Balloon dilatation of pulmonary valve in Tetralogy of fallot's
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《美国医学杂志》
Department of Cardiology, Indraprastha Apollo Hospital, Sarita Vihar, New Delhi, India
Abstract
In some children of Tetralogy of Fallot's (TOF) presenting with progressive cyanosis, are palliative Blalock-Taussing (BT) shunt may be required. There are no reports of this modality of management in India, though this has been practiced in the other countries. The author reports an infant with Tetralogy of Fallot's who successfully underwent ballon dilatation of the pulmonary valve. Review of literature shows 332 patients with TOF undergoing pulmonary valve balloon dilatation as an alternative to BT shunt in 12 studies with significant increase in pulmonary artery 'Z' score and low incidence of conversion to shunt. This modality of management should be considered in selected patients to change a palliative surgery to an intervention.
Keywords: Tof; Balloon dilatation; Shunt
The definitive management of Tetralogy of Fallot's (TOF) is by reparative surgery. In some children presenting with progressive cyanosis, a palliative Blalock-Taussig (BT) shunt may be required. Shunt morbidity maybe significant and interim mortality has also been reported.[1] Recent literature has shown that balloon dilatation of the pulmonary valve is an option which could avoid the shunt and take the patient to a stage where he could have the complete repair as the first and final surgery.[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13] There are no reports of this modality of management in India, though this has been widely practiced in the other countries.[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13] The author reports an infant with tetralogy of Fallot's who was deeply desaturated. The anatomy was considered favorable for balloon dilatation which was carried out successfully and resulted in significant improvement of the patient. We report the case and review the literature to suggest this as a modality to be considered for management of patients as an alternative to BT shunt.
Case report
A 7-month-old child presented with progressive cyanosis and a single episode of spell by history. He had been known to have TOF. After emergency management, evaluation of the anatomy was performed echocardiographically. The patient was noted to have mainly valvular pulmonary stenosis which was accompanied by minimal infundibular hypertrophy and obstruction Figure1. The patient was recommended to have a BT shunt and the option of balloon dilatation was also offered at that stage. The family was subsequently lost to follow up and returned for medical attention only when patient became progressively even more blue. The saturations baseline at that stage were only 55-60% and the child was tachypneic. On propranolol the heart rate was noted to be about 110 bpm indicating good degree of beta-blockade.
Anatomy was evaluated by echocardiogram again and the pulmonary valve was noted to be 4mm in diameter and the main level of obstruction was noted to be valvular. The velocity below the valve and above the infundibulum was noted to be 2m/s while the velocity above the valve was noted to be 4.5m/s. This indicated that the main pathology was at the valve. In addition the child weighed only 4 kg and had not increased in weight over the 3 months. The family was counseled for the options again and opted for balloon dilatation of the pulmonary valve.
Procedure
Under midazolam and fentanyl sedation the child underwent the interventional procedure via right femoral artery and vein being accessed. The initial angiogram confirmed the anatomy and that valvar stenosis was significant. The pulmonary valve annulus measured 6 mm. The valve was crossed using a 4F Right Judkins catheter as the guide for the Terumo 0.018 wire. The wire was exchanged for the 0.018 Road Runner and over this a coronary balloon of 4 mm diameter was taken and inflated to 6 atmospheres followed by a 5.5 mm balloon inflated to the same. Immediately after the deflation of the 5.5 mm balloon the saturation went up to 86% from 60% indicating the stenosis had been relieved. The patient required repeated sodium bicarbonate injections and a single dose of intravenous metoprolol. The patient was discharged the next day after saturations were maintained in the range of high 80s to 90% at rest.
Review of literature
Palliation for TOF was first performed in 1945 in form of a shunt between the systemic circulation and the pulmonary circulation. Though it does improve the oxygenation, but is associated with significant morbidity. In addition, there have been issues about the complication rates of the palliative surgery including that of sudden death and shunt occlusion. There have been several issues concerning the BT shunt; these are enlisted in table1.
Considering all these problems, the option of increasing the central flow has since long been explored. This maybe performed by central shunt: though this would allow blood to flow to both the branch pulmonary arteries, but, it does not overcome the inherent problems associated with a shunt, including that of exposing a child to a palliative surgery. For this reason, pediatric cardiologists have explored the possibility of balloon dilatation of the pulmonary valve. Apart from the non-surgical nature of the procedure, the centralized flow would overcome many of the disadvantages associated with the BT shunt. Such an intervention is not likely to result in converting the physiology to a VSD (increased pulmonary blood flow) considering the fact that the valve is hypoplastic and the balloon dilatation is not carried out to the maximum diameter of the annulus.
Indications and Factors Affecting Outcome
Since this intervention of pulmonary valve balloon dilatation in TOF is an alternative to BT shunt, the indications are the same as those for a BT shunt. They include: 1.Cyanotic spells (not for acute management) and 2. Persistent desaturation as measured by oximetry. If primary repair is not feasible, then BT shunt or pulmonary valve balloon dilatation should be considered. The reasons for not doing a primary repair may include the age of the patient, weight of the patient or pulmonary anatomy being unfavorable. Finally, anomalous coronary artery course is rarely an indication for deferring the primary repair and doing palliative surgery.
When the infundibular obstruction is significant, the outcome is not likely to be favorable with pulmonary valve balloon dilatation. Since infundibular obstruction increases with age, the intervention, by inference, is more likely to be successful at an earlier age i.e. infancy.[5],[13] In addition, authors have looked at the RVOT size and area to predict the outcome and select the cases.[19] The patients where the level of obstruction is valvular, the outcome is most likely to be favorable without a post-procedure spell. If the obstruction is mainly infundibular, the patient is likely to deteriorate post-procedure. If there is a mixed component of both, the valvar component is likely to improve and the patient will benefit. The post-procedure period, though, is likely to be associated with some transient desaturation due to the infundibular narrowing from the ballooning of this area. This delineation of the infundibular and valvar anatomy should be performed echocardiographically by the interventionist himself prior to the procedure.
Outcome of Pulmonary Valve Balloon Dilatation in TOF
Several studies have looked at the outcomes and benefits of improving central blood flow across the pulmonary valve in the TOF patient (summarized in table2. The parameters which have been evaluated include the increase in the pulmonary valve annulus 'z score' (defined as measured diameter-normal mean diameter/standard deviation of mean normal diameter); the increase in pulmonary artery branch size 'z score'; the lack of requirement of a shunt operation and finally the requirement of a transannular patch during the final repair.
In 1988, Rao et al studied 8 infants with congenital cyanotic heart defects, aged 7 days to 10 months with TOF who underwent percutaneous balloon pulmonary valvuloplasty. After balloon valvuloplasty, there was an increase in the pulmonary blood flow index, pulmonary-to-systemic flow ratio, and pulmonary artery pressure and arterial oxygen saturation. Immediate surgical intervention was avoided in all eight patients.[2]
Several other authors have subsequently looked at the outcomes in these directions. They have found the pulmonary annulus z score to increase, the pulmonary artery 'z score' to increase, the branch PA 'z score' to improve apart from the immediate improvement in the saturations of the patient. Other authors have also noted few or no complications.[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13] Some authors have documented serious side-effects. These have mainly been in patients who have been older (where the infundibular hypertrophy is more) or in the newborns where crossing the valve itself maybe a challenge (resulting in perforation, aneurysm formation).[5],[13]
Conclusion
In experienced hands, pulmonary valve balloon dilatation in TOF is a safe intervention with prior selection of the cases and has been reported to improve the oxygen saturation, pulmonary annulus 'z score', branch PA 'z score' and finally reduce the need of transannular patch during the final repair. This modality needs to be offered to the patients in the Indian scenario as an alternative to BT shunt in infancy.
Abbreviations: sig impr = significant improvement; NA= data not available; shunt= refers to BT shunt; TAP= transannular patch; R and L refer to Right and Left.
References
1. Fenton KN, Siewers RD, Rebovich B, Pigula FA. Interim mortality in infants with systemic-to-pulmonary artery shunts. Ann Thorac Surg 2003; 76(1): 152-156.
2. Rao PS, Brais M. Balloon pulmonary valvuloplasty for congenital cyanotic heart defects. Am Heart J 1988; 115(5): 1105-1110.
3. Sreeram N, Saleem M, Jackson M, Peart I, McKay R, Arnold R, Walsh K. Results of balloon pulmonary valvuloplasty as a palliative procedure in tetralogy of Fallot. J Am Coll Cardiol 1991; 18(1): 159-165.
4. Matsuoka S, Ushiroguchi Y, Kubo M, Tatara K, Kitagawa T, Katoh I, Kuroda Y. Balloon pulmonary valvuloplasty for infants with severe tetralogy of Fallot. Jpn Heart J 1993; 34(5): 643-651.
5. Piechaud JF, Delogu AB, Iserin L, Aggoun Y, Cohen L, Sidi D, Kachaner J. Palliative treatment of tetralogy of Fallot by percutaneous dilatation of the right ventricular outflow tract. 40 cases. Arch Mal Coeur Vaiss 1994; 86(5): 573-9.
6. Sluysmans T, Neven B, Rubay J, Lintermans J, Ovaert C, Mucumbitsi J et al. Early balloon dilatation of the pulmonary valve in infants with tetralogy of Fallot's. Risks and benefits. Circulation 1995; 91(5): 1506-11.
7. Hwang B, Lu JH, Lee BC, Hsieng JH, Meng CC. Palliative treatment for tetralogy of Fallot with percutaneous balloon dilatation of right ventricular outflow tract. Jpn Heart J 1995; 36(6): 751-761.
8. Guerin P, Jimenez M, Dos Santos P, Srour S, Choussat A. Percutaneous dilatation of the pulmonary tract in tetralogy of Fallot Arch Mal Coeur Vaiss 1996; 89(5): 541-545.
9. Godart F, Rey C, Muilwijk C, Francart C, Breviere GM, Vaksmann G. Percutaneous pulmonary valvuloplasty in neonates and infants with tetralogy of Fallot. Arch Mal Coeur Vaiss 1996; 89(5): 533-539.
10. Godart F, Rey C, Prat A, Muilwijk C, Francart C, Vaksmann G, Breviere GM. Early and late results and the effects on pulmonary arteries of balloon dilatation of the right ventricular outflow tract in tetralogy of Fallot. Eur Heart J 1998; 19(4): 595-600.
11. Massoud I, Imam A, Mabrouk A, Boutros N, Kassem A, Daouod A, El Hakem MA. Palliative balloon valvoplasty of the pulmonary valve in tetralogy of Fallot. Cardiol Young 1999; 9(1): 24-36.
12. Heusch A, Tannous A, Krogmann ON, Bourgeois M. Balloon valvoplasty in infants with tetralogy of Fallot: effects on oxygen saturation and growth of the pulmonary arteries. Cardiol Young 1999; 9(1): 17-23.
13. Arab SM, Kholeif AF, Zaher SR, Abdel-Mohsen AM, Kassem AS, Qureshi SA. Balloon dilation of the right ventricular outflow tract in tetralogy of Fallot: a palliative procedure. Cardiol Young 1999; 9(1): 11-16.
14. Wang JK, Wu MH, Chang CI, Chiu IS, Lue HC. Balloon angioplasty for obstructed modified systemic-pulmonary artery shunts and pulmonary artery stenoses. J Am Coll Cardiol 2001; 37(3): 940-947.
15. Kuroda O, Sano T, Matsuda H, Nakano S, Hirose H, Shimazaki Y et al. Analysis of the effects of the Blalock-Taussig shunt on ventricular function and the prognosis in patients with single ventricle. Circulation 1987; 76(3 Pt 2): III24-8.
16. Sahoo M, Sahu M, Kale S, Saxena N. Serous fluid leakage following modified Blalock-Taussig operation using PTFE grafts. Indian Heart J 2001; 53(3): 328-331.
17. Parvathy U, Balakrishnan KR, Ranjith MS, Moorthy JS. False aneurysm following modified Blalock-Taussig shunt. Pediatr Cardiol 2002; 23(2): 178-181.
18. Chen Q, Monro JL. Division of modified Blalock-Taussig shunt at correction avoids distortion of the pulmonary artery. Ann Thorac Surg 2001; 71(4): 1265-1266.
19. Rhodes J, O'Brien S, Patel H, Cao QL, Banerjee A, Hijazi ZM. Palliative balloon pulmonary valvuloplasty in tetralogy of fallot: echocardiographic predictors of successful outcome. J Invasive Cardiol 2000; 12(9): 448-451.(Kohli Vikas)
Abstract
In some children of Tetralogy of Fallot's (TOF) presenting with progressive cyanosis, are palliative Blalock-Taussing (BT) shunt may be required. There are no reports of this modality of management in India, though this has been practiced in the other countries. The author reports an infant with Tetralogy of Fallot's who successfully underwent ballon dilatation of the pulmonary valve. Review of literature shows 332 patients with TOF undergoing pulmonary valve balloon dilatation as an alternative to BT shunt in 12 studies with significant increase in pulmonary artery 'Z' score and low incidence of conversion to shunt. This modality of management should be considered in selected patients to change a palliative surgery to an intervention.
Keywords: Tof; Balloon dilatation; Shunt
The definitive management of Tetralogy of Fallot's (TOF) is by reparative surgery. In some children presenting with progressive cyanosis, a palliative Blalock-Taussig (BT) shunt may be required. Shunt morbidity maybe significant and interim mortality has also been reported.[1] Recent literature has shown that balloon dilatation of the pulmonary valve is an option which could avoid the shunt and take the patient to a stage where he could have the complete repair as the first and final surgery.[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13] There are no reports of this modality of management in India, though this has been widely practiced in the other countries.[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13] The author reports an infant with tetralogy of Fallot's who was deeply desaturated. The anatomy was considered favorable for balloon dilatation which was carried out successfully and resulted in significant improvement of the patient. We report the case and review the literature to suggest this as a modality to be considered for management of patients as an alternative to BT shunt.
Case report
A 7-month-old child presented with progressive cyanosis and a single episode of spell by history. He had been known to have TOF. After emergency management, evaluation of the anatomy was performed echocardiographically. The patient was noted to have mainly valvular pulmonary stenosis which was accompanied by minimal infundibular hypertrophy and obstruction Figure1. The patient was recommended to have a BT shunt and the option of balloon dilatation was also offered at that stage. The family was subsequently lost to follow up and returned for medical attention only when patient became progressively even more blue. The saturations baseline at that stage were only 55-60% and the child was tachypneic. On propranolol the heart rate was noted to be about 110 bpm indicating good degree of beta-blockade.
Anatomy was evaluated by echocardiogram again and the pulmonary valve was noted to be 4mm in diameter and the main level of obstruction was noted to be valvular. The velocity below the valve and above the infundibulum was noted to be 2m/s while the velocity above the valve was noted to be 4.5m/s. This indicated that the main pathology was at the valve. In addition the child weighed only 4 kg and had not increased in weight over the 3 months. The family was counseled for the options again and opted for balloon dilatation of the pulmonary valve.
Procedure
Under midazolam and fentanyl sedation the child underwent the interventional procedure via right femoral artery and vein being accessed. The initial angiogram confirmed the anatomy and that valvar stenosis was significant. The pulmonary valve annulus measured 6 mm. The valve was crossed using a 4F Right Judkins catheter as the guide for the Terumo 0.018 wire. The wire was exchanged for the 0.018 Road Runner and over this a coronary balloon of 4 mm diameter was taken and inflated to 6 atmospheres followed by a 5.5 mm balloon inflated to the same. Immediately after the deflation of the 5.5 mm balloon the saturation went up to 86% from 60% indicating the stenosis had been relieved. The patient required repeated sodium bicarbonate injections and a single dose of intravenous metoprolol. The patient was discharged the next day after saturations were maintained in the range of high 80s to 90% at rest.
Review of literature
Palliation for TOF was first performed in 1945 in form of a shunt between the systemic circulation and the pulmonary circulation. Though it does improve the oxygenation, but is associated with significant morbidity. In addition, there have been issues about the complication rates of the palliative surgery including that of sudden death and shunt occlusion. There have been several issues concerning the BT shunt; these are enlisted in table1.
Considering all these problems, the option of increasing the central flow has since long been explored. This maybe performed by central shunt: though this would allow blood to flow to both the branch pulmonary arteries, but, it does not overcome the inherent problems associated with a shunt, including that of exposing a child to a palliative surgery. For this reason, pediatric cardiologists have explored the possibility of balloon dilatation of the pulmonary valve. Apart from the non-surgical nature of the procedure, the centralized flow would overcome many of the disadvantages associated with the BT shunt. Such an intervention is not likely to result in converting the physiology to a VSD (increased pulmonary blood flow) considering the fact that the valve is hypoplastic and the balloon dilatation is not carried out to the maximum diameter of the annulus.
Indications and Factors Affecting Outcome
Since this intervention of pulmonary valve balloon dilatation in TOF is an alternative to BT shunt, the indications are the same as those for a BT shunt. They include: 1.Cyanotic spells (not for acute management) and 2. Persistent desaturation as measured by oximetry. If primary repair is not feasible, then BT shunt or pulmonary valve balloon dilatation should be considered. The reasons for not doing a primary repair may include the age of the patient, weight of the patient or pulmonary anatomy being unfavorable. Finally, anomalous coronary artery course is rarely an indication for deferring the primary repair and doing palliative surgery.
When the infundibular obstruction is significant, the outcome is not likely to be favorable with pulmonary valve balloon dilatation. Since infundibular obstruction increases with age, the intervention, by inference, is more likely to be successful at an earlier age i.e. infancy.[5],[13] In addition, authors have looked at the RVOT size and area to predict the outcome and select the cases.[19] The patients where the level of obstruction is valvular, the outcome is most likely to be favorable without a post-procedure spell. If the obstruction is mainly infundibular, the patient is likely to deteriorate post-procedure. If there is a mixed component of both, the valvar component is likely to improve and the patient will benefit. The post-procedure period, though, is likely to be associated with some transient desaturation due to the infundibular narrowing from the ballooning of this area. This delineation of the infundibular and valvar anatomy should be performed echocardiographically by the interventionist himself prior to the procedure.
Outcome of Pulmonary Valve Balloon Dilatation in TOF
Several studies have looked at the outcomes and benefits of improving central blood flow across the pulmonary valve in the TOF patient (summarized in table2. The parameters which have been evaluated include the increase in the pulmonary valve annulus 'z score' (defined as measured diameter-normal mean diameter/standard deviation of mean normal diameter); the increase in pulmonary artery branch size 'z score'; the lack of requirement of a shunt operation and finally the requirement of a transannular patch during the final repair.
In 1988, Rao et al studied 8 infants with congenital cyanotic heart defects, aged 7 days to 10 months with TOF who underwent percutaneous balloon pulmonary valvuloplasty. After balloon valvuloplasty, there was an increase in the pulmonary blood flow index, pulmonary-to-systemic flow ratio, and pulmonary artery pressure and arterial oxygen saturation. Immediate surgical intervention was avoided in all eight patients.[2]
Several other authors have subsequently looked at the outcomes in these directions. They have found the pulmonary annulus z score to increase, the pulmonary artery 'z score' to increase, the branch PA 'z score' to improve apart from the immediate improvement in the saturations of the patient. Other authors have also noted few or no complications.[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13] Some authors have documented serious side-effects. These have mainly been in patients who have been older (where the infundibular hypertrophy is more) or in the newborns where crossing the valve itself maybe a challenge (resulting in perforation, aneurysm formation).[5],[13]
Conclusion
In experienced hands, pulmonary valve balloon dilatation in TOF is a safe intervention with prior selection of the cases and has been reported to improve the oxygen saturation, pulmonary annulus 'z score', branch PA 'z score' and finally reduce the need of transannular patch during the final repair. This modality needs to be offered to the patients in the Indian scenario as an alternative to BT shunt in infancy.
Abbreviations: sig impr = significant improvement; NA= data not available; shunt= refers to BT shunt; TAP= transannular patch; R and L refer to Right and Left.
References
1. Fenton KN, Siewers RD, Rebovich B, Pigula FA. Interim mortality in infants with systemic-to-pulmonary artery shunts. Ann Thorac Surg 2003; 76(1): 152-156.
2. Rao PS, Brais M. Balloon pulmonary valvuloplasty for congenital cyanotic heart defects. Am Heart J 1988; 115(5): 1105-1110.
3. Sreeram N, Saleem M, Jackson M, Peart I, McKay R, Arnold R, Walsh K. Results of balloon pulmonary valvuloplasty as a palliative procedure in tetralogy of Fallot. J Am Coll Cardiol 1991; 18(1): 159-165.
4. Matsuoka S, Ushiroguchi Y, Kubo M, Tatara K, Kitagawa T, Katoh I, Kuroda Y. Balloon pulmonary valvuloplasty for infants with severe tetralogy of Fallot. Jpn Heart J 1993; 34(5): 643-651.
5. Piechaud JF, Delogu AB, Iserin L, Aggoun Y, Cohen L, Sidi D, Kachaner J. Palliative treatment of tetralogy of Fallot by percutaneous dilatation of the right ventricular outflow tract. 40 cases. Arch Mal Coeur Vaiss 1994; 86(5): 573-9.
6. Sluysmans T, Neven B, Rubay J, Lintermans J, Ovaert C, Mucumbitsi J et al. Early balloon dilatation of the pulmonary valve in infants with tetralogy of Fallot's. Risks and benefits. Circulation 1995; 91(5): 1506-11.
7. Hwang B, Lu JH, Lee BC, Hsieng JH, Meng CC. Palliative treatment for tetralogy of Fallot with percutaneous balloon dilatation of right ventricular outflow tract. Jpn Heart J 1995; 36(6): 751-761.
8. Guerin P, Jimenez M, Dos Santos P, Srour S, Choussat A. Percutaneous dilatation of the pulmonary tract in tetralogy of Fallot Arch Mal Coeur Vaiss 1996; 89(5): 541-545.
9. Godart F, Rey C, Muilwijk C, Francart C, Breviere GM, Vaksmann G. Percutaneous pulmonary valvuloplasty in neonates and infants with tetralogy of Fallot. Arch Mal Coeur Vaiss 1996; 89(5): 533-539.
10. Godart F, Rey C, Prat A, Muilwijk C, Francart C, Vaksmann G, Breviere GM. Early and late results and the effects on pulmonary arteries of balloon dilatation of the right ventricular outflow tract in tetralogy of Fallot. Eur Heart J 1998; 19(4): 595-600.
11. Massoud I, Imam A, Mabrouk A, Boutros N, Kassem A, Daouod A, El Hakem MA. Palliative balloon valvoplasty of the pulmonary valve in tetralogy of Fallot. Cardiol Young 1999; 9(1): 24-36.
12. Heusch A, Tannous A, Krogmann ON, Bourgeois M. Balloon valvoplasty in infants with tetralogy of Fallot: effects on oxygen saturation and growth of the pulmonary arteries. Cardiol Young 1999; 9(1): 17-23.
13. Arab SM, Kholeif AF, Zaher SR, Abdel-Mohsen AM, Kassem AS, Qureshi SA. Balloon dilation of the right ventricular outflow tract in tetralogy of Fallot: a palliative procedure. Cardiol Young 1999; 9(1): 11-16.
14. Wang JK, Wu MH, Chang CI, Chiu IS, Lue HC. Balloon angioplasty for obstructed modified systemic-pulmonary artery shunts and pulmonary artery stenoses. J Am Coll Cardiol 2001; 37(3): 940-947.
15. Kuroda O, Sano T, Matsuda H, Nakano S, Hirose H, Shimazaki Y et al. Analysis of the effects of the Blalock-Taussig shunt on ventricular function and the prognosis in patients with single ventricle. Circulation 1987; 76(3 Pt 2): III24-8.
16. Sahoo M, Sahu M, Kale S, Saxena N. Serous fluid leakage following modified Blalock-Taussig operation using PTFE grafts. Indian Heart J 2001; 53(3): 328-331.
17. Parvathy U, Balakrishnan KR, Ranjith MS, Moorthy JS. False aneurysm following modified Blalock-Taussig shunt. Pediatr Cardiol 2002; 23(2): 178-181.
18. Chen Q, Monro JL. Division of modified Blalock-Taussig shunt at correction avoids distortion of the pulmonary artery. Ann Thorac Surg 2001; 71(4): 1265-1266.
19. Rhodes J, O'Brien S, Patel H, Cao QL, Banerjee A, Hijazi ZM. Palliative balloon pulmonary valvuloplasty in tetralogy of fallot: echocardiographic predictors of successful outcome. J Invasive Cardiol 2000; 12(9): 448-451.(Kohli Vikas)