Predictors of exercise capacity in chronic heart failure

Abnormalities of skeletal muscle rather than of haemodynamicsmay be important determinants of exercise capacity in chronicheart failure. We investigated an array of indicators of centralhaemodynamics and peripheral muscle function to establish whichresting measurements predicted exercise performance. In 20 patients quadriceps strength, resting and peak leg bloodflow and leg muscle cross sectional area were measured. In 18patients average daytime blood pressure and pulse rate, haemodynamicvariables at rest and during exercise, and autonomic activitywere measured. There were correlations between peak oxygen consumptionand quadriceps strength (0.65; P=0.007), thigh muscle crosssectional area (r=0.63; P=0.004), and average daytime systolicblood pressure (r=0.66; P<0.01). There were no correlationswith indices of peripheral blood flow, measures of haemodynamicfunction, or autonomic function. Quadriceps strength was themost important individual correlate of exercise tolerance (r=0.73).With total muscle cross sectional area and left quadriceps strengthalso taken into consideration, 82% of the variation in peakoxygen consumption was explained. Of the haemodynamic variables,only average daytime systolic blood pressure predicted exerciseperformance. The resting variables that best predict exercise performancein chronic heart failure are measures of skeletal muscle functionand bulk, and average daytime systolic blood pressure. Thesefindings suggest that abnormalities in the periphery largelydetermine exercise performance in chronic heart failure, andthat the ability of the heart to generate an adequate bloodpressure response to daily activities is also predictive offunctional status.     

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.     

Heart rate response to graded exercise correlates with aerobic and ventilatory capacity in patients with heart failure

BACKGROUND: Autonomic dysfunction and reduced exercise tolerance are typical features of patients with congestive heart failure (CHF). Baro-chemoreflex balance and organ response may have a common role in conditioning exercise tolerance, ventilation, and chronotropic competence in patients with CHF. HYPOTHESIS: We tested the hypothesis that there is a relationship between functional capacity and chronotropic competence to exercise in CHF. METHODS: In all, 48 stable outpatients with CHF (age 65 +/- 10 years, 41 men, NYHA class 2.1 +/- 0, ejection fraction 31 +/- 7%, peak VO2 16 +/- 4 ml/kg/min) performed cardiopulmonary exercise testing (CPX). Heart rate (HR) response to exercise was assessed by the chronotropic index (CRI). The CRI was calculated by the following formula: CRI = peak HR - rest HR/220 - age - rest HR x 100 (normal value > 80%). The relationship of CRI to peak oxygen consumption (VO2) and ventilation/carbon dioxide production (VE/VCO2) ratio was examined. A group of 33 healthy controls underwent CPX as well. RESULTS: The CRI correlated directly with peak VO2 (r = 0.638, p < 0.001) and inversely with VE/VCO2 (r = -0.492, p < 0.001) in patients with CHF. A CRI < 78% identified patients with CHF and a peak VO2 < 20 ml/kg/min, area under the receiver operating curve (AUROC): 0.76, 95% confidence interval (CI) 0.60-0.92. A CRI < 74% predicted exercise hyperventilation in CHF (AUROC: 0.71 for VE/VCO2 > 30, 95% CI 0.53-0.88). The CRI was not significantly related either to peak VO2 or to VE/VCO2 in the control group. CONCLUSIONS: In patients with mild to moderate CHF, CRI correlates with functional capacity. This relationship adds new data on pathophysiologic grounds and supports the routine incorporation of CRI into CPX interpretation.     

心率减速力评估慢性心衰患者的预后

目的探讨心率减速力对老年慢性心功能不全（CHF）患者预后的预测价值。方法入选安徽省立医院2008年10月至2011年10月住院的老年CHF患者124例,同期选择82例健康患者为对照组,记录其相关临床资料,并进行超声心动图、动态心电图检查。应用相应的分析软件对动态心电图检查结果进行分析,比较不同心功能分级患者DC指标变化的差异;随访12~24个月,终点事件为患者心源性死亡,采用Logisitc回归法分析DC、年龄、高血压、糖尿病、心肌梗死、左室射血分数（LVEF）、血管紧张素转换酶抑制剂（ACEI）对CHF患者死亡的预测能力。结果对照组与心功能不全组比较,DC差别显著,同时DC在心功能Ⅱ级组和Ⅲ级组有明显差异,但在心功能Ⅲ级与心功能Ⅳ级组无差别（p〉0.05）。平均随访（15士8.5）个月,124例患者中,心源性死亡24例,分析显示CHF患者死亡与DC、低LVEF（≤45%）、年龄（≥65岁）、糖尿病、心肌梗死及心功能分级相关。结论DC指标对老年人CHF预后有良好的预测能力。     

Effects of L-arginine on lower limb vasodilator reserve and exercise capacity in patients with chronic heart failure

OBJECTIVE: To determine whether the reactive hyperaemic response of the lower limb increases with improved exercise capacity after acute supplementation with L-arginine, the precursor of nitric oxide, in patients with chronic heart failure. METHODS: 19 patients with chronic heart failure were enrolled in the study. Rest calf blood flow and femoral occlusion induced calf blood flow changes were measured by venous occlusion plethysmography before and after intravenous infusion of 10% L-arginine solution (5 ml/kg for 30 minutes) or placebo. Postexercise calf blood flow was also measured after the experimental infusion. During both postinfusion periods, several exercise capacity indices were determined by a symptom limited cardiopulmonary exercise test using a bicycle ergometer. RESULTS: Baseline calf blood flow, systemic blood pressure, and heart rate showed no significant changes in either of the two experimental conditions. However, the occlusion induced blood flow response was significantly enhanced by L-arginine infusion (mean (SEM) peak flow, 19.6 (1.5) v 28.9 (3.1) ml/min/dl calf tissue; p < 0.01), but not by placebo (peak flow, 19.1 (1.4) v 20.9 (1.8) ml/min/dl calf tissue; NS). Calf blood flow response after exercise was also higher after L-arginine infusion than after placebo (peak flow, 4.8 (0.4) v 6.0 (0.8) ml/min/dl calf tissue; p < 0.05). L-arginine infusion had no significant effect compared with placebo on exercise capacity indices such as peak oxygen uptake (17.1 (1.0) v 15.8 (1.1) ml/min/kg; NS), anaerobic threshold (10.5 (0.6) v 10.4 (0.7) ml/min/kg; NS), and exercise time (296 (23) v 283 (22) s; NS). CONCLUSIONS: Acute supplementation with the nitric oxide precursor L-arginine increased lower limb reactive hyperaemia but did not lead to any significant improvement in exercise capacity in patients with chronic heart failure.     

Prognostic value of changes over time in exercise capacity and echocardiographic measurements in patients with chronic heart failure.

AIMS: This study sought to examine the predictive values of changes over time in exercise capacity and echocardiographic measurements of ventricular dimensions or function in predicting mortality in patients with chronic heart failure. METHODS AND RESULTS: Sixty-two patients with chronic heart failure (58 men, mean [+/-SD] age 60+/-10 years, mean peak oxygen consumption (VO(2)) 18.2+/- 5.9 ml. kg(-1). min(-1), mean left ventricular ejection fraction 38.9+/-15. 8%) who underwent both treadmill exercise testing and echocardiographic examination on two occasions, separated by 19+/-15 months were followed-up for a mean of 17 months (interquartile range 9-30 months). During the follow-up period, 19 patients (30%) died and three (4.8%) underwent heart transplantation. Of measurements taken at a single time-point (visit 2) exercise duration, peak VO(2), ventilatory response to exercise (VE/VCO(2)), left atrial diameter and left ventricular ejection fraction were found, by Cox proportional-hazard analysis, to predict the outcome in these patients (all P<0.05). Of the changes in parameters between visit 1 to visit 2, only changes in peak VO(2)per year (P=0.026) predicted non-transplanted survival (independent of changes in left ventricular ejection fraction and VE/VCO(2)). In Kaplan-Meier survival analysis patients with increased peak VO(2)over time (n=28) showed a better prognosis at 2 years (cumulative survival 75% [95% confidence interval: 56-95%] than those with a decrease in peak VO(2)(n=34, cumulative survival 50% [95% confidence interval: 31-68%]). CONCLUSIONS: Although single estimates of peak VO(2), VE/VCO(2)and left ventricular ejection fraction have significant prognostic importance in patients with chronic heart failure, when monitoring changes over time only peak VO(2)remains a significant predictor of outcome.     

Skeletal muscle myofibrillar protein oxidation and exercise capacity in heart failure

Background Heart failure is characterized by limited exercise tolerance and by a skeletal muscle myopathy with atrophy and shift toward fast fibres. An inflammatory status with elevated pro-inflammatory cytokines and exaggerated free radicals production can worsen muscle damage. We have previously demonstrated in a model of heart failure, the monocrotaline treated rat, that oxidation of skeletal muscle actin, tropomyosin and myosin produces a reduction of contractile efficiency, which may further depress muscle function and exercise capacity. Aims To investigate the presence of oxidized myofibrillar proteins in skeletal muscle of CHF patients by means of the Oxyblot technique and to correlate it with exercise capacity. Methods We have analyzed skeletal muscle biopsies taken from six patients with class III–IV NYHA CHF and four control patients (peak VO₂ 12.8 ± 1.9 vs. 29.7 ± 1.7 ml/kg/min, p < 0.0001). Results and conclusions A correlation between degree of myofibrillar oxidation and exercise capacity measured as peak VO₂ was obtained. In the skeletal muscle of CHF patient there was a much higher level of myofibrillar protein oxidation as expressed by the Oxyblot/Red Ponceau (Oxy/RP) ratio as compared to controls (2.1 ± 0.3 vs. 1.02 ± 0.09, p < 0.0001). The VO₂/Oxy/RP was significantly lower in the CHF patients. Higher levels of muscle oxidation were found in patients with lower exercise capacity with an inverse correlation between Oxyblot and VO₂ values (r ² = 0.83). Returned for 1. Revision: 6 August 2007 1. Revision received: 2 October 2007 Returned for 2. Revision: 8 November 2007 2. Revision received: 9 November 2007     

Isometric exercise for the evaluation of vasodilatory therapy in severe congestive heart failure

Summary There are few data avallable about the hemodynamic effects of isometric handgrip in severe congestive heart failure and its role in the evaluation of vasodilatory therapy. Therefore, we studied 20 patients with dilated cardiomyopathy at rest, during isometric handgrip, and during supine bicycle exercise before and after a single 25-mg dose of captopril. During handgrip, heart rate (p<0.001); systemic vascular resistance (p<0.01); systolic, mean, and diastolic pulmonary artery pressure (p<0.01) increased significantly; stroke volume index fell (p<0.05); wheras mean arterial pressure showed only a small increase, and cardiac index did not change. In contrast, mean arterial pressure and cardiac index increased during dynamic exercise (p<0.001), and peripheral resistance decreased (p<001). During both handgrip and bicycle exercise, captopril induced a decrease of arterial pressure (p<0.01 and p<0.001; respectively), peripheral resistance (p<0.001 and p<0.01; respectively), and systolic (p<0.01 and p<0.001, respectively) mean (p<0.001), and diastolic pulmonary artery pressure (p<0.001). Captopril induced and increase in stroke volume indes (p<0.01) and cardiac index (p<0.001 and p<0.01 respectively) during both types of exercise. The increase in heart rate (p<0.001), systolic (p<0.01), mean (p<0.001), and diastolic pulmonary artery pressure (p<0.01), as well as the increase in stroke volume index (p<0.05) and cardiae index (p<0.001) was significantly higher in dynamic exercise. In contrast, systemic vascular resistance was clearly higher in isometric than in dynamic exercise (p<0.001). After captopril, these changes were nearly the same. Isometric exercise induced—in contrast to dynamic exercise—vasoconstriction which was blunted by the application of captopril. From that it is concluded that because of the different changes in systemic vascular resistance, isometric exercise seems preferable to dynamic exercise in the evaluation of vasodilatory drugs in congestive heart failure.     

老年慢性左心衰竭与右心衰竭患者心肺运动试验特点比较

目的 比较老年慢性左心衰竭与右心衰竭患者心肺运动试验（CPET）特点。方法 入选老年非瓣膜性慢性左心衰竭患者25例[男性20例，年龄（60.2±4.7）岁]，以及年龄、性别、纽约心脏联合会（NYHA）心功能分级匹配的慢性右心衰竭患者25例[男性19例，年龄（61.3±5.7）岁]，排除合并肺部疾病、神经肌肉疾病或贫血等患者，对比其CPET特点。结果 两组患者年龄、性别、体质量指数（BMI）、NYHA心功能分级无明显差异，超声心动图左心室舒张末内径左心衰竭组明显大于右心衰竭组，分别为（66.1±9.0）和（40.4±5.4）mm，左心衰竭组左室射血分数明显低于右心衰竭组，分别为（32.5±11.9）%和（65.8±8.1）%（P＜0.001）。CPET结果显示，左心衰竭组峰值氧耗量（peak VO2）为（1056.6±340.5）ml/min，峰值单位千克体质量的氧耗量（peak VO2/kg）为（15.1±2.7）ml/（min·kg），peak VO2占预计值的百分比为（52±13）%，右心衰竭组分别为（750.9±269.1）ml/min，（11.0±3.2）ml/（min·kg）和（39±11）%，右心衰竭组较左心衰竭组明显降低（P＜0.05）。右心衰竭组峰值氧脉搏（VO2/HR）明显低于左心衰竭组[（6.3±2.2） vs （8.5±3.0）ml/（min·beat），P＝0.016]。右心衰竭组氧耗量与功率比值斜率（VO2/WR slope）明显低于左心衰竭组[（5.1±1.1） vs （6.4±1.8）ml/（min·W），P＝0.014]。与左心衰竭组相比，右心衰竭组每分通气量/每分二氧化碳生量成斜率（VE/VCO2 slope）明显升高[（34.7±8.2） vs （49.5±12.6），P＜0.001]。结论 与左心疾病所致左心衰竭患者相比，即使是相似的NYHA心功能分级，右心衰竭患者运动状态下的心肺功能更差，VE/VCO2 slope更高。     

Chronic vasodilator therapy with flosequinan in congestive heart failure

This study was conducted to determine the long-term effect of flosequinan, a new orally administered arterial and venous dilator, on the clinical course of patients with moderate to severe congestive heart failure. Seventeen patients on chronic digitalis and diuretic therapy were randomized to receive either flosequinan (n = 9) or placebo (n = 8) in a double-blind fashion. Changes in symptomatology, exercise performance, and left ventricular function were assessed serially during the two-month treatment period. During the course of therapy, a modest improvement in the symptom scores and functional classification of the flosequinan-treated patients was observed. Flosequinan evoked a significant increase in maximal exercise capacity. While long-term flosequinan administration also effected a progressive increase in resting heart rate, it did not consistently improve indices of left ventricular systolic function. The addition of chronic vasodilator therapy with flosequinan to standard digitalis-diuretic regimens is capable of inducing clinical improvement in patients with moderate to severe chronic heart failure. Trials involving larger patient populations will be necessary to confirm the results of this preliminary study and to determine the extent of clinical improvement, subpopulations benefited, role in heart failure therapeutics, and so forth.     

Early recovery of oxygen kinetics after submaximal exercise test predicts functional capacity in patients with chronic heart failure.

BACKGROUND: Oxygen (O2) uptake at peak exercise (VO2 peak) is an objective measurement of functional capacity in patients with chronic heart failure (CHF). The significance of recovery O2 kinetics parameters in predicting exercise capacity, and the parameters of submaximal exercise testing have not been thoroughly examined. METHODS AND RESULTS: Thirty-six patients (mean age = 48+/-14 years) with CHF and New York Heart Association functional class I, II, or III, and eight healthy volunteers (mean age = 39+/-13 years) were studied with maximal and submaximal cardiopulmonary exercise testing (CPET). The first degree slope of O2 uptake decay during early recovery from maximal (VO2/t-slope), and submaximal exercise (VO2/t-slope)(sub), were calculated, along with VO2 half-time (T(1/2)VO2). Patients with CHF had a longer recovery of O2 uptake after exercise than healthy volunteers, expressed by a lower VO2/t-slope (0.616+/-0.317 vs. 0.956+/-0.347 l min(-1) min(-1), P=0.029) and greater T(1/2)VO2 (1.28+/-0.30 vs. 1.05+/-0.15 min, P = 0.005). VO2/t-slope correlated with the VO2 peak (r = 0.84, P<0.001), anaerobic threshold (r = 0.79, P<0.001), and T(1/2)VO2, a previously established estimate of recovery O2 kinetics (r = -0.59, P<0.001). (VO2/t-slope)(sub) was highly correlated with VO2/t-slope after maximal exercise (r=0.87, P<0.001), with the VO2 peak (r=0.87, P<0.001) and with T(1/2)VO2 after maximal exercise (r=-0.62, P<0.001). VO2/t-slope after maximal and submaximal exercise was reduced in patients with severe exercise intolerance (F=9.3, P<0.001 and F=12.8, P<0.001, respectively). CONCLUSIONS: Early recovery O2 kinetics parameters after maximal and submaximal exercise correlate closely with established indices of exercise capacity in patients with CHF and in healthy volunteers. These findings support the use of early recovery O2 kinetics after submaximal exercise testing as an index of functional capacity in patients with CHF.     

Iron deficiency predicts impaired exercise capacity in patients with systolic chronic heart failure

Background

Iron is an indispensable element of hemoglobin, myoglobin, and cytochromes, and, beyond erythropoiesis, is involved in oxidative metabolism and cellular energetics. Hence, iron deficiency (ID) is anticipated to limit exercise capacity. We investigated whether ID predicted exercise intolerance in patients with systolic chronic heart failure (CHF).

Methods and Results

We prospectively studied 443 patients with stable systolic CHF (age 54 ± 10 years, males 90%, ejection fraction 26 ± 7%, New York Heart Association Class I/II/III/IV 49/188/180/26). ID was defined as: serum ferritin <100 μg/L or serum ferritin 100–300 μg/L with serum transferrin saturation <20%. Exercise capacity was expressed as peak oxygen consumption (VO₂) and ventilatory response to exercise (VE-VCO₂ slope). ID was present in 35 ± 4% (±95% confidence interval) of patients with systolic CHF. Those with ID had reduced peak VO₂ and increased VE-VCO₂ slope as compared to subjects without ID (peak VO₂: 13.3 ± 4.0 versus 15.3 ± 4.5 mL•min•kg, VE-VCO₂ slope: 50.9 ± 15.8 versus 43.1 ± 11.1, respectively, both P < .001, P < .05). In multivariable models, the presence of ID was associated with reduced peak VO₂ (β = −0.14, P < .01 P < .05) and higher VE-VCO₂ slope (β = 0.14, P < .01 P < .05), adjusted for demographics and clinical variables. Analogous associations were found between serum ferritin, and both peak VO₂ and VE-VCO₂ slope (P < .05).

Conclusions

ID independently predicts exercise intolerance in patients with systolic CHF, but the strength of these associations is relatively weak. Whether iron supplementation would improve exercise capacity in iron-deficient subjects requires further studies.     

Effects of acute exercise on hemorheological, endothelial, and platelet markers in patients with chronic heart failure in sinus rhythm.

BACKGROUND: Chronic heart failure (CHF) is associated with an increased risk of thrombosis and thromboembolic events, including stroke and venous thromboembolism. which may be related to a prothrombotic or hypercoagulable state. Acute vigorous exercise has been associated with activation of hemostasis, and this risk may well be particularly increased in patients with CHF. HYPOTHESIS: The study was undertaken to determine whether acute exercise would adversely affect abnormalities of hemorheological (fibrinogen, plasma viscosity, hematocrit), endothelial (von Willebrand factor), and platelet markers (soluble P selectin) in patients with CHF. METHODS: We studied 22 ambulant outpatients (17 men; mean age 65+/-9 years) with stable CHF (New York Heart Association class II-III and a left ventricular ejection fraction of < or =40%) who were exercised to exhaustion on a treadmill. Results were compared with 20 hospital controls (patients with vascular disease, but free of CHF) and 20 healthy controls. RESULTS: Baseline von Willebrand factor (p = 0.01) and soluble P-selectin (p = 0.006) levels were significantly elevated in patients with CHF when compared with controls. In the patients with CHF who were exercised, plasma viscosity, fibrinogen, and hematocrit levels increased significantly, both immediately post exercise and at 20 min into the recovery period (repeated measures analysis of variance, all p<0.05). There was a positive correlation between exercise workload and the maximal changes in plasma viscosity in the patients with CHF (Spearman r = 0.5, p = 0.02). Plasma viscosity levels increased with exercise in the hospital control group, although no other exercise-induced changes were noted in this group. CONCLUSION: The present study indicates that the hemorheological indices. fibrinogen, and hematocrit specifically increase during acute exercise in patients with CHF. Although moderate exercise should be encouraged in patients with CHF, vigorous exercise should probably be avoided in view of its potential prothrombotic effects in this high-risk group of patients.     

Predictors of cause-specific hospital readmission in patients with heart failure

BACKGROUND: Repeated hospital readmissions are frequent and increasing over time in patients with heart failure (HF). The predictors for readmission in patients with HF are not completely understood. HYPOTHESIS: The study was undertaken to investigate the time course of readmission by specific cause in patients with HF, and to examine the independent effects of HF etiology and left ventricular (LV) function on cause-specific readmissions. METHODS: A retrospective cohort of 493 consecutive patients with HF was followed for readmission for 16.5 +/- 12.3 months. Ischemic etiology of HF was defined as history of myocardial infarction (MI), coronary artery bypass graft (CABG), percutaneous transluminal coronary angioplasty (PTCA), or > or = 70% coronary stenosis. Left ventricular function was assessed echocardiographically. Cause-specific readmissions were classified as HF, cardiovascular disease (CVD) other than HF, and other non-CVD. RESULTS: The annual readmission rate was 56.6%. Median time to readmission was 91 days, with 18.3% patients readmitted within 1 month after discharge. Ischemic etiology independently predicted all-cause readmission: Cox hazard ratio (95% confidence interval): 1.40 (1.11-1.79). This relationship was significant in women (1.83 [1.31-2.55]), but not in men (1.15 [0.82-1.62]), while readmissions were equally frequent in both genders. Similarly, ischemic etiology significantly predicted readmission for CVD in women (4.18 [2.14-8.19]), but not in men (1.49 [0.83-2.67]). However, LV dysfunction independently predicted readmission for recurrent HF (2.44 [1.46-4.08]), while ischemic etiology was not predictive in either gender. CONCLUSIONS: Readmissions for recurrent HF comprise only one-third of total hospital readmissions in patients with HF. Ischemic etiology is a significant predictor of readmission, and most of this effect is mediated through a four-fold increased risk of readmission for CVD other than HF in women. Readmission for recurrent HF is predicted by LV dysfunction but not by ischemic etiology. Patients with HF can be accurately risk stratified for cause-specific readmission with available clinical data.     

Pulmonary hemodynamics and endothelin levels in pacing-induced heart failure: During rest and exercise

Elevated plasma levels of endothelin (ET) have been reported to accompany the development of heart failure (HF), and therefore, this potent vasoconstrictive peptide has been postulated to contribute to the altered pulmonary hemodynamics that occur in this disease process. The overall goal of this study was to examine more carefully the relationship between ET levels in the pulmonary system and pulmonary hemodynamics in the normal and HF states, during both rest and exercise. This study used a porcine model of chronic rapid pacing that has been shown in previous studies to produce left ventricular dysfunction and neurohormonal system activation consistent with the syndrome of HF. Pigs (n = 10) were chronically instrumented to measure pulmonary and systemic hemodynamics, parenchymal flow, and ET content and to obtain blood samples from the pulmonary circuit in the conscious state. Measurements were performed in the normal control state and again following the development of pacing-induced HF (240 beats/min per 21 days), both at rest and during treadmill exercise (3 mph, 15° incline, 12 minutes). With HF, under ambient resting conditions, a threefold increase in pulmonary plasma ET occurred and was accompanied by a fivefold increase in pulmonary vascular resistance. During treadmill exercise, pulmonary plasma ET and pulmonary vascular resistance remained elevated in the HF group when compared with the normal state and were associated with a sixfold decrease in pulmonary parenchymal flow. Pulmonary parenchymal ET content was increased with HF when compared with values for normal control subjects (8.5 ± 0.6 vs 5.6 ± 0.8 fmol ET/mg protein, P < .05). Thus, the findings of this study suggest that in this model of HF, increased ET within the pulmonary circuit contributed to abnormalities in resistive properties and parenchymal flow.     

老年慢性心衰患者运动康复的效果

目的：探讨老年慢性心衰患者实施运动康复的安全性及效果。方法：83例老年慢性心衰患者被随机分为常规护理组（41例,常规护理）和运动康复组（42例,在常规护理基础上接受运动训练）。疗程均为8周,随访12个月。患者心功能以纽约心脏病协会（NYHA）分级表示,以超声心动图测定左室射血分数（LVEF）和左室舒张末期内径（LVEDd）,同时测定6min步行距离（6MWD）,血浆脑钠肽（BNP）水平,代谢当量（METs）,明尼苏达心力衰竭生活质量量表（MLHFQ）评分表示健康相关生活质量,记录12个月内的再入院率和死亡率。结果：两组治疗8周时LVEF、LVEDd、NYHA分级均显著改善（P均〈0．05）,且与常规护理组相比,运动康复组LVEF[（54．7±6．2）％比（65．4±8．7）％]、LVEDd[（49．6±8．3）mm比（40．2±9．3）mm]、NYHA分级[（2．7±0．8）级比（1．9±0．9）级]改善更显著（P〈0．05）;6MWD[（122．7±9．2）m比（175．6±8．7）m]和METs[（5．8±1．8）比（8．4±2．4）]也明显增加（P〈0．01）,血浆BNP水平[（43．4±9．8）pg／ml比（31．7±8．9）pg／ml]明显降低（P〈0．05）;运动康复组康复训练中未发生严重不良事件。12个月时,运动康复组MLH-FQ评分明显高于常规护理组[（68．9±7．9）分比（45．65=8．2）分,P〈0．053,因心衰再入院率明显低于常规护理组（9．5％比24．4％,P〈0．05）。结论：对老年慢性心衰患者实施运动康复安全有效,可明显改善心功能,增强运动耐力,提高生活质量。     

Changes in pulmonary hemodynamics predict benefits in exercise capacity after ACE inhibition in patients with mild to moderate congestive heart failure

Several causes may affect the efficacy of angiotensin-converting enzyme (ACE) inhibitors in congestive heart failure (CHF). The present study was undertaken to identify what factors might predict benefits in exercise capacity after ACE inhibition in 22 patients with mild to moderate CHF. All patients underwent hemodynamic evaluation before and following an oral dose of quinapril (20 mg). They were then treated daily with 20 mg of quinapril and underwent exercise stress test off-drugs 1 day and 6 months later. Patients were grouped according to their relative changes in vascular resistances after quinapril: Group A (n=15) showed a greater decrease in pulmonary vascular resistance (PVR) than in systemic vascular resistance (SVR) (%ΔPVR/%ΔSVR>1). The opposite occurred in Group B (n = 7). Comparison of pretreatment baseline features revealed that the two groups had similar biochemical and hormonal variables, cardiac index, and SVR. Conversely, Group A patients had higher (p<0.05) pulmonary artery pressure and PVR compared with Group B patients. Following quinapril, Group A patients showed a greater (p<0.05) increase in cardiac index than Group B patients, despite a similar reduction in SVR. Accordingly, 1-day drug treatment significantly (p<0.001) increased exercise duration in Group A (+29%), but not in Group B patients (+7%). Benefits in exercise capacity were still significant (p<0.001) 6 months later. It is concluded that (1) ACE inhibitors may significantly increase exercise capacity in most but not all CHF patients; (2) these salutary effects occur predominantly in patients with abnormal pulmonary hemodynamics; (3) although there are many possible mechanisms by which these drugs may benefit CHF, these data favor the effects on veins and/or pulmonary vasculature as being the most clinically important factor.