angioplasty

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Feasibility and effectiveness of repeated balloon dilatation of restenosed congenital obstructions after previous balloon valvuloplasty/angioplasty P. S y a m a s u n d a r Rao, MD, a, b, c O m a r Galal, MD, PhD, b a n d Allen D. Wilson, MD a

Madison, Wis.,

Riyadh, Saudi Arabia, and St. Louis, Mo.

Balloon dilatation of congenital stenotic lesions of the heart and great vessels has been used for more than a decade. Varying incidence of residual obstruction or recurrence, hereafter referred to as restenosis, has been observed at follow-up. The purpose of this study was to evaluate the feasibility and effectiveness of repeated balloon dilatation of restenosed lesions after previous balloon dilatation for pulmonic (PS) and aortic (AS) stenosis and native aortic coarctation (AC). Neonates, infants, and children (n = 176) underwent balloon valvoplasty/angioplasty with reduction (p < 0.001) of peak-to-peak systolic pressure gradients from 91 ± 41 (mean ± SD)mm Hgto25 ± 19mm Hg, from70 ± 20 mm Hgto26 ± 12 mm Hg, andfrom48 _+ 17mmHgto11 ± 9 mm Hg in patients with PS, AS, and AC, respectively. Repeated catheterization or echo-Doppler studies or both were performed from 3 months to 5 years after initial balloon dilatation. Residual gradients at follow-up were 26 ± 26 mm Hg, 34 ___20 mm Hg, and 16 ± 15 mm Hg, respectively, for PS, AS, and AC and remained significantly lower (p < 0.01) compared with gradients before the balloon dilatation. However, when results of individual patients were scrutinized, 9 (11%) of 80 patients with PS, 6 (23%) of 26 patients with AS, and 16 (27%) of 60 patients with AC had restenosis, on the basis of standard criteria. Repeated balloon dilatation was performed with reduction (p < 0.05 to <0.001) of peak-to-peak gradients from 89 ± 40 mm Hg to 38 _+ 20 mm Hg in 9 patients with PS, from 77 mm Hg to 13 mm Hg and 66 mm Hg to 6 mm Hg, respectively, in 2 patients with AS, and from 38 ± 11 mm Hg to 10 ± 6 mm Hg in 12 patients with AC. Echo-Doppler studies, 2 to 6.5 years after repeated balloon dilatation, indicated excellent results, with residual peak instantaneous Doppler gradients of 24 ± 13 mm Hg in PS, 43 ± 20 mm Hg in AS, and 11 ___6 mm Hg in AC groups, respectively. This improvement is irrespective of the cause of restenosis after initial balloon valvuloplasty/angioplasty. From this experience, we con-

Fromthe aDepartmentofPediatrics, DivisionofPediatric Cardiology,University ofWisconsinMedicalSchool;bDepartments ofPediatrics and Cardiovascniar Diseases, Divisionof Pediatric Cardiology,King Faisal Specialist Hospital&ResearchCenter;andCDepartmentofPediatrics, Division ofPediatric Cardiology,St. LouisUniversity Schoolof Medicine/Cardinal Glennon Children'sHospital. Receivedfor publication Oct. 16, 1995;acceptedNov.21, 1995. Reprint requests:P. SyamasundarRao,MD,Professor&Director,Division of Pediatric Cardiology,St. LouisUniversity Schoolof Medicine, 1465 S. Grand Blvd., St. Louis,MO 63104-1095. Copyright© 1996by Mosby-YearBook,Inc. 0002-8703/96/$5.00 + 0 4/1/71983

clude that repeated balloon dilatation is feasible and effective in relieving restenosis after initial balloon valvuloplasty/angioplasty. (Am Heart J 1996;132:403-7.)

Balloon valvuloplasty/angioplasty have been used for more t h a n a decade in the t r e a t m e n t of congenital stenotic lesions of the h e a r t and great vessels. Varying degrees of residual obstruction or recurrence, h e r e a f t e r referred to as restenosis, h a v e been observed at follow-up. The purpose of this s t u d y was to evaluate the feasibility a n d effectiveness of r e p e a t e d balloon dilatation ofrestenosis after previous balloon dilatation of pulmonic stenosis, aortic stenosis, a n d aortic coarctation. SUBJECTS AND METHODS Study subjects. All patients with pulmonic stenosis

(PS), aortic stenosis (AS), and native aortic coarctation (AC) who underwent balloon dilatation at the King Faisal Specialist Hospital and Research Center, Riyadh, between 1983 and 1987 and at the University of Wisconsin Children's Hospital, Madison, Wisconsin, between 1987 and 1993 were included. Pulmonic s t e n o s i s . Between 1983 and 1993, 85 children, aged 1 day to 20 years (7.0 _+ 6.5 years), underwent balloon pulmonary valvuloplasty; the indications for the procedure were a peak-to-peak gradient >50 mm Hg. The technique of balloon valvuloplasty was described previously13 and is not detailed except to state that the balloon-to-pulmonary valve annulus ratio used for valvoplasty was 1.0 in initial cases, whereas in the later patients, it was 1.2 to 1.4. Clinical and echo-Doppler evaluation was performed at 3, 6, and 12 months after valvuloplasty and yearly thereafter. In the first half of the patients, cardiac catheterization was performed 6 to 12 months after valvuloplasty for evaluation of residual gradient. During the latter half of the study, echo-Doppler studies were performed routinely, and cardiac catheterization was undertaken only if repeated balloon pulmonary valvuloplasty was contemplated. Restenosis was deemed to have occurred if the peak-to-peak gradient across the pulmonary valve at catheterization was >50 mm 403

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Hg, and repeated balloon pulmonary valvuloplasty was performed. At the time of repeated balloon valvuloplasty, balloon/annulus ratio was kept at 1.2 to 1.4, and usually, a balloon larger than that used at the initial valvuloplasty was used. After repeated dilatation, follow-up echo-Doppler studies were obtained at 3, 6, and 12 months afterward and yearly thereafter. Aortic stenosis. Twenty-six children aged 6 weeks to 20 years (8.0 _+ 5.6 years) underwent balloon aortic valvuloplasty between 1983 and 1993. Indications for valvuloplasty were peak-to-peak aortic valve gradient ->70 mm Hg, irrespective of symptoms, or a gradient >50 mm Hg with symptoms or ST-T wave changes. Neonates (<30 days old) were excluded from this analysis. The balloon aortic valvuloplasty technique has been described in our previous publicationsJ 6 The balloon/annulus ratio used was 1.0. Follow-up clinical and echo-Doppler evaluations were performed at 3, 6, and 12 months after the procedure and yearly thereafter. During the initial part of the study, routine cardiac catheterizations were performed 6 to 12 months after the procedure, whereas in more recent cases only echo-Doppler studies were performed. Restenosis is defined as residual peak-to-peak gradient across the aortic valve of >50 mm Hg. Criteria for reintervention were same as those used for initial balloon valvuloplasty. The balloon/annulus ratio used was 1.0. Revaluation with echo-Doppler studies was again undertaken 3, 6, and 12 months after valvuloplasty and yearly thereafter. Aortic coarctation. There were 67 infants and children, aged 2 days to 15 years (3.9 -+ 4.3 years) in the native coarctation group during the same period as in PS and AS patients. The indications for balloon angioplasty were bypertension or congestive heart failure or both with a peakto-peak gradient >20 mm Hg across the coarctated segmerit. Again the technique of angioplasty was described in detail in our previous publications, z, 7-zoBalloon diameter used was the average of the isthmus of the aortic arch and the diameter of the descending aorta at the level of the diaphragm. If there was no improvement, balloons as large as the diameter of the descending aorta at the level of the diaphragm were used. The children were monitored with clinical and echo-Doppler studies 3, 6, and 12 months after angioplasty and yearly thereafter. Cardiac catheterization and selective cineangiography also were performed 6 to 12 months after the procedure, as per the protocol for AC. 11 Restenosis is defined as a peak-to-peak gradient across the AC >20 mm Hg and is an indication for repeated angioplasty, along with hypertension, defined as arm-cuff blood pressure ->95th percentile for age from the data of the Second Task Force for Hypertension in Children. m Balloon diameters were larger than those for initial angioplasty but no larger than the diameter of the descending aorta at the level of the diaphragm at the time of repeated angioplasty. Follow-up blood pressure and echo-Doppler studies were performed 3, 6, and 12 months after angioplasty and yearly thereafter. Statistical methods. Data are expressed as mean _+ SD for the continuous, normally distributed values. For data not normally distributed, median and ranges are given.

AmericanHeartJournal

Comparisons of values before and after balloon dilatation were made by two-tailed, paired t tests. Categoric variables were compared with Fisher's exact or other chi-square tests. The level of statistical significance was set at p < 0.05, Bonferroni adjusted, when indicated. RESULTS

Pulmonic stenosis. Balloon p u l m o n a r y valvuloplasty in 85 p a t i e n t s resulted in reduction (p < 0.001) in peak-to-peak systolic p u l m o n a r y v a l v a r gradients from 91 + 41 m m H g to 25 _+ 19 m m Hg. Catheterization (n = 47) and echo-Doppler (n = 33) d a t a at follow-up (10.4 + 7.3 months) revealed a residual g r a d i e n t of 2 6 _+ 26 m m Hg; this is u n c h a n g e d (p > 0.1) from t h a t i m m e d i a t e l y after balloon valvuloplasty and r e m a i n s significantly decreased (p < 0.001) compared with the g r a d i e n t before valvuloplasty (Table I). W h e n r e s u l t s of each p a t i e n t were examined, 9 (11%) of 80 patients in w h o m follow-up d a t a were available h a d restenosis, defined as a peak-to-peak g r a d i e n t >50 m m Hg. R e p e a t e d balloon p u l m o n a r y valvuloplasty was p e r f o r m e d 11 _+ 6 m o n t h s after initial balloon valvuloplasty. In these children, the initial peak-to-peak g r a d i e n t across the pulmonic valve was 98 -+ 45 m m Hg, which was reduced (p < 0.01) to 46 -+ 33 m m H g i m m e d i a t e l y after balloon valvuloplasty. At follow-up 11 m o n t h s later, the g r a d i e n t increased (p < 0.05) to 89 -+ 40 m m Hg. R e p e a t e d balloon valvuloplasty reduced the g r a d i e n t to 38 _+ 20 m m H g (Fig. 1). During the r e p e a t e d balloon valvuloplasty, the balloon/ a n n u l u s ratio (1.24 -+ 0.14) was h i g h e r (p < 0.01) t h a n t h a t used at the initial valvuloplasty (0.96 _+ 0.15). The p e a k i n s t a n t a n e o u s Doppler g r a d i e n t (24 -+ 13 m m Hg) r e m a i n e d low at 18 -+ 11 m o n t h s of f u r t h e r follow-up. For the entire group of p a t i e n t s with PS (n = 80), the residual peak i n s t a n t a n e o u s gradients r e m a i n e d low (17 _+ 15 m m Hg) at the last follow-up, r a n g i n g from a 6 m o n t h s to 9 years. Aortic stenosis. The peak-to-peak systolic p r e s s u r e g r a d i e n t across the aortic valve in 26 children decreased (p <0.001) from 71 -+ 20 m m H g to 26 -+ 12 m m H g after balloon valvuloplasty. At followup (10 _+ 4 months), catheterization (n = 15) and Doppler (n = 11) d a t a revealed a residual g r a d i e n t of 34 _+ 20 m m Hg; this gradient, although increased (p < 0.01) compared with the i m m e d i a t e postvalvuloplasty gradient, continued to be significantly lower (p < 0.001) t h a n t h a t before valvuloplasty (Table I). However, w h e n individual results were scrutinized, 6 (23%) of 26 h a d restenosis, defined as a g r a d i e n t >50 m m Hg. F u r t h e r follow-up for 2 to 9 y e a r s (median, 6 years) did not reveal evidence of late restenosis.

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Rao, Galal, and Wilson 405

Table I. Gradients across obstructive lesions

Condition Before balloon After balloon S h o r t - t e r m follow-up L a t e follow-up

Pulmonic stenosis mean ± SD (N) (mm Hg)

Aortic stenosis mean ± SD (N) (ram Hg)

Aortic coarctation mean ± SD (N) (mm Hg)

91 _+ 41" (85) 25 +_ 19" (85) 26 _+ 2 6 t (80) 17 + 15 II (80)

70 +_ 20* (26) 26 ± 12" (26) 34 -+ 205 (26) 27 ± 11 tl (26)

46 ± 17" (67) 11 _+ 9* (67) 16 ± 15§ (60) 9 ± 99 (60)

*Peak-to-peak gradient during cardiac catheterization. tCombined peak-to-peak catheterization (n = 47) plus Doppler peak instantaneous (n = 33). $Combined peak-to-peak catheterization (n = 15) and Doppler peak instantaneous (n = 11) gradients, §Combined peak-to-peak catheterization (n = 58) and blood pressure (n = 2) gradients. II Doppler peak instantaneous gradients. ~Arm-to-leg peak blood pressure difference.

Of the 6 children with restenosis, 4 children in our early experience underwent surgical valvotomy, and the remaining 2 children had repeated balloon valvuloplasty at a median interval of 9 months (range, 3 to 13 months) after initial balloon valvuloplasty; gradients were reduced from 71 +_ 18 mm Hg to 31 +_ 14 mm Hg (p < 0.001) after reintervention. In 2 children who underwent repeated balloon valvuloplasty, the peak-to-peak gradients were reduced from 77 and 66 mm Hg to 13 and 6 mm Hg, respectively (Fig. 2). The first, a 13-month-old child (whose aortic valve annulus was 13 mm), had balloon valvuloplasty with two 8 mm balloons simultaneously inflated across the aortic valve. The gradient was reduced from 71 to 33 mm Hg. The infant had ventricular fibrillation during the second balloon inflation, from which the infant was brought back to normal rhythm with a DC countershock. At a repeated study 13 months later, the valve annulus again measured 13 mm, and a 12 m m - d i a m e t e r balloon was used for valvuloplasty, with reduction of gradient from 77 to 13 mm Hg. Residual peak instantaneous Doppler gradient 6 years after the repeated balloon procedure was 43 mm Hg, and the patient was asymptomatic. The second patient was a 7-month-old at the time of first balloon valvuloplasty; an 8 mm-diameter balloon was used, with a resultant balloon/annulus ratio of 0.8, and peak-to-peak gradient was reduced from 64 to 31 mm Hg. Six months later, the gradient increased to 66 mm Hg. This time, a larger 12 m m diameter balloon was used (balloon/annulus ratio = 0.9), and the gradient decreased to 6 mm Hg. At a 6.5-year follow-up, residual peak instantaneous Doppler gradient remained low at 20 mm Hg (Fig. 2). For the entire group of 26 children, the residual

Doppler peak instantaneous gradient at last follow-up (3 months to 9 years; median, 6 years) was 27 _+ 15 mm Hg (Table I). Aortic coarctalion. After balloon angioplasty, the peak-to-peak gradients across the AC in 67 neonates, infants, and children decreased (p < 0.001) from 46 _+ 17 mm Hg to 11 _+ 9 mm Hg. At follow-up 14 _+ 11 months later, catheterization (58 patients) and blood pressure (2 patients) data showed a residual gradient of 16 _ 15 mm Hg. Although these gradients are slightly higher (p < 0.05) compared with immediate postangioplasty values, they remain significantly lower (p < 0.001) than those before angioplasty (Table I). However, recoarctation, defined as a residual gradient >20 mm Hg, developed in 15 (25%) of 60 patients. Recoarctation rate was higher (p < 0.01) in neonates (5 [83%] of 6) and infants (7 [39%] of 18) than in children (3 [8%] of 36), respectively. During a follow-up at 6 months to 9 years (median, 5 years), 1 (2%) additional patient had recoarctation. Of the 16 patients with recoarctation, 2 children early in our experience underwent surgical resection with good results. Two additional children, because of long-segment tubular narrowing, also underwent surgery with good results. The remaining 12 children underwent repeat balloon angioplasty. In these 12 children, the initial peak-to-peak systolic pressure gradients were 49 -2_ 17 mm Hg (range, 32 to 78 mm Hg) and were reduced (p < 0.001) to 10 +_ 9 mm Hg by the initial balloon angioplasty. At follow-up catheterization performed 16.5 _+ 17.3 months (range 4 to 53 months) later, the gradient increased significantly (p < 0.001) to 38 _+ 11 mm Hg. Repeat balloon angioplasty reduced (p < 0.001) the gradients to 10 +_ 6 mm Hg (range, 0 to 19 mm Hg; Fig. 3).

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Fig. 1. Results of repeated balloon valvuloplasty in 9 patients who had restenosis. Initial gradients were reduced (p < 0.01) significantly after valvuloplasty (Pre vs 1st B), which returned toward prevalvuloplasty valves at follow-up (FU). Repeated valvuloplasty (2nd B) again reduced gradient (p < 0.05), which remained low at late follow-up (LFU) and continued to be lower than gradients before first (p < 0.001) and second (p < 0.001) balloon valvuloplasty.

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Fig. 2. Gradients before (Pre), after initial balloon valvuloplasty (1st B), at follow-up (FU), after repeated balloon dilatation (2nd B), and at late follow-up 6 and 7 years, respectively, after initial valvuloplasty in 2 patients with restenosis. Note significant decrease in gradient after each balloon dilatation, with recurrence after first balloon dilatation. Gradient remained low after second balloon valvuloplasty.

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Fig, 3. Data are similar to those in Fig. 1 but represent peak gradients in 12 patients with native aortic coarcta-

tion who had recurrences after first balloon angioplasty. risk factors for recurrence identified. The risk factors for restenosis after balloon pulmonary valvuloplasty were (1) balloon/annulus ratio <1.2, and (2) immediate postvalvuloplasty peak-to-peak gradient >30 mm Hg. 14 Similar factors for AS were (1) age at valvuloplasty -<3 years, and (2) immediate postvalvuloplasty gradient >30 m m Hg. 4, 16 The factors associated with recoarctation were (1) age, (2) size of the isthmus, (3) size of the coarctated aortic segment before angioplasty, and (4) size of the coarctated segment after angioplasty; the younger the child and the smaller the diameter of the isthmus and the segment both before and after angioplasty, the greater the probability for recoarctation. 18 Thus the causes of restenosis appear to be age at initial intervention (for aortic stenosis and coarctation), adequacy of balloon dilatation (for pulmonic and aortic stenosis), presumably related to technical factors, technique (for pulmonic stenosis), and anatomic substrate (for aortic coarctation). Whatever the reason was for restenosis, repeated balloon dilatation of recurrent obstruction in PS, AS, and AC in our patients resulted in excellent, immediate gradient relief that persisted at follow-up. DISCUSSION

Peak arm-to-leg pressure difference 26 _+ 15 months after repeated balloon angioplasty (11 _+ 6 mm Hg) remained essentially unchanged (p > 0.1). For the entire group of 60 children, the residual blood pressure-measured gradient at last follow-up (6 months to 9 years; median, 5 years), irrespective of reintervention, was low at 9 _+ 9 mm Hg (Table I). Relation between factors associated with restenosis and effectiveness of repeated balloon dilatation. The

causes ofrestenosis after balloon dilatation ofPS, 13-15 AS,4, 16 and AC 17, is have been investigated by us and

In this study, balloon dilatation of congenital stenotic lesions (PS, AS, and AC) resulted in acute relief of obstruction. Although the group gradients remained low at follow-up, when individual patient results were scrutinized, restenosis was observed in 11%, 23%, and 27%, respectively, in patients with PS, AS, and AC. These rates of recurrences are similar to those observed by other workers, as tabulated elsewhere.3,6, 10 Repeated balloon dilatation was adopted as a treatment option for relieving the recurrent obstruction. Other groups of workers have used surgical intervention after balloon failures. 19, 20

Volume 132, Number 2, Part 1 American Heart Journal

From the good results that we observed in this study, we recommend repeated balloon dilatation as a therapeutic procedure of choice for recurrent obstruction at follow-up after previous balloon valvuloplasty/angioplasty for PS, AS, and AC. In conclusion, balloon dilatation of congenital PS, AS, and native AC produces adequate relief of obstruction. Varying rates of recurrence are observed at follow-up. In patients with restenosis, repeat balloon dilatation is feasible and effective. Irrespective of the cause of restenosis, the gradient reduction is maintained at follow-up. We recommend balloon dilatation as a procedure of choice in the treatment of restenosis after previous balloon valvuloplasty/angioplasty. REFERENCES

1. Rao PS. Transcatheter treatment ofpulmonic stenosis and coarctation of the aorta: the experience with percutaneous balloon dilatation. Br Heart J 1986;56:250-8. 2. Rao PS, Fawzy ME, Solymar L, Mardini MI~ Long-term results of balloon pulmonary valvuloplasty. Am Heart J 1988;115:1291-6. 3. Rao PS. Balloon pulmonary valvuloplasty for isolated pulmonic stenosis. In: Rao PS, editor. Transcatheter therapy in pediatric cardiology. New York: Wiley-Liss, 1993:59-104. 4. Rao PS, Thapar MK, Wilson AD, Levy JM, Chopra PS. Intermediateterm follow-up results of balloon aortic valvuloplasty in infants and children with special reference to causes of restenosis. Am J Cardiol 1989;64:1356-60. 5. Rao PS. Balloon aortic valvuloplasty: a review. Clin Cardiol 1990; 13:458-66. 6. Rao PS. Balloon valvuloplasty for aortic stenosis. In: Rao PS, editor. Transcatheter therapy in pediatric cardiology. New York: Wiley-Liss, 1993:105-27.

Rao, Galal, and Wilson 407 7. Rao PS, Najjar HN, Mardini MK, Solymar L, Thapar MI~ Balloon angioplasty for coarctation of the aorta: immediate and long-term results. AM HEARTJ 1988;115:657-65. 8. Rao PS, Chopra PS. Role of balloon angioplasty in the treatment of aortic coarctation. Ann Thorac Surg 1991;52:621-31. 9. Rao PS. Balloon angioplasty of native coarctation [Letter]. J Am Coll Cardiol 1992;20:750-1. 10. Rao PS. Balloon angioplasty of native aortic coarctation. In: Rao PS, editor. Transcatheter therapy in pediatric cardiology. New York: Wfley-Liss, 1993:153-96. 11. Rao PS, Galal O, Smith PA~ Wilson AD. Five-to-nine year follow-up results of balloon angioplasty of native aortic coarctation in infants and children. J Am Call Cardiol 1996;27:462-70. 12. Task Force on Blood Pressure Control in Children. Report of the Second Task Force on Blood Pressure Control in Children--1987. Pediatrics 1987;79:1-25. 13. Rao PS. Influence of balloon size on the short-term and long-term results of pulmonary valvuloplasty. Tex Heart Inst J 1987;14:57-61. 14. Rao PS, Thapar MK, Kutayli F. Causes ofrestenosis following balloon valvuloplasty for valvar pulmonie stenosis. Am J Cardial 1988;62:97982. 15. Rao PS. Further observations on the role of balloon size on the shortterm and intermediate-torm results of balloon pulmonary valvuloplasty. Br Heart J 1988;60:507-11. 16. Rao PS, Galal O, Wilson AD. Incidence and causes of aortic valve restenosis and insufficiency at long-term follow-up after balloon aortic valvuloplasty in children (Abstract). J Invest Med 1995;43:429. 17. Rao PS, Thapar MK, KutayliF, CareyP. Causes ofrecoarctation after balloon angioplasty ofunoperated aortic coarctation. J Am Coll Cardiol 1989;13:109-15. 18. Rao PS, Koscik R. Validation of risk factors in predicting recoarctation after initially successful balloon angioplasty for native aortic coarctation. Am Heart J 1995;130:116-21. 19. Sreeram N, Kitchiner D, Williams D, Jackson M. Balloon dilatation of the aortic valve after previous surgical valvotomy: immediate and follow-up results. Br Heart J 1994;71:558-60. 20. Minich LL, Beckman RH, Rocchini AP, Heidelberger K, Bove EL. Surgical repair is safe and effective after unsuccessful balloon angioplasty of native coarctation of the aorta. J Am Coll Cardiol 1192;19:389-93.