Balloon Pulmonary Valvuloplasty : A Review

Transcription

1 Clin. Cardiol. 12, (1989) Review Balloon Pulmonary Valvuloplasty : A Review P. s. RAO, M.D. Department of Pediatrics, School of Medicine, University of Wisconsin, Madison, Wisconsin, USA Introduction Balloon dilatation of valvar pulmonic stenosis by a pullback or dynamic technique was described by Rubio and Limon-Lason in 1954,I and by Semb et al. in 1979,z but the technique of static dilatation as it is used now was originally described by Kan and associates in This technique has been used in neonates, infants, children, and adults, and several short-term and a few intermediate term follow-up results of balloon pulmonary valvuloplasty have been reported in the literature.'-23 It may now be considered as the therapeutic procedure of choice for treatment of congenital pulmonary valvar stenosis z1.23 However, several issues with regard to balloon pulmonary valvuloplasty remain either incompletely answered or not thoroughly studied. This review addresses these issues in an attempt to provide some answers; our own experience with balloon pulmonary valvuloplasty performed in 56 consecutive infants and children over a 50-month period ending in December 1987 and follow-up catheterizations in 36 and the experience reportcd in the literature2-22 will be used toward this purpose. The description of the subjects, the procedure of the percutaneous balloon pulmonary valvuloplasty, and the data gathered have been described in our previous publication^^^^^^^^ and will not be detailed here. The study subjects will be divided, as appropriate, into several groups whose characteristics are listed in Table I. A two-tailed Supported in part by a grant from Oscar Rennebohm Foundation, Inc. Address for reprints: Dr. P. Syamasundar Rao Professor of Pediatrics Director, Division of Pediatric Cardiology University of Wisconsin Hospital & Clinics 600 Highland Avenue Madison, WI 53792, USA Received: June 13, 1988 Accepted: October 24, 1988 Student's t-test was used for comparing data between groups, as well as for data obtained before and after valvuloplasty. The Bonfemni correctionz6 was applied when multiple comparisons were made. Frequency distributions were compared using Kmskal-Wallis or Fisher's exact test as appropriate. The level of statistical significance was set at p<0.05. Now, a brief description of the study group: During a 50-month period ending December 1987, 56 infants and children, aged 7 days to 20 years (median, 6 years), underwent balloon dilatation of valvar pulmonic stenosis (Group I). There were 28 boys and 28 girls with weight range of 2.9 to 60.0 kg (mean, 26.0 kg). Following balloon valvuloplasty, the peak systolic pressure in the right ventricle decreased (108.0k43.5 vs. 54.6k20.0 mmhg, p<o.ool) as did the peak systolic pressure gradient across the pulmonic valve (92.4 k42.6 vs mmhg, p<o.ool). The pulmonary artery peak systolic pressure increased from 17.3k5.0 to 22.7k5.6 mmhg (p<o.ool). All patients were discharged home within 24 to 48 hours following the procedure. No patient required surgical intervention. Long-Term Follow-Up Results Percutaneous balloon pulmonary valvuloplasty as it is performed today was first described in 1982,3 and it is therefore understandable that no long-term follow-up data are yet available. Several authors5,10-13,15.z1 recatheterized 6 to 23 patients, 1 week to 17 months following balloon valvuloplasty (Table 11) and reported recurrence rates of 14 to 33%. Our own group comprised 36 children who underwent repeat cardiac catheterization and angiography 6 to 34 months (mean, 11.O months) following balloon valvuloplasty (Group 11). For the group of children in whom follow-up catheterization data were available, the peak systolic pressure gradient across the pulmonic valve (92.6k46.6 vs. 31.4f24.8 mmhg, p<o.ool) and the peak systolic pressure in the right ventricle (109.4 k44.1 vs. 56.9k21.5 mmhg, p<o.ool) decreased, while the pulmonary artery pressure (17.1 f5.0 vs. 23.6k5.7 mmhg, p <0.001) increased immediately after balloon valvuloplasty. The cardiac index (3.3k0.9 vs. 3.2k0.7 l/min/mz, p > 0.1) remained unchanged. Upon follow-up approximately 11 months later, systolic pressure gradient

2 56 Clin. Cardiol. Vol. 12, February 1989 TABLE I Group I Group I1 Group 111 Group IV Group V Group VI Group VII Group VIII Group IX Group X Group XI Groups XI1 Groups XI11 Groups XIV Various groupings used in the text All study patients with isolated valvar pulrnonic stenosis. 56 children, aged 7 days to 20 years Children with follow-up cardiac catheterization data (6-34 months after valvuloplasty) 36 patients Balloon dilatations in which balloon/annulus ratio was 1.O or less (0.89k0.08; range 0.76 to l.o), 12 dilatations Balloon dilatations in which balloon/annulus ratio was more than 1.0 (l.311to.19; range, 1.01 to 1.8), 44 dilatations Balloon dilatations in which balloon/annulus ratio was 1.2 or less (1.031t0.13; range, 0.76 to l.2), 32 dilatations Balloon dilatations in which balloon/annulus ratio was more than 1.2 (1.43kO.13; range, 1.21 to 1.8), 32 dilatations Balloon valvuloplasties in which balloon/ annulus ratio was between 1.21 and 1.5 ( ), 23 dilatations Balloon valvuloplasties in which balloon/ annulus ratio was between 1.51 and 1.8 (1.6*0.09), 9 dilatations Double balloon valvuloplasty (balloon/annulus ratio, ; range, 1.01 to 1.53), 12 patients Single balloon valvuloplasty, matched with Group IX for balloon/annulus ratio (1.19~0.15; range 1.0 to 1.53), 12 patients Good results group (pulmonary valve gradient of 30 mmhg or less at follow-up), 29 patients Poor results group (pulmonary valve gradient >30 mrnhg), 7 patients Dysplastic pulmonary valves, 13 patients Nondysplastic pulmonary valves, 43 patients across the pulmonic valve (30.1 k23.6 mmhg, p<o.ooi) and residual right ventricular peak systolic pressure (55.1 k33.6 mmhg, p<o.001) remain improved when compared with prevalvuloplasty values. The cardiac index ( l/min/m2) did not significantly (p>o. 1) change. Despite improvement as a group, several children developed restenosis of the pulmonary valve (Fig. 1). Seven of the 36 (19%) had pulmonary valve gradients in excess of 30 mmhg. Five of these children underwent repeat balloon valvuloplasty with larger balloons (Fig. 1) and the pulmonary valvar gradients were reduced from 102.4k40.2 to 38.2k12.0 mmhg (p<o.ol). The other two children with residual gradients of 45 and 60 mmhg are being followed clinically. Restenosis rate of 19% in our group is comparable to the 14 to 33% rates reported by other Based on these data, the intermediate term follow-up results appear encouraging and lead us to recommend balloon valvuloplasty as a procedure of choice for treatment of isolated valvar pulmonic stenosis. Further refinement in the technique (to be discussed below) may decrease or abolish the recurrence rate. Despite these good results, much longer term (5-10 years) follow-up data are necessary to further confirm long-term effectiveness of balloon pulmonary valvuloplasty for relief of valvar pulmonic stenosis. How Large a Balloon Should Be Used? RadtkeI6 and we24 evaluated the influence of balloon size on the results of pulmonary valvuloplasty and recommended a balloon to pulmonary valve annulus ratio of 1.2 to 1.4. Such recommendations are arbitrary and were based on (1) the small number of patients,'6,24 (2) the lack of follow-up results, or (3) follow-up results based on a few patients.24 Our experience with 64 consecutive balloon dilatation procedures performed in 56 patients with isolated valvar pulmonic stenosis and 39 follow-up catheterizations in 36 patients was reviewed to examine this issue. Five repeat valvuloplasty procedures were performed at follow-up catheterization and three patients had valvuloplasty sequentially with balloons, resulting in increasingly larger balloon annulus ratios. Thus there were 64 valvuloplasty procedures in 56 patients divided into two groups: Group 111, in which the balloon/annulus ratio was 1.O or less (12 dilatations); and Group IV, in which the ratio was more than 1.0 (52 dilatations) (Table 11). The two groups had similar (p > 0.1) prevalvuloplasty valvar gradients (84.3k39.2 vs. 92.8f42.1 mmhg) (Table 111). Immediately after valvuloplasty there was a significant reduction in pulmonary valve gradient in both Group 111 (84.3k29.2 vs. 43.6k26.8 mmhg, p<0.02) and Group IV (92.8k42.1 vs. 22.4k13.6 mmhg, p<o.ooi), although there was a greater fall in the gradient in Group IV when larger balloons were used. On intermediate term follow-up (which ranged between 6 and 34 months), residual pulmonary valve gradients wert significantly lower (p<o.ool) in Group IV (20.8k18.5 mmhg) than in Group 111 (75.0k49.4 mmhg), suggesting restenosis in Group 111 using small balloons (Table 111). At follow-up, repeat balloon valvuloplasty was required in four Group 111 patients and only one patient from Group IV (p <0.005) (Table IV). Similarly, a higher (p < 0.005) number of patients with residual pulmonary valve gradient in excess of 30 mmhg were present in Group I11 than in Group IV (Table IV). These data suggest that although good immediate results are seen with either small or large balloons, balloons larger than the pulmonary valve annulus produce more sustained relief of pulmonary stenosis. Second, the balloon/annulus ratio cut-off point was increased to 1.2 and balloon valvuloplasties were divided into another two groups (Table I): Group V, in which the

3 P. S. Rao: Balloon pulmonary valvuloplasty 57 TABLE I1 Reference Intermediate term follow up catheterization results of balloon pulmonary valvuloplasty (BPV) from the literature Duration Number of Number of (months) of Poor resulta patients under- patients with follow-up, on follow-up going BPV follow-up mean (rangc) no. (%) Comments Kan et al., 1983 (71) Tynan et al., 1985 (10) Kveselis et a/., 1985 (1 1) Miller, 1986 (12) Sullivan et ul., 1986 ( I 3) Khan et al., 1986 (15) Rey et al., 1988 (21) Rao et a/., 1988 (23) (2-12) 6 -(2-6) 7 12(9-13) 7 4(3-6) (0.25-6) 14 lo(6-14) 23 -(l-17) 36 1 l(6-34) The failure was in patients with dysplastic valve or after previous Brock Both patients underwent surgery Repeat BPV in one patient with 52 mmhg gradient with reduction to 34 mmhg Two patients with gradients of 24 and 22 mmhg at follow-up underwent repeat BPV with excellent results Repeat valvuloplasty in 4 patients with good results Repeat BPV in 5 patients with satisfactory results Repeat BPV in 5 patients with good results OPoor result is defined as pulmonary valve gradient in excess of 30 mmhg at follow-up. bthe pulmonary valve gradient ranged between 31 and 52 mmhg with a mean of 38 mrnhg. ratio was 1.2 or less and Group VI, in which the ratio was more than 1.2. In Group V consisting of 32 dilatations, the mean ratio was while in Group VI, which also consisted of 32 balloon dilatations, the ratio was 1.43 fo. 13. Both of these groups had similar (p >O. I) t E v E Q) -0 E Is) 100? 3 u)?!._ - 0 c u) 50 $ 0 Pre Post FU Repeat Second BPV BPV BPV FU FIG. 1 Longitudinal follow-up data following balloon pulmonary valvuloplasty (BPV). In 29 children (solid lines), the peak systolic pressure gradient across the pulmonic valve improved or remained unchanged on follow-up (FU) when compared to immediate post- BPV gradient. In seven children (interrupted lines), the gradient remained high or increased. Five of these children underwent repeat valvuloplasty with larger balloons with improvement in pulmonary valvar gradients. A second FU study in three patients showed further fall in the gradient in each patient. prevalvuloplasty gradients (Table V). Both groups had significant (p < ) reduction in pulmonary valve gradients both immediately after valvuloplasty and on follow-up (Table V). However, the follow-up gradients in Group VI with larger balloons were lower (p <0.01) than those in Group V with small balloons. Five patients from Group V required repeat balloon dilatation at follow-up while none from Group VI required repeat valvuloplasty (p<o.ool) (Table IV). Also, 7 Group V patients had gradients in excess of 30 mmhg, while Group VI gradients did not reach that high a level on follow-up (p<o.ool) (Table IV). Based on these data, balloons smaller than 1.2 times the pulmonary valve annulus have a significant chance for having residual pulmonary stenosis on followup and, as such, are not recommended. Finally, the results of balloon valvuloplasty with a balloon annulus ratio of l.21 to l.5 (Group VII) were compared with those in which the ratio was in excess of 1.5 (Group VIII), because balloons larger than 1.5 times the size of the valve annulus are reported to produce damage to the right ventricular outflow tract.* In Group VII (23 patients) mean balloon/annulus ratio was 1.36&0.08; while in Group VIII (9 patients), mean balloon/annulus ratio was 1.6 f0.09 (Table I). The pulmonary valve gradients were similar (p>o.l) (Table VI) prior to valvuloplasty in both groups. Significant (p <0.01) reduction of gradient occurred in both groups immediately after valvuloplasty as well as at follow-up catheterization (Table VI). Residual pulmonary valvar gradients immediately

4 58 Clin. Cardiol. Vol. 12, February 1989 TABLE 111 Comparison of Group 111 with balloon/annulus ratio of 1.O or less with Group IV with balloon/annulus ratio > 1.O Group 111 Group IV mean f SD mean f SD p Value prevalvuloplasty, mmhg 84.3f f42.1 immediately after valvuloplasty, mmhg 43.6f26.8" 22.4f 13.6' at follow-up, mmhg 75.O f49.4' 20.8f 18.5' 'p <0.02 when compared with prevalvuloplasty gradients. bp < when compared with prevalvuloplasty gradients. 'p > 0.1 when compared with prevalvuloplasty gradients. >o. 1 <0.01 <0.001 TABLE IV Prevalence of repeat valvuloplasty and significant residual gradients in various groups Number of patients Number of patients needing repeat with pulmonary valve valvuloplasty p Value" gradient >30 mmhg p Value' Group 111 (n= 17) Group IV (n=32) Group V (n=21) Group VI (n= 18) n =number of patients with intermediate term follow-up catheterization. "Fisher's exact test TABLE V Comparison of Group V with balloonlannulus ratio of 1.2 to less with Group VI with balloon annulus ratio > 1.2 Group v Group VI mean f SD mean f SD p Value prevalvuloplasty, mmhg immediately after valvuloplasty, mmhg at follow-up, mmhg 93.4 f k23.5" 42.3f41.6" 89.1 f f18.5" 16.7f7.9" >o. 1 >0.1 >0.01 'p < when compared with prevalvuloplasty gradient. TABLE VI Comparison of Group VII with balloon/annulus ratio of 1.21 to 1.5 with Group VIII with balloon/annulus ratio of 1.51 to 1.8 Group VII Group VIII mean f SD mean f SD p Value prevalvuloplasty, mmhg 91.8 rt f37.4 immediately after valvuloplasty, mmhg 26.7 f20.4' 27.8& 13.3" at follow-up, mmhg 17.2 f 8.4" 14.0 f5.6" 'p <0.001 when compared with prevalvuloplasty gradient. >0.1 <0.1 <o. 1

5 P. S. Rao: Balloon pulmonary valvuloplasty 59 after balloon dilatation and on follow-up (Table VI) were similar (p >O. 1). No patient in either group required repeat balloon dilatation, nor was there any patient with residual pulmonary valvar gradient in excess of 30 mmhg. These data signify that balloons larger than 1.5 times the size of the pulmonary valve annulus offer no advantage over the balloons with a ratio of 1.21 to 1.5. Thus, the data presented in this section indicate that balloons larger than l.2 times the diameter of the pulmonary valve annulus should be used for pulmonary valvuloplasty if restenosis is to be prevented and that there is no advantage to the use of balloons larger than 1.5 times the size of the pulmonary valve annulus. Therefore, balloons which are 1.2 to 1.5 times the diameter of the pulmonary valve annulus are recommended as most ideal for relief of pulmonary stenosis. How Long a Balloon? The majority of workers use 30-mm long balloons in performing pulmonary valvuloplasty. There are no data either from our own series or from the literature to assess whether shorter (20 mm) or longer (40 mm or longer) balloons have any advantages or disadvantages over the conventional 30-mm length balloons. The 20-mm balloons are too short to maintain the balloon center over the pulmonary valve annulus during balloon inflation and, therefore, are not advisable in children and adolescents. The 20-mm balloons are appropriate for neonates and infants. Balloons of 40-mm and longer may impinge upon the tricuspid valve mechanism causing injury to it. Two recent experiences, one causing avulsion of the papillary muscle2* and another causing complete heart blockz9 when 60- and 40-mm long balloons, respectively, were used, suggest that these long balloons should not be used for balloon pulmonary valvuloplasty. Based on this discussion it may be concluded that, until data to the contrary become available, 30-mm balloons should be used when performing valvuloplasty in children. How Many Balloons? Although single balloons are used in the majority of cases, valvuloplasty with simultaneous inflation of two balloons placed across the stenotic pulmonary valve when the pulmonary valve annulus is too large to dilate with ii single balloon has also been reported , Indeed, some authorsz0 advocate use of double-balloon valvuloplasty as a procedure of choice, especially in adults. In order to evaluate this issue, 12 patients from our series who underwent double-balloon valvuloplasty (Group IX) were compared with 12 patients with single-balloon valvuloplasty who were matched for the balloon/annulus ratio (Group X). Effective balloon diameter with double bal- loons was calculated by using a formula that we previously proposed:24 D2 DI Dl+D2+7r(2+ 2 ) 7r where D 1 and D2 are the diameters of the balloons used. The balloon/annulus ratio in Group IX with double balloons (1.19 +_O. 14) was similar (p > 0. l) to that (1.19f0.15) in Group X with single balloon (Table I, Fig. 2). The two groups had similar (p >O. 1) prevalvuloplasty pulmonary valvar gradients (100.5 f28.0 vs f40.1 mmhg), and peak right ventricular systolic pressures (Fig. 2). Immediately following valvuloplasty there was a significant reduction (p<o.ool) in pulmonary valvar gradients in both groups which remained improved (p <0.001) at 6- to 14-month follow-up catheterization (Fig. 3). Residual pulmonary valvar gradients immediately after valvuloplasty and at follow-up catheterization were similar (p>o. 1) in both groups (Fig. 4). These data indicate that results of double-balloon valvuloplasty, though excellent, are only comparable to, not superiorto those observed with single balloon valvuloplasty. The balloon to pulmonary valve annulus ratio as presented in the earlier part of the discussion is perhaps a better determinant of relief of pulmonary valve stenosis than whether a single- or doubleballoon technique is used. The use of the specific formula that we used for calculation of balloon size and balloon/annulus ratio may be criticized, but this formula was simultaneously and independently advocated by usz4 and other~~6joj0~~3~ and fits the best available geometric model. Therefore, I feel that the comparison of double-balloon data with single-balloon data is justified. 2'01 Mean+SD T g s I v) ;. m v 75 f v) rn ; E $ m 0 0 BIA ratio RV pressure PV gradient FIG. 2 Balloon/pulmonary valve annulus (B/A) ratios of Group IX with double balloon valvuloplasty (W) is compared with that of Group X with single-balloon valvuloplasty (B) and found to be similar (p>o. 1). The right ventricular (RV) peak systolic pressure and pulmonary valve (PV) peak systolic pressure gradient in Groups IX and X were also similar (p>o. I) prior to balloon valvuloplasty; these data suggest that severity of pulmonaly valve stenosis is similar in both groups. 25

6 60 Clin. Cardiol. Vol. 12, February 1989 Prior IMM FU F75 75 E 100.g E ti !I 0 0 RV pressure PV gradient RV pressure PV gradient Immediately after FOIIOW-UP FIG. 3 The pulmonary valve peak pressure gradient fell (p <0.001) immediately (IMM) following balloon valvuloplasty with two balloons (H) (Group IX) as well as with one balloon (R) (Group X). On intermediate term follow-up (FU) the gradient remains low (p <0.001) when compared with prevalvuloplasty valves in both groups. These data suggest excellent immediate and intermediateterm results of pulmonaly valvuloplasty both with double- and singleballoon techniques. FIG. 4 Residual right ventricular (RV) pressures and pulmonary valvar (PV) peak systolic pressure gradients immediately after balloon pulmonary valvuloplasty and at intermediate term follow-up were similar in both groups [two balloons (W) and single balloon (B)] p>o.l). These data suggest good results whether a double or a single-balloon technique was used for pulmonary valvuloplasty and that the immediate and follow-up results are similar in both groups. The suggestion by A1 Kasab and associateszo that a double-balloon technique is preferable is based on immediate and short-term (6-week follow-up only) results (but without single-balloon controls) and less systemic hypotension and bradycardia during balloon inflation. Initially we inflated the balloon(s) for 10 s9 for valvuloplasty and we also noticed hypotension9 during balloon inflation, but the blood pressure promptly returned to normal after balloon deflation. More re~ently,~~,*~ we have used 5-s inflation with less hypotension, not too different from that reported with double-balloon techniq~e'~.~~ and without sacrificing the results. Although we and others19 did not find significantly higher complication rates with the double-balloon technique, it does indeed prolong the procedure and involves an additional femoral venous site and the attendant potential complications. Therefore, we would recommend that the double-balloon technique be used when the pulmonary valve annulus is too large to dilate with a commercially available single balloon or when a single balloon cannot be safely passed across the femoral vein, l9 but not because the double-balloon technique gives a better result. Bifoil and trifoil balloon catheters33 may help resolve the problem, but our limited personal experience suggests that these catheters are too bulky and the advantage of less hypotension during valvuloplasty is minimal. In conclusion, the immediate and follow-up results of pulmonary valvuloplasty with two balloons are excellent. These results are similar to those seen with equivalent sized single-balloon valvuloplasty and did not offer additional advantage over single-balloon results. There is no data to support the contention that the double-balloon technique is superior to single-balloon pulmonary valvuloplasty. It is suggested that a double- balloon technique be used when the pulmonary valve annulus is too large to dilate with a commercially available single balloon. Causes of Restenosis Recurrence of pulmonary valve stenosis following balloon valvuloplasty has been reported,s~ but the reason for restenosis at intermediate term follow-up has been studied only to a limited degree. We have systematically investigated the causes of recurrence of pulmonic stenosis following balloon valvuloplasty. 34 On the basis of results of 6-34 months of follow-up catheterization data in 36 children, they were divided into: Group XI with good results (pulmonary valve gradient < 30 mmhg or less), 29 patients; and Group XII with poor results (gradient >30 mmhg), 7 patients (Table I). In Group XI with good results the pulmonary valvar gradient decreased from 90.3f47.7 to 24.8k18.9 mmhg (p < 0.001) immediately following valvuloplasty which fell further to mmhg at follow-up catheterization. In Group XI1 children with poor results, the pulmonary valvar gradient fell from f43.7 to 51.9f29.9 mmhg (p<o.ol). However, on follow-up the gradient (81.1 f41.1 mmhg) returned toward prevalvuloplasty values (p>o.l). At follow-up, Group XI children with good results had lower gradients across the pulmonic valve (15.8k9.7 vs i-41.1 mmhg, p<o.ool) thangroup XI1 children. None of the Group XI children required surgical repair or repeat balloon valvuloplasty. Five children from Group XII, upon restudy at 6 to 23 months (mean 11.6 months) after initial balloon valvuloplasty, were found to have significant restenosis of the pulmonary valve (Fig. 1) and underwent repeat balloon valvuloplasty with larger balloons; the pulmonary valve gradient was reduced

7 ~~ P. S. Rao: Balloon pulmonary valvuloplasty 61 TABLE VII Variables examined by multivariate logistic regression analysis to identify factors responsible for pulmonary valve restenosis following balloon valvuloplasty Age at valvuloplasty Duration of follow-up Pulmonary valve dysplasia, severe or mild Pulmonary valve ring hypoplasia Right ventricular hypoplasia Angiographic infundibular stenosis Right ventricular peak systolic pressure prior to valvuloplasty Pulmonary valve peak systolic pressure gradient prior to valvuloplasty Right ventricular infundibular pressure gradient prior to valvuloplasty Pulmonary valve peak systolic pressure gradient immediately after valvuloplasty Balloon/pulmonary valve annulus ratio Maximum pressure achieved in the balloon Number of balloon dilatations Total duration of balloon inflation Table IV. The relationship between pulmonary valve gradients immediately after valvuloplasty with recurrence of pulmonic stenosis at follow-up is shown in Table VIII, which suggests a high rate of recumnce if the residual gradient is in excess of 30 mmhg. Dysplastic pulmonary valves did not seem to play a role in recurrence and this may have been due to the use of large balloons with dysplastic valves; 10 of the 29 Group XI patients with good results and 3 of the 7 Group XI1 patients with poor results (p > 0.1) had dysplastic pulmonary valves. In conclusion, risk factors that might predispose to recurrence of stenosis following balloon pulmonary valvuloplasty have been identified and include balloon to pulmonary valve annulus ratio less than l.2 and immediate postvalvuloplasty pulmonary gradient in excess of 30 mmhg. A high rate of recurrence can be expected if the immediate postvalvuloplasty gradient is > 30 mmhg and this may serve as a marker to identify potential recurrences. Therefore, it may be advisable to use larger balloons and reduce the valve gradient to less than 30 mmhg at the time of initial balloon valvuloplasty. from 102.4k40.2 to mmhg ( ~~0.01). The remaining two children from Group XI1 had residual gradients of 45 and 60 mmhg on restudy, respectively, at 12 and 7 months following initial balloon valvuloplasty ; no repeat balloon valvuloplasty was performed, but these children are being followed clinically. Fourteen different variables (Table VII) were examined by multivariate logistic regression analysis to identify factors associated with restenosis. Two risk factors were identified and include balloon/annulus ratio of 1.2 or less and residual pulmonary valve gradient in excess of 30 mmhg immediately after balloon valvuloplasty. Higher rate of recurrence, as evidenced by the need for repeat valvuloplasty in a larger number of patients and by the presence of a greater number of patients with gradients in excess of 30 mmhg at follow-up when smaller balloons are used is illustrated in Pressure, Number, and Duration of Balloon Inflation The recommendations for pressure of inflation of the balloon varied between 2 to 8.5 atm3-5~7~9~13~1s~1619.2'.23 and duration of each inflation was suggested to be 5 to 20 s. Anywhere between one to four balloon inflations, 2 to 5 minutes apart, has been suggested. Clearly, no data are available for deciding on which is the best method of inflation. We examined these issues from our data. The inflation characteristics in Group XI with good results were compared with those of Group XI1 with poor results (Table IX). As can be seen there were no significant differences between the groups, suggesting that the outcome of valvuloplasty is not related to these balloon inflation characteristics. We have also looked at the data with arbitrary division of maximum pressure, number of balloon TABLE VIII Relationship between pulmonary valve gradients immediately after valvuloplasty with recurrence of pulmonic stenosis (PS) Residual pulmonary valvar gradient 530 mmhg No. of patients in No. with the specified recurrence group of PS D Value" 25 1 Residual pulmonary valvar gradient >30 mmhg "Fisher's exact test 11 6

8 62 Clin. Cardiol. Vol. 12, February 1989 TABLE IX Balloon inflation characteristics in Group XI with good results and Group XI1 with poor results Inflation characteristic Group XI mean f SD Group XI1 mean f SD p Value Maximum pressure in the balloon, atm Number of balloon inflations Total duration of balloon, s 4.6f f f f 1.O 37.9f 13.5 >o. I >o. I >0.1 TABLE X Influence of maximal pressure of balloon inflation on the immediate and follow-up residual pulmonary valve gradients Maximum pressure of balloon inflation, atm <3 4-5 > 5.0 p Value Pre-BPV gradient, mmhg mean f SD 94.8 f f f45.6 >O. 1 Post-BPV gradient, mmhg mean f SD 24.9f f f26.2 >O.l FU gradient, mmhg mean +SD 43.O f I f f36.4 >o. 1 FU gradient, mmhg (BA ratio < 1.O) mean f SD 24.6 f f f 13.4 >o. 1 The p value was derived by comparing 53 with 4-5, 4-5 with <5.0, and >5 with 53 atm groups. Abbreviations: BA=balloon/annulus ratio, BPV =balloon pulmonary valvuloplasty, FU =follow-up. TABLE XI Influence of number of balloon dilatations on the immediate and follow-up residual pulmonary valve gradients Number of balloon dilatations p Value Pre-BPV gradient, mmhg mean f SD 77.9f f Of 36.0 >0.05 Post-BPV gradient, mmhg meanfsd 22.0f f f 19.7 >0.05 FU gradient, mmhg mean f SD 42.3 fs f f 15.3 >o. 1 FU gradient, mmhg (BA ratio > 1.0) mean f SD 27.2f f f 15.3 >o. 1 The p value was derived by comparing 3 with 4, 4 with 5-7, and 5-7 with 3 dilatation groups. Abbreviations: See Table X. inflations and total duration of balloon inflation (Tables X-XII) and found that higher pressure, larger number, and longer duration of balloon inflation did not favorably influence residual gradients at follow-up, especially when the influence of balloon/annulus ratio was removed. Some investigators5 recommend 7 to 8.5 atmospheres of pressure, which in our opinion, increases the chance of balloon rupture and potential problems associated with rupture. In our own experience, the waisting of the balloon was noted to disappear even at 2 atm of pressure with resultant good valvul~plasty.~ We now routinely perform valvuloplasty sequentially at 3, 4, and 5 atm of pressure inflation. The waisting usually abolishes at 3 or 4 atm. With this protocol, we have not found any balloon ruptures. Initially, we used 10-s inflation and now we use 5-s inflation. The latter produces less hypotension, and

9 P. S. Rao: Balloon pulmonary valvuloplasty 63 TABLE XI1 Influence of total duration of balloon inflation on the immediate and follow-up residual pulmonary valve gradients -~ ~ Total duration of balloon inflation, s < > 40 p Value" Pre-BPV gradient, mmhg mean f SD 87.3 f f k35.2 >0.1 Post-BPV gradient, mmhg mean f SD 25.7f f f20.2 >O. 1 FU gradient, mmhg mean f SD 25.5 k k f 16.7 >O. 1 FU gradient, mmhg (BA ratio < 1.O) mean f SD 25.4 f f f 16.7 >o. 1 "The p value was derived by comparing 525 with 26-40, with >40, and >40 with 525 s groups. Abbreviations: See Table X. this returns to normal a few seconds after deflation. After a successful valvuloplasty we usually repeat the procedure two additional times. We agree with Yeager's ob~ervation~~ that pressures much higher than those required to abolish waisting of the balloon offer no advantage especially as the polyethylene balloons are designed to maintain a relatively uniform diameter even at high pressures. Furthermore, high pressures tend to produce balloon rupture. Shorter inflation-deflation cycle produces minimal hemodynamic disturbances during valvuloplasty. Based on the data presented and on our own experience, we would recommend sequential balloon inflation with 3, 4, and 5 atm of 5-s duration, 5 minutes apart. Dysplastic Pulmonary Valve Dysplastic pulmonary valves have been implicated as a cause of failure following balloon pulmonary val- v~loplasty.~~~~-'~~~'~~~ More recent detailed reports of balloon valvuloplasty in patients with dysplastic pulmonary valve^^^.^^ suggest that poor results may be expected with dysplastic pulmonary valves. A summary of experience reported in the literature is tabulated in Table XIII. Our experience with dysplastic pulmonary valves is contrary to these reports. Therefore, we reviewed the results of balloon valvuloplasty in 13 patients with dysplastic pulmonary valves (Group XIII) from our total experience with 56 patients to assess the outcome of balloon valvuloplasty in dysplastic valves. These results were compared with valvuloplasty results of 43 nondysplastic pulmonary valves (Group XIV). Dysplasia of the pulmonary valve was assessed based on the criteria outlined by Jeffrey, Koretsky, and associate^.^^*^^ When all criteria, namely (a) angiographic appearance of nodular and uneven thickening and poor doming of the valve leaflets (Fig. 5), (b) valve ring hypoplasia (less than mean value for the given body surface area as defined by Rowlatt et al4'), and (c) no post- TABLE XI11 Summary of results of balloon valvuloplasty in patients with pulmonary valve dyspiasia (DPV) from the literature No. of patients Immediate FOIIOW-UP Authorlyear with DPV success (%) success (%) Kan et al., 1984 (5) 1 0 (0) 0 (0) Tynan et al., 1985 (10) 3 0 (0) 0 (0) Miller, 1986 (12) 1 0 (0) - Sullivan et al., 1986 (13) 2 1 (50) 0 (0) Rocchini, Beekman, 1986 (36) 7 0 (0) 3 (43) Musewe et al (37) 5 1 (20) 1 (20) DiSessa et al., 1987 (38) 3 0 (0) - Rey et al., 1988 (21) 4 3 (75) 3 (75) Rao ef al., 1988 (23) 13 9 (69) 10 (77) Total (36) 17 (49)" "Patients without follow-up were excluded for the purpose of calculation of percent success

10 64 Clin. Cardiol. Vol. 12, February 1989 FIG 5 Selected frames from right ventricular (RV) cineangiograms from patients without (A) and with (B) dysplastic pulmonary valves. In A, thickened, domed pulmonary valve leaflets are seen. Note post-stenotic dilatation of the pulmonary artery (PA). In B the pulmonary valve leaflets are unevenly and markedly thickened without doming of the leaflets. There was no jet formation and no post-stenotic dilatation of the pulmonary artery. The pulmonary valve ring is small when compared to norms described by Rowlatt et stenotic dilatation, were present, the pulmonary valve was considered dysplastic. When valve leaflets appeared dysplastic without the presence of one or both the other criteria, the valve was considered mildly dysplastic. A total of 13 dysplastic pulmonary valves were identified, 7 were severely dysplastic and 6 were mildly dysplastic. Balloon valvuloplasty in 13 patients, aged 6 days to 12 years (median, 1 year), with dysplastic pulmonary valves (Group XIII) reduced the pulmonary valve gradient from 77.2k44.2 to 26.8f17.0 mmhg (p<0.001), which remained improved (34.9k34.6 mmhg, p<0.02) at 6-19 months (mean, 10 months) follow-up (Table XIV). Valvuloplasty in 43 patients without dysplastic pulmonary valves (Group XIV) reduced the valve gradient from to 31.1k22.4 mmhg (p<o.ool) immediately following the procedure, which at 6-34 months followup in 23 patients was 29.2k33.5 mmhg (p<o.ool) (Table XIV). The pulmonary valvar gradients (77.2f44.2 vs k41.0 mmhg) prior to valvuloplasty, residual pulmonary valvar gradient (26.8k 17.0 vs f22.4 mmhg) immediately after valvuloplasty, and residual gradient (34.9k34.6 vs. 29.2k33.5 mmhg) at follow-up catheterization were similar (p >O. 1) in both groups (Table XIV. However, the balloon/annulus ratio used in dysplastic pulmonary valve patients (1.3 k0.25) was slightly higher than that used in nondysplastic pulmonary valve patients (1.2f0.24) although this difference did not attain statistical significance (p >O. 1). Two of the 13 dysplastic pulmonary valve patients and 3 of the 23 nondysplastic pulmonary valve patients required repeat TABLE XIV Comparison of Group XI11 with dysplastic pulmonary valves with Group XIV with no pulmonary valve dysplasia Group XI11 mean & SD Group XIV mean + SD p Value prevalvuloplasty, mmhg immediately after valvuloplasty, mmhg at follow-up, nimhg k 17.0" 34.9 f 34.6' O 31.1 k22.4" 29.2 k33.5" >O. 1 >o. 1 >0.1* "p <O.OOl when compared to prevalvuloplasty gradient bp <O.02 when compared to prevalvuloplasty gradient.

11 P. S. Rao: Balloon pulmonary valvuloplasty 65 valvuloplasty (p > 0.1) at follow-up catheterization. Residual pulmonary valvar gradients in excess of 30 mmhg at follow-up were present in 3 of 13 and 4 of 23 (p>o. 1) patients, respectively, with and without dysplastic valves. When all valvuloplasties were divided into those with good results (gradient I 30 mmhg at follow-up) (29 patients, Group XI) and poor results (gradient > 30 mmhg at follow-up) (7 patients, Group XII), the prevalence of dysplastic pulmonary valves respectively in these two Groups was 10 and 3 and was similar (p>o.l). In 10 patients with dysplastic pulmonary valves with good results, the balloon/annulus ratio (1.37f0.22) used for valvuloplasty was larger (p<o.oi) than that (1.04kO. 17) used in three patients with poor results. These data suggest that (I) the results of balloon valvuloplasty in patients with dysplastic valves are comparable to those without, (2) the dysplastic valves were not responsible for recurrence of valve stenosis, and (3) use of large balloons in patients with dysplastic valves may have reduced the chance for recurrence. The reason for the discrepancy in the results of valvuloplasty in patients with dysplastic pulmonary valves is not clear; it may be related to interpretation of clinical and angiographic data in labelling a given patient as having dysplastic pulmonary valves, it may be related to vari- Based on our own experience with teen-age children23 and that of others in ad~lts,~~.~~ infundibular spasm following balloon valvuloplasty appears to be more common in older patients than in young patients. The reason for able degrees of pulmonary valve dyspla~ia,~~,~~,~~ or this is probably related to long-standing right ventricular presence of commissural fusion mixed with dyspla- hypertension and consequent right ventricular hypertrophy sia.36.3s,42 It is generally considered that splitting of com- in older patients. missural f~sion~~.~~ is one of the major mechanisms of In summary, it appears that successful balloon valrelief of valvar stenosis by balloon dilatation. Therefore, vuloplasty is feasible at all ages. it is somewhat surprising that some patients with dysplastic valves would have good results. However, variability of extent of dysplasia and dysplasia mixed with commissural f ~ s i o n ~ can, ~ - to ~ some ~, ~ extent, ~, ~ explain ~ these results. Musewe et al. 37 suggested that if echocardiographic features of commissural fusion are present, catheterization and angiography should be performed to confirm commissural fusion and if it is confirmed, balloon valvuloplasty should be performed. We agree with this approach. However, based on the results presented in the current study, we would recommend balloon valvuloplasty for relief of pulmonary valve obstruction even with angiographic features of pulmonary valve dysplasia. Also, it seems reasonable to use larger balloons than is recommended for nondysplastic pulmonary valves; we personally tend to use balloons large enough to produce balloon/annulus ratios of l.4 to l.5 and tend to avoid ratios in excess of 1.5 for fear of damage to the right ventricular outflow tract.* Applicability to All Ages Although balloon pulmonary valvuloplasty is used most frequently in children, it has also been used successfully in neonates6, and in adults ,47 The experience with pulmonary valvuloplasty in the neonate with critical pulmonary stenosis is limited, and the series with largest numbers contain only single-digit numbers. 21,22 The procedure is more technically difficult but can be accomplished by use of end-hole balloon wedge catheters, small, Hi- Torque guide wires, and low-profile balloon catheter^.^^.^^.^^ The pulmonary outflow tract occlusion during valvuloplasty is well tolerated by continuous administration of prostaglandins to maintain ductal patency. The overall result is perhaps not as favorable as in children. Right ventricular hypoplasia, severe infundibular obstruction, pulmonary valve ring hypoplasia, and pulmonary valvar dysplasia may have an adverse effect on the results of valvuloplasty in neonates with critical pulmonary stenosis. Relief of pulmonary stenosis in adult patients can also be accomplished by balloon valvuloplasty Because of the physical size of the pulmonary valve ring, many adult patients may require balloon valvuloplasty using two balloon^.^^.^^ However, as pointed out earlier in this review, the double-balloon technique is not superior to single-balloon techniques. Mechanism of Valvuloplasty The mechanism of valvuloplasty was assessed by Walls and associates by inspection of valve mechanism by direct vision at they found tearing of valve raphae, tearing of the valve leaflet and avulsion of the valve leaflets, all of which are conceivably the mechanisms by which relief of pulmonary valve obstruction can occur. Direct visual observations by other though limited in numbers, and echocardiographic observation~l~.~~ also indicate similar mechanism. We observed pulmonary valve leaflets in one patient with tetralogy of Fall~t,~~ one year after balloon valvuloplasty and found two commissural tears. The circumferential pressure exerted by balloon inflation is likely to rupture (tear) the weakest part of the valve mechanism. It is likely that the fused commissures are the weakest links that can be broken with balloon dilatation. However, in a given patient, when the fused commissures are strong and cannot be tom, tears in the valve cups or avulsion of the valve leaflets44 can occur. The latter events may cause more severe pulmonary insufficiency which may be reasonably well tolerated.

12 66 Clin. Cardiol. Vol. 12, February 1989 Infundibular Obstruction Several authors reported either persistent right ventricles infundibular gradients or appearance of such gradients following balloon pulmonary valvu10plasty.~~~~~~~ When such infundibular obstruction was severe, propranolol was administered by several groups of workers15,21.23 with variable results. Infundibular resection by surgery was required in two patients In a few studies with follow-up catheterization the infundibular obstruction improved. I From our study group, 10 children had infundibular pressure gradients prior to valvuloplasty ; these ranged between 10 to 135 mmhg (49f45 mmhg). Following valvuloplasty, infundibular gradients disappeared in five patients. The infundibular gradient in the remaining five patients was 29 f 18 mmhg with a range of 5 to 54 mmhg. In four of these patients, the infundibular gradients diminished when compared with prevalvuloplasty gradients, while in one child the gradient remained unchanged at 20 mmhg. In four additional patients without infundibular gradients but with angiographic infundibular narrowing, an infundibular gradient appeared after valvuloplasty; new infundibular gradients were 18, 34, 45, and 50 mmhg (37 f 14 mmhg). Two children with what was thought to be successful balloon valvuloplasty developed systemic level pressures in the right ventricle because of severe infundibular reaction. Propranolol, 0.1 mg/kg was slowly administered intravenously with a resulting decrease in the right ventricular pressures and infundibular gradients. These two and two other patients with infundibular stenosis were given oral propranolol2-3 mg/kg per day in three to four divided doses for approximately 3 months. None of our patients required surgical infundibular resection. 15,48 Of the total of nine patients with infundibular gradients at the end of balloon valvuloplasty, the gradients disappeared at follow-up in four patients. In the remaining five patients with persistent infundibular gradients at follow-up, the gradients were low (10-30 mmhg, mean 21 mmhg); in each patient the gradient at follow-up was less when compared with immediate postvalvuloplasty gradient. The absence of pressure gradient across angiographically narrow right ventricular infundibulum in the presence of a more severe distal Obstruction (valve stenosis) is well kn~wn;~o-~~ this atypical behavior of multiple obstructions may be due to forced vibration with greater energy transfer into the cardiovascular segment upstream from the proximal obstruction than into the segment upstream from the distal obstruction The elastic and pulsatile characteristics of the cardiovascular system are important for expressing this properly Once the valvar gradient was relieved, infundibular gradient appeared. Infundibular gradients immediately following valvuloplasty, if severe (producing near systemic pressure in the right ventricle), may respond to treatment with propranolol. We, indeed, observed significant improve- ment in the gradient following intravenous propranolol (0.1 mg/kg). This response is similar to that observed in patients with surgical pulmonary valvotomy. 53 Although we were able to manage all our patients without surgical resection of the infundibular obstruction, an occasional patient may require infundibular resection Oral propranolol therapy may be required in some patients with significant infundibular obstruction. The infundibular obstruction is expected to regress with time as has been ob- served following surgical pulmonary valv~tomy~~,~~ and balloon valvuloplasty. I3.l Applicability to Patients with Restenosis Following Previous Surgical Pulmonary Valvotomy Some authors10,12 observed poor results of balloon valvuloplasty in patients with previous surgical pulmonary valvotomy; in some of these,i0 pulmonary valve dysplasia is associated with a lack of success. Poor results of balloon valvuloplasty have also been reported in patients with previous surgical pulmonary valvotomy for pulmonary atresia with intact ventricular ~ystem.~. ~ Others18.21 did not specifically comment on the results of balloon valvuloplasty in patients with previous surgery. In our patient population, only two children, aged 3 and 14 years, had previous surgical pulmonary valvotomy, respectively, 1 and 4 years prior to balloon valvuloplasty. The pulmonary valvar gradients were 120 and 146 mmhg and were reduced, respectively, to 48 and 34 mmhg immediately after valvuloplasty. In the first patients, the pulmonary valve gradient fell further to 25 mmhg at a 10- month follow-up catheterization. Based on the available data, successful balloon valvuloplasty can be expected even after recurrence following previous surgical valvotomy and, therefore, balloon valvuloplasty is the treatment of choice for restenosed pulmonary valve following previous surgery. Noninvasive Evaluation of Follow-Up Results of Valvuloplast y Percutaneous balloon pulmonary valvuloplasty is now widely used for the treatment of pulmonary stenosis Thus far, repeat catheterization several months after valvuloplasty has been the method of choice for evaluation of results of pulmonary valvuloplasty. Only a few workers7. I I used noninvasive methods for evaluation of intermediate term results of balloon pulmonary valvuloplasty. Echo-Doppler Evaluation Rocchini and Beekman, 36 Robertson and associatesi8 and we14,23,57 have previously reported echo-doppler

13 P. S. Rao: Balloon pulmonary valvuloplasty 61 follow-up studies after balloon valvuloplasty. Kveselis er af. reported results of Doppler examination in 11 patients months following valvuloplasty; calculated right ventricular outflow gradient was reduced from 86f29 to 38+9 mmhg immediately after valvuloplasty which decreased to 33 k7 mmhg at follow-up, although the difference was not significant. Doppler evidence for pulmonary insufficiency was present in 8 of 11 patients. Similar improvement was noted in a subsequent p~blication~~ involving 28 patients with successful valvuloplasty. Robertson et ~ 1.,~* while analyzing the morphology of right ventricular outflow tract following balloon valvuloplasty, reported follow-up (10.2 k5.6 months) Doppler studies in 18 patients. The calculated pulmonary valvar gradient, having been reduced to 37f23 from 72 f3 I mmhg immediately following valvuloplasty, decreased further to mmhg at follow-up. We have echo-doppler follow-up studies in 43 children for 3 to 36 months (15k6 mo) following valvuloplasty. Two-dimensional-derived M-mode tracings of the right ventricle and left ventricle and pulsed and continuous wave Doppler flow velocity recordings from the right ventricular outflow tract and the main pulmonary artery were recorded as previously rep~rted,~~.~~.~~ initially at 3- to 6-month intervals and subsequently at 12-month intervals. Pulmonary valvar gradient was calculated using modified Bernoulli equation (gradient =4 V22, where V2 is peak Doppler flow velocity in the main pulmonary artery). When the right ventricular outflow tract Doppler flow velocity (V,) was in excess of 1.0 m/s, V, was incorporated into the Bernoulli equation (gradient =4(V22 -V,2). The echo-doppler results were analyzed separately for Group XI with good results and Group XI1 with poor results (Table I). In Group XI patients with good results, the right ventricular end-diastolic dimension decreased, but not significantly (p>0.05), from 19.3f5.4 to 17.1 f5.2 mm immediately after valvuloplasty which decreased further to 15.7f5.0 mm (p<o.ol) at the last available follow-up. The left ventricular end-diastolic dimension did not change immediately following valvuloplasty ( vs. 31.2k7.0 mm, p>o.i) but at follow-up (35.5f7.7 mm) there was a significant increase (p<0.02). The Doppler flow velocity in the main pulmonary artery decreased (p<o.ool) from 4.16k0.8 to 2.86f0.64 m/s immediately following valvuloplasty, which on follow-up was 2.38k0.05 m/s (p<o.ool); when pressure gradient was (calculated, these values, respectively, correspond to 70.9k26.5 (pre), 31.9f15.4 (post) and (at follow-up) mnihg. Doppler evidence for mild pulmonary insufficiency was present in 34 of 43 patients in whom data were available. Longitudinal follow-up Doppler flow velocities in the pulmonary artery are shown in Figure 6. 'These data show that there is rapid reduction of flow velocities immediately following valvuloplasty with further reduction at 3 months follow-up. Subsequently, there was minimal fall, if any. c nr Pre Irnrn Post Months following valvuloplasty Fa. 6 Peak Doppler flow velocities in the main pulmonary artc,ry prior to and immediately after balloon valvuloplasty and at followup as indicated. N indicates the number of patients in whom the data was available. Note the fall in the flow velocity immediately after valvuloplasty with further reduction at 3-month follow-up. There was minimal, if any, change subsequent to the 3-month followup data. By contrast, in Group XI1 with poor results, the right ventricular end-diastolic dimension (22.1 f 10.1 mm) did not change (p > 0. I) either immediately after valvuloplasty (20.3f8.3 mm) nor at follow-up (23.2k 13.8 mm). Similarly, left ventricular end-diastolic dimension (27.9k5.9 mm) did not change (p>o. 1) immediately following (30.3 f7.7 mm) or several months after valvuloplasty (26.2f5.7 mm). Peak Doppler flow velocity in the pulmonary artery prior to valvuloplasty was 3.74k0.5 m/s in Group XII, and remained essentially unchanged (p>o. 1) after valvuloplasty (3.6k0.54) and on followup (3.5 f0.83). Doppler evidence for pulmonary insufficiency was present in 2 of the 7 patients on follow-up. Five of the seven Group XI1 patients underwent repeat valvuloplasty; 7 to 12 months following repeat valvuloplasty the Doppler flow velocity decreased to 2.5 f0.4 m/s (p<o.ool). Doppler's ability to predict pulmonary valvar gradients after valvuloplasty was then evaluated. There were 37 pairs of Doppler and catheterization data obtained within 24 h of each other immediately following pulmonary valvuloplasty. There were 30 pairs of Doppler and catheterization data also obtained within 24 h of each other, 6-36 months following valvuloplasty. There was excellent correlation between Doppler-calculated and catheterization-measured pulmonary valvar gradients at follow-up (r=0.9), while correlation was less than good (r =0.6) immediately following valvuloplasty. These results are similar to those reported by us in a smaller number of subjects.58 No technical or fixed anatomical reason was found.58 The reason appears to be hyperreactive right ventricular outflow tract immediately following balloon valvuloplasty; this was shown in the right ventricu-

14 68 Clin. Cardiol. Vol. 12, February 1989 lar angiography immediately following valvuloplasty but without demonstrable pressure gradient on pressure pullback tracings. No significant changes in ventricular size were observed immediately following valvuloplasty, whether or not the results of valvuloplasty were good. Doppler flow velocity recording, often overestimated residual gradient, probably related to infundibular hyperreactivity. Therefore, echo-doppler studies immediately following valvuloplasty are not reflective of the favorable hemodynamic changes immediately following valvuloplasty. At follow-up, improvement in the echocardiographic size of the right ventricle, Doppler flow velocity in the main pulmonary artery, and calculated pulmonary valve gradient occurred in patients with successful balloon valvuloplasty while no such change was observed in the group of patients with significant residual pulmonary stenosis. The data suggest that intermediate term follow-up echo- Doppler studies are reflective of the hemodynamic improvement. If these studies are confirmed, repeat cardiac catheterization to evaluate intermediate and long-term results of balloon pulmonary valvuloplasty may not be necessary. Although our initial impression was that there was a low incidence of pulmonary valve insufficiency following balloon valvul~plasty,~~~~~ the results of this larger study showed that 34 of 43 (79%) patients with successful balloon valvuloplasty developed pulmonary insufficiency on intermediate follow-up. This is understandable because the balloon valvuloplasty produces commissural splitting and tearing or avulsion of valve leaflets.44 However, the pulmonary insufficiency is minimal and unlikely to be problematic; there was no evidence of right ventricular volume overloading (near normal right ventricle size and no paradoxical septa1 motion) in our echocardiographic studies nor by equilibrium gated radionuclide angiograms reported by Tynan et al.. lo This will have to be watched closely on long-term follow-up studies. Electrocardiographic Studies Rocchini and Kveselis and co-workers7,' and we59 previously reported electrocardiographic changes following valvuloplasty. Kveselis er al. I I observed significant decrease in R-wave voltage in lead V, and leftward shift of frontal plane mean QRS vector in 13 patients, 16k9 months following valvuloplasty. In a recent study60 of 35 patients with electrocardiogram 3 to 34 (mean 11) months following valvuloplasty, we made the following observations. When electrocardiograms immediately prior to and following balloon Valvuloplasty were compared, there was practically no change in mean vectors, QRS voltages, and T waves in any patient. In 30 children with excellent relief of pulmonic stenosis at follow-up, frontal plane mean QRS vector moved toward the left (p<o.ool) from 127f25" to 81 f47" as did the horizontal plane mean QRS vector from 88k36" to 27f51" (p<o.ool). The amplitude of R wave in \Il, 19.0k11.6 mm and V2, 19.7k12.2 mm decreased (p <0.001), respectively, to 9.5 f5.9 mm and f6.1 mm. S-wave amplitudes in V5 and v6, 10.5k6.5 mm and 6.7 k4.7 mm, respectively, decreased (p <0.01) to 5.9f3.9 and 2.9k2.6 mm. The improvement in the electrocardiogram is associated with a decrease in pulmonary valve gradient from 95k50 to mmhg. In five children with significant residual gradient, the electrocardiogram did not show any significant change. Evaluation of the time course of the ECG changes in the group with good results revealed that there WiiS minimal or no improvement in electrocardiographic parameters at the 3-month follow-up visit (p>o.o5 to 0.2), while at 6, 12, and 18-month follow-up visits, there was a significant improvement (p<o.o5 to 0.001) (Fig. 7). Having concluded that the electrocardiogram improves following successful balloon pulmonary valvuloplasty, it was attempted to see if individual postvalvuloplasty elec R amplitude 20 rnrn(lll0 rnv) S amplitude 15 mm(1ilo rnv) pwo 1 c L FIG 7 Precordial voltages, RV,R (0) and RV, (m) (A) and SV5 and SV6 (B) prior to and 3, 6, and 12 months following balloon pulmonary valvuloplasty (BPV). Note that the precordial voltage did not significantly change (p>0.05 to >O. I) at 3-month follow-up, while at 6 and 12 months following BPV there was a significant decrease (p<0.02 to 0.001) in the right ventricular voltages.

15 P. S. Rao: Balloon pulmonary valvuloplasty 69 tmardiograms reflected significant residual valve gradient at follow-up. Thirty pairs of electrocardiographic and pulmonary valve pressure gradient data obtained within 24 h of each other were available for analysis. Fifteen electrocardiograms were interpreted to be normal and their pulmonary valve gradients were low, mmhg (range 4 to 30 mmhg) (Fig. 8). These electrocardiograms and catheterization-measured gradients were obtained 7 to 28 months (12.0k5.5 mo) following balloon valvuloplasty. Ten electrocardiograms were found to have right ventricular hypertrophy and were not significantly different from prevalvuloplasty tracings. These were obtained 6 to 23 months (1Ok5 mo) following valvuloplasty and their right ventricular outflow gradients ranged between 32 and 118 mmhg (55.8k26.4 mmhg) and were higher (p<o.ol) than those seen in the normal electrocardiographic group (Fig. 8). The remaining five electrocardiograms, obtained 6 months following balloon valvuloplasty, were interpreted to have right ventricular hypertrophy but were markedly improved when compared lo prevalvuloplasty electrocardiograms. Their pulmonary valve gradients at catheterization were 5 to 25 mmhg (15.2f9.4 mmhg) and were not significantly different (p>o. 1) from the normal electrocardiogram group (Fig. 8). Three of these patients had repeat electrocardiograms 0 months later (one year after valvuloplasty) and were found to be normal. Thus, the pulmonary gradients less than 30 mmhg are likely to be present in patients with normal electrocardiograms. If right ventricular hypertrophy is present and the electrocardiogram was obtained later than 6 months following valvuloplasty, significant L loo r u) 0s kz 60- E?E -1 9E p.'u 40 - gg lqa I a 0- d dr Normal ECG 0 a. 00 P 0 0 RVH 118 FIG 8 Relationship of postvalvuloplasty electrocardiograms with the residual pulmonary valvar pressure gradient. Note that in the presence of normal electrocardiogram (ECG) the pulmonary valve gradients were low (less than 30 mmhg). Right ventricular hypertrophy (RVH) would indicate significant residual pulmonary valve gradient unless it was obtained less than 6 months after valvuloplasty. Means and standard deviations are marked. p < 0.01 ; ( 0) < 6 months after BPV; ('-1) 6 months after BPV. residual gradient could be expected. Right ventricular hypertrophy in an electrocardiogram obtained at or before 6 months following valvuloplasty does not accurately predict pulmonary valve gradient. In conclusion, electrocardiograms improve following successful pulmonary valvuloplasty and electrocardiogram is a useful adjunct in the evaluation of intermediate temi result of balloon pulmonary valvuloplasty, but electrocardiographic evidence for hemodynamic improvement does not become apparent until after 6 months following balloon valvuloplasty. Comparison with Surgical Results Surgical treatment for valvar pulmonic stenosis has been available for 40 years, since the first description by Brock.61 Consequently, follow-up information after surgery is available in a large number of patients and for long periods of time. Because balloon valvuloplasty is a recent development, it is rather difficult to compare balloon with surgical pulmonary valvuloplasty. However, an attempt will be made to do this. Four representative surgical pulmonary valvuloplasty report^^*-^* were chosen for comparison with balloon valvuloplasty. These authors62-6s followed 50 to 234 patients 4 months to 17 years after surgical relief of pulmonary valve obstruction. Operative mortality vaned between 3 to 14%; the cooperative study involving several institutions had only 3 % mortality in 304 patients presented.6s Poor results at follow-up were noted in zero to 8%; again the cooperative study had 4% poor results at follow-up. Poor result at follow-up is defined as a pulmonary valvar gradient in excess of 50 mmhg. Pulmonary valve insufficiency was reported in all studies. Follow-up catheterization studies following balloon val- vuloplasty,s, lo- 13, Is,, including the current study involved recatheterization in 6 to 36 patients 1 week to 34 months after valvuloplasty (Table 11) and reported 14 to 33% recurrence. No significant mortality has been reported following balloon valvuloplasty. 66 Certainly, the mortality figures and morbidity appear higher following surgery; however, the recurrence rate appears higher following the balloon procedure. It should be noted however, that, with refinement of balloon techniques as indicated elsewherezs and in the earlier sections of this review, the recurrence rate can be reduced to extremely low levels; of the 32 dilatations with balloons larger than 1.2 times the size of the pulmonary valve annulus (Group VI), none required repeat valvuloplasty and none had pressure gradients in excess of 30 mmhg (Tables IV and V). Based on the available information, it is likely that both immediate and follow-up results are better with balloon than with surgical pulmonary valvuloplasty and such a categoric statement can be substantiated when 5- and 10- year follow-up studies of balloon valvuloplasty confirm the current intermediate term follow-up results.

16 70 Clin. Cardiol. Vol. 12, February 1989 Complications Complications during and immediately after balloon pulmonary valvuloplasty have been remarkably minimal. Transient bradycardia, premature beats, and fall in systemic pressure during balloon inflation have been uniformly noted by all workers. These return rapidly to normal following balloon deflation. Systemic hypotension may be minimal during balloon inflation in the presence of a patent foramen ovale because of right-to-left shunt across it, filling the left ventricle.49 Use of double balloonsz0 and of trifoil or bifoil balloon^^^^^^ to allow blood egress from the right ventricle during balloon inflation and shorter periods (5 s) of inflati~n~~.~~ have been advocated to reduce the systemic hypotension. Having had experience with each of these techniques, the author feels that a short period of balloon inflation (5 s or less) is most efficacious without compromising immediate or follow-up results (Table XII). Blood loss requiring transfusion has been reported in many studies. Complete right bundle-branch block,22 transient or permanent complete heart block, cerebrovascular accident,21 loss of conciousness, lo cardiac arrest,68 convulsions, lo balloon rupture at high inflation pressure~,~, ~.~~,~~ tricuspid valve papillary muscle rupture,z8 and severe infundibular obstruction requiring propranolol adrninistrati~n~~~~~~~~ and/or surgical intervention,15,48 though rare, have been reported. Some of these complications may be unavoidable. However, meticulous attention to the details of the technique, use of a balloon of appropriate length, avoiding extremely high inflation pressures, and short inflatioddeflation cycles may prevent or reduce the complications. Holter monitoring for 24 hours following balloon valvuloplasty I revealed premature ventricular contractions (grade 1, Lown criteria) in one-third of the 12 patients so studied. It is not clear from this study whether the premature beats were present prior to valvuloplasty nor how long after valvuloplasty the premature beats persisted. Transient prolongation of the QTc interval following balloon pulmonary valv~loplasty~~ may pose a potential hazard for developing R/T phenomenon in children with ventricular ectopy. The earlier mentioned Holter findings1 I of premature beats following valvuloplasty may have a significance in light of prolongation of QTc interval.70 However, no patient from our series or the many other studies has been known to develop ventricular arrhythmias although two cases of sudden death from ventricular fibrillation shortly after balloon angioplasty of aortic coarctati~n~~.~~ were reported. Whether these arrhythmias are related to QTc prolongation or not, is not known. However, patient monitoring following balloon pulmonary valvuloplasty is warranted. O With regard to complications at intermediate term follow-up, femoral venous occlusion and pulmonary valve insufficiency have been noted. Anywhere between 10 to 29%11.z1,23 of femoral veins through which balloon val- vuloplasty has been performed were noted to be oicluded at follow-up. In the present series 3 of 36 patients (8%) that we restudied following valvuloplasty had blocked femoral vein. It is the consensus that femoral venous occlusion is more common in small infants xi8 Ausculatory evidence for pulmonary valve insufliciency has not been thoroughly scrutinized. Doppler evidence for pulmonary insufficiency appears more sensitive but was studied by only a few investigators Rocchini and Beekman36 reported pulmonary insufficiency in 31 out of 37 (84%) patients while Robertson et al. l8 found mild pulmonary insufficiency in all 29 patients studied. In the current study group, 34 of 43 (79%) patients had Doppler-demonstrable pulmonary insufficiency. However, this was minimal, as evidenced by lack of right ventricular volume overloading (normal-sized right ventricle and no paradoxical septal motion) in this group of patients as well as by equilibrium gated radionuclide angiograms reported by Tynan et al.. lo Although the longer-term follow-up studies should be scrutinized for progressive right ventricular volume overload, the current data suggest that the pulmonary insufficiency produced by balloon valvuloplasty is unlikely to be problematic. Applicability to Complex Cardiac Defects with Pulmonic Stenosis The currently accepted treatment of choice for irifants with cyanotic congenital heart defects with pulmonary oligemia and who are not amendable to total surgical correction is surgical systemic artery-to-pulmonary iirtery anastomosis. Such an operation augments pulmonary blood flow, increases oxygen saturation, and allows the child to grow to an age when total surgical correction can be performed safely. Although the mortality and morbidity associated with such an operation are not high, there are definite disadvantages: the need for longer hospitalization, long-term complications of shunt procedures, and fonnation of scar tissue that may make the total surgical correction more complicated than it would be in a virgin chest. These disadvantages might be avoided if an alternative nonsurgical method for improving pulmonary oligemia was available. Balloon pulmonary valvuloplasty is such a method and was applied to this problem by us46.73 and Boucek et al..74 Boucek et al. 74 performed balloon pulmonary valvuloplasty in seven children (5 with tetralogy of ;allot and 1 each with transposition of the great arteries, ventricular septal defect and pulmonic stenosis, and ventricular inversion, ventricular septal defect, and pulmonis stenosis) and increased their oxygen saturations from 72 k5 % to 83f5% (p<0.005). The pulmonary arterial pressure and pulmonary blood flow increased. At 2-month followup, the hematocrit decreased. All seven patients were followed for 0.5 to 2.8 years; four tetralogy patients underwent total surgical correction, one patient underwent systemic-to-pulmonary shunt and the other two did not

17 P. S. Rao: Balloon pulmonary valvuloplasty 71 require surgical intervention. Lababidi and Wu and Walls et al.,4.44 while evaluating the mechanisms of relief of valve stenosis by balloon valvuloplasty, presented four patients with tetralogy of Fallot in whom they performed balloon pulmonary valvuloplasty. They suggested that in the presence of combined infundibular and valvar pulmonic stenosis, balloon fixation by infundibulum causes retraction of the balloon into the ventricle during systole which may, in turn, cause cusp avulsion. Therefore, they did not recommend balloon valvuloplasty in these patients.44 Our experience with this procedure, including that reported previously46 was in nine infants with congenital cyanotic heart defects, aged 7 days to 10 months, weighing 2.9 to 10.0 kg, who underwent percutaneous balloon pulmonary valvuloplasty as a palliative procedure to improve pulmonary oligemia. The indication for valvuloplasty was cyanotic heart defect not amenable to total surgical correction at the age and size at presentation but at the same time requiring palliation of pulmonary oligemia. The diagnoses in these cases were tetralogy of Fallot in three, transposition of the great arteries (S,D,D) with ventricular septal defect and valvar and subvalvar pulmonic stenosis in three, critical pulmonary stenosis with intact ventricular septum and hypoplastic right ventricle in two, and ventricular inversion, ventricular septal defect, and valvar and subvalvar pulmonic stenosis in the final case. Following balloon valvuloplasty, there was an increase of the arterial oxygen saturation ( % vs. 78.4f 13.6, p<0.05), pulmonary blood flow index (1.83kO.55 to 3.14 f l/min/m2, p < 0.05), pulmonary-to-systemic flow ratio (0.62f0.35 to 1.2f0.6, p<0.05), and pulmonary artery pressure (16.8f7.2 to 29.2f11.1 mmhg, p c 0.02). Immediate surgical intervention was avoided in all nine patients. On follow-up, 4 to 19 months after balloon valvuloplasty, all infants were thriving well with decreased hypoxemia and polycythemia. Follow-up catheterization data are available in eight patients, 3 to 1 1 months following valvuloplasty, and in all, the immediate postballoon valvuloplasty improvement persisted or further improvement was noted. None of the patients had significant elevation of pulmonary arterial systolic pressure (23.1 k5.8 mmhg range mmhg). Two infants with tetralogy of Fallot underwent successful total surgical correction, respectively, 6 and 12 months following balloon valvuloplasty. Another infant with transposition of the great arteries showed evidence of increase in the size of the pulmonary arteries, but because of persistence of hypoxemia, a Blalock-Taussig shunt was performed 6 months following initial balloon valvuloplasty. The other six infants were doing well clinically with continued palliation of pulmonary oligemia. These data suggest that pulmonary valvuloplasty offers an excellent palliation of pulmonary oligemia in cyanotic heart defects, thus avoiding the risks of immediate surgical palliation and paving for a better result of eventual total surgical correction. Based on these data, we recommend balloon pulmonary valvuloplasty to palliate patients with cyanotic heart defects with pulmonary oligemia if the infant s size and./or anatomy are not suitable for total surgical correction, and believe that it is an effective alternative to surgical systemic-to-pulmonary artery anastomosis. Applicability to Porcine Heterograft Stenosis in Pulmonary Position Calcification and development of stenosis of bioprosthetic valves, particularly in children, is well documented. Such calcification and valve dysfunction in the pulmonary position may require replacement of the valved conduit. However, balloon dilatation of the stenotic porcine valve may avoid or postpone reoperation. Waltiman et al. 75 and Lloyd et al. 76 have indeed reported diliitation of the bioprosthetic valves in the pulmonary position. Waldman et al.75 reported four children who developed stenosis of the porcine values 10 to 24 months after their insertion, and who underwent balloon dilatation. The average valve gradient was reduced from 48 to 25 mmhg, and there was only mild pulmonary insufficiency after valvuloplasty. Lloyd et al. 76 presented results of balloon dilatation in six children who developed stenosis of the bioprosthetic valves inserted 4 to 14 years previously. In three children systolic gradients were reduced significantly and no surgical intervention was required. In the other three patients the balloon dilatation did not significantly reduce the gradients. Two of these required conduit replacement and the remaining patient has only a modest degree of stenosis and is being followed clinically. We had experience with dilating three porcine heterografts in pulmonary position which had been placed 4, 12, and 13 years prior to dilatation. In two children gradients of 72 and 68 were, respectively, reduced to 40 and 11 mmhg and are being followed clinically. In the third child, with 79 mmhg gradient, there was no significant reduction in the gradient. This patient also appears to have diffuse narrowing of the conduit, presumably related to peel formation. No complications were encountered in these patients. The mechanism for relief of porcine valve stenosis appears to be related to valve fusion that is seen in some of these patient^.^^.^^ Peel formation, causing conduit stenosis, is not amenable to balloon valvuloplasty. Based on our own experience and that reported in the literature, it seems prudent to try to balloon dilate porcine valve stenosis in an attempt to prevent or postpone second replacement of calcified, stenotic valve. If this is not feasible, replacement may be required. Indications The indications for surgical pulmonary valvotomy are reasonably clear; patients with moderate to severe steno-

18 72 Clin. Cardiol. Vol. 12, February 1989 sis, irrespective of the symptoms, are candidates for surgical relief of the obstru~tion.~~.~~ The indications for balloon valvuloplasty appear less clear and rarely defined. lo Careful examination of all the available revealed that many patients with what may be considered mild pulmonic stenosis (natural history study definiti~n:~~ gradient < 25 mmhg =trivial, 25 to 49 mmhg = mild, 50 to 79 mmhg = moderate, and 2 80 mmhg = severe) underwent balloon valvuloplasty Natural history studies of pulmonic ~tenosis~~,~~ indicated that mild pulmonary stenosis remains mild on follow-up and therefore the advisability of balloon valvuloplasty for mild obstruction could be questioned. My own recommendations are to consider the indications for balloon valvuloplasty to be the same as those used for surgical valvuloplasty and that balloon dilatation should not be performed in patients with gradients less than 50 mmhg. Because noninvasive Doppler estimates of pulmonary valve gradients are reasonably accurate, there would be no reason to catheterize pulmonic stenosis patients unless the Doppler estimate of the gradient is in excess of 50 mmhg. As discussed earlier, previous surgical pulmonary valvuloplasty is not a contraindication for balloon valvuloplasty. Some investigators consider dysplastic pulmonary valves as a relative contraindication for balloon valvuloplasty, but based on the data presented earlier in this review, balloon valvuloplasty is the initial treatment of choice; preferably, large balloons to produce balloon/annulus ratio of l.4 to l.5 should be used. In conclusion, moderate to severe valvar pulmonic stenosis (gradients 2 50 mmhg), irrespective of previous surgical intervention and pulmonary valve dysplasia, is an indication for percutaneous balloon pulmonary valvuloplasty. Pulmonary valve stenosis in association with complex cardiac defects and stenotic porcine valves in the pulmonary position can also be dilated. Summary and Conclusions Balloon pulmonary valvuloplasty has been used successfully over the last few years for the relief of moderate to severe valvar pulmonic stenosis in neonates, infants, children, and adults. Both immediate and intermediate term follow-up results have been well documented by cardiac catheterization studies. Electrocardiographic and echo- Doppler evaluation at follow-up is reflective of the results and may avoid the need for recatheterization. The results of balloon valvuloplasty are either comparable to or better than those reported with surgical valvuloplasty. The causes of restenosis have been identified, and appropriate modifications in the technique, particularly the recommended use of a balloon/annulus ratio of 1.2 to 1.5, should give better results than previously documented. Complications of the procedure have been minimal. Further refinement of the catheters and technique may reduce the complication rate even further. The indications for balloon valvuloplasty have not been clearly defined but should probably be similar to those used for surgical valvotomy ; only patients with moderate to severe valvar pulmonic stenosis are candidates for balloon valvuloplasty. Previous surgery and pulmonary valve dysplasia are not contraindications for balloon valvuloplasty. The procedure is also applicable to pulmonary stenosis associated with other complex cardiac defects and stenosis of bioprosthetic valves in pulmonary position. Miniaturatization of balloon/catheter systems to further reduce the complication rate and documentation of favorable result at 5- to 10-year follow-up are necessary. References I. Rubio V, Limon Lason R: Treatment of pulmonary valvar stenosis and tricuspid stenosis using a modified catheter. 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19 P. S. Rao: Balloon pulmonary valvuloplasty Radtke W, Keane JL, Fellows KE, Lang P, Lock JE: Percutaneous balloon valvotomy of congenital pulmonary stenosis using oversized balloons. J Am Coll Cardiol 8, 909 (1986) 17. Pepine CJ, Gessner IH, Feldman RL: Percutaneous balloon valvuloplasty for pulmonic valve stenosis in the adult. Am J Cardiol 50, 1442 (1983) 18. Robertson M, Benson LN, Smallhorn JF, Musewe N, Freedom RM, Moes CAF, Burrows P, Johnston AE, Burrows FA, Rowe RD: The morphology of the right ventricular outflow tract after percutaneous pulmonary valvotomy: Long term follow up. Br Heart J 58, 239 (1987) 19. Mullins CE, Nihill MR, Vick WG 111, Ludomirsky A, O'Laughlin MP, Bricker JT, Judd VE: Double balloon technique for dilatation of valvar or vessel stenosis in congenital and acquired heart disease. J Am Coll Cardiol 10, 107 (1987) 20. Al Kasab S, Ribeiro P, Al Zaibag M: Use of double balloon technique for percutaneous balloon pulmonary valvotomy in adults. 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20 74 Clin. Cardiol. Vol. 12, February Rao PS: Electrocardiographic changes following balloon dilatation of valvar pulmonic stenosis. Presented at the 13th International Congress on Electrocardiology and 27th International Symposium on Vectorcardiography, Sept , 1986, Washington, DC 60. Rao PS, Solymar L: Electrocardiographic changes following balloon dilatation of valvar pulmonic stenosis. J International Cardiol (in press) 61. Brock RC: Pulmonary valvotomy for the relief of congenital pulmonary stenosis: Report of three cases. Br Med J 1, 1121 ( 1948) 62. Campbell M, Brock R: The results of valvotomy for simple pulmonary stenosis. Br Hear? J 17, 229 (1954) 63. Engle MA, It0 T, Goldberg HP: The fate of the patient with pulmonic stenosis. Circulation 30, 554 (1964) 64. Reid JM, Coleman JC, Stevenson JG, Inall JA, Doig WB: Long-term results of surgical treatment for pulmonary valve stenosis. Arch Dis Child 5 1, 79 (1976) 65. Nugent EW, Freedom RM, Nora JJ, Ellison RC, Rowe RD, Nadas AS: Clinical course of pulmonic stenosis. Circulation 56 (SUPPI I), (1977) 66. Lock JE, Keane JF, Fellows KE: The use of catheter intervention procedures for congenital heart disease (editorial). J Am Coll Cardiol 7, 1420 (1986) 67. Rao PS, Fawzy ME: Double balloon pulmonary valvuloplasty: Comparison with single balloon technique. J International Cardiol (submitted for publication). 68. Fellows KE, Radtke W, Keane JF, Lock JE: Acute complications of catheter therapy for congenital heart disease. Am J Cardiol 60, 679 (1987) 69. Weinhaus L, Lababidi Z: Catheter rupture during balloon valvuloplasty. Am Heart J 113, 1035 (1987) 70. Martin GR, Stanger P: Transient prolongation of the QTc interval after balloon valvuloplasty and angioplasty in children. Am J Cardiol 58, 1233 (1986) 71. Kan JS, White RI Jr, Mitchell SE, Farmiett El, Danahoo JS, Gardner TJ: Treatment of restenosis of coarctation by percutaneous transluminal angioplasty. Circulation 68, 1087 (1983) 72. de Lezo JS, Fernandez R, Sancho M, Concha M, Arizon J, Franko M, Alemany F, Barcones F, Lopez-Rubio F, Valles F: Percutaneous transluminal angioplasty for aortic isthmic coarctation in infancy. Am J Cardiol 54, 1147 (1984) 73. Rao PS: Balloon pulmonary valvuloplasty for complex cyanotic heart defects. Presented at the Pediatric Cardiology 1987, International Congress, Vienna, Austria, February, Boucek MM, Webster HE, Orsmond GS, Ruttenberg HD: Balloon pulmonary valvuloplasty : Palliation for cyanotic heart disease. Am Heart J 115, 318 (1988) 75. Waldman JD, Schoen FJ, Kirkpatrick SE, Mathewson JW, George L, hmberti JJ: Balloon dilatation of porcine bioprosthetic valves in the pulmonary position. Circulation 76, 109 (1987) 76. Lloyd TR, Marvin WJ, Mahoney LT, Lauer RM: Balloon dilatation valvuloplasty of biopmsthetic valves in extracardiac conduits. Am Heart J 114, 268 (1987) 77. McKay CR, Waller BF, Hong R, Rubin N, Reid CL, Rahrmtoola SH: Problems encountered with catheter balloon valvuloplasty of bioprosthetic aortic valves. Am Heart J 115, 463 (1988) 78. Nadas AS: Pulmonary stenosis: Indications for surgery in children and adults. N Engl J Med 287, 1196 (1972) 79. Stevenson JG, Kawabori I: Noninvasive determination of pressure gradients in children: Two methods employing pulsed Doppler echocardiography. J Am Coll Cardiol 3, 179 (1984) 80. Kasturakis D, Allen HD, Goldberg SJ, Sahn DJ, Valdes-Cmz LM: Noninvasive quantitation of stenotic semilunar valve area by Doppler echocardiography. J Am Coll Cardiol 3, 1256 (1984)