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Exercise response in atrial septal defect
Exercise Response in Atria1 Septal Defect ARIANE J. MARELLI,
M.D.
Division of Cardiology Department of Medicine Montreal General Hospital McGill University Montreal, Quebec, Canada
JUAN C. ALEJOS, M.D. Department of Pediatrics University of California School of Medicine Los Angeles, California
Ostium secundum atria1 septal defect accounts for 7% of all congenital cardiac anomalies* and 30% to 40% of congenital cardiac defects in adults >40 years of age.2 Although most patients9S % have cardiovascular symptoms by the age of 4O.j This article describes the responses to exercise before and after surgical closure of atria1 septal defect and reviews the natural history of exercise capacity in these patients and the effects of the patient’s age at the time of surgical repair.
EXERCISE CAPACITY BEFORE SURGICAL REPAIR Patients with atria1 septal defect who have longstanding left-to-right interatrial shunts may develop failure of one or both ventricles4 An elevation of right ventricular diastolic pressure occurs in the dilated, progressively less compliant right ventricle. Eventual right ventricular failure is characterized by a decrease in right ventricular forward Address correspondence to Ariane J. Marelli, M.D., Division of Cardiology, Department of Medicine, Room D237, Montreal General Hospital, 1650 Cedar Avenue, Montreal, Quebec H3G IA4. Canada.
output and a decrease in the left to right shunt. In symptomatic adults, a subnormal resting systemic cardiac output associated with an elevated left ventricular end-diastolic pressure can be demonstrated.5 Bulging of the interventricular septum into the left ventricular outflow tract is believed to account for the documented reduction in left ventricular output as a result of a decrease in left ventricular stroke volume index.6 The impaired response to exercise in patients with atria1 septal defect increases with age.7 Although the atria1 shunt affects the right ventricle most directly, symptoms relate to the size of the shunt and the adaptive responses of both ventricles, the right ventricle to an increase in resting preload as a result of excess volume and the left ventricle to a decrease in resting preload as a result of left-toright shunting and altered ventricular geometry. Venous return, right and left ventricular end-diastolic volume, heart rate, contractility, biventricular stroke volume, and ejection fraction all increase during the normal exercise response, accounting for the observed increase in cardiac output .8-10In both symptomatic and asymptomatic patients, abnormal ventricular reserve can be demonstrated during exercise in those with significant atria1 shunting. Prog Pediatr Cardiol 1993; 2(3):20-23 Copyright 0 1993 by Andover Medical
Atria1
Using radionuclide ventriculography in patients with pulmonary-to-systemic flow ratios >1.5, exercise testing discloses an inability to increase right and left ventricular end-diastolic volume and stroke volume, as well as the right-sided ejection fraction. An increase in heart rate appears to be the most important determinant of the increased left ventricular output. The increase in cardiac output required during exercise is also a function of right and left ventricular afterload, which in turn are determined by pulmonary and systemic vascular resistance. The relatively greater drop in systemic resistance compared to pulmonary resistance accounts for the decrease in left-to-right atria1 shunting observed with exercise. This further reinforces the inability of the right ventricle to maximize its preload when an increase in cardiac output is required to meet metabolic demands.
AGE OF REPAIR AND EXERCISE CAPACITY In patients with atria1 septal defect, the most important factor determining the return to normal cardiovascular function is age at the time of surgical repair.7,10-‘2 However, in patients of all ages, including operable ones over the age of 50, surgical closure of the defect is associated with improvement in New York Heart Association (NYI-IA) functional classification, subjective improvement in symptoms with exercise, and improved performance during exercise testing. ‘O-l3In those with preoperative right ventricular dilation, echocardiography 6 months to 1 year after surgical closure demonstrates persistence of right ventricular enlargement in all of those operated on after 25 years of age and in 60% of those having surgery between 7 and 25 years of age. l2 Despite persistent echocardiographic abnormalities in the older age group, patients show adequate subjective performance and normal measured maximal oxygen uptake during exercise testing.12 Using the ventilatory anaerobic threshold as a measure of cardiorespiratory endurance, children repaired before 5 years of age show a normal response.’ Those having surgery after 5 years of age continue to have a subnormal endurance at 1 to 7 years of follow-up.’ Even in patients having surgery before 5 years of age, however, careful assessment can disclose subtle residual exercise abnormalities.
Septal
Defect
21
In patients with normal exercise endurance times and maximal oxygen uptake, chronotropic limitation can be demonstrated by a subnormal maximal heart rate.7*‘0 When patients whose surgical closure occurred before and after age 6 are compared directly, the younger age group shows a normal exercise endurance response, although measurements are toward the lower limits of normal.” A small percentage of patients in the younger age group also show exercise-induced atria1 arrhythmias and the majority of patients show some persistent abnormality on the 1Blead electrocardiogram. On long-term follow-up, 42% of patients <6 years of age show complete normalization of the chest radiograph, compared with 24% of patients whose repair occurred after age 20. Patients in the older age-group have a lower exercise tolerance and a higher incidence of provocable atria1 arrhythmias.l’ Nonetheless, these patients show distinctive subjective and objective improvements in exercise tolerance after surgery.‘l Surgical repair at early ages results in a better chance of normalization of cardiopulmonary function. However, even in patients undergoing repair before 5 years of age, seemingly normal subjective and objective exercise tolerance does not preclude the development of exercise-induced atria1 arrhythmias and an abnormal chronotropic response.
EXERCISE CAPACITY BEFORE AND AFTER CLOSURE OF ATRIA1 SEPTAL DEFECT After successful closure of atria1 defects, older children and adolescents rarely show clinical evidence of right ventricular dysfunction.14 Although regression of right ventricular dilation may be incomplete, right ventricular size consistently decreases after surgery, as demonstrated by echocardiography and radionuclide ventriculography.‘2,‘5 The presence of right ventricular hypokinesis and depressed ejection fraction before surgery adversely effects the normalization of symptoms and ventricular function after surgery.15 The functional significance of improved, but persistent, right ventricular dilation is less clear. A postoperative study of 14 patients, most of whom had normal resting hemodynamics, demonstrated no differences in maximal oxygen consumption between those with persistent right ventricular dilation and those without it.12 The mechanical effects of right ventricular
22
Progress in Pediatric Cardiology
volume overload on left ventricular function appear to be completely reversible after atria1 septal defect closure, even when repair is undertaken in diastolic dimenadult patients. I6 Left ventricular sion and ejection fraction were measured during exercise radionuclide ventriculography in 11 patients before surgery and 6 months afterward. After surgery, all of the patients had normalization of diastolic dimension with exercise and showed a normal increase in ejection fraction, including 7 who had abnormal preoperative ejection responses. The best predictors of a successful outcome of surgical repair are the presence or absence of pulmonary vascular disease and the level of preoperative pulmonary artery pressure.3*‘7 Patients with preoperative total pulmonary vascular resistance measurements of <7 Wood units show improvement in NYHA functional class, regression of symptoms, radiographic evidence of reduced pulmonary artery enlargement, and electrocardiographic evidence of less right ventricular hypertrophy. A preoperative resistance >15 Wood units is associated with a high mortality. Patients with a measurement from 10 to 14 Wood units have little clinical improvement after surgery, but they have no progression of symptoms over a IZyear period of study. In patients of all ages, surgical closure of an atria1 defect is associated with a variable reduction in pressure in the pulmonary artery, right ventricle, and right atrium. 13,i8In those repaired after 50 years of age, higher preoperative pulmonary artery pressures correlate with persistent episodes of postoperative atria1 fibrillation and a more advanced NYHA functional class. Preoperative pulmonary pressure and age, rather than shunt size, correlate closely with postoperative pulmonary heincrease in pulmodynamics. 3~18A postoperative monary pressure during exercise correlates significantly with the level of preoperative pulmonary artery pressure at rest; the increased pressure can be seen even in the absence of a documented elevation in pulmonary vascular resistance.ls Abnormal pulmonary function tests can be sensitive markers of pulmonary hypertension in patients with atria1 septal defect. Mildly elevated mean pulmonary artery pressure can result in an increase in diffusing capacity, as reflected by the carbon dioxide transfer test.19,20 In patients repaired well into adulthood, measured forced expiratory volume and vital capacity are inversely related to the preop-
erative level of pulmonary artery pressure.13 In patients with mean pulmonary artery pressures >30 mm Hg, pulmonary function tests may remain abnormal even after surgery.19 Patients with mean pulmonary artery pressures >25 mm Hg also show evidence of reduced lung compliance and increased airways resistance. 21These findings suggest that increased pulmonary blood flow associated with even mild pulmonary hypertension can alter pulmonary vascular diffusing capacity and reduce lung compliance to diminish exercise capacity in patients with atria1 septal defect.
SUMMARY Exercise intolerance is one of the most common manifestations of significant atria1 shunting in patients with atria1 septal defect. Several complications of atria1 septal defect affect exercise capacity, including right heart failure, pulmonary hypertension, and atria1 arrhythmias. The patient’s age at the time of surgical repair is the most important determinant of postoperative improvement of cardiopulmonary function. Patients whose surgical correction occurs before 5 years of age are rarely symptomatic on long-term follow-up. In patients having surgery between 5 and 25 years of age, exercise tolerance and maximal oxygen uptake is normal 1 year after surgery, although ventricular dilation persists in half of them. Currently, most children with an atria1 septal defect will have early repair without clinical evidence of cardiac dysfunction. In some, mild residual effects of the interatrial shunt can be unmasked with maximal exercise testing. In patients with a significant interatrial shunt, surgical repair produces an improvement in exercise tolerance at all ages, including those operated on after 50 years of age. The degree of normalization of cardiopulmonary function depends on the patient’s age at repair and the presence or absence of preoperative pulmonary hypertension.
REFERENCES 1. Feldt RH, Porter CJ, Edwards WD, Puga FJ, Seward JB. Defects of the atria1 septum and the atrioventricular canal. In: Adams FH, Emmanouilides GC, Riemenschneider TA, eds. Moss’ Heart Disease in In-
Atria1 Septal Defect
fants, Children, and Adolescents. 4th ed. Baltimore, MD: Williams & Wilkins; 1989:170-175. 2. Perloff JK, Child JS, eds. Congenital Heart Disease in Adults. Philadelphia, PA: Saunders; 1991:24-25. 3. Murphy JG, Gersh BJ, McGoon MD, et al. Longterm outcome after surgical repair of isolated atria1 septal defect. N Engl L Med. 1990;323:1645-1650. 4. Perloff JK. The Clinical Recognition of Congenital Heart Disease. 3rd ed. Philadelphia, Pa: Saunders, 1987:276-278. 5. Flamm MD, Cohn KE, Hancock EW. Ventricular function in atria1 septal defect. Am 1 Med. 1970;48: 286-294. 6. Borow KM, Karp R. Atria1 septal defect: lessons from the past, directions for the future. N Engl I Med. 1990;323:1698-1700. 7. Reybrouk T, Bisschop A, Dumoulin M, van der Hauwaert LG. Cardiorespiratory exercise capacity after surgical closure of atria1 septal defect is influenced by the age of surgery. Am Heart 1. 1991;122:10731078. 8. Peter CA, Bowyer K, Jones RH. Radionuclide analysis of right and left ventricular response to exercise in patients with atria1 and ventricular septal defects. Am Heart J. 983:105:428-435. 9. Ferguson JJ III, Miller MJ, Aroesty JM, Sahagian I’, Grossman W, McKay RG. Assessment of right atria1 pressure-volume relations in patients with and without an atria1 septal defect. 1 Am Co11 Cardiol. 1989; 13:630-636. 10. Perrault H, Drblik SF’, 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 atria1 septal defect. Am 1 Cardiol. 1989;64:213-217. 11. Huysmans HA, Vrakking M, van Boven WJ. Late follow-up after surgical correction of atria1 septal defect of the secundum type. Z Kardiol. 1989; 78(suppl 7):43-45. 12. Pearlman AS, Borer JS, Clark CE, et al. Abnormal
23
right ventricular size and ventricular septal motion after atria1 septal defect closure. Am J Cardiol. 1978;
41:295-301. 13. Cowan ME, Jeffrey RR, Drakeley MJ, Mercer JL, Meade JB, Fabri BM. The results of surgery for atria1 septal defect in patients aged fifty years and over. Eur Heart 1. 1990,11:29-34. 14. Graham TP Jr. Ventricular performance in adults after operation for congenital heart disease. Am 1 Cardiol. 1982;50:612-620. 15. Liberthson RR, Boucher CA, Strauss HW, Dinsmore RE, McKusick KA, Pohost GM. Right ventricular function in adult atria1 septal defect. Am 1 Cardiol. 1981;47:56-60. 16. Bonow RO, Borer JS, Rosing DR, Bacharach SL, Green MV, Kent KM. Left ventricular functional reserve in adult patients with atria1 septal defect preand postoperative studies. Circulation. 1981;63: 1315-1322. 17. Steele PM, Fuster V, Cohen M, Ritter DG, McGoon DC. Isolated atria1 septal defect with pulmonary vascular obstructive disease - long-term follow-up and prediction of outcome after surgical correction. Circulation. 1987;76:1037-1042. 18. Forfang K. Hemodynamic findings before and after surgery for atria1 septal defect of the secundum type in middle-aged patients. Cardiology. 1978;63:1432. 19. Schofield PM, Barber OV, Kingston T. Preoperative and postoperative pulmonary function tests in patients with atria1 septal defect and their relation to pulmonary artery pressure and pulmonary-systemic flow ratio. Br Heart 1. 1985;54:577-582. 20. Yoshioka T, Kunieda T, Naito M, Fukunaga Y, Okubo S, Nakanishi N. Effects of pulmonary hemodynamics on lung function in adult patients with atria1 septal defect. Jpn Circ 1. 1985;49:960-966. 21. Troyer AD, Yernault JC, Englert M. Mechanics of breathing in patients with atria1 septal defect. Am Rev Respir Dis. 1977;115:413-421.
M.D.
Division of Cardiology Department of Medicine Montreal General Hospital McGill University Montreal, Quebec, Canada
JUAN C. ALEJOS, M.D. Department of Pediatrics University of California School of Medicine Los Angeles, California
Ostium secundum atria1 septal defect accounts for 7% of all congenital cardiac anomalies* and 30% to 40% of congenital cardiac defects in adults >40 years of age.2 Although most patients
EXERCISE CAPACITY BEFORE SURGICAL REPAIR Patients with atria1 septal defect who have longstanding left-to-right interatrial shunts may develop failure of one or both ventricles4 An elevation of right ventricular diastolic pressure occurs in the dilated, progressively less compliant right ventricle. Eventual right ventricular failure is characterized by a decrease in right ventricular forward Address correspondence to Ariane J. Marelli, M.D., Division of Cardiology, Department of Medicine, Room D237, Montreal General Hospital, 1650 Cedar Avenue, Montreal, Quebec H3G IA4. Canada.
output and a decrease in the left to right shunt. In symptomatic adults, a subnormal resting systemic cardiac output associated with an elevated left ventricular end-diastolic pressure can be demonstrated.5 Bulging of the interventricular septum into the left ventricular outflow tract is believed to account for the documented reduction in left ventricular output as a result of a decrease in left ventricular stroke volume index.6 The impaired response to exercise in patients with atria1 septal defect increases with age.7 Although the atria1 shunt affects the right ventricle most directly, symptoms relate to the size of the shunt and the adaptive responses of both ventricles, the right ventricle to an increase in resting preload as a result of excess volume and the left ventricle to a decrease in resting preload as a result of left-toright shunting and altered ventricular geometry. Venous return, right and left ventricular end-diastolic volume, heart rate, contractility, biventricular stroke volume, and ejection fraction all increase during the normal exercise response, accounting for the observed increase in cardiac output .8-10In both symptomatic and asymptomatic patients, abnormal ventricular reserve can be demonstrated during exercise in those with significant atria1 shunting. Prog Pediatr Cardiol 1993; 2(3):20-23 Copyright 0 1993 by Andover Medical
Atria1
Using radionuclide ventriculography in patients with pulmonary-to-systemic flow ratios >1.5, exercise testing discloses an inability to increase right and left ventricular end-diastolic volume and stroke volume, as well as the right-sided ejection fraction. An increase in heart rate appears to be the most important determinant of the increased left ventricular output. The increase in cardiac output required during exercise is also a function of right and left ventricular afterload, which in turn are determined by pulmonary and systemic vascular resistance. The relatively greater drop in systemic resistance compared to pulmonary resistance accounts for the decrease in left-to-right atria1 shunting observed with exercise. This further reinforces the inability of the right ventricle to maximize its preload when an increase in cardiac output is required to meet metabolic demands.
AGE OF REPAIR AND EXERCISE CAPACITY In patients with atria1 septal defect, the most important factor determining the return to normal cardiovascular function is age at the time of surgical repair.7,10-‘2 However, in patients of all ages, including operable ones over the age of 50, surgical closure of the defect is associated with improvement in New York Heart Association (NYI-IA) functional classification, subjective improvement in symptoms with exercise, and improved performance during exercise testing. ‘O-l3In those with preoperative right ventricular dilation, echocardiography 6 months to 1 year after surgical closure demonstrates persistence of right ventricular enlargement in all of those operated on after 25 years of age and in 60% of those having surgery between 7 and 25 years of age. l2 Despite persistent echocardiographic abnormalities in the older age group, patients show adequate subjective performance and normal measured maximal oxygen uptake during exercise testing.12 Using the ventilatory anaerobic threshold as a measure of cardiorespiratory endurance, children repaired before 5 years of age show a normal response.’ Those having surgery after 5 years of age continue to have a subnormal endurance at 1 to 7 years of follow-up.’ Even in patients having surgery before 5 years of age, however, careful assessment can disclose subtle residual exercise abnormalities.
Septal
Defect
21
In patients with normal exercise endurance times and maximal oxygen uptake, chronotropic limitation can be demonstrated by a subnormal maximal heart rate.7*‘0 When patients whose surgical closure occurred before and after age 6 are compared directly, the younger age group shows a normal exercise endurance response, although measurements are toward the lower limits of normal.” A small percentage of patients in the younger age group also show exercise-induced atria1 arrhythmias and the majority of patients show some persistent abnormality on the 1Blead electrocardiogram. On long-term follow-up, 42% of patients <6 years of age show complete normalization of the chest radiograph, compared with 24% of patients whose repair occurred after age 20. Patients in the older age-group have a lower exercise tolerance and a higher incidence of provocable atria1 arrhythmias.l’ Nonetheless, these patients show distinctive subjective and objective improvements in exercise tolerance after surgery.‘l Surgical repair at early ages results in a better chance of normalization of cardiopulmonary function. However, even in patients undergoing repair before 5 years of age, seemingly normal subjective and objective exercise tolerance does not preclude the development of exercise-induced atria1 arrhythmias and an abnormal chronotropic response.
EXERCISE CAPACITY BEFORE AND AFTER CLOSURE OF ATRIA1 SEPTAL DEFECT After successful closure of atria1 defects, older children and adolescents rarely show clinical evidence of right ventricular dysfunction.14 Although regression of right ventricular dilation may be incomplete, right ventricular size consistently decreases after surgery, as demonstrated by echocardiography and radionuclide ventriculography.‘2,‘5 The presence of right ventricular hypokinesis and depressed ejection fraction before surgery adversely effects the normalization of symptoms and ventricular function after surgery.15 The functional significance of improved, but persistent, right ventricular dilation is less clear. A postoperative study of 14 patients, most of whom had normal resting hemodynamics, demonstrated no differences in maximal oxygen consumption between those with persistent right ventricular dilation and those without it.12 The mechanical effects of right ventricular
22
Progress in Pediatric Cardiology
volume overload on left ventricular function appear to be completely reversible after atria1 septal defect closure, even when repair is undertaken in diastolic dimenadult patients. I6 Left ventricular sion and ejection fraction were measured during exercise radionuclide ventriculography in 11 patients before surgery and 6 months afterward. After surgery, all of the patients had normalization of diastolic dimension with exercise and showed a normal increase in ejection fraction, including 7 who had abnormal preoperative ejection responses. The best predictors of a successful outcome of surgical repair are the presence or absence of pulmonary vascular disease and the level of preoperative pulmonary artery pressure.3*‘7 Patients with preoperative total pulmonary vascular resistance measurements of <7 Wood units show improvement in NYHA functional class, regression of symptoms, radiographic evidence of reduced pulmonary artery enlargement, and electrocardiographic evidence of less right ventricular hypertrophy. A preoperative resistance >15 Wood units is associated with a high mortality. Patients with a measurement from 10 to 14 Wood units have little clinical improvement after surgery, but they have no progression of symptoms over a IZyear period of study. In patients of all ages, surgical closure of an atria1 defect is associated with a variable reduction in pressure in the pulmonary artery, right ventricle, and right atrium. 13,i8In those repaired after 50 years of age, higher preoperative pulmonary artery pressures correlate with persistent episodes of postoperative atria1 fibrillation and a more advanced NYHA functional class. Preoperative pulmonary pressure and age, rather than shunt size, correlate closely with postoperative pulmonary heincrease in pulmodynamics. 3~18A postoperative monary pressure during exercise correlates significantly with the level of preoperative pulmonary artery pressure at rest; the increased pressure can be seen even in the absence of a documented elevation in pulmonary vascular resistance.ls Abnormal pulmonary function tests can be sensitive markers of pulmonary hypertension in patients with atria1 septal defect. Mildly elevated mean pulmonary artery pressure can result in an increase in diffusing capacity, as reflected by the carbon dioxide transfer test.19,20 In patients repaired well into adulthood, measured forced expiratory volume and vital capacity are inversely related to the preop-
erative level of pulmonary artery pressure.13 In patients with mean pulmonary artery pressures >30 mm Hg, pulmonary function tests may remain abnormal even after surgery.19 Patients with mean pulmonary artery pressures >25 mm Hg also show evidence of reduced lung compliance and increased airways resistance. 21These findings suggest that increased pulmonary blood flow associated with even mild pulmonary hypertension can alter pulmonary vascular diffusing capacity and reduce lung compliance to diminish exercise capacity in patients with atria1 septal defect.
SUMMARY Exercise intolerance is one of the most common manifestations of significant atria1 shunting in patients with atria1 septal defect. Several complications of atria1 septal defect affect exercise capacity, including right heart failure, pulmonary hypertension, and atria1 arrhythmias. The patient’s age at the time of surgical repair is the most important determinant of postoperative improvement of cardiopulmonary function. Patients whose surgical correction occurs before 5 years of age are rarely symptomatic on long-term follow-up. In patients having surgery between 5 and 25 years of age, exercise tolerance and maximal oxygen uptake is normal 1 year after surgery, although ventricular dilation persists in half of them. Currently, most children with an atria1 septal defect will have early repair without clinical evidence of cardiac dysfunction. In some, mild residual effects of the interatrial shunt can be unmasked with maximal exercise testing. In patients with a significant interatrial shunt, surgical repair produces an improvement in exercise tolerance at all ages, including those operated on after 50 years of age. The degree of normalization of cardiopulmonary function depends on the patient’s age at repair and the presence or absence of preoperative pulmonary hypertension.
REFERENCES 1. Feldt RH, Porter CJ, Edwards WD, Puga FJ, Seward JB. Defects of the atria1 septum and the atrioventricular canal. In: Adams FH, Emmanouilides GC, Riemenschneider TA, eds. Moss’ Heart Disease in In-
Atria1 Septal Defect
fants, Children, and Adolescents. 4th ed. Baltimore, MD: Williams & Wilkins; 1989:170-175. 2. Perloff JK, Child JS, eds. Congenital Heart Disease in Adults. Philadelphia, PA: Saunders; 1991:24-25. 3. Murphy JG, Gersh BJ, McGoon MD, et al. Longterm outcome after surgical repair of isolated atria1 septal defect. N Engl L Med. 1990;323:1645-1650. 4. Perloff JK. The Clinical Recognition of Congenital Heart Disease. 3rd ed. Philadelphia, Pa: Saunders, 1987:276-278. 5. Flamm MD, Cohn KE, Hancock EW. Ventricular function in atria1 septal defect. Am 1 Med. 1970;48: 286-294. 6. Borow KM, Karp R. Atria1 septal defect: lessons from the past, directions for the future. N Engl I Med. 1990;323:1698-1700. 7. Reybrouk T, Bisschop A, Dumoulin M, van der Hauwaert LG. Cardiorespiratory exercise capacity after surgical closure of atria1 septal defect is influenced by the age of surgery. Am Heart 1. 1991;122:10731078. 8. Peter CA, Bowyer K, Jones RH. Radionuclide analysis of right and left ventricular response to exercise in patients with atria1 and ventricular septal defects. Am Heart J. 983:105:428-435. 9. Ferguson JJ III, Miller MJ, Aroesty JM, Sahagian I’, Grossman W, McKay RG. Assessment of right atria1 pressure-volume relations in patients with and without an atria1 septal defect. 1 Am Co11 Cardiol. 1989; 13:630-636. 10. Perrault H, Drblik SF’, 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 atria1 septal defect. Am 1 Cardiol. 1989;64:213-217. 11. Huysmans HA, Vrakking M, van Boven WJ. Late follow-up after surgical correction of atria1 septal defect of the secundum type. Z Kardiol. 1989; 78(suppl 7):43-45. 12. Pearlman AS, Borer JS, Clark CE, et al. Abnormal
23
right ventricular size and ventricular septal motion after atria1 septal defect closure. Am J Cardiol. 1978;
41:295-301. 13. Cowan ME, Jeffrey RR, Drakeley MJ, Mercer JL, Meade JB, Fabri BM. The results of surgery for atria1 septal defect in patients aged fifty years and over. Eur Heart 1. 1990,11:29-34. 14. Graham TP Jr. Ventricular performance in adults after operation for congenital heart disease. Am 1 Cardiol. 1982;50:612-620. 15. Liberthson RR, Boucher CA, Strauss HW, Dinsmore RE, McKusick KA, Pohost GM. Right ventricular function in adult atria1 septal defect. Am 1 Cardiol. 1981;47:56-60. 16. Bonow RO, Borer JS, Rosing DR, Bacharach SL, Green MV, Kent KM. Left ventricular functional reserve in adult patients with atria1 septal defect preand postoperative studies. Circulation. 1981;63: 1315-1322. 17. Steele PM, Fuster V, Cohen M, Ritter DG, McGoon DC. Isolated atria1 septal defect with pulmonary vascular obstructive disease - long-term follow-up and prediction of outcome after surgical correction. Circulation. 1987;76:1037-1042. 18. Forfang K. Hemodynamic findings before and after surgery for atria1 septal defect of the secundum type in middle-aged patients. Cardiology. 1978;63:1432. 19. Schofield PM, Barber OV, Kingston T. Preoperative and postoperative pulmonary function tests in patients with atria1 septal defect and their relation to pulmonary artery pressure and pulmonary-systemic flow ratio. Br Heart 1. 1985;54:577-582. 20. Yoshioka T, Kunieda T, Naito M, Fukunaga Y, Okubo S, Nakanishi N. Effects of pulmonary hemodynamics on lung function in adult patients with atria1 septal defect. Jpn Circ 1. 1985;49:960-966. 21. Troyer AD, Yernault JC, Englert M. Mechanics of breathing in patients with atria1 septal defect. Am Rev Respir Dis. 1977;115:413-421.