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Original Article

Achieving Benchmark Results for NeonatalPalliation of Hypoplastic Left HeartSyndrome and Related Anomalies in anEmerging Program

Ali Dodge-Khatami, MD, PhD1, William Z. Chancellor, MS1,Bhawna Gupta, PhD1, Samantha R. Seals, PhD2,Makram R. Ebeid, MD3, Sarosh P. Batlivala, MD3,Mary B. Taylor, MD3,4, and Jorge D. Salazar, MD1

AbstractBackground: Results of surgical management of hypoplastic left heart syndrome (HLHS) and related anomalies are oftencompared to published benchmark data which reflect the use of a variety of surgical and hybrid protocols. We report encouragingresults achieved in an emerging program, despite a learning curve at all care levels. Rather than relying on a single preferredprotocol, surgical management was based on matching surgical strategy to individual patient factors. Methods: From 2010 to2014, a total of 47 consecutive patients with HLHS or related anomalies with ductal-dependent systemic circulation underwentinitial surgical palliation, including 30 Norwood stage I, 8 hybrid stage I, and 9 salvage-to-Norwood procedures. True hybridprocedures entailed bilateral pulmonary artery banding and ductal stenting. In the salvage-to-Norwood strategy, ductal stentingwas withheld in favor of continued prostaglandin infusion in anticipation of a deferred Norwood procedure. Cardiac comor-bidities (obstructed pulmonary venous return, poor ventricular function, and atrioventricular valve regurgitation) and noncardiaccomorbidities influenced the choice of treatment strategies and were analyzed as potential risk factors for extracorporealmembrane oxygenation (ECMO) support or in-hospital mortality. Results: Overall hospital survival was 81% (Norwood 83.3%,hybrid 88%, ‘‘salvage’’ 67%; P¼ .4942). Extracorporeal membrane oxygenation support was used for eight (17%) patients with twosurvivors. For cases with obstructed pulmonary venous return (n ¼ 10, 21%), management choices favored a hybrid or salvagestrategy (P¼ .0026). Aortic atresia (n¼ 22, 47%) was treated by a Norwood or salvage-to-Norwood. No cardiac, noncardiac, orgenetic comorbidities were identified as independent risk factors for ECMO or discharge mortality in a multivariable analysis.Conclusions: Our emerging program achieved outcomes that compare favorably to published benchmark data with respect tohospital survival. These results reflect rigorous interdisciplinary teamwork and a flexible approach to surgical palliation based onmatching surgical strategy to patient factors. With major associated cardiac/noncardiac comorbidity and antegrade coronary flow, atrue hybrid with ductal stenting was our preferred strategy. For high-risk situations such as aortic atresia with obstructed pulmonaryvenous return, the salvage hybrid-bridge-to-Norwood strategy may help achieve survival albeit with increased resource utilization.

KeywordsCHD, hypoplastic left heart syndrome, Norwood operation, outcomes

Submitted December 07, 2014; Accepted May 12, 2015.

Introduction

Since the early 1980s, patients with hypoplastic left heart syn-drome (HLHS) and related anomalies with ductal-dependentsystemic circulation1–3 have been offered surgical palliationwith the Norwood stage I operation in the first few days of lifewith a systemic-to-pulmonary artery (PA) shunt or a right ven-tricle–pulmonary artery (RV-PA) conduit.2,3 A decade later,the true hybrid I palliation, consisting of bilateral PA banding

1 Division of Pediatric and Congenital Heart Surgery, The Children’s HeartCenter, The University of Mississippi Medical Center, Jackson, MS, USA2 Center of Biostatistics and Bioinformatics, The University of MississippiMedical Center, Jackson, MS, USA3 Division of Pediatric Cardiology, The Children’s Heart Center, TheUniversity of Mississippi Medical Center, Jackson, MS, USA4 Division of Pediatric Critical Care, The Children’s Heart Center, TheUniversity of Mississippi Medical Center, Jackson, MS, USA

Corresponding Author:Ali Dodge-Khatami, Division of Pediatric and Congenital Heart Surgery,Children’s Heart Center, University of Mississippi Medical Center, 2500North State Street, Room S345, Jackson, MS 39216, USA.Email: [email protected]

World Journal for Pediatric andCongenital Heart Surgery2015, Vol. 6(3) 393-400ª The Author(s) 2015Reprints and permission:sagepub.com/journalsPermissions.navDOI: 10.1177/2150135115589605pch.sagepub.com

Abbreviations and Acronyms

BT Blalock-TaussigCT computed tomographyECMO extracorporeal membrane oxygenationHLHS hypoplastic left heart syndromeIAA interrupted aortic archICU intensive care unitRV right ventricleRV-PA right ventricle–pulmonary arteryTAPVR total anomalous pulmonary venous returnTGA transposition of the great arteries

and interventional catheter stenting of the ductus arteriosus,emerged as an alternative strategy to treat HLHS and otheranomalies with single-ventricle physiology with arch hypopla-sia.4 However, the indications or ideal candidates to undergoone or the other are still debated, and the outcomes are heavilyinstitution dependent with a fairly steep learning curve beforeattaining expected benchmark results.5 Although performedand described early on in the surgical experience to palliateHLHS by William Norwood himself,6 initial bilateral PA band-ing with maintenance of ductal patency by continuous prosta-glandin infusion followed by a deferred Norwood operationhas somewhat been ignored, and only recently revived as analternative strategy in higher risk candidates.7 This approachto buy time and gain patient stability is referred to in our prac-tice as the ‘‘salvage’’ hybrid-bridge-to-Norwood, also coinedas the ‘‘rapid 2-stage Norwood I’’ by some.7

A new comprehensive Children’s Heart Center was launchedin April 2010 at the only children’s hospital in Mississippi.The goal in serving the state’s population of over 3 millionwas to establish a full-service program to meet the needs ofMississippi’s families. Prior to 2010, congenital heart surgeryof low complexity was being performed in this hospital at arate of two to four cases monthly, without a resident congenitalheart surgeon, without dedicated pediatric cardiac anesthesia,cardiac critical care, perfusion, intensive care nursing, orrespiratory therapy. Patients with congenital heart defects ofmiddle or high complexity were transferred to out-of-statecenters for surgical care. Given the advances in prenatal diag-nosis and neonatal resuscitation, the number of potentiallytreatable patients with HLHS and related anomalies withductal-dependent systemic circulation in need of some formof palliation was increasing.

In April 2010, the congenital heart program was initiated byJ.D.S. A comprehensive program was formed quickly by estab-lishing the essential elements and partnerships necessary, pat-terned after successful centers worldwide. Key investmentsincluded congenital heart–dedicated critical care and nursing,operating rooms and surgical team, cardiac anesthesia, perfu-sion, catheterization laboratory, in-house extracorporeal mem-brane oxygenation (ECMO) program, respiratory therapy,neonatal care and fetal center, imaging, transport, and biweeklypatient management conferences. Recruitment of a strong med-ical codirector (M.B.T.) was of central importance, giving a

leadership structure based on equality and equal empowerment.Investment in and reliance upon the expertise of nursingquickly expanded the team and created a culture of excellence.These systems took some time to put in place fully, requiring aflexible strategy in terms of timing and surgical approach tocomplex congenital heart defects, with a strong focus on notexceeding the capacity of the team. Multidisciplinary roundsare made on every patient, every day, with no exceptions.

With a newly assembled team finding its bearings in all therelated domains of neonatology, perinatal imaging, surgery,pediatric cardiology, anesthesia, critical care, perfusion, andnursing, an individualized approach to clinical decision makingfor babies with HLHS and related anomalies was applied. Thisincluded consideration of the Norwood stage I operation, a truehybrid, or salvage hybrid-bridge-to-Norwood approach, in aneffort to optimize outcomes while the multidisciplinary teamapproach evolved and while we mutually experienced ourprogram’s ‘‘learning curve.’’ We continually evaluated ourexperience with these strategies which were tailored to eachpatient’s anatomy and condition,8 rather than applying a ‘‘onesize fits all’’ approach. Herein we summarize our experience todate, including results and resource utilization.

Patients and Methods

Between April 2010 and June 2014, a total of 47 consecutivebabies with HLHS and/or related anomalies with ductal-dependent systemic circulation, who were born in our centeror transferred from elsewhere in the region, were treated at theChildren’s Heart Center of the University of Mississippi Med-ical Center in Jackson, Mississippi. Our Institutional ReviewBoard approved this retrospective observational study. Ini-tially, all patients with suspected ductal dependency of thesystemic circulation were placed on a continuous intravenousprostaglandin infusion, and the cardiac diagnosis confirmed/made by transthoracic echocardiography and routine screeningfor intracranial malformations/bleeding and renal/abdominalmalformations made by ultrasound. Depending on the presenceor absence of concomitant cardiac or noncardiac comorbidityand patient stability, all patients were discussed in our multidis-ciplinary case conference, and the decision to proceed with asurgical and/or hybrid palliation was reached on a case-by-case basis. In rare instances, new findings or events on the dayof planned surgery resulted in reconsideration of the initialplan and dictated an alternative strategy. Options included aNorwood I operation (n ¼ 30; 27 RV-PA conduit [Sano] and3 modified Blalock-Taussig [BT] shunts), true hybrid with ini-tial bilateral PA banding in the operating room followed byelective patent ductus arteriosus (PDA) stenting in the interven-tional catheter laboratory (n ¼ 8), or salvage hybrid-bridge-to-Norwood consisting of bilateral PA banding and continuousprostaglandin infusion, followed by a deferred Norwood Ioperation a few days later after achieving relative patientstability (n ¼ 9). All patients had aortic arch hypoplasia and/or obstruction with ductal-dependent systemic perfusion. Ven-tricular morphology varied considerably, but in no case was

394 World Journal for Pediatric and Congenital Heart Surgery 6(3)

initial biventricular repair considered to be a feasible alterna-tive to initial functionally univentricular palliation. Diagnosesincluded HLHS (n ¼ 33), truncus arteriosus with a diminutiveright ventricle (RV) and interrupted aortic arch (IAA; n ¼ 2);unbalanced common atrioventricular canal defect with archhypoplasia (n ¼ 3); Shone’s syndrome with IAA and RV dys-function/dilatation (n ¼ 2); Shone’s syndrome with aortic archhypoplasia (n ¼ 2); D-transposition of the great arteries (TGA)with a hypoplastic RV and aortic arch hypoplasia (n¼ 2); tricus-pid atresia with D-TGA, left ventricular outflow tract obstruction,and aortic arch hypoplasia (n¼ 2); and double-inlet left ventriclewith TGA and aortic arch hypoplasia (n¼ 1). Associated cardiacand noncardiac comorbidities are listed in Table 1 and wereincluded as variables in analysis of potential associationsbetween patient factors and end points of requirement of ECMOsupport or hospital mortality (Table 1).

Following an institutional/surgeon-based preference, mostpatients whom we considered to be ‘‘standard-risk’’ HLHS,meaning without cardiac or noncardiac comorbidity, were pri-marily considered for a Norwood I operation with an RV-PAconduit (Sano shunt). Early in the program’s experience, beforestandardizing the operative strategy to include the Sano (RV toPA) shunt, three patients received a modified BT shunt as thesource of pulmonary blood flow. Due to incomplete diagnosis,two patients assessed as ‘‘standard risk’’ and assigned toundergo a primary Norwood I operation required a concomitanttotal anomalous pulmonary venous return (TAPVR) repair(n ¼ 1) or atrial septectomy for intact interatrial septum (n ¼ 1).In other cases, factors that were identified before surgery andwere considered to place the patient in a higher risk categoryincluded associated significant noncardiac or cardiac comor-bidities, and the latter was most often accounted for by eitherTAPVR or an intact atrial septum or highly restrictive intera-trial communication (hereafter referred to as ‘‘obstructedpulmonary venous return,’’ n ¼ 10). The presence of such

factors tended to direct the strategy toward a hybrid proce-dure. Noncardiac and significant cardiac comorbidities arespecified in Table 1. For patients with antegrade coronaryflow, a true hybrid procedure with deployment of a ductalstent was judged an acceptably safe initial palliation as abridge to cavopulmonary anastomosis. Of these patients, oneunderwent TAPVR repair at the time of bilateral PA bandingand one underwent an atrial septectomy. For patients aorticatresia and ductal-dependent coronary blood flow, a salvagehybrid-bridge-to-Norwood strategy was preferred, wherebythe babies initially underwent surgical bilateral PA bandingwith TAPVR repair (n ¼ 5) or atrial septectomy (n ¼ 1) andwere maintained on a continuous prostaglandin infusion.These patients were managed in the intensive care unit (ICU)until general patient stability and/or end-organ recoverywas reached, at which time PA debanding and a deferredNorwood stage I operation were performed. Specifically, aplanned salvage hybrid was done in seven patients, and animprovised salvage was required in two patients, after unex-pected findings in the operating room, including severeabdominal distension and suspected sepsis (in a baby withJacobsen’s syndrome which was ultimately discovered afterthe deferred Norwood) and TAPVR, and another baby withstandard risk HLHS with hemo-pericardium and tamponadeupon sternal entry, in whom only bilateral PA bandings weredone. Among the planned hybrid-bridge-to-Norwood patients,two had severe seizure disorders with either cerebral infarctionand/or subdural hematoma precluding the immediate use ofcardiopulmonary bypass and one had single-ventricle anatomywith arch hypoplasia and associated TGA in whom the greatvessel arrangement precluded PDA stenting.

Statistical Methods

Values are expressed as means and standard deviations. Cate-gorical predictors were compared using the chi-square orFisher’s exact tests, where appropriate. Continuous predictorswere compared using the one-way analysis of variance. Prob-ability of ECMO support and in-hospital mortality wasmodeled using logistic regression, and survival rates were com-pared using the log-rank test. Hypotheses were tested at the .05level of significance. Data were analyzed with SAS software,version 9.3 (SAS Institute, Cary, North Carolina), and Kaplan-Meier curves were produced using Stata statistical software,release 13 (StataCorp, College Station, Texas).

Results

Mean age at surgery was 6.6 + 3.5 days, at a gestational age of37.7 + 2.4 weeks, and was similar across groups based on pal-liative strategy. Similarly, mean birth weight (3.0 + 0.6 kg)and mean weight at surgery (3.1 + 0.7 kg) were comparableamong groups. Prematurity, defined as a gestational age at birthof less than 37 weeks, was present in 23.4% (11 of 47) of thepatients, with prevalence of 20% (6 of 30) in those undergoinga Norwood I operation, 37.5% (3 of 8) of those undergoing a

Table 1. Variables Analyzed With Respect to End Points of ECMOSupport and In-Hospital Mortality.

Noncardiac comorbidities (n ¼ 8)" Intestinal malrotation (4), congenital diaphragmatic hernia,

sepsis, anal atresia, hydronephrosis/renal dysfunction, vascularring, prematurity, and low birth weight (<2.2 kg)

Genetic syndromes (n ¼ 5)" DiGeorge (3), Trisomy 21, and Jacobsen

Cardiac comorbidities" Preoperative mechanical circulatory support (n ¼ 1)" >Moderate systemic ventricular dysfunction (n ¼ 2)" Total anomalous pulmonary venous return (n ¼ 7)" Restrictive interatrial septum (n ¼ 3)" >Moderate semilunar/systemic atrioventricular valve

regurgitation (n ¼ 3)" Cardiac arrest (n ¼ 1)" Cardiac tamponade (n ¼ 1)" Aortic arch hypoplasia (<2 mm)" Heterotaxia syndrome (n ¼ 1)" Cardiomyopathy (n ¼ 1)

Dodge-Khatami et al 395

true hybrid, and 22.2% (2 of 9) in the salvage group. Prenataldiagnosis was available in 34% of cases. Patient characteristicsby treatment strategy are described in Table 2.

Extracorporeal membrane oxygenation support wasrequired postoperatively in 8 (17%) of 47 patients, varyingbetween 5 (19%) of 27 after Norwood/Sano, 1 (33%) of 3 afterNorwood/BT shunt, none after true hybrid, and 2 (22%) of 7after salvage to Norwood (P ¼ .4638). Six (75%) of the eightpatients who required ECMO died before discharge, and six(67%) of the nine total hospital deaths had been on ECMO sup-port. Associated obstructed pulmonary venous return was asso-ciated with choice of initial palliative strategy being either atrue hybrid (2 of 8; 25%) or a salvage hybrid-to-Norwood strat-egy (6 of 9, 67%). That choice was also influenced by the occur-rence of other noncardiac or cardiac comorbidities and by thepresence or absence of antegrade coronary blood flow (aorticatresia). There was sufficient evidence to suggest an imbalanceof obstructed pulmonary veins between the surgical groups(P ¼ .0026). Similarly, the presence of aortic atresia was imbal-anced between the surgical groups (P ¼ .0494) and influencedpalliative strategy, being present in 48% (13 of 27) of patientsundergoing a Norwood/Sano, 33% (1 of 3) undergoing aNorwood/BT shunt, only 13% in true hybrids (1 of 8), and 78%(7 of 9) of those for whom the salvage pathway was selected.

Mean length of ICU stay was 27 + 34 days, and meanlength of hospital stay was 41 + 42 days for the entire cohort.

Length of ICU and hospital stays were significantly shorter forthose directly undergoing a Norwood I operation (mean 19 +19 and 30 + 22 days, respectively), compared to that after atrue hybrid (mean 24 + 18 and 45 + 43 days, respectively)or a salvage hybrid-bridge-to-Norwood (mean 59 + 61 and77 + 69 days, respectively; P ¼ .005 and P ¼ .009, respec-tively). In the salvage group, the interval between bilateralPA banding and deferred Norwood was a mean of 14.3 +10.5 days (range 1-31), which contributed to the comparativelyprolonged length of stay for this group.

Hospital survival for the entire patient group was 81%. Inpatients who underwent a Norwood/Sano, hospital survival was85% (23 of 27). Hospital survival was 67% (2 of 3) after aNorwood/BT shunt. For the combined group of all primaryNorwood I patients, hospital survival was 83.3%. After a truehybrid, hospital survival was 88% and 67% after salvagehybrid-bridge-to-Norwood. There was no statistically signifi-cant difference in hospital survival across treatment groups(P ¼ .9478 and P ¼ .6335 for 30- and 60-day survival, respec-tively; Figure 1). Mortality in the primary Norwood groupincluded 1 patient with HLHS, early in the program’s experi-ence, with a BT shunt who initially had an uneventful courseand delayed sternal closure on postoperative day 2. The patientsubsequently arrested from acute shunt-related hypoxia requiredECMO support, underwent shunt revision, and was successfullyweaned from ECMO two days later with chest closure but finally

Table 2. Patient Characteristics Compared by Treatment Strategies.

All Patients,N ¼ 47

Norwood WithSano, n ¼ 27 (57%)

Norwood with BT,n ¼ 3 (6%)

Hybrid,n ¼ 8 (17%)

Salvage,n ¼ 9 (19%) P Value

Age at surgery (days) 6.6 (3.5) 7.6 (3.1) 5.7 (1.5) 6 (4.9) 4.3 (2.7) .0823Gestational age 37.7 (2.4) 38 (1.2) 38.7 (0.6) 38 (1.1) 36.3 (4.8) .2718Birth weight 3 (0.6) 3.2 (0.5) 3.3 (0.4) 2.6 (0.4) 3 (0.8) .0861Weight at surgery 3.1 (0.7) 3.1 (0.6) 3.2 (0.6) 2.6 (0.5) 3.3 (1) .09916-month survival Yes 35 (74%) 21 (78%) 2 (67%) 6 (75%) 6 (67%) .9058

No 12 (26%) 6 (22%) 1 (33%) 2 (25%) 3 (33%)Hospital mortality Yes 9 (19%) 4 (15%) 1 (33%) 1 (13%) 3 (33%) .4942

No 38 (81%) 23 (85%) 2 (67%) 7 (88%) 6 (67%)ECMO Yes 8 (17%) 5 (19%) 1 (33%) 0 (0%) 2 (22%) .4638

No 39 (83%) 22 (81%) 2 (67%) 8 (100%) 7 (78%)Obstructed pulmonary venous return Yes 10 (21%) 2 (7%) 0 (0%) 2 (25%) 6 (67%) .0026

No 37 (79%) 25 (93%) 3 (100%) 6 (75%) 3 (33%)AVVR Yes 6 (13%) 4 (15%) 0 (0%) 2 (25%) 0 (0%) .4897

No 41 (87%) 23 (85%) 3 (100%) 6 (75%) 9 (100%)Aortic atresia Yes 22 (47%) 13 (48%) 1 (33%) 1 (13%) 7 (78%) .0494

No 25 (53%) 14 (52%) 2 (67%) 7 (88%) 2 (22%)Noncardiac comorbidities Yes 8 (17%) 3 (11%) 0 (0%) 3 (38%) 2 (22%) .2487

No 39 (83%) 24 (89%) 3 (100%) 5 (63%) 7 (78%)Genetic comorbidities Yes 7 (15%) 3 (11%) 0 (0%) 2 (25%) 2 (22%) .6966

No 40 (85%) 24 (89%) 3 (100%) 6 (75%) 7 (78%)HLHS subtype AA/MA 12 (26%) 6 (22%) 0 (0%) 1 (13%) 5 (56%) .3206

AS/MS 7 (15%) 3 (11%) 0 (0%) 3 (38%) 1 (11%)AA/MS 7 (15%) 6 (22%) 0 (0%) 0 (0%) 1 (11%)AS/MA 1 (2%) 1 (4%) 0 (0%) 0 (0%) 0 (0%)N/A 20 (43%) 11 (41%) 3 (100%) 4 (50%) 2 (22%)

Abbreviations: BT, Blalock-Taussig; ECMO, extracorporeal membrane oxygenation; AVVR, atrioventricular valve regurgitation; HLHS, hypoplastic left heartsyndrome; AA, aortic atresia; AS, aortic stenosis; MA, mitral atresia; MS, mitral stenosis; N/A, not applicable.


died from an acute airway obstruction on postoperative day 55.Two deaths occurred in patients having HLHS with associ-ated TAPVR (one with moderate to severe pulmonary valveinsufficiency requiring a Norwood/Sano with pulmonic valvereplacement with a 9 mm aortic homograft) and concomitantTAPVR repair. Both of these required postoperative ECMO,with inability to wean from severely diseased lungs. The twoother mortalities after a primary Norwood/Sano occurredafter uneventful surgeries, acute profound desaturations froma plugged endotracheal tube in one and shunt insufficiency inanother, requiring chest compressions but leading to a down-ward spiral which could not be salvaged, despite ECMO sup-port and/or shunt revision, respectively. After a true hybridprocedure, one death occurred in a patient with Shone’s syn-drome and IAA with RV dysfunction, in whom intrahepaticbleeding and hypovolemic shock developed after accidentalPDA stent deployment in the hepatic veins. The two post-Norwood deaths after salvage hybrid-bridge-to-Norwoodsequences occurred in babies with obstructed pulmonaryveins. In one case, the initial TAPVR repair and bilateralPA bandings required postoperative ECMO support that wascontinued up to the point of conversion from ECMO to con-ventional cardiopulmonary bypass support at the time of theNorwood operation. In the other case, initial salvage strategyallowed stabilization and sternal closure, followed by a suc-cessful Norwood/Sano three weeks later. The baby developedintractable chylothorax, requiring thoracic duct ligation onpostoperative day 40. Multiple intracranial infarcts were dis-covered on computed tomography (CT) scan, and care waswithdrawn at the request of the parents on postoperativeday 55.

Analysis of potential risk factors for end points of need forECMO or in-hospital mortality included consideration ofpatient-related anatomic and demographic data, documentednoncardiac and cardiac comorbidities, and the treatmentstrategy performed (Table 1). By univariate analysis, onlyobstructed pulmonary venous return was associated with the

need for ECMO support (odds ratio 5.5, P ¼ .0412), whileobstructed pulmonary venous return and younger age at sur-gery were associated with hospital mortality (odds ratio8.25, P ¼ .0105 and odds ratio 0.67, P ¼ .0149, respectively;Table 3). However, by multivariable analysis, neither proce-dure type nor any cardiac or noncardiac comorbidity signifi-cantly impacted the need for ECMO support or hospitalmortality (Table 4).

Outcomes at One Year and Relationship With PalliativeStrategy

After the Norwood stage I operation, there were five hospitaldeaths and one interstage mortality. Twenty-two patients haveundergone a cavopulmonary anastomosis of which two diedafter the Glenn and one is awaiting transplantation becauseof poor ventricular function after right coronary artery throm-bosis. One patient was converted to biventricular repair witha Rastelli operation.

After the true hybrid procedure, there have been onehospital mortality; two interstage deaths; one death afterrepair of truncus arteriosus with concomitant PDA stentremoval, bilateral PA debanding, and IAA correction; andfour patients with a successful comprehensive second stagereconstruction.

After the salvage hybrid approach, one mortality occurredprior to the planned deferred Norwood from complete heartblock and asystole. Eight patients went on to a deferred Nor-wood stage I at a mean of 14.3 + 10.5 days (range 1-31 days)after bilateral PA banding of which six survived to hospital dis-charge. As mentioned earlier, one patient experienced intract-able chylothorax and eventual death following withdrawal ofcare after multiple intracranial infarcts were discovered onCT scan. Five patients have undergone a cavopulmonaryanastomosis, with one post-Glenn death in the previously men-tioned patient with Jacobsen’s syndrome. There are four survi-vors at one year following the initial salvage hybrid approach.A program of interstage home monitoring was implemented inMarch 2014, which we hope will have a positive impact on ourone-year outcomes.

Comment

Significant progress in the treatment of HLHS and relatedanomalies with Norwood-type operations or hybrid strategieshas made a disease that was previously considered to be univer-sally fatal in the newborn period, not only a manageable entitybut for which increasingly encouraging survival rates areachieved at the highest performing centers.5 Any strategy topalliate HLHS or related anomalies with ductal-dependent sys-temic circulation is demanding in terms of human and materialresources. Indeed, the intensive care and hospital stay lengthsare among the longest in the care of any congenital heart defect,including the occasional need for perioperative ECMO support,a huge cost in itself.9,10 Accordingly, any aspiring congenitalheart program requires meticulous planning and support from

Figure 1. Probability of survival per treatment group at 60 days. BTindicates Blalock-Taussig.


its hospital administration, when deciding to embark upon themanagement of these most challenging CHD lesions.

Decisions concerning the choice of palliative strategy in thenewborn period depend on institutional preference, experience,and/or expertise, with options including the Norwood stage Iprocedure with either of two methods of providing and regulat-ing pulmonary blood flow, a true hybrid procedure, or a salvagehybrid-bridge-to-Norwood. The purpose of the current retro-spective study was not to compare the three different strategiesbut to describe our emerging program’s experience in surgicalpalliation of HLHS and related anomalies, based on a policy oftrying to optimally match the choice of palliative strategy to theindividual patient. We recognized the importance of imposingstructure, discipline, repetition, and streamlining in the man-agement process so that each member of the care team couldgain confidence and expertise, as exists in established centerstreating HLHS and related anomalies with Norwood operations

and hybrid palliations, with the goal of achieving benchmarkin-hospital survival outcomes. We feel that flexibility in indivi-dualizing palliative strategies, rather than reliance on a singleapproach for all, or nearly all patients, has enabled us toachieve favorable results in a program that is relatively‘‘young,’’ chronologically speaking.

As expertise with Norwood operations and hybrid pallia-tions has increased so have expectations. A 2011 report onvariation in outcomes for benchmark operations in the Societyof Thoracic Surgeons Congenital Heart Surgery Databaserevealed a multicenter aggregate discharge mortality rate of19.3% among patients who underwent a Norwood operationin 2005 to 2009.5 In the initial four years as an emerging con-genital heart program selectively utilizing three treatmentstrategies, we achieved a mortality rate of 19% in 47 consec-utive patients, including some with multiple risk factors suchas associated cardiac and noncardiac comorbidities, genetic

Table 3. Univariate (Unadjusted) Associations.

Predictor

Hospital Mortality ECMO

Odds Ratio (95% CI) P Valuea Odds Ratio (95% CI) P Valuea

Procedure (reference: ‘‘Salvage’’) Norwood: BT 1.00 (0.06-15.99) .5720 1.80 (0.11-29.07) .6738Norwood: Sano 0.35 (0.06-1.99) 0.73 (0.12-4.36)Hybrid 0.29 (0.02-3.52) 0.18 (0.01-5.19)

Obstructed pulmonary venous return 8.25 (1.64-41.55) .0105 5.5 (1.07-28.25) .0412AVVR 2.43 (0.37-15.95) .3555 0.97 (0.1-9.65) .9804Aortic atresia 2.75 (0.60-12.68) .1945 2.16 (0.45-10.32) .3357Noncardiac comorbidities 0.55 (0.06-5.17) .6040 0.65 (0.07-6.19) .7104Genetic comorbidities 0.67 (0.07-6.35) .7247 0.79 (0.08-7.6) .8350Age at surgery 0.67 (0.48-0.92) .0149 0.75 (0.56-1.01) .0625Weight at surgery 0.82 (0.27-2.45) .7153 1.03 (0.33-3.21) .9577Birth weight 1.10 (0.32-3.81) .8834 1.65 (0.43-6.28) .4644Gestational age 1.02 (0.73-1.42) .9067 1.01 (0.72-1.42) .9424

Abbreviations: ECMO, extracorporeal membrane oxygenation; AVVR, atrioventricular valve regurgitation; BT, Blalock-Taussig; CI, confidence interval; OR, oddsratio.aP values are from the omnibus Wald chi-square test.

Table 4. Multivariable Associations.

Predictor

Hospital Mortality ECMO

Odds Ratio (95% CI) P Valuea Odds Ratio (95% CI) P Valuea

Procedure (reference: ‘‘Salvage’’) Norwood: BT 0.14 (0.003-6.87) .6160 24.24 (0.18-3261.80) .3818Norwood: Sano 3.80 (0.04-369.32) 11.43 (0.21-622.00)Hybrid 1.35 (0.04-47.08) 0.16 (0.002-10.57)

Obstructed pulmonary veins 2.26 (0.12-41.08) .5814 7.98 (0.30-212.56) .2147AVVR 43.60 (0.81-2251.90) .0638 3.73 (0.06-247.17) .5383Aortic atresia 1.96 (0.25-15.36) .5215 0.97 (0.13-7.03) .9716Noncardiac comorbidities 0.31 (0.01-7.60) .473 0.75 (0.04-15.90) .8557Genetic comorbidities 2.28 (0.12-44.88) .5875 4.44 (0.28-70.86) .2922Age at surgery 0.58 (0.32-1.06) .077 0.67 (0.38-1.17) .1576Weight at surgery 0.40 (0.03-4.57) .4571 0.68 (0.06-8.34) .7599Birth weight 2.20 (0.12-41.78) .5986 1.81 (0.09-38.21) .7030Gestational age 0.98 (0.65-1.47) .9126 0.90 (0.60-1.35) .6127

Abbreviations: ECMO, extracorporeal membrane oxygenation; AVVR, atrioventricular valve regurgitation; BT, Blalock-Taussig.aP values are from the omnibus Wald chi-square test.


abnormalities, malnutrition, endemic infections, and prematur-ity. For those undergoing a primary Norwood I operation,including those with obstructed pulmonary venous return, hos-pital survival was 83.3%. This compares favorably with manycenters with a long-standing tradition of treating babies withHLHS and stage I palliation reporting surgical survival ratesranging between 76% and 93%.11 Achieving in-hospital bench-mark survival required flexibility in the Norwood/Sano proto-col we set ourselves to follow for standard risk patients, that is,those without associated obstructed pulmonary venous returnor major noncardiac comorbidity. Accordingly, palliation strat-egy was tailored to patient anatomy and general condition,offering a true hybrid for certain anatomical subtypes andfinally the salvage hybrid-bridge-to-Norwood in more desper-ate situations. In such cases, we felt that breaking down thetreatment into two surgical stages would be safer than onelarger operation (with obstructed pulmonary venous return orassociated noncardiac comorbidity).

Indications to offer the true hybrid palliative pathway varytremendously from center to center. Initially conceived as analternative to the Norwood I operation in higher risk surgicalcandidates,4,12 some centers have adopted bilateral PA bandingand ductal stenting as their standard approach for all patientswith HLHS physiology,13 with hospital survival ranging from78.5% to as high as 96.6%.12-14 Our hospital survival with thetrue hybrid approach reached 88%, comparing favorably withpublished results. As our team’s comfort with the Norwood/Sano protocol in standard risk patients materialized, the truehybrid strategy was reserved for higher risk patients with sig-nificant cardiac and noncardiac comorbidity, having ante-grade flow to the coronary arteries. For patients with aorticatresia, the theoretical risk of compromised retrograde flowinto the diminuitive aortic arch and resultant coronary ische-mia steered our decision making away from the true hybrid,which was nonetheless performed in one patient (who didsurvive).

Initially described by Dr Norwood as early as 1981,6 theinitial bilateral PA banding and continuous prostaglandininfusion without ductal stenting, followed by a deferredNorwood operation, never really attracted attention. Whatwe refer to as the salvage hybrid-bridge-to-Norwood, alsocalled the rapid 2-stage Norwood,7 is slowly gaining interestas another possible strategy for very-high-risk patients.15,16

Literature on this approach is scant, reporting survival afterbilateral PA banding from 70.6% to 100%, and 87.5% to100% discharge survival after the deferred Norwood I,7,15,16

most often performed a week after initial palliation (cumula-tive procedure survival of 64.7%-100%). This includes areport from Kitahori et al who included eight patients under-going the Norwood-BT shunt, as well as eight undergoing acombined Norwood and cavopulmonary anastomosis, at amean time of 130 + 88 days after bilateral PA banding.15

In our experience, including patients with obstructed pulmon-ary venous return or cerebral insults precluding the use ofcardiopulmonary bypass, cumulative survival of the two pro-cedures reached 67%, comparable to the London experience.7

In our experience, this was achieved at a high cost in humanand material resources as reflected by a threefold increase inICU stay and more than twofold increase in hospital lengthof stay, when compared to those undergoing a primaryNorwood I operation alone. We acknowledge what couldbe viewed by some as prohibitive in-hospital morbidity andmortality, given the baseline cardiac and noncardiac lesions,which each center will put into its own perspective beforeembarking on such a treatment algorithm. Accordingly, whetherfour of nine patients alive with a Glenn circulation at one yearis considered to be appropriate justification to continue to pur-sue the salvage strategy is an ethical question beyond the scopeof this discussion.

Among our 47 patients, ECMO support was required by8 (17%) patients of which 6 (75%) died. In a recent study oncurrent outcomes of the Norwood operation in patients withmalformations other than HLHS, Alsoufi et al17 resorted toECMO support in 9 (13.8%) of 65 patients, of which 5 died(mortality on ECMO ¼ 56%). Given the implications withregard to human and material resources, it may be argued thatECMO should not be offered after Norwood-type operationsunless outcomes improve, which each program needs to con-sider for itself.

Study Limitations

The limitations of the article are inherent to those of any retro-spective database study. The analysis focuses on outcomes ofthe immediate initial hospital stay during which the first pallia-tion was performed and does not address the ongoing issuespertaining to interstage mortality, suitability for stage II, theresults of either cavopulmonary anastomosis or comprehensivestage II palliation, or further down the single-ventricle path-way, which are beyond the scope of the article. It is explicit thatthe purpose of the study was not to compare the three palliativestrategies but to describe our outcomes based on a protocolimplemented in a learning curve environment, relying on useof the Norwood/Sano procedure for straightforward patients,but further tailored to each patient’s condition with the selec-tive use of alternative strategies, with the goal of achievingbenchmark survival levels.

In summary, in-hospital results comparable to thoseachieved at some experienced centers can be obtained for stan-dard risk patients having HLHS and related anomalies withductal-dependent systemic circulation undergoing a NorwoodI operation, even in the course of an institutional learning curvephase at an emerging program. In patients with associatedsignificant noncardiac and cardiac comorbidity includingobstructed pulmonary venous return, the true hybrid with duc-tal stenting can achieve comparable survival for the initial hos-pital stay. In very-high-risk patients/situations, the salvagehybrid-bridge-to-Norwood may still allow acceptable survivalrates by breaking down the palliation into two surgical stages,with a perceived lower cumulative risk for the initial hospitalstay, albeit at a high cost in human and material resources andcontinuous potential for attrition.


Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect tothe research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, author-ship, and/or publication of this article.

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