Exercise-induced biphasic increase in circulating NT-proBNP levels in patients with chronic heart failure

BACKGROUND: Exercise increases natriuretic peptide levels in chronic heart failure (CHF) patients, but the effect is considered minor. We assessed acute and short-term release (<24 h) of NT-proBNP in CHF patients after a maximal cardiopulmonary exercise test (CPET) and 2 different submaximal training sessions. METHODS AND RESULTS: 102 CHF patients either performed CPET (Group 1), a 1 h endurance (Group 2) or a combined endurance-resistance training session (Group 3). NT-proBNP concentration was determined before, at exercise cessation and after 18-22 h (Protocol A). In 20 patients, samples were obtained before, at exercise cessation, after 15, 30, 45, 60, 90 min, 2, 3, 4, 5, 6, 12, 22 h (Protocol B). Protocol A: At peak exercise, a 15%, 11% and 17% relative increase (p<0.001 vs baseline, all 3 groups) was seen, with a return to baseline after 18-22 h. The increase correlated with indicators of more advanced heart failure. Protocol B: A biphasic pattern was derived with a first peak within 1 h of exercise termination and a second peak (39%, 31% and 33% higher than baseline; p<0.05, all 3 groups) after 4-12 h. CONCLUSIONS: The observed biphasic release of B-type natriuretic peptides supports standardization of sampling, taking recent exercise into account.     

Effect of valsartan added to background ACE inhibitor therapy in patients with heart failure: results from Val-HeFT

AIMS: To investigate the effect of valsartan in the Valsartan-Heart Failure Trial (Val-HeFT) when added to angiotensin-converting enzyme inhibitor (ACEi) alone in patients with heart failure (HF). METHODS: Subjects in Val-HeFT receiving ACEi but not beta-blocker at baseline were analysed; 1532 were assigned to valsartan and 1502 assigned to placebo. Primary outcome events (all-cause mortality, hospitalisation for adjudicated heart failure, sudden death with resuscitation and need for >4 h of parenteral therapy for worsening heart failure) were monitored. RESULTS: Mortality was not affected by valsartan but morbidity endpoints were significantly reduced (36.3% in placebo, 31.0% in valsartan, p=0.002) in patients receiving an ACEi but no beta-blocker. Quality of life (QOL) was significantly improved, ejection fraction (EF) significantly increased, left ventricular (LV) diameter significantly reduced and plasma B-type natriuretic peptide, norepinephrine and aldosterone levels significantly reduced with valsartan compared to placebo. The morbidity benefit was significant in patients on ACEi doses below the median (22% reduction, p=0.003) and not statistically significant in those receiving ACEi doses above the median (14% reduction, p=0.143). CONCLUSION: Valsartan reduces heart failure hospitalisations and slows LV remodelling in patients treated with an ACEi in the absence of beta-blockade, particularly in those on lower doses of ACEi.     

Ventilatory capacity and exercise tolerance in patients with chronic stable heart failure

BACKGROUND: Patients with chronic heart failure complain of breathlessness. This is associated with an increase in the ventilatory response to carbon dioxide production (VE/VCO(2) slope), yet a reduction in the maximal ventilation achieved at peak exercise. We analysed ventilatory capacity in heart failure in relation to exercise capacity. METHODS: We analysed data from 74 patients with chronic stable heart failure [age (S.D.) 50.6 (8.8) years; left ventricular ejection fraction 30 (15)%] and 36 controls [48.9 (11.5) years]. Subjects undertook maximal incremental exercise testing with metabolic gas exchange measurements to derive peak oxygen consumption (VO(2)), the VE/VCO(2) slope and ventilation. Spirometry was used to measure FEV(1) and FVC. Maximal voluntary ventilation (MVV) was calculated as FEV(1)x 35. RESULTS: Peak VO(2) was lower in patients [20.9 (7.5) ml min(-1) kg(-1) vs. 34.5 (10.1); P<0.001] and VE/VCO(2) greater [33.4 (10.7) vs. 26.0 (4.7); P<0.001]. Ventilation at peak exercise was lower in patients [63.5 (20.4) l/min vs. 86.9 (29.5); P<0.001], as was MVV [110.1 (37.9) l/min vs. 136.2 (53.1); P<0.001], but ventilation at peak as a proportion of MVV was the same in patients [60.0 (19.0)%] as controls [65.7 (12.4)%)]. There was an inverse relation between peak VO(2) and VE/VCO(2) slope (r=-0. 62; P<0.001). Percentage predicted FEV(1) correlated with ventilation at peak (r=0.62; P<0.001) and inversely with VE/VCO(2) slope (r=-0.32; P<0.001). There was no relation between percentage of MVV achieved and peak VO(2), or VE/VCO(2) slope. CONCLUSIONS: Although ventilation at peak exercise is lower in patients with heart failure than normal subjects, ventilation is the same proportion of maximal voluntary ventilation. These findings suggest that ventilatory capacity does not limit exercise capacity in heart failure.     

Neurohumoral effects of the new orally active renin inhibitor, aliskiren, in chronic heart failure

BACKGROUND: Suppression of the renin-angiotensin-aldosterone system (RAAS) is therapeutically valuable in chronic heart failure (CHF). RAAS inhibition can be achieved in a number of ways though an orally active renin inhibitor (RI) has never been studied before. We describe the neurohumoral effects of an RI. METHODS AND RESULTS: 27 patients with NYHA class II or III CHF and an ejection fraction 相似文献   

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.     

中性内肽酶在心力衰竭患者淋巴细胞中的表达

目的 :观察中性内肽酶 (NEP)在心力衰竭 (心衰 )患者淋巴细胞中的表达。方法 :分离 30例心衰患者及 10例正常对照者的外周血淋巴细胞 ,分别涂片 ,用免疫组化S ABC的方法检测NEP的表达 ;同时用RT PCR法检测淋巴细胞中的NEPmRNA。结果 :免疫组化发现 30例心衰患者淋巴细胞中均可见阳性染色 ,而 10例对照者均未见NEP的表达 ;RT PCR法检测发现NEP在心衰组表达 ,而对照组未检测到。结论 :NEP在心衰患者外周血淋巴细胞中表达。     

Prognostic value of the 6 min walk test and self-perceived symptom severity in older patients with chronic heart failure.

BACKGROUND: The 6 min walk test (6-MWT) is a simple and popular test for evaluating functional status in patients with chronic heart failure (CHF). However, the prognostic value of the 6-MWT in a large, representative sample of CHF patients, and in patients with different degrees of left ventricular systolic dysfunction (LVSD) remains unclear. METHODS AND RESULTS: Of an initial population of 1592 patients, 212 died representing a crude death rate of 13.3%. In surviving patients, the median time to follow-up period was 36.6 months [inter-quartile range (IQR) 28-45 months]. Five variables remained independent predictors of all-cause mortality; decreasing 6-MWT distance, self-perceived signs of breathlessness at night (SOBAN), beta-blocker usage, elevated log NT-proBNP, and reduced haemoglobin concentration. We also dichotomized our analysis by LVSD status (mild LVSD). For patients with >mild LVSD, 6-MWT remained an important prognostic indicator but not in patients with mild LVSD. The 6-MWT provides little prognostic utility in patients with 相似文献   

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。     

Ventilatory threshold during exercise in patients with mild to moderate chronic heart failure: determination, relation with lactate threshold and reproducibility

Detection of the ventilatory threshold during exercise has been proposed in order to assess exercise tolerance in patients with chronic heart failure. The relation between the different methods of detecting the ventilatory threshold and the lactate threshold, however, and their reproducibility, have not really been assessed. Forty-three patients with chronic heart failure underwent an exercise test with respiratory gas analysis. A lactate threshold could be determined in 36 patients and a ventilatory threshold in 27 to 38 patients, depending on the method of determination of the ventilatory threshold. The greatest number of determinations (38) and the best correlation coefficient with the lactate threshold (r = 0.87 and 0.88, respectively) were obtained with the method of the ventilatory equivalent for oxygen and by averaging the different methods of determination. Reproducibility of the ventilatory threshold was only moderately good (r = 0.83) and less satisfactory than that of the peak oxygen uptake (r = 0.97). We conclude that unless the way of detecting the ventilatory threshold is improved in patients with chronic heart failure, the peak oxygen uptake will remain more reproducible.     

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。     

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.     

低钠血症对慢性心力衰竭的预后价值

目的 探讨慢性心力衰竭患者低钠血症的预后价值.方法 对2007年1月至2013年1月于我院急诊内科住院治疗资料完整的786例慢性心力衰竭患者进行回顾性分析,根据入院24～48 h血清钠离子浓度最低值分为三组：A组,钠离子≥135 mmol/L;B组,钠离子120～135 mmol/L;C组,钠离子≤120 mmol/L.比较各组心功能、血清钾离子浓度、住院病死率等指标.结果 住院期间存活714例,死亡72例,存活组与死亡组平均血清钠离子浓度分别为（134.00±5.83）mmol/L和（121.00±7.15）mmol/L,差异有统计学意义（P＜0.01）,而血清钾离子浓度分别为（4.4±0.6）mmol/L和（4.3±0.8）mmol/L,差异无统计学意义（P＞0.05）.三组住院病死率分别为：A组7.8％（36/461）,B组8.0％（23/289）,C组36.1％（13/36）,C组病死率明显高于A组和B组,差异有统计学意义（P＜0.01）;A组与B组比较差异无统计学意义（P＞0.05）.结论 低钠血症是慢性心力衰竭患者预后不良的重要危险因素.     

美托洛尔治疗慢性心力衰竭目标剂量探讨

目的　探讨美托洛尔在慢性充血性心力衰竭 (心衰 )治疗中的剂量及耐受性。方法　对10 3例心力衰竭伴窦性心律患者在常规心衰治疗基础上加用美托洛尔 ,逐渐加量至目标剂量 ,目标分别为 :①心率下降到 5 0～ 6 5次 /min(不低于 5 0次 /min) ;②稍加剂量心功能下降Ⅰ级 ;③收缩压不低于90mmHg(1mmHg =0 133kPa)。结果　美托洛尔平均维持量为 (72 7± 36 1)mg/d(12 5～ 175mg/d)。其中 6 8例 (6 6 0 % )达心率目标 ,35例 (34 0 % )达心衰目标 ,无一例达血压目标。随访患者多因认识不足或不适当治疗而减量或停用美托洛尔。结论　在治疗期间内 ,心力衰竭 (NYHAⅡ级～Ⅳ级 )患者对合适剂量的美托洛尔耐受性较好。     

Anaemia is an independent predictor of poor outcome in patients with chronic heart failure

Background: Mild anaemia frequently occurs in patients with chronic heart failure (CHF), particularly in the advanced stages of the disease. The correction of anaemia with erythropoietin is a therapeutic possibility. The aim of this study was to assess prospectively the relationship between the prevalence of anaemia (haemoglobin level≤120 g/l) and prognosis in an unselected CHF population. Methods: All consecutive patients with a diagnosis of CHF admitted to our department between January 2000 and April 2000 were considered for the present study. Those with secondary causes of anaemia were excluded. Patients were followed up until November 2001 (>18 months in all survivors), and the end-point of the study was all-cause mortality. Results: A total of 176 patients were enrolled (mean age: 63 years, New York Heart Association (NYHA) classification I/II/III/IV: 15/81/51/29; left ventricular ejection fraction (LVEF): 42%, ischaemic aetiology in 62%). In the whole population the mean haemoglobin level was 140±15 g/l. Anaemia was found in 18 (10%) patients, and was significantly more common in women than in men (18 vs. 7%, respectively, P=0.02) and in those with most severe CHF symptoms (frequency in NYHA I/II/III/IV: 0/9/10/21%, respectively; NYHA IV vs. I–III, P=0.03), but not related to the other clinical indices. Univariate analysis revealed NYHA class III–IV (hazard ratio 3.8, 95% CI: 1.6–8.9, P=0.003), low LVEF <35% (hazard ratio 2.3, 95% CI: 1.0–4.9, P=0.04) and anaemia (hazard ratio 2.9, 95% CI: 1.2–7.2, P=0.02) as predictors of 18-month mortality. In multivariate analysis, anaemia remained an independent predictor of death when adjusted for NYHA class and LVEF (hazard ratio: 2.6, 95% CI: 1.0–6.5, P=0.04). In anaemic patients, 18-month survival was 67% (95% CI: 45–89%) compared to 87% (81–92%) in patients with a normal haemoglobin level (P=0.016). Conclusions: Mild anaemia is a significant and independent predictor of poor outcome in unselected patients with CHF. Correction of low haemoglobin level may become an interesting therapeutic option for CHF patients.     

A mechanistic investigation of ACE inhibitor dose effects on aerobic exercise capacity in heart failure patients.

BACKGROUND: Angiotensin converting enzyme inhibitors at high doses have been shown to improve prognosis of heart failure patients. Their beneficial effects on exercise capacity have been less convincing in large parallel group studies. The objective of this investigation was to explore the mechanisms involved in dose-related functional effects and to test the hypothesis that a trial recommended high dose of lisinopril would improve aerobic exercise capacity and cardiovascular function more than with a low dose. METHODS: Twelve patients with symptomatic heart failure completed a randomized double-blind crossover trial of lisinopril 5 mg o.d. and 20 mg o.d. for 24 weeks, crossing over the doses at 12 weeks. The primary end-point was aerobic exercise capacity, and the secondary end-points were cardiac performance at peak exercise and dobutamine stimulation. RESULTS: The aerobic exercise capacity (primary end-point) was significantly higher during the 5mg per day dosage compared to the 20 mg (1696 vs 1578 ml.min(-1), P=0.016), equivalent to a rise of 1.53 ml.kg(-1)min(-1) from the 19.6 ml.kg(-1)min(-1) with 20mg when normalized by body weight. Seventy-three percent of patients showed greater peak oxygen consumption and peak cardiac power output with the 5mg per day dose than the 20 mg, and none showed the opposite. In terms of cardiac performance, although the results were not statistically significant, there was a consistent pattern showing the same directional changes in favour of the lower dose in peak exercise cardiac power output and cardiac power output at maximal dobutamine. There were no significant differences in the resting values. A total of 24 adverse reactions were reported during the 5 mg phase compared to 38 during the 20 mg phase. CONCLUSIONS: Contrary to expectation, the aerobic exercise capacity of patients was found to be greater with the lower dose of lisinopril, suggesting that therapy with ACE inhibitors for heart failure may require tailoring the doses to the individual to optimize functional benefits in relation to the assumed prognostic benefits.