View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Journal of the American College of Cardiology Vol. 50, No. 25, 2007 © 2007 by the American College of Cardiology Foundation ISSN 0735-1097/07/$32.00 Published by Elsevier Inc. doi:10.1016/j.jacc.2007.07.082 Congenital Heart Disease Outcome and Growth Potential of Left Heart Structures After Neonatal Intervention for Aortic Valve Stenosis Ra K. Han, MD, FRCPC,* Rebecca C. Gurofsky, BSC,* Kyong-Jin Lee, MD, FRCPC,* Anne I. Dipchand, MD, FRCPC,* William G. Williams, MD, FRCSC,† Jeffrey F. Smallhorn, MD, FRCPC,* Brian W. McCrindle, MD, MPH, FRCPC* Toronto, Ontario, Canada Objectives The purpose of this study was to determine trends of growth of left heart structures after intervention for neona- tal aortic valve stenosis. Background The growth potential of left heart structures in neonatal aortic valve stenosis after relief of obstruction might influence risk for subsequent outcomes. Methods From 1994 to 2004, 53 patients underwent neonatal (Յ30 days old) balloon aortic valve dilation. Factors asso- ciated with time-related outcomes (death, reintervention, aortic valve replacement) and longitudinal changes in normalized left heart dimensions were sought. Results The median age at intervention was 3.5 days (range 1 to 30 days). During a median follow-up of 3.2 years rang- ing up to 10.9 years, there were 31 reinterventions on the aortic valve in 21 (40%) patients and 7 deaths (13%). The presence of moderate or severe left ventricular (LV) endocardial fibroelastosis was the only independent pre- dictor for time-related mortality (hazard ratio 22.1; p ϭ 0.004), and a smaller initial aortic valve annulus z-score was a significant independent predictor for aortic valve replacement (hazard ratio 0.63 per 1-U change; p ϭ 0.007). Aortic valve annulus, aortic sinus, and LV dimension z-scores significantly increased over time, whereas mitral valve z-scores remained below normal. The structure’s initial z-score and concomitant size of other left heart structures were significant independent factors associated with subsequent z-scores. Conclusions There is potential catch-up growth of the aortic valve and LV over time for neonates after intervention for aortic valve stenosis. However, the continued hypoplasia of the mitral valve warrants further consideration in the long- term management of these patients. (J Am Coll Cardiol 2007;50:2406–14) © 2007 by the American College of Cardiology Foundation Aortic valve stenosis in neonates is associated with varying deficits in functional status, and need for further interven- degrees of hypoplasia of left heart structures. Fetal echocar- tions. However, the pattern of growth in left heart structures diographic studies have demonstrated the progressive devel- after the relief of left-sided obstruction is unclear, even in opment of hypoplasia of left heart structures related to the absence of hypoplasia. A recent study demonstrated left-sided obstructive lesions (1,2). This hypoplasia adds to potential catch-up growth of the aortic valve and left increased morbidity and mortality for this patient popula- ventricle (LV) in those with smaller left heart structures (5). tion (3). In severe cases, the hypoplasia of left heart However, growth was not the focus of this study, the data structures associated with neonatal aortic valve stenosis provided were descriptive and limited to the aortic valve necessitates univentricular palliation or transplantation (4). annulus and left ventricular end-diastolic (LVED) dimen- In less severe cases, ongoing or progressive hypoplasia or sion, and multivariable longitudinal data analysis for trends growth failure might contribute to subsequent morbidity, and associated factors was not performed. Hence, we sought to determine the trends in longitudinal changes in left heart dimensions and aortic insufficiency and determine factors From the *Division of Cardiology, Department of Pediatrics, and the †Division of associated with clinical outcomes and growth of left heart Cardiovascular Surgery, Department of Surgery, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada. structures for patients with neonatal balloon aortic valve Manuscript received July 5, 2007; accepted July 25, 2007. dilation. JACC Vol. 50, No. 25, 2007 Han et al. 2407 December 18/25, 2007:2406–14 Left Heart Growth in Aortic Valve Stenosis Methods z-scores over time and demo- Abbreviations graphic characteristics, echocar- and Acronyms Patient population. Patients with a diagnosis of aortic diography measurements at pre- Congenital Heart ؍ valve stenosis who underwent neonatal aortic valve dilation CHSS sentation, and at follow-up and at Յ30 days of age at the Hospital for Sick Children in Surgeons Society the degree of aortic and mitral confidence interval ؍ Toronto, Ontario, Canada, from January 1994 to December CI valve stenosis and insufficiency left ؍ were identified from the cardiac catheterization data- LV 2004 were initially tested in a stepwise base. All patients had situs solitus, levocardia, concordant ventricle/ventricular regression model (p Ͻ 0.25 to left ventricular ؍ atrioventricular and ventriculoarterial connections, a left LVED enter); backward selection was aortic arch, and normal venous connections. Patients with end-diastolic used to obtain a final multivari- parameter estimates ؍ initial univentricular palliation were excluded. Patients un- PE able model. Results from these derwent initial percutaneous transcatheter balloon dilation models are given as parameter of the aortic valve with previously described techniques (6). estimates (PE) with standard error that correspond to the Patient demographic characteristics, clinical status before average increase in outcome measure for each increase of 1 intervention and at last follow-up, procedural characteristics measurement unit (or otherwise indicated) in predictor and hemodynamic status, and outcomes were abstracted measurement. All data analyses were performed with SAS from patient records. The study was approved by our statistical software (version 9.1, SAS Institute Inc., Cary, institutional Research Ethics Board, and patient confiden- North Carolina). tiality was maintained. Anatomic measurements. Initial pre-procedural and follow-up post-procedural echocardiograms and echocar- Results diographic reports were reviewed. Measurements of left Patient characteristics. Between January 1994 and De- heart structures were performed offline with electronic cember 2004, 53 patients underwent neonatal balloon aortic calipers and included the standard published (4) morpho- valve dilation. Fetal diagnosis of isolated aortic valve steno- logic and functional characteristics. Measurements were sis was made in 6 (11%) patients. The majority (81%) of normalized for body surface area as z-scores on the basis of patients were male. There were 2 (4%) pre-term neonates published normative data (7). Published normative data was born at 34 and 35 weeks’ gestational age. used rather than institution-specific normative values to The median age at presentation was 2 days (range 0 to 30 facilitate comparison with different institutions. Degree of days). Median weight was 3.4 kg (range 2.0 to 4.5 kg), aortic valve insufficiency was assessed both qualitatively with median length was 50 cm (range 44 to 57 cm), and median a global assessment based on aortic insufficiency jet width body surface area was 0.22 m2 (range 0.16 to 0.26 m2). ratio, LV dilation and function, and diastolic flow reversal in Although 26 (49%) patients presented with a fetal diagnosis the descending aorta and quantitatively with aortic insuffi- or an asymptomatic murmur, 27 (51%) presented with ciency jet width to aortic valve annulus ratio in diastole symptoms of low cardiac output or heart failure. Before the measured offline by a single reviewer. The initial pre- initial intervention, prostaglandin E1 infusion was initiated procedural echocardiographic measurements were used to in 33 (62%) patients, 26 (49%) were mechanically ventilated determine the Congenital Heart Surgeons Society (CHSS) for symptoms or for hospital transfer, and 15 (28%) received score with the published regression equation for critical inotropic medications. aortic stenosis (4) and the Rhodes score (3). Anatomic data. Initial anatomic features on echocardio- Data analysis. Data are presented as frequencies, means gram before the initial intervention are listed in Table 1. with standard deviations (SDs), or median with minimum Decreased LV systolic function (ejection fraction Ͻ55%) and maximum, as appropriate. Time-related survival, time was noted in 25 (47%) patients. Table 2 lists the z-scores of to reintervention, and time to aortic valve replacement were left heart structures at presentation. The initial mitral valve modeled with nonparametric Kaplan-Meier estimates. Fac- dimensions, LV dimension and length, aortic valve annulus, tors associated with these outcomes were sought from aortic root at the sinus, and sinotubular junction were demographic characteristics, medical status at presentation, generally smaller than normal, whereas the ascending aorta and echocardiography measurements with Cox proportion- was larger than normal. The median CHSS score was 0 ate hazard regression. Variables were initially included in a (range Ϫ46 to 55). Only 28 (53%) patients had a negative stepwise model (p Ͻ 0.05 to enter), and those selected were CHSS score, which predicts a survival benefit