Journal of Cardiopulmonary Rehabilitation & Prevention:
Aerobic Exercise Intensity Assessment and Prescription in Cardiac Rehabilitation: A JOINT POSITION STATEMENT OF THE EUROPEAN ASSOCIATION FOR CARDIOVASCULAR PREVENTION AND REHABILITATION, THE AMERICAN ASSOCIATION OF CARDIOVASCULAR AND PULMONARY REHABILITATION, AND THE CANADIAN ASSOCIATION OF CARDIAC REHABILITATION
Mezzani, Alessandro MD1,*; Hamm, Larry F. PhD2; Jones, Andrew M. PhD3,*; McBride, Patrick E. MD, MPH4; Moholdt, Trine PhD5; Stone, James A. MD, PhD6; Urhausen, Axel JP, MD, MPH, PhD7; Williams, Mark A. PhD8
1Salvatore Maugeri Foundation IRCCS, Scientific Institute of Veruno, Exercise Pathophysiology Laboratory, Cardiac Rehabilitation Division, Italy:
2George Washington University Medical Center, School of Public Health and Health Services, Department of Exercise Science, Washington, DC, USA;
3University of Exeter, School of Sport and Health Sciences, UK;
4University of Wisconsin, School of Medicine and Public Health, Department of Medicine, and Medicine and Family Medicine, USA;
5Norwegian University of Science and Technology, KG Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Trondheim, Norway;
6Cardiac Wellness Institute of Calgary, University of Calgary, Libin Cardiovascular Institute of Alberta, Canada;
7Hospital Centre of Luxembourg, Centre of Locomotor System, Sports Medicine and Prevention, CRP-Santé, Luxembourg;
8Creighton University School of Medicine, Division of Cardiology, Department of Medicine, Omaha, USA.
Correspondence: Alessandro Mezzani, Salvatore Maugeri Foundation IRCCS, Scientific Institute of Veruno, Exercise Pathophysiology Laboratory, Cardiac Rehabilitation Division, Via per Revislate 13, 28010 Veruno (NO), Italy. Email: firstname.lastname@example.org
Conflict of interest: None declared.
This article is copublished in the European Journal of Preventive Cardiology.
Received March 14, 2012
Accepted August 16, 2012
Aerobic exercise intensity prescription is a key issue in cardiac rehabilitation, being directly linked to both the amount of improvement in exercise capacity and the risk of adverse events during exercise. This joint position statement aims to provide professionals with up-to-date information regarding the identification of different exercise intensity domains, the methods of direct and indirect determination of exercise intensity for both continuous and interval aerobic training, the effects of the use of different exercise protocols on exercise intensity prescription and the indications for recommended exercise training prescription in specific cardiac patients' groups. The importance of functional evaluation through exercise testing prior to starting an aerobic training program is strongly emphasized, and ramp incremental cardiopulmonary exercise test, when available, is proposed as the gold standard for a physiologically comprehensive exercise intensity assessment and prescription. This may allow a shift from a ‘range-based’ to a ‘threshold-based’ aerobic exercise intensity prescription, which, combined with thorough clinical evaluation and exercise-related risk assessment, could maximize the benefits obtainable by the use of aerobic exercise training in cardiac rehabilitation.
The intensity of aerobic exercise training is a key issue in cardiac rehabilitation. Exercise intensity is directly linked to both the amount of improvement in exercise capacity and the risk of adverse events during exercise, and intensity ranges for aerobic training prescription are included in several guidelines and publications regarding secondary prevention and cardiac rehabilitation.1–4 The purpose of this joint position statement of the European Association for Cardiovascular Prevention and Rehabilitation (EACPR), American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR) and Canadian Association of Cardiac Rehabilitation (CACR) is to provide professionals with a reappraisal of all aspects related to aerobic exercise intensity assessment and prescription, with specific reference to patients with heart disease. Key issues discussed in this statement include: 1) identification of different exercise intensity domains based on the physiological response to constant-work-rate (CWR) exercise; 2) a review of the methods of direct and indirect determination of exercise intensity for both continuous and interval aerobic training; 3) discussion of the potential effects that different exercise protocols may have on exercise intensity prescription; and 4) indications for recommended exercise training prescription in specific cardiac patient groups.
Of note, in addition to intensity, two other major components of the weekly volume of aerobic training are duration and frequency of the exercise sessions.5 As indicated in Domains of exercise intensity: the appropriate basis for exercise prescription below, session duration is intuitively and causally dependent on the chosen exercise intensity, that is, the higher the exercise intensity, the shorter the exercise duration, whereas, regarding training frequency, for the purpose of this paper a frequency of three to four sessions per week will be assumed; it is acknowledged that a higher or lower frequency may require modifications of the exercise intensity prescription. As far as the training modality is concerned, the term ‘continuous’ training used in this position statement is intended as a training modality in which an exercise session can be performed for at least 20 minutes with a mild or moderate sense of fatigue; on the other hand, the term ‘interval’ training refers to shorter exercise sessions that cannot be sustained longer on account of an excessive sense of fatigue. Finally, the terms ‘incremental’ and ‘graded’, as referred to for an exercise test, are used interchangeably throughout the text, and the term ‘exercise test’, whenever quoted, stands for incremental/graded exercise test, unless otherwise specified.
DIRECT EXERCISE INTENSITY ASSESSMENT: PHYSIOLOGICAL BASES
Descriptors of the O2 Transport and Utilization System Response
Aerobic exercise intensity is strictly and causally linked to energy expenditure during effort. In an oxygen-dependent biological system, the latter is mostly described by oxygen uptake (VO2) through the O2 energy equivalent, equal on average to 20 kJ or 5 kcal per litre of O2 consumed. As a consequence, peak VO2 and the first and second ventilatory thresholds (i.e. the physiological descriptors of the O2 transport and utilization system response to exercise) are the gold standard references for the evaluation of aerobic metabolism function and, consequently, for aerobic exercise intensity assessment and prescription. For the purposes of this statement, the terms ‘ventilatory’ and ‘lactate’ threshold are considered interchangeable; those interested in the relationship between blood lactate and ventilatory gases modifications are referred to previously published reviews.6,7
First Ventilatory Threshold
During light to moderate-intensity incremental exercise, aerobic metabolism satisfies almost all of the body's energy needs and blood lactate is not (or is only marginally) elevated above the resting value. However, with increasing effort intensity, a threshold is reached, termed first ventilatory threshold (1stVT), above which blood lactate and pH start to increase and decrease, respectively.6–9 To counteract the ongoing metabolic acidosis, intracellular bicarbonates buffer hydrogen ions generated by lactic acid dissociation and produce CO2 in excess of that produced by aerobic metabolism, which makes the VCO2 versus VO2 relationship become steeper.6–9 The 1stVT can thus be determined by analysing the slope of the VCO2 versus VO2 relationship, and can be identified as the point of transition in the VCO2 versus VO2 slope from less than 1 to greater than 1 (Figure 1(a)).6–9 At the same time, the VE/VO2 ratio inverts its trend in the presence of a still decreasing or constant VE/VCO2, which makes the 1stVT also identifiable as the nadir of the VE/VO2 versus work rate (WR) relationship (Figure 1(b)).6–9 The 1stVT marks the limit between the light to moderate- and the moderate to high- intensity effort domains;10,11 this is reached at around 50–60% of peak VO2 or 60–70% of peak heart rate (HR).6–11
Second Ventilatory Threshold
With increasing exercise intensity and lactic acid production above the 1stVT, a point is reached when intracellular bicarbonates are no longer able to adequately counteract exercise-induced metabolic acidosis.6–9 At this point, respiratory alkalosis develops through a VE increase in excess of VCO2, and this is termed the second ventilatory threshold (2ndVT) or respiratory compensation point'. Simultaneously, the VE/VCO2 ratio inverts its trend (increase versus initial decrease), and the 2ndVT is identifiable as the nadir of the VE/VCO2 versus WR relationship (Figure 1(b)).6–9 The possibility of identifying the 2ndVT depends to a large extent on the gain of the chemoceptive response to metabolic acidosis, which can vary among subjects/patients, thereby making the 2ndVT identification potentially difficult. When identifiable, the 2ndVT is usually attained at around 70–80%peak VO2 and 80–90%peak HR reached during incremental exercise, and it has been proposed to be related to the so-called ‘critical power’ (CP),12 that is, the upper intensity limit for prolonged aerobic exercise13–15 (see Moderate to high-intensity exercise and High to severe-intensity exercise below). However, it is important to recognize that a mechanistic link between 2ndVT and CP has not as yet been proven.
Peak VO2 is defined as the VO2 value, averaged over a 20- to 30-s period, achieved at presumed maximal effort during an exercise test, while performing dynamic work involving large muscle groups.8,9 Peak VO2 may or may not be equal to VO2max (intended as the ‘true’ insuperable upper limit for aerobic power), even if the available evidence suggests that these two concepts are substantially equivalent.16 Achievement of maximal or near-maximal effort (and thus of reliable peak VO2 values) is crucial for correct aerobic training prescription,17 and is often assumed in the presence of one or more of the following criteria:18
* Failure of VO2 and/or HR to increase with further increases in WR;
* Peak respiratory exchange ratio (VCO2/VO2) ≥1.10;
* Post-exercise blood lactate concentration ≥8mmol/L;
* Rating of perceived exertion (RPE) ≥18 in the Borg ‘Category Scale’ or ≥8 in the Borg ‘Category-Ratio Scale’;19
* Patient appearing exhausted.
Of these, a plateau in the VO2 versus WR relationship during incremental exercise is considered the gold standard for the determination of maximal effort, whereas the cut-offs for peak respiratory exchange ratio and post-exercise blood lactate concentration values proposed above are somewhat limited by high inter-individual variability.20
Domains of Exercise Intensity: The Appropriate Basis for Exercise Prescription
Aerobic exercise training of cardiac patients has traditionally been performed using the CWR modality. In this regard, it is noteworthy that the metabolic and gas exchange responses to CWR exercise differ depending on exercise intensity. This allows for the identification of four exercise intensity domains: light to moderate, moderate to high, high to severe, and severe to extreme. The physiological characteristics of the four exercise intensity domains are summarized in Table 1.
Light to Moderate-Intensity Exercise
The light to moderate exercise domain encompasses all WRs engendering steady-state VO2 values below that corresponding to the 1stVT.10,11 During light to moderate CWR exercise, blood acid- base status is not perturbed and blood lactate is not (or is only barely) elevated above the resting value (i.e. 1–2 mmol/L). In this domain, VO2 and ventilation steady-states are attained relatively rapidly following the onset of exercise. The steady-state is attained more rapidly in trained subjects and is typically delayed by aging, prolonged inactivity and chronic diseases. The attainment of an early physiological steady-state has the effect of limiting the contribution of non-oxidative metabolism to energy turnover and reducing the depletion (e.g. phosphocreatine, glycogen) or accumulation (e.g. inorganic phosphate, Hp) of fatigue-related metabolites in the working muscles.10,11 For this reason, exercise is generally well tolerated in this domain and is expected to be sustainable for a long period of time (>30–40 min) with only a modest sense of fatigue.
Moderate to High-Intensity Exercise
This intensity domain comprises those WRs lying between the 1stVT and the CP (Figure 2). CP represents the highest WR still sustainable in conditions of both VO2 and lactate steady-state12–14,21–26 and is a crucial (though seldom used) marker of the upper limit of sustainable prolonged aerobic exercise.27 The CP corresponds to around 60–70%peak WR and peak VO2 and 70–80%peak HR as assessed by incremental exercise testing, but with higher steady-state %peak VO2 and %peak HR values during CWR exercise. This is due to the appearance of a ‘slow component’ of the VO2 kinetics after approximately two to three minutes of the start of CWR exercise in this intensity domain, which is not detectable during incremental exercise.28 The VO2 slow component elevates the VO2 above the VO2 that would be expected for a given WR, resulting in a delayed attainment of the VO2 steady-state (by as much as 10–15 minutes or more). In other words, the VO2 and HR steady-state is reached at a level higher than expected according to the below-1stVT VO2 versus WR relationship10,11,28 (Figures 3 and 4). The VO2 slow component represents a loss of muscle efficiency,29 which elevates the O2 cost of exercise and, for this reason, exercise in the moderate to high domain cannot be sustained for as long as that in the light to moderate domain. However, continuous exercise sessions of 30-minute duration are obtainable in the moderate to high-intensity domain even in patients with a significantly reduced exercise capacity, such as those with chronic heart failure (CHF).30
High to Severe-Intensity Exercise
This intensity domain comprises all the WRs above CP that cause VO2 to reach its peak value with no steady-state attainment.10,11 For the very highest WRs in this intensity domain no VO2 slow component is evident and VO2 may rise with a close to mono-exponential profile that is truncated at peak VO2. Consequently, the high to severe-intensity domain presents a broad range of exercise WRs at which peak VO2 will be reached. In this domain, blood acid-base balance is severely perturbed,25 as reflected by a continuous rise in blood lactate until the exercise is terminated. Of note, the failure to attain a physiological steady-state in the high to severe-intensity domain is also evident regarding skeletal muscle (phosphocreatine) and pH.31 The duration of exercise in this domain is highly predictable21–23 (Figure 2) and is typically in the range of 3–20 min. Given both such a short exercise session duration and the impossibility of a steady-state attainment, this intensity domain can only be used for interval, rather than continuous, aerobic training prescription.
The slow component rise in VO2 during moderate to high- and high to severe-intensity CWR exercise means that VO2 changes not only as a function of WR, but also as a function of time in these domains. Consequently, irrespective of the subject's/patient's peak exercise capacity, without precise stipulation of the exercise conditions and timing of measurements, it is difficult to define a given intensity as a percentage of peak VO2 in these intensity domains.
Severe to Extreme-Intensity Exercise
Given the finite kinetics of VO2, it is inevitable that some WRs are so high that fatigue intervenes before peak VO2 can be achieved. In this domain the tolerable duration of exercise is limited to less than about 3 min.32 Interestingly, due in part to the short duration of exercise before exhaustion occurs, blood lactate at the end of exercise in this domain may not reach such high values as those recorded at the end of high to severe-intensity exercise until exhaustion.
Need for Direct Evaluation of Functional Capacity: The Role of Exercise Testing
The administration of an incremental, that is, graded, exercise test to patients entering outpatient cardiac rehabilitation programs has been recommended since the 1970s.33,34 Current EACPR, AACVPR, CACR, European Society of Cardiology and American Heart Association guidelines for cardiac rehabilitation programs strongly recommend exercise testing as a key component of the initial patient assessment, and address the concept of exercise testing as a tool for exercise training evaluation, risk stratification to determine the required level of supervision and monitoring, and individualized exercise prescription.1–4,35–39 Despite these recommendations, there has been an increasing trend in both Europe and the United States for patients being referred to and entering cardiac rehabilitation without an exercise test. Reasons stated for the lack of testing include shorter hospital stays, more aggressive revascularization interventions, increased sophistication of diagnostic procedures, extreme deconditioning, orthopaedic limitations, left ventricular dysfunction, knowledge of the coronary anatomy, recent and successful coronary revascularization and uncomplicated myocardial infarction.39
For cardiac rehabilitation patients for whom there are no exercise test results, it is recommended that the exercise prescription could be based on the level of exercise performed during the inpatient phase of rehabilitation and recommended home exercise activities, while monitoring for signs and symptoms of exercise incompetence. In this context, it is important to understand the difference between a diagnostic exercise test and one performed to assess the functional capacity for cardiac rehabilitation purposes. A diagnostic exercise test is often carried out in pharmacologic wash-out as one of the initial steps in determining whether signs or symptoms that are present (e.g. chest pain or dyspnoea) are cardiac in origin. At entry into cardiac rehabilitation, patients already have documented cardiac disease; thus, a test administered at this time on current therapy serves primarily as a functional evaluation to quantify exercise capacity, chronotropic and inotropic responses to exercise, and presence and severity of dysrhythmias, as well as identify signs, symptoms, or other clinical evidence of any residual myocardial ischemia. Using an alternative standardized approach to prescribing exercise intensity (e.g. 20 bpm >resting HR) that is not based on current exercise capacity because exercise test data are not available (see Unavailability of exercise testing below), potentially minimizes the beneficial effects of exercise training and is likely to retard patient progress during cardiac rehabilitation. Thus, it is important to administer a functional sign/symptom-limited exercise test prior to patients beginning cardiac rehabilitation. In this regard, an incremental standard exercise test or cardiopulmonary exercise test with respiratory gas analysis (CPX), which is the gold standard for a direct assessment of the exercise intensity descriptors outlined in Descriptors of the O2transport and utilization system response and Domains of exercise intensity: the appropriate basis for exercise prescription above, should be used whenever possible to obtain an exercise prescription tailored on the individual patient's functional capacity and pathophysiological picture.
INDIRECT EXERCISE INTENSITY ASSESSMENT
The Heart Rate Versus VO2 Relationship
HR is widely used for exercise intensity assessment and prescription on the grounds that a linear relationship between HR and both VO2 and WR increase during incremental exercise is known to exist.40,41 Thus, after having measured peak HR, the intensity of effort chosen as the training stimulus is indirectly determined by means of published regression equations42 or tables (Table 2)43 as the percentage of the peak HR value corresponding to a given percentage of peak VO2. On this basis, a ‘target HR range’ is usually proposed in normal subjects ranging between 70 and 85%peak HR.44 In cardiac patients, available guidelines suggest training intensities equal to 40–80%peak VO2,3,44,45 that is, roughly ranging from 50 to 85%peak HR (Table 2). However, it must be considered that intensity classifications such as those shown in Table 2 do not reveal to which precise intensity the 1stVT and 2ndVT correspond in an individual patient. Indeed, %peak HR values commonly used for training prescription both in normal subjects and cardiac patients have been found to be associated with levels of metabolic stress higher than those of both the 1stVT and 2ndVT.46–49 This seems to hold true also for subjects treated with beta-blockers50 and patients with left ventricular dysfunction both on- and off-beta-blocking therapy.51
The Heart Rate Reserve Versus VO2 Reserve Relationship
The concept of HR reserve (HRR) and VO2 reserve (VO2R), defined as the difference between the basal and peak HR and VO2 values, respectively,52–55 are currently used for training prescription purposes. A percentage of HRR (%HRR) equal to 60% has been indicated to correspond to the 1stVT,52,53 and %HRR has been found to equal percentages of VO2R (%VO2R) in both normal individuals undergoing both cycle and treadmill exercise54–56 (Table 2) and in cardiac patients.57 Of note, the ‘VO2 reserve' concept fits closely the need for a precise exercise intensity definition since it describes the true amount of energy one can utilize for maximal effort attainment, taking into account the baseline level. As a consequence, %HRR has been adopted by the American College of Sports Medicine as the gold standard for exercise intensity indirect assessment, and ‘training HRR ranges’ of 60–80 %HRR for persons without overt disease44 and 40–70 %HRR for cardiac patients45 have been proposed. Moreover, a recent systematic review has confirmed the validity of %HRR for both indirect assessment and prescription of aerobic training intensity.58 Of note, it has been demonstrated that %HRR values commonly used for training prescriptions in normal subjects and cardiac patients both on- and off-beta-blockers can correspond to energy expenditures ranging from light to moderate to moderate to high.47,50,59–61 These same values hold true for patients with left ventricular dysfunction.51,62
However, a loss of linearity of both the VO2 versus WR and HR versus WR relationships as peak VO2 is approached has been described in cardiac patients63 in whom chronotropic incompetence may be present due to age-, pathology- and/or drug (beta-blockers)-related sinus node dysfunction.64,65 On this basis, a very high uncertainty in predicting %VO2R values on the basis of %HRR has been demonstrated in CHF patients both on- and off-beta-blockers.66 However, recent data suggest that the %HRR–%VO2R equivalence may be preserved in CHF patients on optimized beta-blocking therapy.67
The RPE Versus VO2 or HR Relationship
RPE is commonly employed in cardiac rehabilitation, either as a primary indicator of exercise intensity or as an adjunct to HR monitoring.19,44,68 Its use is particularly valuable in patients who have difficulty obtaining a reliable or meaningful exercise-related HR, e.g. patients with atrial fibrillation; patients whose HRs may not adequately reflect their level of exertion because of beta-blockade, absence of autonomic cardiac innervation occurring after heart transplantation, chronotropic incompetence or certain types of pacemakers; and patients in whom the ability to physically obtain an accurate pulse is limited due to a variety of reasons. Obtaining a rating of perception of exertion is also of assistance to cardiac rehabilitation staff members when comparing the perceived demands of various exercise devices, for example arm versus leg exercise.
The commonly utilized scales for the RPE include the original ‘Category Scale’ (RPE Borg scale), which rates exercise intensity from 6 to 20, and the ‘Category-Ratio Scale’ (CR10 Borg scale), which utilizes a numerical range from 0 to 10.19 The average RPE range associated with exercise adaptation is 13–16 (‘somewhat hard’ to ‘hard’) on the RPE Borg scale, which is loosely associated with a 70–90% range of peak HR and a 50–85% range of peak VO2 (Table 2). This approximately corresponds to 2.5–6 on the CR10 Borg scale, which is also loosely associated with a 60–90% range of peak HR and approximately 50–85% of peak VO2. Several papers have supported the reliability of RPE for effort intensity assessment and prescription in normal individuals and cardiac patients both off- and on-beta-blockers, with a good correspondence between a value of around 13 and the 1stVT.69–76 However, the response can vary greatly both between and within individuals, dependent as it is upon individual physiologic responses to exercise and perception of effort.77 Moreover, the RPE reported by a patient can be affected by factors other than the physical effort of the exercise, including both psychological factors and environmental conditions. In patients who have a change in the dose of beta-blocker medication, the original calculation of exercise intensity using HR is likely no longer valid.78 In this case, the best approach is to repeat an exercise test, but if this is not possible, a reasonable alternative is to prescribe an exercise intensity based on the reported RPE during exercise prior to the medication change.
Intensity and Volume of Exercise Training
Volume of exercise training is associated with overall energy expenditure expressed in kilocalories, for example kilocalories per week.79 For cardiac patients, the volume goal of exercise training should ultimately reach 1500 kcal/week,44,80–82 although this level may be difficult to attain for some patients, particularly early in the post-hospitalization phase of exercise training. During this period, exercise training intensity is low, frequently in the range 4–6 kcal/min. Hence the importance of both the frequency and duration of exercise sessions. Early post-hospitalization exercise training typically involves a minimum of 20–30 minutes per session, three to four days per week. Using an average of 5 kcal/min and exercising for 30 min, one would expend 150 kcal/session; thus, with 3 sessions/week one would expend approximately 450 kcal (four sessions expending 600 kcal). In order to increase the volume of exercise kcal expenditure to achieve the desired level (1500 kcal/week), one must consider the adjustments of intensity, frequency and duration of activity, modifying a single parameter or a combination of these three parameters. Thus, at a given exercise intensity, for example 5 kcal/min, one would need to ultimately utilize a combination of increases in frequency and duration, as follows:
Equation (Uncited)Image Tools
Unfortunately, although the intensity of effort may be appropriate, the stamina required to exercise for 40 minutes and six days per week may be overwhelming. However, as patients improve their fitness level, and become able to expend, say, 7kcal/min, duration and/or frequency can be adjusted.
Equation (Uncited)Image Tools
As the volume of exercise will impact kilocalorie expenditure, it is important to consider the contribution of all three components of the exercise prescription, namely exercise intensity, duration of activity and frequency of exercise sessions.
EXERCISE INTENSITY PRESCRIPTION
Prescribed Exercise Intensity: General Concepts
The idea proposed in this statement is that aerobic exercise prescription in cardiac patients should be based on the choice of a specific exercise intensity domain determined by: i) the patient's clinical and pathophysiological picture, ii) the peculiar physiological response to and the evidence-based benefits of exercise in the different intensity domains and iii) the goals of the rehabilitation program. This involves a shift from a ‘range-based’ to a ‘threshold-based’ aerobic training prescription, based on data obtained by incremental standard exercise test or CPX in the individual patient.
Of note, some caveats must be taken into account when transferring information obtained from incremental exercise testing to CWR exercise, as underlined in Domains of exercise intensity: the appropriate basis for exercise prescription above and in Figures 3 and 4:
1. Beyond the 1stVT, a given relative exercise intensity expressed as %peak VO2 will result in an energy expenditure higher than expected (moderate to high-intensity domain) or equal to peak VO2 irrespective of the prescribed relative intensity (high to severe-intensity domain) when performing CWR exercise; as a consequence, %peak VO2 must be used with caution as a reference for training intensity prescription in these domains, since the individual patient's actual energy expenditure during CWR exercise is not easily predictable.
2. In the CWR moderate to high-intensity domain some relative intensities may not be easily attainable (‘chequered area’ in Figure 3).
3. As shown in Figure 4, for a given VO2 value, the WRs included in the light to moderate domain are not the same when performing incremental versus CWR exercise. The VO2 versus WR relationship is shifted to the right in the former due to an initial lag in the VO2 increase,83 on the grounds that in CWR exercise the VO2 versus WR values are measured after a VO2 steady-state has been reached, thus excluding the initial VO2 on-response delay. As a consequence, when prescribing CWR training in the light to moderate domain on the basis of incremental exercise data, it is necessary to reduce the WR prescription to a lower iso-VO2 value (Figure 4). The more prolonged the initial lag of the VO2 response to incremental exercise is, the greater the reduction should be and, as a rule of thumb, should amount to around 10 W for a 10 W/min incremental protocol in the general population of cardiac patients. Experimental confirmations are needed as to this point for moderate to high-intensity CWR exercise.
Bearing this in mind, the available evidence supporting the prescription of aerobic training in cardiac patients in the different intensity domains is as follows:
1. Light to moderate-intensity domain. The lowest aerobic training intensity still able to provide a training effect likely depends mostly, in both normal subjects and cardiac patients, on pre-training exercise capacity. In agreement with the lower fitness–lower training stimulus intensity principle,84 intensities even much lower than those corresponding to the 1stVT should be effective in cardiac patients with a markedly reduced exercise capacity. In keeping with this concept, aerobic training intensities as low as 40%peak VO2 (corresponding to about 25%VO2R) have proven to be effective in CHF patients with significantly reduced pre-training peak VO2.85,86 The light to moderate-intensity training is possibly the most indicated for patients with recent hemodynamic decompensation, for those with a high exercise-related risk, and for those in whom a light to moderate training intensity is indicated for clinical/therapeutic reasons (i.e. need for weight loss).
2. Moderate to high-intensity domain. Strong evidence has accumulated with regards to adverse event-free moderate to high-intensity exercise in cardiac patients with both preserved and reduced left ventricular ejection fraction.87–91 Aerobic training in this domain can still be performed in a continuous modality, with reported training sessions of 15–30 min duration.87–91 The possibility to train patients in the moderate to high-intensity domain is noteworthy, especially when considering that cardiac patients with reduced exercise capacity perform daily activities at a higher percentage of their peak VO2 compared with normal subjects. For example, it has been reported that during a six-minute walking test (considered to closely mimic habitual walking activities), CHF patients exercise at a percentage of peak VO2 often above that corresponding to their 1stVT.92–94 In such a pathophysiological context, the capacity to train in steady-state VO2 conditions above the 1stVT could be crucial to avoid fatigue and termination during activities of daily living. In this regard, recent data show that CHF patients may exercise at the CP (i.e. the upper limit of the moderate to high-intensity domain) for 30 minutes without incurring adverse events;30 however, further research is needed to confirm this point.
3. High to severe and severe- to extreme-intensity domains. In recent years, training in the high to severe- and even severe to extreme-intensity domain using interval training has proven effective in improving exercise capacity in different cardiac patient populations,95–97 including stable CHF patients with a pre-training peak VO2 as low as 13 ml/kg per min96 (see Interval training prescription below). As indicated in Domains of exercise intensity: the appropriate basis for exercise prescription above, the upper limit of the high to severe-intensity domain is the highest WR that will allow for the attainment of peak VO2. Of note, times to exhaustion during CWR exercise at 100% peak WR and 135% peak WR have been reported to last on average three minutes and 90 seconds, respectively, not only in both untrained and trained normal subjects but also in CHF patients.30,98
Based on the physiological definition of CWR exercise intensity domains (Table 1), the upper limits of such domains can be defined by using physiological and/or performance parameters as shown in Table 3, where correspondence with exercise intensity classes according to the ACSM exercise intensity classification is also reported. In the absence of a direct assessment of aerobic metabolism descriptors by CPX, effort relative intensities can be expressed as %peak HR, %HRR, %peak WR, or using Borg scales. Generally speaking, and with the limitations reported in The heart rate versus VO2relationship, The heart rate reserve versus VO2reserve relationship and The RPE versus VO2or HR relationship above, intensities close to the 1stVT (50%peak VO2) should lie around 60%peak HR, 50%peak HRR, 50%peak WR, or 12–13 in the RPE Borg scale, whereas intensities close to the 2ndVT (70–80%peak VO2) should lie around 70%peak WR or 15–16 in the RPE Borg scale (Table 3).
Interval Training Prescription
Interval training can be defined as repeated bouts of short-duration, high to severe- or severe to extreme-intensity exercise (i.e. 10 seconds to five minutes), separated by brief periods of lower-intensity CWR exercise allowing for active recovery. The term aerobic interval training (AIT) is often used to describe interval training in the high to severe-intensity domain. Although a significant contribution from anaerobic energetic sources to the total energy yield is unavoidable in this domain, most of the energy needed is still produced aerobically (see Domains of exercise intensity: the appropriate basis for exercise prescription above). Currently, the most used AIT model consists of 10min warm-up followed by 4×4-min intervals at 85–95%peak HR, with active recovery phases of 3 min at ∼70%peak HR (Figure 5). This AIT model has now been used in several studies, both in healthy subjects and in various cardiac patient populations,95,96,99,100 with absolute increases in peak VO2 per exercise session actually remarkably similar among patient groups (Figure 6).
AIT has shown significantly greater cardiovascular effects when compared with isocaloric moderate to high- intensity continuous training, both in coronary artery disease (CAD) and CHF patients95,96 (Figure 6). AIT has also been shown to exert favourable effects on left ventricular systolic function. In healthy men, stroke volume has been shown to increase significantly more after high-intensity AIT compared with lower-intensity training of the same energy expenditure.99 In CHF patients, Wisløff et al.96 found reverse left ventricular remodelling after AIT, while continuous training produced no significant changes in left ventricular volumes and resting haemodynamics; furthermore, left ventricular contractile function was shown to markedly improve only in AIT patients. Also left ventricular diastolic properties have been found to improve significantly more after AIT than after continuous training in both CHF96 and stable CAD subjects.101 Improved endothelial function, reductions in atherosclerosis and better calcium regulation in cardiomyocytes are among the possible explanations for these findings and data in humans seem to confirm basic experimental data.102 Both AIT and moderate to high-intensity continuous training have been found to improve endothelial function in cardiac patients, with significantly larger improvement in brachial artery flow-mediated dilatation after AIT in CHF patients96 and both improvement in endothelial function and reduction in in-stent restenosis in patients with previous percutaneous coronary intervention (PCI) and stent implantation.103 It is reasonable to suggest that higher shear stress during AIT may trigger larger responses than moderate to high-intensity continuous training at the cellular and molecular level and be responsible for the observed effects on endothelial function.104
In contrast to the described 4×4-min AIT model, shorter, sprint-type intervals of all-out severe to extreme- intensity exercise have been shown to induce rapid changes in exercise capacity, improving work performance due to enhanced skeletal muscle energy metabolism with modest effects on peak VO2.105,106 This type of interval training is poorly documented in CAD patients, although some acute effects of severe to extreme-intensity interval training have been reported in stable CAD patients.97,107 However, a study applying two-minute-long severe to extreme-intensity intervals found a similar improvement in peak VO2 to that after more traditional continuous training in CAD patients, but with increased time to exhaustion at 90%VO2R.108
In a clinical setting, AIT can be performed as uphill walking or running on a treadmill according to the 4×4- min protocol. Patients are supposed to exercise with an intensity corresponding to 85–95%peak HR during the high to severe-intensity intervals, which makes patients breathe heavily without experiencing chest or leg pain. To ensure that the relative intensity is maintained throughout the whole training period, the WR should be adjusted continuously based on the individual HR response. In the recovery periods, patients are supposed to exercise at intensities of ∼70%peak HR. In clinical practice, however, it is sometimes necessary to adjust the HR zones, especially the moderate to high-intensity recovery ones, based on the patient's subjective feelings. In the RPE Borg scale, patients should exercise at an intensity of 15–18 in the high to severe-intensity intervals. Exercise modes other than treadmill walking are possible and AIT using an aerobic exercise group setting has been shown to be feasible in CHF patients.109 Although AIT has proven efficient in increasing cardiovascular health in CAD patients, there is still a need to further investigate feasibility, long-term effects and safety aspects of this training modality. In CHF patients, a preserved walking distance on the six-minute walking test was found one year after ending a formal AIT program.110 Moreover, in patients with previous coronary artery by-pass graft a further increase in peak VO2 was seen six months after the end of an AIT rehabilitation period.100 A large ongoing multicentre randomized trial, the Study of MyocArdial Recovery AfTer EXercise Training in Heart Failure (SMARTEX-HF), will address the feasibility, safety and efficacy of AIT in a large group of CHF patients.111
Arm Exercise Intensity Prescription
Peak HR and VO2 values are significantly lower for arm than for leg exercise, likely due to the reduced muscle mass of the arms. Additionally, at the same absolute WRs, the VO2 for arm work is greater than that of leg work, owing to the reduced mechanical efficiency of arm exercise. Consequently, the cardiovascular responses to standardized WRs during arm ergometry are greater, particularly HR and blood pressure, compared with leg exercise.112–116 Exercise prescriptions based upon %peak VO2 derived from treadmill CPX, by way of example, may result in absolute WRs which are substantially greater than what a patient may be able to comfortably achieve during arm ergometry. The exercise prescription generated from %HRR or %peak HR methods attained from standard treadmill or cycle ergometry exercise testing will often provide a safe guideline for the patient, whereby WR can be adjusted to achieve an appropriate HR response. In this regard, it has been suggested that, at a given submaximal WR, for obtaining a HR similar to that obtained during leg ergometry, a WR equal to about two- thirds of the latter should be used during arm ergometry.117
In addition to the differences in physiological responses to acute arm versus leg exercise, the principle of exercise training specificity suggests that cardiovascular and metabolic adaptation to acute exercise is specific to the type of exercise performed and the muscles involved.118 Specifically, training upper limbs or lower limbs results in only minor improvement in submaximal and maximal exercise parameters when testing the untrained limbs. Lastly, the role of arm exercise in a patient whose primary goal is weight loss should be balanced against the patient's need to significantly improve upon the acute exercise response to arm exercise (training adaptation). If the patient has the expectation to resume participation in occupational or recreational activities which require substantial upper limb aerobic capacity, a significant component of the cardiac rehabilitation exercise training program may need to include arm exercise.118–120 However, primarily assigning increased utilization of lower extremity exercise, with their increased exercise efficiency and enhanced ability to exercise at higher absolute WR, may substantially increase the calorie expenditure of the exercise program.
Weight Loss-Targeted Exercise Intensity and Daily Physical Activities Intensity Prescription
Obesity or being overweight affects more than half of the adult populations in the developed world and both are associated with an increased risk of many chronic diseases. A large body of evidence demonstrates that even modest weight loss, as low as 3–5% of body weight, by regular physical activity is associated with decreased chronic disease risk.121 Higher intensity and longer duration physical activity, conducted on a regular basis, are both associated with greater weight loss and less long-term weight gain compared with lower intensity or shorter duration exercise. Weight loss induced by increased daily physical activity without caloric restriction can significantly reduce obesity (particularly abdominal obesity) and insulin resistance. Exercise without overall weight loss reduced abdominal fat and prevented further weight gain.122 Evidence supports that low to moderate-intensity physical activity of 150–250 minutes per week will result in modest weight loss and is effective in preventing weight gain. Higher intensities and longer duration of physical activity (>250 min/week) are associated with significant weight loss.123 Maintenance of weight loss is optimal with low to moderate- or moderate to high-intensity physical exercise of more than 250 min/week duration. A recent systematic review noted a dose–response relationship between the intensity of activity and the loss of visceral fat, with at least 10 METs·h/week of aerobic exercise (brisk walking, light jogging or stationary ergometer usage) required for visceral fat reduction.123 Both men and women benefit from maintaining higher levels of physical activity over a long period of time, but the benefits may be even greater for women.124–126
These results support findings that 30 minutes of activity daily may be sufficient to lose weight and prevent weight gain.127,128 In the STRRIDE study, overweight individuals were randomized to high-, moderate-, or low- activity groups. Although all groups lost weight and body fat, the high-activity group lost more weight and body fat. These findings support the recommendation that higher intensities and longer durations of physical activity are optimal for weight maintenance, but that even moderate activity is beneficial. This study also noted that the positive caloric imbalance observed in the overweight controls was modest and could be reversed by a modest amount of exercise, equivalent to walking 30 minutes every day. However, other observational studies suggest that higher durations of activity may be necessary for middle-aged and older adults. This age-associated effect may be related to the inability of many older adults to exercise at higher intensities, especially initially, and thus longer durations of physical activity and lower intensities are required in order to achieve the negative caloric balance that is sufficient for weight loss.129,130 Moreover, this may be due to the well-documented age-related declines in resting metabolic rate and lean body mass in older adults and suggests that, in addition to activity, reduced energy intake is vital to prevent weight gain with age.131
The results of the research cited above suggest that incorporating physical activity into daily life improves health outcomes, body weight and visceral adiposity. There appears to be a dose–response related to weight loss from light to high-intensity activity, but both light to moderate- and moderate to high-intensity activity may result in significant weight loss when maintained over time, and especially when combined with appropriate caloric intake for body size and daily energy expenditure. Research suggests that a minimum of 30 minutes of light to moderate activity on a daily basis is the threshold to result in weight loss, but that increasing the duration to 45–60 minutes, or increasing the intensity to moderate to high levels, may further enhance weight loss and cardiorespiratory fitness.
Unavailability of Exercise Testing
There is no contemporary, scientifically validated reason for cardiac rehabilitation programs to substitute the current standard of formal incremental exercise test or CPX, including diagnostic 12-lead ECG appraisal, for other assessments of functional capacity (see Need for direct evaluation of functional capacity: the role of exercise testing above). Therefore, cardiac rehabilitation professionals are strongly encouraged to use every option and opportunity to ensure their patients benefit from standard exercise tests or CPX. However, in cardiac rehabilitation programs where these kinds of exercise tests are not available, there are alternative strategies that may assist programs in both stratifying patients with regard to their risk of exercise-associated adverse events and in developing an exercise prescription. In an effort to try to determine subsequent event risk in cardiac rehabilitation populations without exercise testing results, the six-minute walking test has been proposed as a reasonable alternative to a more formal exercise capacity evaluation.132–134 However, the assertion or presumption that the six-minute walking test and CPX are interchangeable is not supported by the current literature.36 Other well-validated and widely utilized classification schemes such as the Canadian Cardiovascular Society (CCS) classification of stable angina pectoris135 and the New York Heart Association (NYHA) functional classification136 have not been adequately studied to fully and completely assess their validity as accurate determinants of myocardial ischemic burden, ventricular function and functional capacity. The above observations not withstanding, in cardiac rehabilitation programs where formal exercise testing cannot be performed or is simply not a readily available service, a risk stratification protocol utilizing the patient's CCS Class, NYHA Class and six-minute walking test has been developed (Table 4).37 Importantly, however, this risk stratification scheme has not been externally validated.
Once a patient's exercise risk has been determined without the aid of a standard exercise test or a CPX, an exercise prescription can be developed using Borg scales and/or subjective tools such as the ‘talk test’.68,137 RPE correlates sufficiently well with exercise HR and VO2 to allow for an exercise prescription to be determined;138,139 an RPE Borg scale rating of 9–12 should be sufficient to elicit light to moderate exertion while remaining below the 1stVT in both patients and normal subjects69–73,140 (see The RPE versus VO2or HR relationship above). In addition, the use of RPE as an acceptable measure of the physiologic response to exercise appears to be valid for patients receiving beta-blockers.76 In the ‘talk test’ or the ‘walk and talk test’, patients should be able to maintain a certain level of exercise and still be able to talk in full sentences. As with RPE, its use in CAD populations to determine levels of physical exertion that approximate those objectively assessed by CPX has not been robustly evaluated. However, considering that its use in healthy populations does appear to correlate with 1stVT141 and VO2R,142 it is thus not unreasonable to consider its use also in patients with CAD.
Indications for aerobic exercise intensity prescription in specific cardiac patient groups are summarized in Table 5; only intensity domain data for which scientific evidence is available in a given cardiac patient group have been included, with grey-shaded areas indicating that there are no available data to warrant a recommendation. Physiological, performance and perceived exertion limits of the different exercise intensity domains are provided in Table 3, and both directly (i.e. by incremental CPX) and indirectly (i.e. by incremental standard exercise test) assessed physiological and performance limits are shown. As already emphasized in Prescribed exercise intensity: general concepts above, the choice between different exercise intensities in a specific patient will depend on the individual's clinical and pathophysiological status, the evidence-based benefits of exercise in the different intensity domains for that specific patient group and the goals of the rehabilitation program. The information provided in this section are to be considered complementary to those furnished by the recently published EACPR paper ‘Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular disease (Part III)’.143
Stable Angina Pectoris
For patients with stable angina pectoris (SAP) secondary to coronary atherosclerosis, the benefits of cardiac rehabilitation are unequivocal and it should be considered standard care for all patients with CAD.144,145 The overwhelming consideration within this population remains exercise safety. The surest way to maximize both patient safety and exercise enjoyment and attain improved cardiorespiratory fitness is to first assess the patient using an incremental standard exercise test or CPX, develop an exercise intensity prescription based on the results of that test and then ensure an adequate warm-up and cooling down period prior to and after, respectively, training sessions.
The purpose of the warm-up is to increase blood flow to the skeletal muscles, in preparation for exercise, and to facilitate coronary vasodilatation. The anti-ischemic benefits of an adequate warm-up, prior to the initiation of light to moderate/moderate to high exercise have been demonstrated.146–148 As far as training intensity is concerned, the current recommendation for persons without SAP is to perform moderate to high-intensity exercise sessions in order to improve cardiorespiratory fitness.149 This same recommendation has been extended to patients with SAP.37 In a number of small studies, moderate to high-intensity exercise training in patients with SAP has been shown to reduce myocardial ischemic burden assessed by either myocardial perfusion scintigraphy150,151 or 24-hour ambulatory electrocardiographic monitoring.152 The mechanisms by which exercise training improves mortality in the SAP population include enhanced metabolic performance of working muscles, reduced endothelial dysfunction, improvements in insulin resistance and favourable adjustments in neurohormonal abnormalities.153
In recent years, research into the most appropriate intensity of exercise training for patients with CAD has focused on the use of AIT (see Interval training prescription above). Although the cardiorespiratory benefits of AIT are well documented in athletes, a recent systematic review of interval training in patients with CAD found only two controlled and five randomized controlled trials, with a total of 213 patients.104 The review found that interval training improved cardiorespiratory fitness, endothelial function and ventricular function and morphology to a greater degree than conventional light to moderate- and moderate to high-intensity continuous aerobic training. In a study on SAP patients, Guiraud and co-workers found that shorter bouts of severe to extreme-intensity exercise (15 seconds compared with 60 seconds) combined with a passive, rather than active, recovery phase, resulted in improved patient comfort and longer time spent at >80% of peak VO2.154 In patients with SAP, it is important that exercise intensity be prescribed at a HR that is below the ischemic threshold;44 for patients with documented silent ischemia, it is critical that patients be instructed to never exceed the upper HR limit for exercise intensity. The purpose of the cool-down period post-exercise is to invoke a return to a resting state. Studies in healthy populations have indicated that a cool-down period following exercise returns both the HR and ventilation toward pre-exercise levels faster than without a cool-down.155,156
In summary, it is suggested that patients with SAP exercise three to five times per week, following an adequate warm-up of five to 15 minutes, at moderate to high intensity (in any case below the ischemic threshold) for a period of 20 to 40 minutes (not including warm-up and cool-down), followed by a cool-down period of five to 10 minutes. Most importantly, patients with SAP should engage in the type of exercise activity they find most enjoyable and, therefore, sustainable.
The same evidence and clinical practice recommendations developed for patients with SAP regarding exercise (seeStable angina pectoris above) are likely applicable to most patients post-PCI. Presently, there is no evidence to suggest that early exercise training and exercise testing post-PCI is either unsafe or adversely affects patient outcomes,157–159 even if high-intensity exercise may actually increase thrombin generation.160 With respect to the best timing to begin an exercise training program of moderate to high intensity, Parker et al. found that exercise testing and training were safe in a low risk post-PCI population less than two weeks after acute PCI for ST-elevation myocardial infarction.161 As post-PCI patients may be at particular risk for failing to increase their physical activity levels and exercise,162 a more rapid access to exercise training may be particularly useful in this population.163 Exercise training programs post-PCI have been consistently associated with improvements in functional capacity;103,157,164–166 conversely, failure to improve functional capacity post-PCI, despite exercise training, may be a marker for coronary artery restenosis.167
Data on the specific effects of exercise intensity on patient outcomes post-PCI are sparse. Munk et al. found that high to severe-intensity interval training helped to reduce six month restenosis in the stented coronary artery segment as assessed by quantitative coronary angiography; this effect was associated with improvements in aerobic capacity and attributed to improved endothelial function and reduced systemic inflammation.103 Other investigators have found similar findings with respect to improved functional capacity and reduced inflammation for post-PCI patients.164,166 Aerobic training may result in increased endothelial NO production and/or reduced NO destruction and this may lead to reduced vascular inflammation and reduced restenosis.168–170 In addition to these benefits, moderate to high-/high to severe-intensity exercise training post-PCI may also improve left ventricular remodeling171 and HR variability.172,173 However, whether such a training modality is safe for all patients post-PCI, particularly those with a history of anterior/apical myocardial infarction, or with poor left ventricular systolic function, and those with a history of CHF, remains to be determined.
Pacemakers and Implantable CardioverterDefibrillators
Patients implanted with permanent pacemakers (PMs) usually follow the same principles for aerobic training intensity prescription as non-PM-implanted patients, provided an adequate chronotropic response to exercise is warranted by the patient's sinus node and/or the device.174 In rate-responsive PM, this is usually the case when the upper-rate limit is matched to the expected training intensity. On the other hand, if an exercising patient's chronotropic response exceeds the PM upper-rate limit, the device should usually produce a Wenckebach pattern to maintain a relatively high HR without risking rapid ventricular responses. If a Wenckebach pattern is produced at exercise intensity levels lower than those prescribed, the upper-rate limit may need to be increased. Of note, patients with VVI PM devoid of rate-adaptive function lack the ability to increase HR. In the absence of rate modulation, the exercise capacity of VVI paced patients may be greatly reduced when compared with those with rate modulation and AV synchrony. However, it has been shown that exercise training may produce significant increases in peak VO2 also in this population.175
Patients with implantable cardioverter defibrillators (ICDs) can undergo aerobic exercise training, but care must be taken to avoid receiving inappropriate shocks during exercise. These could occur in the event that the exercise HR increases so that it is within the programmed ventricular tachycardia zone or if exercise-induced supraventricular tachycardia develops. Exercise intensities in the light to moderate and moderate to high domains have been found effective in improving peak VO2 in patients with an ICD. It is important to note that exercise training intensities used in all of these studies resulted in HRs that were 15–20 beats lower than the ICD threshold for detection and termination of ventricular tachycardia.176–179 Thus, as recently stated, exercise heart rates should not exceed ICD therapy thresholds and ideally be set between 10 and 20 beats below first line therapy thresholds.3
Chronic Atrial Fibrillation
Chronic atrial fibrillation (AF) is a very common arrhythmia, characterized by irregularly irregular atrial and ventricular depolarizations. The prevalence of chronic AF is quite high in patients older than 60 years and the arrhythmia may present as ‘lone’ AF or associated with comorbid conditions, such as CHF or valvular heart disease. Patients with chronic AF frequently have incomplete ventricular filling, which leads to an impaired cardiac output response to exercise, very rapid ventricular rates during effort (possibly exceeding predicted maximum) and, ultimately, reduced peak VO2 and VO2 at 1stVT in comparison with patients in sinus rhythm.180 Patients with CHF and chronic AF show peak VO2 values lower than those of CHF patients in sinus rhythm, but with 1stVT occurring at a higher percentage of peak VO2.181 Training intensities in the light to moderate- and moderate to high-intensity domains have been used in patients with chronic AF, improving both exercise capacity (i.e. peak VO2) and chronotropic response to exercise.182–184 Of note, the highly variable ventricular chronotropic response at submaximal levels of exercise typical of chronic AF patients may render HR of little utility for aerobic training prescription in some patients, making subjective RPE the most reliable means for exercise intensity assessment and prescription. In this regard, given the high prevalence of chronic AF in elderly patients, randomized controlled studies addressing the most effective type of exercise intensity assessment and prescription in this population are strongly needed.
Coronary Surgical Revascularization
Patients who have undergone traditional open-chest coronary artery by-pass graft (CABG) surgery as well as minimally invasive procedures are a substantial proportion of cardiac rehabilitation exercise programming participants, and this group includes many patients who are age 65 years or older.185 Outpatient rehabilitation can be started, as appropriate, within one week of hospital discharge (2–3 weeks post-surgery).186 Exercise prescription methodology is generally the same as that used with CAD patients. Initially, some patients may need lower- intensity or modified exercise because of musculoskeletal discomfort or healing issues at their incision sites, including not only the chest, but possibly also legs and arms. Specifically, patients should completely refrain from upper-extremity aerobic exercise training, for example arm ergometry and resistance training, for 4–6 weeks post-surgery to ensure the stability of the sternum and sternal wound healing. The exception is appropriate upper and lower body stretching and flexibility exercises to promote mobility. In patients with previous CABG, several aerobic training intensities have proven effective,100,187–192 the choice of which will depend on both the level of exercise-related risk and the patient's clinical condition. In this regard, it must be borne in mind that, among patients entering a rehabilitation program after a recent acute cardiac event, those with recent CABG have been found to have the lowest peak VO2.193
Because of the possibility of graft closure, program staff should be alert for new patient complaints of angina pectoris or angina-equivalent symptoms or signs, such as exercise intolerance or new ECG signs of myocardial ischemia. Patients should also be educated regarding these possibilities. Recognizing whether the revascularization was complete or incomplete is valuable in this regard as the latter may increase the likelihood of postsurgical signs and symptoms of residual myocardial ischemia during exercise, which may significantly affect the results of the rehabilitation process.194
Valve repair or replacement
The exercise prescription and training of patients with recent valve replacement or repair is very similar to that used with CABG surgery patients.186,195,196 However, the physical activity of some valvular heart disease patients may have been very restricted for an extended period of time prior to the surgical intervention. Consequently, the resulting low functional capacity may require these patients to initiate, and proceed with, exercise in a conservative fashion, especially during the early stages of the exercise training program.193 Rehabilitation professionals should take care to avoid upper-extremity exercise, as described in Coronary surgical revascularization above. Exercise intensities in the light to moderate- and moderate to high-intensity domains have been used in patients with recent heart valve replacement or repair and balloon valvuloplasty, demonstrating significant effects on exercise capacity and quality of life.197–201 Preliminary data also indicate a possible reverse left ventricular remodelling effect of prolonged aerobic training in patients with previous aortic valve replacement.202 Anticoagulation therapy is very common in patients who have undergone valve surgery; consequently, this necessitates caution for exercise-related injuries and subsequent bleeding. Staff should frequently remind patients undergoing exercise training of the increased risk of such events.
Patients with valvular heart disease but without valve repair or replacement may also be referred for cardiac rehabilitation. In these patients, critical aortic stenosis is a formal contraindication for exercise training. Patients with less-severe aortic stenosis can exercise but may develop symptoms, for example dyspnoea and significant fatigue, at a given WR. Exercise training intensity should be kept under the threshold that precipitates the onset of symptoms, because these symptoms indicate that their cardiac output is not capable of meeting the demands of that level of exercise.
CHF and Left Ventricular Assist Devices
A reduced ability to perform aerobic exercise is the hallmark of the CHF pathophysiological picture.203 It is related to changes in both peripheral and central links of the O2 transport chain from ambient air to the skeletal muscle, the major consequence of which is a reduced cardiac output and peripheral microcirculatory response relative to exercise-related metabolic needs.204,205 Moreover, ventilation is increased at comparable absolute submaximal levels of effort in CHF patients with respect to age-matched normal subjects.206 Among the proposed causes of the increased ventilatory response to exercise are a reduced oxygen-diffusing capacity due to an impairment of alveolar–arterial oxygen transfer,207 an increase in dead space ventilation because of a mismatching of ventilation relative to pulmonary perfusion,206 and an exaggerated ergoreflex response originating in the exercising skeletal muscles during effort.208 Finally, skeletal muscle metabolic potential is also reduced, due to altered redistribution of flow to exercising muscles, endothelial dysfunction and impaired mitochondrial enzymes activity.209 These changes promote a vicious cycle of deterioration involving catabolic drive and reflex neurohormonal over-activation,210 which may lead to disease progression and functional deterioration. As a consequence, in CHF, peak VO2 and VO2 at 1stVT are typically reduced with respect to age-matched normal subjects, and their reduction is proportional to the severity of the syndrome.211 A wide range of aerobic exercise intensities, that is, from light to moderate to high to severe, has been tested in CHF patients. All intensities have been shown to be effective in improving patients' exercise capacity, whereas the ability to induce reverse left ventricular remodelling and improvements in left ventricular ejection fraction has been demonstrated only for moderate to high- and high to severe-intensity aerobic training.85,86,96,212 This offers a wide range of possibilities for the choice of aerobic exercise intensity in CHF, even if more work is needed to investigate safety aspects of high to severe-intensity training in this population (see Interval Training Prescription above).
Among patients with advanced CHF, that is, by definition with severely reduced exercise capacity and presumed high exercise-related risk, left ventricular assist device implantation is increasingly used as a bridge to transplantation or even as permanent therapy. Patients with left ventricular assist devices can often be managed at outpatient clinics, and an early initiation of exercise training after implantation has been reported to be associated with improvements in exercise capacity.213 Walking in the hospital ward as well as aerobic exercise on a cycle ergometer or a treadmill can be performed with the aim of improving exercise capacity. Light to moderate training intensities adjusted at the 1stVT level or possibly even slightly higher (12–14 score in the RPE Borg scale) have succeeded in improving peak VO2 in this population.214–216
Exercise training is recommended for all patients before and after heart transplantation.186,217 Patients with severe heart failure, awaiting heart transplantation, are usually significantly deconditioned due to metabolic changes that occur with heart failure, resulting in significant limitations in the ability to do physical work.218 Functional capacity following transplantation may be affected by the patient's baseline capacity prior to surgery, or by underlying cause(s) of heart failure, the clinical course in the hospital, surgical complications, skeletal muscle weakness, use of corticosteroids and other post-transplant medications and surgical denervation of the heart.219
Given the complexity of hemodynamic and cardiorespiratory responses during incremental exercise in this population, exercise intensity may best be determined by RPE. At the start of training programs, an RPE of 10–12, that is, light to moderate-intensity in the RPE Borg scale, will generally account for the surgical and disease deconditioning as well as any potential exercise issues associated with steroid myopathy.220 If the patient's clinical condition allows, the exercise intensity can gradually increase to moderate to high to enhance patient outcomes. High to severe-intensity aerobic interval training programs have also been evaluated in selected heart transplanted patients and have proven to be safe and effective.221,222 Following heart transplantation, an improvement in functional capacity of approximately 20–50% is associated with participation in a cardiac rehabilitation program.220–223 Exercise should be initially performed in a supervised setting to fully evaluate and monitor the patient's response to aerobic training.
In current cardiac rehabilitation practice, the choice of the aerobic training stimulus intensity in individual patients remains largely a matter of clinical judgement. This European, US and Canadian joint position statement provides evidence-based indications for a shift from a ‘range-based’ to a ‘threshold-based’ aerobic exercise intensity prescription, to be combined with thorough clinical evaluation and exercise-related risk assessment. The importance of functional evaluation through exercise testing prior to starting an aerobic training program is strongly emphasized, and an incremental cardiopulmonary exercise test, when available, is proposed as the gold standard for a physiologically comprehensive exercise intensity assessment and prescription. This would allow professionals to match the unique physiological responses of different exercise intensity domains to the individual patient pathophysiological and clinical status, maximizing the benefits obtainable from aerobic exercise training in cardiac rehabilitation.
This statement was approved by the European Association for Cardiovascular Prevention and Rehabilitation on 28 November 2011, the American Association of Cardiovascular and Pulmonary Rehabilitation Board of Directors on 6 March 2012 and the Canadian Association of Cardiac Rehabilitation on 5 June 2012.
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
1. Gielen S, Mezzani A, Hambrecht R, et al. Cardiac rehabilitation. In: Camm AJ, Lüscher TF, Serruys PW (eds) The ESC textbook of cardiovascular medicine. Oxford: Oxford University Press, 2009, pp.919–954.
2. American Association of Cardiovascular and Pulmonary Rehabilitation. Guidelines for cardiac rehabilitation and secondary prevention programs. Williams MA (ed.) Champaign: Human Kinetics, 2004.
3. European Association for Cardiovascular Prevention and Rehabilitation Committee for Science Guidelines; Corrà U, Piepoli MF, Carré F, et al. Secondary prevention through cardiac rehabilitation: Physical activity counselling and exercise training: Key components of the position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation. Eur Heart J 2010;31:1967–1974.
4. Canadian Association of Cardiac Rehabilitation. Canadian guidelines for cardiac rehabilitation and cardiovascular disease protection. Stone JA, Arthur HM, Suskin N (eds) Winnipeg: CACR, 2009.
5. Hansen D, Dendale P, Berger J, et al. Rehabilitation in cardiac patients: What do we know about training modalities? Sports Med 2005;35:1063–1084.
6. Meyer T, Lucía A, Earnest CP, et al. A conceptual framework for performance diagnosis and training prescription from submaximal gas exchange parameters-theory and application. Int J Sports Med 2005;26(Suppl. 1):S38–S48.
7. Binder RK, Wonisch M, Corrà U, et al. Methodological approach to the first and second lactate threshold in incremental cardiopulmonary exercise testing. Eur J Cardiovasc Prev Rehabil 2008;15:726–734.
8. Measurements during integrative cardiopulmonary exercise testing. In: Principles of exercise testing and interpretation. Wasserman K, Hansen JE, Sue DY, et al. (eds). Baltimore: Lippincott Williams & Wilkins, 2005:pp.76–110.
9. Mezzani A, Agostoni P, Cohen-Solal A, et al. Standards for the use of cardiopulmonary exercise testing for the functional evaluation of cardiac patients: A report from the Exercise Physiology Section of the European Association for Cardiovascular Prevention and Rehabilitation. Eur J Cardiovasc Prev Rehabil 2009;16:249–267.
10. Whipp BJ, Ward SA, Rossiter HB. Pulmonary O2 uptake during exercise: Conflating muscular and cardiovascular responses. Med Sci Sports Exerc 2005;37:1574–1585.
11. Burnley M, Jones AM. Oxygen uptake kinetics as a determinant of sports performance. Eur J Sport Sci 2007;7:63–79.
12. Dekerle J, Baron B, Dupont L, et al. Maximal lactate steady state, respiratory compensation threshold and critical power. Eur J Appl Physiol 2003;89:281–288.
13. Hill DW. The critical power concept. A review. Sports Med 1993;16:237–254.
14. Vandewalle H, Vautier JF, Kachouri M, et al. Work-exhaustion time relationship and the critical power concept. A critical review. J Sports Med Phys Fitness 1997;37:89–102.
15. Whipp BJ, Ward SA. Quantifying intervention-related improvements in exercise tolerance. Eur Resp J 2009;33:1254–1260.
16. Day JR, Rossiter HB, Coats EM, et al. The maximally attainable VO2 during exercise in humans: The peak vs. maximum issue. J Appl Physiol 2003;95:1901–1907.
17. Myers J. Applications of cardiopulmonary exercise testing in the management of cardiovascular and pulmonary disease. Int J Sports Med 2005;26(Suppl. 1):S49–S55.
18. Howley ET, Basset Jr DR, Welch HG. Criteria for maximal oxygen uptake: Review and commentary. Med Sci Sports Exerc 1995;27:1292–1301.
19. Borg G, Borg's. perceived exertion and pain scales. Champaign: Human Kinetics, 1998.
20. Poole DC, Wilkerson DP, Jones AM. Validity of criteria for establishing maximal O2 uptake during ramp exercise tests. Eur J Appl Physiol 2008;102:403–410.
21. Monod H, Scherrer J. The work capacity of a synergic muscle group. Ergonomics 1965;8:329–338.
22. Moritani T, Nagata A, de Vries HA, et al. Critical power as a measure of critical work capacity and anaerobic threshold. Ergonomics 1981;24:339–350.
23. Jones AM, Vanhatalo A, Burnley M, et al. Critical power: implications for the determination of VO2
max and exercise tolerance. Med Sci Sports Exerc 2010;42:1876–1890.
24. Smith CG, Jones AM. The relationship between critical velocity, maximal lactate steady-state velocity and lactate turnpoint velocity in runners. Eur J Appl Physiol 2001;85:19–26.
25. Pringle JS, Jones AM. Maximal lactate steady state, critical power and EMG during cycling. Eur J Appl Physiol 2002;88:214–226.
26. Billat VL, Sirvent P, Py G, et al. The concept of maximal lactate steady state: A bridge between biochemistry, physiology and sport science. Sports Med 2003;33:407–426.
27. Poole DC, Ward SA, Gardner GW, et al. Metabolic and respiratory profile of the upper limit for prolonged exercise in man. Ergonomics 1988;31:1265–1279.
28. Gaesser GA, Poole DC. The slow component of oxygen uptake kinetics in humans. Exerc Sport Sci Rev 1996;24:35–70.
29. Poole DC, Schaffartzik W, Knight DR, et al. Contribution of exercising legs to the slow component of oxygen uptake kinetics in humans. J Appl Physiol 1991;71:1245–1260.
30. Mezzani A, Corrà U, Giordano A, et al. Upper intensity limit for prolonged aerobic exercise in chronic heart failure. Med Sci Sports Exerc 2010;42:633–639.
31. Jones AM, Wilkerson DP, DiMenna F, et al. Muscle metabolic responses to exercise above and below the ‘critical power’ assessed using 31P-MRS. Am J Physiol Regul Integr Comp Physiol 2008;294:R585–R593.
32. Hill DW, Poole DC, Smith JC. The relationship between power and the time to achieve VO2max. Med Sci Sports Exerc 2002;34:709–714.
33. Hellerstein HK, Franklin BA. Exercise testing and prescription. In: Wenger NK, Hellerstein HK (eds) Rehabilitation of the coronary patient. New York: John Wiley and Sons, 1978, p.177.
34. Pollock ML, Ward A, Foster C. Exercise prescription for the rehabilitation of the cardiac patient. In: Pollock ML, Schmidt DH (eds) Heart disease and rehabilitation. Boston, USA: Houghton Mifflin Professional Publishers, 1979, p.414.
35. Balady GJ, Bricker JT, Fletcher GF, et al. ACC/AHA 2002 guideline update for exercise testing. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Exercise Testing). www.acc.org/clinical/guidelines/exercise/dirIndex.htm
(2002, accessed 20 March 2011).
36. Arena R, Myers J, Williams MA, et al. AHA scientific statement. Assessment of functional capacity in clinical and research settings. A scientific statement from the American Heart Association Committee on Exercise, Rehabilitation, and Prevention of the Council on Clinical Cardiology and the Council on Cardiovascular Nursing. Circulation 2007;116:329–343.
37. Stone JA, McCartney, Miller PJ, et al. Risk stratification, exercise testing, exercise prescription, and program safety. In: Stone JA, Arthur HM, Suskin N (eds) Canadian Association of Cardiac Rehabilitation guidelines for cardiac rehabilitation and cardiovascular disease protection. Winnipeg: Canadian Association of Cardiac Rehabilitation, 2009, p.365.
38. Franklin BA, de Jong AT. Exercise prescription. In: American Association of Cardiovascular and Pulmonary Rehabilitation. AACVPR cardiac rehabilitation resource manual. Champaign: Human Kinetics, 2006, p.75.
39. Balady GJ, Williams MA, Ades PA, et al. AHA/AACVPR scientific statement. Core components of cardiac rehabilitation/secondary prevention programs:2007 update. A scientific statement from the American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee, the Council on Clinical Cardiology; the Councils on Cardiovascular Nursing, Epidemiology, and Prevention, and Nutrition, Physical Activity, and Metabolism; and the American Association of Cardiovascular and Pulmonary Rehabilitation. J Cardiopulm Rehabil Prev 2007;27:121–129.
40. Normal values. In: Wasserman K, Hansen JE, Sue DY, et al. (eds) Principles of exercise testing and interpretation. Philadelphia: Lippincott Williams & Wilkins, 2005, pp.160–182.
41. Wilmore JH, Haskell WL. Use of the heart rate-energy expenditure relationship in the individualized prescription of exercise. Am J Clin Nutr 1971;24:1186–1192.
42. Katch V, Weltman A, Sady S, et al. Validity of the relative percent concept for equating training intensity. Eur J Appl Physiol 1978;39:219–227.
43. Tipton CM, Franklin BA. The language of exercise. In: Tipton CM, Sawka MN, Tate CA, et al. (eds) ACSM's advanced exercise physiology. Philadelphia: Lippincott Williams & Wilkins, 2006, pp. 3–10.
44. General principles of exercise prescription. In: Thompson WR, Gordon NF, Pescatello LS (eds) ACSM's guidelines for exercise testing and prescription. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins, 2010, pp.152–182.
45. Durstine JL, Moore G, Painter P, et al. ACSM's exercise management for persons with chronic diseases and disabilities. American College of Sports Medicine. Champaign: Human Kinetics, 2009.
46. Coplan NL, Gleim GW, Nicholas JA. Using exercise respiratory measurements to compare methods of exercise prescription. Am J Cardiol 1986;58:832–836.
47. Goldberg L, Elliot DL, Kuehl KS. Assessment of exercise intensity formulas by use of ventilatory threshold. Chest 1988;94:95–98.
48. Meyer T, Gabriel HH, Kindermann W. Is determination of exercise intensities as percentages of VO2max or HRmax adequate? Med Sci Sports Exerc 1999;31:1342–1345.
49. Scharhag-Rosenberger F, Meyer T, Gäßler N, et al. Exercise at given percentages of VO2max
: Heterogeneous metabolic responses between individuals. J Sci Med Sport 2010;13:74–79.
50. Wonisch M, Hofmann P, Fruhwald FM, et al. Influence of beta-blocker use on percentage of target heart rate exercise prescription. Eur J Cardiovasc Prev Rehabil 2003;10:296–301.
51. Normandin EA, Camaione DN, Clark III BA, et al. A comparison of conventional versus anaerobic threshold exercise prescription methods in subjects with left ventricular dysfunction. J Cardiopulm Rehabil 1993;13:110–116.
52. Karvonen M, Kentala K, Mustala O. The effect of training heart rate: A longitudinal study. Ann Med Exp Biol Fenn 1957;35:307–315.
53. Karvonen J, Vuorimaa T. Heart rate and exercise intensity during sports activities. Practical application. Sports Med 1988;5:303–312.
54. Swain DP, Leutholtz BC. Heart rate reserve is equivalent to %VO2 reserve, not to VO2 %. Med Sci Sports Exerc 1997;29:410–414.
55. Swain DP, Leutholtz BC, King ME, et al. Relationship between % heart rate reserve and % VO2 reserve in treadmill exercise. Med Sci Sports Exerc 1998;30:318–321.
56. Hui SS, Chan JW. The relationship between heart rate reserve and oxygen uptake reserve in children and adolescents. Res Q Exerc Sport 2006;77:41–49.
57. Brawner CA, Keteyian SJ, Ehrman JK. The relationship of heart rate reserve to VO2 reserve in patients with heart disease. Med Sci Sports Exerc 2002;34:418–422.
58. Da Cunha FA, Farinatti Pde T, Midgley AW. Methodological and practical application issues in exercise prescription using the heart rate reserve and oxygen uptake reserve methods. J Sci Med Sport 2011;14:46–57.
59. Goodman LS, McKenzie DC, Taunton JE, et al. Ventilatory threshold and training heart rate in exercising cardiac patients. Can J Sport Sci 1988;13:220–224.
60. Nieuwland W, Berkhuysen MA, van Veldhuisen DJ, et al. Individual assessment of intensity-level for exercise training in patients with coronary artery disease is necessary. Int J Cardiol 2002;84:15–20.
61. Tabet J-Y, Meurin P, Driss AB, et al. Determination of exercise training heart rate in patients on b-blockers after myocardial infarction. Eur J Cardiovasc Prev Rehabil 2006;13:538–543.
62. Strzelczyk TA, Quigg RJ, Pfeifer PB, et al. Accuracy of estimating exercise prescription intensity in patients with left ventricular systolic dysfunction. J Cardiopulm Rehabil 2001;21:158–163.
63. Pathophysiology of disorders limiting exercise. In: Wasserman K, Hansen JE, Sue DY, et al. (eds) Principles of exercise testing and interpretation. Philadelphia: Lippincott Williams & Wilkins, 2005, pp.111–132.
64. Colucci WS, Ribeiro JP, Rocco MB, et al. Impaired chronotropic response to exercise in patients with congestive heart failure. Role of postsynaptic beta-adrenergic desensitization. Circulation 1989;80:314–323.
65. Witte KK, Cleland JG, Clark AL. Chronic heart failure, chronotropic incompetence, and the effects of beta-blockade. Heart 2006;92:481–486.
66. Mezzani A, Corrà U, Giordano A, et al. Unreliability of the %VO2 reserve versus %heart rate reserve relationship for aerobic effort relative intensity assessment in chronic heart failure patients on or off beta-blocking therapy. Eur J Cardiovasc Prev Rehabil 2007;14:92–98.
67. Carvalho VO, Guimarães GV, Bocchi EA. The relationship between heart rate reserve and oxygen uptake reserve in heart failure patients on optimized and non-optimized beta-blocker therapy. Clinics 2008;63:725–730.
68. Borg AV. Psychological bases of perceived exertion. Med Sci Sports Exerc 1982;14:377–381.
69. Noble BJ, Borg G, Jacobs I, et al. A category-ratio perceived exertion scale: Relation to blood and muscle lactate and heart rate. Med Sci Sports Exerc 1983;15:523–528.
70. Purvis JW, Cureton KJ. Rating of perceived exertion at the anaerobic threshold. Ergonomics 1981;24:295–300.
71. Demello JJ, Cureton KJ, Boineau RE, et al. Ratings of perceived exertion at the lactate threshold in trained and untrained men and women. Med Sci Sports Exerc 1987;19:354–362.
72. Eston RG, Williams JG. Reliability of ratings of perceived effort regulation of exercise intensity. Br J Sport Med 1988;22:153–155.
73. Hartzell AA, Freund BJ, Jilka SM, et al. The effect of beta-adrenergic blockade on ratings of perceived exertion during submaximal exercise before and following endurance training. J Cardiopulm Rehabil 1986;6:444–456.
74. Squires RW, Rod JL, Pollock ML, et al. Effect of propranolol on perceived exertion soon after myocardial revascularization surgery. Med Sci Sport Exerc 1982;14:276–280.
75. Dunbar CC, Robertson RJ, Baun R, et al. The validity of regulating exercise intensity by ratings of perceived exertion. Med Sci Sports Exerc 1992;24:94–99.
76. Eston RG, Connolly D. The use of perceived exertion for exercise prescription in patients receiving beta-blocker therapy. Sports Med 1996;21:176–190.
77. Robertson RJ, Noble BJ. Perception of physical exertion methods, mediators, and applications. Med Sci Sports Exerc 1997;25:407–452.
78. Goss FL, Robertson RJ, Haile L, et al. Use of ratings of physical exercise to anticipate treadmill test termination in patients taking beta-blockers. Percept Mot Skills 2011;112:310–318.
79. Haskell WL, Lee IM, Pate RR, et al. Physical activity and public health: Updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Med Sci Sports Exerc 2007;39:1423–1434.
80. Hambrecht R, Wolf A, Gielen S, et al. Effect of exercise on coronary endothelial function in patients with coronary artery disease. New Engl J Med 2000;342:454–460.
81. Niebauer J, Hambrecht R, Velich T, et al. Attenuated progression of coronary artery disease after 6 years of multifactorial risk intervention: role of physical exercise. Circulation 1997;96:2534–2541.
82. Erbs S, Linke A, Hambrecht R. Effects of exercise training on mortality in patients with coronary heart disease. Coron Artery Dis 2006;17:219–225.
83. Whipp BJ. Dynamics of pulmonary gas exchange. Circulation 1987;76:VI18–VI28.
84. Durstine JL, Painter P, Franklin BA, et al. Physical activity for the chronically ill and disabled. Sports Med 2000;30:207–219.
85. Belardinelli R, Georgiou D, Scocco V, et al. Low intensity exercise training in patients with chronic heart failure. J Am Coll Cardiol 1995;26:975–982.
86. Demopoulos L, Bijou R, Fergus I, et al. Exercise training in patients with severe congestive heart failure: Enhancing peak aerobic capacity while minimizing the increase in ventricular wall stress. J Am Coll Cardiol 1997;29:597–603.
87. Oberman A, Fletcher GF, Lee J, et al. Efficacy of high-intensity exercise training on left ventricular ejection fraction in men with coronary artery disease (the Training Level Comparison Study). Am J Cardiol 1995;76:643–647.
88. Adachi H, Koike A, Obayashi T, et al. Does appropriate endurance exercise training improve cardiac function in patients with prior myocardial infarction? Eur Heart J 1996;17:1511–1521.
89. Dubach P, Myers J, Dziekan G, et al. Effect of high intensity exercise training on central hemodynamic responses to exercise in men with reduced left ventricular function. J Am Coll Cardiol 1997;29:1591–1598.
90. Roveda F, Middlekauff HR, Rondon MU, et al. The effects of exercise training on sympathetic neural activation in advanced heart failure: A randomized controlled trial. J Am Coll Cardiol 2003;42:854–860.
91. Van Craenenbroeck EM, Hoymans VY, Beckers PJ, et al. Exercise training improves function of circulating angiogenic cells in patients with chronic heart failure. Basic Res Cardiol 2010;105:665–676.
92. Riley M, McParland J, Stanford CF, et al. Oxygen consumption during corridor walk testing in chronic cardiac failure. Eur Heart J 1992;13:789–793.
93. Faggiano P, D'Aloia A, Gualeni A, et al. Assessment of oxygen uptake during the six-minute walk test in patients with heart failure: preliminary experience with a portable device. Am Heart J 1997;134:203–206.
94. Kervio G, Ville NS, Leclercq C, et al. Cardiorespiratory adaptations during the six-minute walk test in chronic heart failure patients. Eur J Cardiovasc Prev Rehabil 2004;11:171–177.
95. Rognmo Ø, Hetland E, Helgerud J, et al. High intensity aerobic interval exercise is superior to moderate intensity exercise for increasing aerobic capacity in patients with coronary artery disease. Eur J Cardiovasc Prev Rehabil 2004;11:216–222.
96. Wisløff U, Støylen A, Loennechen JP, et al. Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: A randomized study. Circulation 2007;115:3086–3094.
97. Guiraud T, Nigam A, Juneau M, et al. Acute responses to high-intensity intermittent exercise in CHD patients. Med Sci Sports Exerc 2011;43:211–217.
98. Mezzani A, Corrà U, Sassi B, et al. Maximal accumulated oxygen deficit in patients with chronic heart failure. Med Sci Sports Exerc 2006;38:424–432.
99. Helgerud J, Høydal K, Wang E, et al. Aerobic high-intensity intervals improve VO2max more than moderate training. Med Sci Sports Exerc 2007;39:665–671.
100. Moholdt TT, Amundsen BH, Rustad LA, et al. Aerobic interval training versus continuous moderate exercise after coronary artery bypass surgery: A randomized study of cardiovascular effects and quality of life. Am Heart J 2009;158:1031–1037.
101. Amundsen BH, Rognmo Ø, Hatlen-Rebhan G, et al. High-intensity aerobic exercise improves diastolic function in coronary artery disease. Scand Cardiovasc J 2008;42:110–117.
102. Wisløff U, Ellingsen O, Kemi OJ. High-intensity interval training to maximize cardiac benefits of exercise training? Exerc Sport Sci Rev 2009;37:139–146.
103. Munk PS, Staal EM, Butt N, et al. High-intensity interval training may reduce in-stent restenosis following percutaneous coronary intervention with stent implantation: A randomized controlled trial evaluating the relationship to endothelial function and inflammation. Am Heart J 2009;158:734–741.
104. Cornish AK, Broadbent S, Cheema BS. Interval training for patients with coronary artery disease: A systematic review. Eur J Appl Physiol 2011;111:579–589.
105. Gibala MJ, McGee SL. Metabolic adaptations to short-term high-intensity interval training: A little pain for a lot of gain? Exerc Sport Sci Rev 2008;36:58–63.
106. Bailey SJ, Wilkerson DP, DiMenna F, et al. Influence of repeated sprint training on pulmonary O2
uptake and muscle deoxygenation kinetics in humans. J Appl Physiol 2009;106:1875–1887.
107. Meyer P, Guiraud T, Gayda M, et al. High-intensity aerobic interval training in a patient with stable angina pectoris. Am J Phys Med Rehabil 2010;89:83–86.
108. Warburton DE, McKenzie DC, Haykowsky MJ, et al. Effectiveness of high-intensity interval training for the rehabilitation of patients with coronary artery disease. Am J Cardiol 2005;95:1080–1084.
109. Nilsson BB, Westheim A, Risberg MA. Effects of group-based high-intensity aerobic interval training in patients with chronic heart failure. Am J Cardiol 2008;102:1361–1365.
110. Nilsson BB, Westheim A, Risberg MA. Long-term effects of a group-based high-intensity aerobic interval-training program in patients with chronic heart failure. Am J Cardiol 2008;102:1220–1224.
111. Støylen A, Conraads V, Halle M, et al. Controlled study of myocardial recovery after interval training in heart failure: SMARTEX-HF-rationale and design. Eur J Cardiovasc Prev Rehabil 2012;19:151–160.
112. Bevegard S, Freyschuss U, Strandell T. Circulatory adaptation to arm and leg exercise in supine and sitting position. J Appl Physiol 1966;21:37–46.
113. Lazarus B, Cullinane E, Thompson PD. Comparison of the results and reproducibility of arm and leg exercise tests in men with angina pectoris. Am J Cardiol 1981;47:1075–1079.
114. Franklin BA, Vander L, Wrisley D, et al. Aerobic requirements of arm ergometry:implications for exercise testing and training. Physician Sports Med 1983;11:81–90.
115. Miles DS, Cox MH, Bomze JP. Cardiovascular responses to upper body exercise in normals and cardiac patients. Med Sci Sports Exerc 1989;21(Suppl. 5):S126–S131.
116. Balady GJ. Types of exercise. Arm-leg and static-dynamic. Cardiol Clin 1993;11:297–308.
117. Wetherbee S, Franklin BA, Hollingsworth V, et al. Relationship between arm and leg training work loads in men with heart disease. Implications for exercise prescription. Chest 1991;99:1271–1273.
118. Franklin BA, Vander L, Wrisley D, et al. Trainability of arms versus legs in men previous myocardial infarction. Chest 1994;105:262–264.
119. Kellermann JJ, Shemesh J, Fisman EZ, et al. Arm exercise training in the rehabilitation of patients with impaired ventricular function and heart failure. Cardiology 1990;77:130–138.
120. Nyquist-Battie C, Fletcher GF, Fletcher B, et al. Upper-extremity exercise training in heart failure. J Cardiopulm Rehabil Prev 2007;27:42–45.
121. Donnelly JE, Blair SN, Jakicic JM, et al. American College of Sports Medicine Position Stand. Appropriate physical activity intervention strategies for weight loss and prevention of weight regain for adults. Med Sci Sports Exerc 2009;41:459–471.
122. Ross R, Dagnone D, Jones PJ, et al. Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men. Ann Intern Med 2000;133:92–103.
123. Ohkawara K, Tanaka S, Miyachi M, et al. A dose-response relation between aerobic exercise and visceral fat reduction: Systematic review of clinical trials. Intern J Obes 2007;31:1786–1797.
124. Hankinson AL, Daviglus ML, Bouchard C, et al. Maintaining a high physical activity level over 20 years and weight gain. JAMA 2010;304:2603–2610.
125. Jakicic JM, Marcus BH, Gallagher KI, et al. Effect of exercise duration and intensity on weight loss in overweight, sedentary women: A randomized trial. JAMA 2003;290:1323–1330.
126. Nicklas BJ, Wang X, You T, et al. Effect of exercise intensity on abdominal fat loss during calorie restriction in overweight and obese postmenopausal women: A randomized, controlled trial. Am J Clin Nutr 2009;89:1042–1052.
127. Slentz CA, Duscha BD, Johnson JL, et al. Effects of the amount of exercise on body weight, body composition, and measures of central obesity: STRRIDE-a randomized controlled study. Arch Intern Med 2004;164:31–39.
128. Saris WH, Blair SN, van Baak MA, et al. How much physical activity is enough to prevent unhealthy weight gain? Outcome of the IASO 1st Stock Conference and consensus statement. Obes Rev 2003;4:101–114.
129. Lee IM, Djoussé L, Sesso HD, et al. Physical activity and weight gain prevention. JAMA 2010;303:1173–1179.
130. Di Pietro L, Dziura J, Blair SN. Estimated change in physical activity level (PAL) and prediction of 5-year weight change in men: The Aerobics Center Longitudinal Study. Int J Obes Relat Metab Disord 2004;28:1541–1547.
131. Goodpaster BH, DeLany JP, Otto AD, et al. Physical activity is vital for those with severe obesity in losing weight. In a lifestyle intervention of those with severe obesity, physical activity resulted in clinically significant weight loss and favourable changes in cardiometabolic risk factors. JAMA 2010;304:1795–1802.
132. Rostagno C, Olivo G, Comeglio M, et al. Prognostic value of 6-minute walk corridor test in patients with mild to moderate heart failure: Comparison with other methods of functional evaluation. Eur J Heart Fail 2003;5:247–252.
133. Moalla W, Gauthier R, Maingourd Y, et al. Six-minute walking test to assess exercise tolerance and cardiorespiratory responses during training program in children with congenital heart disease. Int J Sports Med 2005;26:756–762.
134. Ross RM, Murthy JN, Wollak ID, et al. The six-minute walk test accurately estimates mean peak oxygen uptake. BMC Pulm Med 2010;26:10–31.
135. Dagenais GR, Armstrong PW, Théroux P, et al. CCS Ad Hoc Committee for Revising the CCS Grading of Stable Angina. Revisiting the Canadian Cardiovascular Society grading of stable angina pectoris after a quarter of a century of use. Can J Cardiol 2002;18:941–944.
136. Gülec S, Ertas F, Tutar E, et al. Exercise performance in patients with dilated cardiomyopathy: relationship to resting left ventricular function. Int J Cardiol 1998;247–253.
137. Fletcher GF, Balady GJ, Amsterdam EA, et al. Exercise standards for testing and training: A statement for healthcare professionals from the American Heart Association. Circulation 2001;104:1694–1740.
138. Chen MJ, Fan X, Moe ST. Criterion-related validity of the Borg ratings of perceived exertion scale in healthy individuals: A meta-analysis. J Sports Sci 2002;20:873–899.
139. Mielke M, Housh TJ, Malek MH, et al. The development of rating of perceived exertion-based tests of physical working capacity. J Strength Cond Res 2008;22:293–302.
140. Rynders CA, Angadi SS, Weltman NY, et al. Oxygen uptake and ratings of perceived exertion at the lactate threshold and maximal fat oxidation rate in untrained adults. Eur J Appl Physiol 2011;111:2063–2068.
141. Foster C, Porcari JP, Anderson J, et al. The talk test as a marker of exercise training intensity. J Cardiopulm Rehabil Prev 2008;28:24–30; quiz 31–32.
142. Norman JF, Hopkins E, Crapo E. Validity of the counting talk test in comparison with standard methods of estimating exercise intensity in young healthy adults. J Cardiopulm Rehabil Prev 2008;28:199–202.
143. Vanhees L, Rauch B, Piepoli M, et al. Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular disease (Part III). Eur J Prev Cardiol Epub ahead of print 23 January 2012. DOI:10.1177/2047487312437063.
144. Clark AM, Hartling L, Vandermeer B, et al. Meta-analysis: Secondary prevention programs for patients with coronary artery disease. Ann Intern Med 2005;143:659–672.
145. Kavanagh T, Mertens DJ, Hamm LF, et al. Prediction of long-term prognosis in 12,169 men referred for cardiac rehabilitation. Circulation 2002;106:666–671.
146. Kelion AD, Webb TP, Gardner MA, et al. The warm-up effect protects against ischemic left ventricular dysfunction in patients with angina. J Am Coll Cardiol 2001;37:705–710.
147. Joy M, Cairns AW, Sprigings D. Observations on the warm-up phenomenon in angina pectoris1. Br Heart J 1987;58:116–21.
148. Noël M, Jobin J, Poirier P, et al. Different thresholds of myocardial ischemia in ramp and standard Bruce protocol exercise tests in patients with positive exercise stress tests and angiographically demonstrated coronary arterial narrowing. Am J Cardiol 2007;99:921–924.
149. Warburton DE, Charlesworth S, Ivery A, et al. A systematic review of the evidence for Canada's Physical Activity Guidelines for Adults. Int J Behav Nutr Phys Act 2010;11:39.
150. Linxue L, Nohara R, Makita S, et al. Effect of long-term exercise training on regional myocardial perfusion changes in patients with coronary artery disease. Jpn Circ J 1999;63:73–78.
151. Todd IC, Bradnam MS, Cooke MB, et al. Effects of daily high-intensity exercise on myocardial perfusion in angina pectoris. Am J Cardiol 1991;68:1593–1599.
152. Todd IC, Ballantyne D. Effect of exercise training on the total ischemia burden: An assessment by 24 hour ambulatory electrocardiographic monitoring. Br Heart J 1992;68:560–566.
153. Casillias JM, Gremeaux V, Damak S, et al. Exercise training for patients with cardiovascular disease. Ann Readapt Med Phys 2007;50:403–418.
154. Guiraud T, Juneau M, Nigam A, et al. Optimization of high intensity interval exercise in coronary artery disease. Eur J Appl Physiol 2010;108:733–740.
155. Takahashi T, Okada A, Hayano J, et al. Influence of cool-down exercise on autonomic control of heart rate during recovery from dynamic exercise. Front Med Biol Eng 2002;11:249–259.
156. Koyama Y, Koike A, Yajima T, et al. Effects of ‘cool-down’ during exercise recovery on cardiopulmonary systems in patients with coronary artery disease. Jpn Circ J 2000;64:191–196.
157. Che L, Wang LM, Jiang JF, et al. Effects of early submaximal cardiopulmonary exercise test and cardiac rehabilitation for patients with acute myocardial infarction after percutaneous coronary intervention: A comparative study. Zhonghua Yi Xue Za Zhi 2008;88:1820–1823.
158. Goto Y, Sunida H, Usehima K, et al. Safety and implementation of exercise testing and training after coronary stenting in patients with acute myocardial infarction. Circ J 2002;66:930–936.
159. Pavy B, Iiiou MC, Meurin P, et al.; Functional Evaluation and Cardiac Rehabilitation Working Group of the French Society of Cardiology. Safety of exercise training for cardiac patients: Results of the French registry of complications during cardiac rehabilitation. Arch Intern Med 2006;166:2329–2334.
160. Chen YW, Chen JK, Wang JS. The relationship between shear stress and flow-mediated dilatation: implications. J Physiol 2005;568:357–369.
161. Parker K, Stone JA, Arena R, et al. An early cardiac access clinic significantly improves cardiac rehabilitation participation and completion rates in low risk STEMI patients. Can J Cardiol 2011;27:619–627.
162. Reid RD, Morrin LI, Pipe AL, et al. Determinants of physical activity after hospitalization for coronary artery disease: The Tracking Exercise After Cardiac Hospitalization (TEACH) study. Eur J Cardiovasc Prev Rehabil 2006;13:529–537.
163. Munk PS, Larsen AI. Training after percutaneous coronary interventions – an undervalued option? Tidsskr Nor Laegforen 2007;127:1365–1367.
164. Astengo M, Dahl A, Karlssson T, et al. Physical training after percutaneous coronary interventions in patients with stable angina: Effects on working capacity, metabolism, and markers of inflammation. Eur J Cardiovasc Prev Rehabil 2010;17:349–354.
165. Belardinelli R, Paolini I, Cianci G, et al. Exercise training intervention after coronary angioplasty: The ETICA trial. J Am Coll Cardiol 2001;37:1891–1900.
166. Kim YJ, Shin YO, Bae JS, et al. Beneficial effects of cardiac rehabilitation and exercise after percutaneous coronary intervention on hsCRP and inflammatory cytokines in CAD patients. Pflugers Arch 2008;455:1081–1088.
167. Lan C, Chen SY, Chiu SF, et al. Poor functional recovery may indicate restenosis in patients after coronary angioplasty. Arch Phys Med Rehabil 2003;84:1023–1027.
168. Gielen S, Sandri M, Erbs S, et al. Exercise-induced modulation of endothelial nitric oxide production. Curr Pharm Biotechnol 2011;12:1375–1384.
169. Padilla J, Harris RA, Rink LD, et al. Characterization of the brachial artery shear stress following walking exercise. Vasc Med 2008;13:105–111.
170. Pyke KE, Tschakovsky ME. The relationship between shear stress and flow-mediated dilatation: Implications for the assessment of endothelial function. J Physiol 2005;568:357–369.
171. Zheng H, Luo M, Shen Y, et al. Effects of 6 months exercise training on ventricular remodelling and autonomic tone in patients with acute myocardial infarction and percutaneous coronary intervention. J Rehabil Med 2008;40:776–779.
172. Tsai MW, Chie WC, Kuo TB, et al. Effects of training on heart rate variability after coronary angioplasty. Phys Ther 2006;86:626–636.
173. Munk PS, Butt N, Larsen AI. High-intensity interval exercise training improves heart rate variability in patients following percutaneous coronary intervention for angina pectoris. Int J Cardiol 2010;145:312–314.
174. Sharp CT, Busse EF, Burgess JJ, et al. Exercise prescription for patients with pacemakers. J Cardiopulm Rehabil 1998;18:421–431.
175. Superko HR. Effects of cardiac rehabilitation in permanently paced patients with third-degree heart block. J Cardiac Rehab 1983;3:561–568.
176. Fan S, Lyon CE, Savage PD, et al. Outcomes and adverse events among patients with implantable cardiac defibrillators in cardiac rehabilitation: A case-controlled study. J Cardiopulm Rehabil Prev 2009;29:40–43.
177. Dougherty CM, Glenny RW, Kudenchuk PJ, et al. Testing an exercise intervention to improve aerobic conditioning and autonomic function after an implantable cardioverter defibrillator (ICD). Pacing Clin Electrophysiol 2010;33:973–980.
178. Belardinelli R, Capestro F, Misiani A, et al. Moderate exercise training improves functional capacity, quality of life, and endothelium-dependent vasodilation in chronic heart failure patients with implantable cardioverter defibrillators and cardiac resynchronization therapy. Eur J Cardiovasc Prev Rehabil 2006;13:818–825.
179. Vanhees L, Kornaat M, Defoor J, et al. Effect of exercise training in patients with an implantable cardioverter defibrillator. Eur Heart J 2004;25:1120–1126.
180. Atwood JE, Myers J, Sullivan M, et al. Maximal exercise testing and gas exchange in patients with chronic atrial fibrillation. J Am Coll Cardiol 1988;11:508–513.
181. Agostoni P, Emdin M, Corrà U, et al. Permanent atrial fibrillation affects exercise capacity in chronic heart failure patients. Eur Heart J 2008;29:2367–2372.
182. Mertens DJ, Kavanagh T. Exercise training for patients with chronic atrial fibrillation. J Cardiopulm Rehabil 1996;16:193–196.
183. Vanhees L, Schepers D, Defoor J, et al. Exercise performance and training in cardiac patients with atrial fibrillation. J Cardiopulm Rehabil 2000;20:346–352.
184. Hegbom F, Stavem K, Sire S, et al. Effects of short-term exercise training on symptoms and quality of life in patients with chronic atrial fibrillation. Int J Cardiol 2007;116:86–92.
185. Thomas RJ, King M, Lui K, et al. AACVPR.ACCF/AHA 2010 update: Performance measures on cardiac rehabilitation for referral to cardiac rehabilitation/secondary prevention services. J Cardiopulm Rehabil Prev 2010;30:279–288.
186. Williams MA, Ades PA, Hamm LF, et al. Clinical evidence for a health benefit from cardiac rehabilitation: An update. Am Heart J 2006;152:835–841.
187. Williams MA, Maresh CM, Esterbrooks DJ, et al. Early exercise training in patients older than age 65 years compared with that in younger patients after acute myocardial infarction or coronary artery bypass grafting. Am J Cardiol 1985;55:263–266.
188. Daida H, Squires RW, Allison TG, et al. Sequential assessment of exercise tolerance in heart transplantation compared with coronary artery bypass surgery after phase II cardiac rehabilitation. Am J Cardiol 1996;77:696–700.
189. Goodman JM, Pallandi DV, Reading JR, et al. Central and peripheral adaptations after 12 weeks of exercise training in post-coronary artery bypass surgery patients. J Cardiopulm Rehabil 1999;19:144–150.
190. Adachi H, Itoh H, Sakurai S, et al. Short-term physical training improves ventilatory response to exercise after coronary arterial bypass surgery. Jpn Circ J 2001;65:419–423.
191. Plüss CE, Billing E, Held C, et al. Long-term effects of an expanded cardiac rehabilitation programme after myocardial infarction or coronary artery bypass surgery: A five-year follow-up of a randomized controlled study. Clin Rehabil 2011;25:79–87.
192. Hsu CJ, Chen SY, Su S, et al. The effect of early cardiac rehabilitation on health-related quality of life among heart transplant recipients and patients with coronary artery bypass graft surgery. Transplant Proc 2011;43:2714–2717.
193. Ades PA, Savage PD, Brawner CA, et al. Aerobic capacity in patients entering cardiac rehabilitation. Circulation 2006;113:2706–2712.
194. Ades PA, Grunvald MH, Weiss RM, et al. Usefulness of myocardial ischemia as predictor of training effect in cardiac rehabilitation after acute myocardial infarction or coronary artery bypass grafting. Am J Cardiol 1989;63:1032–1036.
195. Butchart EG, Gohlke-Barwolf C, Antunes MJ, et al. Working Groups on Valvular Heart Disease, Thrombosis, and Cardiac Rehabilitation and Exercise Physiology, European Society of Cardiology. Recommendations for the management of patients after heart valve surgery. Eur Heart J 2005;26:2463–2471.
196. American College of Cardiology/American Heart Association Task Force on Practice Guidelines; Society of Cardiovascular Anesthesiologists; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons, Bonow RO, Carabello BA, Kanu C, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): Developed in collaboration with the Society of Cardiovascular Anesthesiologists: Endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. Circulation 2006;114:e84–e231.
197. Sire S. Physical training and occupational rehabilitation after aortic valve replacement. Eur Heart J 1987;8:1215–1220.
198. Habel-Verge C, Landry F, Desaulniers D, et al. Physical fitness improves after mitral valve replacement. Can Med Assoc J 1987;136:142–147.
199. Jairath N, Salerno T, Chapman J, et al. The effect of moderate exercise training on oxygen uptake post-aortic/mitral valve surgery. J Cardiopulm Rehabil 1995;15:424–430.
200. Douard H, Chevalier L, Labbe L, et al. Physical training improves exercise capacity in patients with mitral stenosis after balloon valvuloplasty. Eur Heart J 1997;18:464–469.
201. Meurin P, Iliou MC, Ben Driss A, et al.; Working Group of Cardiac Rehabilitation of the French Society of Cardiology. Early exercise training after mitral valve repair: A multicentric prospective French study. Chest 2005;128:1638–1644.
202. Pressler A, Scherr J, Eichinger W, et al. Left ventricular remodeling with intensive exercise after aortic valve replacement. J Heart Valve Dis 2011;20:91–93.
203. Cohen-Solal A, Chabernaud JN, Gourgon R. Comparison of oxygen uptake during bicycle exercise in patients with chronic heart failure and in normal subjects. J Am Coll Cardiol 1990;16:80–85.
204. Sullivan MJ, Cobb FR. Central hemodynamic response to exercise in patients with chronic heart failure. Chest 1992;101(Suppl. 5):340S–346S.
205. Esposito F, Mathieu-Costello O, Shabetai R, et al. Limited maximal exercise capacity in patients with chronic heart failure: Partitioning the contributors. J Am Coll Cardiol 2010;55:1945–1954.
206. Wasserman K, Zhang YY, Gitt A, et al. Lung function and exercise gas exchange in chronic heart failure. Circulation 1997;96:2221–2227.
207. Puri S, Baker BL, Dutka DP, et al. Reduced alveolar capillary membrane diffusing capacity in chronic heart failure. Its pathophysiological relevance and relationship to exercise performance. Circulation 1995;91:2769–2774.
208. Piepoli M, Clark AL, Volterrani M, et al. Contribution of muscle afferents to the hemodynamic, autonomic, and ventilatory responses to exercise in patients with chronic heart failure:effects of physical training. Circulation 1996;93:940–952.
209. Clark AL, Poole-Wilson PA, Coats AJ. Exercise limitation in chronic heart failure: Central role of the periphery. J Am Coll Cardiol 1996;28:1092–1102.
210. Floras JS. Clinical aspects of sympathetic activation and parasympathetic withdrawal in heart failure. J Am Coll Cardiol 1993;22:72A–84A.
211. Weber KT, Janicki JS, McElroy PA. Determination of aerobic capacity and the severity of chronic cardiac and circulatory failure. Circulation 1987;76:VI40–VI45.
212. Giannuzzi P, Temporelli PL, Corrà U, et al. ELVD-CHF Study Group. Antiremodeling effect of long-term exercise training in patients with stable chronic heart failure: Results of the Exercise in Left Ventricular Dysfunction and Chronic Heart Failure (ELVD-CHF) trial. Circulation 2003;108:554–559.
213. Humphrey R. Exercise physiology in patients with left ventricular assist devices. J Cardiopulm Rehabil 1997;17:73–75.
214. Mettauer B, Geny B, Lonsdorfer-Wolf E, et al. Exercise training with a heart device: A hemodynamic, metabolic, and hormonal study. Med Sci Sports Exerc 2001;33:2–8.
215. Ueno A, Tomizawa Y. Cardiac rehabilitation and artificial heart devices. J Artif Organs 2009;12:90–97.
216. Laoutaris ID, Dritsas A, Adamopoulos S, et al. Benefits of physical training on exercise capacity, inspiratory muscle function, and quality of life in patients with ventricular ssist devices long-term postimplantation. Eur J Cardiovasc Prev Rehabil 2011;18:33–40.
217. Leon AS, Franklin BA, Costa F, et al. Cardiac rehabilitation and secondary prevention of coronary heart disease. An AHA scientific statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity), in collaboration with the American Association of Cardiovascular and Pulmonary Rehabilitation. Circulation 2005;111:369–376.
218. Conraads VM, Becker PJ. Exercise in heart failure: Practical guidance. Heart 2010;96:2025–2031.
219. Kavanagh T. Exercise training in patients after heart transplantation. Hertz 1991;16:243–250.
220. Braith RW, Edwards DG. Exercise following heart transplantation. Sports Med 2000;30:171–192.
221. Zoll J, N'Guessan B, Ribera F, et al. Preserved response of mitochondrial function to short-term endurance training in skeletal muscle of heart transplant recipients. J Am Coll Cardiol 2003;42:126–132.
222. Hermann TS, Dall CH, Christensen SB, et al. Effect of high intensity exercise on peak oxygen uptake and endothelial function in long-term heart transplant recipients. Am J Transplant 2011;11:536–541.
223. Kobashigawa JA, Leaf DA, Lee N, et al. A controlled trial of exercise rehabilitation after heart transplantation. New Engl J Med 1999;340:272–277.
Aerobic training; energy expenditure; peak VO2; ventilatory thresholds; cardiac rehabilitation
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