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Beta-blocker therapy has been shown to improve cardiac function and prognosis in patients with idiopathic dilated cardiomyopathy (DCM). However, whether beta-blockers reduce severe ventricular arrhythmias and sudden cardiac death has not been clarified. The present study was designed to investigate the effects of beta-blockers on non-sustained ventricular tachycardia (VT) and sudden cardiac death in patients with DCM. Sixty-five patients with DCM treated with diuretics, digitalis and angiotensin-converting enzyme inhibitors were assigned to receive beta-blockers (n = 33) or not (n = 32). Mean follow-up was 53+/-30 months. The echocardiographic indices of cardiac function, the incidence of non-sustained VT on Holter monitoring electrocardiograms, and sudden cardiac death rate were compared between the 2 groups. Comparable improvement in cardiac function on echocardiograms was found in the 2 treatment groups. The patient group treated with beta-blockers showed a significant reduction in the prevalence of VT (from 43 to 15%, p<0.05) and the development of new episodes of VT (5 vs. 16%) compared to the group without beta-blockers. The sudden cardiac death rate did not differ between the 2 groups. The results of the present study suggest that beta-blockers are effective in reducing severe ventricular arrhythmias in patients with DCM.

Dilated cardiomyopathy (DCM) results in part from genetic disorders. Recently, missense mutations of the cardiac actin gene have been reported to cause DCM. We studied 136 Japanese DCM cases to elucidate how frequently the gene mutations are involved in its pathogenesis. Genomic DNA samples were obtained from 136 DCM cases (107 males, 29 females), containing 30 familial DCM (5 confirmed and 25 suspected). All six exons of the cardiac actin gene were analyzed by polymerase chain reaction, single-strand conformation polymorphism, and sequencing. We detected no mutations of the disease causation previously reported (G867A or A1014G) but two silent mutations (G979C and C1018T) in exon 6 and one point mutation (T1080A) in the 3'-untranslated region. As a result of screening 128 healthy subjects, these novel silent mutations were found to be mere genetic polymorphisms, not responsible for the disease. Although some genetic polymorphisms exist in the cardiac actin gene, mutations of the gene are rarely responsible for DCM, at least in the Japanese patients., (Copyright 1999 Wiley-Liss, Inc.)

Some recent trials have shown that angiotensin-converting enzyme (ACE) inhibitors and/or beta blockers can improve left ventricular (LV) function and decrease LV mass in patients with idiopathic dilated cardiomyopathy (IDC). We assessed the prevalence and predictors of patients with IDC that showed marked reverse remodeling (a decrease in LV end-diastolic dimension > or = 5 mm to a final LV end-diastolic dimension < or = 55 mm and an increase in percent LV fractional shortening > or = 5% to a final percent fractional shortening of > or = 25% and a decrease in LV mass > or = 10%) after 2 years of intensive therapy with ACE inhibitors and/or beta blockers. In 78 patients with IDC (mean age 51 +/- 14 years), the clinical, echocardiographic, hemodynamic, laboratory, and endomyocardial biopsy data were evaluated at diagnosis and serial echocardiography was performed for 2 years. After 2 years of therapy, 20 of 78 patients (26%) showed marked reverse remodeling. Multivariate analysis revealed that higher systolic blood pressure (135 +/- 17 vs 120 +/- 16 mm Hg, p <0.001) and lower pulmonary arterial wedge pressure (7 +/- 3 vs 12 +/- 8 mm Hg, p <0.01) at diagnosis were independent predictors of reverse remodeling. Then, we further analyzed the prognosis of these patients for a mean of 50 +/- 32 months; 5-year survival (p <0.02) and event-free rates (p = 0.001) were better in patients with reverse remodeling than in patients without reverse remodeling.

We report a family with Becker muscular dystrophy (BMD) presenting with cardiac involvement. The proband was a 41-year-old Japanese man who was hospitalized with exertional dyspnea and muscle weakness. Cardiac examination showed findings consistent with dilated cardiomyopathy. Dystrophin immunohistochemical analysis showed a discontinuous patchy staining pattern in cardiac and skeletal muscles biopsied from the proband. His brothers had high creatine kinase (CK) activity and abnormal electrocardiogram. Dystrophin gene analysis revealed that the proband and his brothers had G-to-T transversion at the terminal nucleotide of exon13. We conclude that the mutated dystrophin gene may cause cardiac involvement as a symptom precedent to skeletal muscle involvement.

To investigate the prevalence, clinical characteristics, and prognosis of familial cases of idiopathic dilated cardiomyopathy (IDC), family screenings were carried out in 117 IDC patients and their relatives. Familial occurrence was suspected in 29 families (25%). Ten families (9%) with 24 patients were confirmed to be familial, but the other 19 families (16%) remained suspected. The age at the time of diagnosis was lower and the cardiac symptoms tended to be milder in the familial group than in the non-familial group, but there were no differences in other clinical parameters. There was also no difference in the survival rate. However, when only NYHA class III and IV patients were selected, the 1-year and 5-year survival rates were lower in the familial group than in the non-familial group. Congestive heart failure was the most common cause of death in the non-familial group, while sudden death was the most common cause of death in the familial group. Among familial IDC patients who were deceased, the left ventricular end-diastolic pressure was higher and the cardiac index was lower at the time of diagnosis than those in patients who were still alive. We conclude that, since the prognosis of familial IDC patients is poor once their cardiac symptoms become severe, early diagnosis and treatment are extremely important.

To determine the effect of recent advances in medical management on the survival of patients with dilated cardiomyopathy (DCM), 103 patients with DCM were studied. The subjects were divided into 3 groups based upon the time of initial medical treatment at our institute: Group I, between 1976 and 1981, 20 patients; Group II, between 1982 and 1985, 27 patients; and Group III, between 1986 and 1991, 56 patients. The clinical, Holter electrocardiographic and echocardiographic findings, the pharmacologic treatments used, and the clinical outcomes for the 3 groups of patients were compared. During the follow-up period, which averaged 27 months, 31 deaths related to cardiac disease occurred. The 4 year survival rate was 76% in Group III, 49% in Group II and 35% in Group I; the difference in survival rate between Groups I and III was significant (p < 0.01). At the initial evaluation, no differences were found among the 3 groups in the incidences of advanced heart failure (NYHA functional class III or IV), atrial fibrillation or complex ventricular arrhythmias. Neither diastolic blood pressure nor heart rate differed among the 3 groups, but Group III patients were older and had significantly higher systolic blood pressures than Group I patients (p < 0.05, for both comparisons). There were no differences among the 3 groups in % fractional shortening, left ventricular end-systolic wall stress or left ventricular wall thickness, but left ventricular dimensions were significantly smaller in Group III than in Group I (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The pathomorphologic features of hypertrophic cardiomyopathy simulating dilated cardiomyopathy in the late stage (HCM-DCM) were compared with those of ordinary hypertrophic cardiomyopathy (HCM). Seven autopsied hearts with HCM-DCM and 11 with HCM were assessed quantitatively using an image analyzer. Unlike HCM, significant left ventricular enlargement and wall thinning were observed in HCM-DCM, and the percentage areas of massive fibrosis and disarray were significantly greater. In HCM-DCM, the disarray was distributed diffusely, whereas massive fibrosis was distributed more intensively in the ventricular septum and anterior wall than in the lateral and posterior wall. Narrowing of intramyocardial small arteries was observed more frequently in HCM-DCM, especially in the ventricular septum and anterior wall, than in HCM. These results suggest that the enlargement and wall thinning of the left ventricle in HCM-DCM are attributable to non-uniform progression of massive fibrosis, which is closely related to small-arterial lesions.

Twenty-three patients with dilated cardiomyopathy (DCM) were treated with metoprolol and their clinical courses compared with those of 26 patients untreated with beta-blocking agents (non beta group). Of the 23 patients treated with metoprolol, 20 (beta group) were treated for 6 months or longer, while the remaining 3 patients were intolerant of the drug and suffered aggravation of heart failure. In the beta group, 2 deaths occurred, while of the remaining 18 patients 4 were considered clinically improved in NYHA class 6 or 12 months later, and none suffered clinical deterioration during the follow-up period. In the non-beta group, clinical improvement was found in 2 patients and deterioration of functional class in 10. Heart rate and pressure rate product were significantly decreased by 1 month after the treatment with metoprolol. At that time, blood pressures, systolic and diastolic left ventricular dimensions, indices of systolic function (% FS, mVcf) and exercise capacity had not changed, while cardiac output was decreased and systemic peripheral vascular resistance was significantly increased. In the beta group, significant improvements in left ventricular dimensions, systolic function and exercise tolerance were delayed and observed within 3 to 6 months during the follow-up period, while no such improvements occurred in patients of the non-beta group. During the follow-up period, 2 patients of the beta group and 10 patients of the non-beta group died. The survival curve for patients of the beta group, prepared using the Kaplan Meier's Method, was better than that for patients of the non-beta group. Metoprolol was therefore found to be useful for treatment of DCM.

To identify the evidence of presymptomatic manifestations of dilated cardiomyopathy (DCM), we studied 30 patients with latent DCM (mean 37 +/- 14 years) who satisfied the following criteria: 1) left ventricular (LV) systolic function was slightly reduced; 2) LV end-diastolic dimension (< 54 mm) and coronary arteries were normal. The incidence of ECG abnormalities was relatively high; nonspecific ST-T changes were the most common (90%). The incidence of grade 3 or 4 ventricular premature contractions according to Lown's classification on 24 hour ambulatory ECGs was 50%. Perfusion defects were observed in 83% on the thallium-201 images. Right ventricular biopsy showed that the interstitial fibrosis was milder (9 +/- 9%) in the study subjects than in 32 patients with DCM (17 +/- 8%) who were treated in our hospital, but there were no significant differences in the diameters of the myofibers (15 +/- 4 vs 17 +/- 4 microns) between the 2 groups. During the follow-up study, deterioration of LV dysfunction was observed in 3 patients. One patient died suddenly. These findings proved the importance of the early detection and characterization of latent state of DCM.

Twenty-two patients with dilated cardiomyopathy (DCM) were treated with metoprolol and their clinical courses were compared with those of 26 patients untreated with beta-blocking agents (non beta group). Of the 22 patients treated with metoprolol, 19 (beta group) were treated for a long period, 3 patients left the study within its first 6 months. Using the NYHA classification, 4 patients of the beta group were evaluated as having clinically improved, while none was aggravated, excluding 2 cases of death which occurred during the follow up period. In the non-beta group, clinical improvement was found for 2 patients and aggravation in functional class for 10. The left ventricular diameter was significantly decreased and parameters of systolic function and exercise tolerance were significantly improved in patients of the beta group, while no such improvements occurred in patients of the non-beta group. Twenty-four-hour ECG monitoring demonstrated a significant reduction in incidences of ventricular extrasystole in the beta group but not in those of the non-beta group. Improvement of arrhythmias, evaluated using Lown's grading system, was also identified more frequently in the beta group than in the non-beta group. During the follow-up period, 2 patients of the beta group and 10 patients of the non-beta group died. The survival curve for patients of the beta group prepared using the Caplan Meier Method was better than that for patients of the non-beta group. Metoprolol was therefore found to be useful for treatment of DCM.

The hearts of 28 necropsy cases with DCM and 10 control cases were analysed to elucidate the role of myocarditis and fibrosis in dilated cardiomyopathy (DCM). The extent of fibrosis and myocyte diameter were measured in the transverse sections of the left ventricle. The degree and pattern of fibrosis varied widely from case to case. The DCM cases were then classified into 3 groups: 1) Group Ia, 8 cases with mild diffuse fibrosis; 2) Group Ib, 9 cases with severe diffuse fibrosis and 3) Group II, 11 cases with segmental fibrosis. Myocardial fibrosis and hypertrophy were significantly more prominent in Groups Ib and II than in the control group (p less than 0.01), but no differences were observed between Group Ia and the control group. Thus, it is reasonable to attribute the chronic CHF and LV dilatation in Groups Ib and II to the extensive myocardial fibrosis. In contrast, it is not reasonable to attribute the chronic CHF and LV dilatation in Group Ia to myocardial fibrosis. Focal lymphoid cell infiltration was graded to assess inflammatory changes. Group II showed more prominent inflammatory changes than the other 2 groups (p less than 0.05). Thus, it is possible that myocarditis is an etiologic factor for DCM with a segmental pattern of fibrosis.

We report 5 patients, who had no cardiac abnormalities at their initial evaluation but progressed to dilated cardiomyopathy (DCM) during a mean follow-up period of 8.2 years. Their echocardiograms revealed increases in left ventricular (LV) end-diastolic dimensions, deterioration of LV contractions, and reduction in the LV wall thickness. Electrocardiographic changes were developed of rhythm disturbances, intensified ST-segment and T-wave changes, and the prolonged QRS durations. These findings, especially those of electrocardiography, seemed to be important for an early detection and characterization of DCM.

To investigate the causative factors of dilated cardiomyopathy (DCM), 29 DCM patients were echocardiographically and histopathologically compared with 17 patients with specific heart muscle diseases mimicking DCM. These consisted of 6 cases of myocarditis and 11 of alcoholic heart muscle disease. Myocarditis patients had less dilation of the left ventricle, more marked segmental wall motion abnormality on admission and more extensive myocardial fibrosis than patients with alcoholic heart muscle disease and DCM. Four myocarditis patients died of congestive heart failure before showing a marked dilatation of the left ventricle. The alcoholic heart muscle disease patients revealed diffuse wall motion abnormality on admission. Out of these 8 patients who had abstained showed amelioration. However, in 3 who had not abstained, both wall motion abnormality and dilatation of the left ventricle markedly progressed and 2 died of congestive heart failure. Although the DCM patients as a group showed deterioration throughout the follow-up period, individual patients revealed a variety of echocardiographic and pathological findings, which led to the regrouping of 29 patients with DCM into 2 subgroups. One group had characteristic features similar to these of patients with myocarditis, and the other had characteristics similar to these of patients with alcoholic heart muscle disease. These findings suggested that different causative factors might coexist in DCM.

Regional wall motion abnormality in 28 patients with dilated cardiomyopathy (DCM) was evaluated by M-mode and two-dimensional echocardiography (2DE) before and during dobutamine administration. In 6 autopsied hearts obtained from deceased cases during the follow up period, the relationship between regional myocardial fibrosis and wall motion abnormality was investigated. Left ventricular wall was divided into 11 segments by 2DE. The wall motion of each segment was evaluated and scored into 4 degrees (0: normokinesis, 1: hypokinesis, 2: severe hypokinesis, 3: akinesis or dyskinesis), and the total sum of wall motion abnormality scores in 11 segments (TWS) for each case was calculated. Wall motion abnormality was observed in 231 of the total 308 segments, and in 121 of the 231 segments, the severity of the wall motion abnormality was reduced by dobutamine administration. The rate of fibrosis was lower in segments with improved wall motion abnormality than in those without improvement. Sixteen deteriorated or deceased cases during the follow up period (D group) had larger TWS than 12 non-deteriorated cases (ND group), but percent fractional shortening (%FS) obtained by M-mode echocardiography was not significantly different between the 2 groups. The changes in %FS and TWS by dobutamine (delta%FS, %delta TWS) were significantly larger in ND group than in D group. The cases with %delta TWS greater than or equal to 45% were all in the ND group, and all deceased cases had the value of %delta TWS less than or equal to 36%. Thus, the observation of regional wall motion by dobutamine loading echocardiography was useful for evaluating regional histopathological findings and prognosis in patients with DCM.

In order to investigate the usefulness of antiarrhythmic drugs in patients with dilated cardiomyopathy (DCM), 42 patients with DCM were studied using 24 h ambulatory ECG monitoring, echocardiography and right ventricular endomyocardial biopsy. All 42 patients had ventricular arrhythmias with a Lown's classification of grade II or greater (grade IVb, 25; IVa, 7; III, 7; II, 3). The patients with grade IV arrhythmias tended to have greater dilating of the left ventricle and more pronounced interstitial myocardial fibrosis than patients with lower grades. Following procainamide and/or disopyramide treatment the severity of the ventricular arrhythmias improved in 12 (29%) of the 42 patients, did not change in 27 patients (64%), and deteriorated in 3 patients (7%). Treatment with aprindine or mexiletine was effective in 7 (50%) of the 14 patients who did not respond to procainamide and/or disopyramide. Although there were no significant differences in left ventricular dimension and contractility between patients in each group who did and did not respond to antiarrhythmic treatment, those who did respond had less interstitial myocardial fibrosis. Thus, in the procainamide and/or disopyramide treated group the percent interstitial fibrosis in responding vs nonresponding patients was 10.3 +/- 4.1% vs 18.7 +/- 8.3% (p less than 0.05) respectively, while in the group treated with aprindine or mexiletine these figures were 13.0 +/- 3.2% vs 26.1 +/- 7.9% (p less than 0.02), respectively. In conclusion, the effect of antiarrhythmic drugs in DCM was dependent on the severity of the pathological changes in the myocardium, and antiarrhythmic drugs should be appropriately used for the management of ventricular arrhythmias in DCM.

Two cases with mitral valve prolapse (MVP), without any other cardiac abnormalities at the initial evaluation, developed the clinical features mimic to dilated cardiomyopathy (DCM) during follow-up period. Case 1. A 40-year-old man visited our hospital in May 1982 to evaluate a heart murmur. A standard 12-lead electrocardiogram (ECG) showed an abnormal Q wave in lead III. Echocardiography revealed MVP, but neither dilatation nor wall motion abnormality of the left ventricle (LV) were observed. Thallium-201 scintigraphy revealed an abnormal thallium uptake at the apex and inferior wall. He had no episode of acute myocardial infarction or myocarditis, but complete right bundle branch block developed, thus, he was hospitalized in October 1984. He had no coronary artery lesions, and had only mild mitral regurgitation on left ventriculography. The motion of the interventricular septum and apex was reduced on echocardiogram and a persistent perfusion defect was observed at the inferior wall and the interventricular septum on Tl-201 scintigrams. In December 1985, he experienced an Adams-Stokes attack due to complete atrioventricular block. Echocardiographically, the left ventricle enlarged, and the wall motion abnormalities and a perfusion defect on Tl-201 scintigrams were relatively severe. Case 2. A 46-year-old woman occasionally experienced palpitation of short duration and chest oppression since 1977. She was admitted to our hospital because of cardiac symptoms in 1982. A heart murmur of Levine II was heard and a standard 12-lead ECG showed single supraventricular extrasystole and T wave inversion in lead III and aVF. Echocardiography revealed MVP and mild mitral regurgitation, but neither dilatation nor wall motion abnormality of the LV was observed. During 6-year follow-up period, permanent atrial fibrillation developed and LV developed dilatation and wall motion abnormalities progressed. Thus, during follow-up periods, DCM-like features developed in two cases who had had MVP as a sole echocardiographic abnormality with systolic murmur and non-specific ECG changes. We consider that these two may be important cases who may show a relation between cardiomyopathic process and MVP.

Although the prognosis of dilated cardiomyopathy (DCM) is poor, some patients occasionally follow favorable clinical courses and have significant improvement in cardiac function. To elucidate the mechanism of such improvement, we compared the clinical and pathological findings of 54 cases with DCM, including 12 cases with significant improvement (Dd less than 55 mm, %FS greater than 22%) during two years' follow-up (improved group), 26 without significant improvement (unimproved group), and 16 who died within two years (decreased group). Percent fractional shortening (%FS) in the deceased group was less than that in the unimproved group (12.4 +/- 3.9 vs 17.2 +/- 6.2, p less than 0.01). Pulmonary capillary pressure (PC) and % fibrosis in the deceased group were greater than those in the unimproved group [(22.7 +/- 9.5 vs 11.4 +/- 4.2 mmHg, p less than 0.001), (21.7 +/- 9.9 vs 13.4 +/- 3.6, p less than 0.01)], respectively. Although Dd, Ds, %FS, end-diastolic wall thickness (Thd), and PC in the improved group were not different from those in the unimproved group. End-systolic wall stress (WSes) in the improved group was greater than that in the unimproved group (376 +/- 73 vs 319 +/- 60 g/cm2, p less than 0.02), but % fibrosis was less in the improved group (7.6 +/- 3.4 vs 13.4 +/- 3.6, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate the clinical role of afterload in progression of dilated cardiomyopathy (DCM), a loading examination (study 1) and a follow-up study (study 2) were carried out, using echocardiography, and analysed with Force-Velocity relation (FVR). FVR was defined as the relation between end-systolic wall stress (WSes) and mean circumferential fiber shortening velocity (mVcf). In study 1, the cardiac responses to angiotensin II loading in 30 cases with DCM (17 cases with presumed causes, and 13 without) were observed. These cardiac responses could be described by a hyperbola (Y = 197/(X + 9) + 0.04, r = 0.63) on the graph of FVR, and each response also seemed to fit the hyperbola (Y = a/(X + 9) + 0.04). This "a" value differed according to the presumed causes, and had an inverse correlation with % fibrosis in the biopsied cardiac muscle (Y = 0.86 + 29.9, r = -0.64, p less than 0.02). In study 2, during a mean clinical course of 3.7 years, the cardiac function (mVcf) in 19 out of 25 cases with DCM changed inversely with the changes of WSes on FVR. The "a" value calculated by the same method as study 1 did not differ before and after the follow-up. It did, however, vary according to the clinical outcome. These results suggest that afterload plays an important role in progression of DCM, and that an evaluation of cardiac function employing FVR may be helpful for assessing the myocardial damage, causative factors, and the prognosis of DCM.

The relationship between left ventricular thrombus and left ventricular dynamics in dilated cardiomyopathy (DCM) was studied by echocardiography and postmortem examination. The subjects were 57 patients with DCM, 40 were survival patients examined by echocardiography and 17 were autopsy patients. Systemic or pulmonary embolism occurred in 10 of 57 patients, 4 of 40 survival patients and 6 of 17 autopsy patients. Intracardiac thrombus was detected in 11 of 40 survival patients and was found in 8 of 17 autopsy patients. Left ventricular segmental wall motion abnormalities were observed in all 40 patients examined by two-dimensional echocardiography and apical dyskinesis or akinesis was observed more frequently in patients with left ventricular thrombus than in patients without left ventricular thrombus. Of 33 patients examined by pulsed Doppler echocardiography, Doppler ejection flow signals in the apical long axis view were recorded in 9% at the apex, in 17% at the middle portion and in 57% at the portion near the interventricular septal center. The signals at the portion near the interventricular septal center were recorded in only 2 patients with left ventricular thrombus but in 66% of patients without left ventricular thrombus. Systemic or pulmonary embolism and intracardiac thrombus occurred less frequently in patients treated with warfarin than in patients without warfarin. These results indicate that endomyocardial and blood flow disorders of the left ventricle play important roles in the occurrence of left ventricular thrombus and that anticoagulant therapy is useful for the prevention of systemic or pulmonary embolism and cardiac thrombus.

A 40-year-old man was admitted to our hospital in May 1982 for evaluation of a heart murmur. A standard 12-lead electrocardiogram (ECG) showed an abnormal Q wave in lead III. Echocardiography revealed prolapse of the anterior mitral valve leaflet (MVP), but neither dilatation nor wall motion abnormalities of the left ventricle (LV) were observed. Thallium-201 scintigraphy revealed an abnormal thallium uptake at the apex and inferior wall. He had no episode of acute myocardial infarction or myocarditis, but complete right bundle branch block suddenly appeared, and he was hospitalized in October 1984. He had no coronary artery lesions, and only mild mitral regurgitation on left ventriculography. The motion of the interventricular septum and apex was reduced on echocardiography and a persistent perfusion defect was observed at the inferior wall and the interventricular septum on T1-201 scintigraphy. In December 1985, he experienced an Adams-Stokes attack due to complete atrioventricular block. Echocardiographically, the left ventricle became enlarged and the wall motion abnormality and a perfusion defect on T1-201 scintigrams were of relatively severe degree. Thus, left ventricular dilatation and wall motion abnormality may progress in some cases of MVP as it did in this one. We consider this case a very interesting one in speculating on the relationship between MVP and DCM.

To investigate left ventricular function and the prognosis of patients with dilated cardiomyopathy (DCM), regional wall motion of the left ventricle of 38 patients with DCM was observed before and during dobutamine infusion (8 micrograms/kg X min) by two-dimensional echocardiography (2DE). The left ventricle was divided into 11 segments and the severity of wall motion abnormality (WMA) was classified into 4 grades, i.e. akinesis or dyskinesis (A), severe hypokinesis (SH), hypokinesis (H) and normokinesis (N), and numerical scores were assigned to each grade of WMA as follow; A: 3, SH: 2, H: 1, and N: 0. In the 38 patients with DCM, the number of segments with WMA was 8.3 +/- 2.9 (mean +/- SD). Among 418 segments in the 38 patients, we observed A in 71 segments, SH in 104 segments, H in 140 segments, and N in 103 segments. The WMA was not uniform in the left ventricle, and severe WMA was observed in the apex (WMA score: 2.0 +/- 1.0), while the grades of WMA in the lateral and posterior walls were mild (WMA score: 0.8 +/- 1.1) compared with those of other segments. The total sums of the WMA scores in 11 segments for each patient (TWMAS) were significantly greater in patients with severe heart failure (New York Heart Association [NYHA] functional class III or IV) than in patients with mild heart failure (NYHA class I or II) (22.0 +/- 5.2 and 9.9 +/- 4.9, p less than 0.001). TWMAS correlated with the cardiac index (CI) (r = -0.58, p less than 0.005) and pulmonary capillary pressure (PCP) (r = 0.68, p less than 0.001). In 242 segments of 22 patients, whose regional wall motion was observed before and during dobutamine administration, wall motion was improved by one grade in 82 of 170 segments with WMA before dobutamine infusion; i.e. regional wall motion changed from A to SH in six segments, from SH to H in 31 segments, and from H to N in 45 segments with dobutamine administration. According to the change in grade of TWMAS induced by dobutamine administration, 22 patients with DCM were classified into two groups: a good response group (% change of TWMAS greater than or equal to 40%), and a poor response group (% change of TWMAS less than 40%). The poor response group had ventricular tachycardia more frequently, more severe heart failure, lower CI and higher PCP than the good response group.(ABSTRACT TRUNCATED AT 400 WORDS)

A two and a half year follow-up study of segmental left ventricular wall motion was performed by two-dimensional echocardiography for 26 patients with dilated cardiomyopathy (DCM). Segmental analysis of left ventricular wall motion abnormalities (WMA) was performed using 11 segments obtained by short- and long-axis views of the left ventricle. Wall motion in each segment was classified and assigned a numerical score as normal (0), hypokinetic (1), severely hypokinetic (2), and akinetic or dyskinetic (3). Based on this categorization, a wall motion abnormality index (WMAI) was derived as an overall assessment of left ventricular asynergy. The intersegmental standard deviation of the wall motion abnormality score was used as an index of left ventricular asynergy (non-uniformity index: NUI). During the follow-up period, the wall motion abnormality index increased in all of the 26 patients (from 1.23 to 1.82, p less than 0.001), but the non-uniformity index did not change (from 0.72 to 0.73). When comparing the non-uniformity index among three groups classified according to the grade of wall motion abnormality, both at the initial and during follow-up studies, the moderate wall motion abnormality group (1.0 less than or equal to WMAI less than 2.0) had larger non-uniformity indexes (0.83, 0.84) than the other groups, and the severe non-uniformity index (greater than or equal to 0.9) was observed solely in the moderate group. In the follow-up study, these 26 patients were categorized in two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The present study clarified the relationship between wall motion and myocardial flow in dilated cardiomyopathy (DCM). Two-dimensional echocardiography (2-DE) was performed in 14 patients before and after dobutamine (DOB) drip infusion (8 micrograms/kg/min). Thallium-201 emission computed tomography (ECT) was performed after dobutamine infusion and three hours thereafter. The left ventricle was divided into nine segments. In each segment, the degrees of defects were scored from 0 (normal) to 3 (complete defect), and the severity of wall motion abnormalities was scored from 0 (normal) to 3 (akinesis) by visual inspection. 1. Perfusion defects on ECT images were observed during dobutamine infusion in all patients. Redistribution was observed in nine of 14 (64%) patients. 2. During infusion, 38 (81%) of 47 segments without defects showed normal wall motion, but 44 (86%) of 51 segments with defects showed wall motion abnormalities. 3. Redistribution was observed in 18 (35%) of 51 segments, and these segments showed lower incidence of wall motion abnormalities as compared to the other segments (94% vs 45%, p less than 0.001). 4. After infusion, the segments with redistribution frequently showed improved wall motion as compared to the other segments (56% vs 18%, p less than 0.05). These results indicate that redistribution on the ECT image is observed in some patients with dilated cardiomyopathy after dobutamine administration. This may be due to the capacity of the drug to increase myocardial flow in proportion to the increase of oxygen demand.

Relationships between segmental left ventricular wall motion abnormalities and myocardial fibrosis at autopsy were examined in 12 patients who died of dilated cardiomyopathy. In each case, wall motion abnormalities were assessed by two-dimensional echocardiograms for 11 segments, and semiquantitatively evaluated as normokinesis (N) to hypokinesis (H), severe hypokinesis (SH) or akinesis (A). From the necropsy specimens, the myocardial fibrosis ratio was histologically quantitated using a point-counting method in each segment corresponding to the echocardiographic segment. Wall motion abnormalities and the fibrosis ratio correlated significantly in a total of 132 segments of the 12 patients, but there were some discordances. The cases were then categorized in uniform and non-uniform groups based on the patterns of myocardial fibrosis. Wall motion abnormalities correlated much better with the fibrosis ratio in a total of 44 segments among four cases with non-uniform fibrosis, whereas no significant correlation was found in a total of 88 segments in eight cases with uniform fibrosis. The latter group had more severe segmental wall motion abnormalities in the interventricular septum than in the left ventricular free wall; and in the apical portion rather than in the basal portion, although no significant difference was observed in the fibrosis ratio among these regions. Patients with non-uniform fibrosis had higher incidences of chest pain and sudden deaths and a significantly larger left ventricular end-diastolic dimension on M-mode echocardiogram as compared to those with uniform fibrosis. Pathologically, in the former group, the heart was heavier, the mean left ventricular fibrosis ratio was significantly higher, and there was a greater incidence of infiltration of the myocardium by mononuclear cells, but there was no difference in the mean left ventricular wall thickness. These results suggest that myocardial fibrosis mainly contributes to the wall motion abnormalities in cases with non-uniform fibrosis which may be caused by chronic myocarditis, but not in cases with uniform fibrosis. In the latter group, other factors such as reduced contractility of the myocardial cells or lack of a compensatory mechanism for wall stress seem to play important roles in causing left ventricular wall motion abnormalities.

In 18 patients with dilated cardiomyopathy (DCM), the effects of a new cardiotonic agent, TA-064, given in both consecutive and intermittent (3 days on, 11 days off) oral doses were studied for 3 months by echocardiography and endomyocardial biopsy. After 3 months of consecutive administration, 11 patients (61%) had improved symptomatically and the %FS increased (p less than 0.001) and LVDd decreased (p less than 0.05), but the other 7 patients had not improved. At the pretreatment state these 7 patients in whom TA-064 was not effective had smaller %FS (p less than 0.01) and larger LVDd (p less than 0.05) than the 11 patients in whom the drug was effective. The non-effective group also had more severe myocardial fibrosis (p less than 0.05) and cellular hypertrophy (p less than 0.01) than the effective group. After 3 months of intermittent administration in 10 patients in whom consecutive administration had been proved effective, 7 patients sustained symptomatic improvement and increased %FS (p less than 0.01), but the other 3 patients did not sustain the improvement. The latter group had smaller %FS, larger LVDd and more severe myocardial fibrosis than the former group at the pretreatment state. These results indicate that the effects of TA-064 are dependent on the severity of basal cardiac function and myocardial damage, and that in patients with milder DCM, the effects can be sustained by intermittent administration.

In some cases of dilated cardiomyopathy (DCM) perfusion defects are demonstrable by Tl-201 imaging at rest. This study clarified the mechanism by which the Tl scan can show myocardial perfusion defects in patients with DCM by means of Tl-201 single-photon emission computed tomography (ECT) utilizing a rotating gamma camera to assess three-dimensional T1 distribution in the myocardium. Thirteen patients with DCM were studied by conventional planar and ECT imaging, and the degree of defects was determined visually. Perfusion defects were observed in 11 of 13 cases (85%) by planar imaging and in all 13 (100%) by ECT imaging. The mean defect score was higher in ECT than in planar imaging (4.15 +/- 1.46 vs 2.23 +/- 1.46, p less than 0.025). A comparative study of defect scores and left ventricular ejection fractions (EF) using gated cardiac blood pool scans established a negative correlation on ECT imaging (r= -0.64), and no correlation on planar imaging (r= -0.38). There was no statistically significant correlation between perfusion defects on planar imaging and regional wall motion abnormalities as observed by two-dimensional echocardiography (2-DE). In contrast, most of the segments with severe defects (defect score greater than or equal to 2) on ECT images showed high grade wall motion abnormalities on 2-DE. Both perfusion defects and wall motion abnormalities in DCM may be closely related to the fibrosis or scar formation in the myocardium. These results indicated that T1-201 myocardial scintigraphy, especially ECT imaging, is of great value in the clinical assessment of patients with DCM.

Twenty-one members of a family were traced for three generations including the propositus, who had typical dilated cardiomyopathy (DCM)-like features. Clinical, radiological, electrocardiographic and echocardiographic examinations were performed for 13 of 16 still living. Five of 21 members died including three of sudden death. Among living 16 members, five had congestive heart failure, greater than grade III of the NYHA, and cardiomegaly on chest radiography in five. Left ventricular hypertrophy, abnormal Q waves, and ST-T changes were observed on electrocardiography in two, five and eight members, respectively. Echocardiography revealed asymmetric septal hypertrophy (ASH) in four, two of whom had systolic anterior motion (SAM) of the mitral valve. Two had features simulating DCM, and five had mitral valve prolapse. Among six patients with ASH or features simulating DCM, four had cardiac catheterization, coronary angiography and endomyocardial biopsy. None had significant coronary stenosis, but all had high left ventricular end-diastolic pressure (LVEDP) (23 +/- 7 mmHg). Endomyocardial biopsy showed moderate myocardial cellular hypertrophy, interstitial myocardial fibrosis, nuclear changes and myocardial disarrangement, with features characteristic of HCM. In this family with malignant HCM, patients had various clinical features including typical HCM, simulated DCM, DCM coexisted with mitral valve prolapse, and sudden death occurred frequently.

The purpose of this study was to elucidate the clinical features of right ventricular (RV) dysplasia, a recently described clinical entity characterized by RV myopathic changes and ventricular tachycardia of left bundle branch block morphology. Five cases were reported, in which the diagnosis was established according to the criteria of Marcus. Case 1, a 33-year-old man, was referred to us for evaluation of his paroxysmal ventricular tachycardia of five years duration. Case 2, a 38-year-old man, was admitted because of shock caused by ventricular tachycardia. In both cases, the QRS configurations during ventricular tachycardia were those of the left bundle branch block pattern, and electrocardiograms during sinus rhythm showed T wave inversions in the right precordial leads and late ventricular potentials. Two-dimensional echocardiography, radionuclide angiography and contrast angiography disclosed RV dilatation and dysfunction with normal left ventricular (LV) function. The biopsied myocardium from the right and left ventricles in Case 2 revealed myocytolysis, a paucity of myofibrils and proliferation of collagen fibers. Case 3, a 73-year-old woman began to experience exertional dyspnea since 16 years of age. Her treatment consisted of bed rest, diuretics and digitalis. In December 1983, her New York Heart Association functional class was III, and physical examinations disclosed a Levine III/VI systolic murmur suggestive of tricuspid regurgitation, jugular vein dilatation, hepatomegaly, and pretibial edema. Electrocardiogram showed atrial fibrillation, incomplete right bundle branch block and T wave inversions in the precordial leads. Chest radiograph revealed marked cardiomegaly (cardiothoracic ratio of 92%). Echocardiography, radionuclide angiography and contrast angiography revealed marked RV dilatation, depressed ejection fraction (RV end-diastolic volume index of 342 ml/m2, and RV ejection fraction of 28%). Case 4, a 20-year-old man, was admitted with a chief complaint of palpitation. Case 5, a 19-year-old man, was referred to us for the evaluation of asymptomatic cardiomegaly, and his cardiothoracic ratio was 54%. A 12-lead electrocardiogram showed right bundle branch block and T wave inversions in the right precordial leads. Ambulatory electrocardiography revealed frequent premature ventricular complexes of the left bundle branch block pattern. Echocardiography, radionuclide angiography, and contrast angiography disclosed RV dilatation and dysfunction in both cases, and mild LV dilatation and dysfunction (LV end-diastolic volume index of 149 ml/m2, LV ejection fraction of 48%) in Case 4.(ABSTRACT TRUNCATED AT 400 WORDS)

Thallium-201 (Tl) single photon emission computed tomography (SPECT) after dipyridamole infusion (0.56 mg/kg) was performed in 23 patients with hypertrophic non-obstructive cardiomyopathy (HNCM) and in seven patients with HCM simulating dilated cardiomyopathy (HCM-DCM) to clarify the mechanism and clinical significance of decreased coronary vasodilatory reserve. The coronary vasodilatory reserve in the hypertrophied area assessed by SPECT was compared with the findings of echocardiography, left ventriculography and endomyocardial biopsy. 1. Eleven patients with HNCM had no perfusion defects in the hypertrophied area (group I), but the other 12 patients (52.2%) had such defects (group II). All seven patients with HCM-DCM had perfusion defects in the anterior or septal walls (group III). Redistribution was observed in 11 of the 12 patients in group II and in three of the seven patients in group III. 2. The regional washout rate was relatively low in the upper septum in group II and in the anterior wall and upper septum in group III. Thus, coronary vasodilatory reserve in the hypertrophied area was decreased in groups II and III. 3. Echocardiographically, the degree of hypertrophy did not differ between groups I and II, but the latter had significantly greater left ventricular diastolic dimension (42.3 mm vs 49.5 mm: p less than 0.05) and lower percent fractional shortening (%FS) (43.7% vs 35.6%: p less than 0.05). However, group III showed thinner left ventricular wall, much greater diastolic dimension (60.9 mm vs 49.5 mm: p less than 0.05), and lower %FS (24.0% vs 35.6%: p less than 0.05) than did those of group II. 4. On left ventriculography, those in group II showed larger left ventricular end-diastolic volume index (93.9 ml/m2 vs 79.7 ml/m2: p less than 0.05) than that of group I. Left ventricular ejection fraction showed the same tendency, but this was not statistically significant. 5. On endomyocardial biopsy, the specimens of the patients in group II had significantly higher percent fibrosis than did those of group I (11.4% vs 6.8%: p less than 0.05). These findings suggest that the mechanism of decreased coronary vasodilatory reserve in the hypertrophied area may be related to myocardial fibrosis, and this decrease may induce left ventricular dysfunction and compensatory dilatation.

To evaluate the relation between cardiac function and myocardial damage in patients with dilated cardiomyopathy (DCM), we compared echocardiographic parameters and histopathologic findings of the biopsied myocardium in 50 cases with DCM. As wall motion is much influenced by the increased afterload in cases with large ventricles, we generated a new contractile parameter, Force-Velocity Product (FVP). FVP was defined as the result obtained by multiplying mean circumferential fiber shortening velocity by noninvasive end-systolic wall stress. FVP correlated with percent fibrosis in the myocardium, which was reflected by no other echocardiographic parameter. We also evaluated the prognostic values of the echocardiographic and histopathologic parameters. FVP had the highest value among them. We conclude that FVP is a very useful clinical parameter, with the further advantage of being obtained noninvasively.

To evaluate the significance of left ventricular (LV) hypertrophy in patients with dilated cardiomyopathy (DCM), 50 patients seen between 1976 and 1983 were studied echocardiographically. We categorized the patients as four groups according to the degree of LV dilatation or hypertrophy. Group consisted of 17 patients with mild to moderate LV dilatation without hypertrophy (LV end-systolic I dimension: Ds less than 60 mm, LV wall thickness at end-systole: WTs less than 15 mm). Group II, 12 with mild to moderate LV dilatation and hypertrophy (Ds less than 60 mm, WTs greater than or equal to 15 mm). Group III, eight with marked LV dilatation and hypertrophy (Ds greater than or equal to 60 mm, WTs greater than or equal to 15 mm), and Group IV, 13 with marked LV dilatation without hypertrophy (Ds greater than or equal to 60 mm, WTs less than 15 mm). Twenty patients had LV hypertrophy and 30 patients were without LV hypertrophy at the start of this study. New York Heart Association functional classes, cardiothoracic ratio and ECG findings at the first study did not show any statistically significant differences among the four groups. During the prospective follow-up of 2.7 years in average, eight patients died of congestive heart failure including five of Group IV, and three of Group I who had progressive LV dilatation. Three patients of Group I, II and III died suddenly. Ambulatory ECGs showed life-threatening ventricular arrhythmias in all 32 patients studied.(ABSTRACT TRUNCATED AT 250 WORDS)

The value of redistribution thallium-201 (T1-20(1] emission computed tomography (ECT) using dipyridamole for evaluating coronary circulation was analyzed in 18 patients with dilated cardiomyopathy (DCM). After maximal inducible coronary vasodilation (dipyridamole, 0.56 mg/kg), 2 mCi T1-201 was administered, and dipyridamole ECT data at 10 minutes and delayed ECT data at 3 hours after the injection were collected. Image interpretation was made visually. The results were as follows: In all cases, perfusion defects were observed on the dipyridamole images, and eight (45%) had redistribution on their delayed images. Patients with redistribution had better left ventricular function (% fractional shortening 24.7 +/- 7.0 versus 18.0 +/- 5.0) by two-dimensional echocardiography. Segments with redistribution showed less severe wall motion abnormalities compared with segments without redistribution. It is concluded that redistribution thallium ECT imaging using dipyridamole is a useful tool for the evaluation of coronary circulation of patients with DCM.

Echocardiography was performed for 246 patients with hypertension. Among the 246 patients, echocardiographic features simulating dilated cardiomyopathy (DCM) were observed in 12. These patients had past history of hypertension and prominent left ventricular dilatation with reduced left ventricular contractility, but no left ventricular wall thickening. To elucidate the mechanism producing DCM-like features in patients with hypertension, the clinical and echocardiographic findings of the 12 hypertensive patients (HT-DCM) were compared with those of 50 hypertensive patients without dilated left ventricles and of 31 patients with DCM. On admission, all patients with HT-DCM had congestive heart failure (CHF) without high blood pressure and their echocardiograms revealed the abnormal findings described above. There were no differences of the clinical and echocardiographic findings on admission between HT-DCM and DCM. Following medical treatment, relatively early improvement of CHF was noted in all patients with HT-DCM; the LV dimension decreased and diffuse wall motion abnormality improved steadily with gradual elevation of blood pressure during the follow-up periods. The LV function of most patients with HT-DCM improved markedly but never reached normal levels. There were no significant differences the right ventricular endomyocardial biopsy findings of between DCM and HT-DCM. It was suggested the DCM-like features in these cases are caused, not only by hypertension, but by other factors, as well.

To diagnose latent dilated cardiomyopathy (latent DCM), we performed loading echocardiography with Angiotensin II and ergometer exercise in 41 patients. Twenty-one patients were suspected of having latent DCM because of histories, of heart failure of myocarditis; 10 patients had DCM; and 10 normal persons served as controls. On angiotensin II loading, cardiac function deteriorated in the DCM group, but it was maintained in the normal controls. Nine patients in the latent DCM group showed the same pattern as normals (L1-group), and 12 did as the DCM group (L2-group). Although % fractional shortening, end-diastolic and end-systolic dimensions of the left ventricle did not differ between the L1 and L2-groups, the A/R, the ratio of the pulsed Doppler echocardiogram at the left ventricular inflow tract, was larger and the exercise change of the % fractional shortening and exercise tolerance were less in the L2-group than in the L1-group. Furthermore, the biopsy findings of the L2-group were similar to those of the DCM group in terms of myocardial degeneration, myocardial hypertrophy and interstitial fibrosis. Thus, patients in the L2-group were thought to have a risk for DCM, and were cases of latent DCM. Angiotensin II loading is thought to be useful for diagnosing such cases.

To investigate the pathogenesis and pathophysiology of dilated cardiomyopathy (DCM), we studied 28 patients with DCM by echocardiography and endomyocardial biopsy, and compared their findings with those of 34 patients including eight with myocarditis, seven with alcoholics, 12 with hypertensives and seven patients with hypertrophic cardiomyopathy. All 12 patients in the hypertensive group had congestive heart failure without accompanying high blood pressure, and prominent dilatation and uniform wall motion abnormality of the left ventricle observed echocardiographically on admission. After medical management, both heart failure and the echocardiographic abnormalities gradually resolved. Those in the alcoholic group had larger left ventricles and uniform wall motion abnormality compared to those in the other groups. The myocarditis and hypertrophic cardiomyopathy groups had smaller left ventricles, non-uniform wall motion and larger % myocardial fibrosis. Both ventricles in the hypertrophic cardiomyopathy group were thicker than those of the other three groups. Each patient with DCM had individual echocardiographic abnormalities, which could be categorized as two subsets depending on the degree of left ventricular dilatation and uniformity of the wall motion. The one was characterized by a prominently dilated left ventricle and uniform wall motion abnormality similar to the alcoholic group, and the other had less marked left ventricular dilatation and heterogeneous wall motion abnormality similar to the myocarditis group. From these findings, it was suggested that there are common factors to specific myocardial disease in the pathogenesis and pathophysiology of DCM, and thus, DCM might include many subsets of different etiologies.