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Myocarditis is a common cardiological disease. New molecular biological and immunohistological methods have confirmed the persistence of viral infection and chronic myocardial inflammation in a considerable number of patients. A causal link between viral myocarditis and the development of dilated cardiomyopathy has been recognized. This has prognostic implications and helps for the decision of a specific immunosuppressive, immunomodulatory and antiviral therapy.

Seventy-seven consecutive patients with dilated cardiomyopathy underwent left ventricular endomyocardial biopsy. In 20 biopsies (26%) enteroviral RNA was detected by in-situ hybridization. After an average observation period of more than 2 years only one patient had died in the enterovirus positive (ev+) group compared with 11 deaths and four heart transplantations in the enterovirus negative (ev-) group. After a mean follow-up of 16 +/- 9 months haemodynamic evaluation of the surviving ev+ patients showed significantly better results with respect to left ventricular ejection fraction and left ventricular end-diastolic diameter. The four ev+ patients with haemodynamic deterioration were given interferon-alpha, 3 million units subcutaneously every other day for six months. No severe side effects were seen and all four patients improved according to their haemodynamic and clinical parameters. In two of the four patients enteroviral RNA was not detectable in a subsequent biopsy.

Cultured human myocardial fibroblasts of pediatric origin seem to be a useful species-specific model for studying various heart diseases which involve the myocardial interstitium, for example enterovirus heart disease. Cells were propagated from small samples of human ventricular tissues (0.2 g) obtained from standard surgical procedure for the correction of Fallot-tetralogy. Cultured cells exhibited typical fibroblastoid morphology over a period of 4 months and were uniformly immunoreactive with a monoclonal antibody directed against prolyl-4-hydroxylase, a marker enzyme of fibroblasts. Infection of cell cultures with coxsackievirus B3, a cardiotropic enterovirus, resulted in a typical carrier-state type of virus persistence. Average virus titers of 2.3 x 10(5) plaque-forming units/ml (SD = 9.9 x 10(4)) were maintained over a period of up to 10 weeks by productive infection of about 8-10% of the cell population. Coxsackievirus B3 carrier cultures of human myocardial fibroblasts were used to evaluate in vitro the long-term antiviral effects of recombinant interferon alpha-2a and natural human interferon-alpha. Recombinant interferon-alpha reduced virus yields by 90% with a concentration of 423 IU/ml, whereas with natural interferon-alpha a 90% reduction of virus yields was achieved with concentrations as low as 21 IU/ml. Antiviral effects of both recombinant and natural interferon-alpha were highly specific and not related to inhibition of cell-proliferation (< 50% with interferon-alpha concentrations as high as 6250 IU/ml). Since effective concentrations of interferon-alpha can be easily attained in vivo with subcutaneous application, interferon-alpha (in particular: natural interferon-alpha) may become useful in the treatment of patients with enterovirus myocarditis and enterovirus induced dilated cardiomyopathy.

The myocardial uptake of indium-111 antimyosin indicates the presence of ongoing myocyte damage. To evaluate the role of this finding in patients with idiopathic dilated cardiomyopathy (IDC), 36 patients were studied by planar and SPECT antimyosin imaging. The diagnosis of IDC was based on coronary angiography and left ventricular endomyocardial biopsy. The antimyosin scan was evaluated qualitatively from SPECT images and assessed quantitatively by a count density index (CDI) which measured the tracer activity over the heart relative to the lung and sternal region (normal value less than 1.20). Group 1 consisted of 13 patients (36%) with an increased myocardial antimyosin uptake, while 23 patients had a normal antimyosin scan (group 2). Clinical data, pulmonary artery pressures, gated blood pool ejection fraction and histomorphometry of endomyocardial biopsies were similar in both groups. During a follow-up of 21 +/- 12 months there were two cardiac deaths in group 1 and 10 deaths in group 2 (P = 0.12). The 2-year survival rate was 81% and 59%, respectively. During follow-up, there was no significant change in haemodynamic parameters in either group, but there was a slight improvement in functional NYHA class in group 1 (P < 0.05). No association was found between the presence of myocardial enterovirus infection, determined in 17 patients by in situ hybridization and the antimyosin scan (P = 0.5 g). Myocardial antimyosin uptake was found in a high percentage of patients with IDC, indicating ongoing myocyte damage. This finding was not related to any clinical, haemodynamic, morphological parameter, or enterovirus infection. Myocyte damage is a distinct feature in a subgroup of patients with IDC unrelated to any known causes of myocellular destruction. This subgroup showed a trend towards a more favourable clinical outcome.

Many physicians assume that a reliable diagnosis of idiopathic dilated cardiomyopathy can be made by noninvasive methods, mainly echocardiography. On the other hand, use of endomyocardial biopsy in those patients who have undergone left heart catheterization and who demonstrate left ventricular dysfunction of unknown origin is increasing. Therefore the purpose of this study was to investigate the yield of that diagnostic strategy in patients with the tentative diagnosis of idiopathic dilated cardiomyopathy. Between 1980 and 1988, 3.2% of our 15,442 patients were diagnosed as having idiopathic dilated cardiomyopathy on the basis of left heart catheterizations and coronary angiograms. Idiopathic dilated cardiomyopathy was diagnosed in 444 patients on the basis of clinical data and results of noninvasive tests before catheterization, but in only 295 of these cases was the diagnosis confirmed by means of coronary angiography and left heart catheterization (predictive value of noninvasive tests is 66%). The remaining 34% of patients demonstrated extensive coronary artery disease (13%), significant valvular heart disease (11%), and other or no heart disease (10%). The diagnostic sensitivity of noninvasive tools (patient history, ECG, stress test, echocardiography) was only 59%. Left heart catheterization can easily be combined with endomyocardial biopsy. With the use of histologic techniques, specific heart muscle diseases were detectable in 3.5% of 209 patients, but in only 1% could therapeutic consequences be determined. Thus coronary angiography and left heart catheterization are mandatory for the correct diagnosis of idiopathic dilated cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

A 64-year-old female patient with a prosthetic mitral valve suffered from recurrent typical angina and dyspnea. Left heart catheterization excluded a dysfunction of the prosthesis and coronary artery disease (CAD). A stress thallium scan demonstrated an ischemic reaction. An antimyosin scintigram was positive, indicating myocytal membrane disruption. Serological tests were suspicious for systemic lupus erythematosus (SLE). Therefore, an endomyocardial biopsy (EMB) was performed and a severe alteration of an intramyocardial artery, comparable with chronic SLE, was diagnosed. EMB is a useful diagnostic tool in patients with typical chest pain, positive thallium and anti-myosin scintigrams, however exclusion of CAD.

The etiology of idiopathic dilated cardiomyopathy (DCM) is yet unknown; this study aimed at further differentiation of the disease by means of enzyme histochemistry. Endomyocardial biopsies from the left ventricle of 40 DCM patients and 5 control specimens had enzymes examined histochemically and semiquantitatively and analyzed according to staining intensities of nicotinamide adenine dinucleotide tetrazolium reductase (NADH-TR), succinate dehydrogenase, cytochrome c oxidase, lactate dehydrogenase and acid phosphatase (aPh). In DCM, the NADH-TR activity was elevated as compared to controls, indicating impaired mitochondrial oxidative phosphorylation. However, a concrete relation of enzyme histochemical intensity to anamnestic, hemodynamic or histomorphometric data could not be determined, except for the fact that the intensity of the lysosomal enzyme aPh was elevated in DCM patients with a relatively high left ventricular ejection fraction. The results demonstrate an interindependence of structural, hemodynamic and historical parameters as well as enzyme concentrations in DCM. Thus, a pathological change in the enzyme concentrations tested here cannot be responsible for the functional myocardial impairment in DCM.

In isolated papillary muscles of cats the changes in Ca inward current and isometric contractile force following a decrease of extracellular pH from 7.4 to 5.5 were studied. The Ca current was analyzed (a) by measuring the upstroke velocity of Ca-mediated action potentials and (b) in voltage clamp experiments using the double sucrose gap technique. 1. At a pH of 5.5 the upstroke velocity of the Ca-mediated action potential decreased to 65% of the control, while overshoot and action potential duration remained almost unchanged. Furthermore, the relative refractory period was prolonged and in some cases, a "Wenckebach-like" phenomenon occurred. In voltage clamp experiments, the slow inward current was found to be diminished to 50-60% of the initial control value and over a broad voltage range the current voltage relationship curve was shifted to weaker currents. Acidosis did not influence the steady state inactivation but altered the kinetics of inactivation of the slow inward current and induced an increase of tauinactivation and taurecovery. This indicates that acidosis exerts a complex effect on the slow membrane channel. 2. The normal response of the Ca current towards variations of the extracellular Ca concentration (0.5-4 mM) or towards the addition of the beta-stimulating compound isoproterenol (2 mg/l) was not altered by the lowered extracellular pH. 3. In the acid medium, isometric contractile force declined to 40% of the control value within 25 min and, thus, reacted stronger than the Ca current. This indicates that those forms of acidosis used in the present experiments caused their negative inotropic effect not exclusively via a depression of the Ca current. Rather an additional intracellular effect has to be assumed which finally leads to a reduced activity of the contractile system. 4. At pH 5.5 excess Ca (4 mM) induced the same quantitative response of the contractile system as obtained at normal pH. In contrast, the positive-inotropic effect of 2 mg/l isoproterenol was more pronounced, whilst the sensitivity of the Ca inward current towards this beta-stimulating compound remained unchanged.

Objective: To assess the potential for recovery of impaired microvascular function in collateral dependent myocardium after recanalisation of a chronic total coronary occlusion and the determinants of this recovery. Patients and design: 120 patients underwent a successful recanalisation of a chronic total coronary occlusion (duration > 2 weeks) and a follow up angiography after a mean (SD) of 5.0 (1.2) months. The coronary flow velocity reserve (CFVR) and the fractional flow reserve were measured after recanalisation and at follow up. Global and regional left ventricular (LV) function were analysed by quantitative angiography. Results: Microvascular dysfunction, defined by a CFVR C 2.0 and a fractional flow reserve ⩾ 0.75, was observed in 55 (46%) patients after recanalisation. Microvascular function improved during follow up in 24 (20%). The CFVR increased during follow up from 2.01 (0.58) to 2.50 (0.79) (p < 0.001), due to a decrease in basal average peak velocity from 30.7 (14.9) cm/s to 25.5 (13.3) cm/s (p = 0.001). Improved microvascular function was associated with an improved regional LV function, shown by a correlation between increased wall motion severity index and increased CFVR (r = 0.38, p = 0.003). The major determinant of microvascular dysfunction at baseline was the presence of diabetes mellitus (odds ratio 4.3, 95% confidence interval 1.8 to 10.2), which remained so at follow up (odds ratio 4.1, 95% confidence interval 1.3 to 13.4). Improvement of LV function was not impaired by the presence of microvascular dysfunction after recanalisation. Conclusions: The frequently observed microvascular dysfunction after recanalisation of a chronic total coronary occlusion is a transient phenomenon in most patients and is influenced by the presence of diabetes mellitus. It does not impede the recovery of LV function. Improved regional LV function is associated with improved microvoscular function. [ABSTRACT FROM AUTHOR]