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Journal of the American College of Cardiology Vol. 53, No. 19, 2009© 2009 by the American College of Cardiology Foundation ISSN 0735-1097/09/$36.00Published by Elsevier Inc. doi:10.1016/j.jacc.2009.02.018

EDITORIAL COMMENT

alloon Atrial Septostomyet’s Take a Closer Look*

alph Mosca, MD

ew York, New York

dvances in the treatment of patients with congenital heartisease (CHD) have led to a significant improvement inatient survival. Neonatal cardiac procedures, which carried10% to 40% mortality rate 20 years ago, now are routinelyerformed with survival rates approaching 90% to 97% (1).lthough continued improvement is possible, efforts areow being concentrated on reducing perioperative morbid-

ty, in particular, neurologic damage and its sequellae. Brainnjury, neurologic events, and subsequent neurodevelop-

ental impairment vary by lesion, but in aggregate are faroo common (2–4).

See page 1807

In order to begin to tackle this problem we must firstnderstand its origins. The developing brain, albeit plasticnd malleable, is at particular risk during the fetal andeonatal period. Patients with CHD are known to haveoncomitant neurologic abnormalities (5,6). Intrauterineerebral blood flow varies with each particular lesion (7) andost-natal hypoxemia, hypotension, and elevated oxygenemand may exacerbate pre-existing injuries. Intravascular

nterventions may be associated with further neurologictresses (8). Considerable discussion continues concerninghe risk factors for brain injury during cardiopulmonaryypass (CPB). Improved techniques have permitted greatdvances in surgical therapy; however, they carry the risk oferebral emboli, pressure-related damage to cerebral vascu-ature, and the potential for ischemia and reperfusion injury.otal CPB time, flow rates, the rate and degree of cooling,eriods of hypothermic circulatory arrest, regional perfusion9,10) techniques, hematocrit, and acid-based strategies allave the ability to affect cerebral perfusion. The besttrategies are still being studied and may vary according toesion (11). Genetic polymorphisms likely affect the mannern which an individual patient will respond to CPB and theesulting inflammation and reperfusion injury (12). Perhaps

Editorials published in the Journal of the American College of Cardiology reflect theiews of the authors and do not necessarily represent the views of JACC or themerican College of Cardiology.

bFrom the Department of Surgery, Columbia University Medical Center, New

ork, New York.

f equal importance, post-operative cardiac output and thenfluences of any post-operative complications must beonsidered as well (13). Finally, familial and socioeconomicnfluences work to shape neurodevelopmental outcomesfter hospital discharge (14).

In this issue of the Journal, Beca et al. (15) sought toetermine the prevalence and pattern of brain injury innfants with transposition of the great arteries (TGA)ompared with other complex CHD and to define the riskf balloon atrial septostomy (BAS) for brain injury. Thetudy was undertaken in part as a response to other reportselineating the disturbingly high rate of brain injury in thisopulation and the disparate results in regard to the patternsf damage, white matter injury (WMI) as opposed toschemic arterial strokes (16). In particular, the practice ofoutine elective BAS has been questioned as contributory inhese injuries (17).

When introduced, the technique of BAS was the mostmportant single factor influencing survival in patients withGA. Creating a nonrestrictive atrial communication opti-izes mixing at the atrial level, improving systemic arterial

xygen content and cardiac output as well as lowering lefttrial pressure. These beneficial effects often lead to a rapidtabilization of these neonates and improve their conditionefore they undergo a major neonatal operation. Initially, aumber of neurologic complications were noted after BAS,rimarily relating to balloon rupture and embolization ofalloon fragments. These have been minimized with newerquipment and techniques. BAS has also simplified theechnical aspects of the arterial switch procedure, allowingor efficient left- and right-sided drainage on CPB with aingle atrial cannula. Given these benefits, it is importanthat any findings that impugn the use of BAS be verified.

A number of recent publications have underscored theigh prevalence of neurologic injury in newborns withHD as well as neurobehavioral abnormalities. The naturef these injuries, their relationship to the underlying CHD,nd the pre-supposed etiology vary widely, however. Mc-uillen et al. (16) found pre-operative brain injury to occur

n approximately 40% of patients. The majority of theseatients suffered ischemic strokes and all had undergoneecent BAS. These incriminatory findings were confounded,owever, by the presence of lower arterial oxygen satura-ions, lower Apgar scores, and a greater incidence ofemodynamic instability in this same cohort. The currenttudy by Beca et al. (15) also revealed a high incidence ofre-operative brain injury (30%). The pattern of injury wasredominantly WMI. Strokes were uncommon. The au-hors were not able to indentify any risk factors for thesenjuries. They found no association between BAS and brainnjury in the patients with TGA. Finally, brain injuryccurred with equal frequency in other diagnostic subsets.The disparate findings of the 2 studies are difficult to

econcile. It is apparent that neurologic abnormalities and

rain injury are far too common in patients with CHD. The

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1813JACC Vol. 53, No. 19, 2009 MoscaMay 12, 2009:1812–3 BAS for TGA and Neurologic Insult: Causality?

ast majority of these injuries likely has its substrate in theetal and early neonatal period and may be exacerbated byntraoperative and post-operative variables. The finding thathere were no identifiable risk factors for brain injury in theurrent study may be more evidence that newborns withHD have widespread abnormalities in brain maturation,aking them vulnerable to any further stressors. One

riticism of both papers is that baseline magnetic resonancemaging (MRI) scans were not performed before the inter-ention in question (BAS). Yet, given the emergent naturef some of the septostomy procedures, MRI scans beforehese interventions might not be feasible.

BAS has become a low-risk procedure with a number ofenefits including improved intra-atrial mixing, lowering ofeft atrial pressure, and simplification of the operativerocedure in some surgeons’ hands. Whenever a reporturfaces condemning a time-honored procedure we shouldarefully scrutinize these findings and not be too quick tobandon it. Following the McQuillen et al. (16) paper,hich may with time prove quite valid, not only wereediatric cardiologists beginning to change their practices,ut adult cardiologists used this information to generalize tohe treatment of patients with patent foramen ovale (18).pplying this rationale to the approximately 40 millionatients in the U.S. with a patent foramen ovale would haveignificant clinical and financial implications. A randomizedontrolled trial in patients with TGA who are hemodynam-cally stable would be helpful. Patients would be randomizedo a control group (no BAS) or treatment group (BAS).ewborn MRI scans and neurologic examination would

hen be followed by repeat evaluations after BAS and in theost-operative period. This may begin to dissect the relativeontributions of the factors mentioned by all of the authors.urther study must continue into all potential causes ofeurologic injury and methods to minimize its occurrence.f this occurs, I have no doubt that in 40 years, theseorbidities, as was the case with perioperative mortality,ill be largely historic in nature.

eprint requests and correspondence: Dr. Ralph Mosca, Direc-or, Pediatric Cardiac Surgery, CHONY #274, Columbia Univer-ity Medical Center, 3959 Broadway, New York, New York

0032. E-mail: rm891@columbia.edu. K

s

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1. Schreiner RS, Rider AR, Myers JW, et al. Microemboli detection andclassification by innovative ultrasound technology during simulatedneonatal cardiopulmonary bypass at different flow rates, perfusionmodes, perfusate temperatures. ASAIO 2008;54:316–24.

2. Gaynor WJ, Gerdes M, Zackai EH, et al. Apolipoprotein E genotypeand neurodevelopmental sequelae of infant cardiac surgery. J ThoracCardiovasc Surg 2003;126:1736–45.

3. Dominguez TE, Wernovsky G, Gaynor WJ. Cause and prevention ofcentral nervous system injury in neonates undergoing cardiac surgery.Semin Thorac Cardiovasc Surg 2007;19:269–77.

4. Karl TR, Hall S, Ford G, et al. Arterial switch with full-flowcardiopulmonary bypass and limited circulatory arrest: neurodevelop-mental outcome. J Thorac Cardiovasc Surg 2004;127:213–22.

5. Beca J, Gunn J, Coleman L, et al. Pre-operative brain injury innewborn infants with transposition of the great arteries occurs at ratessimilar to other complex congenital heart disease and is not related toballoon atrial septostomy. J Am Coll Cardiol 2009;53:1807–11.

6. McQuillen PS, Barkovich JA, Hamrick SEG, et al. Temporal andanatomic risk profile of brain injury with neonatal repair of congenitalheart defects. Stroke 2007;38:736–41.

7. McQuillen PS, Hamrick SEG, Perez MJ, et al. Balloon atrialseptostomy is associated with preoperative stroke in neonates withtransposition of the great arteries. Circulation 2006;113:280–5.

8. Cheng TO. That balloon atrial septostomy is associated with preop-erative stroke in neonates with transposition of the great arteries isanother powerful argument in favor of therapeutic closure of everypatent foramen ovale. Am J Cardiol 2006;98:277–8.

ey Words: transposition of the great vessels y brain injuries y ballooneptostomy.