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.     

Blunted increase in plasma adenosine levels following dipyridamole stress in dilated cardiomyopathy patients

BACKGROUND: Heart failure is characterized by chronically increased adenosine levels, which are thought to express a protective anti-heart failure activation of the adenosinergic system. The aim of the study was to assess whether the activation of adenosinergic system in idiopathic dilated cardiomyopathy (IDC) can be mirrored by a blunted increase in plasma adenosine concentration following dipyridamole stress, which accumulates endogenous adenosine. METHODS: Two groups were studied: IDC patients (n = 19, seven women, mean age 60 +/- 12 years) with angiographically confirmed normal coronary arteries and left ventricular ejection fraction <35%; and normal controls (n = 15, six women, mean age 68 +/- 5 years). Plasma adenosine was assessed by high-performance liquid chromatography methods in blood samples from peripheral vein at baseline and 12 min after dipyridamole infusion (0.84 mg kg-1 in 10 min). RESULTS: At baseline, IDC patients showed higher plasma adenosine levels than controls (276 +/- 27 nM L-1 vs. 208 +/- 48 nM L-1, P < 0.001). Following dipyridamole, IDC patients showed lower plasma adenosine levels than controls (322 +/- 56 nM L-1 vs. 732 +/- 250 nM L-1, P < 0.001). The dipyridamole-induced percentage increase in plasma adenosine over baseline was 17% in IDC and 251% in controls (P < 0.001). By individual patient analysis, 18 IDC patients exceeded (over the upper limit) the 95% confidence limits for normal plasma adenosine levels at baseline, and all 19 exceeded (below the lower limit) the 95% confidence limits for postdipyridamole plasma adenosine levels found in normal subjects. CONCLUSION: Patients with IDC have abnormally high baseline adenosine levels and--even more strikingly--blunted plasma adenosine increase following dipyridamole infusion. This is consistent with a chronic activation of the adenosinergic system present in IDC, which can be measured noninvasively in the clinical theatre.     

Increased level of HLA-DR-expressing T lymphocytes in peripheral blood from patients with idiopathic dilated cardiomyopathy

Peripheral blood leukocytes from 14 patients with idiopathic dilated cardiomyopathy (IDC), 13 patients with ischemic congestive heart failure, and 12 controls were characterized using different antibodies. The proportions of B lymphocytes, T lymphocytes, and the different T lymphocyte subsets were estimated. No difference between the three groups could be found in the various T and B cells subpopulations. Using a two-color direct immunofluorescence technique, the occurrence of circulating T helper/inducer (Leu-3a) and T cytotoxic/suppressor cells (Leu-2a) expressing HLA-DR antigens was examined. Only IDC patients demonstrated increased levels of HLA-DR-positive T helper/inducer cells (2.8 +/- 2.4%) and T cytotoxic/suppressor cells (2.8 +/- 2.3%) as compared with patients with ischemic congestive heart failure (0.8 +/- 0.7 and 1.0 +/- 1.0%, respectively) and controls (0.6 +/- 0.5 and 0.9 +/- 0.6%, respectively). When individual IDC patients were studied, 4 out of 12 patients had an increased level of HLA-DR-expressing T helper/inducer cells, and 7 out of 12 patients had elevated HLA-DR-positive T cytotoxic/suppressor cells. The findings suggest that activation of the T lymphocytes may be of importance in the pathogenesis of IDC.     

Transcardiac increase in tumor necrosis factor-alpha and left ventricular end-diastolic volume in patients with dilated cardiomyopathy

BACKGROUND: It remains unclear whether tumor necrosis factor (TNF)-alpha and interleukin-6 (IL-6) are secreted from the failing heart and whether there is a relationship between the transcardiac gradients of these cytokines and left ventricular (LV) remodeling. AIMS: This study evaluated the relationship between transcardiac gradients of cytokines and LV volume and function in congestive heart failure patients with dilated cardiomyopathy (DCM). METHODS AND RESULTS: We measured the plasma levels of TNF-alpha and IL-6 in the aortic root (Ao) and the coronary sinus (CS) in 60 patients with DCM. There was no difference in plasma IL-6 between the Ao and the CS. However, the plasma TNF-alpha level was significantly higher in the CS than that in the Ao. There was a significant correlation between the transcardiac gradient of plasma TNF-alpha and the LV end-diastolic volume index (LVEDVI) and LV ejection fraction. According to stepwise multivariate analyses, the transcardiac increase of TNF-alpha showed an independent and significantly positive relationship with a large LVEDVI. CONCLUSIONS: These results indicate that the elevated plasma TNF-alpha is partly derived from the failing heart in patients with DCM and that TNF-alpha plays a potential role in structural LV remodeling in patients with DCM.     

Immunologic studies in patients with dilated cardiomyopathy]

In 10 cases of dilated cardiomyopathy the HLA-loci (A, B, C, DR) and marker expression on lymphocytes were studied. In this group the T4/T8-ratio was decreased and interleukin-2-expression was increased in relation to normals or patients with chronic coronary heart disease, respectively. 9 patients had the HLA-A1 or HLA-A2-locus in their siblings. In correlation analysis between immunological and hemodynamic parameters a good correlation of the number of NK-cells to the ejection fraction (r = 0.79) and negative correlation of helpercells (CD4) to the cardiac output were found (r = -0.80). The results of this attempt suggest an immunological pathogenesis of the dilated cardiomyopathy.     

Cardiac PPARalpha expression in patients with dilated cardiomyopathy

BACKGROUND: The peroxisome proliferator-activated receptor alpha (PPARalpha) is a central regulator of myocardial fatty acid (FA) metabolism implicated in the pathogenesis of heart failure. AIMS: To characterize PPARalpha regulation in human dilated cardiomyopathy (DCM), we studied the expression of cardiac PPARalpha, cardiac carnitine palmitoyl-transferase I (CPT-1), a major PPARalpha target gene, and of the cardiac glucose transporter GLUT-4 in patients with DCM. METHODS: Left ventricular biopsies were taken from patients with DCM (n=16) and control subjects (n=15), and mRNA expression was quantitated using real-time PCR (SYBR((R))Green) and protein expression was measured by Western immunoblotting. RESULTS: Left ventricular PPARalpha mRNA levels were significantly increased in the DCM group compared to the control group (136+/-25.4% vs. control, p<0.01). Consistently, DCM patients had a significantly higher cardiac CPT-1 mRNA expression (147+/-51% vs. control, p<0.05) compared to the control group. Cardiac GLUT-4 expression was similar in both groups. CONCLUSION: Elevated cardiac PPARalpha levels followed by an induction of cardiac CPT-1 expression may result in increased fatty acid metabolism for cardiac energy production in DCM, suggesting a specific cardiac metabolic program in human DCM compared to other types of cardiomyopathy.     

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.     

Left atrial functional reserve in patients with nonischemic dilated cardiomyopathy: an echocardiographic dobutamine study

OBJECTIVE: To evaluate left atrial functional reserve in patients with chronic heart failure and nonischemic dilated cardiomyopathy (DCM). BACKGROUND: Left ventricular functional status has been investigated using echocardiographic dobutamine. METHODS: In 35 consecutive patients (29 men and 6 women; mean +/- SD age, 42.37 +/- 13.5 years), peak oxygen consumption (O(2)max) was measured; the day after, a low-dose dobutamine (5 to 10 micro g/kg/min, of 5 min each step) study was performed. Left atrial volumes at mitral valve opening, onset of left atrial systole, and mitral valve closure were measured by using two-dimensional echocardiography. Left atrial active emptying volume (LAEV) [volume at onset of atrial systole - minimal volume] was calculated, as was left atrial active emptying fraction (LAEF): [(volume at onset of atrial systole - minimal volume)/volume at onset of atrial systole] x 100. The changes (values obtained after inotropic stimulation minus those obtained at baseline) of the above-mentioned echocardiographic variables were considered as left atrial functional reserve. RESULTS: In the entire study group after dobutamine infusion, increases in LAEV (3.34 +/- 7.54 mL, p = 0.01) and LAEF (6 +/- 13.2%, p = 0.01) were observed. The changes in the above-mentioned parameters were correlated with O(2)max values (r = 0.73 and r = 0.71, respectively; p < 0.001). After inotropic stimulation, LAEV and LAEF were increased in patients with O(2)max values > 14 mL/kg/min (5.62 +/- 7.28 mL and 10.04 +/- 13.13%, respectively) and decreased in patients with O(2)max values < 14 mL/kg/min (- 1.08 +/- 6.13 mL and - 1.6 +/- 9.9%, respectively; p = 0.01 for both). CONCLUSION: Echocardiographic dobutamine can evaluate left atrial functional reserve in patients with nonischemic DCM.     

Prognostic value of an abnormal signal-averaged electrocardiogram in patients with nonischemic dilated cardiomyopathy

The usefulness of an abnormal signal-averaged ECG (SAECG) for the risk stratification of patients with dilated cardiomyopathy was studied prospectively in 76 patients. Multiple analysis showed that an abnormal SAECG predicted cardiac mortality (p = 0.0046), sudden cardiac death, and the need for resuscitation (p = 0.003); however, it did not predict death from heart failure and heart transplantation.     

Silent cerebral infarction in patients with dilated cardiomyopathy: echocardiographic correlates

BACKGROUND: Patients with dilated cardiomyopathy (DCM) have an increased risk of thromboembolic events. Incidence of silent cerebral infarction (SCI) has not been investigated in these patients. The aim of this study was to investigate the incidence of SCI in patients with DCM and to determine its associations with echocardiographic parameters. METHODS AND RESULTS: Seventy-two patients (mean age 62+/-12 years) with DCM underwent cranial magnetic resonance imaging in addition to transthoracic and transesophageal echocardiographic examination. A total of 56 age-matched healthy volunteers served as a control group for comparison SCI prevalence. Prevalence of SCI was significantly higher in patients with DCM (35% vs. 3.6%; p<0.001). In DCM group, patients with SCI had significantly impaired left ventricular systolic function, higher frequency of restrictive diastolic filling, moderate to severe left atrial spontaneous echo contrast (SEC), aortic SEC, and complex atherosclerosis or calcified plaques in the aorta. In logistic regression analysis, type of diastolic filling emerged as the only independent risk factor for SCI (p<0.001). When the type of diastolic filling was removed from the analysis, ejection fraction, marked left atrial SEC, complex-calcified aortic atheroma and age appeared as the other independent risk factors (p = 0.003, p = 0.009, p = 0.013 and p = 0.018, respectively). CONCLUSION: SCI is a frequent finding in DCM patients. Impaired systolic function, restrictive filling pattern, presence of moderate to severe left atrial SEC, and complex atherosclerosis in the aorta are the factors contributing to the development of SCI.     

扩张型心肌病40例心电图分析

目的:分析扩张型心肌病(DCM)的心电图改变,为临床诊断治疗提供依据。方法:回顾分析40例≤50岁DCM患者的心电图资料,总结DCM心电图特点。结果:DCM患者的心电图均有异常,其中以心律失常最多见(77.5%),其他依次为ST-T改变(70%),传导阻滞(45%),房室肥大(40%),异常Q波(30%),低电压(10%)等。结论:DCM有多种心电图表现,其多发、多样、顽固的心律失常对扩张型心肌病早期诊断有重要意义。