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Results of the Bruce Treadmill Test in Children After Arterial Switch Operation for Simple Transposition of the Great Arteries
Results of the Bruce Treadmill Test in Children After Arterial Switch Operation for Simple Transposition of the Great Arteries Martial Massin, MD, Hedwig Ho ¨ vels-Gu¨rich, MD, Sabine Da ¨ britz, Bruno Messmer, MD, and Go ¨ tz von Bernuth, MD
MD,
Children who underwent arterial switch operation for simple transposition of the great arteries in the neonatal period are now reaching an age when exercise testing becomes feasible. This study was conducted to assess exercise tolerance and electrocardiographic response to exercise stress in 50 asymptomatic children, aged 4 to 9 years, using the Bruce walking treadmill protocol to voluntary exhaustion. Heart rate and blood pressure response to exercise stress, endurance time, and electrocardiographic changes were analyzed and compared with those of age-matched normal children. Forty-seven patients had normal exercise capacity and parameters. One patient, whose coronary angiogram showed occlusion of the left main coronary artery, developed electrocardiographic signs of myocardial ischemia during ex-
ercise. In 1 patient with a single right coronary artery ostium and in another, who underwent a neonatal internal mammary bypass graft for obstruction of the right coronary artery, the resting electrocardiogram showed ventricular premature complexes and exercise stressinduced salvos of ventricular tachycardia. We conclude that most of the children who underwent the neonatal arterial switch operation for simple transposition of the great arteries have a normal exercise capacity. Exercise testing appears to be useful in detecting ischemic damage or exercise-induced arrhythmias possibly secondary to reduced coronary flow reserve. Q1998 by Excerpta Medica, Inc. (Am J Cardiol 1998;81:56 – 60)
rterial switch operation is actually considered the surgical treatment of choice for repair of transA position of the great arteries in the newborn. This
patients, aged 4 to 9 years (mean 6 SD 5.6 6 1.5), participated in the study. There were 40 boys and 10 girls. All children were within the fifth and the 95th percentiles for height and weight. All procedures were explained in detail to both children and parents who had agreed to take part in the study, and informed consent was obtained for each participant. Five patients had a ventricular septal defect at the time of surgery which was small and left untouched in 3 patients (in 2 of these, the defect subsequently closed spontaneously) and was surgically closed through the right atrium in 2 patients. One patient also had a mild aortic coarctation that was not repaired. Origin and course of the coronary arteries before arterial switch operation was as follows: in 47 patients, the right coronary artery arose from the right sinus, and the left coronary artery, which branched into the anterior descending and circumflex arteries, arose from the left sinus. One of these patients had a short intramural course of the right coronary artery. In 2 patients, there was a single coronary artery that arose from the right sinus and branched into the right coronary, left anterior descending, and circumflex arteries. In 1 patient, both coronary arteries arose close together with a double ostium from the right sinus with a short intramural course of the left coronary artery. Surgery was performed under deep hypothermic (18°C) circulatory arrest. A 30 ml/kg cardioplegic crystalloid (Bretschneider) solution was infused to provide myocardial protection. Surgery was performed by 2 surgeons from our institution, both of whom followed the same guidelines: when cardiopul-
operation involves transection and reanastomosis of both great arteries above the sinuses of Valsalva and translocation of the coronary arteries. The long-term success of this procedure depends principally on the adequate function of the left ventricle and on the continued patency and adequate functioning of the coronary arteries. Limited data are available with respect to the exercise tolerance of patients with simple transposition of the great arteries who underwent neonatal anatomic repair, because they are only now reaching an age when exercise testing becomes feasible. They are thought to have a low prevalence of left ventricular dysfunction,1–7 but ischemia may result from coronary kinking, stenosis, or occlusion, or from reduced coronary flow reserve.2,3,5–9
METHODS
Patients: Eligibility criteria for participation in this study included (1) an arterial switch operation in our institution during the neonatal period, (2) age .48 months, (3) no physical limitations (New York Heart Association functional class 1), no symptoms and no cardioactive medications, (4) no prior experience with the treadmill and no opportunity for practice. Fifty
From the Departments of Pediatric Cardiology, and Cardiovascular Surgery, Aachen, Germany. Manuscript received June 30, 1997; revised manuscript received and accepted October 6, 1997. Address for reprints: Martial Massin, MD, Division of Pediatric Cardiology, CHR Citadelle, Bd 12e` de Ligne, 1, B-4000 Lie`ge, Belgium.
56
©1998 by Excerpta Medica, Inc. All rights reserved.
0002-9149/98/$19.00 PII S0002-9149(97)00863-1
monary bypass was established and circulatory arrest performed, the ductus arteriosus was dissected out, divided, and ligated. The aorta was transected 1 cm above the aortic valve and the coronary ostia were excised with a U-shaped cuff of aortic sinus wall. The main pulmonary artery was transected just proximal to the origin of the right branch. The coronary arteries were implanted using 7-0 absorbable PDS suture material into 2 defects created by trapdoor flaps just above the pulmonary valve. The Lecompte maneuver10 was performed. The proximal main pulmonary artery, which bears the translocated coronary arteries, was then anastomosed with 6-0 PDS material to the ascending aorta, and the distal artery was anastomosed also using 6-0 PDS material to the neopulmonary artery, and repaired with 2 U-shaped autologous pericardial patches to fill the gaps in the posterior wall caused by the excision of the coronary ostia. The mean age at surgery was 6 days (SD 2.5, range 2 to 12). The postoperative course was unremarkable for 49 of the 50 patients. The patient with a short and unnoticed intramural course of the right coronary artery, which was damaged during excision, required immediately after the arterial switch operation an internal mammary bypass graft to the right coronary artery; this artery appeared malperfused at the end of the arterial switch operation.11 All patients underwent selective cardiac catheterization and cineangiography about 1 year after the operation. All cineangiograms were reviewed at the time of the study. The patient with an internal mammary bypass graft had a mild stenosis at the site of anastomosis to the right coronary artery. The child with both coronary arteries arising from the right sinus and short intramural course of the left coronary artery had previously unsuspected left main coronary artery occlusion, and developed adequate collaterals with retrograde opacification of the obstructed vessel visualized during angiography. Except for these 2 patients, the coronary arteries showed no stenosis or kinking. In 3 patients, regional wall abnormalities were detected: inferior and posterobasal segments in the child with the mammary bypass, anterobasal and anterolateral segments in the child with the coronary occlusion, and a posterobasal segment in the child with ‘‘usual’’ coronary arteries. The electrocardiogram and echocardiogram were recorded before the exercise treadmill test was conducted. Study protocol and testing: Treadmill exercise testing was performed using the Bruce walking treadmill protocol to voluntary exhaustion on a Jaeger LE3000 treadmill (Erich Jaeger, Ho¨chberg, Germany). All tests were performed under standardized conditions in a stable laboratory environment. The children maintained their normal diet before the day of testing and ate only a light carbohydrate meal at least 2 hours before the test procedure. Only light physical activity was performed on the day before testing, and on the test day, children did not exercise before their laboratory visit. On their visit to the laboratory, the children
were given adequate explanation of the proposed protocol and objectives. Children with infections were not allowed to participate in the laboratory test. We adhered to the original Bruce walking protocol for children consisting of seven 3-minute stages12: (1) 1.7 miles/hour at a slope of 10%, (2) 2.5 miles/hour at a slope of 12%, (3) 3.4 miles/hour at a slope of 14%, (4) 4.2 miles/hour at a slope of 16%, (5) 5.0 miles/ hour at a slope of 18%, (6) 5.5 miles/hour at a slope of 20%, and (7) 6.0 miles/hour at a slope of 22%. The children were not permitted to hold onto the guard rails of the treadmill when walking, except to maintain their balance at change of stage. They were encouraged to push themselves to the limit and the test was stopped when the children refused to continue the test despite encouragement. Monitoring continued for at least 10 minutes after the end of the test. One doctor was always present. A harness was used for safety purposes. The electrocardiogram was continuously monitored using 6 of the 12 leads alternatively (Megarcart electrocardiograph, Siemens, Germany). Heart rate was obtained by measuring the interval between 5 R waves at rest, at the end of each 3-minute exercise stage, at the end of maximal exercise, and at 2 and 5 minutes of the recovery period. Blood pressure at rest and at the end of maximal exercise was measured on the right arm using a sphygmomanometer (Dinamap compact 8103, Critikon, Johnson & Johnson Sante´, Chatenay-Malabry, France) with cuffs of various sizes, and the double product (heart rate–systolic blood pressure product) was calculated. Endurance time and electrocardiographic changes were also analyzed. Results were reviewed and compared with those of age-matched healthy, nonathletic children taken from the published data.12,13
RESULTS Forty-seven patients had a normal exercise capacity and normal cardiovascular parameters. The maximal heart rate at peak exercise was 186.9 6 10.2 beats/min, but .180 beats/min in all cases. Endurance time was .90th percentile in 7 patients, between the 75th and the 90th percentile in 11, between the 50th and the 75th percentile in 14, between the 25th and the 50th percentile in 7, between the 10th and the 25th percentile in 7, and ,10th percentile in 1. This last child did not produce a near maximal effort, pushing the emergency stop button by joke. During exercise testing, all patients remained asymptomatic. Of the 47 patients, none had electrocardiographic evidence of ischemia or arrhythmias. One patient had ventricular extrasystoles at rest, which disappeared during the test. Another patient had a delta wave at rest, which did not disappear during the exercise test. Three patients showed a pathologic response to exercise stress: The child with the occlusion of the left main coronary artery, aged 4 years, had a normal resting electrocardiogram but developed a classic ischemic response with a 0.8 mV ST-segment depression in leads V4 to V6, appearing suddenly at a heart rate of 170 beats/min (Figure 1), leading to discontin-
CONGENITAL HEART DISEASE/TRANSPOSITION OF THE GREAT ARTERIES
57
The mobilization and translocation of the coronary arteries remains the most technically challenging aspect of the arterial switch operation; it carries the combined risk of primary ischemic injury and late problems with coronary artery kinking, stenosis, or occlusion. Several investigators described late coronary occlusion or stenosis.2,3,5– 8 Their incidence was 3% of the 366 patients whose cineangiograms had been reviewed by Tanel et al9 and 7.8% of the 64 patients of Bonnet et al8 who underwent selective coronary an-
giography. There have been sporadic reports of myocardial ischemia or sudden death in children after arterial switch repair, possibly related to inadequate coronary perfusion.2,3,5,7,9 To our knowledge, our study presents the third published data on exercise tolerance in children after arterial switch operation. The first was from Weindling et al in 1994,14 who performed resting and exercise myocardial perfusion scans using technetium-99m methoxyisobutyl isonitril (sestamibi). Exercise capacity was determined with a modified Bruce protocol. They found that all patients had exercise capacities within normal limits, although some had levels in the low normal range. Myocardial perfusion scan abnormalities were common (95.6% of the patients, 24.7% of the left ventricular segments) but generally lessened with exercise. This finding, the normal exercise tolerance, and the lack of symptoms or electrocardiographic changes suggested normal myocardial perfusion during the physiologic stress of exercise in children up to age 8 years after an arterial switch operation. In a second study, Bonnet et al8 performed exercise tests in 49 patients. Three patients had electrocardiographic evidence of ischemia, 2 during recovery and 1 during exercise. None of these 3 children had pathologic coronary angiography. Other studies using thallium-201 myocardial scintigraphy investigated the prevalence of myocardial perfusion abnormalities both at rest15,16 and with pharmacologic stress.17 These abnormalities are rarely correlated with electrocardiographic, echocardiographic, or angiographic changes, so that their clinical significance is questionable. Fukushima et al16 supposed that these abnormalities probably reflect arteriolar or capillary processes below the resolution of coronary angiography, resulting from inhomogeneous myocardial protection, embolism, or other intraoperative insults. This hypothesis could explain the exercise electrocardiographic abnormalities in the 3 cases of Bonnet et al8 with normal coronary artery angiography. Coronary flow reserve is a physiologic variable that assesses the ability of coronary flow to increase under hyperemic stimulation. Evaluation of patients with coronary artery disease has shown significant discrepancies between anatomically defined lesion severity and functional significance.18 Abnormal coronary flow reserve and abnormal radionuclide exercise test results have been found in adults with normal coronary angiograms.19 Three patients in our study had electrocardiographic signs of myocardial ischemia or exercise-induced ventricular arrhythmias possibly secondary to reduced coronary flow reserve. Two of them had myocardial perfusion abnormalities at rest and left ventricular regional wall motion abnormalities. Coronary occlusion with inadequate collateralization, previous myocardial infarction, and unusual origin and course of the coronary arteries (by themselves or by increasing the risk of intraoperative insults leading to coronary lesions at the arteriolar level) are the probable causes of decreased coronary reserve in our 3 patients with pathologic findings. Many questions remain about long-term develop-
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JANUARY 1, 1998
FIGURE 1. Electrocardiogram of patient 1: ST-segment depression in leads V4 to V6 at a heart rate of 170 beats/min.
uation of the exercise test. One of the 2 patients with a single right coronary artery ostium, aged 4 years, had ventricular premature complexes but no signs of myocardial ischemia at rest, and exercise testing exacerbated the ventricular ectopic activity and further induced salvos of ventricular tachycardia (Figure 2). The child remained asymptomatic, the test was not terminated, and his endurance time was normal. The resting electrocardiogram of the patient with an internal mammary bypass graft, aged 7 years, showed Q waves in II, aVF, and III as sequelae of a neonatal myocardial infarction and ventricular premature complexes at rest. Exercise testing exacerbated ventricular ectopic activity and further induced salvos of ventricular tachycardia (Figure 3). His endurance time was reduced. A new cardiac catheterization with left ventriculography and coronary angiography was performed in those 3 children, and confirmed the findings of the selective catheterization that had been performed about 1 year after the operation. Thallium-201 myocardial scintigraphy was not performed in the child with the single right coronary artery ostium because consent of the parents could not be obtained, but it was performed in the 2 other patients, showing twiceimpaired myocardial perfusion of the segments that were hypokinetic on the left ventriculogram.
DISCUSSION
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FIGURE 2. Electrocardiogram of patient 2: exercise-induced salvos of ventricular tachycardia.
FIGURE 3. Electrocardiogram of patient 3: exercise-induces salvos of ventricular tachycardia.
ment of coronary circulation after coronary reimplantation, including the evolution of atherosclerosis and coronary flow reserve. Combining our results with those in other published reports,8,9,14 we can consider that late coronary artery complications are uncommon in patients who have undergone neonatal arterial switch operation for simple transposition of the great arteries. Most children with coronary artery stenosis or occlusion are asymptomatic, and exercise testing did not seem to be useful in detecting such abnormalities in the study of Bonnet et al.8 Their detection in asymptomatic young patients without electrocardiographic signs of myocardial ischemia at rest or during
exercise, or echocardiographic left ventricular regional wall motion abnormalities, has no direct clinical implication because aortocoronary bypass, coronary artery trunk reimplantation, or coronary artery dilatation is not then recommended in view of the important limitations of the different treatments in young children, and of the unclear clinical relevance of cardiac dependence on a single coronary artery with good collateral circulation.8,9 On the contrary, ischemic damage or exercise-induced arrhythmias possibly secondary to reduced coronary flow reserve are potentially life-threatening complications that need to be detected and treated promptly. Their detection appears to be strongly improved by exercise testing and we recommend that all children exercise who have undergone a neonatal arterial switch operation for simple transposition of the great arteries; also, it is necessary to perform left ventriculography and coronary angiography in children with positive exercise test results. Our results are encouraging, but potential late complications associated with inadequate coronary perfusion remain a concern that must be dealt with in long-term follow-up studies.
1. Colan SD, Trowitzsch E, Wernovsky G, Sholler G, Sanders S, Castaneda A. Myocardial performance after arterial switch operation for transposition of the great arteries with intact ventricular septum. Circulation 1988;78:132–141. 2. Di Donato RM, Wernovsky G, Walsh EP, Colan SD, Lang P, Wessel DL, Jonas RA, Mayer JE Jr, Castaneda AR. Results of the arterial switch operation for transposition of the great arteries with ventricular septal defect: surgical considerations and midterm follow-up data. Circulation 1989;80:1689 –1705. 3. Kramer HH, Rammos S, Krian A, Krogmann O, Ostermeyer J, Korbmacher B, Buhl R. Intermediate-term clinical and hemodynamic results of the neonatal arterial switch operation for complete transposition of the great arteries. Int J Cardiol 1992;36:13–22. 4. Serraf A, Lacour-Gayet F, Bruniaux J, Touchot A, Losay J, Comas J, Sousa Uva M, Planche´ C. Anatomic correction of the transposition of the great arteries in neonates. J Am Coll Cardiol 1993;22:193–200. 5. Tsuda E, Imakita M, Yagihara T, Ono Y, Echigo S, Takahashi O, Kamiya T.
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Late death after arterial switch operation for transposition of the great arteries. Am Heart J 1992;124:1551–1557. 6. Wernovsky G, Hougen TJ, Walsh EP, Sholler GF, Colan SD, Sanders SP, Parness IA, Keane JF, Mayer JE, Jonas RA, Castaneda AR, Lang P. Midterm results after the arterial switch operation for transposition of the great arteries with intact ventricular septum: clinical, hemodynamic, echocardiographic, and electrophysiologic data. Circulation 1988;77:1333–1344. 7. Yamaguchi M, Hosokawa Y, Imai Y, Kurosawa H, Yasui H, Yagihara T, Okamoto F, Wakaki N. Early and midterm results of the arterial switch operation for transposition of the great arteries in Japan. J Thorac Cardiovasc Surg 1990;100:261–269. 8. Bonnet D, Bonhoeffer P, Pie´chaud JF, Aggoun Y, Sidi D, Planche´ C, Kachaner J. Long-term fate of the coronary arteries after the arterial switch operation in newborns with transposition of the great arteries. Heart 1996;76:274 –279. 9. Tanel RE, Wernovsky G, Landzberg MJ, Perry SB, Burke RP. Coronary artery abnormalities detected at cardiac catheterization following the arterial switch operation for transposition of the great arteries. Am J Cardiol 1995;76:153–157. 10. Lecompte Y, Zannini L, Hazan E, Jarreau MM, Bex JP, Viet Tu T, Neveux JY. Anatomic correction of transposition of the great arteries: new technique without use of a prosthetic conduit. J Thorac Cardiovasc Surg 1981;82:629 – 631. 11. Grabitz R, Messmer BJ, Seghaye MC, Engelhardt W, Mu¨hler E, von Bernuth G. Internal mammary artery bypass graft for impaired coronary perfusion after neonatal arterial switch operation. Eur J Cardiothorac Surg 1992;6:388 –390. 12. Cumming G, Everatt D, Hastman L. Bruce treadmill test in children: normal values in a clinic population. Am J Cardiol 1978;41:69 –75.
13. Maffulli N, Greco R, Greco L, D’Alterio D. Treadmill exercise in Neapolitan children and adolescents. Acta Paediatr 1994;83:106 –112. 14. Weindling SN, Wernovsky G, Colan SD, Parker JA, Boutin C, Mone SM, Castello J, Castaneda AR, Treves ST. Myocardial perfusion, function and exercise tolerance after the arterial switch operation. J Am Coll Cardiol 1994;23: 424 – 433. 15. Bjo¨rkhem G, Evander E, White T, Lundstro¨m NR. Myocardial scintigraphy with 201-thallium in pediatric cardiology: a review of 52 cases. Pediatr Cardiol 1990;11:1–7. 16. Fukushima H, Satou S, Satou I, Iwatani H, Tsuda E, Nakamura H, Ono Y, Kohata T, Kamiya T. Thallium-201 myocardial imaging in cases involving transposition of the great arteries after the arterial switch operation. Kokyo-ToJunkan 1992;40:485– 490. 17. Vogel M, Smallhorn JF, Trusler GA, Freedom RM. Echocardiographic analysis of regional left ventricular wall motion in children after the arterial switch operation for complete transposition of the great arteries. J Am Coll Cardiol 1990;15:1417–1423. 18. White CW, Wright CB, Doty DB, Hiratza LF, Eastham CL, Harrison DG, Marcus ML. Does visual interpretation of the coronary arteriogram predict the physiologic importance of a coronary stenosis? N Engl J Med 1984;310:819 – 824. 19. Legrand V, Hodgson J, Bates ER, Aueron FM, Mancini GBJ, Smith JS, Gross MD, Vogel RA. Abnormal coronary flow reserve and abnormal radionuclide exercise test results in patients with normal coronary angiograms. J Am Coll Cardiol 1985;6:1245–1253.
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MD,
Children who underwent arterial switch operation for simple transposition of the great arteries in the neonatal period are now reaching an age when exercise testing becomes feasible. This study was conducted to assess exercise tolerance and electrocardiographic response to exercise stress in 50 asymptomatic children, aged 4 to 9 years, using the Bruce walking treadmill protocol to voluntary exhaustion. Heart rate and blood pressure response to exercise stress, endurance time, and electrocardiographic changes were analyzed and compared with those of age-matched normal children. Forty-seven patients had normal exercise capacity and parameters. One patient, whose coronary angiogram showed occlusion of the left main coronary artery, developed electrocardiographic signs of myocardial ischemia during ex-
ercise. In 1 patient with a single right coronary artery ostium and in another, who underwent a neonatal internal mammary bypass graft for obstruction of the right coronary artery, the resting electrocardiogram showed ventricular premature complexes and exercise stressinduced salvos of ventricular tachycardia. We conclude that most of the children who underwent the neonatal arterial switch operation for simple transposition of the great arteries have a normal exercise capacity. Exercise testing appears to be useful in detecting ischemic damage or exercise-induced arrhythmias possibly secondary to reduced coronary flow reserve. Q1998 by Excerpta Medica, Inc. (Am J Cardiol 1998;81:56 – 60)
rterial switch operation is actually considered the surgical treatment of choice for repair of transA position of the great arteries in the newborn. This
patients, aged 4 to 9 years (mean 6 SD 5.6 6 1.5), participated in the study. There were 40 boys and 10 girls. All children were within the fifth and the 95th percentiles for height and weight. All procedures were explained in detail to both children and parents who had agreed to take part in the study, and informed consent was obtained for each participant. Five patients had a ventricular septal defect at the time of surgery which was small and left untouched in 3 patients (in 2 of these, the defect subsequently closed spontaneously) and was surgically closed through the right atrium in 2 patients. One patient also had a mild aortic coarctation that was not repaired. Origin and course of the coronary arteries before arterial switch operation was as follows: in 47 patients, the right coronary artery arose from the right sinus, and the left coronary artery, which branched into the anterior descending and circumflex arteries, arose from the left sinus. One of these patients had a short intramural course of the right coronary artery. In 2 patients, there was a single coronary artery that arose from the right sinus and branched into the right coronary, left anterior descending, and circumflex arteries. In 1 patient, both coronary arteries arose close together with a double ostium from the right sinus with a short intramural course of the left coronary artery. Surgery was performed under deep hypothermic (18°C) circulatory arrest. A 30 ml/kg cardioplegic crystalloid (Bretschneider) solution was infused to provide myocardial protection. Surgery was performed by 2 surgeons from our institution, both of whom followed the same guidelines: when cardiopul-
operation involves transection and reanastomosis of both great arteries above the sinuses of Valsalva and translocation of the coronary arteries. The long-term success of this procedure depends principally on the adequate function of the left ventricle and on the continued patency and adequate functioning of the coronary arteries. Limited data are available with respect to the exercise tolerance of patients with simple transposition of the great arteries who underwent neonatal anatomic repair, because they are only now reaching an age when exercise testing becomes feasible. They are thought to have a low prevalence of left ventricular dysfunction,1–7 but ischemia may result from coronary kinking, stenosis, or occlusion, or from reduced coronary flow reserve.2,3,5–9
METHODS
Patients: Eligibility criteria for participation in this study included (1) an arterial switch operation in our institution during the neonatal period, (2) age .48 months, (3) no physical limitations (New York Heart Association functional class 1), no symptoms and no cardioactive medications, (4) no prior experience with the treadmill and no opportunity for practice. Fifty
From the Departments of Pediatric Cardiology, and Cardiovascular Surgery, Aachen, Germany. Manuscript received June 30, 1997; revised manuscript received and accepted October 6, 1997. Address for reprints: Martial Massin, MD, Division of Pediatric Cardiology, CHR Citadelle, Bd 12e` de Ligne, 1, B-4000 Lie`ge, Belgium.
56
©1998 by Excerpta Medica, Inc. All rights reserved.
0002-9149/98/$19.00 PII S0002-9149(97)00863-1
monary bypass was established and circulatory arrest performed, the ductus arteriosus was dissected out, divided, and ligated. The aorta was transected 1 cm above the aortic valve and the coronary ostia were excised with a U-shaped cuff of aortic sinus wall. The main pulmonary artery was transected just proximal to the origin of the right branch. The coronary arteries were implanted using 7-0 absorbable PDS suture material into 2 defects created by trapdoor flaps just above the pulmonary valve. The Lecompte maneuver10 was performed. The proximal main pulmonary artery, which bears the translocated coronary arteries, was then anastomosed with 6-0 PDS material to the ascending aorta, and the distal artery was anastomosed also using 6-0 PDS material to the neopulmonary artery, and repaired with 2 U-shaped autologous pericardial patches to fill the gaps in the posterior wall caused by the excision of the coronary ostia. The mean age at surgery was 6 days (SD 2.5, range 2 to 12). The postoperative course was unremarkable for 49 of the 50 patients. The patient with a short and unnoticed intramural course of the right coronary artery, which was damaged during excision, required immediately after the arterial switch operation an internal mammary bypass graft to the right coronary artery; this artery appeared malperfused at the end of the arterial switch operation.11 All patients underwent selective cardiac catheterization and cineangiography about 1 year after the operation. All cineangiograms were reviewed at the time of the study. The patient with an internal mammary bypass graft had a mild stenosis at the site of anastomosis to the right coronary artery. The child with both coronary arteries arising from the right sinus and short intramural course of the left coronary artery had previously unsuspected left main coronary artery occlusion, and developed adequate collaterals with retrograde opacification of the obstructed vessel visualized during angiography. Except for these 2 patients, the coronary arteries showed no stenosis or kinking. In 3 patients, regional wall abnormalities were detected: inferior and posterobasal segments in the child with the mammary bypass, anterobasal and anterolateral segments in the child with the coronary occlusion, and a posterobasal segment in the child with ‘‘usual’’ coronary arteries. The electrocardiogram and echocardiogram were recorded before the exercise treadmill test was conducted. Study protocol and testing: Treadmill exercise testing was performed using the Bruce walking treadmill protocol to voluntary exhaustion on a Jaeger LE3000 treadmill (Erich Jaeger, Ho¨chberg, Germany). All tests were performed under standardized conditions in a stable laboratory environment. The children maintained their normal diet before the day of testing and ate only a light carbohydrate meal at least 2 hours before the test procedure. Only light physical activity was performed on the day before testing, and on the test day, children did not exercise before their laboratory visit. On their visit to the laboratory, the children
were given adequate explanation of the proposed protocol and objectives. Children with infections were not allowed to participate in the laboratory test. We adhered to the original Bruce walking protocol for children consisting of seven 3-minute stages12: (1) 1.7 miles/hour at a slope of 10%, (2) 2.5 miles/hour at a slope of 12%, (3) 3.4 miles/hour at a slope of 14%, (4) 4.2 miles/hour at a slope of 16%, (5) 5.0 miles/ hour at a slope of 18%, (6) 5.5 miles/hour at a slope of 20%, and (7) 6.0 miles/hour at a slope of 22%. The children were not permitted to hold onto the guard rails of the treadmill when walking, except to maintain their balance at change of stage. They were encouraged to push themselves to the limit and the test was stopped when the children refused to continue the test despite encouragement. Monitoring continued for at least 10 minutes after the end of the test. One doctor was always present. A harness was used for safety purposes. The electrocardiogram was continuously monitored using 6 of the 12 leads alternatively (Megarcart electrocardiograph, Siemens, Germany). Heart rate was obtained by measuring the interval between 5 R waves at rest, at the end of each 3-minute exercise stage, at the end of maximal exercise, and at 2 and 5 minutes of the recovery period. Blood pressure at rest and at the end of maximal exercise was measured on the right arm using a sphygmomanometer (Dinamap compact 8103, Critikon, Johnson & Johnson Sante´, Chatenay-Malabry, France) with cuffs of various sizes, and the double product (heart rate–systolic blood pressure product) was calculated. Endurance time and electrocardiographic changes were also analyzed. Results were reviewed and compared with those of age-matched healthy, nonathletic children taken from the published data.12,13
RESULTS Forty-seven patients had a normal exercise capacity and normal cardiovascular parameters. The maximal heart rate at peak exercise was 186.9 6 10.2 beats/min, but .180 beats/min in all cases. Endurance time was .90th percentile in 7 patients, between the 75th and the 90th percentile in 11, between the 50th and the 75th percentile in 14, between the 25th and the 50th percentile in 7, between the 10th and the 25th percentile in 7, and ,10th percentile in 1. This last child did not produce a near maximal effort, pushing the emergency stop button by joke. During exercise testing, all patients remained asymptomatic. Of the 47 patients, none had electrocardiographic evidence of ischemia or arrhythmias. One patient had ventricular extrasystoles at rest, which disappeared during the test. Another patient had a delta wave at rest, which did not disappear during the exercise test. Three patients showed a pathologic response to exercise stress: The child with the occlusion of the left main coronary artery, aged 4 years, had a normal resting electrocardiogram but developed a classic ischemic response with a 0.8 mV ST-segment depression in leads V4 to V6, appearing suddenly at a heart rate of 170 beats/min (Figure 1), leading to discontin-
CONGENITAL HEART DISEASE/TRANSPOSITION OF THE GREAT ARTERIES
57
The mobilization and translocation of the coronary arteries remains the most technically challenging aspect of the arterial switch operation; it carries the combined risk of primary ischemic injury and late problems with coronary artery kinking, stenosis, or occlusion. Several investigators described late coronary occlusion or stenosis.2,3,5– 8 Their incidence was 3% of the 366 patients whose cineangiograms had been reviewed by Tanel et al9 and 7.8% of the 64 patients of Bonnet et al8 who underwent selective coronary an-
giography. There have been sporadic reports of myocardial ischemia or sudden death in children after arterial switch repair, possibly related to inadequate coronary perfusion.2,3,5,7,9 To our knowledge, our study presents the third published data on exercise tolerance in children after arterial switch operation. The first was from Weindling et al in 1994,14 who performed resting and exercise myocardial perfusion scans using technetium-99m methoxyisobutyl isonitril (sestamibi). Exercise capacity was determined with a modified Bruce protocol. They found that all patients had exercise capacities within normal limits, although some had levels in the low normal range. Myocardial perfusion scan abnormalities were common (95.6% of the patients, 24.7% of the left ventricular segments) but generally lessened with exercise. This finding, the normal exercise tolerance, and the lack of symptoms or electrocardiographic changes suggested normal myocardial perfusion during the physiologic stress of exercise in children up to age 8 years after an arterial switch operation. In a second study, Bonnet et al8 performed exercise tests in 49 patients. Three patients had electrocardiographic evidence of ischemia, 2 during recovery and 1 during exercise. None of these 3 children had pathologic coronary angiography. Other studies using thallium-201 myocardial scintigraphy investigated the prevalence of myocardial perfusion abnormalities both at rest15,16 and with pharmacologic stress.17 These abnormalities are rarely correlated with electrocardiographic, echocardiographic, or angiographic changes, so that their clinical significance is questionable. Fukushima et al16 supposed that these abnormalities probably reflect arteriolar or capillary processes below the resolution of coronary angiography, resulting from inhomogeneous myocardial protection, embolism, or other intraoperative insults. This hypothesis could explain the exercise electrocardiographic abnormalities in the 3 cases of Bonnet et al8 with normal coronary artery angiography. Coronary flow reserve is a physiologic variable that assesses the ability of coronary flow to increase under hyperemic stimulation. Evaluation of patients with coronary artery disease has shown significant discrepancies between anatomically defined lesion severity and functional significance.18 Abnormal coronary flow reserve and abnormal radionuclide exercise test results have been found in adults with normal coronary angiograms.19 Three patients in our study had electrocardiographic signs of myocardial ischemia or exercise-induced ventricular arrhythmias possibly secondary to reduced coronary flow reserve. Two of them had myocardial perfusion abnormalities at rest and left ventricular regional wall motion abnormalities. Coronary occlusion with inadequate collateralization, previous myocardial infarction, and unusual origin and course of the coronary arteries (by themselves or by increasing the risk of intraoperative insults leading to coronary lesions at the arteriolar level) are the probable causes of decreased coronary reserve in our 3 patients with pathologic findings. Many questions remain about long-term develop-
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FIGURE 1. Electrocardiogram of patient 1: ST-segment depression in leads V4 to V6 at a heart rate of 170 beats/min.
uation of the exercise test. One of the 2 patients with a single right coronary artery ostium, aged 4 years, had ventricular premature complexes but no signs of myocardial ischemia at rest, and exercise testing exacerbated the ventricular ectopic activity and further induced salvos of ventricular tachycardia (Figure 2). The child remained asymptomatic, the test was not terminated, and his endurance time was normal. The resting electrocardiogram of the patient with an internal mammary bypass graft, aged 7 years, showed Q waves in II, aVF, and III as sequelae of a neonatal myocardial infarction and ventricular premature complexes at rest. Exercise testing exacerbated ventricular ectopic activity and further induced salvos of ventricular tachycardia (Figure 3). His endurance time was reduced. A new cardiac catheterization with left ventriculography and coronary angiography was performed in those 3 children, and confirmed the findings of the selective catheterization that had been performed about 1 year after the operation. Thallium-201 myocardial scintigraphy was not performed in the child with the single right coronary artery ostium because consent of the parents could not be obtained, but it was performed in the 2 other patients, showing twiceimpaired myocardial perfusion of the segments that were hypokinetic on the left ventriculogram.
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FIGURE 2. Electrocardiogram of patient 2: exercise-induced salvos of ventricular tachycardia.
FIGURE 3. Electrocardiogram of patient 3: exercise-induces salvos of ventricular tachycardia.
ment of coronary circulation after coronary reimplantation, including the evolution of atherosclerosis and coronary flow reserve. Combining our results with those in other published reports,8,9,14 we can consider that late coronary artery complications are uncommon in patients who have undergone neonatal arterial switch operation for simple transposition of the great arteries. Most children with coronary artery stenosis or occlusion are asymptomatic, and exercise testing did not seem to be useful in detecting such abnormalities in the study of Bonnet et al.8 Their detection in asymptomatic young patients without electrocardiographic signs of myocardial ischemia at rest or during
exercise, or echocardiographic left ventricular regional wall motion abnormalities, has no direct clinical implication because aortocoronary bypass, coronary artery trunk reimplantation, or coronary artery dilatation is not then recommended in view of the important limitations of the different treatments in young children, and of the unclear clinical relevance of cardiac dependence on a single coronary artery with good collateral circulation.8,9 On the contrary, ischemic damage or exercise-induced arrhythmias possibly secondary to reduced coronary flow reserve are potentially life-threatening complications that need to be detected and treated promptly. Their detection appears to be strongly improved by exercise testing and we recommend that all children exercise who have undergone a neonatal arterial switch operation for simple transposition of the great arteries; also, it is necessary to perform left ventriculography and coronary angiography in children with positive exercise test results. Our results are encouraging, but potential late complications associated with inadequate coronary perfusion remain a concern that must be dealt with in long-term follow-up studies.
1. Colan SD, Trowitzsch E, Wernovsky G, Sholler G, Sanders S, Castaneda A. Myocardial performance after arterial switch operation for transposition of the great arteries with intact ventricular septum. Circulation 1988;78:132–141. 2. Di Donato RM, Wernovsky G, Walsh EP, Colan SD, Lang P, Wessel DL, Jonas RA, Mayer JE Jr, Castaneda AR. Results of the arterial switch operation for transposition of the great arteries with ventricular septal defect: surgical considerations and midterm follow-up data. Circulation 1989;80:1689 –1705. 3. Kramer HH, Rammos S, Krian A, Krogmann O, Ostermeyer J, Korbmacher B, Buhl R. Intermediate-term clinical and hemodynamic results of the neonatal arterial switch operation for complete transposition of the great arteries. Int J Cardiol 1992;36:13–22. 4. Serraf A, Lacour-Gayet F, Bruniaux J, Touchot A, Losay J, Comas J, Sousa Uva M, Planche´ C. Anatomic correction of the transposition of the great arteries in neonates. J Am Coll Cardiol 1993;22:193–200. 5. Tsuda E, Imakita M, Yagihara T, Ono Y, Echigo S, Takahashi O, Kamiya T.
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Late death after arterial switch operation for transposition of the great arteries. Am Heart J 1992;124:1551–1557. 6. Wernovsky G, Hougen TJ, Walsh EP, Sholler GF, Colan SD, Sanders SP, Parness IA, Keane JF, Mayer JE, Jonas RA, Castaneda AR, Lang P. Midterm results after the arterial switch operation for transposition of the great arteries with intact ventricular septum: clinical, hemodynamic, echocardiographic, and electrophysiologic data. Circulation 1988;77:1333–1344. 7. Yamaguchi M, Hosokawa Y, Imai Y, Kurosawa H, Yasui H, Yagihara T, Okamoto F, Wakaki N. Early and midterm results of the arterial switch operation for transposition of the great arteries in Japan. J Thorac Cardiovasc Surg 1990;100:261–269. 8. Bonnet D, Bonhoeffer P, Pie´chaud JF, Aggoun Y, Sidi D, Planche´ C, Kachaner J. Long-term fate of the coronary arteries after the arterial switch operation in newborns with transposition of the great arteries. Heart 1996;76:274 –279. 9. Tanel RE, Wernovsky G, Landzberg MJ, Perry SB, Burke RP. Coronary artery abnormalities detected at cardiac catheterization following the arterial switch operation for transposition of the great arteries. Am J Cardiol 1995;76:153–157. 10. Lecompte Y, Zannini L, Hazan E, Jarreau MM, Bex JP, Viet Tu T, Neveux JY. Anatomic correction of transposition of the great arteries: new technique without use of a prosthetic conduit. J Thorac Cardiovasc Surg 1981;82:629 – 631. 11. Grabitz R, Messmer BJ, Seghaye MC, Engelhardt W, Mu¨hler E, von Bernuth G. Internal mammary artery bypass graft for impaired coronary perfusion after neonatal arterial switch operation. Eur J Cardiothorac Surg 1992;6:388 –390. 12. Cumming G, Everatt D, Hastman L. Bruce treadmill test in children: normal values in a clinic population. Am J Cardiol 1978;41:69 –75.
13. Maffulli N, Greco R, Greco L, D’Alterio D. Treadmill exercise in Neapolitan children and adolescents. Acta Paediatr 1994;83:106 –112. 14. Weindling SN, Wernovsky G, Colan SD, Parker JA, Boutin C, Mone SM, Castello J, Castaneda AR, Treves ST. Myocardial perfusion, function and exercise tolerance after the arterial switch operation. J Am Coll Cardiol 1994;23: 424 – 433. 15. Bjo¨rkhem G, Evander E, White T, Lundstro¨m NR. Myocardial scintigraphy with 201-thallium in pediatric cardiology: a review of 52 cases. Pediatr Cardiol 1990;11:1–7. 16. Fukushima H, Satou S, Satou I, Iwatani H, Tsuda E, Nakamura H, Ono Y, Kohata T, Kamiya T. Thallium-201 myocardial imaging in cases involving transposition of the great arteries after the arterial switch operation. Kokyo-ToJunkan 1992;40:485– 490. 17. Vogel M, Smallhorn JF, Trusler GA, Freedom RM. Echocardiographic analysis of regional left ventricular wall motion in children after the arterial switch operation for complete transposition of the great arteries. J Am Coll Cardiol 1990;15:1417–1423. 18. White CW, Wright CB, Doty DB, Hiratza LF, Eastham CL, Harrison DG, Marcus ML. Does visual interpretation of the coronary arteriogram predict the physiologic importance of a coronary stenosis? N Engl J Med 1984;310:819 – 824. 19. Legrand V, Hodgson J, Bates ER, Aueron FM, Mancini GBJ, Smith JS, Gross MD, Vogel RA. Abnormal coronary flow reserve and abnormal radionuclide exercise test results in patients with normal coronary angiograms. J Am Coll Cardiol 1985;6:1245–1253.
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