- Email: [email protected]
Exercise Capacity and Exercise Hypertension After Surgical Repair of Isolated Aortic Coarctation
Exercise Capacity and Exercise Hypertension After Surgical Repair of Isolated Aortic Coarctation Alfred Hager, MD*, Simone Kanz, MD, Harald Kaemmerer, MD, VMD, and John Hess, MD There are contradictory reports whether exercise capacity is reduced in patients on longterm follow-up after coarctation repair. Data from unselected patient groups are missing. In a cross-sectional, long-term follow-up study of a tertiary congenital cardiology referral center, 260 patients (30.2 ⴞ 11.4 years old, 84 women), after surgical repair for isolated aortic coarctation (age at surgery 11.5 ⴞ 11.2 years), underwent a symptom-limited exercise test. Peak workload was 180 ⴞ 52 W, significantly less than the age- and height-related reference values (p <0.0005). A peak workload under 80% of expected was found in 200 patients (77%). Exercise performance of the patients was independent from age at surgery, type of surgery, or the systolic brachial-ankle blood pressure difference. The only exercise-limiting factor found was the chronic administration of diuretics to treat hypertension (p ⴝ 0.005). Exercise hypertension, defined as a systolic blood pressure >2 SD above the load-dependent reference value, was found in 73 patients (28%). It was independently related to the systolic brachial-ankle blood pressure difference (p <0.0005) and diuretics administration (p ⴝ 0.037). In conclusion, most patients after coarctation repair have a reduced exercise performance. This reduction is not related to the surgical results. Particularly, as these patients are at risk of early atherosclerosis, exercise should be promoted as primary prevention after restenosis, aortic or cerebral aneurysms, and severe exercise hypertension are ruled out. © 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;101:1777–1780)
Even after successful repair, many patients with aortic coarctation are hypertensive1 and show signs of preterm atherosclerosis.2– 4 They often seek medical advice for sport counseling for primary prevention. However, recent studies5,6 suggested that exercise capacity is reduced in adult patients with coarctation but did not address the reasons for the impairment. One reason for such results in these studies might be the consecutive sampling of data in tertiary centers over-representing more severely affected patients. In contrast, 2 studies showed a normal exercise performance in children after coarctation repair.7,8 Therefore, we analyzed exercise data in the context of our COArctation Long-term Assessment (COALA) study,1 a prospective, fairly complete cross-sectional study of all patients who underwent surgery in our institutions, to test the hypothesis whether coarctation patients have a reduced exercise capacity. Methods Inclusion and exclusion criteria of the COALA study were recently reported.1 In short, from 1974 to 1999, 404 patients born before 1985 underwent surgical repair of isolated aortic coarctation in our institution (Table 1). Of these 404 eligible patients, 21 deceased, 26 moved to remote or un-
Department of Pediatric Cardiology and Congenital Heart Disease, Deutsches Herzzentrum München, Technische Universität München, Germany. Manuscript received December 19, 2007; revised manuscript received and accepted February 2, 2008. This work was supported by Herzkind e.V., Braunschweig, Germany. *Corresponding author: Tel: ⫹49-89-1218-1650, fax: ⫹49-89-1218-3013. E-mail address: [email protected] (A. Hager). 0002-9149/08/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2008.02.072
known areas, and 83 patients denied a follow-up examination at our institution. One patient had to be excluded because of a lusoric artery. Another 13 patients did not perform the exercise test because of suspected aortic aneurysm in 6 patients, mental retardation in 3 patients, noncooperation in 2 patients, and fibula aplasia and pregnancy in 1 patient each. Table 1 lists the demographic and surgical data of the remaining 260 patients. The study was approved by the ethical board of the Medical Faculty of the Technische Universität München. Written informed consent was obtained from every patient. All follow-up examinations were performed by 2 of the authors (A.H., S.K.) according to a standardized protocol.1 Systolic blood pressure was measured at all 4 limbs by placing a Doppler probe distal to the cuff. A brachial-ankle difference was calculated as the systolic blood pressure difference between the systolic blood pressure value at the right arm and legs. Ambulatory blood pressure was measured at the right upper arm by an oscillometric device (90207 and 90217 ABP Monitor; Spacelabs Medical Inc., OSI Systems Inc., Hawthorne, California). A symptom-limited exercise test was performed on an upright, electronically braked bicycle. The WHO protocol was used starting with 25 W and increasing workload by 25 W every 2 minutes.9 The electrocardiogram was monitored continuously; blood pressure was measured manually every 2 minutes. Restenosis was defined as a systolic brachial-ankle blood pressure difference ⬎20 mm Hg.10 Hypertension at exercise was defined as a peak systolic blood pressure ⬎2 SD above the age- and workload-dependent reference value:11 mean ⫾ 2 SD (mm Hg) ⫽ 111.2 ⫹ 0.310 ⫻ age (years) ⫹ 0.334 ⫻ work rate (watts) ⫾ 2 ⫻ 17.9. A reduced exercise capacity was defined www.AJConline.org
1778
The American Journal of Cardiology (www.AJConline.org)
Table 1 Surgical data of primary coarctation repair
Men/Women Calendar year of surgery Age at surgery (yrs) Type of surgery Resection and end-to-end anastomosis Resection and tube graft interposition Subclavian flap aortoplasty Patch aortoplasty Direct aortoplasty Extra-anatomic bypass Subclavian-aortic anastomosis
Patients Eligible (n ⫽ 404)
Patients Studied (n ⫽ 260)
266/138 (66%/34%) 1982 ⫾ 5 (1974–99) 11.3 ⫾ 11.0 (0–56)
176/84 (68%/32%) 1982 ⫾ 6 (1974–99) 11.5 ⫾ 11.2 (056)
303 (75%)
192 (74%)
85 (21%)
58 (22%)
4 (1%)
3 (1%)
4 (1%) 3 (0.7%) 2 (0.5%) 3 (0.7%)
4 (2%) 1 (0.4%) 1 (0.4%) 1 (0.4%)
Data expressed as number (percent) or mean ⫾ SD (range).
as a peak workload (peak W in watts) ⬍80% of the reference value:12 Women:peakW ⫽ [137.7 ⫻ height共m兲 ⫺ 23.1] ⁄ (1 ⫹ exp(0.064 ⫻ [age共years) ⫺ 75.9])) Men:peakW ⫽ [244.6 ⫻ height共m兲 ⫺ 92.1] ⁄ (1 ⫹ exp(0.038 ⫻ [age共years兲 ⫺ 77.3])) Data were analyzed with SPSS 15.0 software (SPSS, Inc., Chicago, Illinois). A p value ⬍0.05 was considered to be significant. Results are shown as mean ⫾ SD. The primary hypothesis of whether peak workload differs from the individual age- and height-related reference value was tested with a 2-sided paired t test. The same test was applied for the second hypothesis, whether systolic blood pressure at peak exercise differs from age- and workload-dependent reference value. Risk factors, peak workload, and exercise blood pressure, respectively, were expressed as percentage of the individual reference value. Multiple regression analyses were performed, including surgical factors (age at surgery, type of surgery), follow-up factors (follow-up time period, current age), and current blood pressure status (brachial-ankle blood pressure difference, current medication, and current ambulatory blood pressure data, including dipping). Results The patients reached a peak workload of 180 ⫾ 52 W or 2.5 ⫾ 0.7 W/kg, which was significantly less than the age- and height-related reference values of 258 ⫾ 54 W (p ⬍0.0005). A peak workload ⬍80% of expected was found in 200 patients (76.9%; Figure 1). In the multiple regression analysis, exercise performance was solely dependent on the administration of diuretics as antihypertensive drug treatment with a better performance of patients without diuretics (p ⫽ 0.005). Exercise capacity was independent from age at surgery (p ⫽ 0.333), calendar year of surgery (p ⫽ 0.252), type of surgery (end-to-end anastomosis, p ⫽
0.142; tube graft, p ⫽ 0.391; others, p ⫽ 0.148), follow-up time interval (p ⫽ 0.194) or age at follow-up (p ⫽ 0.110), the residual systolic blood pressure gradient at the former coarctation site (p ⫽ 0.214), mean systolic/diastolic daytime/nighttime/24-h ambulatory blood pressure (p ⫽ 0.191 to 0.669), or other medication (p ⫽ 0.178). Systolic blood pressure at peak exercise was 201 ⫾ 32 mm Hg, which was significantly higher than the individual sex- and workload-dependent reference values (181 ⫾ 17 mm Hg; p ⬍0.0005). Exercise hypertension, defined as a systolic blood pressure ⬎2 SD above the load-dependent reference value, was found in 73 patients (28.1%; Figure 2). Multiple regression analysis revealed that systolic blood pressure at exercise was independently related to the residual gradient measured as systolic brachial-ankle blood pressure difference (p ⬍0.0005) and administration of diuretics (p ⫽ 0.037). Exercise-induced hypertension was less prevalent in patients without gradient and on diuretics. In addition to these factors, there was no further significant independent correlation to age at surgery (p ⫽ 0.232), calendar year of surgery (p ⫽ 0.267), type of surgery (end-to-end anastomosis, p ⫽ 0.264; tube graft, p ⫽ 0.507; others, p ⫽ 0.278), follow-up time (p ⫽ 0.242) or age at follow-up (p ⫽ 0.571), or medication other than diuretics (p ⫽ 0.237). Discussion This rather complete and high-numbered cross-sectional study showed that more than 3/4 of patients, after coarctation repair, did not reach normal exercise capacity. Exercise limitation was not related to surgical factors, either perioperative factors or to the hemodynamic outcome in the long-term follow-up, such as occurrence of restenosis or hypertension. The data correspond with the recently published data from Diller et al5 and Gratz et al.6 They analyzed consecutively sampled adults with different kinds of congenital heart anomalies sent for exercise evaluation. Even in patients with coarctation, they found a significantly reduced exercise capacity. Balderston et al7 and Norozi et al8 reported contrasting findings but described children with a mean age of 12 and 8 years, respectively. Age might be the explanation for this discrepancy. Fredriksen et al13 showed, in patients with congenital heart disease (including coarctation), a decline in exercise capacity beginning already at puberty, whereas healthy adolescents still increase aerobic power in this life span. There are 2 reasons for that early decline: the reduced aortic compliance or physical deconditioning by overprotection and “cardiac neurosis.” Rhodes et al.14 investigated the switch to anaerobic metabolism during a progressive cardiopulmonary exercise test. They reported an early reliance on anaerobic metabolism during exercise, even in patients without restenosis. There was only a trend towards a lower peak oxygen uptake in their small study group of 15 patients. They hypothesized that the flow disturbances in the aortic arch during exercise may persist even after apparently successful surgery and cause the early reliance on anaerobic metabolism. They graded a poor physical conditioning caused by psychological factors like overprotection as unlikely because patients with formerly persistent arterial duct, who also had a lateral thoracotomy, showed a normal aerobic metabolism during exercise. How-
Congenital Heart Disease/Exercise Capacity After Coarctation Repair
1779
Figure 1. Peak workload expressed as percentage of age- and height-related reference value in 260 patients with isolated aortic coarctation, depicting that less than 1/4 of the patients (23%) achieved a normal exercise capacity within 80% to 120% of expected.
Figure 2. Systolic blood pressure at peak workload expressed as SD score according to the age- and workload-related reference value in 260 patients with isolated aortic coarctation, depicting that more than 1/4 of the patients (28%) were hypertensive during exercise. This exercise hypertension was more, but not exclusively, prevalent in patients with current restenosis (brachial-ankle blood pressure difference ⬎20 mm Hg).
ever, this persistent-arterial-duct group was significantly younger than the coarctation group (mean age of 13 vs 19 years). In contrast to this study, Bjarnason-Wehrens et al15
recently found motor developmental deficits in children with rather simple congenital heart defects even without residual sequels. The authors speculated that overprotection might have
1780
The American Journal of Cardiology (www.AJConline.org)
curtailed normal physical activity, neuromotor development, and, probably, physical conditioning. In our study, we found no relation between exercise capacity and the residual gradient at the coarctation site. Therefore, our data favor poor physical conditioning as the explanation for the reduced exercise capacity. In a second analysis, we confirmed the increased incidence of exercise hypertension in patients after coarctation repair. This increase was strongly but not exclusively related to the residual gradient at the stenosis. The data also showed that, even after reducing the current definition of restenosis (brachial-ankle difference ⬎20 mm Hg) to lower cut-off values, the overall prevalence of exercise hypertension is not explained in total. Even in patients with an optimal blood pressure situation, that is, a systolic blood pressure at the legs higher than at the right arm, the prevalence of exercise hypertension was substantial. This result confirms that arterial hypertension in coarctation patients is not only attributed to restenosis16,17 but also related to medial wall changes18,19 with increased aortic stiffness.2,20 –22 Therefore, the diagnostic value of blood pressure measurements at exercise to differentiate restenosis from reduced aortic compliance is limited.23,24 In contrast, exercise-induced hypertension has shown to be a predictor of arterial hypertension in patients without coarctation.25 At the moment, however, there is not enough evidence to start antihypertensive drug treatment in patients who are hypertensive only at exercise. An unresolved question concerns the acute risk of exercise hypertension. Despite the absence of definitive evidence of what blood pressure values might be dangerous, a threshold of 250/115 mm Hg was suggested as the point where a clinical exercise test should be stopped.26 In patients after coarctation repair, however, there are further concerns about undetected cerebral27 and aortic28 aneurysms and whether they progress with regular exercise. 1. Hager A, Kanz S, Kaemmerer H, Schreiber C, Hess J. Coarctation Long-term Assessment (COALA): significance of arterial hypertension in a cohort of 404 patients up to 27 years after surgical repair of isolated coarctation of the aorta, even in the absence of restenosis and prosthetic material. J Thorac Cardiovasc Surg 2007;134:738 –745. 2. Brili S, Dernellis J, Aggeli C, Pitsavos C, Hatzos C, Stefanadis C, Toutouzas P. Aortic elastic properties in patients with repaired coarctation of aorta. Am J Cardiol 1998;82:1140 –1143. 3. Vriend JJ, De Groot E, Kastelein JJ, Mulder BJ. Carotid and femoral B-mode ultrasound intima-media thickness measurements in adult post-coarctectomy patients. Int Angiol 2004;23:41– 46. 4. Meyer AA, Joharchi MS, Kundt G, Schuff-Werner P, Steinhoff G, Kienast W. Predicting the risk of early atherosclerotic disease development in children after repair of aortic coarctation. Eur Heart J 2005;26:617– 622. 5. Diller GP, Dimopoulos K, Okonko D, Li W, Babu-Narayan SV, Broberg CS, Johansson B, Bouzas B, Mullen MJ, Poole-Wilson PA, Francis DP, Gatzoulis MA. Exercise intolerance in adult congenital heart disease: comparative severity, correlates, and prognostic implication. Circulation 2005;112:828 – 835. 6. Gratz A, Hess J, Hager A. Quality of life and exercise capacity in 497 patients with congenital heart disease. Clin Res Cardiol 2007;96:675. 7. Balderston SM, Daberkow E, Clarke DR, Wolfe RR. Maximal voluntary exercise variables in children with postoperative coarctation of the aorta. J Am Coll Cardiol 1992;19:154 –158. 8. Norozi K, Gravenhorst V, Hobbiebrunken E, Wessel A. Normality of cardiopulmonary capacity in children operated on to correct congenital heart defects. Arch Pediatr Adolesc Med 2005;159:1063–1068.
9. Fletcher GF, Balady GJ, Amsterdam EA, Chaitman B, Eckel R, Fleg J, Froelicher VF, Leon AS, Pina IL, Rodney R, Simons-Morton DA, Williams MA, Bazzarre T. Exercise standards for testing and training: a statement for healthcare professionals from the American Heart Association. Circulation 2001;104:1694 –1740. 10. Cohen M, Fuster V, Steele PM, Driscoll D, McGoon DC. Coarctation of the aorta. Long-term follow-up and prediction of outcome after surgical correction. Circulation 1989;80:840 – 845. 11. Heck H, Rost R, Hollmann W. Normwerte des Blutdrucks bei der Fahrradergometrie. Deutsche Zeitschrift für Sportmedizin 1984;35:243–249. 12. Wohlfart B, Farazdaghi GR. Reference values for the physical work capacity on a bicycle ergometer for men–a comparison with a previous study on women. Clin Physiol Funct Imaging 2003;23:166 –170. 13. Fredriksen PM, Ingjer F, Nystad W, Thaulow E. A comparison of VO2(peak) between patients with congenital heart disease and healthy subjects, all aged 8 –17 years. Eur J Appl Physiol Occup Physiol 1999;80:409 – 416. 14. Rhodes J, Geggel RL, Marx GR, Bevilacqua L, Dambach YB, Hijazi ZM. Excessive anaerobic metabolism during exercise after repair of aortic coarctation. J Pediatr 1997;131:210 –214. 15. Bjarnason-Wehrens B, Dordel S, Schickendantz S, Krumm C, Bott D, Sreeram N, Brockmeier K. Motor development in children with congenital cardiac diseases compared to their healthy peers. Cardiol Young 2007:1–12. 16. Hauser M, Kuehn A, Wilson N. Abnormal responses for blood pressure in children and adults with surgically corrected aortic coarctation. Cardiol Young 2000;10:353–357. 17. Gunthard J, Buser PT, Miettunen R, Hagmann A, Wyler F. Effects of morphologic restenosis, defined by MRI after coarctation repair, on blood pressure and arm-leg and Doppler gradients. Angiology 1996;47:1073–1080. 18. Isner JM, Donaldson RF, Fulton D, Bhan I, Payne DD, Cleveland RJ. Cystic medial necrosis in coarctation of the aorta: a potential factor contributing to adverse consequences observed after percutaneous balloon angioplasty of coarctation sites. Circulation 1987;75:689 – 695. 19. Niwa K, Perloff JK, Bhuta SM, Laks H, Drinkwater DC, Child JS, Miner PD. Structural abnormalities of great arterial walls in congenital heart disease: light and electron microscopic analyses. Circulation 2001;103:393– 400. 20. Vogt M, Kuhn A, Baumgartner D, Baumgartner C, Busch R, Kostolny M, Hess J. Impaired elastic properties of the ascending aorta in newborns before and early after successful coarctation repair: proof of a systemic vascular disease of the prestenotic arteries? Circulation 2005; 111:3269 –3273. 21. de Divitiis M, Pilla C, Kattenhorn M, Zadinello M, Donald A, Leeson P, Wallace S, Redington A, Deanfield JE. Vascular dysfunction after repair of coarctation of the aorta: impact of early surgery. Circulation 2001;104:I-165–170. 22. de Divitiis M, Pilla C, Kattenhorn M, Donald A, Zadinello M, Wallace S, Redington A, Deanfield J. Ambulatory blood pressure, left ventricular mass, and conduit artery function late after successful repair of coarctation of the aorta. J Am Coll Cardiol 2003;41:2259 –2265. 23. Swan L, Goyal S, Hsia C, Hechter S, Webb G, Gatzoulis MA. Exercise systolic blood pressures are of questionable value in the assessment of the adult with a previous coarctation repair. Heart 2003;89:189 –192. 24. Carano N, Agnetti A, Barone A, Squarcia M, Squarcia U. Exercise test in detecting anomalous behaviour of blood pressure in patients successfully operated on for coarctation of the aorta. Pediatr Med Chir 1999;21:105–109. 25. Miyai N, Arita M, Miyashita K, Morioka I, Shiraishi T, Nishio I. Blood pressure response to heart rate during exercise test and risk of future hypertension. Hypertension 2002;39:761–766. 26. Gibbons RJ, Balady GJ, Beasley JW, Bricker JT, Duvernoy WF, Froelicher VF, Mark DB, Marwick TH, McCallister BD, Thompson PD, Winters WL, Yanowitz FG, Ritchie JL, Cheitlin MD, Eagle KA, Gardner TJ, Garson A, Lewis RP, O’Rourke RA, Ryan TJ. ACC/AHA Guidelines for Exercise Testing. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Exercise Testing). J Am Coll Cardiol 1997;30:260 –311. 27. Connolly HM, Huston J 3rd, Brown RD, Warnes CA, Ammash NM, Tajik AJ. Intracranial aneurysms in patients with coarctation of the aorta: a prospective magnetic resonance angiographic study of 100 patients. Mayo Clin Proc 2003;78:1491–1499. 28. Augustin N, Kaemmerer H, Porner M, Meinhardt G, Hess J, Lange R. Images in cardiovascular medicine. Giant aortic aneurysm after patch repair of coarctation. Circulation 2006;113:e297– e298.
Even after successful repair, many patients with aortic coarctation are hypertensive1 and show signs of preterm atherosclerosis.2– 4 They often seek medical advice for sport counseling for primary prevention. However, recent studies5,6 suggested that exercise capacity is reduced in adult patients with coarctation but did not address the reasons for the impairment. One reason for such results in these studies might be the consecutive sampling of data in tertiary centers over-representing more severely affected patients. In contrast, 2 studies showed a normal exercise performance in children after coarctation repair.7,8 Therefore, we analyzed exercise data in the context of our COArctation Long-term Assessment (COALA) study,1 a prospective, fairly complete cross-sectional study of all patients who underwent surgery in our institutions, to test the hypothesis whether coarctation patients have a reduced exercise capacity. Methods Inclusion and exclusion criteria of the COALA study were recently reported.1 In short, from 1974 to 1999, 404 patients born before 1985 underwent surgical repair of isolated aortic coarctation in our institution (Table 1). Of these 404 eligible patients, 21 deceased, 26 moved to remote or un-
Department of Pediatric Cardiology and Congenital Heart Disease, Deutsches Herzzentrum München, Technische Universität München, Germany. Manuscript received December 19, 2007; revised manuscript received and accepted February 2, 2008. This work was supported by Herzkind e.V., Braunschweig, Germany. *Corresponding author: Tel: ⫹49-89-1218-1650, fax: ⫹49-89-1218-3013. E-mail address: [email protected] (A. Hager). 0002-9149/08/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2008.02.072
known areas, and 83 patients denied a follow-up examination at our institution. One patient had to be excluded because of a lusoric artery. Another 13 patients did not perform the exercise test because of suspected aortic aneurysm in 6 patients, mental retardation in 3 patients, noncooperation in 2 patients, and fibula aplasia and pregnancy in 1 patient each. Table 1 lists the demographic and surgical data of the remaining 260 patients. The study was approved by the ethical board of the Medical Faculty of the Technische Universität München. Written informed consent was obtained from every patient. All follow-up examinations were performed by 2 of the authors (A.H., S.K.) according to a standardized protocol.1 Systolic blood pressure was measured at all 4 limbs by placing a Doppler probe distal to the cuff. A brachial-ankle difference was calculated as the systolic blood pressure difference between the systolic blood pressure value at the right arm and legs. Ambulatory blood pressure was measured at the right upper arm by an oscillometric device (90207 and 90217 ABP Monitor; Spacelabs Medical Inc., OSI Systems Inc., Hawthorne, California). A symptom-limited exercise test was performed on an upright, electronically braked bicycle. The WHO protocol was used starting with 25 W and increasing workload by 25 W every 2 minutes.9 The electrocardiogram was monitored continuously; blood pressure was measured manually every 2 minutes. Restenosis was defined as a systolic brachial-ankle blood pressure difference ⬎20 mm Hg.10 Hypertension at exercise was defined as a peak systolic blood pressure ⬎2 SD above the age- and workload-dependent reference value:11 mean ⫾ 2 SD (mm Hg) ⫽ 111.2 ⫹ 0.310 ⫻ age (years) ⫹ 0.334 ⫻ work rate (watts) ⫾ 2 ⫻ 17.9. A reduced exercise capacity was defined www.AJConline.org
1778
The American Journal of Cardiology (www.AJConline.org)
Table 1 Surgical data of primary coarctation repair
Men/Women Calendar year of surgery Age at surgery (yrs) Type of surgery Resection and end-to-end anastomosis Resection and tube graft interposition Subclavian flap aortoplasty Patch aortoplasty Direct aortoplasty Extra-anatomic bypass Subclavian-aortic anastomosis
Patients Eligible (n ⫽ 404)
Patients Studied (n ⫽ 260)
266/138 (66%/34%) 1982 ⫾ 5 (1974–99) 11.3 ⫾ 11.0 (0–56)
176/84 (68%/32%) 1982 ⫾ 6 (1974–99) 11.5 ⫾ 11.2 (056)
303 (75%)
192 (74%)
85 (21%)
58 (22%)
4 (1%)
3 (1%)
4 (1%) 3 (0.7%) 2 (0.5%) 3 (0.7%)
4 (2%) 1 (0.4%) 1 (0.4%) 1 (0.4%)
Data expressed as number (percent) or mean ⫾ SD (range).
as a peak workload (peak W in watts) ⬍80% of the reference value:12 Women:peakW ⫽ [137.7 ⫻ height共m兲 ⫺ 23.1] ⁄ (1 ⫹ exp(0.064 ⫻ [age共years) ⫺ 75.9])) Men:peakW ⫽ [244.6 ⫻ height共m兲 ⫺ 92.1] ⁄ (1 ⫹ exp(0.038 ⫻ [age共years兲 ⫺ 77.3])) Data were analyzed with SPSS 15.0 software (SPSS, Inc., Chicago, Illinois). A p value ⬍0.05 was considered to be significant. Results are shown as mean ⫾ SD. The primary hypothesis of whether peak workload differs from the individual age- and height-related reference value was tested with a 2-sided paired t test. The same test was applied for the second hypothesis, whether systolic blood pressure at peak exercise differs from age- and workload-dependent reference value. Risk factors, peak workload, and exercise blood pressure, respectively, were expressed as percentage of the individual reference value. Multiple regression analyses were performed, including surgical factors (age at surgery, type of surgery), follow-up factors (follow-up time period, current age), and current blood pressure status (brachial-ankle blood pressure difference, current medication, and current ambulatory blood pressure data, including dipping). Results The patients reached a peak workload of 180 ⫾ 52 W or 2.5 ⫾ 0.7 W/kg, which was significantly less than the age- and height-related reference values of 258 ⫾ 54 W (p ⬍0.0005). A peak workload ⬍80% of expected was found in 200 patients (76.9%; Figure 1). In the multiple regression analysis, exercise performance was solely dependent on the administration of diuretics as antihypertensive drug treatment with a better performance of patients without diuretics (p ⫽ 0.005). Exercise capacity was independent from age at surgery (p ⫽ 0.333), calendar year of surgery (p ⫽ 0.252), type of surgery (end-to-end anastomosis, p ⫽
0.142; tube graft, p ⫽ 0.391; others, p ⫽ 0.148), follow-up time interval (p ⫽ 0.194) or age at follow-up (p ⫽ 0.110), the residual systolic blood pressure gradient at the former coarctation site (p ⫽ 0.214), mean systolic/diastolic daytime/nighttime/24-h ambulatory blood pressure (p ⫽ 0.191 to 0.669), or other medication (p ⫽ 0.178). Systolic blood pressure at peak exercise was 201 ⫾ 32 mm Hg, which was significantly higher than the individual sex- and workload-dependent reference values (181 ⫾ 17 mm Hg; p ⬍0.0005). Exercise hypertension, defined as a systolic blood pressure ⬎2 SD above the load-dependent reference value, was found in 73 patients (28.1%; Figure 2). Multiple regression analysis revealed that systolic blood pressure at exercise was independently related to the residual gradient measured as systolic brachial-ankle blood pressure difference (p ⬍0.0005) and administration of diuretics (p ⫽ 0.037). Exercise-induced hypertension was less prevalent in patients without gradient and on diuretics. In addition to these factors, there was no further significant independent correlation to age at surgery (p ⫽ 0.232), calendar year of surgery (p ⫽ 0.267), type of surgery (end-to-end anastomosis, p ⫽ 0.264; tube graft, p ⫽ 0.507; others, p ⫽ 0.278), follow-up time (p ⫽ 0.242) or age at follow-up (p ⫽ 0.571), or medication other than diuretics (p ⫽ 0.237). Discussion This rather complete and high-numbered cross-sectional study showed that more than 3/4 of patients, after coarctation repair, did not reach normal exercise capacity. Exercise limitation was not related to surgical factors, either perioperative factors or to the hemodynamic outcome in the long-term follow-up, such as occurrence of restenosis or hypertension. The data correspond with the recently published data from Diller et al5 and Gratz et al.6 They analyzed consecutively sampled adults with different kinds of congenital heart anomalies sent for exercise evaluation. Even in patients with coarctation, they found a significantly reduced exercise capacity. Balderston et al7 and Norozi et al8 reported contrasting findings but described children with a mean age of 12 and 8 years, respectively. Age might be the explanation for this discrepancy. Fredriksen et al13 showed, in patients with congenital heart disease (including coarctation), a decline in exercise capacity beginning already at puberty, whereas healthy adolescents still increase aerobic power in this life span. There are 2 reasons for that early decline: the reduced aortic compliance or physical deconditioning by overprotection and “cardiac neurosis.” Rhodes et al.14 investigated the switch to anaerobic metabolism during a progressive cardiopulmonary exercise test. They reported an early reliance on anaerobic metabolism during exercise, even in patients without restenosis. There was only a trend towards a lower peak oxygen uptake in their small study group of 15 patients. They hypothesized that the flow disturbances in the aortic arch during exercise may persist even after apparently successful surgery and cause the early reliance on anaerobic metabolism. They graded a poor physical conditioning caused by psychological factors like overprotection as unlikely because patients with formerly persistent arterial duct, who also had a lateral thoracotomy, showed a normal aerobic metabolism during exercise. How-
Congenital Heart Disease/Exercise Capacity After Coarctation Repair
1779
Figure 1. Peak workload expressed as percentage of age- and height-related reference value in 260 patients with isolated aortic coarctation, depicting that less than 1/4 of the patients (23%) achieved a normal exercise capacity within 80% to 120% of expected.
Figure 2. Systolic blood pressure at peak workload expressed as SD score according to the age- and workload-related reference value in 260 patients with isolated aortic coarctation, depicting that more than 1/4 of the patients (28%) were hypertensive during exercise. This exercise hypertension was more, but not exclusively, prevalent in patients with current restenosis (brachial-ankle blood pressure difference ⬎20 mm Hg).
ever, this persistent-arterial-duct group was significantly younger than the coarctation group (mean age of 13 vs 19 years). In contrast to this study, Bjarnason-Wehrens et al15
recently found motor developmental deficits in children with rather simple congenital heart defects even without residual sequels. The authors speculated that overprotection might have
1780
The American Journal of Cardiology (www.AJConline.org)
curtailed normal physical activity, neuromotor development, and, probably, physical conditioning. In our study, we found no relation between exercise capacity and the residual gradient at the coarctation site. Therefore, our data favor poor physical conditioning as the explanation for the reduced exercise capacity. In a second analysis, we confirmed the increased incidence of exercise hypertension in patients after coarctation repair. This increase was strongly but not exclusively related to the residual gradient at the stenosis. The data also showed that, even after reducing the current definition of restenosis (brachial-ankle difference ⬎20 mm Hg) to lower cut-off values, the overall prevalence of exercise hypertension is not explained in total. Even in patients with an optimal blood pressure situation, that is, a systolic blood pressure at the legs higher than at the right arm, the prevalence of exercise hypertension was substantial. This result confirms that arterial hypertension in coarctation patients is not only attributed to restenosis16,17 but also related to medial wall changes18,19 with increased aortic stiffness.2,20 –22 Therefore, the diagnostic value of blood pressure measurements at exercise to differentiate restenosis from reduced aortic compliance is limited.23,24 In contrast, exercise-induced hypertension has shown to be a predictor of arterial hypertension in patients without coarctation.25 At the moment, however, there is not enough evidence to start antihypertensive drug treatment in patients who are hypertensive only at exercise. An unresolved question concerns the acute risk of exercise hypertension. Despite the absence of definitive evidence of what blood pressure values might be dangerous, a threshold of 250/115 mm Hg was suggested as the point where a clinical exercise test should be stopped.26 In patients after coarctation repair, however, there are further concerns about undetected cerebral27 and aortic28 aneurysms and whether they progress with regular exercise. 1. Hager A, Kanz S, Kaemmerer H, Schreiber C, Hess J. Coarctation Long-term Assessment (COALA): significance of arterial hypertension in a cohort of 404 patients up to 27 years after surgical repair of isolated coarctation of the aorta, even in the absence of restenosis and prosthetic material. J Thorac Cardiovasc Surg 2007;134:738 –745. 2. Brili S, Dernellis J, Aggeli C, Pitsavos C, Hatzos C, Stefanadis C, Toutouzas P. Aortic elastic properties in patients with repaired coarctation of aorta. Am J Cardiol 1998;82:1140 –1143. 3. Vriend JJ, De Groot E, Kastelein JJ, Mulder BJ. Carotid and femoral B-mode ultrasound intima-media thickness measurements in adult post-coarctectomy patients. Int Angiol 2004;23:41– 46. 4. Meyer AA, Joharchi MS, Kundt G, Schuff-Werner P, Steinhoff G, Kienast W. Predicting the risk of early atherosclerotic disease development in children after repair of aortic coarctation. Eur Heart J 2005;26:617– 622. 5. Diller GP, Dimopoulos K, Okonko D, Li W, Babu-Narayan SV, Broberg CS, Johansson B, Bouzas B, Mullen MJ, Poole-Wilson PA, Francis DP, Gatzoulis MA. Exercise intolerance in adult congenital heart disease: comparative severity, correlates, and prognostic implication. Circulation 2005;112:828 – 835. 6. Gratz A, Hess J, Hager A. Quality of life and exercise capacity in 497 patients with congenital heart disease. Clin Res Cardiol 2007;96:675. 7. Balderston SM, Daberkow E, Clarke DR, Wolfe RR. Maximal voluntary exercise variables in children with postoperative coarctation of the aorta. J Am Coll Cardiol 1992;19:154 –158. 8. Norozi K, Gravenhorst V, Hobbiebrunken E, Wessel A. Normality of cardiopulmonary capacity in children operated on to correct congenital heart defects. Arch Pediatr Adolesc Med 2005;159:1063–1068.
9. Fletcher GF, Balady GJ, Amsterdam EA, Chaitman B, Eckel R, Fleg J, Froelicher VF, Leon AS, Pina IL, Rodney R, Simons-Morton DA, Williams MA, Bazzarre T. Exercise standards for testing and training: a statement for healthcare professionals from the American Heart Association. Circulation 2001;104:1694 –1740. 10. Cohen M, Fuster V, Steele PM, Driscoll D, McGoon DC. Coarctation of the aorta. Long-term follow-up and prediction of outcome after surgical correction. Circulation 1989;80:840 – 845. 11. Heck H, Rost R, Hollmann W. Normwerte des Blutdrucks bei der Fahrradergometrie. Deutsche Zeitschrift für Sportmedizin 1984;35:243–249. 12. Wohlfart B, Farazdaghi GR. Reference values for the physical work capacity on a bicycle ergometer for men–a comparison with a previous study on women. Clin Physiol Funct Imaging 2003;23:166 –170. 13. Fredriksen PM, Ingjer F, Nystad W, Thaulow E. A comparison of VO2(peak) between patients with congenital heart disease and healthy subjects, all aged 8 –17 years. Eur J Appl Physiol Occup Physiol 1999;80:409 – 416. 14. Rhodes J, Geggel RL, Marx GR, Bevilacqua L, Dambach YB, Hijazi ZM. Excessive anaerobic metabolism during exercise after repair of aortic coarctation. J Pediatr 1997;131:210 –214. 15. Bjarnason-Wehrens B, Dordel S, Schickendantz S, Krumm C, Bott D, Sreeram N, Brockmeier K. Motor development in children with congenital cardiac diseases compared to their healthy peers. Cardiol Young 2007:1–12. 16. Hauser M, Kuehn A, Wilson N. Abnormal responses for blood pressure in children and adults with surgically corrected aortic coarctation. Cardiol Young 2000;10:353–357. 17. Gunthard J, Buser PT, Miettunen R, Hagmann A, Wyler F. Effects of morphologic restenosis, defined by MRI after coarctation repair, on blood pressure and arm-leg and Doppler gradients. Angiology 1996;47:1073–1080. 18. Isner JM, Donaldson RF, Fulton D, Bhan I, Payne DD, Cleveland RJ. Cystic medial necrosis in coarctation of the aorta: a potential factor contributing to adverse consequences observed after percutaneous balloon angioplasty of coarctation sites. Circulation 1987;75:689 – 695. 19. Niwa K, Perloff JK, Bhuta SM, Laks H, Drinkwater DC, Child JS, Miner PD. Structural abnormalities of great arterial walls in congenital heart disease: light and electron microscopic analyses. Circulation 2001;103:393– 400. 20. Vogt M, Kuhn A, Baumgartner D, Baumgartner C, Busch R, Kostolny M, Hess J. Impaired elastic properties of the ascending aorta in newborns before and early after successful coarctation repair: proof of a systemic vascular disease of the prestenotic arteries? Circulation 2005; 111:3269 –3273. 21. de Divitiis M, Pilla C, Kattenhorn M, Zadinello M, Donald A, Leeson P, Wallace S, Redington A, Deanfield JE. Vascular dysfunction after repair of coarctation of the aorta: impact of early surgery. Circulation 2001;104:I-165–170. 22. de Divitiis M, Pilla C, Kattenhorn M, Donald A, Zadinello M, Wallace S, Redington A, Deanfield J. Ambulatory blood pressure, left ventricular mass, and conduit artery function late after successful repair of coarctation of the aorta. J Am Coll Cardiol 2003;41:2259 –2265. 23. Swan L, Goyal S, Hsia C, Hechter S, Webb G, Gatzoulis MA. Exercise systolic blood pressures are of questionable value in the assessment of the adult with a previous coarctation repair. Heart 2003;89:189 –192. 24. Carano N, Agnetti A, Barone A, Squarcia M, Squarcia U. Exercise test in detecting anomalous behaviour of blood pressure in patients successfully operated on for coarctation of the aorta. Pediatr Med Chir 1999;21:105–109. 25. Miyai N, Arita M, Miyashita K, Morioka I, Shiraishi T, Nishio I. Blood pressure response to heart rate during exercise test and risk of future hypertension. Hypertension 2002;39:761–766. 26. Gibbons RJ, Balady GJ, Beasley JW, Bricker JT, Duvernoy WF, Froelicher VF, Mark DB, Marwick TH, McCallister BD, Thompson PD, Winters WL, Yanowitz FG, Ritchie JL, Cheitlin MD, Eagle KA, Gardner TJ, Garson A, Lewis RP, O’Rourke RA, Ryan TJ. ACC/AHA Guidelines for Exercise Testing. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Exercise Testing). J Am Coll Cardiol 1997;30:260 –311. 27. Connolly HM, Huston J 3rd, Brown RD, Warnes CA, Ammash NM, Tajik AJ. Intracranial aneurysms in patients with coarctation of the aorta: a prospective magnetic resonance angiographic study of 100 patients. Mayo Clin Proc 2003;78:1491–1499. 28. Augustin N, Kaemmerer H, Porner M, Meinhardt G, Hess J, Lange R. Images in cardiovascular medicine. Giant aortic aneurysm after patch repair of coarctation. Circulation 2006;113:e297– e298.