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Among the cardiomyopathies,--dilated cardiomyopathy (dcm), hypertrophic cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy--, dcm is the most frequent entity. Its prevalence in the United States amounts to 36 cases per 100,000 inhabitants, men being almost 3-fold more involved than women. The etiology of dcm is very heterogenous; 50% of the cases are due to idiopathic dcm whereas the other half comprises a broad spectrum of various etiologies such as myocarditis, ischemic heart disease, peripartal cardiomyopathy, hypertension, HIV infection, toxic cardiomyopathy and others. In 20 to 30% of the cases of idiopathic dcm a genetic transmission of the disease has been found. Another 20 to 30% of idiopathic dcm are associated with inflammatory and immunological phenomena. Infectious myocarditis with enteroviruses, especially with coxsackie-virus type B has been suggested to be an important trigger for an immune-mediated dcm. In both, familiar dcm and infection with coxsackie-virus B, an impairment of constituents of the myocardial cytoskeleton has been shown. This is regarded as a possible pathogenetic mechanism in the development of dcm.

Endomyocardial biopsy in cardiac transplantation is still the most exact test (gold standard) to confirm or exclude a suspected rejection. Up to now, all available noninvasive tests suffer from a low sensitivity and specificity. For a further reduction of biopsies early available noninvasive methods are desirable. In the data presented a comparison between histological findings and heart volume measurements is shown in 40 patients (112 histological findings) after orthotopic cardiac transplantation. In 46 cases with no evidence of histological rejection the echocardiographically or radiologically determined heart volume was 869 +/- 142 ml/1.73 m2 body surface area, compared to 1026 +/- 178 ml/1.73 m2 in 29 cases with mild cardiac rejection. In 37 cases with a moderate or severe rejection heart volume as 1094 +/- 181 ml/1.73 m2. The diagnosis of a moderate or severe rejection by biopsy is combined with a heart volume above 950 ml/1.73 m2 with a sensitivity of 78% and a specificity of 73%. Intramyocardial edema as well as an increase in right and left ventricular volumes due to heart failure may be the causes for heart volume increase in rejection. Thus, heart volume measurement which can be performed easily during routine echocardiography gives additional information about whether a rejection has to be assumed or can be excluded. Today, sensitivity and specificity of the test does not allow a reduction of biopsy frequency. Further investigations are necessary to analyze the course of heart volume changes during an episode of rejection.

Indium-111-labeled Fab fragment imaging using a murine antimyosin monoclonal antibody (Myoscint, Centocor, Leiden) was evaluated for efficacy in detecting cardiac allograft rejection. Diagnosis of rejection was made by endomyocardial biopsy with four to five samples taken for each procedure. Eighty-one studies were performed in 25 patients (21 men, four women, mean age 50 +/- 9 years) from 2 weeks to 45 months after cardiac transplantation. 0.5 mg of the monoclonal antibody labeled with 60 MBq Indium-111 (Antimyosin-Fab-DTPA) was administered i.v. Planar scintigraphic images were obtained in LAO 45 and anterior projections as well as "half-body-scintigrams" 48 h after injection. Using the regions-of-interest-(ROI)technique the relative uptake over the lung and the heart was determined and an index of In-111 uptake was calculated. A heart-to-lung ratio of 1.5 or higher was considered indicative for moderate to severe rejection. Specificity was 86% (nine false-positive In-111 studies in 68 negative biopsy studies), sensitivity was 85% (two false-negative In-111 studies in 13 pathological biopsy studies). It is concluded that the In-111 method has a high sensitivity and specificity in detecting heart transplant rejection and may be useful in the monitoring of patients in the chronic phase after heart transplantation. The 48-h delay in establishing the diagnosis limits the applicability in acute severe rejection.

Five patients with hypertrophic cardiomyopathy developed left-ventricular dilatation and congestive heart failure during an observation period of 16-29 years. In one patient cardiac transplantation had to be performed. The initial predominant symptoms of outflow-tract obstruction and diastolic dysfunction developed into progressive left-ventricular systolic failure. The question of whether this is a well-defined subgroup of patients with hypertrophic cardiomyopathy, or whether hypertrophic cardiomyopathy turns into a phase of left-ventricular dilatation and failure after some years remains to be elucidated by long-term studies.

A case is reported of right ventricular outflow obstruction caused by hypertrophic cardiomyopathy. The pressure gradient between the inflow tract and the outflow tract of the right ventricle was 84 mm Hg. Resection of the hypertrophic muscle bundles practically eliminated the obstruction leaving only an insignificant subvalvular gradient of 2 mm Hg. Histologic examination revealed cardiac muscle cell hypertrophy and disorganization.

Left ventricular function was investigated by radionuclide ventriculography in 13 patients (11 male, two female) with hypertrophic cardiomyopathy, aged from 22-57 years (mean 45.5 years) at rest and during exercise. Ten patients had hypertrophic obstructive cardiomyopathy with maximal left ventricular outflow tract gradients of 64-290 mmHg (mean 147 mmHg). Left ventricular enddiastolic pressure of all patients ranged from 8-35 mmHg (mean 21 mmHg). Radionuclide ventriculography was performed without therapy, after acute application of a single oral dose of gallopamil (50 mg), and after longterm treatment for 3 weeks (50 mg tid). Ejection fraction at rest after single dose increased from 69.2% to 72.9% (p less than 0.02), peak ejection rate (PER) increased from 333.5 to 362.0/s (p less than 0.01) and peak filling rate (PFR) from 284.5 to 316.5/s (p less than 0.02). Under exercise single dose as well as longterm treatment led to a slight but significant shift in the ratio of PFR/PER (from 1.02 to 1.12 after single dose [p less than 0.04], and to 1.18 with longterm treatment [p less than 0.03]). There was no correlation between the individual response to gallopamil treatment and histopathological parameters such as hypertrophy or fibrosis. These data demonstrate that gallopamil in patients with hypertrophic cardiomyopathy leads to an improvement mainly in left ventricular diastolic function which appears to be most effective under exercise.

Eleven patients with hypertrophic cardiomyopathy were investigated by repeated radionuclide ventriculography. Nine of them were studied for the first time while under long-term treatment for 14 to 84 months. In all eleven patients radionuclide ventriculography was performed after a withdraw of verapamil for at least 14 days or before the onset of therapy respectively (control period). A third investigation was carried out 60 to 90 min after acute administration of 90 mg oral verapamil. A last radionuclide ventriculography was performed following 2 weeks of therapy with 480 mg oral verapamil. After acute administration heart rate significantly increased from 69 +/- 10 to 80 +/- 15/min. EDV was in the normal range. Left ventricular global ejection parameters showed no significant changes except for minimal decrease in ejection time from 309 +/- 29 to 278 +/- 50 ms after acute verapamil administration. The sectorial ejection fraction improved in apical sectors in relation to the basal one, while the global EF remained constant. The ventricular global peak filling rate increased significantly from 283 +/- 61 to 325 +/- 64%/EDV/s after acute administration of verapamil and the sectorial peak filling rate increased in apical sectors compared to basal sectors following acute administration as well as long-term therapy. After withdrawal of verapamil, six out of 11 patients showed a homogeneous left ventricular delay of contraction by means of the Fourier phases which were normalized under short- and long-term verapamil treatment. In conclusion, verapamil caused a marked improvement of the left ventricular contraction delay without significant changes in global systolic function.