Peripheral blood levels of matrix metalloproteinases in patients referred for percutaneous balloon mitral valve commissurotomy

BACKGROUND AND AIM OF THE STUDY: Inflammation may play a central role in the progression of stenotic valvular heart disease. Serum levels of matrix metalloproteinases (MMPs), markers of extracellular matrix (ECM) turnover and potential markers of active inflammation, have been recently demonstrated in several inflammatory processes. The present study was designed to examine whether systemic evidence of ECM turnover was present in advanced stenotic mitral valve disease. METHODS: Serum levels of MMP-1, -3 and -9 were measured in 114 patients with mitral stenosis referred for percutaneous balloon mitral valve commissurotomy, and compared to those in 48 healthy, age- and gender-matched controls. RESULTS: Serum levels of MMP-1, -3 and -9 did not vary according to hemodynamic profile or heart failure class at the time of blood sampling. Levels of MMP-1 and -3 were not significantly different between those patients with mitral stenosis and controls. The level of MMP-9 was significantly higher in patients with mitral stenosis than in controls, and did not appear to be altered by commissurotomy. CONCLUSION: Serum levels of MMP-9 were elevated in patients with mitral stenosis, providing further evidence that inflammation and ECM remodeling plays an important role in the pathophysiology of valvular heart disease.     

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in hypertension and their relationship to cardiovascular risk and treatment: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)

BACKGROUND: Hypertension results in structural changes to the cardiac and vascular extracellular matrix (ECM). Matrix metalloproteinases (MMP) and their inhibitors (TIMP) may play a central role in the modulation of this matrix. We hypothesized that both MMP-9 and TIMP-1 would be abnormal in hypertension, reflecting alterations in ECM turnover, and that their circulating levels should be linked to cardiovascular (CHD) and stroke (CVA) risk scores using the Framingham equation. Second, we hypothesized that treatment would result in changes in ECM indices. METHODS: Plasma MMP-9 and TIMP-1 were measured before and after treatment (median 3 years) from 96 patients with uncontrolled hypertension participating in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Pretreatment values were compared to circulating MMP-9 and TIMP-1 levels in 45 age- and sex-matched healthy controls. RESULTS: Circulating pretreatment MMP-9 and TIMP-1 levels were significantly higher in patients with hypertension than in the normotensive controls (P =.0041 and P =.0166, respectively). Plasma MMP-9 levels decreased, and TIMP-1 levels increased after treatment (P =.035 and P =.005, respectively). Levels of MMP-9 correlated with CHD risk (r = 0.317, P =.007) and HDL cholesterol (r = -0.237, P =.022), but not CVA risk. There were no significant correlations between TIMP-1 and CVA or CHD scores. CONCLUSIONS: Increased circulating MMP-9 and TIMP-1 at baseline in patients with hypertension could reflect an increased deposition and retention of type I collagen at the expense of other components of ECM within the cardiac and vascular ECM. After cardiovascular risk management, MMP-9 levels decreased and TIMP-1 levels increased. Elevated levels of MMP-9 also appeared to be associated with higher Framingham cardiovascular risk scores. Our observations suggest a possible role for these surrogate markers of tissue ECM composition and the prognosis of cardiovascular events in hypertension.     

Apparently normal mitral valves in patients with heart failure demonstrate biochemical and structural derangements: an extracellular matrix and echocardiographic study

OBJECTIVES: This study assessed apparently normal mitral valves from patients with congestive heart failure (CHF) using biochemical and echocardiographic measures of extracellular matrix (ECM) and anatomy. BACKGROUND: Mitral regurgitation (MR) is frequently found in patients with CHF. This MR is considered purely functional, yet animal studies suggest that altered left ventricular (LV) function leads to increased cellularity and fibrosis of the mitral valve. Therefore, we hypothesized that patients with CHF might have partly organic MR, via dysfunctional valvular remodeling. METHODS: Mitral valves from transplant recipient hearts of patients with CHF (23 dilated, 14 ischemic) were analyzed for deoxyribonucleic acid (DNA), collagen, glycosaminoglycan (GAG), and water concentrations and compared with autopsy controls. Cardiac dimensions and functional parameters (measured from recent echocardiograms) were compared with biochemical parameters using a repeated measures generalized linear model. RESULTS: The mitral valves in CHF had up to 78% more DNA (p <0.03), 59% more GAGs (p <0.02), and 15% more collagen (p <0.007), but 7% less water (p <0.05) than normal. The absence of anterior leaflet redundancy was associated with these deranged biochemical measures (p <0.03). Associations were found between leaflet thickness and DNA concentration (+, p=0.003), annular diameter and chordal collagen (+, p=0.03), and water concentration and both left atrial diameter (-, p=0.008) and LV collagen concentration (-, p=0.04). CONCLUSIONS: Mitral valves in CHF are biochemically different from normal, with ECM changes that are influenced by the altered cardiac dimensions. This remodeling suggests that MR in patients with CHF may not be purely functional, and that these valves are not "normal."     

脂联素对慢性心力衰竭伴糖尿病患者的影响

目的:探讨脂联素与心力衰竭(心衰)患者心功能、前脑钠肽(pro-BNP)及高敏C反应蛋白(hs-CRP)等生化及生物标志物指标的相关性,以及脂联素与心衰尤其是合并糖尿病者预后的关系。方法:选择慢性心衰患者203例,分为伴有糖尿病组93例和不伴有糖尿病组110例。健康对照组60名。将患者全因死亡、猝死作为终点事件,随访1年,采用酶联免疫吸附法测定其血清脂联素、pro-BNP及hs-CRP水平。结果:心衰组脂联素水平较正常对照组明显升高(P<0.01),心衰伴糖尿病组较心衰不伴糖尿病组脂联素水平有所下降(P<0.05)。体质量指数(BMI)、心功能分级、慢性肾功能不全、pro-BNP、三酰甘油(TG)及高密度脂蛋白(HDL)是脂联素水平的独立影响因素。脂联素是心衰病死率的独立预测因子(P<0.05)。结论:慢性心衰患者血清脂联素水平明显升高,且与心衰严重程度(心功能分级)正相关,但伴有糖尿病者脂联素水平有所降低,脂联素是慢性心衰患者预后的独立预测因子。     

Serum levels of collagen type-I degradation markers are associated with vascular stiffness in chronic heart failure patients

BACKGROUND: Chronic heart failure (CHF) induces peripheral vasoconstriction, endothelial dysfunction and arterial stiffness by activation of various neurohormonal pathways. The abnormal collagen turnover observed in CHF may be attributed not only to myocardial remodelling, but also to vascular remodelling. However, the effect of collagen metabolism on progressive large artery stiffening in the setting of CHF is understudied. AIMS: The present study was undertaken to investigate the association between circulating markers of collagen turnover and vascular stiffness in patients with CHF. METHODS: Eighty patients (mean age 65+/-11 years, 68 men) with stable CHF and in sinus rhythm, were studied. Serum concentrations of carboxy-terminal telopeptide of collagen type I (CITP) and amino-terminal propetide of procollagen type I (PINP), markers of collagen type I degregation and synthesis respectively, were measured in all patients. Pulse wave velocity (PWV) and augmentation index (AIx) of aortic pulse wave form, markers of arterial stiffness, were also determined by applanation tonometry. RESULTS: Peripheral PWV was inversely associated with serum CITP levels (r=-0.585, p<0.001). AIx although weakly was negatively correlated with serum CITP levels (r=-0.285, p=0.01). Multiple regression analysis showed that peripheral PWV remained independently associated with serum CITP levels after adjustment for all confounding variables. CONCLUSIONS: Findings from the present study imply a possible link between altered collagen metabolism and peripheral vascular stiffness in CHF.     

Predictors of congestive heart failure in patients on maintenance hemodialysis.

BACKGROUND: Cardiovascular disease is a major cause of death in patients on maintenance hemodialysis (HD). Predictors of congestive heart failure (CHF) events in patients on HD were investigated, focusing on left ventricular (LV) function. METHODS AND RESULTS: One hundred consecutive patients on HD were followed for at least 5 years after index examination performed 1 day after the last HD session. Tests included M-mode and Doppler echocardiography and plasma brain natriuretic peptide (BNP) and hemoglobin (Hb) concentration measurements. Patients with atrial fibrillation or poor echocardiographic images were excluded. Confounding factors included diabetes mellitus (DM), hypertension, age, HD duration, LV fractional shortening, E/A of transmitral flow velocity pattern, Tei index, LV mass index (LVMI), BNP level, Hb, and use of antihypertensive or antiarrhythmic drugs. Six CHF events occurred during 1,703+/-565 days. DM and Hb <10 g/dl were identified as independent predictors of CHF events in a stepwise Cox regression model after DM, LVMI, BNP, and Hb <10 g/dl were selected in the univariate analysis. The hazard ratio (confidence interval) was 10.96 (1.49-80.44) for DM, and 23.00 (2.41-219.76) for Hb <10 g/dl. The estimated hazard across time was constant (T_COV*DM; p=0.726, T_COV*Hb <10 g/dl; p=0.681) by time-dependent covariates analysis. CONCLUSION: In patients on maintenance HD, DM and anemia (Hb <10 g/dl), but not echo-derived cardiac function, predicted CHF events.     

慢性充血性心力衰竭患者血浆中C-反应蛋白、肾上腺髓质素及内皮素水平变化的研究

目的 :以血浆 C-反应蛋白 ( CRP)的浓度作为体内细胞因子激活程度的指标 ,研究心力衰竭时细胞因子激活后 CRP的变化及对肾上腺髓质素 ( ADM)及内皮素 - 1( ET- 1)等血管活性物质的影响。　　方法 :CRP采用散射比浊法测定 ,ET- 1及 ADM采用放射免疫分析法测定。对 3 0例失代偿性心功能衰竭患者 (为心力衰竭组 )及 2 5例心功能正常的原发性高血压患者 (为心功能代偿组 )血浆 CRP、ADM及 ET- 1的浓度进行测定。　　结果 :心力衰竭组血浆 CRP、ADM及 ET- 1浓度较心功能代偿组均明显升高 ;在心力衰竭组 ,不同心功能 ( NYHA)分级的患者随心功能衰竭加重 ,血浆 CRP及 ADM的浓度均有所升高 ,而 ET- 1浓度在不同心功能分级的患者中无显著差异 ;心力衰竭组患者血浆 CRP浓度及 ADM浓度呈正相关。　　结论 :慢性充血性心力衰竭患者体内存在着细胞因子、ADM及 ET- 1的激活 ,细胞因子活化可能通过促进 ADM等的合成作用于心力衰竭的体液调节 ,但与 ET- 1的活化没有明显的关系。     

Interleukin-6, tissue factor and von Willebrand factor in acute decompensated heart failure: relationship to treatment and prognosis.

Arterial thrombotic and thromboembolic complications are increased in congestive heart failure (CHF), and are a particular problem in acute decompensated heart failure, which carries a poor prognosis. As interleukin-6 (IL-6) has been shown to induce the potent procoagulant tissue factor (TF) in experimental models, we hypothesized that the pro-inflammatory IL-6 may be one mechanism contributing to thrombosis in heart failure, mediated via endothelial expression of TF on activated/damaged cells [indicated by plasma von Willebrand factor (vWF)]. Seventy-seven patients (67% men, New York Heart Association class III-IV, 87%) with acute CHF were recruited, and were compared with 53 chronic stable CHF patients in sinus rhythm (66% men, New York Heart Association class III-IV, 2%) and 37 healthy controls (68% men). Acute CHF patients in sinus rhythm had elevated baseline levels of IL-6 (P < 0.0001), TF (P = 0.041) and vWF (P < 0.0001) (all measured by enzyme-linked immunosorbent assay) compared with both chronic CHF and healthy control groups. A correlation exists in acute CHF between baseline TF and IL-6 (Spearman r = 0.64, P < 0.0001). After 3 months treatment, with control or alleviation of heart failure symptoms in 40 patients, there was a fall in levels of IL-6 (P < 0.0001) and vWF (P < 0.0001), but levels still remained significantly higher than healthy controls. Patients who died at 6 months follow-up also had higher baseline levels of IL-6 (P = 0.008), TF (P = 0.037) and vWF (P = 0.039) when compared with those who remained alive. Elevated IL-6 may contribute to the thrombotic and thromboembolic complications in acute heart failure, in a process mediated via increased TF and vWF. Improvement of symptoms and plasma markers after treatment of acute CHF and prediction of prognosis by the markers may be useful in the clinical setting.     

Studies on apoptosis and fibrosis in skeletal musculature: a comparison of heart failure patients with and without cardiac cachexia

Apoptosis has been found in skeletal muscles of patients with chronic heart failure (CHF) and has been associated with exercise intolerance. In CHF, cachexia is characterized by neurohormonal activation and muscle wasting. Neurohormonal activation can lead to cell death and fibrosis. The purpose of the study was to determine the severity of apoptosis and fibrosis in skeletal muscles of patients with CHF and cachexia and its relationship to exercise intolerance in these patients. Skeletal muscle biopsies of 21 patients with CHF (eight with cachexia) and four healthy controls of similar age have been studied by in situ end labeling (ISEL) for apoptosis and by the Picrosirius Red technique for collagen. Apoptosis in skeletal muscles was detected by ISEL in 52% of the patients with CHF (11 out of 21) and in none of the controls. CHF patients with apoptosis-positive skeletal muscles had impaired exercise tolerance (peak oxygen consumption 11.4+/-5.7 vs. 16.91+/-6.6, P=0.029). Increased collagen was detected by Picrosirius Red in eight out of 21 patients with CHF and in none of the controls. Increased collagen (fibrosis) was detected in six out of eight patients with cachexia and in two out of 13 patients without cachexia (P=0.01). Peak oxygen consumption and apoptosis were similar in cachectic and non-cachectic patients. Thus, the skeletal musculature of patients with cardiac cachexia is characterised by the presence of fibrosis. Apoptosis was not found to be more frequent in cachectic CHF patients. Our data support the hypothesis that cachexia contributes by a different mechanism to skeletal muscle myopathy of CHF patients and different mechanisms are implicated in deterioration of exercise tolerance and progression to cardiac cachexia.     

Propeptide of procollagen type I (PIP) and outcomes in decompensated heart failure

BACKGROUND: Changes in extracellular matrix are recognized as a contributing factor in the cardiac remodeling process. Several studies have addressed the value of turnover markers of collagen as predictors of death or new heart failure episodes. The aim of the present study was to evaluate the relationship between peripheral serum concentration of propeptide of procollagen type I (PIP) and outcomes in patients with decompensated heart failure. METHODS: A total of 111 patients admitted to our Unit between September 2000 and May 2003 for decompensated heart failure were analyzed. Death from any cause or due to heart failure and readmission were considered primary endpoints. RESULTS: The mean PIP concentration was 80.84+/-36.40 ng/mL. The PIP serum level was significantly higher among those patients who suffered some endpoint during follow-up (88.12+/-37.31 ng/mL vs 73.13+/-34.06 ng/mL; p=0.029). Twenty-five (22.52%) of the 111 patients died during the 21 months of follow-up, and 54 (48.6%) were readmitted with new bouts of heart failure. Using Cox proportional hazards regression analyses, serum PIP levels, systolic dysfunction, and diabetes mellitus were identified as independent predictors of death. Serum PIP levels, age, and sex were independent predictors of new heart failure episodes and readmission. CONCLUSION: A single serum measurement of PIP seems to have prognostic value in patients with decompensated heart failure. Accordingly, patients with higher values of PIP at decompensation are at a higher risk of death or readmission during follow-up.     

外周血核因子-κB及sFas/sFasL活性与心力衰竭严重程度的相关性

目的:探讨充血性心力衰竭(CHF)患者外周血单个核细胞(PBMCs)核因子-κB(NF-κB) 和血浆sFas/sFasL活性变化的意义。方法: 采用ELISA法检测76例CHF患者和30例对照组PBMCs的核蛋白提取物NF-κB和血浆sFas/sFasL的活性,并与患者心功能及超声心动图参数相比较,分析其与心功能及心肌重构的关系。结果: CHF患者PBMCs中NF-κB及血浆sFas/sFasL活性高于对照组,二者与心脏收缩功能相关指标呈显著负相关,与心肌重构相关指标呈显著正相关,并且NF-κB的活化与sFas/sFasL水平呈正相关(P<0.05)。结论: CHF患者NF-κB及sFas/sFasL活性明显增高, 并与心功能恶化及心肌重构程度密切相关。     

强离子隙在慢性心力衰竭患者中的水平改变及临床意义

目的探讨强离子隙(SIG)水平在慢性心力衰竭(CHF)患者中的改变及其与CHF患者心功能、N末端B型利钠肽前体(NT-proBNP)水平的相关性。方法选择CHF患者90例,根据心功能(NYHA)分级分为心功能Ⅱ级组30例、心功能Ⅲ级组30例和心功能Ⅳ级组30例;根据CHF病因分为冠心病组25例、高血压性心脏病组45例和扩张型心肌病组20例;选择健康体检者35例作为对照组,在测定血气、电解质等的基础上,应用Stewart-Figge方法学的方程式计算SIG,采用电化学免疫法测定NT-proBNP。结果与对照组比较,心功能Ⅱ、Ⅲ和Ⅳ级组患者SIG[(5.54±2.23)mmol/L、(7.65±3.12)mmol/L和(10.54±3.84)mmol/L vs(1.70±0.81)mmol/L]、NT-proBNP[(114.85±36.23)ng/L、(476.30±79.45)ng/L和(782.50±99.38)ng/L vs(42.74±11.29)ng/L]水平明显升高;且心功能Ⅱ、Ⅲ和Ⅳ级组间SIG水平比较,差异有统计学意义(P<0.05)。与治疗前比较,不同心功能组治疗后SIG和NT-proBNP水平明显下降,差异有统计学意义(P<0.01)。GHF患者SIG与NT-proBNP呈正相关(r=0.424,P<0.01)。结论 CHF患者血清SIG水平明显升高,且随着心功能不全程度的加重而升高,与NT-proBNP存在一定的相关性,对CHF的早期诊断、风险评估及治疗评价均具有指导意义。     

慢性心衰患者炎症细胞因子表达及其与心功能的关系

目的观察慢性心力衰竭（CHF）患者外周血炎症细胞因子白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、纤维蛋白原（FG）、超敏C-反应蛋白（hs—CRP）水平变化及其与心功能状况的关系。方法选择60例CHF患者为病例组,包括冠心病30例、高血压性心脏病14例、心肌病16例（扩张型心肌病10例、肥厚型心肌病6例）。另外选择40例年龄、性别与病例组相匹配的健康受试者作为对照组。所有受试者均测定外周血IL-1β、IL-6、TNF—α、FG、hs—CRP水平和血脂（TC、TG、LDL—C、HDL—C）,同时询问吸烟史、高血压病史及糖尿病史。CHF患者评估NYHA心功能分级。结果CHF患者外周血炎症细胞因子IL-1β、IL-6、TNF—α、FG、hs—CRP水平显著高于对照组（P〈0．01）;不同病因心衰患者间IL-1β、IL-6、TNF—α、FG、hs—CRP水平差异无统计学意义（P〉0．05）;不同NYHA心功能分级组间IL-18、IL-6、TNF—α、FG、hs—CRP水平差异存在统计学意义（P〈0．05或P〈0．01）。结论CHF患者外周血炎症细胞因子IL-1β、IL-6、TNF—α、FG、hs—CRP水平显著高于对照组,不同NYHA心功能分级组间IL-1β、IL-6、TNF—α、FG、hs—CRP水平差异存在统计学意义。它们之间可能有相互作用,共同参与CHF的发病机制。     

Microvascular abnormalities in chronic heart failure: a cross-sectional analysis

OBJECTIVES: Similar to what has been found in hypertension, elevated peripheral resistance in chronic heart failure (CHF) might be related to microvascular constriction and rarefaction. Our objective was to evaluate both structural and functional microvascular changes in patients with CHF in relation to left ventricular function and neurohumoral activation. METHODS: In 25 patients with mild and severe CHF (New York Heart Association class I-II [n = 11] and class III-IV [n = 14]) and 10 age-matched healthy subjects, we studied microvascular density, diameters, and morphology of the bulbar conjunctiva and skin nailfold using intravital microscopy. RESULTS: Total conjunctival microvascular density was higher in patients with mild heart failure compared with healthy controls, whereas it was lower in severe heart failure (medians, 6.75, 4.31, and 3.56 mm/mm2, respectively, p < 0.01). In patients with heart failure, venular density was correlated with left ventricular ejection fraction. Nailfold capillary recruitment during postocclusive reactive hyperemia, a measure of functional reserve capacity, was impaired in patients with severe CHF (p < 0.05). Furthermore, in severe CHF, more abnormal capillaries and enlarged diameters were found in the nailfold (p < 0.05). CONCLUSIONS: In heart failure, several microvascular abnormalities occur that differ, depending on the severity of this condition.     

依那普利对充血性心力衰竭患者血浆儿茶酚胺和血淋巴细胞β受体的影响

本文测定54例充血性心力衰竭(CHF)患者血浆儿茶酚胺[CA:包括去甲肾上腺素(NA)、肾上腺素(A)、多巴胺(DA)]和血淋巴细胞β受体密度(L-BAR),并以15例正常人作为对照。结果表明,CHF患者血浆CA显著增高,其中NA增高更为突出,可反映心功能的受损程度;L-BAR仅重症者显著降低;NA、A与L-BAR呈显著负相关。依那普利(Enalapril)治疗后,NA显著降低,A、DA和L-BAR无明显变化,心功能改善。     

慢性充血性心力衰竭患者心率变异性及其昼夜节律变化

目的分析慢性充血性心力衰竭(CHF)患者心率变异性(HRV)及其昼夜节律的变化,了解CHF患者自主神经功能损害与心功能的关系。方法用24小时动态心电图分析38例CHF患者,20例心功能代偿的心血管病患者心功能代偿组,16例健康体检者对照组的HRV时域指标。比较三组间HRV指标的差异;计算CHF患者HRV昼夜指标差异,分析CHF患者24小时HRV指标变化与心功能NYHA分级的关系。结果心功能代偿组24小时HRV时域指标SDNN、SDANN和SDNNindex较对照组显著下降P<0.01、0.05和0.05rMSSD和pNN50与对照组无显著差别P>0.05;CHF组的HRV各指标均显著低于对照组均P<0.01且昼夜指标变化无差异;将CHF组分为心功能Ⅱ级组n=20和心功能≥Ⅲ级n=18两个亚组结果发现心功能≥Ⅲ级的HRV各指标明显低于心功能Ⅱ级组P<0.01。结论心血管病患者可能在心功能代偿期时自主神经的平衡就已受到损害当出现CHF时交感活性增强迷走神经张力进一步下降,自主神经调节昼夜节律性丧失,且HRV指标的下降与心功能损害程度相关因此HRV时域指标可作为评价CHF预后指标之一。     

Enhanced expression of inflammatory cytokines and activation markers in T-cells from patients with chronic heart failure

OBJECTIVE: Increasing evidence supports a role for inflammation in chronic heart failure (CHF). However, the source and the mechanism for this immune activation are unknown. To address this issue we investigated the gene expression of cytokines and the surface expression of activity markers in T-cells and monocytes from CHF patients and healthy controls. METHODS: Gene expression of cytokines was analysed by real-time RT-PCR and activation markers by flow cytometry in 14 CHF patients and nine healthy controls. Surface expression of activation markers for T-cells and monocytes were analysed by flow cytometry. RESULTS: T-cells from CHF patients showed enhanced gene expression of chemokines, ligands in the tumor necrosis factor superfamily, as well as the inflammatory cytokines interferon-gamma and interleukin-18 with similar pattern in ischemic (n=5) and idiopathic cardiomyopathy (n=9). In contrast, no differences in cytokine gene expression were found comparing monocytes from CHF patients and controls. Moreover, T-cells from CHF patients had enhanced surface expression of the activation markers CD69 and CD25, while there was no upregulation of the monocyte activation marker CD32 in these patients. CONCLUSION: T-cells may be a part of the inflammatory response during CHF independent of the etiology of the disorder. Intervention preventing unwanted T-cell activation could represent a new target in the treatment of CHF.     

Profile of cognitive impairment in chronic heart failure

OBJECTIVES: To determine the frequency and pattern of cognitive dysfunction in outpatients with chronic congestive heart failure (CHF) and to identify the corresponding demographic and clinical correlates.
DESIGN: Case-control study.
SETTING: Outpatient clinic in a community hospital.
PARTICIPANTS: Sixty-two outpatients with CHF, 53 controls diagnosed with cardiovascular disease uncomplicated by CHF (cardiac controls), and 42 healthy controls were investigated.
MEASUREMENTS: Neuropsychological assessment included tests of mental speed, executive function, memory, language, and visuospatial function. Composite z -scores for five cognitive domains and mean z -score for overall cognitive performance were computed. The cutoff score to indicate cognitive impairment was defined as the overall healthy participants' cognitive z -score minus 2 standard deviations. Independent demographic and clinical predictors of cognitive impairment were identified using linear regression analysis.
RESULTS: Patients with CHF showed a pattern of general cognitive impairment, including impairment of executive function, memory, language, mental speed, and attention. Twenty-five percent ( P =.04) of patients with CHF were classified as cognitively impaired, compared with 15% of the cardiac controls and 4% of the healthy controls. Independent predictors of cognitive impairment in patients with CHF were estimated intelligence, New York Heart Association class, and presence of the apolipoprotein (Apo)E ɛ4 allele.
CONCLUSION: Cognitive dysfunction is relatively common in patients with CHF, with deficits being most prominent in the domains of executive function, memory, language, and mental speed. Disease severity and ApoE genotype are likely to be important determinants for cognitive impairment in patients with chronic CHF.     

交感神经皮肤反应对评价慢性心力衰竭患者植物神经损害的意义

目的:探讨慢性心力衰竭(CHF)患者交感神经皮肤反应(SSR)的变化及其临床意义.方法:对72例CHF患者行SSR检测,并与30例对照组比较.结果:与对照组比较,CHF患者SSR检测起始潜伏期(Lat)延长和峰-峰波幅值(Amp)降低,随着心功能损害程度的加重出现Lat逐渐延长、Amp逐渐降低,甚至SSR波形消失(P<...     

Congestive heart failure is a rare event in patients receiving imatinib therapy

A recent preclinical study suggested that imatinib may be cardiotoxic in some patients. We reviewed all reported serious adverse events of cardiac adverse events occurring in patients on clinical trials involving imatinib. Among 1276 patients enrolled, 22 (1.7%) were identified as having symptoms that could be attributed to systolic heart failure. The median age was 70 years (range, 49 to 83 years). The median time from start of imatinib therapy was 162 days (range, 2-2045 days). At the time these events were reported, 8 (0.6%) were considered possibly or probably related to imatinib. A total of 18 patients had previous medical conditions predisposing to cardiac failure: congestive heart failure (CHF; 6 [27%] patients), diabetes mellitus (6 [27%] patients), hypertension (10 [45%] patients), coronary artery disease (CAD; 8 [36%] patients), arrhythmia (3 [14%] patients), and cardiomyopathy (1 [5%] patient). Of the 22 patients, 11 continued imatinib therapy with dose adjustments and management for the CHF symptoms without further complications. Imatinib therapy as a causal factor of CHF is uncommon, mainly seen in elderly patients with preexisting cardiac conditions. Patients with previous cardiac history should be monitored closely and treated aggressively with standard medical therapy, including diuretics, if they develop symptoms suggestive of heart failure.