Upregulation of cell adhesion molecules and the presence of low grade inflammation in human chronic heart failure

BACKGROUND: In the present study, the hypothesis was tested that cell adhesionmolecules are expressed in failing human hearts and that a chronicinflammatory process contributes to chronic degeneration knownto occur in cardiac incompetence. The cell adhesion molecules:ICAM-1, VCAM-1, PECAM-1, and E-selectin were studied, in additionto cellular markers of inflammation. METHODS AND RESULTS: Tissue was obtained at transplantation from patients with eithermyocarditis, chronic ischaemic heart disease, or dilated cardiomyopathy.Controls were taken from patients with normal ventricles. Celladhesion molecules were qualitatively evaluated and countedusing specific antibodies and confocal microscopy. Additionally,semiquantitative evaluation of the presence of the CD3 antigen(T-lymphocytes), CD68 (macrophages), CD11a/CD18 (ICAM-1 receptor)and human tumour necrosis factor- were used as indicators ofchronic inflammation. PECAM-1 stained all endothelial cellsbut ICAM-1 was only present in 80% of all capillaries in controltissue. The ratio ICAM-1/PECAM-1 was significantly enhancedin all groups of diseased hearts. Myocytes in myocarditic heartsexpressed ICAM-ICAM. CD3 positive lymphocytes, CD68 positivemacrophages and CD11a/;CD18 positive cells were more abundantlypresent than in control. Macrophages expressing tumour necrosisfactor- were found in failing myocardium but not in controltissue. CONCLUSION: Independent of the cause of heart failure, chronic low gradeinflammation is present in failing human myocardium. This maysignificantly contribute to the structural deterioration thatis the basis of reduced cardiac function in congestive heartfailure.     

Effects of exercise training on diastolic and systolic dysfunction in patients with chronic heart failure

BACKGROUNDChronic heart failure (CHF) is a complex syndrome characterized by a progressive reduction of the left ventricular (LV) contractility, low exercise tolerance, and increased mortality and morbidity. Diastolic dysfunction (DD) of the LV, is a keystone in the pathophysiology of CHF and plays a major role in the progression of most cardiac diseases. Also, it is well estimated that exercise training induces several beneficial effects on patients with CHF. AIMTo evaluate the impact of a cardiac rehabilitation program on the DD and LV ejection fraction (EF) in patients with CHF.METHODSThirty-two stable patients with CHF (age: 56 ± 10 years, EF: 32% ± 8%, 88% men) participated in an exercise rehabilitation program. They were randomly assigned to aerobic exercise (AER) or combined aerobic and strength training (COM), based on age and peak oxygen uptake, as stratified randomization criteria. Before and after the program, they underwent a symptom-limited maximal cardiopulmonary exercise testing (CPET) and serial echocardiography evaluation to evaluate peak oxygen uptake (VO_2peak), peak workload (W_peak), DD grade, right ventricular systolic pressure (RVSP), and EF.RESULTSThe whole cohort improved VO_2peak, and W_peak, as well as DD grade (P < 0.05). Overall, 9 patients (28.1%) improved DD grade, while 23 (71.9%) remained at the same DD grade; this was a significant difference, considering DD grade at baseline (P < 0.05). In addition, the whole cohort improved RVSP and EF (P < 0.05). Not any between-group differences were observed in the variables assessed (P > 0.05).CONCLUSIONExercise rehabilitation improves indices of diastolic and systolic dysfunction. Exercise protocol was not observed to affect outcomes. These results need to be further investigated in larger samples.     

Comprehensive local muscle training increases aerobic working capacity and quality of life and decreases neurohormonal activation in patients with chronic heart failure

BACKGROUND: Beneficial training outcomes have been reported in patients with chronic heart failure (CHF) following leg exercise training. However, data from more comprehensive training programs are limited. The aim of this study was to test the hypothesis that exercise training applying the concept of comprehensive local muscle training can improve aerobic and functional working capacity as well as quality of life in patients with CHF. METHODS: Twenty-four men and women [age 63+/-9 years (mean+/-S.D.)] with stable, moderate chronic heart failure (left ventricular ejection fraction 30+/-10%), were investigated in a randomized controlled study with a training group of 16 patients and a control group of 8 patients. The training was performed as an aerobic resistance training by activating all the main muscle groups, one at a time. The patients exercised for 1 h, three times per week for 8 weeks. RESULTS: Patient groups did not differ at baseline. Peak oxygen uptake (8%, P<0.03), the distance walked in a 6-min walking test (11%, P<0.002), the health-related quality of life (P<0.001) and plasma norepinephrine levels at rest (32%, P<0.003) and at submaximal intensities (P<0.03) improved after training. No changes were found in the control group, except for decreased peak oxygen uptake (P<0.02) and quality of life scores (P<0.03). CONCLUSIONS: Since comprehensive physical training activating a minor muscle mass at a time markedly improves exercise capacity and quality of life and reduces catecholamine levels, it can be recommended for the rehabilitation of patients with CHF under supervision of a physical therapist.     

The effect of physical training on skeletal muscle in patients with chronic heart failure

BACKGROUND: The improvement of exercise capacity in patients with chronic heart failure (CHF) by physical training has been connected with reversal of the abnormalities in muscle fiber distribution and with the reduced activity of the enzymes of oxidative metabolism in skeletal muscle. However, the change in fiber type distribution induced by training is controversial and in previous studies the activities of the rate-limiting enzymes of the metabolic pathways have not been measured. AIMS: To examine the effect of dynamic training on percentage distribution of muscle fibers, on activities of the rate-limiting enzymes of the metabolic pathways and on electrophysiology in skeletal muscle. METHODS: A total of 27 patients with stable CHF (NYHA class II-III) were randomized to a training (N=12) or a control (N=15) group. The training group exercised on a bicycle ergometer for 30 min three times a week for 3 months using a load corresponding to 50-60% of their peak oxygen consumption. This was followed by a 3-month training period at home according to personal instructions. The control group did not change its physical activities. We studied muscle histology and measured the activities of the rate-limiting enzymes of anaerobic glycolysis (phosphofructokinase, PFK), glycogenolysis (phosphorylase), citric acid cycle (alpha-ketoglurate dehydrogenase, KGDH) and fatty acid oxidation (carnitinepalmitoyl transferase I and II, CPT I and II) from biopsies of the vastus lateralis muscle at baseline and after 3 and 6 months. Muscle strength and strength endurance with surface EMG and macro EMG of the right knee extensors were also determined. RESULTS: Exercise capacity, particularly submaximal, improved in the training group. The activity of PFK rose significantly but that of the other enzymes did not when compared with the change in the controls. Training had no effect on the percentage distribution of slow-twitch and fast-twitch muscle fibers or on capillary density around these fibers in skeletal muscle. Maximum voluntary force, strength endurance and the function of motor units remained unaffected. CONCLUSIONS: Dynamic training results in improved exercise endurance in CHF. In skeletal muscle, the capacity of anaerobic glycolysis is increased but that of the citric acid cycle and fatty acid oxidation is not. Furthermore, the improvement in exercise endurance seems to be independent of changes in the percentage distribution of muscle fibers, capillarity or electrophysiological factors.     

老年慢性充血性心力衰竭的运动康复疗效

目的：观察老年慢性充血性心力衰竭的康复治疗效果。方法：选择老年慢性充血性心衰患者35例，其中20例为治疗组，15例为对照组，进行一定程序的康复训练。结果：治疗组比对照组症状有明显改善，血压、心率亦明显下降，生活质量有所提高。结论：康复运动对心衰是有益的，从而对所有的慢性心力衰竭患者均限制活动的观点提出了疑问。     

慢性充血性心力衰竭外周甲状腺素水平变化

目的 :观察评价慢性心血管病 ,尤其是慢性心衰患者甲状腺功能正常病态综合症 (SES)发生情况并探讨其病理生理意义。方法 :病史大于 2年的慢性心衰 (CHF)病人 5 4例和同期住院非CHF的慢性心血管病人 2 0例 ,病情平稳后抽取空腹血临床生化检验和甲状腺素测定。SES定义为血清总 3 碘甲腺原氨酸 (T3)低于正常值的低限 (<0 8ng/ml) ,4 碘甲腺原氨酸 (T4 )和促甲状腺素正常。结果 :74例受试者中有 33例发生SES ,CHF者发生率达 5 1% (2 8/ 5 4) ,SES的发生率随心功能不全加重而增高。SES与非SES的CHF病人心功能 (NYHA分级 )、左室舒张末径 (LVEDD)和射血分数 (LVEF)、T4 均值均有明显差异 ,但临床特征 ,肝、肾功能指标差别不显著。慢性心血管病人存在SES ,心功能不全程度越重 ,其发生率越高。结论 :肝、肾功能状态不是CHF病人发生SES的主要决定因素。认识CHF病人SES现象为临床综合治疗CHF可会提供一些非常有价值的思路。     

Influence of carvedilol on the benefits of physical training in patients with moderate chronic heart failure

AIMS: To evaluate prospectively the impact of carvedilol on a short-term physical training program in stable patients with moderate chronic heart failure (CHF), and to analyze parameters predictive of improvement after training. METHODS AND RESULTS: Thirty-eight patients with CHF were referred for cardiac rehabilitation. Etiology was ischemic in 26 patients, dilated in 12 patients and left ventricular ejection fraction was <35%. Patients were classified into three groups: group 1 (n=14)=ACE inhibitors, diuretics and digitalis; group 2 (n=11)=idem group 1+cardioselective beta-blocker; group 3 (n=13)=idem group 1+carvedilol. Exercise tests with VO2 measurement were performed before and after a 4-week exercise training program. Patients with carvedilol experienced a 16.6% increase in peak VO2 which was similar to the 13.9% increase in the group with cardioselective beta-blocker and to the 18.5% in the group without beta-blocker. Moreover non-ischemic etiology of CHF was the only parameter predictive of improvement after training (P=0.02). CONCLUSION: Addition of carvedilol did not alter benefits of a short-term physical training program in patients with moderate CHF. No baseline characteristic except for etiology of CHF was predictive of a response to training.     

Incidence of renal dysfunction over 6 months in patients with chronic heart failure due to left ventricular systolic dysfunction: contributing factors and relationship to prognosis.

AIMS: To determine the prevalence and incidence of renal dysfunction (RD) in patients with chronic heart failure (CHF), to identify contributory factors and predictors of worsening renal function (WRF), and to explore the relationship between RD and mortality. METHODS AND RESULTS: Prospective data on 1216 patients with CHF were analysed. The glomerular filtration rate (GFR) was used to determine renal function, and WRF was defined as an increase in serum creatinine of >26.5 micromol/L (>0.3 mg/dL). The prevalence of RD defined as a GFR of <60 mL/min was 57%. During 6 months, WRF occurred in 161 (13.0%) patients. Predictors of WRF were vascular disease, the use of thiazide diuretics, and a baseline urea >9 mmol/L. Two hundred and sixty-three (21.6%) patients died, and baseline RD and WRF both predicted a higher mortality (P<0.001), whereas an improvement in renal function over the first 6 months predicted a lower mortality (hazard ratio 0.8, 95% confidence interval 0.6-1.0). CONCLUSION: In ambulatory patients with CHF, RD is common, commonly deteriorates over a relatively short period of time, is unlikely to recover substantially, and augurs a poor prognosis.     

A randomized controlled trial of inspiratory muscle training in stable chronic heart failure

Aims To assess whether a domiciliary programme of specific inspiratorymuscle training in stable chronic heart failure results in improvementsin exercise tolerance or quality of life. Methods and results We conducted a randomized controlled trialof 8 weeks of inspiratory muscle training in 18 patients withstable chronic heart failure, using the Threshold^\Rtrainer.Patients were randomized either to a training group inspiringfor 30min daily at 30% of maximum inspiratory mouth pressure,or to a control group of ‘sham’ training at 15%of maximum inspiratory mouth pressure. Sixteen of the 18 patientscompleted the study. Maximum inspiratory mouth pressure improvedsignificantly in the training group compared with controls,by a mean (SD) of 25·4 (11·2) cmH₂O (P=0·04).There were, however, no significant improvements in treadmillexercise time, corridor walk test time or quality of life scoresin the trained group compared with controls. Conclusion Despite achieving a significant increase in inspiratorymuscle strength, this trial of simple domiciliary inspiratorymuscle training using threshold loading at 30% of maximum inspiratorymouth pressure did not result in significant improvements inexercise tolerance or quality of life in patients with chronicheart failure.     

慢性心力衰竭患者动态心率震荡分析

目的：探讨窦性心率震荡（HRT）的新测量指标动态心率震荡（TD）及HRT测量指标震荡初始（TO）、震荡斜率（TS）在慢性心力衰竭（CHF）患者中的变化,分析其与传统高危预测指标的相关性及预测CHF患者价值。方法纳入2011年9月~2013年6月在天津市胸科医院就诊的CHF患者120例作为CHF组,同期纳入非器质性心脏病患者30例作为对照组,将CHF组按NYHA分级分为轻度CHF组（心功能Ⅰ~Ⅱ级,n=72）和中重度CHF组（心功能Ⅲ~Ⅳ级,n=48）。所有患者行放射免疫法检测B型脑钠肽（BNP）水平,超声心动图检查左房内径（LAD）、左室舒张末径（LVEDD）、左室射血分数（LVEF）;24 h动态心电图检查记录心率变异性时域（SDNN）、平均心率、室性早搏前心率（HRVPC）以及RR间期,计算HRT指标（包括TO、TS和TD）。比较各组之间的差异,分析HRT各指标与年龄、性别、LAD、LVEDD、LVEF、BNP的相关性。结果与对照组相比,CHF组SDNN缩短[（95.67±30.22） msvs.（131.65±20.71）ms],TO和TD更高[TO：（-1.50±2.71）%vs.（0.61±1.95）%;TD：（0.012±0.004）mm/RRIvs.（0.063±0.031）mm/RRI],LAD和LVEDD更高[LAD：（36.11±2.24）mmvs.（47.65±2.13）mm;LVEDD：（43.65±7.33）mmvs.（62.13±8.70）mm],BNP明显升高[（80.05±32.30）pg/ml vs.（941.00±139.17）pg/ml],TS和LVEF更低[TS：（12.13±3.67）vs.（6.80±5.33）;LVEF：（67.30±5.21）% vs.（38.22±12.75）%],而且随着CHF程度的加重,上述改变更加明显。CHF组TO与TS、LVEF、SDNN负相关（P＜0.05）;TS与SDNN正相关（P＜0.05）,与HRVPC、BNP负相关（P＜0.05）。结论 CHF患者HRT明显减弱,其中TO和TS均受到SDNN的影响,而TD与HRVPC、SDNN、LVEF、BNP指标无关。     

康复医疗在慢性充血性心衰病人治疗中的应用（附42例报告）

目的 :观察在慢性心衰病人临床治疗中配合应用康复医疗的作用。方法 :42例 度慢性充血性心衰病人 ,按心功能分级 ( ～ 级 )分成 3组。待病情稳定后开始分阶段的康复运动 ,同时进行教育、心理调整。结果 :病人全部康复 ,出院时心功能均达 级 ,平均住院时间为 14.5 5± 7.0 2天 ,安全性达 95 % (40 / 42 )。结论 :慢性心衰病人临床治疗中配合应用本康复程序可以达到早下床、早活动、早出院 ,促进康复的目的 ,且安全性高。     

慢性心力衰竭患者运动康复训练方式的研究进展

随着医疗技术进步、心血管发病率逐年增加和世界人口老龄化进程的推进,心力衰竭的患病率逐年攀升,且存在5年存活率低、再入院率高及预后不良等严重问题.随着以运动为主的心脏康复的快速发展,心力衰竭患者采用运动训练作为非药物治疗手段显得尤为重要.心力衰竭患者的运动训练方式包括有氧训练、阻抗训练、呼吸肌训练及神经肌肉电刺激等.但临...     

Response of the oxygen uptake efficiency slope to exercise training in patients with chronic heart failure

BACKGROUND: The oxygen uptake efficiency slope (OUES) is a new exercise parameter that provides prognostic power in patients with CHF. Little is known about the effects of exercise training (ET) on OUES. AIM: To describe the response of OUES to 6 months of ET in CHF patients and compare its evolution to that of other exercise variables. METHODS: 35 patients with CHF (NYHA II-III, age 54+/-9y, LVEF 31+/-10%) performed 3 maximal exercise tests, i.e. at the start, middle and end of a 6 month ET program. OUES, PeakVO(2), ventilatory anaerobic threshold (VAT) and slope VE/VCO(2) were determined. RESULTS: OUES, peakVO(2), VAT, slope VE/VCO(2), peak Watt, 6MWT and NYHA-class improved during the first part of the ET period (p<0.05). Only VAT, peak Watt and 6MWT continued to improve during the second part of the ET period (p<0.05) Improvements in OUES correlated better with improvements in peakVO(2) (r=0.77, p<0.001), than changes in other prognostic variables. DISCUSSION: OUES improves significantly after 6 months of ET. Changes in peakVO(2) correlate best with changes in OUES. OUES is sensitive to ET and can be used to evaluate the progression of exercise capacity in CHF patients.     

Autonomic function in elderly patients with chronic heart failure

AIMS: Autonomic function (AF) is attenuated by heart failure (HF). Reports have been based on studies of young patients with systolic heart failure (SHF). However, HF is a disease of older patients who are more likely to have diastolic heart failure (DHF). We investigated whether age alters AF in elderly HF patients and whether the haemodynamic type of HF influences AF. METHOD AND RESULTS: Thirty-six elderly HF (Framingham criteria) patients (11 with SHF, 25 with DHF) and 21 matched healthy subjects underwent simple bedside AF tests. Compared with the reference values for healthy adults, the mean E:I ratios and the median 30:15 ratios standing were all essentially normal. The median 30:15 ratios tilt and the mean Valsalva ratios were all significantly below the reference value (P for all cases <0.050). Comparing three groups, there were no significant differences for mean E:I ratio (P=0.111), 30:15 tilt (P=0.619) and 30:15 standing (P=0.167), whereas there were significant differences for the mean Valsalva ratios (P=0.001). The mean Valsalva ratio of the SHF patients was significantly lower than that for the DHF patients (P<0.001) which in turn was significantly lower than the result of the healthy subjects (P<0.001). CONCLUSION: There is an age-related impairment in AF with further impairment occurring in patients with HF. However, the severity of autonomic dysfunction is less in patients with DHF compared with patients with SHF.     

慢性心力衰竭患者的心率变异性分析

目的 探讨慢性心力衰竭患者心率变异性的变化。方法 观察76例心力衰竭患者（观察组）和24例健康人（对照组）的心率变异性时域指标,比较两组各指标及与心功能程度NYHA分级、原发病和心力衰竭类型的关系。结果 观察组较对照组SDNN、SDANN显著降低（P均〈0.05、〈0.01）。心功能Ⅳ级者较Ⅱ、Ⅲ级SDNN、SDANN显著降低（P〈0.05、〈0.01）。右侧心力衰竭者较对照组SDNN、SDANN显著降低（P均〈0.01）;全心心力衰竭者较对照组和单侧心力衰竭SDNN、SDANN均显著降低（P〈0.01、〈0.05）。各种病因者较对照组SDANN均显著降低（P〈0.05、0.01）,但各种病因者差异无显著性意义（P〉0.05）结论 慢性心力衰竭患者HRV部分指标变化可作为判定慢性心力衰竭严重程度的参考指标;各项指标变化可能与原发病无关,但部分似与心力衰竭类型有关。     

Increased myocardial expression of osteopontin in patients with advanced heart failure

The expression of the adhesion protein osteopontin (OP) is associated with cardiac hypertrophy and is significantly increased after transition to heart failure in experimental animal models. We, therefore, hypothesized that OP could be upregulated in heart failure in humans. In the present study, we investigated the expression of OP in myocardial biopsies obtained from patients with heart failure due to dilated cardiomyopathy (mean LVEF=30.3+/-4.4%, mean+/-S.D., n=10, group A) compared to patients with a normal left-ventricular ejection fraction (mean LVEF=61+/-11.2%, n=9; group B). Myocardial immunoreactivity for OP was examined using two different antibodies against OP. The expression of cardiac myocyte OP was significantly upregulated in group A in comparison to group B (P<0.0001). Both groups also displayed OP immunoreactivity in non-myocytes, including vascular smooth muscle cells and cardiac fibroblasts (P=not significant). Statistical analysis revealed a significant correlation of increased OP immunoreactivity in cardiac myocytes of patients with impaired left ventricular function, assessed by hemodynamic data (LVEF, RVEF, LVESVI, LVEDVI and LVEDP, R=-0.828, -0.671, 0.751, 0.685 and 0.461, respectively; all P<0.05). Furthermore, OP expression correlated with cardiac myocyte hypertrophy (mean diameter 21.0+/-1.8 microm in group A and 16.6+/-2.1 microm in group B; P<0.0001). In conclusion, the present study indicates, that factors and/or mechanisms involved in heart failure in patients with dilated cardiomyopathy, lead to induction of OP expression in humans.     

Plasma semicarbazide-sensitive amine oxidase (SSAO) is an independent prognostic marker for mortality in chronic heart failure.

AIMS: Experimental evidence has suggested that semicarbazide-sensitive amine oxidase is involved in vascular endothelial damage and in the process of atherosclerosis, through the formation of reactive aldehydes, hydrogen peroxide and ammonia from endogenous substrates. Recent evidence indicates that semicarbazide-sensitive amine oxidase may be identical with the vascular adhesion protein-1. In patients with diabetes mellitus and chronic heart failure the plasma activity is raised relative to the severity of the disease. The prognostic value of plasma semicarbazide-sensitive amine oxidase is not known. METHODS AND RESULTS: Plasma semicarbazide-sensitive amine oxidase activity was measured at baseline in patients with moderate to severe chronic heart failure who participated in a large European study (PRIME-II). The 372 patients who took part in a pre-defined substudy in The Netherlands were investigated and a survival follow-up (maximum 5.4 years, mean 3.4 years) was carried out. Within the follow-up period 195 patients died. Plasma semicarbazide-sensitive amine oxidase was higher at baseline in those who died than in the survivors (653+/-258 vs 540+/-242 mU. l(-1), P<0.001). Dividing the patients into two groups according to plasma values above or below the median value of 550 mU. l(-1), semicarbazide-sensitive amine oxidase was found to be a prognostic parameter for survival, both in univariate (P<0.0001) and in multivariate (P=0.0106) analysis. Semicarbazide-sensitive amine oxidase values >550 mU. l(-1)had a 1. 50 (95% CI, 1.10-2.04) times increased risk of death. CONCLUSION: The finding that plasma semicarbazide-sensitive amine oxidase is an independent prognostic marker for mortality in chronic heart failure supports the concept that an elevated plasma semicarbazide-sensitive amine oxidase level has deleterious effects, possibly due to vascular endothelial damage.     

Urotensin II in patients with chronic heart failure

BACKGROUND: Human Urotensin II (hU-II) is the most potent vasoconstrictor known to date. HU-II receptors are predominant in the human heart and arterial vessels, suggesting hU-II to be of importance as a cardiovascular mediator. METHODS: We studied 32 consecutive patients (60+/-12 years) with chronic heart failure (CHF) and 10 control subjects (54+/-12 years, n.s.) with cardiopulmonary exercise testing. Blood samples for the measurement of plasma hU-II and big-endothelin-1 (big-ET1) were obtained at rest and at peak exercise. RESULTS: Peak VO(2) was significantly higher in controls than in CHF patients (19.8+/-3.8 vs. 14.7+/-3.6 ml min(-1) kg(-1), P<0.001). Big-ET1 levels were increased in CHF compared to controls at rest (2.8+/-1.8 vs. 1.7+/-0.1 fmol/ml, P<0.01) and at peak exercise (2.7+/-1.7 vs. 1.6+/-0.2 fmol/ml, P<0.005). HU-II concentrations were comparable in patients with CHF and controls at rest (2990+/-1104 vs. 3290+/-508 pg/ml, n.s.) and peak exercise (3063+/-1185 vs. 3213+/-1188 pg/ml, n.s.). Resting hU-II levels demonstrated no correlation with peak VO(2) in controls or CHF patients. CONCLUSIONS: The measurement of circulating plasma levels of hU-II does not seem to be very helpful in studying the effects of hU-II in human cardiovascular regulation. A local paracrine or autocrine mediator effect of hU-II in CHF is possible.