Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nanyang Technological University on 04/24/15 For personal use only.
Review
Cardiopulmonary exercise testing in adults with congenital heart disease Expert Rev. Cardiovasc. Ther. 12(7), 863–872 (2014)
Abigail May Khan*1, Stephen M Paridon2,3 and Yuli Y Kim13 1 Division of Cardiology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA 2 Division of Cardiology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA 3 The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA *Author for correspondence: [email protected]
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Adults with congenital heart disease (CHD) are at high risk for morbidity and mortality. Identifying those who are at highest risk of complications can be challenging, in part because self-reported functional status is not a reliable indicator of physiological status. Individuals with CHD may present with exercise limitation due to a variety of cardiac and non-cardiac causes. Cardiopulmonary exercise testing (CPET) provides an integrated assessment of cardiac, pulmonary, and metabolic function and can identify the source of exercise limitation in many patients. Because CPET parameters have also been associated with outcome in adults with CHD, CPET has recently emerged as an important prognostic indicator in this population. KEYWORDS: cardiopulmonary exercise testing • congenital heart disease • exercise capacity • heart failure • pediatrics
Dramatic improvements in the treatment of infants and children with congenital heart disease (CHD) have resulted in an increase in the number of adults living with CHD (ACHD). Healthcare providers are now tasked with the ongoing surveillance and management of these individuals, who have an elevated risk of morbidity and mortality [1,2]. There is a strong need for methods to identify patients at risk of future cardiac events, as well as to identify those who have the greatest potential to benefit from surgical and interventional procedures. In this setting, cardiopulmonary exercise testing (CPET) has emerged as an important clinical tool. The literature regarding cardiac stress testing in the adult population has primarily focused on the diagnosis of suspected coronary disease. ACHD patients, however, are more likely to develop dyspnea and exercise intolerance unrelated to underlying ischemia. In addition to cardiac limitations, abnormalities of the pulmonary, musculoskeletal and metabolic systems are relatively common in this population. CPET offers the distinct benefit of providing insight not only into cardiac physiology, but also into the pulmonary, musculoskeletal and other systems responsible for the body’s integrated response to exercise. In this review, we will focus on the clinical interpretation of CPET results as they relate to individuals with ACHD. We will also discuss the data supporting the use of 10.1586/14779072.2014.919223
CPET as a risk assessment tool in the growing population of adults with CHD. A brief overview of CPET
CPET measures the simultaneous response of the cardiovascular and respiratory systems to exercise. It must be performed in a dedicated testing laboratory using a specialized system with the capability to measure gas exchange, in addition to monitoring of physical working capacity, blood pressure and pulse oximetry. Continuous electrocardiographic monitoring is also performed during the test. Measurements of pulmonary function both at rest and exercise are routinely performed. All of these parameters are then integrated to identify sources of exercise limitation. The process of performing CPET is beyond the scope of general interest and is discussed in further detail elsewhere [3]. However, it is important for ordering clinicians to understand the impact of exercise modality on test results. CPET can be performed using either a cycle ergometer or a treadmill. Treadmill exercise testing is the more common modality in the USA, while cycle tests are more common in other areas [3]. A principal benefit of treadmill testing is a greater level of patient comfort and familiarity as compared with cycle testing. Untrained subjects will often terminate cycle testing due to quadriceps fatigue, achieving a
2014 Informa UK Ltd
ISSN 1477-9072
863
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nanyang Technological University on 04/24/15 For personal use only.
Review
Khan, Paridon & Kim
peak oxygen consumption (VO2peak), which is approximately 10–20% lower than that obtained by a treadmill test [3,4]. The principal drawback of treadmill testing is the inability to accurately measure work rate. The energy required for body movement at a given grade and speed is impacted by the multiple levels of communication between the subject and the treadmill during exercise (e.g., the handrails, blood pressure cuff and mouthpiece). The degree of this impact is difficult to quantify for any given exercise test and therefore obtaining an accurate measurement of work rate from a treadmill test is difficult. Artifact in ventilatory and circulatory measurements is also introduced by torso movement during exercise treadmill testing. While the risk of artifact may be higher with a treadmill test, the potential for technical errors, such as an erroneously low blood pressure or oxygen saturation at peak exercise, must be recognized on any CPET, regardless of testing modality. Safety may also be a concern in treadmill use on physically fragile patients. As mentioned above, the VO2peak obtained by a treadmill test is generally higher than that obtained by a cycle test [4,5]. Measured oxygen pulse and ventilatory threshold also tend to be higher on treadmill tests. This should be taken into account when comparing results across testing modalities and in the use of protocol appropriate normative data. Detailed discussions of exercise physiology are available elsewhere [3]. However, a basic understanding of this topic is required for the interpretation of test results. During exercise, the cardiac output increases to ensure sufficient oxygen delivery to the muscles. In normal individuals, augmentation of the cardiac output occurs via increases in both heart rate and stroke volume. In addition, blood flow is redirected away from less active tissue beds to exercising muscle, and oxygen extraction from the blood is increased. In order to adequately clear carbon dioxide (CO2) from the blood, the minute ventilation (VE) increases along with the work rate. In normal individuals, increased blood flow to the lungs is matched by an increase in VE, maintaining a balance between ventilation and perfusion. Ventilation–perfusion mismatch can occur in the setting of cardiac disease (increased ventilation is not matched by increased perfusion) or in the setting of pulmonary disease (increased perfusion is not adequately matched by increased ventilation). In the earlier stages of exercise, the oxygen uptake (VO2), the CO2 output, and the VE all increase linearly with the work rate. In the later stages of exercise, blood flow to the exercising muscles is inadequate to meet the demands of aerobic metabolism (~5 l/min of cardiac output per liter of VO2) and the muscles begin to metabolize anaerobically. At this point, the CO2 output increases more rapidly than the VO2 as a consequence of the need to buffer increased lactic acid production, an easily identifiable feature of the so-called ventilatory anaerobic threshold (VAT) on an exercise test. Standard CPET measures & their interpretation Peak work rate
The peak work rate is the maximal amount of power output (work/time) achieved by a subject during an exercise test. It is a 864
measure of the exercise capacity. The measurement of work rate is straightforward during cycle ergometry but more complicated during treadmill exercise. In treadmill exercise testing, the endurance time is used as a surrogate for work rate. This time can be compared with age- and gender-adjusted normal values, assuming that a standard protocol is utilized [6,7]. In CPET, other more descriptive measures, such as VO2peak, obviate the need to rely on exercise time as the primary measure of exercise capacity. Heart rate response
The identification of an abnormal heart rate response to exercise is of diagnostic importance in patients with ACHD [8]. An increase in heart rate and stroke volume is necessary to augment the cardiac output in response to exercise. An insufficient heart rate response to exercise results in a lower VO2peak. Clinically, this manifests as decreased exercise tolerance. In normal individuals, the heart rate increases linearly in response to exercise. The maximum expected heart rate at peak exercise is related roughly to age by the following equation: Peak heart rate = 220 – age (in years)
[Equation 1]
It is important to note that this formula is considered an estimate and may not be accurate in some populations [9,10]. Alternate formulas have been derived but are not in widespread use in clinical practice. Chronotropic incompetence (CI) refers to the inability of the heart rate to increase appropriately with exercise and is generally defined as failure to achieve at least 85% of the ageexpected maximum heart rate. The evidence suggests that CI is common in ACHD [11–13]. In one study of 345 adolescents and adults, 34% met criteria for CI, which in this study was defined as failure to reach 80% of the maximum predicted heart rate [13]. CI was most common in those with single ventricle physiology and those who had undergone an atrial switch procedure. It may also be seen in those lesions that require trans-section of the aorta as part of the repair such as the arterial switch operation (ASO) for D-transposition of the great arteries. These procedures disrupt the sympathetic innervation to the heart and may limit chronotropic response. Other methods of quantifying the chronotropic response to exercise include the heart rate reserve, the chronotropic index and the heart rate recovery. The calculation of these measures and the data supporting their use in ACHD is described in TABLE 1. Blood pressure
In normal individuals, the systolic blood pressure increases in response to exercise while the diastolic blood pressure remains relatively stable. The failure of the systolic blood pressure to increase at least 20–30 mmHg above resting levels or a fall in systolic blood pressure during exercise is considered abnormal. This finding, when present, may be related to severe dysfunction of the systemic ventricle or obstruction to aortic outflow. It can also be seen in the setting of myocardial ischemia or medications such as b-blockers. While current consensus guidelines do not specifically define a cut-off for a hypertensive response to exercise, Expert Rev. Cardiovasc. Ther. 12(7), (2014)
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Equal to the peak heart rate – resting heart rate; measures the ability of the heart rate to increase in response to exercise Equal to the difference between peak heart rate and the measured heart rate at a specific time in recovery. Reflects the reactivation of vagal tone after cessation of exercise
Normally occurs at 45–65% of VO2peak
ACHD-specific data are lacking although nomograms exist for normal individuals
>1.10 if a maximal test was achieved
Review
Cardiopulmonary exercise testing in adults with congenital heart disease Expert Rev. Cardiovasc. Ther. 12(7), 863–872 (2014)
Abigail May Khan*1, Stephen M Paridon2,3 and Yuli Y Kim13 1 Division of Cardiology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA 2 Division of Cardiology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA 3 The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA *Author for correspondence: [email protected]
informahealthcare.com
Adults with congenital heart disease (CHD) are at high risk for morbidity and mortality. Identifying those who are at highest risk of complications can be challenging, in part because self-reported functional status is not a reliable indicator of physiological status. Individuals with CHD may present with exercise limitation due to a variety of cardiac and non-cardiac causes. Cardiopulmonary exercise testing (CPET) provides an integrated assessment of cardiac, pulmonary, and metabolic function and can identify the source of exercise limitation in many patients. Because CPET parameters have also been associated with outcome in adults with CHD, CPET has recently emerged as an important prognostic indicator in this population. KEYWORDS: cardiopulmonary exercise testing • congenital heart disease • exercise capacity • heart failure • pediatrics
Dramatic improvements in the treatment of infants and children with congenital heart disease (CHD) have resulted in an increase in the number of adults living with CHD (ACHD). Healthcare providers are now tasked with the ongoing surveillance and management of these individuals, who have an elevated risk of morbidity and mortality [1,2]. There is a strong need for methods to identify patients at risk of future cardiac events, as well as to identify those who have the greatest potential to benefit from surgical and interventional procedures. In this setting, cardiopulmonary exercise testing (CPET) has emerged as an important clinical tool. The literature regarding cardiac stress testing in the adult population has primarily focused on the diagnosis of suspected coronary disease. ACHD patients, however, are more likely to develop dyspnea and exercise intolerance unrelated to underlying ischemia. In addition to cardiac limitations, abnormalities of the pulmonary, musculoskeletal and metabolic systems are relatively common in this population. CPET offers the distinct benefit of providing insight not only into cardiac physiology, but also into the pulmonary, musculoskeletal and other systems responsible for the body’s integrated response to exercise. In this review, we will focus on the clinical interpretation of CPET results as they relate to individuals with ACHD. We will also discuss the data supporting the use of 10.1586/14779072.2014.919223
CPET as a risk assessment tool in the growing population of adults with CHD. A brief overview of CPET
CPET measures the simultaneous response of the cardiovascular and respiratory systems to exercise. It must be performed in a dedicated testing laboratory using a specialized system with the capability to measure gas exchange, in addition to monitoring of physical working capacity, blood pressure and pulse oximetry. Continuous electrocardiographic monitoring is also performed during the test. Measurements of pulmonary function both at rest and exercise are routinely performed. All of these parameters are then integrated to identify sources of exercise limitation. The process of performing CPET is beyond the scope of general interest and is discussed in further detail elsewhere [3]. However, it is important for ordering clinicians to understand the impact of exercise modality on test results. CPET can be performed using either a cycle ergometer or a treadmill. Treadmill exercise testing is the more common modality in the USA, while cycle tests are more common in other areas [3]. A principal benefit of treadmill testing is a greater level of patient comfort and familiarity as compared with cycle testing. Untrained subjects will often terminate cycle testing due to quadriceps fatigue, achieving a
2014 Informa UK Ltd
ISSN 1477-9072
863
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nanyang Technological University on 04/24/15 For personal use only.
Review
Khan, Paridon & Kim
peak oxygen consumption (VO2peak), which is approximately 10–20% lower than that obtained by a treadmill test [3,4]. The principal drawback of treadmill testing is the inability to accurately measure work rate. The energy required for body movement at a given grade and speed is impacted by the multiple levels of communication between the subject and the treadmill during exercise (e.g., the handrails, blood pressure cuff and mouthpiece). The degree of this impact is difficult to quantify for any given exercise test and therefore obtaining an accurate measurement of work rate from a treadmill test is difficult. Artifact in ventilatory and circulatory measurements is also introduced by torso movement during exercise treadmill testing. While the risk of artifact may be higher with a treadmill test, the potential for technical errors, such as an erroneously low blood pressure or oxygen saturation at peak exercise, must be recognized on any CPET, regardless of testing modality. Safety may also be a concern in treadmill use on physically fragile patients. As mentioned above, the VO2peak obtained by a treadmill test is generally higher than that obtained by a cycle test [4,5]. Measured oxygen pulse and ventilatory threshold also tend to be higher on treadmill tests. This should be taken into account when comparing results across testing modalities and in the use of protocol appropriate normative data. Detailed discussions of exercise physiology are available elsewhere [3]. However, a basic understanding of this topic is required for the interpretation of test results. During exercise, the cardiac output increases to ensure sufficient oxygen delivery to the muscles. In normal individuals, augmentation of the cardiac output occurs via increases in both heart rate and stroke volume. In addition, blood flow is redirected away from less active tissue beds to exercising muscle, and oxygen extraction from the blood is increased. In order to adequately clear carbon dioxide (CO2) from the blood, the minute ventilation (VE) increases along with the work rate. In normal individuals, increased blood flow to the lungs is matched by an increase in VE, maintaining a balance between ventilation and perfusion. Ventilation–perfusion mismatch can occur in the setting of cardiac disease (increased ventilation is not matched by increased perfusion) or in the setting of pulmonary disease (increased perfusion is not adequately matched by increased ventilation). In the earlier stages of exercise, the oxygen uptake (VO2), the CO2 output, and the VE all increase linearly with the work rate. In the later stages of exercise, blood flow to the exercising muscles is inadequate to meet the demands of aerobic metabolism (~5 l/min of cardiac output per liter of VO2) and the muscles begin to metabolize anaerobically. At this point, the CO2 output increases more rapidly than the VO2 as a consequence of the need to buffer increased lactic acid production, an easily identifiable feature of the so-called ventilatory anaerobic threshold (VAT) on an exercise test. Standard CPET measures & their interpretation Peak work rate
The peak work rate is the maximal amount of power output (work/time) achieved by a subject during an exercise test. It is a 864
measure of the exercise capacity. The measurement of work rate is straightforward during cycle ergometry but more complicated during treadmill exercise. In treadmill exercise testing, the endurance time is used as a surrogate for work rate. This time can be compared with age- and gender-adjusted normal values, assuming that a standard protocol is utilized [6,7]. In CPET, other more descriptive measures, such as VO2peak, obviate the need to rely on exercise time as the primary measure of exercise capacity. Heart rate response
The identification of an abnormal heart rate response to exercise is of diagnostic importance in patients with ACHD [8]. An increase in heart rate and stroke volume is necessary to augment the cardiac output in response to exercise. An insufficient heart rate response to exercise results in a lower VO2peak. Clinically, this manifests as decreased exercise tolerance. In normal individuals, the heart rate increases linearly in response to exercise. The maximum expected heart rate at peak exercise is related roughly to age by the following equation: Peak heart rate = 220 – age (in years)
[Equation 1]
It is important to note that this formula is considered an estimate and may not be accurate in some populations [9,10]. Alternate formulas have been derived but are not in widespread use in clinical practice. Chronotropic incompetence (CI) refers to the inability of the heart rate to increase appropriately with exercise and is generally defined as failure to achieve at least 85% of the ageexpected maximum heart rate. The evidence suggests that CI is common in ACHD [11–13]. In one study of 345 adolescents and adults, 34% met criteria for CI, which in this study was defined as failure to reach 80% of the maximum predicted heart rate [13]. CI was most common in those with single ventricle physiology and those who had undergone an atrial switch procedure. It may also be seen in those lesions that require trans-section of the aorta as part of the repair such as the arterial switch operation (ASO) for D-transposition of the great arteries. These procedures disrupt the sympathetic innervation to the heart and may limit chronotropic response. Other methods of quantifying the chronotropic response to exercise include the heart rate reserve, the chronotropic index and the heart rate recovery. The calculation of these measures and the data supporting their use in ACHD is described in TABLE 1. Blood pressure
In normal individuals, the systolic blood pressure increases in response to exercise while the diastolic blood pressure remains relatively stable. The failure of the systolic blood pressure to increase at least 20–30 mmHg above resting levels or a fall in systolic blood pressure during exercise is considered abnormal. This finding, when present, may be related to severe dysfunction of the systemic ventricle or obstruction to aortic outflow. It can also be seen in the setting of myocardial ischemia or medications such as b-blockers. While current consensus guidelines do not specifically define a cut-off for a hypertensive response to exercise, Expert Rev. Cardiovasc. Ther. 12(7), (2014)
informahealthcare.com
Equal to the peak heart rate – resting heart rate; measures the ability of the heart rate to increase in response to exercise Equal to the difference between peak heart rate and the measured heart rate at a specific time in recovery. Reflects the reactivation of vagal tone after cessation of exercise
Normally occurs at 45–65% of VO2peak
ACHD-specific data are lacking although nomograms exist for normal individuals
>1.10 if a maximal test was achieved
