Effects of exercise training on abnormal ventilatory responses to exercise in patients with chronic heart failure

Patients with chronic heart failure frequently report shortness of breath during daily activities as their primary symptom. In recent years, many efforts have been made by researchers to explain the mechanisms that underlie the characteristic heightened ventilatory response to activity in patients with chronic heart failure. The degree to which the ventilatory response to exercise is heightened parallels the severity of the disease, and measuring the ventilatory gas exchange response to exercise can help quantify the patient's response to therapy. Prior to the 1990s, patients with chronic heart failure were generally discouraged from participating in programs of exercise training. However, in the last decade, studies have demonstrated that exercise training is quite safe for these patients, and a multitude of benefits have been reported. Among the benefits of training are improvements in the abnormal ventilatory response to exercise. Although many mechanisms could potentially explain this response, it appears most likely that this improvement after training is due to a reduction in lactate accumulation and an attenuation of the heightened muscle receptor reflex response that occurs in chronic heart failure. This article reviews the mechanisms of dyspnea in chronic heart failure, along with recent studies assessing the effects of training on abnormal ventilatory responses to exercise in these patients. (c)2000 by CHF, Inc.     

Low-intensity exercise training delays heart failure and improves survival in female hypertensive heart failure rats

Exercise training improves functional capacity and quality of life in patients with heart failure. However, the long-term effects of exercise on mortality associated with hypertensive heart disease have not been well defined. In the present study, we investigated the effect of low-intensity exercise training on disease progression and survival in female spontaneously hypertensive heart failure rats. Animals with severe hypertension (16 months old) were treadmill trained (14.5 m/min, 45 min/d, 3 d/wk) until they developed terminal heart failure or were euthanized because of age-related complications. Exercise delayed mortality resulting from heart failure (P<0.001) and all causes (P<0.05) and transiently attenuated the systolic hypertension and contractile dysfunction observed in the sedentary animals but had no effect on cardiac morphology or contractile function in end-stage heart failure. Training had no effect on terminal myocardial protein expression of antioxidant enzymes, calcium handling proteins, or myosin heavy chain isoforms but was associated with higher cytochrome oxidase activity in cardiac mitochondria (P<0.05) and a greater mitochondrial content of cardiolipin, a phospholipid that is essential for optimal mitochondrial energy metabolism. In conclusion, low-intensity exercise training significantly delays the onset of heart failure and improves survival in female hypertensive heart failure rats without eliciting sustained improvements in blood pressure, cardiac function, or expression of several myocardial proteins associated with the cardiovascular benefits of exercise. The effects of exercise on cytochrome oxidase and cardiolipin provide novel evidence that training may improve prognosis in hypertensive heart disease by preserving mitochondrial energy metabolism.     

Exercise training improves function of circulating angiogenic cells in patients with chronic heart failure

Alterations in circulating angiogenic cells (CAC) and endothelial progenitor cells (EPC), known to contribute to endothelial repair, could explain the reversal of endothelial function in response to exercise training. Moreover, training-induced vascular remodeling might affect the acute response of EPC and CAC following a single exercise bout. We studied the impact of exercise training on CAC function and numbers of CD34⁺/KDR⁺ EPC in patients with chronic heart failure (CHF) and we assessed the effect of acute exercise on CAC and EPC in sedentary and trained patients. Twenty-one sedentary CHF patients underwent 6-month exercise training and were compared to a non-trained control group (n = 17) and 10 healthy age-matched subjects. At baseline and follow-up, flow-mediated dilation was assessed and graded exercise testing (GXT) was performed. Before and immediately after GXT, CAC migratory capacity was assessed in vitro and circulating CD34⁺/KDR⁺ EPC were quantified using flow cytometry. At baseline, CAC migration was significantly impaired in sedentary CHF patients but normalized acutely after GXT. Training corrected endothelial dysfunction, which coincided with a 77% increase in CAC migration (P = 0.0001). Moreover, the GXT-induced improvement detected at baseline was no longer observed after training. Numbers of CD34⁺/KDR⁺ EPC increased following 6-month exercise training (P = 0.021), but were not affected by GXT, either prior or post-training. In conclusion, the present findings demonstrate for the first time that exercise training in CHF reverses CAC dysfunction and increases numbers of CD34⁺/KDR⁺ EPC, which is accompanied by improvement of peripheral endothelial function. The acute exercise-induced changes in CAC function wane with exercise training, suggesting that repetitive exercise bouts progressively lead to functional endothelial repair.     

Nocturnal continuous positive airway pressure improves ventilatory efficiency during exercise in patients with chronic heart failure

OBJECTIVES: Chronic heart failure is closely related to impaired cardiorespiratory reflex control, including decreased ventilatory efficiency during exercise (Ve/Vco(2)-slope) and central sleep apnea (CSA). Continuous positive airway pressure (CPAP) and nocturnal oxygen therapy alleviate CSA. The aim of the present study was to compare the effects of nocturnal CPAP and oxygen therapy on Ve/Vco(2)-slope. DESIGN AND SETTING: Prospective controlled trial at a university hospital. PATIENTS: Twenty-six stable patients with chronic heart failure and CSA. INTERVENTION AND MEASUREMENTS: Ten patients received nocturnal oxygen, and 16 patients were assigned to CPAP treatment. At baseline and after 12 weeks of treatment, symptom-limited cardiopulmonary exercise testing was performed on a cycle ergometer. Expiratory gas was analyzed breath by breath for evaluation of ventilation and ventilatory efficiency in combination with arteriocapillary blood gas analysis during rest and exercise. RESULTS: CPAP treatment significantly reduced the Ve/Vco(2)-slope (31.2 +/- 1.6 vs 26.2 +/- 1.0, p = 0.005) and improved the left ventricular ejection fraction (LVEF) [31.7 +/- 2.6% vs 35.7 +/- 2.7%, p = 0.041]. CPAP treatment significantly reduced the apnea-hypopnea index (AHI) [35.9 +/- 4.0/h vs 12.2 +/- 3.6/h, p = 0.002]. Peak oxygen consumption (Vo(2)) [16.2 +/- 1.1 L/min/kg vs 16.3 +/- 1.2 L/min/kg, p = 0.755] remained similar after CPAP treatment. Oxygen therapy reduced the AHI (28.8 +/- 3.2/h vs 8.7 +/- 4.1/h, p = 0.019), but did not improve exercise capacity (peak Vo(2), 15.4 +/- 1.5 L/min/kg vs 15.6 +/- 1.9 L/min/kg, p = 0.760), LVEF (30.9 +/- 2.4% vs 32.5 +/- 2.3%, p = 0.231), or the Ve/Vco(2)-slope (30.0 +/- 1.5 vs 29.8 +/- 1.5, p = 0.646). CONCLUSION: Nocturnal CPAP and oxygen therapy alleviate CSA to a similar degree. Only CPAP therapy may improve ventilatory efficiency during exercise and may have favorable effects on LVEF. Therefore, our data suggest that CPAP is advantageous compared to oxygen in the treatment of CSA in patients with chronic heart failure.     

Prognostic power of ventilatory responses during submaximal exercise in patients with chronic heart disease

BACKGROUND: Although parameters obtained during submaximal exercise are known to be useful for predicting mortality in cardiac patients, it has been a matter of debate whether the submaximal parameters are superior to peak oxygen uptake (VO(2)). For this purpose, we aimed to determine the best index among exercise variables in predicting long-term mortality in patients with chronic heart disease. METHODS: The study population consisted of 385 consecutive patients with chronic heart disease who performed a symptom-limited incremental exercise test on a cycle ergometer. Breath-by-breath respiratory gas analysis was used to estimate the peak VO(2), the ratio of the increase in VO(2) to the increase in work rate (WR) [VO(2)/Delta WR], and the ratio of the increase in minute ventilation E to the increase in carbon dioxide output (VCO(2)) [Delta VE/Delta VCO(2)]. RESULTS: After 1,899 +/- 495 days of follow-up (mean +/- SD), 33 cardiovascular-related deaths occurred. Nonsurvivors achieved lower peak VO(2), lower VO(2)/Delta VWR, and higher Delta VE/Delta VCO(2) compared to the survivors. In the univariate Cox proportional hazards analysis, peak VO(2), VO(2)/Delta VWR, and Delta VE/Delta VCO(2) were found to be significant prognostic indexes of survival. However, multivariate analysis revealed O(2)/Delta VWR as an independent predictor of mortality and Delta VE/delta VCO(2) as a slightly weaker predictor. In this analysis, the prognostic power of peak O(2) was insignificant. CONCLUSION: Submaximal respiratory gas indexes are very likely to be more sensitive than peak VO(2) for predicting poor survival in ambulatory patients with chronic heart disease.     

Exercise training in heart failure improves quality of life and exercise capacity

Aims Benefit from exercise training in heart failure has mainly beenshown in men with ischaemic disease. We aimed to examine theeffects of exercise training in heart failure patients 75 yearsold of both sexes and with various aetiology. Methods and Results Fifty-four patients with stable mild-to-moderate heart failurewere randomized to exercise or control, and 49 completed thestudy (49% 65 years; 29% women; 24% non-ischaemic aetiology;training, n=22; controls, n=27). The exercise programme consistedof bicycle training at 80% of maximal intensity over a periodof 4 months.Improvements vs controls were found regarding maximalexercise capacity (6±12 vs –4±12% [mean±SD],P<0·01)and global quality-of-life (2 [1] vs 0 [1] units [median {inter-quartilerange}],P<0·01), but not regarding maximal oxygenconsumption or the dyspnoea–fatigue index. All of thesefour variables significantly improved in men with ischaemicaetiology compared with controls (n=11). However, none of thesevariables improved in women with ischaemic aetiology (n=5),or in patients with non-ischaemic aetiology (n=6). The trainingresponse was independent of age, left ventricular systolic function,and maximal oxygen consumption. No training-related adverseeffects were reported. Conclusion Supervised exercise training was safe and beneficial in heartfailure patients 75 years, especially in men with ischaemicaetiology. The effects of exercise training in women and patientswith non-ischaemic aetiology should be further examined.     

Lactate production during maximal and submaximal exercise in patients with chronic heart failure

In patients with chronic heart failure whose cardiac output response to exercise is impaired, determination of anaerobic threshold may provide a useful and objective approach to grade the severity of heart failure. In such patients performing upright treadmill exercise to exhaustion, this study examined the reproducibility of the response of cardiac output and mixed venous lactate concentration when the exercise test was repeated the same or next day, the nature of this response after rest and exercise cardiac output levels were augmented by the cardiotonic agent amrinone and the response of lactate during symptom-limited submaximal exercise performed at either aerobic or anaerobic levels of work for each patient. Findings were: 1) the response of cardiac output and mixed venous lactate was reproducible (p less than 0.05) when assessed either the same or the next day; 2) when exercise cardiac output was increased (p less than 0.05) by oral amrinone therapy, the increase in lactate was delayed (p less than 0.05) to higher levels of muscular work and this was not true when cardiac output was unchanged; and 3) only submaximal anaerobic exercise was symptom limited and associated with an increase in lactate concentration. Thus, the lactate response and anaerobic threshold determination should prove useful to assess the severity of chronic stable heart failure and its response to pharmacologic intervention. The submaximal anaerobic exercise test may provide additional insights into the effort intolerance these patients experience.     

步行训练对老年慢性心力衰竭患者心脏功能康复的影响

目的:观察步行训练方式对老年慢性心力衰竭患者心功能康复的效果和安全性。方法:295例Ⅱ～Ⅲ级慢性心功能不全的老年患者随机被分为康复组(152例)和对照组(143例),康复组在药物治疗基础上进行步行训练,对照组只进行药物治疗。经过6个月的随访,对比两组治疗前、后的血压、静息心率、6min步行距离、心脏超声的左室射血分数(LVEF)和左室舒张末期内径(LVEDd)等的变化情况。结果:运动训练前不同组间一般情况、血压、静息心率、6min步行距离和左室功能无明显差异(P0.05);运动训练6个月后各组死亡情况没有差别;步行运动训练组总再次住院率(20.4%∶33.6%)和因心血管疾病再次住院率(11.8%∶22.8%)明显低于对照组(P均0.05);与运动训练前及对照组治疗后比较,康复组治疗后静息心率明显下降[(72.1±15.7)次/min,(74.3±16.8)次/min∶(66.8±12.4)次/min],6min步行距离[(284.9±104.7)m,(296.1±134.5)m∶(328.6±124.2)m]和LVEF[(33.4±9.7)%,(30.4±9.6)%∶(35.9±10.9)%]均明显增加(P均0.01);血压和LVEDd无明显变化(P0.05)。结论:一定强度的步行训练对老年慢性充血性心力衰竭患者心脏功能的康复是安全和有效的。     

Amrinone and exercise performance in patients with chronic heart failure

Whether cardiotonic agents can improve the ability of patients with chronic heart failure to exercise remains unknown. Accordingly, the circulatory and respiratory response of 11 patients with severe heart failure refractory to digitalis, diuretic drugs and vasodilators was assessed during upright treadmill exercise before, within 24 hours and after 4 weeks of therapy with amrinone. The purpose of this study was to determine the ability of amrinone therapy to improve exercise hemodynamics, effort tolerance and aerobic capacity of these patients. Acute intravenous administration of amrinone (1.8 ± 0.1 mg/kg body weight) produced the following changes (mean values ± standard error of the mean) in hemodynamic variables during supine rest; increased cardiac index (from 2.04 ± 0.39 to 2.99 ± 0.38 liters/min per m²; p <0.01) and reduced pulmonary wedge pressure (from 24 ± 6 to 14 ± 6 mm Hg; p <0.01) without altering heart rate or mean arterial pressure. Within 24 hours after administration of amrinone, wedge pressure decreased at the onset of (from 25 ± 7 to 14 ± 7 mm Hg) and throughout exercise (p <0.01), whereas the exercise response of cardiac output, arteriovenous oxygen difference, heart rate, pulmonary and systemic vascular resistances, maximal oxygen uptake and the pattern of ventilation remained similar to control values. However, after 4 weeks of amrinone therapy, exercise and aerobic capacities were increased 44 and 48 percent (p <0.03), respectively, whereas the ventilatory response was unchanged. Thus, amrinone is a potent cardiotonic agent that acutely improves the function of the failing heart at rest and during exercise; the maximal aerobic capacity was increased after 4 weeks of therapy. Amrinone therefore appears to hold promise for the management of patients with chronic heart failure.     

Exercise training in patients with chronic heart failure improves endothelial function predominantly in the trained extremities.

The present study investigates whether lower-limb dominant exercise training in patients with chronic heart failure (CHF) improves endothelial function primarily in the trained lower extremities or equally in the upper and lower extremities. Twenty-eight patients with CHF were randomized to the exercise or control group. The exercise group underwent cycle ergometer training for 3 months while controls continued an inactive sedentary lifestyle. Exercise capacity (6-min walk test) and flow-mediated vasodilation in the brachial and posterior tibial arteries were evaluated. After 3 months, walking performance increased only in the exercise group (488+/-16 to 501+/-14 m [control]; 497+/-23 to 567+/-39 m [exercise, p<0.05]). The flow-mediated vasodilation in the brachial arteries did not change in either group (4.2+/-0.5 to 4.5+/-0.4% [control]; 4.3+/-0.5 to 4.6+/-0.4% [exercise]), but that in the posterior tibial arteries increased only in the exercise group (4.1+/-0.5 to 4.1+/-0.3% [control]; 3.6+/-0.3 to 6.4+/-0.6% [exercise, p<0.01]). Cycle ergometer training improved flow-mediated vasodilation in the trained lower limbs, but not in the untrained upper limbs. Exercise training appears to correct endothelial dysfunction predominantly by a local effect in the trained extremities.     

Central adaptations to exercise training in patients with chronic heart failure

In chronic heart failure patients, the increase of peak VO₂ observed after a period of aerobic training is currently attributed more to peripheral (skeletal muscle) than central (heart) adaptations. This paper reviews the current scientific evidence regarding the existence or the absence of significant training-induced adaptations of peak cardiac output and its determinants in patients with chronic heart failure due to left ventricular systolic dysfunction. It is concluded that, on the basis of available literature, a training-induced significant increase of peak cardiac output with respect to pre-training values does exist in the chronic heart failure population. Such an effect is due to adaptations of the main cardiac output determinants, that is, heart rate and stroke volume, whose relative contribution to the cardiac output increase will vary in the single patient due to variability in the individual response to the training stimulus. Moreover, these data emphasize both the safety and even the central morpho-functional benefits of aerobic training programs in the chronic heart failure population, setting the stage for an even more widespread use of this non-pharmacologic intervention in the everyday clinical practice. As most studies considered in this review were conducted in the pre-beta-blockers era, the possibility to extend the conclusions of this paper to chronic heart failure patients on beta-blocking therapy remains to be verified.     

Exercise training decreases ventilatory requirements and exercise-induced hyperinflation at submaximal intensities in patients with COPD

STUDY OBJECTIVES: We hypothesized that endurance exercise training would reduce the degree of hyperinflation for a given level of exercise and thereby improve submaximal exercise endurance. METHODS: Twenty-four patients with COPD (mean FEV(1), 36.4 +/- 8.5% of predicted [+/- SD]) undertook a high-intensity cycle ergometer exercise training program for 45 min, three times a week for 7 weeks. Before and after training, the patients performed both an incremental exercise test to maximum and a constant work rate (CWR) test on a cycle ergometer at 75% of the peak work rate obtained in the pretraining incremental test. Ventilatory variables were measured breath-by-breath, and inspiratory capacity (IC) was measured every 2 min to assess changes in end-expiratory lung volume. RESULTS: After training, the increase in peak oxygen uptake was not statistically significant; however, the peak work rate increased by 12.9 +/- 10.3 W (p < 0.01). For the CWR test performed at the same work rate both before and after training, ventilation and breathing frequency (f) were lower after training (average, 1.97 L/min and 3.2 breaths/min, respectively; p < 0.01) and IC was greater (by an average of 133 mL, p < 0.05), signifying decreased hyperinflation. The increase in IC at the point of termination in the shortest CWR test for each individual (defined as isotime) correlated well with both the decreased f (r = 0.63, p = 0.001) and with the increase in CWR exercise endurance (average, 13.1 min, r = 0.46, p = 0.023). CONCLUSIONS: Exercise training in patients with severe COPD dramatically improves submaximal exercise endurance. Decreased dynamic hyperinflation may, in part, mediate the improvement in exercise endurance by delaying the attainment of a critically high inspiratory lung volume.     

Impaired glucose tolerance worsens exercise capacity and ventilatory response to exercise in patients with chronic heart failure

BACKGROUND: There is increasing evidence for the importance of peripheral abnormalities in the pathogenesis and progression of heart failure (HF). Recently, glucose and insulin metabolism abnormalities have been intensively investigated in patients with HF. AIM: To investigate whether coexistence of impaired glucose tolerance (IGT) may decrease exercise tolerance and influence ventilatory response to exercise in patients with systolic HF. METHODS: Maximal cardiopulmonary exercise test with evaluation of peak VO2 and VE/VCO2 slope and oral glucose tolerance test were performed in 64 clinically stable patients with HF and LVEF <45%. RESULTS: Impaired glucose tolerance was diagnosed in 26 (41%) patients and normal glucose tolerance (NGT) in 38 (59%) patients. There were no significant differences in baseline clinical characteristics or LVEF between groups. There were significant differences in peak VO2 between IGT and NGT (15.4+/-4.1 vs. 18.7+/-4.2 ml/kg/min respectively; p=0.003) and VE/VCO2 slope (35.7+/-7.3 vs. 31.8+/-5.7 respectively; p=0.02). The IGT was independently related to peak VO2 and VE/VCO2 slope in multivariate regression analysis. CONCLUSION: The IGT is associated with worse exercise capacity and ventilatory response to exercise in patients with HF.