Clinical Outcomes, Program Evolution, and Pulmonary Artery Growth

Osami Honjo, MD, PhD, Lee N. Benson, MD, Holly E. Mewhort, BSc, Dragos Predescu, MD, Helen Holtby, MD, Glen S. Van Arsdell, MD, and Christopher A. Caldarone, MD Labatt Family Heart Centre, Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada

Background. Hybrid strategies for single ventricle palliation may differ from Norwood strategies in terms of anatomic and physiologic growth stimuli to the pulmonary arteries (PA), hemodynamics, resource utilization, and survival. Few studies have directly compared these strategies. Methods. In all, 58 patients underwent Norwood (Blalock-Taussig shunt; n ⴝ 39) or hybrid (n ⴝ 19) single ventricle palliation (2004 to 2007). Hemodynamics, PA morphology, hemodynamics, resource utilization, and survival were reviewed. Results. At pre–stage 2 evaluation, there were nonsignificant trends toward lower ventricular end-diastolic pressure, higher mixed venous saturation, and larger Nakata and lower lobe indices in the hybrids. Mean PA pressures were not different between groups. Four Norwood patients (10%) underwent transplantation before stage 2 palliation. Forty-two patients underwent stage 2 palliation (bidirectional cavopulmonary shunt or stage 2 hybrid (aortic arch reconstruction and bidirectional cavopulmonary shunt). Requirement for PA plasty, postoper-

ative CVP, stage 2 survival, and 1-year survival were similar between groups. Combined (stage 1 plus stage 2) intubation time, intensive care unit time, and hospital length of stay was shorter for hybrids in comparison with Norwood survivors (p < 0.05). Comparison of resource utilization at the time of arch reconstruction (Norwood procedure or stage 2 hybrid), demonstrated a time-related trend toward improvement (weak negative correlation: intubation, rho ⴝ ⴚ0.386, p ⴝ 0.172; intensive care unit stay, rho ⴝ ⴚ0.487, p ⴝ 0.077; hospital stay, rho ⴝ ⴚ0.429, p ⴝ 0.126) in the hybrid group, but not in the Norwood group. Conclusions. Hybrid palliation does not have a significant adverse impact on PA development, with comparable PA growth and hemodynamics. The demonstration of equivalent survival, diminished hospital utilization, and trends indicating ongoing refinement of the hybrid strategy warrants a prospective randomized trial.

T

hemodynamic instability leading to significant morbidity and mortality [2, 3]. A contributor to perioperative Norwood deaths may be related to the presence of an “in-parallel” circulation after a “big” operation. Survivors to stage 2 procedures, however, typically have welldeveloped pulmonary vasculature and undergo a cavopulmonary anastomosis associated with low risk of morbidity and mortality. The hybrid palliative strategy of bilateral pulmonary artery (PA) bands and ductal stent has emerged as an alternative to Norwood palliation for neonates with hypoplastic left heart syndrome (HLHS) [4 – 6]. An intuitive but unproven theoretical advantage of this strategy is the avoidance of cardiopulmonary bypass and aortic arch reconstruction in the neonatal period and deferring these procedures until the stage 2 procedure at 4 to 6 months of age when the patient is hypothetically more able to tolerate a “big” operation. An important aspect of the hybrid strategy is the presence of an “in-series” circula-

he objective of stage 1 surgical palliation for single ventricle physiology is to provide an unobstructed systemic outflow tract, unrestrictive intra-atrial communication, a controlled source of the pulmonary blood flow, and a reliable source of coronary blood flow. The Norwood procedure meets these requirements by means of aortic arch reconstruction along with Damus-KayStansel anastomosis, atrial septectomy, and placement of a systemic-to-pulmonary shunt [1]. Norwood procedures require the use of deep hypothermic circulatory arrest (DHCA) or regional cerebral perfusion for aortic arch reconstruction and are associated with postoperative

Accepted for publication March 23, 2009. Presented at the Forty-fifth Annual Meeting of The Society of Thoracic Surgeons, San Francisco, CA, Jan 26 –28, 2009. Address correspondence to Dr Caldarone, Division of Cardiovascular Surgery, Hospital for Sick Children, 555 University Ave, Toronto, Ontario, M5G 1X8, Canada; e-mail: [email protected].

© 2009 by The Society of Thoracic Surgeons Published by Elsevier Inc

(Ann Thorac Surg 2009;87:1885–93) © 2009 by The Society of Thoracic Surgeons

0003-4975/09/$36.00 doi:10.1016/j.athoracsur.2009.03.061

PEDIATRIC CARDIAC

Clinical Outcomes, Program Evolution, and Pulmonary Artery Growth in Single Ventricle Palliation Using Hybrid and Norwood Palliative Strategies

1886

HONJO ET AL OUTCOMES WITH HYBRID VERSUS NORWOOD STRATEGY

PEDIATRIC CARDIAC

tion after the extensive stage 2 operation, which may contribute to improved hemodynamic stability. There are, however, important potential disadvantages of the hybrid strategy including interstage vulnerability to coronary malperfusion secondary to obstruction to retrograde arch flow [6, 7], potential restriction of the atrial septal communication requiring reintervention, and mechanical distortion of the branch PAs due to band malposition, resulting in excessive (or inadequate) pulmonary blood flow and inadequate preparation of the pulmonary vasculature for cavopulmonary shunt. In this study, we directly compare our nonrandomized experience with hybrid and Norwood strategies within a single institution. In addition to survival, effectiveness of the hybrid approach in terms of PA growth and preservation of ventricular function are important comparative endpoints. Finally, a gross comparison of resource utilization and time-related trends was undertaken to allow assessment of the learning curve with the newer hybrid strategy and the more established Norwood strategy.

Patients and Methods We conducted a retrospective study of the patients with HLHS or its variants who underwent staged single ventricle palliation between January 2004 and December 2007. The Research Ethics Board at the Hospital for Sick Children approved this retrospective study, and patient consent was waived. Seventy-six consecutive patients with HLHS and its variants had been treated at the Hospital for Sick Children. The patients who underwent stage 1 palliation with a right ventricle to PA shunt (n ⫽ 10) or hybrid procedure as an interim procedure for planned heart transplantation or for salvage procedures (n ⫽ 8) were excluded from the study. No patients in the Norwood group had an operation for salvage purposes. Subsequently, 58 patients who underwent classic Norwood procedure with a Blalock-Taussig (BT) shunt (Norwood group, n ⫽ 39) or hybrid stage 1 palliation (hybrid group, n ⫽ 19) were included in the analysis. Diagnosis and profile are shown in Table 1. Type of surgical palliation was decided through interdisciplinary conferences on a case-by-case basis, which was strongly influenced by cardiologist and family preference [6] with no specific decision-making protocol.

Ann Thorac Surg 2009;87:1885–93

Table 1. Diagnosis and Clinical Profile Norwood (n ⫽ 39)

Hybrid (n ⫽ 19)

Hypoplastic left heart syndrome AA/MA 6 AA/MS 8 AS/MA 2 AS/MS 10 DILV, TGA 5 TA, TGA, VSD 3 DORV 2 Unbalanced AVSD 1 l-TGA, TA 1 Criss-cross heart 1 TAPVD 2 Left isomerism 1 Age at stage 1 (day) 11.9 ⫾ 19 Median 6 Body weight at stage 1 (kg) 3.6 ⫾ 0.6 Median 3.6

3 1 1 7 0 2 1 3 1 0 0 1 8.9 ⫾ 6 7.5 3.3 ⫾ 0.6 3.5

Diagnosis

p Value

NS NS

AA ⫽ aortic atresia; AS ⫽ aortic stenosis; AVSD ⫽ atrioventricular septal defect; DORV ⫽ double-outlet right ventricle; MA ⫽ mitral atresia; MS ⫽ mitral stenosis; NS ⫽ not significant; TA ⫽ tricuspid atresia; TAPVD ⫽ total anomalous pulmonary venous drainage; TGA ⫽ transposition of the great arteries; VSD ⫽ ventricular septal defect.

(n ⫽ 8) [8]. In the latter portion of the experience, balloon atrial septostomy was performed as a subsequent procedure. Atrial septal stents were placed when decompression of the left atrium was insufficient with conventional balloon atrial septostomy. Milrinone was commonly administered in the postoperative period. NORWOOD PROCEDURE. The Norwood procedure was performed using standard surgical techniques, including aortic arch reconstruction with a pulmonary homograft patch, atrial septectomy, and placement of BT shunt under DHCA with selective cerebral perfusion. The distal PA stump was directly closed without a patch. Delayed sternal closure was used in the majority of the cases. The patients were treated with systemic vasodilation therapy, typically with phenoxybenzamine and milrinone, as described [3].

Stage 1 Palliation

Stage 2 Palliation

The surgical technique was derived from reports by Akintuerk and colleagues [5] and Galantowicz and coworkers [4] and has been previously reported [6]. Briefly, through a median sternotomy, bilateral PA banding was achieved by placing a 3.5-mm polytetrafluoroethylene graft (PTFE [W. L. Gore & Associates, Flagstaff, AZ]), which was longitudinally divided and wrapped around the branch PAs. The ductal stent was then deployed through a purse-string on the main PA under fluoroscopic guidance. A reverse BT shunt was placed in patients with aortic atresia or severely restricted antegrade aortic flow considered to be at risk for obstruction to retrograde flow through the aortic isthmus

HYBRID STAGE 2 PALLIATION. Comprehensive hybrid stage 2 palliation was performed under DHCA with selective cerebral perfusion. The aortic arch reconstruction was achieved with a pulmonary homograft patch or, more recently, using retained stented duct tissue (n ⫽ 5) [9]. Pulmonary artery debanding and reconstruction with bilateral PA plasty was performed using an autologous pericardial patch. Bidirectional cavopulmonary shunt (BCPS) was subsequently achieved using standard techniques. CONVENTIONAL STAGE 2 PALLIATION. The procedure was performed under mild hypothermic cardiopulmonary bypass. The BT shunt was divided. Bidirectional cavopul-

HYBRID STAGE 1 PROCEDURE.



1887

PEDIATRIC CARDIAC

Fig 1. Clinical outcomes of the patients who underwent hybrid or Norwood-type single ventricle palliation. (BCPS ⫽ bidirectional cavopulmonary shunt.)

monary shunt was typically anastomosed to the PA where the BT shunt was previously placed. Bilateral PA plasty was commonly performed using an autologous pericardial patch. All procedures were performed with an on-pump beating heart unless an intracardiac procedure was needed.

Evaluation of Pulmonary Artery Growth and Ventricular Function Angiograms and hemodynamic measurements on the cardiac catheterizations were retrospectively reviewed. Diameters of right and left PAs were measured at the hilum just proximal to the takeoff of the branching vessels in the anterioposterior projection. The Nakata index was then calculated as the sum of the right and left PA cross-sectional areas indexed to the patient’s body surface area [10]. Diameters of lower lobe arteries were measured immediately distal to their origin. Lower lobe index (LLI) was calculated as the summation of the right and left lower lobe branch cross-sectional areas indexed to the patient’s body surface area [11]. Symmetry of the pulmonary architecture was evaluated with Hilum index ratio (right PA index/left PA index) and LLI ratio (right LLI/left LLI). Pulmonary artery pressures were measured by a 4F end-hole catheter. If a catheter could not pass

through the PA bands, pulmonary vein wedge pressures were measured at bilateral pulmonary veins.

Evaluation of Program Development Because hybrid stage 2 procedures and Norwood stage 1 procedures are considered the “big” operation in the respective management strategies, comparisons of resource utilization were made by adding the stage 1 and stage 2 variables for each strategy. Combined (stage 1 plus stage 2) duration of intubation time, length of intensive care unit stay, and hospital stay for index hospital stays are reported. Patients who did not survive to stage 2 procedure and those who remained in hospital from stage 1 through their stage 2 procedure were excluded. To evaluate time-related trends in program performance to reflect learning curves, comparisons were made between the “big” operation in each strategy (e.g., Norwood stage 1 procedure and hybrid stage 2 procedures).

Statistical Analysis Data are presented as means ⫾ SD. The level of statistical significance was set at p ⫽ 0.05. Differences between the groups were analyzed by Mann-Whitney U test. Differ-

Table 2. Pre–Stage 2 Palliation Cardiac Catheterization Pre–Stage 2 Catheterization

Norwood (n ⫽ 29)

Hybrid (n ⫽ 15)

p Value

Age (months) Body weight (kg) Ventricular end-diastolic pressure (mm Hg) Right mean PA pressure (mm Hg) Left mean PA pressure (mm Hg) Qp/Qs Arterial saturation (%) Mixed venous saturation (%)

4.2 ⫾ 1.7 5.8 ⫾ 1.1 8.8 ⫾ 5.1 13.2 ⫾ 4.2 13.5 ⫾ 3.7 0.81 ⫾ 0.3 74.4 ⫾ 4.5 54.1 ⫾ 7.8

4.3 ⫾ 1.1 5.8 ⫾ 1.0 6.6 ⫾ 1.5 11.2 ⫾ 3.2 13.6 ⫾ 5.5 0.83 ⫾ 0.25 79 ⫾ 5 60.6 ⫾ 9.6

0.22 0.693 0.246 0.262 0.481 0.597 0.69 0.641

PA ⫽ pulmonary artery;

Qp/Qs ⫽ pulmonary-to-systemic flow ratio.

1888



Fig 2. Angiograms at pre–stage 2 cardiac catheterization in hybrid and Norwood groups. (A) Bilateral branch pulmonary arteries are demonstrated by selective injection into the Blalock-Taussig shunt in a Norwood patient. (B, C) Selective angiograms of branch pulmonary arteries in a hybrid patient are shown.

PEDIATRIC CARDIAC

ences between the right and left PA sizes were analyzed by Student’s t test. Freedom from death or transplantation was analyzed using Kaplan-Meier survival analysis, and survival was compared between the groups with the log rank test. Correlation between time and duration of hospital utilization was analyzed with the Spearman correlation test.

Results There were no significant differences in age and body weight at stage 1 palliation between groups (p ⫽ nonsignificant; Table 1,). There were 4 operative or interim deaths (21%) in the hybrid group, and 8 operative or interim deaths (20.5%) in the Norwood group (Fig 1). Four patients (10.4%) in the Norwood group underwent heart transplantation after stage 1 palliation for progressive ventricular failure: 2 patients underwent transplantation during the early interim stage, and the remaining 2 patients underwent transplantation based on the pre– stage 2 cardiac catheterization data.

Pre–Stage 2 Catheterization and Pulmonary Artery Growth Forty-four patients (all hospital survivors after stage 1 palliation, 76% of the entire cohort) underwent pre–stage 2 cardiac catheterization. Hemodynamic comparisons between the groups are shown in Table 2. There are no differences in age and body weight at the catheterization between the groups. There is a nonsignificant trend toward lower ventricular end-diastolic pressure and higher mixed venous saturation in the hybrid group. Mean PA pressures are equivalent between the groups. No differences are noted on pulmonary-to-systemic flow ratio (Qp/Qs) and arterial saturation between the groups. Fig 3. The graph showing Nakata index (A) and lower lobe index (B) at pre–stage 2 catheterization in hybrid and Norwood groups. Nakata index and lower lobe index are equivalent between the groups. Vertical bars represent standard deviation and horizontal bars across boxes represent median values.

Representative PA angiograms are shown in Figure 2. There are nonsignificant trends toward larger Nakata index and LLI in the hybrid group compared with the Norwood group (Nakata index: hybrid 291 ⫾ 136 versus Norwood 246 ⫾ 126, p ⫽ 0.532; LLI: 142 ⫾ 41 versus 123 ⫾ 64, p ⫽ 0.335; Fig 3). There are no differences in absolute diameters of branch PAs at hilum and lower lobe branches between the groups (Table 3). The right LLI is significantly higher in the Norwood group compared with that in the hybrid group, whereas there is a nonsignificant trend toward larger left LLI in the hybrid group compared with that in the Norwood group (p ⫽ 0.08). In terms of symmetry of the PA architectures in both groups, the Norwood group has a significantly larger right PA index compared with the left PA index (172 ⫾ 84 m2/mm2 versus 91 ⫾ 53 m2/mm2, p ⫽ 0.001) but has equal LLI (80 ⫾ 52 m2/mm2 versus 57 ⫾ 24 m2/mm2, p ⫽ 0.20). The hybrid group has the same trends, which are the larger right PA index (177 ⫾ 99 m2/mm2 versus 133 ⫾ 52 m2/mm2, p ⫽ 0.016) and equal LLI (65 ⫾ 18 m2/mm2 versus 76 ⫾ 31 m2/mm2, p ⫽ 0.23). As a result, the hilum index ratio shows asymmetric PA growth at the hilum in both groups, of which the Norwood group has more disproportional pattern, and equally grown lower lobe branches in both groups (Table 3).

Ventricular Function and Atrioventricular Valve Regurgitation Echocardiographic data at the time of pre–stage 2 evaluation are summarized in Figure 4. All hybrid patients had normal ventricular function. Seven Norwood patients (26%) had mild ventricular dysfunction, and 2 (7.4%) had severe ventricular dysfunction and were listed for heart transplantation. The atrioventricular valve was moder-



1889

Right PA diameter (mm) Left PA diameter (mm) Right LL branch diameter (mm) Left LL branch diameter (mm) Right PA index (mm2/m2) Left PA index (mm2/m2) Right LL index (mm2/m2) Left LL index (mm2/m2) Hilum index ratio LL index ratio LL ⫽ lower lobe;

Norwood (n ⫽ 29)

Hybrid (n ⫽ 15)

p Value

7.6 ⫾ 1.9 5.6 ⫾ 1.5 4.4 ⫾ 1.7 4.5 ⫾ 0.9 172 ⫾ 84 91 ⫾ 53 80 ⫾ 52 57 ⫾ 24 2.1 ⫾ 1.0 0.99 ⫾ 0.73

8 ⫾ 2.3 6.4 ⫾ 1.6 4.9 ⫾ 0.8 5.3 ⫾ 1.0 177 ⫾ 99 113 ⫾ 52 65 ⫾ 18 76 ⫾ 31 1.67 ⫾ 0.73 0.96 ⫾ 0.39

0.284 0.53 0.119 0.65 0.362 0.515 0.05 0.08 0.215 0.144

PA ⫽ pulmonary artery.

ately incompetent in 1 hybrid patient (7%) and 4 Norwood patients (15%).

tions. The patient died of progressive hypoxia and secondary respiratory infection.

Stage 2 Palliation

Program Development

Forty-two patients (72%) underwent stage 2 palliation. Operative details are shown in Table 4. No differences were noted in age and body weight between the groups. Patch plasty of the branch PAs was performed in the vast majority of the patients in both groups as part of our institutional surgical strategy. Two patients in the Norwood group and 1 in the hybrid group concomitantly underwent atrioventricular valve repair. Intraoperative central venous pressure after stage 2 procedures was higher in the hybrid group. There was 1 postoperative death (6.6%) in the hybrid group. The patient had a right aortic arch, and the arch reconstruction resulted in compression of the PAs and bronchi. The patient required stent placement in the branch PAs and subsequently underwent BCPS takedown and placement of a BT shunt. The patient died of multiorgan failure 37 days after stage 2 palliation. There were 2 stage 2 deaths (7.4%) in the Norwood group. Both patients had the history of extracorporeal membrane oxygenation (ECMO) support after stage 1 palliation. Both patients had significant hypoxia after stage 2 palliation. One patient was supported with ECMO and subsequently underwent takedown of BCPS anastomosis and placement of a central shunt but was unable to be weanws off ECMO. The other patient was persistently hypoxemic, presumably owing to occluded upper systemic veins as a result of two previous ECMO cannula-

Combined (stage 1 plus stage 2) intubation time, length of intensive care unit stay, and hospital stay during index hospitalizations are significantly shorter in the hybrid group compared with those in the Norwood group (p ⬍ 0.05 in all comparisons; Fig 5). The time-related trends comparing Norwood stage 1 and hybrid stage 2 procedures are shown in Figure 6. There are time-related trends toward improvement in intubation time, intensive care unit stay, and hospital stay for hybrid stage 2 procedures that do not reach statistical significance. The Norwood patients have no evidence of time-related trends toward reductions in these variables.

Follow-Up After Stage 2 Procedures The median follow-up period is 25 months (mean, 26; range, 1 to 56) and is complete in all patients. There were 2 late deaths (7.4%) in the Norwood group. One patient had bilateral superior vena cava with hypoplastic branch PAs and progressive hypoxia developed associated with significant arteriovenous collateral formation, requiring multiple coil embolizations and, eventually, placement of an additional central shunt. The patient died 13 months after stage 2 palliation. Another patient had progressive ventricular dysfunction, underwent transplant, and died at home 5 months after transplantation. There were no late deaths in the hybrid group. Fig 4. Echocardiographic findings at pre–stage 2 evaluation in (A) hybrid group (n ⫽ 15) and (B) Norwood group (n ⫽ 27). One dot represents 1 patient. (AVVR ⫽ atrioventricular valve regurgitation.)

PEDIATRIC CARDIAC

Table 3. Pulmonary Artery Measurement at Pre–Stage 2 Cardiac Catheterization

1890



Table 4. Comparisons in Operative Details Between Norwood and Hybrid Groups Stage 2 Palliation

Conventional BCPS (n ⫽ 27)

Stage 2 Hybrid (n ⫽ 15)

p Value

Age (m) Body weight (kg) Pulmonary artery plasty (%) Postoperative CVP (mm Hg) Intubation time (days) Intensive care unit stay (days) Operative mortality (%)

6.1 ⫾ 2 6.6 ⫾ 1.3 88 (24/27) 17.4 ⫾ 6 4.8 ⫾ 9.2 15.8 ⫾ 44.6 7.4 (2/27)

6.3 ⫾ 1 6.8 ⫾ 0.9 77 (10/13) 18.6 ⫾ 3 4.7 ⫾ 4.9 7.3 ⫾ 5.9 6.6 (1/15)

0.047 0.471 0.57 0.064 0.95 0.21 0.624

PEDIATRIC CARDIAC

BCPS ⫽ bidirectional cavopulmonary shunt;

CVP ⫽ central venous pressure.

There is no difference in 1-year death or transplantation-free survival (hybrid 73.7% versus Norwood 69.2%, p ⫽ 0.836). Two patients (1 in each group) required atrioventricular valve replacement for progressive valve insufficiency. Most recent echocardiography for all survivors obtained at the median of 29 months (range, 3 to 49) after stage 2 palliation showed that the majority (85%) of the patients in the hybrid group had well-maintained ventricular function and competent atrioventricular valve. There was no new development of ventricular dysfunction in the Norwood group. Currently, 6 patients in the hybrid group and 15 patients in the Norwood group have completed the Fontan operation with no hospital or late mortality (Fig 1).

Comment Hybrid palliation has evolved as an alternative to Norwood palliation based on an unproven assumption that

Fig 5. Bar graph showing the comparisons of combined (stage 1 and stage 2) intubation time and length of stay (LOS) in the intensive care unit (ICU) and hospital between the groups. The hybrid group (gray bars) has a significantly shorter intubation time and length of stay in the ICU and hospital (*p ⬍ 0.05) compared with the Norwood group (black bars).

the less invasive stage 1 palliation in the hybrid strategy would improve overall survival. In the present study, comparison of a nonrandomized concurrent cohort of patients undergoing Norwood and hybrid palliation, there was no measurable difference in survival. Another important measure of a palliative strategy is the promotion of PA growth to create better Fontan candidates. Potential problems associated with bilateral PA banding as a part of stage 1 hybrid palliation include (1) excessively loose bands that may not protect pulmonary vasculature, resulting in pulmonary hypertension at the time of stage 2 procedures; (2) excessively loose bands that may also contribute to ventricular volume overload and subsequent ventricular failure; and (3) excessively tight bands that may provide inadequate pulmonary blood flow and fail to facilitate adequate PA growth. In the current study, we found that PA growth with the hybrid strategy was not detectably different than that in the Norwood group. The left lower lobe indexes tended to be lower in the Norwood group and may be related to aortic arch reconstruction-related distortion of the left PA. Because the hybrid patients are not at risk for arch reconstruction-related distortion of the left PA until after the stage 2 procedure, we will need to observe this variable as the hybrid group reaches their Fontan procedures. Our previous report showed higher Qp/Qs in patients undergoing hybrid stage 1 palliation compared with Norwood patients immediately after the stage 1 palliation (Qp/Qs: hybrid 1.7 ⫾ 1.0 versus Norwood 1.2 ⫾ 0.5) [12]. At the time of stage 2 procedure, the present study demonstrated that the two palliation strategies provide equivalent Qp/Qs at pre–stage 2 catheterization. It can be hypothesized that a higher Qp/Qs in the hybrid patients at stage 1 palliation might have decreased over time because of functional tightening of the bands due to somatic growth. Interestingly, pre–stage 2 mean PA pressure was equivalent between the two palliation strategies. Despite relatively high Qp/Qs after stage 1 procedures [12], no patient in the hybrid group had progressive ventricular failure requiring heart transplantation in this series. The patients tolerated the comprehensive stage 2 palliation well, and the post–stage 2 outcomes have so far been equivalent between the groups. Thus, a period of elevated Qp/Qs in the absence of cardioplegic arrest and



1891

PEDIATRIC CARDIAC

Fig 6. Correlation graphs showing the timerelated trends toward improvements in resource utilization, including intubation time, length of intensive care unit (ICU) stay and hospital stay comparing stage 2 hybrid versus stage 1 Norwood procedure. The x-axis represents calendar dates and the y-axis represents duration of the resource utilization. There are weak negative correlations between time and duration of resource utilization in the hybrid group, but no such trends are seen in stage 1 Norwood procedure.

cardiopulmonary bypass appears to be well tolerated, with rare interstage mortality or loss of ventricular function. Further scrutiny of the preservation of ventricular function and interstage mortality in the hybrid group will be important to support (or refute) this hypothesis. One of the most important advantages of hybrid palliation is to defer the largest surgical intervention until the patient is as much as 6 months old. Cavopulmonary connection allows patients to have in-series circulation at the end of surgery rather than in-parallel circulation of the Norwood physiology. Although the comprehensive stage 2 palliation is a bigger operation than a Norwood stage 2, the present study showed that hybrid stage 2 palliation had equivalent clinical outcomes compared with that of the Norwood procedure. Despite having DHCA and extensive aortic arch reconstruction, the majority of patients were extubated in the first 48 hours. The 1 death after stage 2 palliation was directly attributable to technical problems with the reconstruction of a right aortic arch with resulting PA and bronchial compression. That was an issue of geometry and would have been the same problem using a Norwood or hybrid strategy. Other recent clinical studies have reported that the mortality rate associated with stage 2 hybrid palliation ranges between 8% and 25% [7, 13, 14]. Ongoing refine-

ments of surgical techniques to simplify the comprehensive stage 2 palliation in our experience are associated with time-related trends toward improvements in intubation time, intensive care unit time, and hospital length of stay. The data suggest that the procedure is continuing to evolve in our hands and may further improve in the future. Although beyond the scope of the present study, the most important comparison of the two strategies may be to test the hypothesis that delaying aortic arch reconstruction to stage 2 procedures at 4 to 6 months of age results in superior functional neurologic outcomes.

Study Limitation A major limitation of this study is its retrospective, nonrandomized nature, which could have resulted in a bias in patient selection between groups. We did not have an institutional protocol that allocated patients to one strategy versus the other. Patients considered to be at particularly high risk for a Norwood procedure were considered salvage patients and were not included in the analysis. There may have been a small nonquantifiable bias toward putting patients perceived to be at mildly elevated risk for the Norwood procedure into the hybrid management strategy.

1892


PEDIATRIC CARDIAC

Evaluation of ventricular function was based on subjective nonblinded observations of cardiologists, not on quantitative measurement. Nakata index and LLI were measured on anterior-posterior projection. However, some hybrid patients only had anterior oblique projection to visualize whole branch PAs. Measurement of the PA diameters may not be totally accurate. Pulmonary artery pressures were measured by two different methods, namely, direct measurement be a 4F end-hole catheter or pulmonary vein wedge pressure because direct measurement of the PA pressure by a catheter passed through a tight PA band may artificially lower the distal PA pressure. Pulmonary vein pressures were used when this problem was suspected. The use of two different techniques may have increased heterogeneity in the accuracy of PA pressure measurements. Finally, assessment of PA growth and outcome will require further follow-up through the Fontan procedure. In conclusion, hybrid palliation provides equivalent anatomic PA growth without obvious adverse effects on the peripheral pulmonary vasculature. Hemodynamics at pre–stage 2 palliation are comparable with those of Norwood palliation, and ventricular performance is preserved. The demonstration of equivalent survival, diminished hospital utilization, and trends indicating ongoing refinement of the hybrid strategy supports our plan to design a prospective randomized trial comparing these palliation strategies.

References 1. Norwood WI, Lang P, Hansen DD. Physiologic repair of aortic atresia-hypoplastic left heart syndrome. N Engl J Med 1983;308:23– 6. 2. Mahle WT, Spray TL, Gaynor JW, Clark BJ. Unexpected death after reconstructive surgery for hypoplastic left heart syndrome. Ann Thorac Surg 2001;71:61–5. 3. De Oliveira NC, Ashburn DA, Khalid F, et al. Prevention of early sudden circulatory collapse after the Norwood operation. Circulation 2004;110(Suppl 1):II133– 8.


4. Galantowicz M, Cheatham JP. Lessons learned from the development of a new hybrid strategy for the management of hypoplastic left heart syndrome. Pediatr Cardiol 2005;26: 190 –9. 5. Akintuerk H, Michel-Behnke I, Valeske K, et al. Stenting of the arterial duct and banding of the pulmonary arteries: basis for combined Norwood stage I and II repair in hypoplastic left heart. Circulation 2002;105:1099 –103. 6. Caldarone CA, Benson L, Holtby H, Li J, Redington AN, Van Arsdell GS. Initial experience with hybrid palliation for neonates with single-ventricle physiology. Ann Thorac Surg 2007;84:1294 –300. 7. Bacha EA, Daves S, Hardin J, et al. Single-ventricle palliation for high-risk neonates: the emergence of an alternative hybrid stage I strategy. J Thorac Cardiovasc Surg 2006;131: 163–71. 8. Caldarone CA, Benson LN, Holtby H, Van Arsdell GS. Main pulmonary artery to innominate artery shunt during hybrid palliation of hypoplastic left heart syndrome. J Thorac Cardiovasc Surg 2005;130:e1–2. 9. Caldarone CA, Honjo O, Benson LN, Van Arsdell GS. Modification of stage II procedure after hybrid palliation (bilateral pulmonary artery banding and ductal stenting) for hypoplastic left-sided heart syndrome: modified arch reconstruction with retained stented ductus patch. J Thorac Cardiovasc Surg 2007;134:1588 –9. 10. Nakata S, Imai Y, Takanashi Y, et al. A new method for the quantitative standardization of cross-sectional areas of the pulmonary arteries in congenital heart diseases with decreased pulmonary blood flow. J Thorac Cardiovasc Surg 1984;88:610 –9. 11. Reddy VM, McElhinney DB, Moore P, Petrossian E, Hanley FL. Pulmonary artery growth after bidirectional cavopulmonary shunt: is there a cause for concern? J Thorac Cardiovasc Surg 1996;112:1180 –92. 12. Li J, Zhang G, Benson L, et al. Comparison of the profiles of postoperative systemic hemodynamics and oxygen transport in neonates after the hybrid or the Norwood procedure: a pilot study. Circulation 2007;116(Suppl):I179 – 87. 13. Galantowicz M, Cheatham JP, Phillips A, et al. hybrid approach for hypoplastic left heart syndrome: intermediate results after the learning curve. Ann Thorac Surg 2008;85: 2063–71. 14. Pizarro C, Murdison KA, Derby CD, Radtke W. Stage II reconstruction after hybrid palliation for high-risk patients with a single ventricle. Ann Thorac Surg 2008;85:1382– 8.

DISCUSSION DR FRANK PIGULA (Boston, MA): I have a question for you for clarification. Over that time period that this study was conducted, what were the criteria you used for a patient to undergo hybrid versus standard Norwood operation? And can you speculate, does that have anything to do with the trends in lower utilization or lower hospital stay that you saw. DR HONJO: We don’t have any specific criteria whether we go for Norwood or a hybrid. We decide the particular procedure in case-by-case basis on the conference, and also that involves the parents’ opinion and the cardiologist’s opinion, which might bias the strategy. DR JACEK MOLL (Lodz, Poland): I would like to ask you one question. You have the same mortality in both groups, but you said that ventricular function was better preserved in the hybrid group. What was the cause of death of those patients, in first and second group, was there any difference in the cause of death?

Because generally 20% is high mortality, let’s say, and even in Norwood operation, but in hybrid it should be much less. DR HONJO: The mortality related to stage 1 hybrid is partly the technical issue, which is within the range of learning curve, because we include all cases from the beginning of this series. And none of them who died after stage 1 hybrid were related to poor ventricular function, whereas in the Norwood group, 4 or 5 patients actually got transplant because of poor ventricular function in the first 6 months, which is substantial. And also, if we look at the ventricular function of the patient at pre–stage 2 echocardiography, more than a quarter of the patients in the Norwood group have actually reduced ventricular function, whereas none of the patients in hybrid have reduced function. DR MOLL: But did you have a patient in this hybrid group with foramen ovale restriction? And if yes, what did you do for those patients?


DR HONJO: Because we didn’t address anything for the atrial septum at the stage 1 hybrid, the vast majority of patients required a balloon septostomy plus/minus stent placement at the atrial septum, which I didn’t mention in this presentation. But more than three quarters of the patients actually need the—


1893

DR JOSEPH FORBESS (Dallas, TX): I wanted to take just a few seconds to ask you about study design. I noticed that you excluded 8 hybrids that were on patients that you termed “salvage” or then went to transplant. I did see on your Norwood column, however, you included the patients that crossed over to transplant. Why you made that distinction in your study design?

DR MOLL: Stent implantation?

DR MARK GALANTOWICZ (Columbus, OH): I enjoyed your presentation and certainly all the contributions your group has made to the thinking with the hybrid approach. At this point we have performed about 100 hybrid stage 1 procedures, 60 comprehensive stage 2 procedures, and have 30 patients through their Fontan. Many of our results are similar to yours. But the thing that’s becoming clearer is there are subgroups within the hypoplast family, as we all know, and this hybrid technique may turn out to be best for a certain subgroup while a more traditional Norwood will work better for another subgroup. Figuring out those differences will take a study that is powered with many more patients than your study or any that we have put together. So I would encourage you and all of us in the congenital community to consider a multicenter trial, perhaps in the wake of the Norwood/Sano trial that should be completing up here pretty soon. Thank you.

DR HONJO: That’s the 8 patients? DR FORBESS: Yes. DR HONJO: That the 8 patients who were excluded from the study in the hybrid group, either that’s the decision was made for primary transplant—then we did the hybrid procedure as an interim palliation for the transplant to secure the pulmonary vasculature and then balance the circulation— or there were a couple patients who were done hybrid for salvage, in which patient condition was really poor, and to stabilize the hemodynamics we did the hybrid, which is not standard for a single ventricle palliation. That’s why we exclude 8 patients. DR FORBESS: Just as a show of hands, how many people, if you are doing hybrids, are predominantly doing your hybrids in the salvage case? [Show of hands.] So, not very many. These salvage HLHS cases and patients being prepared for transplant have comprised our hybrid Norwood group.

PEDIATRIC CARDIAC

DR HONJO: No, the atrial septotomy plus/minus stent placement. I don’t have exact number how many patients have stent, but more than one third of patients actually required a stent at the atrial septum.