- Email: [email protected]
Aerobic capacity in adults with various congenital heart diseases
Aerobic Capacity in Adults With Various Congenital Heart Diseases Per Morten Fredriksen, PT, EP PhD, Gruschen Veldtman, MD, Sloane Hechter, BSc, Judith Therrien, MD, Alice Chen, BSc, Mohammed Ali Warsi, MSc, Marc Freeman, MD, Peter Liu, MD, Samuel Siu, MD, Erik Thaulow, MD, PhD, and Gary Webb, MD As an increasing number of patients with congenital heart disease reach adulthood, more information is needed regarding outcomes. The first signs of impaired heart function may appear during exercise testing. The aim of the present study was to establish mean values for maximal oxygen uptake in adults with various congenital heart diseases. Patients from 6 major diagnostic groups were identified, including patients with atrial septal defect (ASD, n ⴝ 93), transposition of the great arteries corrected with the Mustard procedure (n ⴝ 84), congenitally corrected transposition of the great arteries (CCTGA, n ⴝ 41), Tetralogy of Fallot (n ⴝ 168), Ebstein’s anomaly (n ⴝ 37), and Modified Fontan procedure (n ⴝ 52). Diminished maximal oxygen uptake was found in all diagnostic groups across age compared with healthy subjects. A significant decrease in maximal oxygen uptake with aging was found in those with ASD (p <0.0001), CCTGA (p ⴝ 0.01), and Tetralogy of Fallot (p
<0.0001). There was no significant decline, however, in Ebstein’s anomaly (p ⴝ 0.270), Fontan procedure (p ⴝ 0.182), and in the Mustard patients (p ⴝ 0.188). All patients achieved significantly lower heart rates than predicted (mean for all groups, p <0.0001). Forced vital capacity values (3.51 L, mean SD ⴞ 1.02) were lower than predicted values (4.10 L, mean SD ⴞ 0.90, p <0.0001) for all patients groups except those with ASD. Mean values, however, were within the accepted 20% range of variance. This study showed diminished aerobic capacity in all diagnostic groups when compared with a healthy population. The maximal oxygen uptake values across age groups can be used as reference values in patients with similar diagnoses and as the basis for further research. 䊚2001 by Excerpta Medica, Inc. (Am J Cardiol 2001;87:310 –314)
n increasing body of information is available with respect to the prognoses of the different A congenital heart disease diagnoses. Congenital heart
strated by a decreasing aerobic capacity. Exercise capacity in patients with congenital heart disease compared with a healthy population is not always meaningful. It may therefore be of interest to establish mean values for different diagnostic groups. These reference values may give important information against which to compare an individual patient’s exercise capacity with comparable physiology and circulation. Although detailed analysis of each patient group has been completed, the aim of this study was to establish reference values of aerobic capacity and lung function in adults with various congenital heart diseases.
1
disease comprises a very heterogenous group, from simple atrial septal defect (ASD) to more complex diagnoses such as congenitally corrected transposition of the great arteries (CCTGA), Tetralogy of Fallot (ToF), transposition of the great arteries corrected with the Mustard procedure (Mustard), Ebstein’s anomaly, and Fontan circulation (Fontan). Previous papers have shown a diminished aerobic capacity and lung function in children, adolescents, and adults with various congenital heart diseases compared with a healthy population.2–12 Less information is available on the course of aerobic capacity across age groups in adults. Most clinical strategies used to assess heart function are based on variables measured at rest. However, it may be that the first signs of impaired heart function appear during exercise testing, demonFrom the University Health Network, University of Toronto Cardiac Centre for Adults, Ontario, Canada; and Rikshospitalet, The National Hospital, University of Oslo, Oslo, Norway. This study was supported in part by The Norwegian Association for Children with Congenital Heart Disorder, The Norwegian Lung and Heart Association, the National Foundation of Public Health in Norway, Oslo, Norway; and The National Heart Research Fund, Leeds, United Kingdom. Manuscript received May 18, 2000; revised manuscript received and accepted August 14, 2000. Address for reprint: Gary Webb, MD, The Toronto General Hospital (University Health Network), University of Toronto Congenital Cardiac Centre for Adults, 200 Elizabeth Street, 12th-215 EN, Toronto, Ontario, M5G 2C4, Canada. E-mail: [email protected].
310
©2001 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 87 February 1, 2001
METHODS
Patient population: A total of 5,733 patients are listed in the database at the University of Toronto Congenital Cardiac Center for Adults. Listed patients include inactive and actively followed patients. Late mortality (⬎18 years) occurred in 295 patients. Cardiopulmonary exercise tests were performed in 475 patients (230 male and 245 female patients) who attended the clinic as outpatients for follow-up and enrolled in the study. Six major diagnostic groups: ASD, CCTGA, Ebstein, Fontan, Mustard, and repaired ToF were identified (Table 1). The median age at test was 30 years (range 16 to 71) and median age at surgery was 9 years (range 0 to 72). More details are listed in Table 2. The exercise tests were conducted over a 14-year period (1985 to 1999), with most tests performed during 1998 to 1999 (61%). Patients were 0002-9149/01/$–see front matter PII S0002-9149(00)01364-3
brated before tests using known values of oxygen and carbon dioxide. During the test, heart rate and ventiListed Mortality Inactive Active Exercise Test lation were measured continuously. Patients ⬎18 Yrs (%) Patients Patients (% of active) Measurements of maximal blood ASD 540 19 (3.5) 368 172 93 (54.1) pressure were obtained in Mustard, CCTGA 131 28 (21.4) 26 58† 41 (70.1) CCTGA, and Fontan patients, but Ebstein 97 7 (9.5) 8 82 37 (45.1) not in ASD, Ebstein, and ToF paFontan 131 17 (13.0) 24 107 52 (48.6) ‡ tients; thus, it was not a part of the Mustard 152 15 (9.9) 25 117 84 (71.8) ToF 494 35 (7.1) 87 372 168 (45.2) procedure in these patients. Oxygen saturation was obtained using a finTotal 1,545 121 (7.2) 538 908 475 (52.3) ger probe (Nellcor Puritan Bennet *This table also represents the number of patients used in this study. The ASD group is patients with NPB290, St. Louis, Missouri) in all only ASD (closed or open) and no associated diseases. † groups except in patients with ASD, Seventeen were excluded because of Fontan procedure, 1 patient had a heart transplant, and 1 had a heart and lung transplant. because this was not a part of their ‡ Five of the deceased patients are registered as active in the table because exercise data exist. Listed test procedure. Before the exercise patients are all patients in the database. Active patients are patients who are actively followed at a tests, spirometry (Sensor-Medics, regular basis. Yorba Linda California) tests were conducted according to American Thoracic Society standards with measurements of forced expiratory volume in 1 secTABLE 2 Descriptive Data Including Gender Distribution, Age ond and forced vital capacity (FVC). All patients at Test, and Age at Surgery started at 20 W for warm-up for the first minute. Age at Age at Workload was increased by 20 W every 2 minutes Men Women Test (yrs) Surgery (yrs)* until the patient experienced leg fatigue or other limASD 30 63 41 (17–71) 25 (1–72) iting symptoms. The American College of Sports CCTGA 25 23 31 (19–55) 12 (1–49) Medicine guidelines for ending an exercise test were Ebstein 27 46 33 (18–50) 34 (8–45) followed.14 Fontan 27 25 27 (18–45) 18 (5–36) Statistics: Data were analyzed using SPSS 9.0 for Mustard 56 28 23 (18–38) 2 (1–10) ToF 87 80 32 (19–64) 7 (1–55) Windows (SPSS Inc., Chicago, Illinois). Median values with range were used descriptively to compare *Only those who underwent surgery are included. maximal oxygen consumption in patients with a healthy population. Differences in FVC and maximal heart rate between patients and predicted values were TABLE 3 Number of Patients with Measurements in Each Variable analyzed with the Student’s t test. Max. Max. Analysis of maximal oxygen conMax. Max. Systolic Diastolic sumption across age groups and diOxygen Heart Blood Blood Oxygen agnostic groups was done with Uptake Rate Pressure Pressure Saturation % FVC 1-way analysis of variance. Multi(ml 䡠 kg⫺1min⫺1) (beats/min) (mm Hg) (mm Hg) (%) Predicted variate linear regression modeling All 459 459 141 141 265 462 (stepwise backward elimination seASD 93 93 — — — 93 lection procedure) was used to examCCTGA 29 29 27 27 24 32 Ebstein 37 37 — — 29 37 ine the relation between age at test, Fontan 51 51 39 39 23 52 maximal heart rate, gender, FVC, Mustard 81 81 75 75 35 80 and outcome variable of maximal ToF 168 168 — — 154 168 oxygen consumption in all groups in Max. ⫽ maximal. aggregate adjusted for lesion type. In analysis of these cross-sectional data, the age of the patients was used as a also subdivided into a surgical group (palliative and surrogate for time as it would have been used in a repaired procedures) and a nonsurgical group to assess longitudinal dataset. Pearson’s correlation was used to the differences in measured values (Table 2). The determine the relation between maximal oxygen connumber of patients tested within each variable is dis- sumption and maximal heart rate. A p value ⬍0.05 played in Table 3. The reference values were obtained was regarded as statistically significant. from a Canadian survey of 23,000 people in 1988. Cardiopulmonary test: Cardiopulmonary tests were RESULTS performed at Toronto General Hospital on an ergomeAerobic capacity: A significant decrease in maximal ter cycle (Elema, Solna, Sweden). Continuous mea- oxygen consumption with aging was found in patients surements of expired gas values were analyzed every with ASD (p ⬍0.0001), CCTGA (p ⫽ 0.01), and ToF 30 seconds (Amtech VO2 Oxygen Analyzer S-3A/I, (p ⬍0.0001). In Ebstein (p ⫽ 0.270), Fontan (p ⫽ Pittsburgh, Pennsylvania). The analyzer was cali- 0.182) and Mustard (p ⫽ 0.188) patients, however, no TABLE 1 Distribution of Various Diagnostic Groups at The Toronto Congenital Cardiac Centre for Adults*
CONGENITAL HEART DISEASE/AEROBIC CAPACITY WITH CONGENITAL HEART DISEASE
311
FIGURE 1. Median maximal oxygen uptake in all patient groups compared with normal values. All values are the median of men and women. The healthy values are from a Canadian population (n ⴝ 23,000). The table shows the number of patients in each age group.
significant decline was observed. Compared with healthy subjects, severely diminished maximal oxygen Max. Max. consumption values were found in Max. Max. Systolic Diastolic all diagnostic groups across age (FigOxygen Heart Blood Blood Oxygen ure 1). There was a large variation in Uptake Rate Pressure Pressure Saturation % FVC (ml 䡠 kg⫺1 min⫺1) (beats/min) (mm Hg) (mm Hg) (%) Predicted the results of maximal oxygen consumption in all groups (mean range All 19.8 ⫾ 6.9 146 ⫾ 28 161 ⫾ 29 80 ⫾ 20 94 ⫾ 5 85 ⫾ 17 from 6 to 45 ml 䡠 kg ⫺1 䡠 min⫺1), with ASD 19.8 ⫾ 7.3 146 ⫾ 30 — — — 97 ⫾ 20 CCTGA 19.7 ⫾ 7.4 142 ⫾ 28 152 ⫾ 19 81 ⫾ 13 92 ⫾ 8 84 ⫾ 15 the Fontan group showing the signifEbstein 18.6 ⫾ 7.1 144 ⫾ 30 — — 92 ⫾ 4 77 ⫾ 3 icantly lowest values (Table 4 and Fontan 15.9 ⫾ 4.0 139 ⫾ 25 150 ⫾ 30 77 ⫾ 18 87 ⫾ 5 74 ⫾ 17 Figure 1). When analyzing the effect Mustard 20.0 ⫾ 6.3 147 ⫾ 25 170 ⫾ 29 86 ⫾ 23 89 ⫾ 5 81 ⫾ 13 of patients who underwent the MusToF 21.1 ⫾ 7.2 149 ⫾ 27 — — 94 ⫾ 3 84 ⫾ 17 tard procedure, repaired ToF and *Men and women are analyzed together. The number of patients is listed in Table 3. Fontan circulation were not included. Max. ⫽ maximal. Within each of the other groups (ASD, Ebstein, and CCTGA), no statistical differences were found with respect to surgical interventions performed and the variables of maximal oxygen consumption and FVC. Heart rate: All patients achieved significantly lower heart rate than predicted (mean heart rate obtained was 146 beats/min (mean ⫾ SD, 28) versus mean heart rate predicted 187 beats/min (mean ⫾ SD, 11; p ⬍0.0001). However, Figure 2 shows an overall significant relation between maximal oxygen consumption and maximal heart rate (r ⫽ 0.48, p ⬍0.0001). Within each diagnostic group the relation varied between r ⫽ 0.27 and 0.54; these were significant except for the Fontan patients (p ⫽ 0.059). Lung function: The obtained values of FVC (SD 3.51 ⫾ 1.02) in most patients with congenital heart disease were significantly lower than predicted values (SD 4.10 ⫾ 0.90, p ⬍0.0001). However, patients with ASD achieved approximately the same values as preFIGURE 2. Relation between heart rate and maximal oxygen updicted. In Fontan and Ebstein patients and in the older take (VO2max) in patients with congenital heart disease. mls ⴝ Mustard patients the values of percent-predicted FVC maximal oxygen uptake in milliliter 䡠 minⴚ1) TABLE 4 Mean ⫾ SD Exercise Test and Static Lung Function Data for the Entire Sample, Subdivided into Diagnostic Groups
312 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 87
FEBRUARY 1, 2001
FIGURE 3. FVC for all patient groups are shown in percentage of predicted values.14 The table shows the number of patients in each age group.
were much lower than mean predicted values (Table 4 and Figure 3).
DISCUSSION In the present study severely diminished aerobic capacity was revealed in all groups with congenital heart disease compared with a healthy population. A similar pattern was found regarding static lung function. Aerobic capacity: The severely diminished values of maximal oxygen consumption in some of the diagnoses compared with values in healthy subjects were somewhat surprising. Even patients with closed ASDs did not do as well as healthy subjects. One might expect that at least patients with surgically corrected ASD would obtain near-normal values, as reported by other investigators.10,15 Diminished maximal oxygen consumption in these patients may be due to an abnormal increase in pulmonary artery pressure during exercise.16 Reduced daily physical activity level may also partially explain the low values. Our study does not show a decrease in maximal oxygen consumption with age in the Ebstein, Fontan, and Mustard patients. The number of Ebstein patients in the 2 oldest groups was small (5 and 3 patients, respectively), which may explain why there was no significant change, even though the slope decreases in Figure 1. The increased maximal oxygen consumption shown in the oldest Mustard patients may be explained by the number of men in that age group (7 of 8 patients), because men have higher mean maximal oxygen consumption than women.2 In the Fontan patients, other investigators have previously reported the absence of a decline with age in maximal oxygen
consumption as well.17 However, results opposing this have also been stated.18 The severely reduced cardiac output may mask the effect of age. Significant differences with regard to maximal oxygen consumption were found between the diagnostic groups, with the lowest values in the Fontan patients. These results can be expected because of the limited ability to increase cardiac output in patients with 1 ventricle or without a right ventricle. The other groups showed no large differences. These findings indicate that despite the different anatomy and physiology associated with these conditions, other factors may contribute to diminished aerobic capacity. A low level of daily physical activity may partly explain these results. Obscure peripheral factors may be a result of such low activity levels, and will negatively affect the exercise capacity. The most important use of cardiopulmonary tests is therefore to perform serial measurements of the same patients. The results should be compared to reveal changes over time. As the present data show, a decrease in maximal oxygen consumption with age is expected in some diagnoses. However, an abrupt decline or a steeper decrease than expected should be treated with caution and adequate treatment should be initiated. To reveal significant changes, cardiopulmonary tests should be performed at every consultation as a routine follow-up of patients with any type of congenital heart disease. Heart rate: The relation between maximum heart rate and maximal oxygen consumption indicates that chronotropic incompetence may partly explain the diminished aerobic capacity in the different diagnostic groups. This is in agreement with a previous study.2
CONGENITAL HEART DISEASE/AEROBIC CAPACITY WITH CONGENITAL HEART DISEASE
313
Lung function: Except with the ASD patients, all groups had diminished lung function compared with normal values. The data in the present study show normal lung function in the ASD group; however, there have been reported reduced lung function values in patients with ASD as well.9 The severely diminished FVC in the Fontan patients, which is also reported by others, may be due to a restrictive respiratory pattern.19,20 Diaphragmatic palsy after surgery, respiratory muscle weakness, or a restrictive thoracic cage may also contribute to their limitations. Oxygen saturation: Overall, patients with congenital heart disease had reduced oxygen saturation at maximum exercise compared with the expected 97% to 100% (Table 4). The Fontan patients showed severely depressed saturation at maximal exercise as reported by other investigators.21 It has been suggested that, in the absence of a right-to-left shunt, the decrease in saturation may be due to abnormal distribution and perfusion in the lung.19 More surprising was the desaturation in the Mustard patients. A possible explanation could be a leak in the baffle. Interestingly, in an analysis of a subgroup of Mustard patients undergoing ultrasound, no leak was noted. A baffle leak during exercise could explain this phenomenon; however, information in this area is lacking. Investigations into this hypothesis are currently under way at the University of Toronto Congenital Cardiac Center for Adults. Study limitations: The values are based on a crosssectional sample, and not on a longitudinal sample, which may contribute to the relatively large variation in the results. The variation across age groups may be due to the limited number of patients in some of the oldest age groups. An unequal distribution of men and women in some age groups could also contribute to the large variation in the Mustard cohort. This study is limited by the follow-up constraints inherent in caring for adults with congenital heart diseases. Many of our patients reside outside Toronto, and those that are well may be less interested in returning to our center for cardiopulmonary testing. Our 475 patients may therefore represent a biased sample toward patients with functional limitations and poor exercise capacity. Conclusion: This study revealed severely diminished aerobic capacity in all diagnostic groups when compared with a healthy population. Declining values with aging were displayed in ToF, ASD, and CCTGA patient groups. Possible explanations for the reduced values are low habitual physical activity level, chronotropic incompetence, and diminished lung volumes. Cardiopulmonary testing as a routine follow-up
314 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 87
should be mandatory to reveal changes in exercise capacity as a sign of diminishing cardiac function. The maximal oxygen consumption values across age groups for the various congenital heart diseases can be used as reference values and for further research. 1. Dore A. Adult congenital heart disease: a new challenge. Perspect Cardiol 1999;15:43–51. 2. Fredriksen PM, Ingjer F, Nystad W, Thaulow E. A comparison of VO2peak between patients with CHD and healthy subjects, all aged 8 –17 years. Eur J Appl Physiol 1999;80:409 – 416. 3. Driscoll DJ, Offord KP, Feldt RH, Schaff HV, Puga FJ, Danielson GK. Fiveto fifteen-year follow-up after Fontan operation. Circulation 1992;85:469 – 496. 4. Harrison DA, Liu P, Walters JE, Goodman JM, Siu SC, Webb GD, Williams WG, McLaughlin PR. Cardiopulmonary function in adult patients late after Fontan repair. J Am Coll Cardiol 1995;26:1016 –1021. 5. Weipert J, Koch W, Haehnel JC, Meisner H. Exercise capacity and mid-term survival in patients with tricuspid atresia and complex congenital cardiac malformations after modified Fontan-operation. Eur J Cardiothorac Surg 1997;12: 574 –580. 6. Conte S, Jashari R, Eyskens B, Gewillig M, Dumoulin M, Daenen W. Homograft valve insertion for pulmonary regurgitation late after valveless repair of right ventricular outflow tract obstruction. Eur J Cardiothorac Surg 1998;15: 143–149. 7. Bjarke B. Oxygen uptake and cardiac output during submaximal and maximal exercise in adult subjects with totally corrected tetralogy of Fallot. Acta Med Scand 1975;197:177–186. 8. Wessel HU, Paul MH. Exercise studies in tetralogy of Fallot: a review. Pediatr Cardiol 1999;20:39 – 47. 9. Sulc J, Andrle V, Hruda J, Hucin B, Samanek M, Zapletal A. Pulmonary function in children with atrial septal defect before and after heart surgery. Heart 1998;80:484 – 488. 10. Helber U, Baumann R, Seboldt H, Reinhard U, Hoffmeister HM. Atrial septal defect in adults: cardiopulmonary exercise capacity before and 4 months and 10 years after defect closure. J Am Coll Cardiol 1997;29:1345–1350. 11. Nakanishi N, Yoshioka T, Fujii T, Hashizume T, Okano Y, Oozono K, Takaki H, Tamai J, Okubo S, Kunieda T. Comparison of exercise capacity evaluated by cardiopulmonary exercise test and hemodynamic parameters in patients with atrial septal defect. Kokyu to Junkan. Respir Circ 1992;40:789 –795. 12. Paridon SM, Humes RA, Pinsky WW. The role of chronotropic impairment during exercise after the Mustard operation. J Am Coll Cardiol 1991;17:729 –732. 13. Jones NL. The interpretation of stage 1 exercise test results. In: Trumbold C, ed. Clinical Exercise Testing. 1st ed. Philadelphia: WB Saunders, 1988:158 –185. 14. James FW, Blomqvist CG, Freed MD, Miller WW, Moller JH, Nugent EW, Riopel DA, Strong WB, Wessel HU. Standards for exercise testing in the pediatric age group. American Heart Association Council on Cardiovascular Disease in the Young. Ad hoc committee on exercise testing. Circulation 1982; 66:1377A-1397A. 15. Reybrouck T, Bisschop A, Dumoulin M, Van der Hauwaert LG. Cardiorespiratory exercise capacity after surgical closure of atrial septal defect is influenced by the age at surgery. Am Heart J 1991;122:1073–1078. 16. Oelberg DA, Marcotte F, Kreisman H, Wolkove N, Langleben D, Small D. Evaluation of right ventricular systolic pressure during incremental exercise by Doppler echocardiography in adults with atrial septal defect. Chest 1998;113: 1459 –1465. 17. Nir A, Driscoll DJ, Mottram CD, Offord KP, Puga FJ, Schaff HV, Danielson GK. Cardiorespiratory response to exercise after the Fontan operation: a serial study. J Am Coll Cardiol 1993;22:216 –220. 18. Warnes CA. Tricuspid atresia and univentricular heart after the Fontan procedure. Cardiol Clin 1993;11:665– 673. 19. Shachar GB, Fuhrman BP, Wang Y, Lucas RVJ, Lock JE. Rest and exercise hemodynamics after the Fontan procedure. Circulation 1982;65:1043–1048. 20. Fredriksen PM, Therrien J, Veldtman G, Warsi MA, Liu P, Siu S, Williams W, Granton J, Webb GD. Lung function and aerobic capacity in adult patients following modified Fontan procedure. Heart 2001; in press. 21. Iserin L, Chua TP, Chambers J, Coats AJ, Somerville J. Dyspnoea and exercise intolerance during cardiopulmonary exercise testing in patients with univentricular heart. The effects of chronic hypoxaemia and Fontan procedure. Eur Heart J 1997;18:1350 –1356.
FEBRUARY 1, 2001
<0.0001). There was no significant decline, however, in Ebstein’s anomaly (p ⴝ 0.270), Fontan procedure (p ⴝ 0.182), and in the Mustard patients (p ⴝ 0.188). All patients achieved significantly lower heart rates than predicted (mean for all groups, p <0.0001). Forced vital capacity values (3.51 L, mean SD ⴞ 1.02) were lower than predicted values (4.10 L, mean SD ⴞ 0.90, p <0.0001) for all patients groups except those with ASD. Mean values, however, were within the accepted 20% range of variance. This study showed diminished aerobic capacity in all diagnostic groups when compared with a healthy population. The maximal oxygen uptake values across age groups can be used as reference values in patients with similar diagnoses and as the basis for further research. 䊚2001 by Excerpta Medica, Inc. (Am J Cardiol 2001;87:310 –314)
n increasing body of information is available with respect to the prognoses of the different A congenital heart disease diagnoses. Congenital heart
strated by a decreasing aerobic capacity. Exercise capacity in patients with congenital heart disease compared with a healthy population is not always meaningful. It may therefore be of interest to establish mean values for different diagnostic groups. These reference values may give important information against which to compare an individual patient’s exercise capacity with comparable physiology and circulation. Although detailed analysis of each patient group has been completed, the aim of this study was to establish reference values of aerobic capacity and lung function in adults with various congenital heart diseases.
1
disease comprises a very heterogenous group, from simple atrial septal defect (ASD) to more complex diagnoses such as congenitally corrected transposition of the great arteries (CCTGA), Tetralogy of Fallot (ToF), transposition of the great arteries corrected with the Mustard procedure (Mustard), Ebstein’s anomaly, and Fontan circulation (Fontan). Previous papers have shown a diminished aerobic capacity and lung function in children, adolescents, and adults with various congenital heart diseases compared with a healthy population.2–12 Less information is available on the course of aerobic capacity across age groups in adults. Most clinical strategies used to assess heart function are based on variables measured at rest. However, it may be that the first signs of impaired heart function appear during exercise testing, demonFrom the University Health Network, University of Toronto Cardiac Centre for Adults, Ontario, Canada; and Rikshospitalet, The National Hospital, University of Oslo, Oslo, Norway. This study was supported in part by The Norwegian Association for Children with Congenital Heart Disorder, The Norwegian Lung and Heart Association, the National Foundation of Public Health in Norway, Oslo, Norway; and The National Heart Research Fund, Leeds, United Kingdom. Manuscript received May 18, 2000; revised manuscript received and accepted August 14, 2000. Address for reprint: Gary Webb, MD, The Toronto General Hospital (University Health Network), University of Toronto Congenital Cardiac Centre for Adults, 200 Elizabeth Street, 12th-215 EN, Toronto, Ontario, M5G 2C4, Canada. E-mail: [email protected].
310
©2001 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 87 February 1, 2001
METHODS
Patient population: A total of 5,733 patients are listed in the database at the University of Toronto Congenital Cardiac Center for Adults. Listed patients include inactive and actively followed patients. Late mortality (⬎18 years) occurred in 295 patients. Cardiopulmonary exercise tests were performed in 475 patients (230 male and 245 female patients) who attended the clinic as outpatients for follow-up and enrolled in the study. Six major diagnostic groups: ASD, CCTGA, Ebstein, Fontan, Mustard, and repaired ToF were identified (Table 1). The median age at test was 30 years (range 16 to 71) and median age at surgery was 9 years (range 0 to 72). More details are listed in Table 2. The exercise tests were conducted over a 14-year period (1985 to 1999), with most tests performed during 1998 to 1999 (61%). Patients were 0002-9149/01/$–see front matter PII S0002-9149(00)01364-3
brated before tests using known values of oxygen and carbon dioxide. During the test, heart rate and ventiListed Mortality Inactive Active Exercise Test lation were measured continuously. Patients ⬎18 Yrs (%) Patients Patients (% of active) Measurements of maximal blood ASD 540 19 (3.5) 368 172 93 (54.1) pressure were obtained in Mustard, CCTGA 131 28 (21.4) 26 58† 41 (70.1) CCTGA, and Fontan patients, but Ebstein 97 7 (9.5) 8 82 37 (45.1) not in ASD, Ebstein, and ToF paFontan 131 17 (13.0) 24 107 52 (48.6) ‡ tients; thus, it was not a part of the Mustard 152 15 (9.9) 25 117 84 (71.8) ToF 494 35 (7.1) 87 372 168 (45.2) procedure in these patients. Oxygen saturation was obtained using a finTotal 1,545 121 (7.2) 538 908 475 (52.3) ger probe (Nellcor Puritan Bennet *This table also represents the number of patients used in this study. The ASD group is patients with NPB290, St. Louis, Missouri) in all only ASD (closed or open) and no associated diseases. † groups except in patients with ASD, Seventeen were excluded because of Fontan procedure, 1 patient had a heart transplant, and 1 had a heart and lung transplant. because this was not a part of their ‡ Five of the deceased patients are registered as active in the table because exercise data exist. Listed test procedure. Before the exercise patients are all patients in the database. Active patients are patients who are actively followed at a tests, spirometry (Sensor-Medics, regular basis. Yorba Linda California) tests were conducted according to American Thoracic Society standards with measurements of forced expiratory volume in 1 secTABLE 2 Descriptive Data Including Gender Distribution, Age ond and forced vital capacity (FVC). All patients at Test, and Age at Surgery started at 20 W for warm-up for the first minute. Age at Age at Workload was increased by 20 W every 2 minutes Men Women Test (yrs) Surgery (yrs)* until the patient experienced leg fatigue or other limASD 30 63 41 (17–71) 25 (1–72) iting symptoms. The American College of Sports CCTGA 25 23 31 (19–55) 12 (1–49) Medicine guidelines for ending an exercise test were Ebstein 27 46 33 (18–50) 34 (8–45) followed.14 Fontan 27 25 27 (18–45) 18 (5–36) Statistics: Data were analyzed using SPSS 9.0 for Mustard 56 28 23 (18–38) 2 (1–10) ToF 87 80 32 (19–64) 7 (1–55) Windows (SPSS Inc., Chicago, Illinois). Median values with range were used descriptively to compare *Only those who underwent surgery are included. maximal oxygen consumption in patients with a healthy population. Differences in FVC and maximal heart rate between patients and predicted values were TABLE 3 Number of Patients with Measurements in Each Variable analyzed with the Student’s t test. Max. Max. Analysis of maximal oxygen conMax. Max. Systolic Diastolic sumption across age groups and diOxygen Heart Blood Blood Oxygen agnostic groups was done with Uptake Rate Pressure Pressure Saturation % FVC 1-way analysis of variance. Multi(ml 䡠 kg⫺1min⫺1) (beats/min) (mm Hg) (mm Hg) (%) Predicted variate linear regression modeling All 459 459 141 141 265 462 (stepwise backward elimination seASD 93 93 — — — 93 lection procedure) was used to examCCTGA 29 29 27 27 24 32 Ebstein 37 37 — — 29 37 ine the relation between age at test, Fontan 51 51 39 39 23 52 maximal heart rate, gender, FVC, Mustard 81 81 75 75 35 80 and outcome variable of maximal ToF 168 168 — — 154 168 oxygen consumption in all groups in Max. ⫽ maximal. aggregate adjusted for lesion type. In analysis of these cross-sectional data, the age of the patients was used as a also subdivided into a surgical group (palliative and surrogate for time as it would have been used in a repaired procedures) and a nonsurgical group to assess longitudinal dataset. Pearson’s correlation was used to the differences in measured values (Table 2). The determine the relation between maximal oxygen connumber of patients tested within each variable is dis- sumption and maximal heart rate. A p value ⬍0.05 played in Table 3. The reference values were obtained was regarded as statistically significant. from a Canadian survey of 23,000 people in 1988. Cardiopulmonary test: Cardiopulmonary tests were RESULTS performed at Toronto General Hospital on an ergomeAerobic capacity: A significant decrease in maximal ter cycle (Elema, Solna, Sweden). Continuous mea- oxygen consumption with aging was found in patients surements of expired gas values were analyzed every with ASD (p ⬍0.0001), CCTGA (p ⫽ 0.01), and ToF 30 seconds (Amtech VO2 Oxygen Analyzer S-3A/I, (p ⬍0.0001). In Ebstein (p ⫽ 0.270), Fontan (p ⫽ Pittsburgh, Pennsylvania). The analyzer was cali- 0.182) and Mustard (p ⫽ 0.188) patients, however, no TABLE 1 Distribution of Various Diagnostic Groups at The Toronto Congenital Cardiac Centre for Adults*
CONGENITAL HEART DISEASE/AEROBIC CAPACITY WITH CONGENITAL HEART DISEASE
311
FIGURE 1. Median maximal oxygen uptake in all patient groups compared with normal values. All values are the median of men and women. The healthy values are from a Canadian population (n ⴝ 23,000). The table shows the number of patients in each age group.
significant decline was observed. Compared with healthy subjects, severely diminished maximal oxygen Max. Max. consumption values were found in Max. Max. Systolic Diastolic all diagnostic groups across age (FigOxygen Heart Blood Blood Oxygen ure 1). There was a large variation in Uptake Rate Pressure Pressure Saturation % FVC (ml 䡠 kg⫺1 min⫺1) (beats/min) (mm Hg) (mm Hg) (%) Predicted the results of maximal oxygen consumption in all groups (mean range All 19.8 ⫾ 6.9 146 ⫾ 28 161 ⫾ 29 80 ⫾ 20 94 ⫾ 5 85 ⫾ 17 from 6 to 45 ml 䡠 kg ⫺1 䡠 min⫺1), with ASD 19.8 ⫾ 7.3 146 ⫾ 30 — — — 97 ⫾ 20 CCTGA 19.7 ⫾ 7.4 142 ⫾ 28 152 ⫾ 19 81 ⫾ 13 92 ⫾ 8 84 ⫾ 15 the Fontan group showing the signifEbstein 18.6 ⫾ 7.1 144 ⫾ 30 — — 92 ⫾ 4 77 ⫾ 3 icantly lowest values (Table 4 and Fontan 15.9 ⫾ 4.0 139 ⫾ 25 150 ⫾ 30 77 ⫾ 18 87 ⫾ 5 74 ⫾ 17 Figure 1). When analyzing the effect Mustard 20.0 ⫾ 6.3 147 ⫾ 25 170 ⫾ 29 86 ⫾ 23 89 ⫾ 5 81 ⫾ 13 of patients who underwent the MusToF 21.1 ⫾ 7.2 149 ⫾ 27 — — 94 ⫾ 3 84 ⫾ 17 tard procedure, repaired ToF and *Men and women are analyzed together. The number of patients is listed in Table 3. Fontan circulation were not included. Max. ⫽ maximal. Within each of the other groups (ASD, Ebstein, and CCTGA), no statistical differences were found with respect to surgical interventions performed and the variables of maximal oxygen consumption and FVC. Heart rate: All patients achieved significantly lower heart rate than predicted (mean heart rate obtained was 146 beats/min (mean ⫾ SD, 28) versus mean heart rate predicted 187 beats/min (mean ⫾ SD, 11; p ⬍0.0001). However, Figure 2 shows an overall significant relation between maximal oxygen consumption and maximal heart rate (r ⫽ 0.48, p ⬍0.0001). Within each diagnostic group the relation varied between r ⫽ 0.27 and 0.54; these were significant except for the Fontan patients (p ⫽ 0.059). Lung function: The obtained values of FVC (SD 3.51 ⫾ 1.02) in most patients with congenital heart disease were significantly lower than predicted values (SD 4.10 ⫾ 0.90, p ⬍0.0001). However, patients with ASD achieved approximately the same values as preFIGURE 2. Relation between heart rate and maximal oxygen updicted. In Fontan and Ebstein patients and in the older take (VO2max) in patients with congenital heart disease. mls ⴝ Mustard patients the values of percent-predicted FVC maximal oxygen uptake in milliliter 䡠 minⴚ1) TABLE 4 Mean ⫾ SD Exercise Test and Static Lung Function Data for the Entire Sample, Subdivided into Diagnostic Groups
312 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 87
FEBRUARY 1, 2001
FIGURE 3. FVC for all patient groups are shown in percentage of predicted values.14 The table shows the number of patients in each age group.
were much lower than mean predicted values (Table 4 and Figure 3).
DISCUSSION In the present study severely diminished aerobic capacity was revealed in all groups with congenital heart disease compared with a healthy population. A similar pattern was found regarding static lung function. Aerobic capacity: The severely diminished values of maximal oxygen consumption in some of the diagnoses compared with values in healthy subjects were somewhat surprising. Even patients with closed ASDs did not do as well as healthy subjects. One might expect that at least patients with surgically corrected ASD would obtain near-normal values, as reported by other investigators.10,15 Diminished maximal oxygen consumption in these patients may be due to an abnormal increase in pulmonary artery pressure during exercise.16 Reduced daily physical activity level may also partially explain the low values. Our study does not show a decrease in maximal oxygen consumption with age in the Ebstein, Fontan, and Mustard patients. The number of Ebstein patients in the 2 oldest groups was small (5 and 3 patients, respectively), which may explain why there was no significant change, even though the slope decreases in Figure 1. The increased maximal oxygen consumption shown in the oldest Mustard patients may be explained by the number of men in that age group (7 of 8 patients), because men have higher mean maximal oxygen consumption than women.2 In the Fontan patients, other investigators have previously reported the absence of a decline with age in maximal oxygen
consumption as well.17 However, results opposing this have also been stated.18 The severely reduced cardiac output may mask the effect of age. Significant differences with regard to maximal oxygen consumption were found between the diagnostic groups, with the lowest values in the Fontan patients. These results can be expected because of the limited ability to increase cardiac output in patients with 1 ventricle or without a right ventricle. The other groups showed no large differences. These findings indicate that despite the different anatomy and physiology associated with these conditions, other factors may contribute to diminished aerobic capacity. A low level of daily physical activity may partly explain these results. Obscure peripheral factors may be a result of such low activity levels, and will negatively affect the exercise capacity. The most important use of cardiopulmonary tests is therefore to perform serial measurements of the same patients. The results should be compared to reveal changes over time. As the present data show, a decrease in maximal oxygen consumption with age is expected in some diagnoses. However, an abrupt decline or a steeper decrease than expected should be treated with caution and adequate treatment should be initiated. To reveal significant changes, cardiopulmonary tests should be performed at every consultation as a routine follow-up of patients with any type of congenital heart disease. Heart rate: The relation between maximum heart rate and maximal oxygen consumption indicates that chronotropic incompetence may partly explain the diminished aerobic capacity in the different diagnostic groups. This is in agreement with a previous study.2
CONGENITAL HEART DISEASE/AEROBIC CAPACITY WITH CONGENITAL HEART DISEASE
313
Lung function: Except with the ASD patients, all groups had diminished lung function compared with normal values. The data in the present study show normal lung function in the ASD group; however, there have been reported reduced lung function values in patients with ASD as well.9 The severely diminished FVC in the Fontan patients, which is also reported by others, may be due to a restrictive respiratory pattern.19,20 Diaphragmatic palsy after surgery, respiratory muscle weakness, or a restrictive thoracic cage may also contribute to their limitations. Oxygen saturation: Overall, patients with congenital heart disease had reduced oxygen saturation at maximum exercise compared with the expected 97% to 100% (Table 4). The Fontan patients showed severely depressed saturation at maximal exercise as reported by other investigators.21 It has been suggested that, in the absence of a right-to-left shunt, the decrease in saturation may be due to abnormal distribution and perfusion in the lung.19 More surprising was the desaturation in the Mustard patients. A possible explanation could be a leak in the baffle. Interestingly, in an analysis of a subgroup of Mustard patients undergoing ultrasound, no leak was noted. A baffle leak during exercise could explain this phenomenon; however, information in this area is lacking. Investigations into this hypothesis are currently under way at the University of Toronto Congenital Cardiac Center for Adults. Study limitations: The values are based on a crosssectional sample, and not on a longitudinal sample, which may contribute to the relatively large variation in the results. The variation across age groups may be due to the limited number of patients in some of the oldest age groups. An unequal distribution of men and women in some age groups could also contribute to the large variation in the Mustard cohort. This study is limited by the follow-up constraints inherent in caring for adults with congenital heart diseases. Many of our patients reside outside Toronto, and those that are well may be less interested in returning to our center for cardiopulmonary testing. Our 475 patients may therefore represent a biased sample toward patients with functional limitations and poor exercise capacity. Conclusion: This study revealed severely diminished aerobic capacity in all diagnostic groups when compared with a healthy population. Declining values with aging were displayed in ToF, ASD, and CCTGA patient groups. Possible explanations for the reduced values are low habitual physical activity level, chronotropic incompetence, and diminished lung volumes. Cardiopulmonary testing as a routine follow-up
314 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 87
should be mandatory to reveal changes in exercise capacity as a sign of diminishing cardiac function. The maximal oxygen consumption values across age groups for the various congenital heart diseases can be used as reference values and for further research. 1. Dore A. Adult congenital heart disease: a new challenge. Perspect Cardiol 1999;15:43–51. 2. Fredriksen PM, Ingjer F, Nystad W, Thaulow E. A comparison of VO2peak between patients with CHD and healthy subjects, all aged 8 –17 years. Eur J Appl Physiol 1999;80:409 – 416. 3. Driscoll DJ, Offord KP, Feldt RH, Schaff HV, Puga FJ, Danielson GK. Fiveto fifteen-year follow-up after Fontan operation. Circulation 1992;85:469 – 496. 4. Harrison DA, Liu P, Walters JE, Goodman JM, Siu SC, Webb GD, Williams WG, McLaughlin PR. Cardiopulmonary function in adult patients late after Fontan repair. J Am Coll Cardiol 1995;26:1016 –1021. 5. Weipert J, Koch W, Haehnel JC, Meisner H. Exercise capacity and mid-term survival in patients with tricuspid atresia and complex congenital cardiac malformations after modified Fontan-operation. Eur J Cardiothorac Surg 1997;12: 574 –580. 6. Conte S, Jashari R, Eyskens B, Gewillig M, Dumoulin M, Daenen W. Homograft valve insertion for pulmonary regurgitation late after valveless repair of right ventricular outflow tract obstruction. Eur J Cardiothorac Surg 1998;15: 143–149. 7. Bjarke B. Oxygen uptake and cardiac output during submaximal and maximal exercise in adult subjects with totally corrected tetralogy of Fallot. Acta Med Scand 1975;197:177–186. 8. Wessel HU, Paul MH. Exercise studies in tetralogy of Fallot: a review. Pediatr Cardiol 1999;20:39 – 47. 9. Sulc J, Andrle V, Hruda J, Hucin B, Samanek M, Zapletal A. Pulmonary function in children with atrial septal defect before and after heart surgery. Heart 1998;80:484 – 488. 10. Helber U, Baumann R, Seboldt H, Reinhard U, Hoffmeister HM. Atrial septal defect in adults: cardiopulmonary exercise capacity before and 4 months and 10 years after defect closure. J Am Coll Cardiol 1997;29:1345–1350. 11. Nakanishi N, Yoshioka T, Fujii T, Hashizume T, Okano Y, Oozono K, Takaki H, Tamai J, Okubo S, Kunieda T. Comparison of exercise capacity evaluated by cardiopulmonary exercise test and hemodynamic parameters in patients with atrial septal defect. Kokyu to Junkan. Respir Circ 1992;40:789 –795. 12. Paridon SM, Humes RA, Pinsky WW. The role of chronotropic impairment during exercise after the Mustard operation. J Am Coll Cardiol 1991;17:729 –732. 13. Jones NL. The interpretation of stage 1 exercise test results. In: Trumbold C, ed. Clinical Exercise Testing. 1st ed. Philadelphia: WB Saunders, 1988:158 –185. 14. James FW, Blomqvist CG, Freed MD, Miller WW, Moller JH, Nugent EW, Riopel DA, Strong WB, Wessel HU. Standards for exercise testing in the pediatric age group. American Heart Association Council on Cardiovascular Disease in the Young. Ad hoc committee on exercise testing. Circulation 1982; 66:1377A-1397A. 15. Reybrouck T, Bisschop A, Dumoulin M, Van der Hauwaert LG. Cardiorespiratory exercise capacity after surgical closure of atrial septal defect is influenced by the age at surgery. Am Heart J 1991;122:1073–1078. 16. Oelberg DA, Marcotte F, Kreisman H, Wolkove N, Langleben D, Small D. Evaluation of right ventricular systolic pressure during incremental exercise by Doppler echocardiography in adults with atrial septal defect. Chest 1998;113: 1459 –1465. 17. Nir A, Driscoll DJ, Mottram CD, Offord KP, Puga FJ, Schaff HV, Danielson GK. Cardiorespiratory response to exercise after the Fontan operation: a serial study. J Am Coll Cardiol 1993;22:216 –220. 18. Warnes CA. Tricuspid atresia and univentricular heart after the Fontan procedure. Cardiol Clin 1993;11:665– 673. 19. Shachar GB, Fuhrman BP, Wang Y, Lucas RVJ, Lock JE. Rest and exercise hemodynamics after the Fontan procedure. Circulation 1982;65:1043–1048. 20. Fredriksen PM, Therrien J, Veldtman G, Warsi MA, Liu P, Siu S, Williams W, Granton J, Webb GD. Lung function and aerobic capacity in adult patients following modified Fontan procedure. Heart 2001; in press. 21. Iserin L, Chua TP, Chambers J, Coats AJ, Somerville J. Dyspnoea and exercise intolerance during cardiopulmonary exercise testing in patients with univentricular heart. The effects of chronic hypoxaemia and Fontan procedure. Eur Heart J 1997;18:1350 –1356.
FEBRUARY 1, 2001