Frequency and clinical characteristics of dilated cardiomyopathy caused by desmin gene mutation in a Japanese population.

AIMS: Dilated cardiomyopathy is partly caused by a mutation of some cytoskeletal or nuclear envelope proteins. It has been confirmed recently that a missense mutation of the gene encoding desmin, a cytoskeletal protein, can cause dilated cardiomyopathy. This study was aimed at elucidating the frequency and clinical characteristics of dilated cardiomyopathy caused by desmin mutation. METHODS AND RESULTS: We examined 265 Japanese patients with dilated cardiomyopathy (217 sporadic cases and 48 probands of familial dilated cardiomyopathy). The exon 8 of the desmin gene, the critical region for the pathogenesis of dilated cardiomyopathy, was analysed by polymerase chain reaction, single-strand conformation polymorphism and sequencing. The same missense mutation (Ile451Met) as reported previously was detected in three patients (1.1%). All these patients were male and sporadic, and more likely to be accompanied by characteristics such as younger age at diagnosis, lower fractional shortening and ejection fraction than each mean value of sporadic cases. The chronological changes in cardiac function were inconsistent in the three patients. CONCLUSION: The missense mutation (Ile451Met) of the desmin gene can be the genetic cause of dilated cardiomyopathy, although with very low frequency. The ages at diagnosis were younger and the cardiac function had deteriorated further than general cases of sporadic dilated cardiomyopathy.

Comparison of results of intracoronary implantation of the Plamaz-Schatz stent with conventional balloon angioplasty in chronic total coronary arterial occlusion.

We compared angiographic and clinical outcomes after successful revascularization of chronic total coronary arterial occlusion with the placement of the Palmaz-Schatz stent (43 patients) and conventional balloon angioplasty (53 patients). After the procedure, the coronary stent led to a greater minimal lumen diameter than conventional balloon angioplasty (2.6 vs 1.7 mm, p < 0.001), resulting in a smaller residual stenosis (6.5% vs 36.7%, p < 0.001). At 6-month follow-up, there was no significant difference in late loss between the groups, resulting in a larger minimal lumen diameter at follow-up in the stent group (1.8 vs 1.1 mm, p < 0.001). The incidence of restenosis was lower in the stent group (27.9% vs 56.6%, p < 0.005). The frequency of the combination of myocardial infarction and coronary artery bypass graft surgery tended to be less in the stent group (2.3% vs 11.3%, P = 0.09). Placement of the Palmaz-Schatz stent improved left ventricular ejection fraction by 26% in patients who had reduced left ventricular function (p < 0.05), but conventional balloon angioplasty did not. Thus, placement of the Palmaz-Schatz stent provided a wider lumen than did conventional balloon angioplasty and, therefore, reduced the incidence of restenosis in chronic total coronary arterial occlusion. The lower restenosis rate of coronary stenting would be beneficial for long-term clinical outcome in patients with chronic total occlusion.

Hepatocellular carcinoma complicating biliary cirrhosis caused by biliary atresia: report of a case.

A case of hepatocellular carcinoma complicating biliary cirrhosis caused by biliary atresia is reported. The patient had persistent severe jaundice with hepatosplenomegaly. A liver tumor was suspected because of the elevated serum alpha-fetoprotein and was shown by ultrasonography at 6 years of age. The tumor was treated with percutaneous ethanol injection therapy (PEIT). Nine months after initiation of PEIT, the patient died of massive bleeding from a metastatic tumor.

The effect of recent advances in pharmacologic management on the prognosis of dilated cardiomyopathy.

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)

Prognostic significance of atrial fibrillation in dilated cardiomyopathy.

We evaluated the relation of atrial rhythm to a clinical course of treatment in 147 patients diagnosed with dilated cardiomyopathy (DCM). Thirty-six of the patients (24%) had either transient (9 patients) or persistent (27 patients) atrial fibrillation (AF). Compared with DCM patients with sinus rhythm (SR), the AF patients did not differ in age, left ventricular (LV) dimension, fractional shortening, or hemodynamic parameters, but the AF patients had slightly larger left atria. After a mean follow-up of 3.8 +/- 2.9 years, the NYHA functional classifications in the AF patients improved in 20 of the 36 (56%), whereas those of the SR patients improved in only 30 (27%) (p < 0.01). The actuarial 5-year survival rate was significantly better for AF patients than for SR patients (93% versus 68%, p < 0.05). LV function remained unchanged in SR patients but improved significantly in AF patients, particularly in patients with transient AF and with "rate-controlled" AF (those with a mean heart rate of less than 90 beats/min). This study suggests that atrial fibrillation may result in significant LV dysfunction, which is reversible in some cases once the arrhythmia is controlled. Aggressive antiarrhythmic therapy should be considered for patients initially diagnosed with dilated cardiomyopathy and atrial fibrillation.

Short- and mid-term follow-up results after percutaneous transvenous mitral commissurotomy.

This study reports the clinical follow-up for 6 months of 52 patients who underwent percutaneous transvenous mitral commissurotomy (PTMC). PTMC resulted in an increase in mitral valve area from 1.1 +/- 0.3 to 1.7 +/- 0.4 cm2 (p < 0.0001), a decrease in mean left atrial pressure from 16 +/- 7 to 13 +/- 5 mmHg (p < 0.0001), and an increase in exercise time from 4.6 +/- 2.1 to 6.3 +/- 2.3 min (p < 0.0001). At 6 months follow-up, mitral valve area was unchanged (1.7 +/- 0.4 cm2). Of 52 patients, 33 showed clinical improvement and 19 had no clinical improvement after PTMC. Univariate analysis showed (1) younger age, (2) echocardiographic score of 8 or less, (3) existence of mitral regurgitation of less than grade 2 after PTMC, and (4) amelioration in left atrial dimension, mean pulmonary artery pressure and exercise time after PTMC as correlative factors for clinical improvement. In conclusion, PTMC was an effective procedure for mitral stenosis, especially in younger patients with an echocardiographic score of 8 or less. Change in left atrial dimension was a good indicator of the effectiveness of PTMC.

Congestive heart failure in the elderly--echocardiographic insights.

One hundred and seventy-two patients (110 were greater than or equal to 65 years and 62 were less than 65 years) with congestive heart failure (CHF) were prospectively evaluated to determine various pathophysiologic mechanisms of CHF. The incidence of CHF with normal left ventricular (LV) systolic function was higher in elderly (30% vs 12%, p less than 0.05). Of the 110 elderly patients, LV systolic function was impaired in 77. Fifty-five patients had LV dilatation without increased wall thickness, and the clinical diagnosis was "dilated cardiomyopathy in the elderly". Twenty-two patients had hypertrophied LV and a high incidence of hypertension, and they were diagnosed as "hypertensive heart failure" due to contractile dysfunction. On the contrary, the remaining 33 patients did not have impaired LV contractile function. Thirteen patients lacking LV hypertrophy had enlarged atria. CHF was induced by reduced chamber compliance called "the stiff heart syndrome". Twenty patients had hypertrophied LV and a high incidence of hypertension. They were diagnosed as having "hypertensive hypertrophic cardiomyopathy of the elderly" and abnormalities of diastolic function accounted for the CHF. Since echocardiography can easily and accurately diagnose the pathophysiologic mechanism of CHF, an increased awareness of its occurrence in the elderly and use of echocardiography would reduce diagnostic and therapeutic errors.

[Clinical features of latent dilated cardiomyopathy].

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.

Evaluation of biventricular interaction in various cardiac diseases by pulsed Doppler echocardiography.

We evaluated the biventricular interaction in various cardiac diseases by pulsed Doppler echocardiography. A/R (atrial peak filling velocity/rapid peak filling velocity) from inflow wave and PEP/ET (pre-ejection period/ejection time) from outflow wave were measured as parameters of both ventricular function. In 20 normal cases, A/R and PEP/ET correlated well between the right and left ventricles, respectively. In 6 cases with pulmonary hypertension, both values of A/R and PEP/ET were higher than those in normal cases in the right ventricle, but not in the left ventricle. In 15 cases with left ventricular infarction, these values were higher than those in normal cases. Not only in the left ventricle but also in the right ventricle, and good correlation between both ventricles was observed in each parameter. In 15 cases with hypertrophic nonobstructive cardiomyopathy and 15 cases with dilated cardiomyopathy, both values of A/R and PEP/ET in the both ventricles were also higher than those in normal cases, respectively, however, both parameters did not correlate with the both ventricles. It is suggested that the right ventricular function is influenced not only by the afterload or interventricular septal function, but also by the myocardial property of the right ventricle itself, in cases with cardiomyopathies.

Orbital fractures: surface coil MR imaging.

Twenty-six patients with orbital fractures diagnosed with plain radiography and computed tomography were examined with surface coil magnetic resonance (MR) imaging. Fifteen patients had blow-out fractures, and 11 had maxillofacial complex fractures. In all patients with blow-out fractures, the location of the fracture was precisely indicated by the presence of prolapsed orbital fat. Incarceration of the extraocular muscle or orbital fat was correctly diagnosed with MR imaging, which was less sensitive in depicting maxillofacial fractures but was useful in assessment of soft-tissue involvement. Postoperative follow-up MR studies provided valuable information about the cause of motility impairment. While T1-weighted images are useful for the detection of the fracture site, both T1- and T2-weighted images are usually necessary for evaluating soft-tissue lesions. The results of this study indicate that surface coil MR imaging is an important adjunct procedure in the diagnosis and treatment of orbital fractures.

Effects of long-term beta-blockade (metoprolol) therapy in patients with dilated cardiomyopathy.

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 role of myocarditis and myocardial fibrosis in dilated cardiomyopathy. Analysis of 28 necropsy cases.

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.

[Pericardial effusion in acute myocardial infarction: clinical feature and significance].

To determine the incidence and clinical significance of pericardial effusion after acute myocardial infarction, two-dimensional echocardiography was serially performed in 137 consecutive patients. Pericardial effusion was observed in 45 patients (33%), of whom 22 were followed until they recovered and were discharged. Pericardial effusion was more frequent in patients with anterior acute infarction than those with inferior acute infarction, and so it was in non-recanalized patients than in recanalized ones. Patients with pericardial effusion had higher peak levels of creatine kinase, higher wall motion score indices, and higher defect scores of thallium imagings. The improvement of regional wall motion at an infarct zone in patients with pericardial effusion was less regardless of the successful early recanalization. These results show that pericardial effusion is a common event in patients with acute myocardial infarction and observation of transition of pericardial effusion is important for predicting prognosis.

[Progression from latent cardiomyopathy to dilated cardiomyopathy: a review of five cases].

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.

Analysis of ventricular arrhythmias in patients with dilated cardiomyopathy--relationship between the effects of antiarrhythmic agents and severity of myocardial lesions.

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.

Intraocular lesions in patients with systemic disease: findings on MR imaging.

Twenty-one intraocular lesions associated with various systemic diseases in 15 patients were studied by MR imaging. The disorders included diabetes mellitus, cardiovascular disease, Behçet disease, sarcoidosis, and ankylosing spondylitis. MR was performed on a 0.5-T system using a surface-coil technique. Ophthalmoscopic visualization of the fundus was precluded by the presence of opaque media in all cases. MR was found to be effective in demonstrating intraocular bleeding, vitreous opacity, detached lesions of the posterior pole, and eyeball deformity. Surface-coil MR is a useful adjunct in the evaluation of the eyes affected by systemic diseases, especially in patients with opaque media.

[Mitral valve prolapse as an initial clinical feature of dilated cardiomyopathy: report of two cases].

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.

Intraocular lesions in patients with systemic disease: findings on MR imaging.

Twenty-one intraocular lesions associated with various systemic diseases in 15 patients were studied by MR imaging. The disorders included diabetes mellitus, cardiovascular disease, Behçet disease, sarcoidosis, and ankylosing spondylitis. MR was performed on a 0.5-T system using a surface-coil technique. Ophthalmoscopic visualization of the fundus was precluded by the presence of opaque media in all cases. MR was found to be effective in demonstrating intraocular bleeding, vitreous opacity, detached lesions of the posterior pole, and eyeball deformity. Surface-coil MR is a useful adjunct in the evaluation of the eyes affected by systemic diseases, especially in patients with opaque media.