Effectiveness of long-term beta-blocker therapy for dilated cardiomyopathy—echocardiographical follow-up

To evaluate the effectiveness of long-term beta-blocker therapy for dilated cardiomyopathy (DCM), two groups (Group I: 18 patients, Group II: 17 patients) with DCM divided by the order at the entry were followed echocardiographically for 16.9 +/- 3.0 months in Group I and 21.4 +/- 3.9 months in Group II. Metoprolol (final dose: 60 mg/day) was administered in Group I, but not in Group II (the control), although the conventional treatment for heart failure was continued. The left ventricular end-systolic dimension and ejection fraction assessed by echocardiography improved significantly after 6 months in Group I, but not in Group II, even after 48 months, although there were no significant differences in baseline data between the two groups. The end-diastolic dimension decreased significantly after 12 months in Group I only. It was estimated, using the point count method on a left ventricular endomyocardial biopsy specimen taken at entry, that the improvement (delta EF) of the ejection fraction 12 months after metoprolol administration inversely correlated (r = -0.677, p less than 0.01) with percent fibrosis, indicating that the more myocardium remains, the more improvement is expected. These findings suggested a favorable effect of beta blockade in DCM, especially in cases with less fibrosis, showing that the endomyocardial biopsy could be of clinical use in selecting candidates for chronic beta-blocker therapy in DCM.     

Effect of beta-blocker therapy in elderly patients with dilated cardiomyopathy.

The aim of this study was to evaluate whether beta-blocker therapy can be safely administered to and improve cardiac function of elderly patients with dilated cardiomyopathy (DCM). Echocardiography and measurement of the concentrations of natriuretic peptides were carried out in 67 patients with DCM before and after 6 months of beta-blocker therapy: 20 patients >/=65 years of age (older group); 47 <65 years of age (younger group). In all patients, beta-blocker was safely administered and well tolerated. There was no significant difference in the dose of beta-blocker between 2 groups. A reduction in the left ventricular dimensions and an associated increase in ejection fraction occurred in both treatment groups. The beta-blocker treatment resulted in a significant decrease in the concentrations of natriuretic peptides in both groups. In conclusion, beta-blocker therapy is well-tolerated and has similar effects on cardiac function in older and younger patients with DCM.     

Predictors of appropriate implantable cardioverter-defibrillator therapy in patients with idiopathic dilated cardiomyopathy

Evaluating predictors of appropriate implantable cardioverter-defibrillator (ICD) therapy in patients with idiopathic dilated cardiomyopathy (IDC) may be helpful in developing risk stratification strategies for these patients. Fifty-four patients with IDC underwent ICD implantation and were followed up. Twenty-three patients (42%) had a class I indication for ICD implantation; the remaining patients underwent implantation for multiple risk factors for sudden death including left ventricular dysfunction, nonsustained ventricular tachycardia, syncope, or positive electrophysiologic study results. Clinical, electrocardiographic, and electrophysiologic data were collected. Appropriate ICD therapy was defined as an antitachycardia pacing therapy or shock for tachyarrhythmia determined to be either ventricular tachycardia or ventricular fibrillation. Appropriate ICD therapy was observed in 23 patients (42%). There was a significant difference in use of beta-blocker therapy between patients who did and did not have appropriate ICD therapy (p <0.0003). Cox regression analysis identified the following univariate predictors (p <0.1): class I indication (p <0.005) and lack of use of beta-blocker therapy (p <0.0007). In multivariate analysis, only lack of beta-blocker use (relative risk 0.15, 95% confidence intervals 0.05 to 0.45; p <0.0007) was identified as a predictor of appropriate ICD therapy. Of the patients who received ICD therapy, only 4 (17%) were taking beta blockers, whereas 21 of the 31 patients (68%) who did not receive ICD therapy were treated with beta blockers (p <0.0003). In patients with IDC selected for ICD implantation, the most consistent predictor of appropriate ICD therapy was lack of beta-blocker use. Attempts should be made to administer beta blockers to these patients, if tolerated.     

Effect of beta-blocker therapy on severe ventricular arrhythmias in patients with idiopathic dilated cardiomyopathy

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.     

Myocardial integrated ultrasonic backscatter in patients with dilated cardiomyopathy: prediction of response to beta-blocker therapy

BACKGROUND: Myocardial integrated backscatter (IB) imaging has been reported to be useful for ultrasonic tissue characterization and delineation of myocardial viability or fibrosis. beta-Blocker therapy has beneficial effects for patients with dilated cardiomyopathy (DCM), but there are no clear findings that indicate which patients with DCM will respond to this therapy. This study was performed to evaluate whether myocardial IB analysis can predict the response to beta-blocker therapy. METHODS AND RESULTS: We prospectively performed echocardiographic examination with IB analysis in 29 patients with DCM (20 men, 9 women) before starting bisoprolol therapy and in 15 normal subjects. Standard echocardiographic examination and IB analysis in the left ventricular wall in the 2-dimensional short-axis view were performed and the magnitude of cyclic variation (CV) of IB and calibrated myocardial IB intensity (subtracted pericardial) were obtained from the interventricular septum and the left ventricular posterior wall. Sixteen patients responded to bisoprolol therapy and 13 did not respond after 12 months of full-dose therapy. Calibrated myocardial IB intensity was lower in responders relative to nonresponders in both the interventricular septum (responders, -20.1 +/- 3.6 dB vs nonresponders, -9.8 +/- 5.1 dB, P <.0001; controls, -20.1 +/- 4.4 dB) and posterior wall (responders, -20.6 +/- 3.6 dB vs nonresponders, -14.6 +/- 4.2 dB, P =.0002; controls, -22.7 +/- 3.3 dB). Also, the lower the myocardial intensity in the interventricular septum or posterior wall, the better left ventricular systolic function improved after beta-blocker therapy. However, CV was lower in both DCM groups than in the controls, and CV in the interventricular septum was lower in nonresponders than in responders (responders, 4.0 +/- 4.1 dB vs nonresponders, -0.8 +/- 6. 1 dB, P <.02; controls, 8.3 +/- 2.4 dB). In addition, CV in the posterior wall showed no difference between the 2 DCM groups (responders, 5.6 +/- 1.3 dB vs nonresponders, 5.1 +/- 3.5 dB, P = not significant; controls, 9.6 +/- 2.5 dB). Also, the percent fibrosis on right ventricular endomyocardial biopsy specimens showed no distinctions between these 2 groups (responders, 25.1% +/- 16.1% vs nonresponders, 24.9% +/- 15.0%, P = not significant). CONCLUSIONS: These findings suggest that left ventricular myocardial IB data, especially IB intensity, provide useful information for predicting the response to beta-blocker therapy in patients with DCM. However, right ventricular endomyocardial biopsy findings do not appear to contribute to discriminating between the 2 groups.     

Cell therapy in dilated cardiomyopathy

A forty-one-year-old male with systolic heart failure, FC-III NYHA, clinical stage C due to dilated cardiomyopathy was submitted to an autologous transplant of the mononuclear fraction of bone marrow via coronary artery system through heart catheterism. Two months after the procedure, there was a decrease in plasma BNP and cardiac area reduction at the thorax X-ray and nuclear magnetic resonance. The echocardiogram showed decrease of the secondary regurgitation and mitral ring dilatation. There was a better performance at the ergospirometry, with increase of the maximum oxygen consumption and consequent reduction in drug therapy. The absence of adverse events characterized by clinical/hemodynamic instability, enzymatic alteration or electrocardiogram demonstrate the safety and feasibility of this procedure carried out and described with pioneering spirit in dilated cardiomyopathy.     

Effect of beta-blocker therapy on myocardial perfusion defects in thallium-201 scintigraphy in patients with dilated cardiomyopathy

BACKGROUND: The beneficial effects of beta-blocker therapy in patients with heart failure have been confirmed. However, the effects of beta-blockers on myocardial perfusion defects are unclear. The aim of this study was to evaluate the effect of beta-blockers on myocardial perfusion defects estimated by thallium-201 myocardial scintigraphy in patients with dilated cardiomyopathy (DCM) and to investigate the relationships between beta-blocker treatment and myocardial damage and cardiac function. METHODS:201Tl and echocardiography were performed in 37 patients before and after 6 months of beta-blocker therapy. Extent score (ES) by 201Tl was used to quantitate myocardial perfusion defects before and after treatment. RESULTS: ES was significantly decreased by beta-blocker therapy. According to the change in ES, DCM patients were classified into three groups, patients who improved, patients showing no change and patients who deteriorated. In the improvement and no-change groups, beta-blocker therapy induced a reduction in left ventricular dimensions and an associated increase in ejection fraction. However, in the deterioration group, left ventricular dimensions and ejection fraction were unchanged. There was a significant relationship between the change in left ventricular dimension at end-diastole and the change in ES. CONCLUSIONS: beta-Blocker therapy could attenuate myocardial perfusion defects in some patients with DCM. The improvement in left ventricular function associated with beta-blocker therapy may be related to the attenuation in myocardial perfusion defects.     

Use of thallium-201 myocardial scintigraphy for the prediction of the response to beta-blocker therapy in patients with dilated cardiomyopathy.

This study was performed to evaluate whether thallium-201 myocardial scintigraphy (Tl-201) and iodine-123-metaiodobenzylguanidine (MIBG) myocardial scintigraphy could predict the usefulness of beta-blocker therapy in patients with dilated cardiomyopathy (DCM). Tl-201 and MIBG were performed in 47 patients before beta-blocker therapy. Patients were classified into group A, if their cardiac function improved, and group B, whose function remained unchanged. Two types of extent score (ES) by Tl-201 were proposed to quantitate myocardial damage, mean-2SD (ES-2) and mean-3SD (ES-3). The ES difference between ES-2 and ES-3 was calculated, and according to ES and ES difference, DCM cases were classified into 3 groups: mild-defect type (mild-type), moderate-defect type (moderate-type) and severe-defect type (severe-type). The heart-to-mediastinum (H/M) MIBG uptake ratio was evaluated, and the percent washout ratio of myocardial MIBG was obtained from these data. Group A comprised 18 mild-type, 14 moderate-type and 1 severe-type cases, and group B comprised 5 mild-type, 4 moderate-type and 5 severe-type cases. A significant relation was observed between the defect type on Tl-201 and the response to beta-blocker therapy (p=0.0090). Both H/M MIBG uptake ratios and washout ratio were not significantly different in the 2 groups. Tl-201 may be useful for predicting the response to beta-blocker therapy in patients with DCM.     

Evaluation of exercise-induced T wave changes in patients with idiopathic dilated cardiomyopathy before and after beta-blocker therapy

INTRODUCTION: Ventricular repolarization abnormalities are thought to contribute to lethal ventricular arrhythmias in patients with idiopathic dilated cardiomyopathy (DCM). The purpose of this study was to evaluate exercise-induced T wave changes in DCM patients before and after beta-blocker therapy to investigate repolarization abnormalities. METHODS AND RESULTS: Treadmill exercise testing was performed in 20 DCM patients and 50 normal subjects. T wave amplitude (TA: baseline to T wave apex; mV) and recovery time (RT: QRS onset to the maximum dV/dt point of the T wave; msec) were measured before and 1 minute after peak exercise. TA was averaged in the right and left precordial leads (TA(V1-3), TA(V4-6)). RT was normalized to the maximum QT interval in the 12-lead ECG and expressed as the %RT (%RT). %RT was also averaged in the precordial leads (%RT(V1-3), %RT(V4-6)). After exercise, TA increased and %RT decreased in both groups. In DCM patients, TA(V1-3) was greater and TA(V4-6) was less than in normal subjects before and after exercise. There was no difference in %RT(V1-3) between the groups, but %RT(V4-6) was greater in DCM patients both before and after exercise. DCM patients repeated the same evaluation after 6 months of oral beta-blocker therapy. Compared with measurements before beta-blocker therapy, TA(V1-3) and %RT(V1-3) did not change. However, TA(V4-6) increased and %RT(V4-6) decreased significantly both before and after exercise. CONCLUSION: DCM patients showed small TA and large %RT in the left precordial leads at rest as well as after exercise. Chronic beta-blocker therapy in DCM patients normalized these ventricular repolarization abnormalities.     

干细胞移植有望治疗扩张型心肌病?

近年来,干细胞移植在心脏疾病治疗中取得了一定的成果,临床研究已证实其在急性心肌梗死中的有效性及安全性,这为扩张型心肌病的治疗带来了新曙光。现有研究表明,干细胞移植治疗扩张型心肌病可能是一种安全有效的干预措施,但仍存在许多问题有待解决。     

Familial dilated cardiomyopathy in patients transplanted for idiopathic dilated cardiomyopathy

OBJECTIVE: To evaluate the prevalence, clinical features, and pattern of inheritance of familial dilated cardiomyopathy (DCM) in heart transplant patients. PATIENTS AND METHOD: Patients with idiopathic DCM who had undergone heart transplantation were invited to participate. Patients with alcohol abuse were excluded. A clinical evaluation, 12-lead ECG, echocardiogram, blood tests, and DNA extraction were performed in patients and relatives. Familial DCM was defined as the presence of at least one relative with idiopathic DCM. Possible familial DCM was considered when at least one relative had left ventricular enlargement (LVE) (> 112% predicted LVEDD). RESULTS: One hundred and ninety-nine relatives of 43 families were studied. DCM was familial in 11 probands (25.6%) and possibly familial in 11 (25.6%). Fifteen relatives had DCM (7.5%), 26 (13.1%) LVE, and 5 (2.5%) hypertrophic cardiomyopathy. The pattern of inheritance was autosomal dominant in most families. Five probands (3 with familial DCM) had antecedents of consanguinity and possible recessive inheritance. Six probands (14%, 1 with familial DCM) had relatives with conduction system defects. Creatine kinase was moderately increased in 9 relatives (4.5%), 3 of them with LVE. Fifteen patients had at least moderate alcohol intake. Three of them had familial DCM (relatives without alcohol abuse) and 6 had possible familial DCM. CONCLUSIONS: The prevalence of familial DCM is high in patients who undergo heart transplant. Left ventricular enlargement, conduction system abnormalities, and elevated creatine kinase may be early markers of familial disease. Hypertrophic cardiomyopathy is present in some relatives of patients with idiopathic DCM. Familial DCM is present in patients with a previous diagnosis of alcoholic DCM.     

Immunoadsorption therapy for dilated cardiomyopathy and pulmonary arterial hypertension

Dilated cardiomyopathy (DCM) which is a common cause of heart failure is often related to elevated levels of autoantibodies (AABs) against cardiac structural or functional proteins. Among several AABs which react against cardiac cellular proteins that have been detected in sera from DCM patients, those against β₁-adreno-receptors (β₁-ARs) appeared particularly relevant from a pathophysiological point of view. During the last 15 years several studies evaluating the short-term efficacy of imunoadsorption (IA) in idiopathic DCM have shown improvement in cardiac function and patient outcome. However, the invasive and complicated aspects of the IA, which is also costly, have limited its broad clinical application as long as only its short-term efficacy has been definitely proved.Autoimmunity is also suspected to play a key role in the pathogenesis of pulmonary arterial hypertension (PAH). Recently we identified functional AABs against the α₁-AR and/or the endothelin-A-receptor (ETA) in sera of patients with PAH. These AABs activate the receptors like corresponding agonists but, unlike the agonists, the AABs induce long-lasting stimulatory effects and do not desensitize the receptors. The AABs against the α₁-AR and the ETA-receptor belong to IgG3 and IGg2 subclass, respectively, and can be removed by IA. The first 5 potential transplant candidates with idiopathic PAH who underwent IA showed good results after this therapy.This update aims to summarize the present knowledge about the role of AABs in the etiopathogenesis of DCM and PAH and the potential therapeutic benefits of AAB removal by IA. Special attention is focused on the therapeutic benefits of IA for patients with life-threatening end-stage disease where all pharmacological therapeutic options are exhausted.     

Long-term beta-blocker vasodilator therapy improves cardiac function in idiopathic dilated cardiomyopathy: a double-blind, randomized study of bucindolol versus placebo

PURPOSE: Bucindolol is a potent nonselective beta-blocking agent with vasodilatory properties. In this study, we evaluated the effects of long-term bucindolol therapy in the treatment of heart failure from idiopathic dilated cardiomyopathy. PATIENTS AND METHODS: Patients were eligible for enrollment if they had symptomatic heart failure, idiopathic dilated cardiomyopathy, and left ventricular ejection fraction less than 0.40. All patients received an initial test dose of 12.5 mg bucindolol orally every 12 hours for two or three doses. Patients tolerating the test dose were randomly assigned (double-blind) to receive bucindolol or placebo in a 3:2 ratio. Study medication was begun at a dose of 12.5 mg orally every 12 hours and gradually increased over a 1-month period until either a maximum tolerated dose or a target dose of 100 mg every 12 hours was reached. Study medication was then continued for an additional 2 months. RESULTS: A total of 24 patients were enrolled into the study. Twenty-three patients tolerated bucindolol test challenge; 14 were randomized to receive bucindolol, and nine were randomly assigned to receive placebo. The placebo group (age 56 +/- 2 years) was significantly older than the bucindolol group (46 +/- 3 years), but by all other clinical and hemodynamic parameters the two groups were comparable. Twenty-two of 23 patients completed the study. Patients treated with bucindolol had significant improvements in clinical heart failure symptoms and in resting hemodynamic function, including an increase of left ventricular ejection fraction (0.26 +/- 0.02 to 0.35 +/- 0.09, p = 0.003), cardiac index (2.2 +/- 0.1 to 2.5 +/- 0.4 L/minute/m2, p = 0.014), and left ventricular stroke work index (25 +/- 3 to 35 +/- 7 g.m/m2, p = 0.002) and a decrease in pulmonary artery wedge pressure (17 +/- 3 to 10 +/- 5 mm Hg, p = 0.005) and heart rate (86 +/- 3 to 75 +/- 9 beats/minute, p = 0.012). Patients treated with bucindolol also had a significant increase in exercise left ventricular ejection fraction (0.26 +/- 0.03 to 0.32 +/- 0.14, p = 0.015) and reduction in questionnaire-measured symptoms (p = 0.007) and New York Heart Association functional class (p less than 0.001). However, total treadmill exercise duration and maximal oxygen consumption with exercise did not change. No changes in rest or exercise parameters were observed in the placebo-treated group. Central venous plasma norepinephrine concentration decreased significantly in the bucindolol-treated group (423 +/- 79 to 212 +/- 101 pg/mL, p = 0.010), but was unchanged in the placebo-treated group. CONCLUSION: Bucindolol is well tolerated in patients with idiopathic dilated cardiomyopathy and congestive heart failure, and therapy for 3 months is associated with improved resting cardiac function, improved heart failure symptoms, and a reduction in venous norepinephrine concentration.     

扩张型心肌病发病机制和治疗的研究新动向

冠心病、高血压、心肌病在心血管疾病的发病中占据主导地位,也是导致心力衰竭的主要病因。近年,随着降压药物的大规模投入研究,高血压的有效治疗包括对靶器官的保护已见成效,冠状动脉介入技术的迅猛发展,又使千千万万的患得到了及时有效的血管再通,挽救了更多的生命。然而心肌病尤其是扩张型心肌病（dilated cardiomyopathy,DCM）的发病有上升趋势,预后极差,国外曾报道5年病死率约50．O％,国内报道2年病死率为41．2％、     

Plasma brain natriuretic peptide as a novel therapeutic indicator in idiopathic dilated cardiomyopathy during beta-blocker therapy: a potential of hormone-guided treatment

BACKGROUND: Plasma brain natriuretic peptide (BNP) is a sensitive and specific marker of left ventricular (LV) function. In the treatment of heart failure, especially in idiopathic dilated cardiomyopathy (IDC), beta-blocker (BB) therapy has been established as a powerful strategy. The purpose of this study was to analyze relationships between changes in BNP level and LV function during BB therapy in patients with IDC. METHODS: In 30 patients with IDC who had already received conventional therapy, measurement for plasma BNP and norepinephrine levels and echocardiographic indices were evaluated before and 2 and 6 months after carvedilol in 21 patients and at baseline and after 6 months in 9 patients who did not receive carvedilol. RESULTS: After 6 months carvedilol treatment significantly improved LV end-diastolic dimension (LVEDD) (65 +/- 8 to 61 +/- 8 mm) and LV ejection fraction (LVEF) (34% +/- 13% to 43% +/- 12%) with intergroup differences; it significantly decreased BNP (127 +/- 113 to 69 +/- 92 pg/mL) with no intergroup difference; however, it did not decrease norepinephrine. BNP correlated strongly with LVEDD, LVEF, and LV mass index in carvedilol-treated patients. The degree of change in BNP correlated with that in LVEDD or LVEF 6 months after carvedilol. All 14 patients with decreased or unchanged BNP levels showed an increase in LVEF, and 4 of 7 with a rise in BNP had decreased or unchanged LVEF. According to receiver operating characteristic analysis, the optimal BNP levels for detecting LVEF <35% before and after carvedilol were 75.5 and 69 pg/mL, respectively. CONCLUSION: Plasma BNP levels may accurately reflect alteration in LV function and structure and can be used as a therapeutic indicator for risk stratification in patients with IDC during BB therapy.     

扩张型心肌病患者心脏再同步化治疗的疗效观察

目的:观察在组织多普勒指导下对药物难治性扩张型心肌病(DCM)充血性心力衰竭的心脏再同步化治疗(CRT)的疗效。方法:选择18例经药物治疗后无效的DCM充血性心力衰竭患者行CRT。术前行二维超声心动图和组织多普勒检查,术后1周在组织多普勒指导下行房室和室间延迟优化。术后1个月、3个月、6个月及1年随访患者的临床症状,并比较各项参数的变化。结果:CRT后①心功能从Ⅲ～Ⅳ级改善为Ⅰ～Ⅲ级,左室射血分数由(26.42±6.7)%增加到(33.44±6.0)%,P<0.01;②左室舒张末内径由(75.31±8.52)mm减少至(67.24±10.57)mm,P<0.05;③左右室间收缩时间差、左室内不同步指数有显著改善,但随着术后时间的延长无明显变化。结论:CRT可以改善DCM患者的左、右室间和左室内收缩活动不同步,逆转心室扩大,提高心功能,其近期疗效显著。