tion, did not change significantly over the course of the follow-up period.

. . . The severity of asymptomatic AS increased during

the first 6 months of life. The increase in obstruction that occurred in our group likely reflects an increase in stroke volume that accompanied the rapid somatic growth of these children during the first few months of life The increase in blood flow across a fixed stenotic orifice would account for the increase in gradient.

Whereas studies in the adult population have found the degree of initial obstruction to be highly correlated with the subsequent rate of progression of valvular AS, this is not the case in neonates identified with AS. A rapid rate of progression may occur irrespective of the initial transvatvular pressure gradient, thus making it

impossible to identify which neonates will have rapid progression of their disease.

We conclude that asymptomatic AS may progress rapidly during the first 6 months of life. This rapid rate of progression occurs independently of the sever- ity of the initial obstruction.

1. El-Sad G. Galioto FM. Mullins CE, .McNamara IX. Natural bemodynamic his- tory of congenital sonic stenosis in children. Am J Cardiol 1972:3o:kl2. 2 Friedman WF, Modhnser J, Morgan JK. Serial hemodynamic observations in children with vlllvular aortlc stenosis. Cirrrrlution 1971:63:91-97. 3. Wagner HR. Ellison C. Kcanc JF, Ilumphries JO. Nadas AS. Clinical COUDT in aollic s1crxx1s. cxt-&fton 1977:56:47-55. 4. Cohen LS. Fricdmel WF. Hmunwald E. Natural hislnrq of mild con@fal BOT- tic xrenosis clucidatcd by seri;d hemcdynamic studies. Am J Cardiol 1972:30:1-S. 5. Hohn AR, t’rwgh SV. Moore AAD. Aortic slcnorir. Cif~rr/nnon lY65;3:4 12. 6. Herman W. Yabek SM. Fripp RR. Hursstan R. hledical managcmont of three asymptomstic infants with scvcrc valvular xmic srer~os~s. PEdiUlr- CurdM~l 1988;9: 237 242.

Midterm Outcome After Pulmonary Balloon Valvuloplasty in Patients Younger Than

One Year of Age Giuseppe Santoro, MD, Roberto Formigari, MD, Duccio Di Carlo, MD,

Luciano Pasquini, MD, and Luigi Ballerini, MD

I solated vatvular pulmonary stenosis (PS) is one of the most common cardiac defects.l*2 Over time it has been

shown that percutaneous balloon valvuloplasty also is a safe and effective method for treating this cardiac mal- formation in the pediatric population3. 9 In neonates and infants, a substantial reduction in transvalvular pressure gradient during a short-term follow-up has been demon- strated.ss,9 However, few data on longer term efficacy of this procedure in a wide and homogeneous popula- tion of neonates and infants are available.tO~” This study assesses the midterm follow-up results of pulmonary bal- loon valvuloplasty for isolated PS in infants <I year of age.

. . . Between September 1985 and December 1993, 81

patients <l year of age with isolated PS underwent bal- loon valvuloplasty at our unit. Ten patients were <l month old and 71 ranged from 1 to I2 months of age (mean I56 f 108 days [range I to 3651). Mean weight was 5.3 f 2.8 kg (range 2.4 to 8.6). Situs solitus was diagnosed in all but 1 patient who had left isomerism. Two patients had the Noonan syndrome. Critical PS (i.e., right-to-left shunt at atrial level or ductus-dependent pul- monary circulation, or both) in neonates, and clinical impairment (i.c., poor growth or signs of right ventric- ular [ RV] failure, or both) and/or Doppler instantaneous peak pressure gradient ~36 mm Hg in infants were indi- cations for pulmonary valvuloplasty. Parental informed consent was obtained before the procedure. Percuta-

From the Pediatric Cardiology and Cardiac Surgery Dcportmenb, Ospedale Eambinc: Geslj, Piaz;/a S. Orroirro, 4. 0016.5 Rome, Italy. Monuxrrpt received Au@ 25, 1994; rewscd manuscript feceived and accepted November 22, 1994

neous femoral vein access was used in all but 1 patient with left isomerism, in whom a transjugular approach was undertaken because of inferior vena cava intcrrup- tion. At cardiac catheterization, RV pressure, transval- var pressure gradient, RV:left ventricular (LV) pressure ratio, and pulmonary and systemic artery pressures were recorded. With RV angiography in the posteroanterior and lateral views, pulmonary valvular annulus size was evaluated: it was considered hypoplastic when its diam- eter was below 2 SDS of normal values for age. The pul- monary valve was considered dysplastic when clinical, echocardiographic, and angiographic criteria were met.st2 Based on the annular size, catheters ranging from 4 to 7 Fr with 6 to 18 mm balloons were used. Balloon diam- eter:pulmonary annulus ratio was calculated. Two bal- loons wcrc used simultaneously when the annulus was too large to be dilated with 1 balloon without damaging the femoral vein entry. A successful procedure was defined as a postdilation transvalvar pressure gradient ~25 mm Hg, an RV:LV pressure ratio ~0.5, as well as a reduction in cyanosis in neonates, alone or in combi- nation. Results were also analyzed according to patients’ age (i.e., neonates and infants).

At discharge, Doppler transvalvular instantaneous peak pressure gradient was obtained as a noninvasive baseline value. Then, clinical examination, electrocardi- ography, and echo-Doppler were performed at 1, 3, 6, and 12 months of follow-up, and yearly thereafter.

Results are expressed as mean + SD. Statistical analy- sis was performed by 2-tailed paired or unpaired Stu- dent’s t test and chi-square test.

At the procedure, mean balloon:annulus ratio was 1.4 f 0.2. Six patients had pulmonary valvular dysplasia and 5 had pulmonary annulus hypoplasia. A double-balloon valvuloplasty was performed in 1 patient. Among neo-

BRIEF REPORTS 637

nates, 3 had ductus-dependent pulmonary circulation and 7 had RV pressure over systemic level with a right- to-left shunt at the atrial level. Among infants, 12 had transvalvar pressure gradient ~50 mm Hg. After balloon valvuloplasty, RV pressure decreased from 85 If: 28 mm Hg (range 40 to 140) to 43 + 17 mm Hg (range 22 to 90) (p <O.OOl). Transvalvar pressure gradient decreased from 67 f 27 mm Hg (range 30 to 138) to 23 f 14 mm Hg (range 5 to 60) (p <O.OOOl), a 66% immediate reduc- tion in the gradient across the RV outflow tract. Pul- monary artery pressure did not change significantly. Sys- temic arterial systolic pressure increased from 78 f 14 to 85 + 13 mm Hg (p ~0.05). RV:LV pressure ratio decreased from 1.1 + 0.3 (range 0.6 to 1.8) to 0.5 f 0.2 (range 0.3 to 0.8) (p <O.OOl) (Figure 1). Two infants had transient infundibular reaction soon after the procedure, which disappeared after a few days of P-blocker treat- ment. Before valvuloplasty, the RV:LV pressure ratio was higher in patients ~1 month of age than in older patients (1.5 C 0.3 vs 1.0 + 0.3, respectively, p <0.05), but post- procedure values did not differ between the 2 groups (0.6 f 0.2 vs 0.5 + 0.3, respectively, p = NS) (Figure 2). Patients with abnormal annulovalvular morphology did

01

VlLV pressure ratio ....................................................................................

.......................................................

Before After

FIGURE 1. Right ventricular (RV):left venh-icular (Lv) pressure ratio before and after pulmonary valvuloplasty.

RV/LV pressure ratio 21

”

Before After

FIGURE 2. Right ventricular (RV):left ventricular (Lv) pressure ratio before and after pulmonary valvuloplasty according to

FIGURE 3. Time course of transvalvar gradient after pulmonary valvuloplasty during follow-up period. RV = right ventricular;

patient’s age. PA = pulmonary artery.

not differ in predilation transvalvular pressure gradienf compared with the remaining patients (81 + 32 vs 66 + 24 mm Hg, p = NS), but postprocedure values were sta- tistically different (31 f 18 vs 21 f 12 mm Hg, p ~0.02). Overall success rate of valvuloplasty was 88% (71 of 81 procedures), not significantly different between neonates (90%) and infants (87%). Ten patients, 1 younger and 9 older than 1 month of age, needed surgical valvulotomy, which was performed a few days after unsuccessful valvuloplasty. In 2 patients (1 younger and 1 older than 1 month of age), the dilation catheter could not be manip- ulated across the RV outflow tract, whereas in the remaining patients the procedure was ineffective. Three of 6 patients with dysplastic valve (50%), including 1 with heterotaxic syndrome, and 2 of 5 patients with hypoplastic annulus (40%) needed surgical valvotomy. On the whole, valvuloplasty was unsuccessful in 5 of 11 patients with abnormal valve versus 5 of 70 patients with normal valvular morphology (p qO.002).

Four patients had major complications (4.9%): 1 neonate had seizures early after the procedure; one 2- month-old patient had infundibular tear during dilata- tion; 2 patients, 4 and 10 months old, respectively, devel- oped endocarditis 3 months after valvuloplasty, and 1 of them died. Overall mortality was 1.2% (1 of 81). At dis- charge, Doppler peak pressure gradient was 28 f 11 mm Hg, 22% higher than peak-to-peak gradient measured at cardiac catheterization (p = NS).

Three patients were lost to follow-up. During follow- up, no late clinical complications were recorded. At elec- trocardiography, RV pressure overload signs decreased and no significant arrhythmia was recorded. At echo- cardiography, no patient had more than mild pulmonary regurgitation. After a follow-up of 515 23 months (range 6 to 96, median 46.5) Doppler peak pressure gradient was 24 + 6 mm Hg, not statistically different from the baseline value recorded at hospital discharge (Figure 3). Also in neonates, after a follow-up period of 35 f 28 months (range 6 to 94), peak pressure gradient did not significantly change from baseline values (29 + 17 vs 26 + 5 mm Hg, p = NS). Only 1 patient underwent suc- cessful redilation after 36 months; his residual tmnsval- var pressure gradient of 18 mm Hg had increased to 50

RV-PA pressure gradient (mm Hg) I””

_____________--____.---------------.

1 1 -----j _____ >:_.Z _----- I---- _‘I ----.

0 Before After 1 mo 6 mos 1 yr 2 yrs 6 yrs

1

638 THE AMERICAN JOURNAL OF CARDIOLOGY@’ VOL. 75 MARCH 15, 1995

mm Hg. On the whole, actuarial freedom from revalvu- loplasty is 98% at average follow-up (51 months).

. . . Our data show that pulmonary balloon valvuloplasty

also successfully reduces transvalvar pressure gradient in neonates and infants. The age at the procedure does not significantly influence immediate results. In fact, although predilation RV:LV pressure ratio in neonates was’signif- icantly higher than in older patients, postprocedure val- ues did not differ between the 2 groups. Conversely, according to other studies,JJ,J3*J4 valvular dysplasia or annulus hypoplasia, or both, ncgativcly influenced the efficacy of the procedure. ln fact, in our series, about 50% of patients with annulovalvular anomaly needed surgery after an unsuccessful valvuloplasty. Pulmonary valvulo- plasty is a safe method, as confirmed by a low incidence of major complications and no in-hospital death. Only 1 patient died, 3 months after valvuloplasty due to endo- carditis, and WC believe that this complication could be preventable by a routine antibiotic prophylaxis.

During a midterm follow-up, no patient had clinical and instrumental complications. At Doppler analysis, transvalvar pressure gradient did not change significant- ly, showing a normal annulovalvular growth. Previous studicsJ0~“~J3*J4 have not clearly evaluated the risk of rcstenosis after successful valvuloplasty. In fact, they pooled data of patients of different ages (i.e., infants, children, and young adults), and hence with difterent growth potential. Infants and nconatcs. unlike young adults, could conceivably show a progressive recurrcncc of stenosis after an initial gradient relief due to an abnor- mal growth capacity of the pulmonary valvular annulus. According to this hypothesis, some investigators suggest a positive relation between young age (<2 years) at pro- cedure and restenosis.13 However, this finding has not been confirmed in other studiesJJ,J4 and our data show a long-lasting ellicacy of a successful pulmonary valvulo- plasty either in neonates or in infants. In fact, only 1 of 71 successfully treated patients (1.4%/c), who had normal annulovalvular morphology, had restenosis over time; he eventually underwent additional successful valvuloplasty.

In conclusion, pulmonary balloon valvuloplasty is a useful, safe, and probably definitive procedure in the treatment of isolated PS in patients ~1 year of age. Because RV pressure overload can also be effec- tively reduced in neonates and infants, with a low incidence of complications and low risk of restenosis, we see no reason to delay valvuloplasty until a later stage of life.

1. Ferenw C. Ruhin JD. McCancr RJ. Hrenner JI. Xeill CA, Pcrty I.W. llepoer Sl. Downing JM. Congenival heart discase: presence at live hinh: the HaItimore- Washington Infant S~dy. Am J Lpd~miol 1985; I2 I:3 l--36. 2. Fyler DC. Trends. In: I:yler DC. ed. badan’ Pediatric Cardiology. .Mosby-Year Book. St. Louis, 1992:273--281. 3. Rildrkc W, Keanc JF. Fellows KE:.. Lang P. Irxk JE. Percutaneous ballcon vaivo- tomy of congenital pulmonq a!ncsi~ using ovcni~ccl balloons. J Am Cdl Cor- did 1986:8:%l9 915. 4. Fontes VT;. Sousa JE, l<sreves CA, Silva MV. Cane .MN. Maldonado G. l%- monay val\~oplas~y. Experience of 100 cases. Inr .I Cnrdrol 1988;21:33.5 -342. 5. Ah-Khan MA. al Youxf S. Huhra JC. Bricker JT, Mullins Ch, Sawyer W. Crh- ical pulmonq valve stcnosi?; m patients less than 1 year of age: trcamxnt with pcrcutancous grad&ma1 hallow pulmonary valv~dopl;~s~y. Am Heorr J 1980; I 17: 1008 1014. 6. L;~dusans W, Qurcshi SA, Parsons JM, Arab S, Baker PJ. ‘l’ynan M. Halloon dilatation of critical steoo%s of the pulmonary valve in neonates. Hr Hm~rr J lYYl):63:362-367. 7. Tomet.& NP, Gibbs JL. Weil J. Balloon valvuloplar~y of critical sonic and pul- monary stenosis in rhe premature neonate. INI J COI-dml 1991;30:248-249. 8. Rao PS. Balloon dilatation in infants and children wjith dysplasic puhnonxy valve: zhon renn and mtennediate term resuhs. Am llrurr J IYY8;l 16: 1168-l I?. 9. Schmalu AA, Bcin G. Gravinghoff L. Hogel K, Hcmrich F, Ilofwttcr R, I.indingcr A. Kallfclu HC. Kramer HH. Mennicker I!. Halloon valvuloplarty of pulmonary wnosi\ m infarm and childrcn~(n)perative study of the German So& ety of Pediatric Cardiology. kio- Hrar-t J 19X9; IO:967 97 I, IO. Kao PS, Fan/y ME, Solymx I., Mardini MK. lung ~crm results of balloon pulmonq valvulopla~ty of valvar pulmonq stenosis. Am llrorr J IYXX: 1 Ii: 1291 1296. 11. Witsenbure .M. Talcma M, Rohmer I. Hess J. Balloon valvulopla>ty for p.d- monary steno& in children over 6 months of age: inihal recuhs and long-term fol- lowup. Ew I/cart J 1993; 14: 16.57-1660. 12. .Marant;r PM. Ilutha JC, Mullins CF. .Murphy DJ. Nihdl MR. Ludomirshi A. Yoon GY. l&x~lu of halloon ~alvuloplasty in typical and dysplasric pulmonq valve wnosis: Doppler echocardiography follow-up. J Am Co// Cordiol 1988:: 2: 17fwl7Y. 13. &Gindle BW. Kan JS. Long-term rcault?, after halloon pulmonary vi~l\vlo- plasty. C;rculu~;on 199l;X3:lY 15-1922. 14. McCrindle BW. for the Valvuloplasty and Angiopkwy of Congenital Anom- alies (VAC.4) Registry Invesrigarors. Independenr predictors of long-term rcw11~ after balloon pulmonary valvuloplas~y. ~irculorio~r 1994;89: 3751 1759.

Quantitation of Left-to-Right Shunts in Secundum Atrial Septal Defect by Two-Dimensional Contrast

Echocardiography With Use of Albunex Hiroyuki Okura, MD, Junichi Yoshikawa, MD, Kiyoshi Yoshida, MD,

and Takashi Akasaka, MD

T wo-dimensional echocardiography is widely used for noninvasive detection of atria1 septal defect (ASD).J,2

Contrast echocardiography and Doppler color flow imaging has facilitated the diagnosis of ASD.3-5 More- over. the quantitative approach with pulsed Doppler has also been applied in clinical scttings.69 Rcccntly, a new

From !hc DepartTent of Cardiology, K&e Genera Llosp;t(~l, b’,ina- tqmu-rukamxh; 4-6, Chuo-w, KODC 650, Japan. Nwwscript

rcccwd Aagul 1 .9Yn; revised manusclipl received Novenbe: 14, i99L, end occepkd November ‘5

transpulmonary contrast agent, sonicated albumin, has been shown to cross the pulmonary vasculaturc and opacify the left side of the heart after peripheral venous injection without significant hemodynamic changes. Quantitative contrast echocardiographic approaches were reported by some investigators based on the indi- cator dilution theory.‘O I2 Quantitation of left-to-right shunts by 2-dimensional contrast echocardiography has not been reported. In this study, we evaluated the left- to-right shunt ratio by 2-dimensional contrast echocar-

fwtt WOKIS 639