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* From the Departments of Cardiovascular Surgery (Drs. Ercisli, Vural, Sener, and Tasdemir) and Cardiology (Dr. Tufeckioglu), Yuksek Ihtisas Hospital of Turkey, Ankara, Turkey; and the Ankara Physical Medicine and Rehabilitation Education and Research Hospital (Drs. Gokkaya and Koseoglu), Ankara, Turkey.
Correspondence to: Kerem M. Vural, MD, N. Tandogan cad. 5/6 Kavaklidere, 06540 Ankara, Turkey; e-mail: kvural{at}tr.net
| Abstract |
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Design: The aerobic exercise capacity of 15 adult patients (mean [± SD] age, 21 ± 6; age range, 9 to 30 years) undergoing successful total correction at a mean age of 12 ± 5 years (patients) was compared to healthy, matched control subjects by using right ventricle echocardiography, resting spirometry, and cardiopulmonary exercise tests at a mean postoperative time of 7.5 ± 4.6 years.
Setting: Tertiary care referral centers.
Patients: Fifteen adult patients (mean age, 21 ± 6 years; age range, 9 to 30 years) undergoing successful total correction at a mean age of 12 ± 5 (patients) and 15 healthy, matched volunteers (control subjects).
Results: There was evidence for a slight right ventricular diastolic dysfunction in the patients. Mean FVC (88 ± 9% vs 109 ± 12% predicted, respectively) and FEV1 (89 ± 9% vs 109 ± 12% predicted, respectively), although being within the normal range, were also decreased in comparison to those of control subjects (p < 0.0001). Maximal oxygen consumption (
O2max) decreased in both groups (55 ± 16% vs 61 ± 23% predicted, respectively; p = 0.5); however, there were more individuals with severely decreased values among the patients (p = 0.05).
O2 at the anaerobic threshold was also decreased in patients (33 ± 15% vs 51 ± 8% predicted, respectively; p = 0.004). The maximum tolerable exercise time was 17.3 ± 4.5 min in patients vs 21.2 ± 6.4 min in control subjects (p = 0.06).
Conclusions: The exercise capacity after delayed repair was good in general compared to matched control subjects; however, exercise capacity may be slightly limited by ventilatory dysfunction, low anaerobic threshold, and lack of physical fitness despite New York Heart Association class improvement after undergoing the operation.
Key Words: exercise test exercise tolerance metabolism quality of life respiratory function tests tetralogy of Fallot
| Introduction |
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The primary goal of the present study was to investigate exercise tolerance in subjects after "delayed repair" of the tetralogy of Fallot, and to compare those results to an age-matched and sex-matched group of healthy subjects. To determine the distinct role of cardiac, respiratory, or peripheral factors in the multifactorial exercise capacity limitation, we studied right ventricle dynamics, lung function, and exercise performance both in patients and in an active, but non-sporting control group.
| Materials and Methods |
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Echocardiographic Evaluation of Right Ventricular Functions
Echocardiographic assessment was performed (GE Vingmed System Five; CVS; Aliso Viejo, CA) device, using two-dimensional echocardiography, pulsed wave Doppler echocardiography, continuous Doppler echocardiography, and tissue Doppler techniques. The right ventricular ejection fraction (RVEF) was calculated by single-plane volume subtraction method via the apical four-chamber view.
Resting Spirometry
Resting spirometry was repeated three times for each individual, and the best measurement was recorded. Before the exercise tests, resting spirometry (SensorMedics; Yorba Linda, CA) was conducted according to European Respiratory Society standards, and FVC, FEV1, forced expiratory flow rate (midexpiratory phase), peak expiratory flow rate, vital capacity, maximum voluntary ventilation (MVV), and tidal volume were measured. The results were also described as the percentage of predicted values calculated from equations that had been reported as norms.
Cardiopulmonary Exercise Test (Ergospirometry)
All individuals were subjected to a symptom-limited treadmill test on an electronically braked treadmill ergometer accompanied by a computerized module (
max 29; SensorMedics; Yorba Linda, CA), gradually increasing the exercise load to the point of fatigue, according to modified Bruce protocol. Previously published guidelines for contraindications and criteria for ending an exercise test were used.3 A standard open-circuit method was used to collect expired gas through a breathing apparatus mounted on a face mask. The analyzer was calibrated before each test using known concentrations of oxygen and carbon dioxide. Continuous measurements of expired gas values were analyzed at 20-s intervals. Oxygen saturation was measured via a photometer applied to the ear lobe.
Measured Parameters and Physiologic Limits:
During the test, measurements of BP, ECG, heart rate (HR), HR reserve (ie, predicted HR actual HR at peak exercise; considered abnormal if exceeds 15 beats/min), respiratory rate, oxygen consumption (
O2), maximum minute ventilation (
Emax), carbon dioxide output, respiratory exchange ratio (RER), and pulse oximetric saturation (SpO2), end-tidal carbon dioxide, end-tidal oxygen, and carbon dioxide production (
E/
CO2) were recorded continuously. A maximal
O2 (
O2max) level of < 85% predicted was considered to be under the normal limits, and a value < 60% was considered to be severely decreased. The
O2 value at the anaerobic threshold (
O2at) [ie, the
O2 value at which oxygen demand exceeds the ability of the circulation to sustain the aerobic metabolism and the anaerobic metabolism begin to support the exercise] was recorded (ie, the
O2at) and was considered to be abnormal if it was < 40% of the predicted
O2max. Breathing reserve (BR) was calculated as the percentage of the
Emax/MVV ratio and was interpreted as a ventilatory limitation to exercise if > 75%. The metabolic equivalent (MET) was calculated as follows: 1 MET equals 3.5 mL of O2/kg/min. The physiologic dead space ventilation (VD/VT), which is a useful parameter in determining ventilation/perfusion imbalance, was calculated at rest (VD/VTrest) and at peak exercise (VD/VTpeak). VD/VTrest values of > 0.3 to 0.4 and VD/VTpeak values of 0.19 to 0.21 were regarded as dead space ventilation. The decrease in SpO2 during exercise (
SpO2 = SpO2 at rest SpO2 at peak exercise) was regarded as abnormal if it was > 4%, and the exercise SpO2 was considered to be markedly decreased if it was < 84%.
RER was used as an "index of maximal exertion," since RER is an extremely useful guide to the exercise supervisor, indicating the ensuing attainment of exertion. Values of < 1.0 at peak exercise generally signify inadequate effort or poor motivation on the part of the patient. An RER value of 1.15 to 1.20 during exercise has been suggested as subsidiary evidence that a "true"
O2max has been attained.4
Statistical Analysis
All statistical analyses were performed using a statistical software package (SPSS, version 6.0; SPSS Inc; Chicago, IL). Values are given as the mean ± SD. Comparisons between the groups were made by Student t test, Wilcoxon matched pairs signed rank test, Mann Whitney U test,
2 test, and Fisher exact test where applicable. The Pearson correlation test was applied to analyze correlations among the parameters. A p value
0.05 was considered to be statistically significant.
| Results |
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Comparison Between the Patients and Control Subjects
There was no difference between the patients and control subjects in regard to sex, age, height, weight, hemoglobin level, and hematocrit level (Table 1
).
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O2max had been attained. This implied good reliability for the ergospirometric test.
O2max:
Although the mean difference between patients and control subjects was not significant statistically (27 ± 8 vs 27 ± 10 mL/kg/min, respectively; p = 0.9) [Table 4], there were more individuals with severely decreased (ie, < 60% of the predicted)
O2max among the patients (12 individuals) than among the control subjects (7 individuals; p = 0.05) [Table 5 , Fig 1
]. The mean
O2max for both patients and control subjects were below the predicted values.
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O2at:
The average
O2at was significantly decreased for patients (1.11 ± 0.45 L/min) compared to that for control subjects (1.57 ± 0.24 L/min; p = 0.02). The
O2at was 33 ± 15% predicted in patients vs 51 ± 8% predicted in control subjects (p = 0.006) [Tables 4 , 5, Fig 2
).
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HR: There was no significant difference between the groups in regard to average HR (in beats per minute or percent predicted) and HR reserve. The increase in HR as a response to exercise was abnormal in six patients and three control subjects (p = 0.2).
Emax:
No difference was detected between the groups in regard to mean
Emax (patients, 70 ± 20 L/min; control subjects, 91 ± 42 L/min; p = 0.09) and its percent predicted (patients, 62 ± 12% predicted; control subjects, 66 ± 21% predicted; p = 0.4).
BR (
Emax/MVV Ratio):
The mean BR was 62 ± 12% in patients vs 66 ± 21% in control subjects (p = 0.4), with values well within the normal range in both groups.
E/
CO2 Ratio:
The
E/
CO2 ratio was abnormal (> 40) in four patients and one control subject (p = 0.3). The mean
E/
CO2 ratio was higher in patients (39.5 ± 6.8) than in control subjects (31.8 ± 4.9; p = 0.01).
VD/VTrest and VD/VTpeak: The mean VD/VTrest was higher in patients (0.53 ± 0.04) than in control subjects (0.46 ± 0.08; p = 0.004). VD/VTrest was abnormal in 14 patients and 11 control subjects (p = 0.05). The mean VD/VTpeak was 0.25 ± 0.09 in patients and 0.19 ± 0.10 in control subjects (p = 0.1). The VD/VTpeak was abnormal in 12 patients five control subjects (p = 0.004). These results represent a ventilation/perfusion mismatch due to insufficient ventilation and probably VD/VT both at rest and at peak exercise.
SpO2:
Mean resting SpO2 (patients, 94 ± 4%; control subjects, 93 ± 4%; p = 0.4), SpO2 at peak exercise (patients, 84.93 ± 3.15%; control subjects, 85.64 ± 2.85%; p = 0.5), and respiratory rate at peak exercise (patients, 44 ± 5 breaths/min; control subjects, 40 ± 9 breaths/min; p = 0.2) did not differ between the groups. Exercise SpO2 was within normal limits (> 84%) in both groups. However, the
SpO2 exceeded 4% in both patients (9.2 ± 5.5%) and control subjects (6.9 ± 5.6%).
The mean maximum tolerable exercise duration was 17.3 ± 4.5 min in patients vs 21.2 ± 6.4 min in control subjects (p = 0.06). The reason for the termination of the test was general fatigue in all subjects. A positive correlation existed between age and exercise duration (r = 0.446; p = 0.013). Please refer to Tables 4and 5 for more detailed ergospirometric data.
| Discussion |
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Having a sufficient physical activity level during everyday life is essential to cope with the necessities of social, business, and private life. The cardiac limitations in patients with tetralogy of Fallot are expected to improve to a great extent after total correction; however, there are references to decreased aerobic capacity despite greatly improved NYHA functional class in these patients even after a successful repair. Among the possible reasons are residual lesions or surgical complications.346 After eliminating the presence of such factors by hemodynamic examinations, efforts should be directed toward the assessment of exercise response and the possible factors responsible for this limitation. There are three major determinants of exercise tolerance, namely, cardiac, respiratory, and peripheral (ie, skeletal muscle) factors.7
Exercise testing is a useful objective marker of functional capacity in patients undergoing surgical corrective procedures for congenital heart disease.8910 In this study, cardiopulmonary exercise tests were performed in 15 patients undergoing total corrective surgery to assess their exercise capacity and to compare them to an active, non-sporting, age-matched and sex-matched group. We studied possible relations among ventilation, exercise capacity, and right ventricular function. Among the possible limitations of this study are the relatively small sampling population and the lack of comparison to preoperative ergospirometry due to the potential hazards of strenuous exercise on a population with uncorrected cyanotic heart disease.
There are many references to the benefits of early repair in this subset of patients.12 James et al1 demonstrated an inverse correlation between the age at operation and exercise capacity. Others have reported5 no influence of the age at operation on oxygen use during exercise and exercise capacity. Another parameter that may be affected by the age of the subject at the time of surgery is exercise capacity and duration. Rowe et al5 suggested that undergoing surgery before the age of 11 years does not have a negative impact on exercise tolerance, but that after that age there may remain sequelae in exercise capacity due to long-lasting myocardial hypoxia. Our patients underwent surgical repair at a considerably old age (mean age at operation: 12 ± 5 years), and therefore we aimed to investigate the extent to which they benefited from the delayed repair.
Impaired right heart function due to residual lesions or developmental issues is one factor that is held responsible for poor exercise capacity in these patients.5611 However, we found that, apart from slightly disturbed diastolic functions, the right ventricular functions were very much in the normal range. The decrease in the average RVEF in patients compared to that in control subjects was significant statistically, but not clinically. Further, ejection fraction is a highly afterload-dependent parameter, and the right ventricular afterload in patients was higher than that in control subjects due to mild residual outflow gradients. There is a good possibility that intracavitary right ventricular pressure may further increase during exercise, and this may also contribute to the exercise limitation.
There have been reports emphasizing the role of decreased pulmonary capacity on limited exercise tolerance. After total surgical correction, NYHA class improves to a great extent in these patients; however, the ventilatory parameters may remain limited during exercise as well as at rest as revealed by spirometry due to residual lung pathology.512 Zapletal et al12 and Hruda et al13 found abnormal resting spirometry in 93% of the preoperative patients and in 83% of the postoperative patients undergoing intracardiac repair for tetralogy of Fallot. They interpreted these results as a sign of permanent sequelae of early lung damage from abnormal pulmonary hemodynamics. Right ventricular outflow tract obstruction in patients with tetralogy of Fallot is associated with low pulmonary blood flow, which may lead to poor bronchopulmonary tree and parenchymal development as well as small airway obstruction.21415 Although the gas-exchange unit is believed to continue its development until the age of 8 years, the great majority of our patients were beyond that age. At that point, the retardation may not compensable. Therefore, correction at an earlier age is also preferred for a normal pulmonary development. According to Lillehei and colleagues,16 a relatively low residual peak systolic pulmonary gradient (ie, < 20 mm Hg) leads to a normal pulmonary artery and annulus development, while high residual gradients tend to increase with time. Lillehei et al16 emphasized the importance of the amount of pulmonary blood flow on the development of the pulmonary artery and its branches. In this context, a relatively low residual gradient and mild pulmonary insufficiency in our series may be the reason for the seemingly unrestricted development of main pulmonary arteries and, consequently, their almost equal diameters in comparison to those of control subjects. Therefore, negatively affected pulmonary parenchymal development due to underlying right-sided cardiac malformation is not expected if this has not already occurred before the surgical correction. In our study, although the resting spirometry revealed significantly lower FVC and FEV1 values in patients than in control subjects, they were within normal predicted range. Further, BR was within the normal range in both groups, implying no respiratory limitation to exercise.
There remains another determinant of exercise tolerance; the peripheral factors, which can be expressed as skeletal muscle condition. Our study revealed low
O2max values as well as
O2at values, not only in patients undergoing total corrective surgery but also in the healthy matched control subjects, most probably due to sedentary lifestyle and lack of physical fitness in both groups. RER values of approximately 1.1 imply a good motivation to exercise and that a satisfactory level of effort has been achieved by the subjects.3 Another important parameter in estimating exercise tolerance is exercise duration. There was a difference of borderline significance (p = 0.06) between the patients and the healthy control subjects in terms of the mean maximum tolerable exercise duration (17.3 ± 4.5 vs 21.2 ± 6.4 min, respectively). Further, there were significantly more subjects with abnormally decreased
O2max among the patients (n = 12) than among control subjects (n = 7; p = 0.05). Again, the
O2at was significantly lower in patients than in control subjects (p = 0.006). Therefore, a limitation to exercise to some degree should be present in these patients. The reason that the difference did not become significant in terms of
O2max may be the limited number of subjects in the sampling volume.
| Conclusion |
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This implies that the pathologic responses that are not manifested during daily life may be possible to uncover by cardiopulmonary exercise testing. The poor exercise tolerance in our patients may be due partly to the lack of a continuous postoperative cardiovascular and pulmonary rehabilitation program. Therefore, we think that patients should enter a complete postoperative cardiopulmonary rehabilitation program and be encouraged to exercise, as far as their hemodynamic condition allows, since it has been proven possible to greatly improve the exercise tolerance in these patients by establishing a reasonable, appropriate cardiopulmonary rehabilitation program.91718 The information obtained by ergospirometry is not only useful in the evaluation of these patients, but is also necessary to establish safe, yet effective exercise guidelines for postoperative rehabilitation.
| Footnotes |
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E/
CO2 = carbon dioxide production;
Emax = maximum minute ventilation;
O2 = oxygen consumption;
O2at = oxygen consumption at the anaerobic threshold;
O2max = maximal oxygen consumption Received for publication November 2, 2004. Accepted for publication January 12, 2005.
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