Exercise testing and training in patients with peripheral vascular disease and lower extremity amputation.

Patients with peripheral vascular disease have a high risk of coronary artery disease. The risk is even greater when the peripheral vascular disease leads to lower extremity amputation. Exercise testing using lower extremity exercise has been the "gold standard" for screening for coronary artery disease, but many patients with peripheral vascular disease and those with amputations have difficulty doing this type of exercise. Arm exercise ergometry has been shown to be a safe and effective alternative for the detection of coronary artery disease in patients who cannot do leg exercise. This test has also been used to determine safe exercise levels and may be able to predict the ultimate level of prosthetic use in amputees. Exercise training with arm ergometry also improves cardiovascular efficiency and upper body strength in poorly conditioned patients. Studies are needed to appreciate fully the role of exercise testing and training in the recovery of these patients after amputation.     

Relationship of Exercise Capacity and Left Ventricular Dimensions in Patients with a Normal Ejection Fraction. An Exploratory Study

Objectives

Extreme endurance exercise is known to be associated with an enlargement of the left ventricular (LV) chamber, whereas inactivity results in inverse changes. It is unknown if these dimensional relationships exist in patients.

Methods

We analyzed the relationship of exercise capacity and LV dimension in a cohort of sequential patients with a normal ejection fraction undergoing stress echocardiography. In a total of 137 studies the following questions were addressed: (a) is there a difference in LV dimensions of patients with an excellent exercise capacity versus patients with a poor exercise capacity, (b) how is LV dimension and exercise capacity affected by LV wall thickness and (c) how do LV dimensions of patients who are unable to walk on a treadmill compare to the above groups.

Results

Patients with a poor exercise capacity or who are unable to physically exercise have a 34 percent smaller LV cavity size when compared to patients with an excellent exercise capacity (p<0.001). This reduction in LV chamber size is associated with concentric LV hypertrophy and a reciprocal increase in resting heart rate. In addition, cardiac output reserve is further blunted by chronotropic incompetence and a tachycardia-induced LV volume reduction. In conclusion the relationship of exercise capacity and cardiac dimensions described in extreme athletes also applies to patients. Our exploratory analysis suggests that patients who cannot sufficiently exercise have small LV cavities.     

Exercise training in chronic heart failure: mechanisms and therapies

Decreased exercise capacity negatively affects the individuals’ ability to adequately perform activities required for normal daily life and, therefore, the independence and quality of life. Regular exercise training is associated with improved quality of life and survival in healthy individuals and in cardiovascular disease patients. Also in patients with stable heart failure, exercise training can relieve symptoms, improve exercise capacity and reduce disability, hospitalisation and probably mortality. Physical inactivity can thus be considered a major cardiovascular risk factor, and current treatment guidelines recommend exercise training in patients with heart failure in NYHA functional classes II and III. Exercise training is associated with numerous pulmonary, cardiovascular, and skeletal muscle metabolic adaptations that are beneficial to patients with heart failure. This review discusses current knowledge of mechanisms by which exercise training is beneficial in these patients.     

Study protocol: EXERcise and Cognition in Sedentary adults with Early-ONset dementia (EXERCISE-ON)

ABSTRACT: BACKGROUND: Although the development of early-onset dementia is a radical and invalidating experience for both patient and family there are hardly any non-pharmacological studies that focus on this group of patients. One type of a non-pharmacological intervention that appears to have a beneficial effect on cognition in older persons without dementia and older persons at risk for dementia is exercise. In view of their younger age early-onset dementia patients may be well able to participate in an exercise program. The main aim of the EXERCISE-ON study is to assess whether exercise slows down the progressive course of the symptoms of dementia. METHODS: One hundred and fifty patients with early-onset dementia are recruited. After completion of the baseline measurements, participants living within a 50 kilometre radius to one of the rehabilitation centres are randomly assigned to either an aerobic exercise program in a rehabilitation centre or a flexibility and relaxation program in a rehabilitation centre. Both programs are applied three times a week during 3 months. Participants living outside the 50 kilometre radius are included in a feasibility study where participants join in a daily physical activity program set at home making use of pedometers. Measurements take place at baseline (entry of the study), after three months (end of the exercise program) and after six months (follow-up). Primary outcomes are cognitive functioning; psychomotor speed and executive functioning; (instrumental) activities of daily living, and quality of life. Secondary outcomes include physical, neuropsychological, and rest-activity rhythm measures. DISCUSSION: The EXERCISE-ON study is the first study to offer exercise programs to patients with early-onset dementia. We expect this study to supply evidence regarding the effects of exercise on the symptoms of early-onset dementia, influencing quality of life.Trial registrationThe present study is registered within The Netherlands National Trial Register (ref: NTR2124).     

An extension to the compartmental model of type 1 diabetic patients to reproduce exercise periods with glycogen depletion and replenishment

The purpose of this work is to present the main interactions promoted by exercise and synthesize them into mathematical equations. It is intended to extend the ability of the compartmental glucose-insulin model introduced by Sorensen [1985. A physiologic model of glucose metabolism in man and its use to design and assess improved insulin therapies for diabetes. Ph.D. Dissertation, Chemical Engineering Department, MIT, Cambridge] to reproduce variations in the blood glucose concentration induced by exercise in diabetic patients and to complement the previous work by Lenart and Parker [2002. Modeling exercise effects in type I diabetic patients. In: Proceedings of the 15th Triennial World Congress, Barcelona, Spain] and Lenart, DiMascio and Parker [2002. Modeling glycogen-exercise interactions in type I diabetic patients. In: Proceedings of the A.I.Ch.E. Annual Meeting, Indianapolis, IN]. The immediate consequences of exercise are incorporated in this research: redistribution of blood flows, increments in peripheral glucose and insulin uptakes, and increment in hepatic glucose production. The extended model was verified with experimental data for light and moderate intensity exercise. In addition, data extrapolation was introduced to simulate heavy intensity exercise. The hepatic glycogen reservoir limits the peripheral glucose uptake for prolonged exercise. Therefore, the depletion and replenishment of hepatic glycogen were modeled, looking to reproduce the blood glucose levels for a type 1 diabetic patient during a normal day, with meal intakes, insulin infusions and/or boluses, and a predefined exercise regime. From the extensive simulation evaluation, it is found that the new exercise model provides a good approximation to the available experimental data from literature.     

Exercise testing as a diagnostic entity in mitochondrial myopathies

Exercise intolerance is one of the most common symptoms in patients with mitochondrial myopathies (MM). At the whole body level, this is characterized by a reduction in maximal oxygen consumption (VO2max) with an excessive carbon dioxide production (VCO2), increased rating of perceived exertion and a hyperdynamic circulatory response at a given exercise intensity. Fewer patients with MM display overt muscle atrophy and weakness even in the absence of a peripheral neuropathy. At the level of the skeletal muscle, the abnormal exercise response in MM patients is characterized by an increase in; delivery of oxygen relative to extraction (reduced myoglobin or hemoglobin desaturation), lactate production, phosphocreatine hydrolysis and time of post-exercise PCr and ADP recovery. Classically, the characterization of exercise intolerance is performed using cycle ergometry with measurements of VO2, VCO2, respiratory exchange ratio (RER = VCO2/VO2), heart rate, minute ventilation, rating of perceived exertion, and cardiac output (where available). Exercise protocols to maximum or for a given time period at a set workload can differentiate MM from controls with a sensitivity of 0.63-0.75 and a specificity of 0.70-0.90. Modified hand-grip exercise protocols, especially if coupled with simultaneous measurements of myoglobin/hemoglobin desaturation (near infra-red spectroscopy) or venous oxygenation, can achieve similar or higher levels of sensitivity and specificity. Similarly, exercise coupled with muscle phosphocreatine/Pi ratios, PCr, pH or ADP recovery kinetics, determined using magnetic resonance spectroscopy are useful in differentiating MM, but are limited by availability, experience and cost. In summary, aerobic exercise testing with some measurement of oxygen consumption can be performed in most institutions and can provide valuable information in the both the work-up of patients with suspected MM as well as in the monitoring of therapy in such patients.     

Impact of exercise training on cardiovascular disease and risk

Epidemiological studies in large cohorts support the notion that physical fitness is associated with reduced cardiovascular mortality and hospitalization due to cardiovascular disease. During the last 20 years even the concept of resting inactive after a myocardial infarction has dramatically changed and nowadays patients are mobilized and included into exercise training programs very shortly after the insult. Unfortunately, these beneficial effects of exercise training are independent of the genetic background and are only observed in case the training program is not paused for a longer time. Therefore, to take advantage of the effects of exercise training in health care the challenge for the future is to increase exercise compliance by offering interesting and effective exercise training programs. At the physiological and molecular level, exercise training affects several organs like the vascular system and the skeletal muscle. Changes elicited by regular exercise training range in the vascular system from increasing vasodilation due to an elevation of bioavailable nitric oxide to a shift in the catabolic/anabolic balance in the peripheral skeletal muscle. In this review we discuss the healthy benefit of exercise training and the molecular changes triggered by exercise training in the setting of secondary prevention.     

Muscle mechanoreceptor sensitivity in heart failure

Prior work in animals suggests that muscle mechanoreceptor control of sympathetic activation (MSNA) during exercise in heart failure (HF) is heightened and that muscle mechanoreceptors are sensitized by metabolic by-products. We sought to determine whether 1) muscle mechanoreceptor control of MSNA is enhanced in HF patients and 2) lactic acid sensitizes muscle mechanoreceptors during rhythmic handgrip (RHG) exercise in healthy humans and patients with HF. Dichloroacetate (DCA), which reduces the production of lactic acid, or saline control was infused in 12 patients with HF and 13 controls during RHG. MSNA was recorded (microneurography). After saline was administered and during exercise thereafter, MSNA increased earlier in HF compared with controls, consistent with baseline-heightened mechanoreceptor sensitivity. In both HF and controls, MSNA increased during the 3-min exercise protocol, consistent with further sensitization of muscle mechanoreceptors by metabolic by-product(s). During posthandgrip circulatory arrest, MSNA returned rapidly to baseline levels, excluding the muscle metaboreceptors as mediators of the sympathetic excitation during RHG. To isolate muscle mechanoreceptors from central command, we utilized passive exercise in 8 HF and 11 controls, and MSNA was recorded. MSNA increased significantly during passive exercise in HF but not in controls. In conclusion, muscle mechanoreceptors mediate the increase in MSNA during low-level RHG exercise in healthy humans, and this muscle mechanoreceptor control is augmented further in HF. Neither lactate generation nor the fall in pH during RHG plays a central role in muscle mechanoreceptor sensitization. Finally, muscle mechanoreceptors in patients with HF have heightened basal sensitivity to mechanical stimuli resulting in exaggerated early increases in MSNA.     

Exertional dyspnea in mitochondrial myopathy: clinical features and physiological mechanisms

Exertional dyspnea limits exercise in some mitochondrial myopathy (MM) patients, but the clinical features of this syndrome are poorly defined, and its underlying mechanism is unknown. We evaluated ventilation and arterial blood gases during cycle exercise and recovery in five MM patients with exertional dyspnea and genetically defined mitochondrial defects, and in four control subjects (C). Patient ventilation was normal at rest. During exercise, MM patients had low Vo(2peak) (28 ± 9% of predicted) and exaggerated systemic O(2) delivery relative to O(2) utilization (i.e., a hyperkinetic circulation). High perceived breathing effort in patients was associated with exaggerated ventilation relative to metabolic rate with high VE/VO(2peak), (MM = 104 ± 18; C = 42 ± 8, P ≤ 0.001), and Ve/VCO(2peak)(,) (MM = 54 ± 9; C = 34 ± 7, P ≤ 0.01); a steeper slope of increase in ΔVE/ΔVCO(2) (MM = 50.0 ± 6.9; C = 32.2 ± 6.6, P ≤ 0.01); and elevated peak respiratory exchange ratio (RER), (MM = 1.95 ± 0.31, C = 1.25 ± 0.03, P ≤ 0.01). Arterial lactate was higher in MM patients, and evidence for ventilatory compensation to metabolic acidosis included lower Pa(CO(2)) and standard bicarbonate. However, during 5 min of recovery, despite a further fall in arterial pH and lactate elevation, ventilation in MM rapidly normalized. These data indicate that exertional dyspnea in MM is attributable to mitochondrial defects that severely impair muscle oxidative phosphorylation and result in a hyperkinetic circulation in exercise. Exaggerated exercise ventilation is indicated by markedly elevated VE/VO(2), VE/VCO(2), and RER. While lactic acidosis likely contributes to exercise hyperventilation, the fact that ventilation normalizes during recovery from exercise despite increasing metabolic acidosis strongly indicates that additional, exercise-specific mechanisms are responsible for this distinctive pattern of exercise ventilation.     

Cyclooxygenase products sensitize muscle mechanoreceptors in healthy humans

Evidence in healthy animals and humans is accumulating that the muscle mechanoreceptors play an important role in mediating sympathetic activation during exercise, especially rhythmic exercise. Furthermore, muscle mechanoreceptors appear to be sensitized acutely during exercise by metabolic by-products, although the identity of these by-products remains unknown. The purpose of this study was to determine whether the metabolic by-products 1) prostaglandins and/or 2) adenosine sensitize muscle mechanoreceptor control of muscle sympathetic nerve activity (MSNA) in normal humans during rhythmic exercise. MSNA was recorded using microneurography. Muscle mechanoreceptors were activated by low-level rhythmic forearm exercise for 3 min. In 16 healthy humans, intra-arterial indomethacin was infused into the exercising arm to inhibit synthesis of cyclooxygenase products. In 18 healthy humans, intra-arterial aminophylline was infused into the exercising arm to block adenosine receptors. During saline control, MSNA increased significantly during exercise. Inhibition of cyclooxygenase during exercise dramatically and virtually completely eliminated the reflex sympathetic activation. Inhibition of adenosine receptors with aminophylline had no effect on the sympathetic activation during muscle mechanoreceptor stimulation. In conclusion, muscle mechanoreceptors are sensitized by cyclooxygenase products, but not by adenosine, during 3 min of low-level rhythmic handgrip exercise in healthy humans. Further studies of other metabolic by-products and of patients with enhanced muscle mechanoreceptor sensitivity, such as patients with heart failure, are warranted.     

Local exercise and oxidative stress in chronic obstructive broncho-pneumopathies: preliminary results

The role of altered peripheral muscle function in exercise intolerance of chronic obstructive pulmonary disease (COPD) is now well established. However, the mechanisms underlying this phenomen, have not been determined. One hypothesis is that the oxidative stress, that leads to tissue injury may be involved. A recent study has shown that general exercise caused systemic oxidative stress in COPD patients. However, the origin of this stress was not absolutely clear: airways, muscle, both, or other? The aim of this study was first to determine with a systemic approach, whether systemic oxidative stress occur in patients who perform local exercise and then with a muscular needle biopsy approach, to confirm the muscular origin of this oxidative stress. METHODS: In each approach, 7 COPD patients moderate to severe and 7 age-matched subjects performed an endurance test consisting of dynamic strength of the quadriceps against 40% (systemic approach) or 30% (biopsy approach) of maximal voluntary strength at an imposed regular pace until exhaustion. RESULTS: The results showed in each approach, that endurance test duration was significantly decreased in the COPD patients (p < 0.05). In systemic approach, the results showed that blood vitamin E at rest was significantly decreased in the COPD (p < 0.001), with a significant increase in superoxide anion release by stimulated phagocytes (p < 0.001). Local exercise induced, only in COPD, a significant increase in serum MDA (p < 0.05), which is an index of oxidative stress. In the biopsy approach, the results showed that local exercise induced in COPD an increase in muscular levels of MDA. A significant increase in muscular peroxidase glutathion activity (antioxidant) occurred after exercise only in normal subjects (p < 0.05). In conclusion, this study in COPD, confirms the altered peripheral muscle function, reveals a deficit in blood vitamin E and suggest that local muscular exercise causes a muscular oxidative stress in these patients. Further studies are needed to confirm these results and evaluate the implication of this oxidative stress in the myopathy of COPD.     

Implications of exercise training in mtDNA defects--use it or lose it?

Whether regular exercise is beneficial or should be avoided is a question currently unsettled in patients with heteroplasmic mitochondrial DNA (mtDNA) disorders of skeletal muscle. Deleterious effects of habitual physical inactivity superimposed upon impaired mitochondrial oxidative phosphorylation may contribute to varying degrees of exercise intolerance in these patients. Endurance exercise training is widely known to improve exercise capacity in healthy subjects and various chronic-disease patient populations. Although we have shown that beneficial physiological and biochemical responses to training increase exercise tolerance in patients with mtDNA defects, knowledge of the muscle adaptive response to endurance training within the setting of mitochondrial heteroplasmy remains limited. In order to determine advisability of endurance training as therapy, it remains to be established whether potential endurance training-induced increases in mutant mtDNA levels may be offset by increases in absolute wild-type mtDNA levels, and whether chronic inactivity leads to a selective down-regulation of wild-type mtDNA. Resistance training utilizes a different adaptive exercise approach to induce the transfer of normal mitochondrial templates from satellite cells to mature muscle fibers of patients with sporadic mtDNA disorders. The efficacy and safety of this approach needs to be further established. Our current inability to clearly advise patients to "use it or lose it" underscores the immediate urgency of studying the effects of exercise on skeletal muscle of patients with heteroplasmic mtDNA defects.     

Effect of aerobic and resistance exercise on central hemodynamic responses in severe chronic heart failure.

Exercise is now considered an important component of management in chronic heart failure (CHF), but little is known about central hemodynamic changes that occur during different exercise modalities in these patients. Seventeen patients (ejection fraction 25 +/- 2%) undertook brachial artery and right heart catheterization and oxygen consumption assessment at rest, during submaximal and peak cycling (Cyc), and during submaximal upper and lower limb resistance exercise. Cardiac output (CO) increased relative to baseline during peak Cyc (P < 0.05) but did not change during submaximal Cyc or upper or lower limb exercise. Heart rate (HR) was lowest during upper limb exercise and progressively increased during lower limb exercise, submaximal Cyc, and peak Cyc, with significant differences between each of these (P < 0.01). Conversely, stroke volume (SV) decreased during submaximal Cyc and lower limb exercise and was lower during peak and submaximal Cyc and lower limb exercise than during upper limb exercise (P < 0.05). CHF patients are dependent on increases in HR to increase CO during exercise when SV may decline. Resistance exercise, performed at appropriate intensity, induces a similar hemodynamic burden to aerobic exercise in patients with CHF.     

Effect of acute high-intensity interval exercise on postexercise biventricular function in mild heart failure

We studied the acute effect of high-intensity interval exercise on biventricular function using cardiac magnetic resonance imaging in nine patients [age: 49 ± 16 yr; left ventricular (LV) ejection fraction (EF): 35.8 ± 7.2%] with nonischemic mild heart failure (HF). We hypothesized that a significant impairment in the immediate postexercise end-systolic volume (ESV) and end-diastolic volume (EDV) would contribute to a reduction in EF. We found that immediately following acute high-intensity interval exercise, LV ESV decreased by 6% and LV systolic annular velocity increased by 21% (both P < 0.05). Thirty minutes following exercise (+30 min), there was an absolute increase in LV EF of 2.4% (P < 0.05). Measures of preload, left atrial volume and LV EDV, were reduced immediately following exercise. Similar responses were observed for right ventricular volumes. Early filling velocity, filling rate, and diastolic annular velocity remained unchanged, while LV untwisting rate increased 24% immediately following exercise (P < 0.05) and remained 18% above baseline at +30 min (P < 0.05). The major novel findings of this investigation are 1) that acute high-intensity interval exercise decreases the immediate postexercise LV ESV and increases LV EF at +30 min in patients with mild HF, and this is associated with a reduction in LV afterload and maintenance of contractility, and 2) that despite a reduction in left atrial volume and LV EDV immediately postexercise, diastolic function is preserved and may be modulated by enhanced LV peak untwisting rate. Acute high-intensity interval exercise does not impair postexercise biventricular function in patients with nonischemic mild HF.     

Persons with multiple sclerosis show altered joint kinetics during walking after participating in elliptical exercise

Patients with multiple sclerosis (MS) experience abnormal gait patterns and reduced physical activity. The purpose of this study was to determine if an elliptical exercise intervention for patients with MS would change joint kinetics during gait toward healthy control values. Gait analysis was performed on patients with MS (n = 24) before and after completion of 15 sessions of supervised exercise. Joint torques and powers were calculated, while also using walking velocity as a covariate, to determine the effects of elliptical exercise on lower extremity joint kinetics during gait. Results show that elliptical exercise significantly altered joint torques at the ankle and hip and joint powers at the ankle during stance. The change in joint power at the ankle indicates that, after training, patients with MS employed a walking strategy that is more similar to that of healthy young adults. These results support the use of elliptical exercise as a gait training tool for patients with MS.     

回春医疗保健操运动对老年2 型糖尿病患者血糖和血脂水平的影响

目的：探讨规律性回春医疗保健操运动对2 型糖尿病老年患者血糖、血脂水平的影响。方法：选择28例老年2 型糖尿病患者 为研究对象,并将其随机分为运动干预组和对照组。运动干预组在前期药物治疗和饮食控制不变的情况下,采用为期12 周回春 医疗保健操进行运动干预,对照组仅给予药物治疗和饮食控制,而不进行运动干预,监测和比较两组患者实验前后血糖、血脂等 指标的变化。结果：运动干预组患者接受12 周回春医疗保健操干预后,受试者空腹血糖、胆固醇、低密度脂蛋白水平均较运动干 预前显著下降,差异均具有统计学意义(P<0.05)。结论：长期的规律性回春医疗保健操运动可有效降低老年2 型糖尿病患者血糖、 血脂水平,且安全易操作,可作为老年2 型糖尿病的临床辅助疗法。     

Optimizing the therapeutic benefits of exercise in Type 2 diabetes.

Other than diet and medication, exercise is considered one of the three cornerstones of good diabetes treatment. Nevertheless, current clinical guidelines on Type 2 diabetes provide no detailed information on the modalities of effective exercise intervention in the treatment of Type 2 diabetes. Based on a review of currently available literature, exercise modalities are being identified to maximize the benefits of exercise intervention in the treatment of different Type 2 diabetes subpopulations. Both endurance and resistance types of exercise have equal therapeutic strength to improve metabolic control in patients with Type 2 diabetes. When applying endurance-type exercise, energy expenditure should be equivalent to approximately 1.7-2.1 MJ/exercise bout on 3 but preferably 5 days/wk. In sarcopenic or severely deconditioned patients with Type 2 diabetes, focus should lie on the implementation of resistance-type exercise to attenuate and/or reverse the decline in skeletal muscle mass and strength. Before choosing the most appropriate exercise modalities, the patient's disease stage should be well characterized, and an ECG-stress test should be considered. Based on baseline aerobic fitness, level of co-morbidities, body composition, and muscle strength, patients should be provided with an individually tailored exercise intervention program to optimize therapeutic value. A multidisciplinary individualized approach and continued exercise training under personal supervision is essential to enhance compliance and allow long-term health benefits of an exercise intervention program.     

Visualization of elusive structures using intracardiac echocardiography: Insights from electrophysiology

Echocardiography has the ability to noninvasively explore hemodynamic variables during pharmacologic or exercise stress test in patients with heart failure. In this review, we detail some important potential applications of stress echocardiography in patients with heart failure. In patients with coronary artery disease and chronic LV dysfunction, dobutamine stress echocardiography is able to distinguish between viable and fibrotic tissue to make adequate clinical decisions. Exercise testing, in combination with echocardiographic monitoring, is a method of obtaining accurate information in the assessment of functional capacity and prognosis. Functional mitral regurgitation is a common finding in patients with dilated and ischaemic cardiomyopathy and stress echocardiography in the form of exercise or pharmacologic protocols can be useful to evaluate the behaviour of mitral regurgitation. It is clinical useful to search the presence of contractile reserve in non ischemic dilated cardiomyopathy such as to screen or monitor the presence of latent myocardial dysfunction in patients who had exposure to cardiotoxic agents. Moreover, in patients with suspected diastolic heart failure and normal systolic function, exercise echocardiography could be able to demonstrate the existence of such dysfunction and determine that it is sufficient to limit exercise tolerance. Finally, in the aortic stenosis dobutamine echocardiography can distinguish severe from non-severe stenosis in patients with low transvalvular gradients and depressed left ventricular function.     

Exercise prescription for patients with a Fontan circulation: current evidence and future directions

It is well documented that children with a Fontan circulation have a reduced exercise capacity. One of the modalities to improve exercise capacity might be exercise training. We performed a systematic literature review on the effects of exercise training in patients with a Fontan circulation. Six published studies were included that reported on the effects of exercise training in 40 patients. All studies had a small sample size and/or did not include a control group. Based on the six published studies we can conclude that children who have undergone a Fontan operation and who are in a stable haemodynamic condition can safely participate in an exercise training programme and that exercise training results in an improved exercise capacity. However, more research is needed to establish the optimal exercise mode, dose-response relation, and the effects of exercise training on cardiac function, peripheral muscle function, physical activity, and health-related quality of life. (Neth Heart J 2007; 15:142-7.) Based on the six published studies we can conclude that children who have undergone a Fontan operation and who are in a stable haemodynamic condition can safely participate in an exercise training programme and that exercise training results in an improved exercise capacity. However, more research is needed to establish the optimal exercise mode, dose-response relation, and the effects of exercise training on cardiac function, peripheral muscle function, physical activity, and health-related quality of life. (Neth Heart J 2007; 15:142-7.)