Different response of patients with idiopathic and ischaemic dilated cardiomyopathy to exercise training

We looked at the benefits and complications of a home-based exercise programme in patients with ischaemic and idiopathic dilated cardiomyopathy. Twenty-four patients with left ventricular end-diastolic dimension >6.5 cm and fractional shortening <25% entered a cross-over trial of 8 weeks training versus 8 weeks rest. Echocardiography, electrocardiogram and cardiopulmonary exercise testing were performed at baseline, after training and after detraining. Training resulted in a higher peak oxygen consumption (26.5 versus 21.3 ml/kg/min, P=0.004), a higher peak heart rate (161 versus 152 bpm, P=0.02) and improved well-being. Patients with idiopathic dilated cardiomyopathy showed a significant increase in exercise time (879 versus 828 s, P=0.03) and peak oxygen consumption (31.3 versus 24.3 ml/kg/min, P=0.02) and a decrease in left ventricular end-diastolic dimension (6.4 versus 6.9 cm, P=0.01) and end-systolic dimension (5.3 versus 5.8 cm, P=0.04) in contrast to those with coronary artery disease, who developed a reduction in septal excursion and shortening rate following training. Complications of training were more common in those patients with ischaemic cardiomyopathy, greater left ventricular dimensions, poorer exercise tolerance and greater ventilation drive at baseline, and included fluid retention and exercise-induced ventricular tachycardia. We found that this group of patients with a dilated, poorly functioning left ventricle can safely derive benefit from a home-based exercise programme, particularly those of idiopathic origin, but they should be closely monitored for the development of complications.     

T-lymphocyte subsets in patients with idiopathic dilated cardiomyopathy

T-cell subsets were measured in the peripheral blood of 33 patients with heart failure from idiopathic dilated cardiomyopathy, 22 patients with heart failure from other causes, and 33 normal controls. Mean T-suppressor cell percentage was 30% in normals, 21% in patients with idiopathic dilated cardiomyopathy whose duration of symptoms was less than 1 year (P = 0.0005), and 26% in those with symptoms for greater than 1 year (P = 0.05). Similarly, percentage of T-suppressor cells in the group with heart failure from causes other than idiopathic dilated cardiomyopathy was significantly lower (23%; P = 0.005) in those with short duration of symptoms. When both heart failure groups were combined those with symptoms for less than 1 year had significantly lower T-suppressor frequencies (22%) than those with symptoms for more than 1 year (P = 0.015). Multivariate analysis identified duration of symptoms and age as the only independent predictors of T-suppressor cell frequencies. Decreased percentage of T-suppressor cells in patients with idiopathic dilated cardiomyopathy may be an epiphenomenon related to duration of heart failure. This should be taken into account in assigning an etiologic mechanism for T-suppressor cells in idiopathic dilated cardiomyopathy.     

Circulating tenascin-C levels in patients with idiopathic dilated cardiomyopathy

Circulating serum tenascin-C (an extracellular matrix glycoprotein) levels in patients with idiopathic dilated cardiomyopathy (IDC) were measured. Serum tenascin-C levels were increased in proportion to the severity of left ventricular dysfunction in patients with IDC. The associations of serum tenascin-C levels with serum troponin T and procollagen type III aminoterminal peptide levels suggest that increased levels of serum tenascin-C indicate ongoing replacement fibrosis after myocardial damage in IDC.     

扩张型心肌病新型抗钙通道抗体的发现

目的:观察扩张型心肌病(DCM)患者血清中是否独立存在抗心肌细胞L型钙离子通道(Human Cav1.2)自身抗体(简称:抗钙通道抗体)。方法:以合成多肽片段作为抗原,用ELISA法检测DCM患者(DCM组)及正常人(正常对照组)(各60例)血清中的抗钙通道抗体和抗心肌细胞线粒体内膜ADP/ATP载体蛋白(ANT)抗体。用亲合层析法提纯DCM患者(DCM组)血清中的抗钙通道抗体,以制备的大鼠抗Human Cav1.2α1亚单位多克隆抗体作为阳性对照,用免疫印记技术,免疫荧光组织化学技术检测DCM患者血清中抗钙通道抗体。结果:ELISA检测60例DCM患者中29例抗钙通道抗体阳性(29/60,阳性率48.33%),明显高于正常对照组(4/60,6.67%,P<0.01)。抗钙通道抗体和抗ANT抗体检出结果无一致性(P>0.05)。免疫印记中亲合层析法提纯的DCM患者抗钙通道抗体可特异地识别240000的多肽(Human Cav1.2α1c亚单位),结果与阳性对照相符。抗钙通道抗体经抗原充分吸附后特异性识别被阻断。免疫荧光实验显示,抗钙通道抗体能特异性地结合在大鼠心室肌细胞膜上。结论:DCM患者血清中存在新型的抗钙通道抗体。     

The magnitude of left ventricular myocardial hypertrophy related to the degree of its dysfunction in patients with dilated cardiomyopathy (DCM).

The aim of the study was to analyze the relationship between the magnitude of left ventricular (LV) hypertrophy and selected haemodynamic parameters reflecting LV systolic and diastolic function. The "hypertrophy-function" relationship was evaluated in 22 patients with dilated cardiomyopathy (DCM) and in patients with left ventricular dilatation resulting from volume overload due to valve disease (DVOL). The parametres of systolic and diastolic left ventricular function were obtained from right- and left-heart catheterization and quantitative angiocardiography, DCM patients were divided into subgroups depending on the magnitude of hypertrophy and degree of dilatation: Ia- moderate hypertrophy (100 g/m2 < LVMI < 175 g/m2). Ib- massive hypertrophy (LVMI > 175 g/m2); IIa- mass/volume ratio (M/V) < 1.1, and IIb - M/V > 1.1. It was found that the magnitude of myocardial hypertrophy and the M/V ratio do not affect the degree of systolic and diastolic dysfunction in patients with DCM. Myocardial hypertrophy accompanying dilatation due to DCM and DVOL showed very similar progression of impairment of isovolumetric systole and relaxation. Significant differences in EF, LVMDP and LVEDP may result from a different degree of total LV volume stiffness as a consequence of various mechanisms of hypertrophy in DCM and DVOL.     

Coronary endothelial dysfunction in patients with acute-onset idiopathic dilated cardiomyopathy

Objectives. This study sought to determine whether coronary endothelial dysfunction exists in patients with acute-onset idiopathic dilated cardiomyopathy (DCM) and to explore its relation to recovery of left ventricular systolic function in this patient population.Background. Coronary endothelial dysfunction exists in chronic DCM, but its importance in the development and progression of ventricular dysfunction is not known. To address this issue we studied coronary endothelial function in patients with idiopathic DCM <6 months in duration and explored the relation between coronary endothelial function and subsequent changes in left ventricular ejection fraction (LVEF).Methods. Ten patients with acute-onset idiopathic DCM (duration of heart failure symptoms 2.0 ± 0.4 months [mean ± SEM]) and 11 control patients with normal left ventricular function underwent assessment of coronary endothelial function during intracoronary administration of the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilator adenosine. Coronary cross-sectional area (CSA) was determined by quantitative coronary angiography and coronary blood flow (CBF) by the product of coronary CSA and CBF velocity measured by an intracoronary Doppler catheter. Patients with DCM underwent assessment of left ventricular function before and several months after the study.Results. Acetylcholine infusion produced no change in coronary CSA in control patients but significant epicardial constriction in patients with DCM (−36 ± 11%, p < 0.01). These changes were associated with increases in CBF in control patients (+118 ± 49%, p < 0.01) but no change in patients with DCM. Infusion of adenosine produced increases in coronary caliber and blood flow in both groups. Follow-up assessment of left ventricular function was obtained in nine patients with DCM 7.0 ± 1.7 months after initial study, at which time LVEF had improved by ≥0.10 in four patients. Multiple linear regression revealed a positive correlation between both the coronary CSA (r² = 0.57, p < 0.05) and CBF (r² = 0.68, p < 0.01) response to acetylcholine and the subsequent improvement in LVEF.Conclusions. Coronary endothelial dysfunction exists at both the microvascular and the epicardial level in patients with acute-onset idiopathic DCM. The preservation of coronary endothelial function in this population is associated with subsequent improvement in left ventricular function.     

特发性扩张型心肌病与HLA-A*基因的关联研究

目的探讨特发性扩张型心肌病（idiopathic dilated cardiomyopathy，IDC）易感的分子机制和确立一种人类主要组织相容性复合体（HLA—A＊）基因的检测方法。方法采用聚合酶链式反应和顺序特异性引物（PCR—SSP）基因分析方法，对31例特发性扩张型心肌病患者及29例无血缘关系的健康人的HIA—A＊各等位基因及亚基因进行检测分析，并将该方法与其他检测HIA等位基因的方法进行对比。结果HIA—A＊ 03基因与IDC呈正相关（RR=4．697，P〈0．05），其他HIA—A＊各等位基因未见异常。结论HIA—A＊03基因可能是北方汉族人IDC的致病易感基因之一。采用的方法（PCR—SSP）具有快速、简便、敏感、准确和可靠等优点，值得推广。     

C-reactive protein and aortic stiffness in patients with idiopathic dilated cardiomyopathy

BACKGROUND: Previous studies have shown an association between C-reactive protein (CRP)and arterial stiffness in most cardiovascular diseases. Increased CRP levels and arterial stiffness have been considered independent predictors of cardiovascular mortality in cardiovascular disease and even in the general population. OBJECTIVE: The aim of this study was to investigate the relationship between CRP, a marker of systemic inflammation and aortic stiffness in patients with idiopathic dilated cardiomyopathy (DCMP). METHODS: Serum CRP levels and aortic stiffness parameters were measured in DCMP patients (n= 37) and age- and gender-matched control subjects (n= 30). High-sensitivity CRP levels were determined by an immunonephelometry assay. Aortic strain (AS) and aortic distensibility (AD) were calculated from the aortic diameters measured using M-mode echocardiography and blood pressure obtained by sphygmomanometry. RESULTS: Serum levels of CRP in DCMP patients were higher than in the control subjects (5.47 +/- 2.06 mg/L and 2.35 +/- 0.47 mg/L, P < 0.001, respectively). AS and AD were significantly decreased in DCMP patients compared to the controls (P < 0.001 and P < 0.001, respectively). There were positive correlations between CRP, and (r = 0.3.64, P = 0.027) smoking (r = 0.3.56, P = 0.024), and increasing age (r = 0.587, P < 0.001), and negative correlations between CRP, and DBP (r =-0.485, P < 0.001), diameter change (DC; r =-0.493, P < 0.001), AS (r =-0.526, P < 0.001), and AD (r =-0.626, P < 0.001). CONCLUSION: We have shown that there is a significant relation between high serum CRP levels and impaired aortic stiffness in patients with idiopathic DCMP. These findings may indicate an important role of CRP in the pathogenesis of impaired aortic stiffness in idiopathic DCMP.     

Carnitine deficiency in patients with coeliac disease and idiopathic dilated cardiomyopathy

BACKGROUND AND AIMS: Idiopathic dilated cardiomyopathy (IDCM) and coeliac disease (CD) are two pathological conditions which may lead, by different mechanisms, to malabsorption of various micronutrients, including carnitine, active in cardiac metabolism. The aim of the present investigation was primarily to evaluate differences in serum concentrations of total carnitine between IDCM patients and patients with IDCM associated with CD and then also to evaluate, in the latter, the effect of a gluten-free diet on serum concentrations of total carnitine. METHOD AND RESULTS: Serum carnitine was determined by enzymatic spectrophotometric assay in three groups of individuals: group A, 10 patients (5 males, 5 females), mean age 46.5+/-10.8 years, presenting isolated IDCM; group B, 3 patients (2 males, 1 female), mean age 34+/-8 years, with IDCM+CD; and group C, 10 healthy subjects (5 males, 5 females), mean age 38.6+/-11.1 years. All patients with IDCM belonged to class NYHA I-II. Mean concentrations of total serum carnitine in the group of patients with isolated IDCM (group A) were found to be lower than in the controls (group C). The concentrations in patients with IDCM associated with CD (group B) were lower than in the control group and also lower than in the isolated IDCM (group A). After 2 years on a gluten-free diet, patients presenting IDCM associated with CD showed a progressive increase in mean serum carnitine levels compared to values observed prior to the diet. CONCLUSIONS: Patients presenting IDCM associated with CD show a greater decrease in serum total carnitine levels than patients presenting the isolated form of IDCM. A gluten-free diet, in these patients, leads to a progressive increase in serum levels of this substance.     

Ca2+ uptake by cardiac sarcoplasmic reticulum from patients with idiopathic dilated cardiomyopathy

We measured Ca2+ uptake by sarcoplasmic reticulum prepared from left ventricular myocardium obtained from six nonfailing human hearts and nine excised hearts from patients with class IV idiopathic dilated cardiomyopathy. Ca2+ uptake had a Vmax of 593 +/- 82 nmol/mg-min, a K0.5 of 0.68 +/- 0.07 microM, and an nHill of 1.7 +/- 0.1 in the nonfailing hearts. The corresponding values in the excised failing hearts were 593 +/- 36 nmol/mg-min, 0.63 +/- 0.03 microM, and 1.6 +/- 0.1. The beta-receptor density in crude sarcolemma prepared from left ventricular myocardium was 110.0 +/- 15.3 fmol/mg in the unmatched donors and 52.1 +/- 4.5 fmol/mg in the excised failing hearts. These results suggest that abnormal Ca2+ handling in idiopathic dilated cardiomyopathy in humans is not the result of any intrinsic alteration of Ca2+ uptake by sarcoplasmic reticulum.     

HLA-DR antigen linkage of anti-beta receptor antibodies in idiopathic dilated and ischaemic cardiomyopathy.

OBJECTIVE--Immunological mechanisms have been implicated in the pathogenesis of human dilated cardiomyopathy. The presence of autoantibodies against the beta 1 adrenoceptor in a substantial proportion of patients with dilated cardiomyopathy has been described and an association between the HLA-DR4 phenotype and anti-beta receptor antibodies has been identified. The objective of the present study was to examine whether the presence of such antibodies in ischaemic cardiomyopathy was limited to specific HLA-DR phenotypes. DESIGN--The HLA-DR dependence of anti-beta receptor antibodies detected by a ligand binding inhibition assay in patients with dilated cardiomyopathy (n = 68) was compared with that in patients with ischaemic cardiomyopathy (n = 73). RESULTS--38% of the patients with dilated cardiomyopathy and 22% of those with ischaemic cardiomyopathy had serum anti-beta receptor antibodies. In dilated cardiomyopathy, the presence of anti-beta receptor antibodies was linked to the HLA-DR4 phenotype (that is, 50% of patients with this phenotype were antibody positive) whereas, in those with ischaemic cardiomyopathy HLA-DR1 was over-represented (that is, 37% of the patients with the HLA-DR1 phenotype were antibody positive compared with 17% of the HLA-DR1 negative patients). In both disease entities, the HLA-DR3 phenotype was virtually absent in the anti-beta receptor antibody group. CONCLUSIONS--These results suggest that the presence of anti-beta receptor antibodies is under immune genetic control that may depend on the nature of the underlying disease process.     

HLA-DR antigen linkage of anti-beta receptor antibodies in idiopathic dilated and ischaemic cardiomyopathy.

OBJECTIVE--Immunological mechanisms have been implicated in the pathogenesis of human dilated cardiomyopathy. The presence of autoantibodies against the beta 1 adrenoceptor in a substantial proportion of patients with dilated cardiomyopathy has been described and an association between the HLA-DR4 phenotype and anti-beta receptor antibodies has been identified. The objective of the present study was to examine whether the presence of such antibodies in ischaemic cardiomyopathy was limited to specific HLA-DR phenotypes. DESIGN--The HLA-DR dependence of anti-beta receptor antibodies detected by a ligand binding inhibition assay in patients with dilated cardiomyopathy (n = 68) was compared with that in patients with ischaemic cardiomyopathy (n = 73). RESULTS--38% of the patients with dilated cardiomyopathy and 22% of those with ischaemic cardiomyopathy had serum anti-beta receptor antibodies. In dilated cardiomyopathy, the presence of anti-beta receptor antibodies was linked to the HLA-DR4 phenotype (that is, 50% of patients with this phenotype were antibody positive) whereas, in those with ischaemic cardiomyopathy HLA-DR1 was over-represented (that is, 37% of the patients with the HLA-DR1 phenotype were antibody positive compared with 17% of the HLA-DR1 negative patients). In both disease entities, the HLA-DR3 phenotype was virtually absent in the anti-beta receptor antibody group. CONCLUSIONS--These results suggest that the presence of anti-beta receptor antibodies is under immune genetic control that may depend on the nature of the underlying disease process.