of heart lipid peroxidation can occur prior to onset of cardiac dilatation, and therefore may be involved in its pathogenesis. DESIGN--Ventricular lipid peroxidation capacity and superoxide dismutase activity were measured in controls and in turkeys with spontaneous cardiomyopathy at various ages (newly hatched, 7-10 d, and 1-2 months) and stages of the disease. SUBJECTS--46 turkeys with naturally occurring dilated cardiomyopathy and 29 age matched controls were used at hatch, 7-10 d, and 1-2 months of age. MEASUREMENTS AND MAIN RESULTS--Heart lipid peroxidation, measured by thiobarbituric acid reactive substances (malondialdehyde), was found to be reduced not only in the dilated hearts of 1-2 months old cardiomyopathic turkeys [114(SEM 10) v 176(21) nmol.100 mg-1 protein, p = 0.023] but also in the non-dilated hearts of 9-10 day old cardiomyopathic turkeys [135(17) v 274(35) nmol.100 mg-1 protein, p = 0.004]. Ventricular superoxide dismutase activity was similar in control and cardiomyopathic turkeys at all stages and there was the expected increase with age. In control turkeys ventricular superoxide dismutase activity in 1-2 month old birds, at 718(52) nitrite units.100 mg-1 protein, was significantly higher than values in 7-10 day old turkeys [398(31) nitrite units.100 mg-1 protein, p = 0.001]. CONCLUSIONS--Decreased lipid peroxidation capacity is present in the dilated hearts of spontaneously cardiomyopathic turkeys. However, it is also decreased in cardiomyopathic turkeys at 9-10 d (the time of highest mortality) prior to the onset of cardiac dilatation. Therefore, alterations in heart lipid composition may be involved in the pathogenesis of this cardiomyopathy and not simply a result of the cardiac dilatation/hypertrophy process.     

Increased arterial oxygen content--an important compensatory mechanism in chronic moderate heart failure.

STUDY OBJECTIVE--The aim was to determine whether there is a compensatory increase in arterial oxygen content to a hypokinetic circulation in ambulant patients with chronic moderate heart failure caused by dilated cardiomyopathy. DESIGN - Central haemodynamics, arterial oxygen content, arterial haemoglobin concentration, arterial oxygen saturation, and blood gases were measured during a 6 min supine exercise test on a symptom related submaximal workload. At rest, total body haemoglobin was determined. PATIENTS--19 patients with chronic stable moderate heart failure caused by dilated cardiomyopathy, treated with diuretics and digoxin, were studied. MEASUREMENTS AND MAIN RESULTS--During exercise arterial oxygen content correlated inversely with the cardiac index (r = 0.66, p less than 0.01). The two determinants of arterial oxygen content, arterial haemoglobin concentration and arterial oxygen saturation, also correlated inversely with the cardiac index (r = 0.60, p less than 0.01 and r = 0.70, p less than 0.001 respectively). Cardiac index during exercise correlated inversely with total body haemoglobin (r = 0.73, p less than 0.001). CONCLUSIONS--A hypokinetic circulation during daily living induces an increase in arterial oxygen content in patients with chronic stable moderate heart failure caused by dilated cardiomyopathy. Renal hypoperfusion may play a role in stimulating the erythropoiesis and exertional hyperventilation in raising arterial oxygen saturation.     

Cardiac and skeletal myopathy associated with cardiac dysrhythmias

Electrophysiologic studies, echocardiograms, cardiac catheterizations and histologic and biochemical analyses of skeletal muscle biopsies were performed in 10 patients (aged 10 to 37 years, mean 21) who had dysrhythmias as the initial manifestation of cardiomyopathy. Presenting symptoms and signs attributable to dysrhythmias included sudden cardiac arrest in 2 patients, syncope in 3, presyncope in 3 and palpitations in 2. There was no clinical evidence of skeletal muscle weakness in any patient. Multicatheter electrophysiologic evaluation established diagnoses of ventricular tachycardia in 6 patients, primary atrial tachycardia in 2 and third degree infra-Hisian heart block in 1 patient. One patient presenting with palpitations had no inducible arrhythmia or conduction disturbance. Echocardiographic, angiographic and hemodynamic studies demonstrated previously unsuspected dilated cardiomyopathy in 7 patients and restrictive cardiomyopathy in 3. Skeletal muscle histologic characteristics were abnormal in all 10 patients; increases in lipid droplets and endomysial fibrosis were the characteristic findings. Serum free carnitine and short- and long-chain acylcarnitine were normal in 9 patients. However, skeletal muscle long-chain acylcarnitine was reduced in 9 patients. These findings support the concept that in certain patients presenting with dysrhythmias, the dysrhythmia may be a manifestation of cardiac and skeletal (that is, generalized) myopathy.     

A new variant of type IV glycogenosis with primary cardiac manifestation and complete branching enzyme deficiency: In vivo detection by heart muscle biopsy

Type IV glycogenosis (polyglucosan body disease) is a rare congenitalautosomal recessive inherited disorder, caused by lack of thebranching enzyme (amylo-1, 4–1, 6 transglucosidase). Thisdeficiency leads to storage of abnormal glycogen (polyglucosanbodies) in the liver and other tissues. The clinical onset ofthe disease is insidious with non-specific gastrointestinalsymptoms followed by progressive hepatic failure. Usually patientsdie due to hepatic cirrhosis within 4 years. Sometimes myopathyof the heart and skeletal muscle is also present. In these cases,the clinical onset is often later than in typical cases. We report on two brothers with primarily cardiac manifestationand late onset of the disease. The older one started to sufferfrom progressive dilated cardiomyopathy at the age of 18 years,presenting with severe heart failure, hepatosplenomegaly, ascitesand peripheral oedema. He also demonstrated myopathy and muscularatrophy especially of the shoulder and lower limbs. Initiallyhe improved on medical therapy, but one year later severe heartfailure recurred followed shortly afterwards by sudden cardiacdeath. Right heart and skeletal muscle biopsies were performedwhile he was alive. These, as well as the autopsy, revealedmassive accumulation of polyglucosan bodies. In both heart andskeletal muscle, complete branching enzyme deficiency couldbe proven. His 14-year-old brother showed similar clinical findingsof mild dilated cardiomyopathy. His muscle biopsy also revealedpolyglucosan body myopathy. Thus, in young patients presentingwith congestive cardiomyopathy, type IV glycogenosis has tobe considered in the differential diagnosis.