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Cardiorespiratory Response to Exercise After Venous Switch Operation for Transposition of the Great Arteries* Douard, MD; Laurent Labbe, MD; Jean Louis Barat, MD; Paul Broustet, MD; Eugene Baudet, MD; and Alain Choussat, MD Jean Herve Study objective: This study reports on the cardiorespiratory response to graded exercise in patients after venous switch operation for transposition of the great arteries. Design: Several small studies have documented a diminished exercise tolerance after Mustard repair for transposition of the great arteries; little information exists, however, about long-term cardiorespiratory exercise performance in patients who have had the Senning procedure. Patients: This prospective study reports on the serial long-term (mean, 11 ±2.8 years) cardiopul¬ monary exercise performance of 43 patients (age, 12±3.1 years) who underwent a Senning procedure, with no significant postoperative abnormalities. Forty-three matched healthy chil¬ dren were also studied as a control group. Measurements and results: All underwent exercise testing (Bruce protocol) with metabolic gas exchange to determine parameters at 3 min, anaerobic threshold, similar heart rate (150 beats/min), and peak exercise. Time of exercise was 10.5±1.9 min in patients and 13.4±2 min in control subjects (p=0.0001). Overall, patients reached 73% of peak oxygen uptake achieved by control subjects (32.6±5.6 vs 44.7±6 mL/kg/min). Chronotropic response (188±15.7 vs 166.5±19.6 beats/min [p=0.0001]) and oxygen pulse (7.4±2.9 vs 10.7±4.2 mL/beat [p=0.0002]) were lower in patients at peak exercise. Patients had a greater respiratory response to exercise: both respiratory rate and ventilatory equivalent for carbon dioxide were significantly higher at all stages of exercise. Exercise capacity assessed by peak oxygen uptake was correlated with time elapsed since surgical repair (r=0.48; p=0.001). Conclusions: It is concluded that even in asymptomatic patients, exercise endurance and respiratory response are generally altered as much as 11 ±2.8 years after venous switch operation, although early surgical repair is predictive of a better long-term functional result. (CHEST 1997; 111:23-29) Key words: exercise testing; Senning; transposition of great vessels Abbreviations: ASO=atrial switch operation; AT=anaerobic (ventilatory) threshold; RR=respiratory rate; TGA=transposition of great arteries; Vco2=carbon dioxide output; Ve minute ventilation; Vo2=oxygen uptake; = Vt=tidal volume A ¦**- lthough the arterial switch operation is now frequently the procedure of choice for correct¬ ing transposition of the great arteries (TGA), most adolescents and young adults born with TGA owe their survival to the atrial switch operation (ASO).12 Mustard and Senning procedures result in low early morbidity and mortality, but longterm results have shown an increased incidence of arrhythmia,3-6 sudden deaths, and a decrease in Hopital Cardiologique 1996; revision accepted July 29. Manuscript received February 14, Service des Epreuves d'Ejfort, Reprint requests: Dr. Douard, Hopital Cardiologique, 33604 Pessac, France. *From the Cardiology Department of Haut Leveque, Pessac, France. functional capacity,718 probably because the mor¬ phologic right ventricle may be unable to function as successfully as a morphologic left ventricle in the systemic position for long periods of time.19-23 Previous investigators have described a limited cardiorespiratory response to exercise in patients who have had ASO.6-91416 However, these series were limited in number, did not always analyze gas and included patients especially oper¬ exchange,with ated on the Mustard technique. Therefore, the present study was undertaken to evaluate exercise tolerance in a larger series of 43 patients who had undergone a Senning procedure, with special attention to cardiopulmonary response. CHEST 7111/1/ JANUARY, 1997 Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21742/ on 05/06/2017 23 Materials and ent temperature, barometric pressure, and water vapor. Methods Peak Vo2 defined as the maximal value of Vo2 obtained during the last 30 s of exercise. Oxygen pulse was calculated as the ratio of Vo2 was Subjects The forty-three patients (11 girls, 32 boys) underwent ASO at our cardiologic hospital department between 1977 and 1988; after operation, they had yearly clinical, ECG, and echocardio¬ graphic examinations. All patients had at least one postoperative catheterization. Twenty-six patients had simple transposition, defined as TGA with an otherwise normal heart, whereas the remainder had additional associated defects, including ventricu¬ lar septal defect (seven patients) or ventricular outflow obstruc¬ tion (ten patients). At the time of the study, 11 patients had mild obstruction, pulmonary stenosis (<40 mm Hg), 5 had atrial baffle and 1 had important tricuspid regurgitation. Two patients had permanent pacemakers. All considered themselves asymptomatic and most of them took part in gym at school. Mean age at surgical repair was 9.6±5.6 months, and the postoperative interval ranged from 6.5 to 18.3 years (mean, 11 ±2.8 years). Two patients were taking cardiac medications at the time of their exercise study; these were diuretics (one patient) and beta-blockers (one pa¬ tient). As a control group, 43 healthy voluntarily enrolled children from local schools were also studied; none had a sport activity elsewhere. They were matched for age, sex, height, and weight to TGA patients Exercise (Table 1). out exercise by an exercise ECG system (Marquette Case 15; Electronics Inc; Milwaukee). A 15-lead ECG was obtained with the patient at rest, and at 1-min intervals for 5 min after exercise testing. BP was measured at each workload with a mercury sphygmomanometer. Gas was measured directly through open-circuit spirometry Marquette (Medical Graphic Corporation CPX System, St. Paul, Minn) by a first-responding oxygen analyzer and an infrared carbon dioxide analyzer. Minute ventilation (Ve), oxygen uptake (Vo2), carbon dioxide output (Vco2), and derived variables were measured for each breath. Before each exercise study, the system was cali¬ brated with known volumes of airflow and precise gas mixtures. Gas exchange and flow measurements were corrected for ambi- 1.Comparison ofAnthropometric and Exercise Subjects Variables in Patients and Control Control Patients (n=43) Age, Statistical Methods analyses were performed using software (Mac Statview are reported as mean values ±SD. Differences between mean values were calculated by analysis of variance with repeated measurements. Differences were considered statisti¬ cally significant at the p<0.05 level. Linear regression analysis was used to study the correlation between exercise time or age of surgery and the different indexes of cardiopulmonary tolerance. The 512). Data Testing This study was undertaken with the approval of the local ethics committee, and written informed consent from each subject's parents was obtained. Treadmill exercise testing was performed using a Bruce protocol. All children were encouraged by an nurse to exercise to exhaustion. experienced Heart rate and rhythm were monitored continuously through¬ Table the concomitant heart rate. Anaerobic threshold was deter¬ mined mainly by the V slope method, in addition to the following conventional criteria: an increase, after a period of stability or reduction in ventilatory equivalent for oxygen (Ve/Vo2) and a steeper increase in the gas exchange ratio. Vo2 at anaerobic threshold was also expressed in percent of the maximal oxygen consumption. The relationship between both respiratory rate (RR) and ventilation (Ve) against carbon dioxide production (Vco2) was calculated as indexes of the ventilation response. All parameters were examined at four reference time points, ie, the third minute of the test, anaerobic threshold, 150 beats/min if reached, and peak exercise. to yr Weight, kg cm Height, BSA* m2 Rest heart rate, beats/min Rest systolic BP, mm Hg Peak heart rate, beats/min Peak systolic BP, mm Hg Endurance time, min *BSA=body surface area. 12±3.1 38.2±15.9 145±17 1.12±0.31 85.7±15 100±10 166±20 122±16 10.5±1.9 Subjects (n=43) p Value NS 12.8±3.4 44.6±15 NS 154±19NS 1.39±0.32 NS 99±15 0.0001 109±13 0.002 188±16 0.0001 140±23 0.0001 13.4±2 0.0001 Results Characteristics of the patients and control groups summarized in Table 1. No significant differ¬ found between patients and control with subjectssurface area. respect to age, sex, weight, height, and body Compliance with the study exer¬ cise was excellent for all children. Fatigue or breathlessness were the only reasons to stop exercise. Mean heart rates at rest on ECG were 87±15.1 beats/min in patients and 99.2± 14.9 beats/min in the normal group (p=0.0001). All normal subjects and 36 of 43 patients were in sinus rhythm at rest; 5 patients had intermittent junctional rhythm; 2 pa¬ tients were paced because of sinus node dysfunction. All patients but one developed sinus tachycardia with exercise; 6 patients had significant atrial (n=3) or ventricular (n=3) arrhythmias during exercise. At control subjects achieved a signifi¬ peak exercise,heart rate (187.8±16.1 vs 166.5±19.6 cantly higher are ences were beats/min; p=0.0001). Twenty-one patients were unable to reach 80% of their theoretical maximal heart rate, and 6 patients did not achieve 150 beats/min at the end of exercise; the relation¬ ship between chronotropic response and Vo2 was y=3.1 x+47.2 in control subjects and y=4.2 x+31.3 in patients, where y=heart rate (beats/min) and x=Vo2 in mL/min/kg (Fig 1). Maximal exercise heart rate showed no correlation with either age at the time of operation or age at the time of exercise testing. However, maximal heart rate was weakly correlated with peak Vo2 in patients (r=0.29, p=0.05). Systolic BP was also different at rest (pa- 24 Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21742/ on 05/06/2017 Clinical Investigations -55 O Controls . Patients a 45 O ./ "E 35 '5. W o cr 25 1000 VC02 2000 (ml/min) 1600 §, O Controls . Patients 1400 0 E 1200 o > 1000CO 800 600 25 35 Respiratory 45 rate 55 (/min) RR=Vco2 relationships in patients and control Top: exercise. Data are expressed as mean±SEM, at subjects during the third minute of exercise, AT, 150 beats/min, and peak exercise. Bottom: average Vt-RR relationships in patients and control subjects during exercise. Two asterisks indicate p<0.001; three asterisks, p<0.0001. Figure 5. absent in normal subjects. However, peak Vo2 decrease (.27%) is only partially explained by chronotropic alteration ( 12%) after atrial repair. This chronotropic limitation may not be specific to atrial repair but might be a common denominator to all intracardiac repair, as the cardiopulmonary bypass has been associated with surgical fibroprocedure elastosis that could directly or indirectly disrupt the integrity of the sinus mode.14 The other cause suggested for limited capacity after venous switch operation is an inadaptation of the right ventricle in the systemic position. Several and especially isoechocardiographic, angiographic, exercise studies have shown ventricular hypotopic kinesia and a decrease in stroke volume.1923 Although right ventricle dilatation may be a compen¬ satory mechanism for chronotropic insufficiency,6 C02 rebreathing and isotopic measurements of car¬ diac flow showed a decrease in stroke volume during exercise testing under constant maximal load.9 In our was study, oxygen pulse, an indirect indicator of the stroke volume, was decreased at the end of testing (7.4±2.9 vs 10.7±4.2 mL/beat; p<0.001) and at submaximal loads. In normal children and adolescents, oxygen pulse correlates better than peak Vo2 with morphometric parameters, particularly body surface.25 In our pa¬ tients and control subjects, these correlations were excellent but with different coefficients. Although our study unfortunately confirms that children treated with the Senning technique have a functional limitation close to that in chil¬ long-term dren operated on a few years earlier with the Mustard operation, it does show for the first time an inverse relationship between time since intervention and ulterior aerobic capacity (r=0.48; p=0.001), while there is no significant correlation between the age of patients (or control subjects) and peak Vo2. We observed no significant relationship between age at surgery and maximal heart rate or 02 pulse at peak effort. Unlike previous series in which no association was noted between time since intervention and exercise capacity, it seems that the earlier the chil¬ dren are operated on with the Senning technique, the better their ultimate effort capacity. Our patients were all operated on by the same surgeon, and were operated on as quickly as possible when functional tolerance was poor (persistent cya¬ nosis despite an efficient atrioseptostomy of Rashkind-Miller). It may be that submitting the right ventricle early to conditions of systemic load leads to better long-term tolerance, with exercise capacities similar to those in patients operated on with an arterial switch technique.26 The ventilatory adaptation of our patients during exercise testing was also quite different from that of normal patients and is reminiscent of the modifica¬ tions described in cardiac insufficiency.27'28 There is, in fact, an excess ventilatory response as measured by the respiratory frequency (or overall ventilation) to the production of C02.29 Such anoma¬ compared lies have also been described more recently after Fontan procedures and repair of tetralogy of Fallot.30 However, we found no correlation between respi¬ ratory equivalents for C02 measured at the end of exercise and peak Vo2 in patients or control subjects, previous report.24 The relationship is all the more disturbed as the limitation of effort capacity increases, was also ab¬ normal in our patients. This disturbance is associated contrary to a Vt-RR, which with a decrease in Vt at the end of effort than acceleration in respiratory frequency. How¬ ever, the mechanisms involved in this abnormal ventilatory response are not well understood. Unfor¬ tunately our patients did not have additional respimore with an CHEST / 111 / 1 / JANUARY, 1997 Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21742/ on 05/06/2017 27 12 o> 60 r \ | 55 50 v. 45 E 40 35 a; 3 Controls Patients 30 10 Lil (/) -J D a. CM o 10 O 150 b/min Figure 2. Box plots of the values of Vo2 during exercise in control subjects and patients at the third minute of the test, AT, 150 beats/min, and peak exercise. The central dot is the sample mean. The bottom and top edges of the box are the sample 25th and 75th percentiles. pulse at the end of exercise was strongly correlated with body surface area in the patient group (r=0.89; but with a lower slope relationship (con¬ p=0.0001) trol subjects, y=11.2 x-4.78; patients, y=8.3 x.2.8, where y=oxygen pulse and x=body surface area). During exercise, the patient group had a Ve lower than control subjects (46±18.7 vs 69.3±30.1 L/min; of exercise. However, the p<0.0001) at the end was very different between the ventilatory pattern two groups: the increase of tidal volume (Vt) was lower during exercise in patients. Patients had a greater respiratory response to exercise with RR/ Vco2 and Ve/Vco2 showing significant increases at all stages of exercise. Figure 5 shows the Vt-RR for each group. We found no significant relationshipbetween correlation Ve/Vco2 and Vo2 at the end of exercise. All these differences in cardiopulmonary parame¬ also present for the Senning subgroup with or without additional defects. ters were Discussion Comparisons of cardiopulmonary function in pa¬ 0 c O Controls . Patients .Q % 25 £ 20 2" tients S 11 having undergone 2.5 10 venous 5 7.5 Age at surgery (months) 12.5 Figure 3. Relation between 15 17.5 switch 20 operation 22.5 . peak Vo2 (mL/min/kg) (months) at surgery in patients. MAXV02 and age 4 6 8 Exercise time 10 12 14 (min) Figure 4. Oxygen pulse (mL/beat) in normal subjects and Data (mean±SEM) were obtained at the third minute patients. of exercise, AT, 150 beats/min, and peak exercise. Two asterisks indicate p<0.001. maxi¬ subjects have indicated different to exercise.7-8 and performances adaptations However, most studies have focussed on patients who had the Mustard procedure. Reybrouck et al15 alone recently reported a small series of 20 patients followed up 7.3 years after a Senning operation. The is shorter sim¬ follow-up for the Senning recent. procedure Better long-term ply because it is morecould ex¬ theoretically be uses capacity performance with the because it Senning operation, pected viable atrial tissue. We report herein the exclusively TGA of on series operated patients (n=43) largest the operated on with exclusively includingwithpatients 10 than a of more Senning procedure follow-up 11 6.5 to 18.3; mean, ±2.8). years (from to matched control subjects, our pop¬ Compared ulation had a reduced aerobic capacity with shorter exercise time (-22%), peak Vo2 (-27%), or Vo2 at aerobic threshold (.29%). Although our patients were asymptomatic, the slope of Vo2 vs workload with different increase was reduced as in with normal mum patients stages of heart failure.24 The results from the present study are in agreement with the previous report of Reybrouck et al16 and with similar cardiopulmonary alterations observed after Mustard operations.91415 Exercise performance limitation after atrial repair has been attributed to an impaired chronotropic group, had a response.6 Our patients, as a combined mean resting heart rate that was significantly less than normal; on exercise stress testing, the rhythm reverted to sinus in all patients but remained lower at the end of exercise (166 ±20 vs 188±16 beats/min; p=0.0001). Twenty-one patients were unable to reach 80% of their theoretical maximal heart rate. We found a weak correlation between maximal heart rate and peak Vo2 in patients (r^O.29; p=0.05) that 26 Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21742/ on 05/06/2017 Clinical Investigations -55 O Controls . Patients a 45 O ./ "E 35 '5. W o cr 25 1000 VC02 2000 (ml/min) 1600 §, O Controls . Patients 1400 0 E 1200 o > 1000CO 800 600 25 35 Respiratory 45 rate 55 (/min) RR=Vco2 relationships in patients and control Top: exercise. Data are expressed as mean±SEM, at subjects during the third minute of exercise, AT, 150 beats/min, and peak exercise. Bottom: average Vt-RR relationships in patients and control subjects during exercise. Two asterisks indicate p<0.001; three asterisks, p<0.0001. Figure 5. absent in normal subjects. However, peak Vo2 decrease (.27%) is only partially explained by chronotropic alteration ( 12%) after atrial repair. This chronotropic limitation may not be specific to atrial repair but might be a common denominator to all intracardiac repair, as the cardiopulmonary bypass has been associated with surgical fibroprocedure elastosis that could directly or indirectly disrupt the integrity of the sinus mode.14 The other cause suggested for limited capacity after venous switch operation is an inadaptation of the right ventricle in the systemic position. Several and especially isoechocardiographic, angiographic, exercise studies have shown ventricular hypotopic kinesia and a decrease in stroke volume.1923 Although right ventricle dilatation may be a compen¬ satory mechanism for chronotropic insufficiency,6 C02 rebreathing and isotopic measurements of car¬ diac flow showed a decrease in stroke volume during exercise testing under constant maximal load.9 In our was study, oxygen pulse, an indirect indicator of the stroke volume, was decreased at the end of testing (7.4±2.9 vs 10.7±4.2 mL/beat; p<0.001) and at submaximal loads. In normal children and adolescents, oxygen pulse correlates better than peak Vo2 with morphometric parameters, particularly body surface.25 In our pa¬ tients and control subjects, these correlations were excellent but with different coefficients. Although our study unfortunately confirms that children treated with the Senning technique have a functional limitation close to that in chil¬ long-term dren operated on a few years earlier with the Mustard operation, it does show for the first time an inverse relationship between time since intervention and ulterior aerobic capacity (r=0.48; p=0.001), while there is no significant correlation between the age of patients (or control subjects) and peak Vo2. We observed no significant relationship between age at surgery and maximal heart rate or 02 pulse at peak effort. Unlike previous series in which no association was noted between time since intervention and exercise capacity, it seems that the earlier the chil¬ dren are operated on with the Senning technique, the better their ultimate effort capacity. Our patients were all operated on by the same surgeon, and were operated on as quickly as possible when functional tolerance was poor (persistent cya¬ nosis despite an efficient atrioseptostomy of Rashkind-Miller). It may be that submitting the right ventricle early to conditions of systemic load leads to better long-term tolerance, with exercise capacities similar to those in patients operated on with an arterial switch technique.26 The ventilatory adaptation of our patients during exercise testing was also quite different from that of normal patients and is reminiscent of the modifica¬ tions described in cardiac insufficiency.27'28 There is, in fact, an excess ventilatory response as measured by the respiratory frequency (or overall ventilation) to the production of C02.29 Such anoma¬ compared lies have also been described more recently after Fontan procedures and repair of tetralogy of Fallot.30 However, we found no correlation between respi¬ ratory equivalents for C02 measured at the end of exercise and peak Vo2 in patients or control subjects, previous report.24 The relationship is all the more disturbed as the limitation of effort capacity increases, was also ab¬ normal in our patients. This disturbance is associated contrary to a Vt-RR, which with a decrease in Vt at the end of effort than acceleration in respiratory frequency. How¬ ever, the mechanisms involved in this abnormal ventilatory response are not well understood. Unfor¬ tunately our patients did not have additional respimore with an CHEST / 111 / 1 / JANUARY, 1997 Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21742/ on 05/06/2017 27 ratory function tests (including vital capacity, pulmo¬ nary diffusing properties, lung distensibility, etc) and our study cannot elucidate this discussion. But as in patients with cardiac insufficiency, the relationship between ventilation and C02 production was not linear in our patients, so there is growing support for another stimulus being involved, particularly a mus¬ cular ergoreflex.27 This could explain the benefits of training observed in recent years in patients physical with cardiac insufficiency,31 and also in children operation.32 operated on byinvenous switch Our study a large series of patients mainly the Senning technique and with a operated on withconfirms that atrial repair is associ¬ follow-up long ated with a limitation in maximal aerobic capacity with an early anaerobic AT. Although patients may be asymptomatic, they have an inadapted ventilatory response to exercise. Chronotropic insufficiency and especially the already documented relative inadaptation of the right ventricle to exercise should make clinicians vigilant about the long-term outcome of these patients. However, it would seem that inter¬ ventions performed earlier with the Senning tech¬ nique lead to better long-term exercise capacity, thus reopening the debate concerning the respective ad¬ vantages of the arterial2633 with venous switch oper¬ ation. linguistic assistance. Ray Helbing 1987; 60:346-50 5 Gillette PC, Wampler DG, Shannon C, et al. Use of cardiac pacing after the Mustard operation for transposition of the great arteries. J Am Coll Cardiol 1986; 7:138-41 Paridon SM, Humes RA, Pinsky WW. The role of chrono¬ tropic impairment during exercise after the Mustard opera¬ tion. J Am Coll Cardiol 1991; 17:729-32 Darvell FJ, Rossi IR, Rossi MB, et al. Intermediate to late term results of Mustard's procedure for complete transposi¬ tion of the great arteries with an intact ventricular septum. Br J 1988; 59:468-73 Ensing GJ, Heise CT, Driscoll DJ. Cardiovascular response to exercise after the Mustard operation for simple and complex transposition of the great vessels. Am J Cardiol 1988; 62: Heart 8 617-22 after the Mustard operation in transposition of the great arteries. Am J Cardiol 1983; 51:1526-29 12 Musewe NN, Reisman J, Benson LN, et al. Cardiopulmonary adaptation at rest and during exercise 10 years after Mustard atrial repair for transposition of the great arteries. Circulation 1988; 77:1055-61 13 Myridakis DJ, Ehlers KH, Engle MA. Late follow-up after venous switch operation (Mustard procedure) for simple and complex transposition of the great arteries. Am J Cardiol 1994; 74:1030-36 14 Perrault H, Drblik SP, Montigny M, et al. Comparison of cardiovascular adjustments to exercise in adolescents 8 to 15 years of age after correction of tetralogy of Fallot, ventricular septal defect or atrial septal defect. Am J Cardiol 1989; 64:213-17 15 16 Reybrouck T, Dumoulin M, Van der Hauwaert LG. Cardio¬ respiratory exercise testing after venous switch operation in children with complete transposition of the great arteries. Am J Cardiol 1988; 61:861-65 Reybrouck T, Gewillig M, Dumoulin M, et al. Cardiorespi¬ exercise performance after Senning operation for ratory transposition of the great arteries. Br Heart J 1993; 70:175-79 Transposition of the great arteries: late results in adolescents and adults after the Mustard 18 WA, Hansen B, Ottenkamp J, et al. Long-term results of atrial correction for transposition of the great arteries: comparison of Mustard and Senning operations. J Thorac Cardiovasc Surg 1994; 108:363-72 2 Turina M, Siebenmann R, Nussbaumer P, et al. Long-term look after atrial correction of transposition of the great arteries. J Thorac Cardiovasc Surg 1988; 95:828-35 3 Beerman LB, Neches WH, Flicker FJ, et al. Arrhythmias in transposition of the great arteries after the Mustard opera¬ tion. Am J Cardiol 1983; 51:1530-34 4 Byrum CJ, Bove EL, Sondheimer HM, et al. Sinus node shift after the Senning procedure compared with the Mustard procedure for transposition of the great arteries. Am J Cardiol 7 478-82 11 Mathews RA, Flicker FJ, Beerman LB, et al. Exercise studies Cooke for his References 6 Oxygen uptake transient kinetics during constant-load exercise in children after oper¬ ations of ventricular septal defect, tetralogy of Fallot, trans¬ position of the great arteries, or tricuspid valve atresia. Am J Cardiol 1994; 74:166-69 10 Hochreiter C, Snyder MS, Borer JS, et al. Right and left ventricular performance 10 years after Mustard repair of transposition of the great arteries. Am J Cardiol 1994; 74: 17 Warnes CA, Somerville J. ACKNOWLEDGMENT: We thank Dr. 1 9 Gildein P, Mocellin R, Kaufmehl K. 19 procedure. Br Heart J 1987; 58:148-55 Bowyer JJ, Busst CM, Till JA, et al. Exercise ability after Mustard's operation. Arch Dis Child 1990; 65:865-70 Dihmis WC, Hutter JA, Joffe HS, et al. Medium-term clinical results after the Senning procedure with haemodynamic and angiographic evaluation of the venous pathways. 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Anaerobic metabolism as indicator of aerobic function during exercise in cardiac patients. J Am Coll Cardiol 1992; 20:120-26 25 Cooper DM, Weiler-Rawell D, Whipp BJ, et al. Aerobic parameters of exercise as a function of body size during growth in children. J Appl Physiol 1984; 56:628-34 26 Weindling SN, Wernovsky G, Colan SD, et al. Myocardial perfusion, function and exercise tolerance after the arterial switch operation. J Am Coll Cardiol 1994; 23:424-31 27 Clark A, Coats A. The mechanisms underlying the increased ventilatory response to exercise in chronic stable heart failure. an 28 Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21742/ on 05/06/2017 Clinical Investigations Eur Heart J 1992; 13:1698-1708 28 Clark AL, Poole-Wilson PA, Coats AJ.S. Relation between dioxide production in patients with ventilation and carbon chronic heart failure. J Am Coll Cardiol 1992; 20:1326-32 29 Yokoyama H, Sato H, Hori M, et al. A characteristic change in ventilation mode during exertional dyspnea in patients with chronic heart failure. Chest 1994; 106:1007-13 30 Clark AL, Gatzoulis MA, Redington AN. Ventilatory re¬ sponses to exercise in adults after repair of tetralogy of Fallot. Br Heart J 1995; 73:445-49 31 McKelvie RS, Teo KK, McCartney N, et al. Effects of exercise training in patients with congestive heart failure: a critical review. J Am Coll Cardiol 1995; 25:789-96 32 Bradley L, Gallioto EM, Hansen DA, et al. Effect of intense aerobic training on exercise performance in children after surgical repair of tetralogy of Fallot and transposition of the great arteries. Am J Cardiol 1985; 56:816-18 33 Hayes AM, Baker EJ, Kakadeker A, et al. Influence of anatomic correction for transposition of the great arteries on myocardial perfusion: radionuclide imaging with technetium-99 m 2-methoxy isobutyl isonitrile. J Am Coll Cardiol 1994; 24:769-77 CHEST / 111 / 1 / JANUARY, 1997 Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21742/ on 05/06/2017 29