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Abstract

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OBJECTIVES

The primary objectives were to examine utilization of the Hybrid versus the Norwood procedure for patients with hypoplastic left heart syndrome or variants and the impact on hospital mortality. The Hybrid procedure was 1st used at our institution in 2004.

METHODS

Review of all subjects undergoing the Norwood or Hybrid procedure between 1 January 1984 and 31 December 2022. The study period was divided into 8 eras: era 1, 1984–1988; era 2, 1989–1993; era 3, 1994–1998; era 4, 1999–2003; era 5, 2004–2008; era 6, 2009–2014; era 7, 2015–2018 and era 8, 2019–2022. The primary outcome was in-hospital mortality. Mortality rates were computed using standard binomial proportions with 95% confidence intervals. Rates across eras were compared using an ordered logistic regression model with and adjusted using the Tukey–Kramer post-hoc procedure for multiple comparisons. In the risk-modelling phase, logistic regression models were specified and tested.

RESULTS

The Norwood procedure was performed in 1899 subjects, and the Hybrid procedure in 82 subjects. Use of the Hybrid procedure increased in each subsequent era, reaching 30% of subjects in era 8. After adjustment for multiple risk factors, use of the Hybrid procedure was significantly and positively associated with hospital mortality.

CONCLUSIONS

Despite the increasing use of the Hybrid procedure, overall mortality for the entire cohort has plateaued. After adjustment for risk factors, use of the Hybrid procedure was significantly and positively associated with mortality compared to the Norwood procedure.

Hypoplastic left heart syndrome, Norwood procedure, Hybrid procedure, Congenital heart disease

INTRODUCTION

Aortic atresia or stenosis along with mitral atresia or stenosis and hypoplasia of the left ventricle was initially described by Lev in 1952 and referred to as ‘hypoplasia of the aortic tract complexes’ [1]. The term ‘hypoplastic left heart syndrome’ was coined in 1958 by Noonan and Nadas [2]. Hypoplastic left heart syndrome (HLHS) and similar structural variants were almost uniformly fatal until the advent of the Norwood procedure [1]. The 1st report of a palliative operation for HLHS was in 1977 by Doty and Knott [3]. In 1983, Norwood et al. reported the 1st successful palliative procedure for HLHS [4].

While results of the Norwood procedure improved over the ensuing 10 years, mortality and morbidity remained high. In 1993, Gibbs and associates described transcatheter stenting of the ductus arteriosus with pulmonary banding as initial palliation for HLHS [5]. Akintuerk and colleagues subsequently reported ductal stenting with pulmonary artery banding followed by the combination of neoaortic reconstruction and superior cavopulmonary connection [6]. There has been increasing use of the Hybrid procedure (bilateral pulmonary artery bands with the maintenance of ductal patency) as an alternative strategy for initial surgical intervention that avoids cardiopulmonary bypass and can serve as a ‘bridge’ to deferred Norwood, comprehensive stage 2 operation or heart transplantation, especially in patients at high-risk for mortality [7–9].

We previously reported early outcomes for 1663 neonates who underwent the Norwood procedure between January 1984 and May 2014 at our institution [10]. While hospital mortality had improved overall, it had plateaued in recent years (11–16%). The Hybrid procedure was 1st used at our institution in 2004 as an alternative strategy for initial surgical intervention. The primary objectives of this study were to examine utilization of the Hybrid versus the Norwood procedure and the impact on hospital mortality for patients with HLHS or variants.

PATIENTS AND METHODS

This is a single-centre retrospective review. All subjects who underwent a Norwood or Hybrid procedure at the Children’s Hospital of Philadelphia between 1 January 1984 and 31 December 2022 were included. There were no exclusion criteria. Subjects were classified as Norwood or Hybrid based on the initial procedure, i.e. a subject who underwent a Hybrid procedure followed by a Norwood is classified as Hybrid. All data presented here were abstracted from paper charts and electronic medical records. The choice of surgical procedure was determined by the attending surgeon after a multi-disciplinary conference and not by protocol.

Ethics statement

This study was approved by the Children’s Hospital of Philadelphia Institutional Review Board for the Protection of Human Subjects (IRB 14-010817, approved 25 June 2014) and the requirement for subject-informed consent was waived.

Data analysis

Data were summarized and described for the entire cohort, and survival estimates were computed using discharge status for the entire group and further assessed by era. Subsequently, risk-factor models were specified and tested to identify factors most likely to influence discharge status for the entire sample. Then, in phase II, we directed our efforts towards better understanding the differences between 2 discrete subgroups of the broader cohort: children receiving either the Norwood procedure or a Hybrid procedure. Descriptive statistics were computed for each group and compared. Variables identified in the prior risk-factor modelling analysis were used to compare survival at discharge for the 2 groups. A more complete description of methods used in each phase is provided below. All data were analysed using SAS v9.4 (TS Level 1M6).

Phase I (entire cohort)

Descriptive

Simple descriptive statistics were computed using parametric and nonparametric measures of central tendency (mean, median) and variability (SD, range, IQR0.25, 0.75) for all relevant variables. Histograms and frequency counts were generated for variables that were dichotomous or categorical in nature.

Survival

Binomial point estimates for survival status at hospital discharge were computed for the sample as a whole and for each of the 8 eras: era 1 (1984–1988), era 2 (1989–1993), era 3 (1994–1998), era 4 (1999–2003), era 5 (2004–2008), era 6 (2009–2014), era 7 (2015–2018) and era 8 (2019–2022), complete with 95% confidence intervals. Survival estimates were compared with a logistic regression model and adjusted using the Tukey–Kramer post-hoc procedure for multiple comparisons. This adjustment was necessary to account for an inflated type I error rate when conducting multiple difference tests with the same end-point across eras reflecting commonalities in practice.

Risk-modeling

Seventeen generalized linear (logistic regression) models were specified and tested. Survival status was 1st regressed onto era, and then onto each of 16 different patient-related factors, individually, after adjusting for era—specifically to estimate a variable’s impact on survival in the presence of a given era. A best-fitting multiple covariate model was specified and tested, using 5 covariates [anomalous pulmonary venous connection (APVR), atrioventricular valve regurgitation (AVVR), gestational age (<37 weeks), genetic anomaly and race], selected from among candidates in the models (Wald P-values <0.05). The criterion for statistical significance was set at the unadjusted α = 0.05 level.

Phase II (Norwood versus Hybrid cohorts)

Comparison of surgical interventions

Characteristics of children receiving either the Norwood procedure or a Hybrid procedure were described and compared for selected variables using a two-sample test of medians for continuous data, required by the skewed and non-normative nature of the continuous distributions, or a chi-square or Fisher’s exact test for categorical data (required by small cell counts), depending upon distributional patterns and expected cell counts. Only records of children born in 2004 (eras 5–8) or later were used for this phase because the Hybrid procedure was not used in previous eras. The criterion for statistical significance was set at the unadjusted α = 0.05 level.

Survival analysis

Building on information obtained in the previous analyses, survival status was regressed onto surgical intervention (Norwood, Hybrid) and a dichotomous measure of number of risk factors after adjusting for race and era. The composite risk factor variable was defined as 2 or more risk factors among the presence of APVR, AVVR, preterm birth (binary version of gestational age), genetic anomaly, low surgical weight and status of the atrial septum. Criteria for statistical significance were identical to those noted above. Data used for the final model reported here were 99.87% complete. We only had 5 missing values, 1 outcome value (discharge status) and 4 values for race. Our data were complete for all other variables (era, composite risk factors and surgical intervention). Hence, data were analysed using complete case analysis for 755 of the 760 children in the sample. Supplemental analyses were computed by calculating and examining the distribution of risk factors across eras for children receiving the Norwood and children receiving a Hybrid procedure, respectively. No formal tests of significance were computed.

Propensity score matching

To guard against the potential for selection bias resulting from systematic differences in physiology, patient profiles or surgeon preference over the course of the study, logit propensity scores were derived by regressing surgical intervention onto gender, race, year of 1st operation and HLHS subtype as potential confounders. Propensity scores were then used to match cases between the 2 surgical intervention groups using a 1:1 nearest neighbour matching strategy without replacement (caliper width of 0.25) for eras 5–8. Raw and standardized mean score differences as well as reduction in bias and variance ratios of binary and continuous terms were evaluated for balance between the 2 groups. Four covariates were determined to be well balanced between the 2 groups, and the derived dataset was used to estimate a treatment effect, this time for a sensitivity analysis [11–14] (Supplementary Material, Table S1).

RESULTS

During the study period, 1981 subjects underwent an initial procedure for HLHS. The Norwood procedure was performed in 1899 of these subjects. The Hybrid procedure was 1st used in 2004 (era 5) and was performed in 82 subjects in total. One subject had not been discharged from the hospital and was excluded from the survival analysis. Once introduced into practice, use of the Hybrid procedure increased in subsequent eras, reaching a high of 30% of subjects in the last era (2019–2022). (Fig. 1) Operative mortality for the entire cohort progressively decreased until era 5 and plateaued thereafter (Fig. 2 and Table 1). Operative mortality for the Hybrid procedure has exceeded mortality for the Norwood procedure in all 4 eras since its introduction (Fig. 2). Hospital mortality for the Norwood procedure in eras 5–8 tended to be lower compared to era 4 (Fig. 2). A pair-wise analysis of mortality rates across all 8 eras demonstrates the differences over the study (Table 1).

Utilization of Norwood and Hybrid Procedure by era.
Figure 1:

Utilization of Norwood and Hybrid Procedure by era.

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Operative mortality by era.
Figure 2:

Operative mortality by era.

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Table 1:
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Post-hoc comparison of morality rates across eras (n = 1979)

Era 1Era 2Era 3Era 4Era 5Era 6Era 7Era 8
Mortality rate1984–19881989–19931994–19981999–20032004–20082009–20142015–20182019–2022
π (95% CI)(n = 301)(n = 448)(n = 223)(n = 249)(n = 275)(n = 202)(n = 135)(n = 146)
Era 1 40.9 (35.3–46.4)0.5750.107<0.001<0.001<0.001<0.001<0.001
Era 2 34.2 (29.8–38.5)0.0620.898<0.001<0.001<0.0010.0010.002
Era 3 29.2 (23.2–35.1)0.0060.1930.005<0.0010.0850.0490.098
Era 4 14.9 (10.4–19.3)<0.001<0.001<0.0010.9600.9971.0001.000
Era 5 11.6 (7.8–15.4)<0.001<0.001<0.0010.2770.6490.9860.881
Era 6 17.3 (12.1–22.6)<0.001<0.0010.0040.4770.0790.9991.000
Era 7 14.8 (8.8–20.8)<0.001<0.0010.0020.9910.3650.5411.000
Era 8 16.3 (10.4–22.3)<0.001<0.0010.0050.6960.1780.8060.727
All eras 24.7 (22.8–26.6)
Era 1Era 2Era 3Era 4Era 5Era 6Era 7Era 8
Mortality rate1984–19881989–19931994–19981999–20032004–20082009–20142015–20182019–2022
π (95% CI)(n = 301)(n = 448)(n = 223)(n = 249)(n = 275)(n = 202)(n = 135)(n = 146)
Era 1 40.9 (35.3–46.4)0.5750.107<0.001<0.001<0.001<0.001<0.001
Era 2 34.2 (29.8–38.5)0.0620.898<0.001<0.001<0.0010.0010.002
Era 3 29.2 (23.2–35.1)0.0060.1930.005<0.0010.0850.0490.098
Era 4 14.9 (10.4–19.3)<0.001<0.001<0.0010.9600.9971.0001.000
Era 5 11.6 (7.8–15.4)<0.001<0.001<0.0010.2770.6490.9860.881
Era 6 17.3 (12.1–22.6)<0.001<0.0010.0040.4770.0790.9991.000
Era 7 14.8 (8.8–20.8)<0.001<0.0010.0020.9910.3650.5411.000
Era 8 16.3 (10.4–22.3)<0.001<0.0010.0050.6960.1780.8060.727
All eras 24.7 (22.8–26.6)

π: mortality rate/proportion of deceased patients relative to all patients surgically treated in a given era. Significance values adjusted for multiplicity of inter-era comparisons are presented above the principal diagonal, while the ‘unadjusted’ significance values for the same comparisons are presented below the diagonal.

Table 1:
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Post-hoc comparison of morality rates across eras (n = 1979)

Era 1Era 2Era 3Era 4Era 5Era 6Era 7Era 8
Mortality rate1984–19881989–19931994–19981999–20032004–20082009–20142015–20182019–2022
π (95% CI)(n = 301)(n = 448)(n = 223)(n = 249)(n = 275)(n = 202)(n = 135)(n = 146)
Era 1 40.9 (35.3–46.4)0.5750.107<0.001<0.001<0.001<0.001<0.001
Era 2 34.2 (29.8–38.5)0.0620.898<0.001<0.001<0.0010.0010.002
Era 3 29.2 (23.2–35.1)0.0060.1930.005<0.0010.0850.0490.098
Era 4 14.9 (10.4–19.3)<0.001<0.001<0.0010.9600.9971.0001.000
Era 5 11.6 (7.8–15.4)<0.001<0.001<0.0010.2770.6490.9860.881
Era 6 17.3 (12.1–22.6)<0.001<0.0010.0040.4770.0790.9991.000
Era 7 14.8 (8.8–20.8)<0.001<0.0010.0020.9910.3650.5411.000
Era 8 16.3 (10.4–22.3)<0.001<0.0010.0050.6960.1780.8060.727
All eras 24.7 (22.8–26.6)
Era 1Era 2Era 3Era 4Era 5Era 6Era 7Era 8
Mortality rate1984–19881989–19931994–19981999–20032004–20082009–20142015–20182019–2022
π (95% CI)(n = 301)(n = 448)(n = 223)(n = 249)(n = 275)(n = 202)(n = 135)(n = 146)
Era 1 40.9 (35.3–46.4)0.5750.107<0.001<0.001<0.001<0.001<0.001
Era 2 34.2 (29.8–38.5)0.0620.898<0.001<0.001<0.0010.0010.002
Era 3 29.2 (23.2–35.1)0.0060.1930.005<0.0010.0850.0490.098
Era 4 14.9 (10.4–19.3)<0.001<0.001<0.0010.9600.9971.0001.000
Era 5 11.6 (7.8–15.4)<0.001<0.001<0.0010.2770.6490.9860.881
Era 6 17.3 (12.1–22.6)<0.001<0.0010.0040.4770.0790.9991.000
Era 7 14.8 (8.8–20.8)<0.001<0.0010.0020.9910.3650.5411.000
Era 8 16.3 (10.4–22.3)<0.001<0.0010.0050.6960.1780.8060.727
All eras 24.7 (22.8–26.6)

π: mortality rate/proportion of deceased patients relative to all patients surgically treated in a given era. Significance values adjusted for multiplicity of inter-era comparisons are presented above the principal diagonal, while the ‘unadjusted’ significance values for the same comparisons are presented below the diagonal.

We evaluated the impact of patient-specific risk factors on mortality using logistic regression for the entire cohort. In univariate modelling, the following factors were associated with an increased risk of operative mortality: older age at surgery, APVR, moderate or severe AVVR, lower birth weight, earlier era of surgery, younger gestational age, suspected or confirmed genetic anomaly, HLHS subtype, preterm birth (<37 weeks), race other than white and lower weight at the time of surgery (Table 2). Of note, ascending aorta diameter, sex and HLHS subtype were not associated with risk of mortality. In the best-fitting multiple covariate model, APVR, moderate or severe AVVR, gestational age, genetic anomaly and race were statistically significantly associated with mortality after adjusting for era.

Table 2:
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Single and multiple covariate risk factor models for in-hospital mortality, 1984–2022 (n = 1981)

Single covariate modelsa
Best fitting multiple covariate model
Adjusted for era
Adjusted for era
Potential risk factorsnβ (SEM)OR (0.95CI)P-valueβ (SEM)OR (0.95CI)P-value
Ascending aorta (mm)1617–0.05 (0.04)0.95 (0.88–1.02)0.14
Age at Norwood (days)19800.00 (0.00)1.00 (1.00–1.01)0.03
Anomalous pulmonary veins (reference: none)19420.42 (0.11)2.31 (1.51–3.54)<0.010.35 (0.12)2.00 (1.26–3.18)<0.01
Atrioventricular valve regurgitation (reference: none)19550.24 (0.08)1.62 (1.18–2.22)<0.010.22 (0.09)1.56 (1.09–2.22)0.01
Birth weight (kg)1901–0.84 (0.10)0.43 (0.36–0.52)<0.01
Era (reference: 1984–1988)1980<0.01<0.01
 1989–19930.67 (0.11)0.75 (0.56–1.02)0.92 (0.13)0.68 (0.48–0.96)
 1994–19980.44 (0.14)0.60 (0.41–0.86)0.67 (0.16)0.53 (0.34–0.81)
 1999–2003–0.42 (0.17)0.25 (0.17–0.38)–0.44 (0.18)0.17 (0.11–0.28)
 2004–2008–0.70 (0.17)0.19 (0.12–0.29)–0.80 (0.18)0.12 (0.07–0.20)
 2009–2014–0.23 (0.17)0.30 (0.20–0.47)–0.34 (0.18)0.19 (0.12–0.31)
 2015–2018–0.42 (0.22)0.25 (0.15–0.43)–0.52 (0.23)0.16 (0.09–0.29)
 2019–2022–0.30 (0.20)0.28 (0.17–0.46)–0.79 (0.23)0.12 (0.07–0.22)
Gestational age (weeks)1860–0.23 (0.03)0.80 (0.75–0.84)<0.01–0.24 (0.03)0.79 (0.75–0.84)<0.01
Gender (reference: male)19800.10 (0.05)1.23 (0.99–1.52)0.06
Genetic anomaly (reference: none)19800.36 (0.07)2.07 (1.55–2.76)<0.010.31 (0.08)1.85 (1.35–2.52)<0.01
HLHS subtype (reference: AA/MA)b19490.03
 AA/MS0.17 (0.11)1.16 (0.84–1.59)
 AS/MA, AS/MS–0.33 (0.11)0.70 (0.50–0.98)
 Variant0.14 (0.09)1.12 (0.86–1.46)
Intact atrial septum (reference: no)19580.12 (0.07)1.28 (0.96–1.71)0.09
Preterm birth (kg, reference: no)19560.61 (0.07)3.40 (2.54–4.56)<0.01
Race (reference: Caucasian)1971<0.01<0.01
 African American–0.00 (0.10)1.50 (1.11–2.03)–0.11 (0.11)1.23 (0.88–1.730)
 Other0.41 (0.10)2.27 (1.69–3.03)0.43 (0.11)2.11 (1.54–2.89)
Weight at surgery (reference: weight <2.5 kg)1976–0.52 (0.08)0.35 (0.26–0.48)<0.01
Intercept18158.36 (1.11)
Single covariate modelsa
Best fitting multiple covariate model
Adjusted for era
Adjusted for era
Potential risk factorsnβ (SEM)OR (0.95CI)P-valueβ (SEM)OR (0.95CI)P-value
Ascending aorta (mm)1617–0.05 (0.04)0.95 (0.88–1.02)0.14
Age at Norwood (days)19800.00 (0.00)1.00 (1.00–1.01)0.03
Anomalous pulmonary veins (reference: none)19420.42 (0.11)2.31 (1.51–3.54)<0.010.35 (0.12)2.00 (1.26–3.18)<0.01
Atrioventricular valve regurgitation (reference: none)19550.24 (0.08)1.62 (1.18–2.22)<0.010.22 (0.09)1.56 (1.09–2.22)0.01
Birth weight (kg)1901–0.84 (0.10)0.43 (0.36–0.52)<0.01
Era (reference: 1984–1988)1980<0.01<0.01
 1989–19930.67 (0.11)0.75 (0.56–1.02)0.92 (0.13)0.68 (0.48–0.96)
 1994–19980.44 (0.14)0.60 (0.41–0.86)0.67 (0.16)0.53 (0.34–0.81)
 1999–2003–0.42 (0.17)0.25 (0.17–0.38)–0.44 (0.18)0.17 (0.11–0.28)
 2004–2008–0.70 (0.17)0.19 (0.12–0.29)–0.80 (0.18)0.12 (0.07–0.20)
 2009–2014–0.23 (0.17)0.30 (0.20–0.47)–0.34 (0.18)0.19 (0.12–0.31)
 2015–2018–0.42 (0.22)0.25 (0.15–0.43)–0.52 (0.23)0.16 (0.09–0.29)
 2019–2022–0.30 (0.20)0.28 (0.17–0.46)–0.79 (0.23)0.12 (0.07–0.22)
Gestational age (weeks)1860–0.23 (0.03)0.80 (0.75–0.84)<0.01–0.24 (0.03)0.79 (0.75–0.84)<0.01
Gender (reference: male)19800.10 (0.05)1.23 (0.99–1.52)0.06
Genetic anomaly (reference: none)19800.36 (0.07)2.07 (1.55–2.76)<0.010.31 (0.08)1.85 (1.35–2.52)<0.01
HLHS subtype (reference: AA/MA)b19490.03
 AA/MS0.17 (0.11)1.16 (0.84–1.59)
 AS/MA, AS/MS–0.33 (0.11)0.70 (0.50–0.98)
 Variant0.14 (0.09)1.12 (0.86–1.46)
Intact atrial septum (reference: no)19580.12 (0.07)1.28 (0.96–1.71)0.09
Preterm birth (kg, reference: no)19560.61 (0.07)3.40 (2.54–4.56)<0.01
Race (reference: Caucasian)1971<0.01<0.01
 African American–0.00 (0.10)1.50 (1.11–2.03)–0.11 (0.11)1.23 (0.88–1.730)
 Other0.41 (0.10)2.27 (1.69–3.03)0.43 (0.11)2.11 (1.54–2.89)
Weight at surgery (reference: weight <2.5 kg)1976–0.52 (0.08)0.35 (0.26–0.48)<0.01
Intercept18158.36 (1.11)
a

All single covariate models were adjusted for era; however, era was tested individually, as a categorical covariate with no additional adjustments.

b

HLHS subtypes: AA/MA: aortic atresia/mitral atresia; AA/MS: aortic atresia/mitral stenosis; AS/MA, AS/MS: aortic stenosis/mitral atresia and aortic stenosis/mitral stenosis (combined for modelling due to small sample sizes); Variant: HLHS variant.

HLHS: hypoplastic left heart syndrome.

Table 2:
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Single and multiple covariate risk factor models for in-hospital mortality, 1984–2022 (n = 1981)

Single covariate modelsa
Best fitting multiple covariate model
Adjusted for era
Adjusted for era
Potential risk factorsnβ (SEM)OR (0.95CI)P-valueβ (SEM)OR (0.95CI)P-value
Ascending aorta (mm)1617–0.05 (0.04)0.95 (0.88–1.02)0.14
Age at Norwood (days)19800.00 (0.00)1.00 (1.00–1.01)0.03
Anomalous pulmonary veins (reference: none)19420.42 (0.11)2.31 (1.51–3.54)<0.010.35 (0.12)2.00 (1.26–3.18)<0.01
Atrioventricular valve regurgitation (reference: none)19550.24 (0.08)1.62 (1.18–2.22)<0.010.22 (0.09)1.56 (1.09–2.22)0.01
Birth weight (kg)1901–0.84 (0.10)0.43 (0.36–0.52)<0.01
Era (reference: 1984–1988)1980<0.01<0.01
 1989–19930.67 (0.11)0.75 (0.56–1.02)0.92 (0.13)0.68 (0.48–0.96)
 1994–19980.44 (0.14)0.60 (0.41–0.86)0.67 (0.16)0.53 (0.34–0.81)
 1999–2003–0.42 (0.17)0.25 (0.17–0.38)–0.44 (0.18)0.17 (0.11–0.28)
 2004–2008–0.70 (0.17)0.19 (0.12–0.29)–0.80 (0.18)0.12 (0.07–0.20)
 2009–2014–0.23 (0.17)0.30 (0.20–0.47)–0.34 (0.18)0.19 (0.12–0.31)
 2015–2018–0.42 (0.22)0.25 (0.15–0.43)–0.52 (0.23)0.16 (0.09–0.29)
 2019–2022–0.30 (0.20)0.28 (0.17–0.46)–0.79 (0.23)0.12 (0.07–0.22)
Gestational age (weeks)1860–0.23 (0.03)0.80 (0.75–0.84)<0.01–0.24 (0.03)0.79 (0.75–0.84)<0.01
Gender (reference: male)19800.10 (0.05)1.23 (0.99–1.52)0.06
Genetic anomaly (reference: none)19800.36 (0.07)2.07 (1.55–2.76)<0.010.31 (0.08)1.85 (1.35–2.52)<0.01
HLHS subtype (reference: AA/MA)b19490.03
 AA/MS0.17 (0.11)1.16 (0.84–1.59)
 AS/MA, AS/MS–0.33 (0.11)0.70 (0.50–0.98)
 Variant0.14 (0.09)1.12 (0.86–1.46)
Intact atrial septum (reference: no)19580.12 (0.07)1.28 (0.96–1.71)0.09
Preterm birth (kg, reference: no)19560.61 (0.07)3.40 (2.54–4.56)<0.01
Race (reference: Caucasian)1971<0.01<0.01
 African American–0.00 (0.10)1.50 (1.11–2.03)–0.11 (0.11)1.23 (0.88–1.730)
 Other0.41 (0.10)2.27 (1.69–3.03)0.43 (0.11)2.11 (1.54–2.89)
Weight at surgery (reference: weight <2.5 kg)1976–0.52 (0.08)0.35 (0.26–0.48)<0.01
Intercept18158.36 (1.11)
Single covariate modelsa
Best fitting multiple covariate model
Adjusted for era
Adjusted for era
Potential risk factorsnβ (SEM)OR (0.95CI)P-valueβ (SEM)OR (0.95CI)P-value
Ascending aorta (mm)1617–0.05 (0.04)0.95 (0.88–1.02)0.14
Age at Norwood (days)19800.00 (0.00)1.00 (1.00–1.01)0.03
Anomalous pulmonary veins (reference: none)19420.42 (0.11)2.31 (1.51–3.54)<0.010.35 (0.12)2.00 (1.26–3.18)<0.01
Atrioventricular valve regurgitation (reference: none)19550.24 (0.08)1.62 (1.18–2.22)<0.010.22 (0.09)1.56 (1.09–2.22)0.01
Birth weight (kg)1901–0.84 (0.10)0.43 (0.36–0.52)<0.01
Era (reference: 1984–1988)1980<0.01<0.01
 1989–19930.67 (0.11)0.75 (0.56–1.02)0.92 (0.13)0.68 (0.48–0.96)
 1994–19980.44 (0.14)0.60 (0.41–0.86)0.67 (0.16)0.53 (0.34–0.81)
 1999–2003–0.42 (0.17)0.25 (0.17–0.38)–0.44 (0.18)0.17 (0.11–0.28)
 2004–2008–0.70 (0.17)0.19 (0.12–0.29)–0.80 (0.18)0.12 (0.07–0.20)
 2009–2014–0.23 (0.17)0.30 (0.20–0.47)–0.34 (0.18)0.19 (0.12–0.31)
 2015–2018–0.42 (0.22)0.25 (0.15–0.43)–0.52 (0.23)0.16 (0.09–0.29)
 2019–2022–0.30 (0.20)0.28 (0.17–0.46)–0.79 (0.23)0.12 (0.07–0.22)
Gestational age (weeks)1860–0.23 (0.03)0.80 (0.75–0.84)<0.01–0.24 (0.03)0.79 (0.75–0.84)<0.01
Gender (reference: male)19800.10 (0.05)1.23 (0.99–1.52)0.06
Genetic anomaly (reference: none)19800.36 (0.07)2.07 (1.55–2.76)<0.010.31 (0.08)1.85 (1.35–2.52)<0.01
HLHS subtype (reference: AA/MA)b19490.03
 AA/MS0.17 (0.11)1.16 (0.84–1.59)
 AS/MA, AS/MS–0.33 (0.11)0.70 (0.50–0.98)
 Variant0.14 (0.09)1.12 (0.86–1.46)
Intact atrial septum (reference: no)19580.12 (0.07)1.28 (0.96–1.71)0.09
Preterm birth (kg, reference: no)19560.61 (0.07)3.40 (2.54–4.56)<0.01
Race (reference: Caucasian)1971<0.01<0.01
 African American–0.00 (0.10)1.50 (1.11–2.03)–0.11 (0.11)1.23 (0.88–1.730)
 Other0.41 (0.10)2.27 (1.69–3.03)0.43 (0.11)2.11 (1.54–2.89)
Weight at surgery (reference: weight <2.5 kg)1976–0.52 (0.08)0.35 (0.26–0.48)<0.01
Intercept18158.36 (1.11)
a

All single covariate models were adjusted for era; however, era was tested individually, as a categorical covariate with no additional adjustments.

b

HLHS subtypes: AA/MA: aortic atresia/mitral atresia; AA/MS: aortic atresia/mitral stenosis; AS/MA, AS/MS: aortic stenosis/mitral atresia and aortic stenosis/mitral stenosis (combined for modelling due to small sample sizes); Variant: HLHS variant.

HLHS: hypoplastic left heart syndrome.

The patients selected for the Hybrid procedure were a high-risk cohort (Tables 3 and 4) Compared to those undergoing the Norwood procedure, patients selected for the hybrid were more likely to have an HLHS variant (47.6% vs 29.9%, P = 0.001), be born preterm (42.7% vs 12.1%, P < 0.001), have a genetic anomaly (46.3% vs. 21.7%, P < 0.001), have moderate-to-severe AVVR (24.4% vs 10.2%, P < 0.001), have atrial septal restriction (19.5% vs 11.6%, P = 0.042) and have weight ≤2.5 kg at the time of surgery (34.2% vs 13.3%, P < 0.001). Patients selected for the Hybrid procedure were more likely to have multiple risk factors (Table 4). Every patient selected for the Hybrid had at least 1 risk factor. In every era, the majority of patients selected for the Hybrid had 2 or more risk factors (Fig. 3). When comparing a Hybrid procedure with the Norwood procedure, the Hybrid was significantly positively associated with hospital mortality (P < 0.001) after adjusting for era (P = 0.47), race (P < 0.001) and presence of multiple risk factors (composite risk factor variable) (P = 0.049). We tested for an interaction between type of surgical intervention and number of risk factors, and the distribution of risk factors observed for the Hybrid group was not significantly different from the distribution observed in the Norwood group (P = 0.30).

Risk factors by procedure and era.
Figure 3:

Risk factors by procedure and era.

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Table 3:
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Comparison of patient characteristics for Norwood versus Hybrid subgroups

Norwood (n = 678)
Hybrid (n = 82)
VariableMean (SD)Median (IQR)Mean (SD)Median (IQR)P-value
Continuous factors
 Ascending aorta (mm)3.6 (1.9)3.2 (2.0–5.0)4.4 (1.9)4.0 (3.0–5.8)<0.001
 Age at Norwood (days)5.5 (9.0)4.0 (2.5–6.0)9.7 (16.2)5.2 (3.4–9.6)0.036
 Birth weight (kg)3.1 (0.6)3.2 (2.8–3.5)2.7 (0.7)2.9 (2.1–3.2)<0.001
 Gestational age (weeks)38.1 (1.7)38.0 (37.0–39.0)36.2 (2.8)37.0 (34.0–38.0)<0.001
 Year of Norwood2011 (2006–2016)2019 (2013–2020)<0.001
Categorical factors
n (%)n (%)
APVR0.007
 None653 (96.3)73 (89.0)
 Present25 (3.7)9 (11.0)
AVVR<0.001
 No/trace/mild609 (89.8)62 (75.6)
 Moderate/severe69 (10.2)20 (24.4)
Era<0.001
 2004–2008268 (39.5)7 (8.5)
 2009–2014186 (27.4)16 (19.5)
 2015–2018120 (17.7)15 (18.3)
 2019–2022104 (15.3)44 (53.7)
Sex0.292
 Male421 (62.1)46 (56.1)
 Female257 (37.9)36 (43.9)
Genetic anomaly<0.001
 Normal531 (78.3)44 (53.7)
 Confirmed/suspect147 (21.7)38 (46.3)
HLHS subtype0.001
 AA/MA227 (33.5)13 (15.8)
 AA/MS121 (17.8)12 (14.6)
 AS/MA; AS/MS127 (18.7)18 (22.0)
 HLHS variant203 (29.9)39 (47.6)
Atrial septal restriction0.042
 None599 (88.4)66 (80.5)
 Yes79 (11.6)16 (19.5)
Preterm birth<0.001
 Term (37+ weeks)596 (87.9)47 (57.3)
 Preterm (<37 weeks)82 (12.1)35 (42.7)
Race0.266
 Caucasian406 (60.1)46 (57.5)
 African American108 (16.0)9 (11.2)
 Other162 (24.0)25 (31.2)
Weight at surgery<0.001
 ≤2.5 kg90 (13.3)28 (34.2)
 2.5 kg +588 (86.7)54 (65.8)
Norwood (n = 678)
Hybrid (n = 82)
VariableMean (SD)Median (IQR)Mean (SD)Median (IQR)P-value
Continuous factors
 Ascending aorta (mm)3.6 (1.9)3.2 (2.0–5.0)4.4 (1.9)4.0 (3.0–5.8)<0.001
 Age at Norwood (days)5.5 (9.0)4.0 (2.5–6.0)9.7 (16.2)5.2 (3.4–9.6)0.036
 Birth weight (kg)3.1 (0.6)3.2 (2.8–3.5)2.7 (0.7)2.9 (2.1–3.2)<0.001
 Gestational age (weeks)38.1 (1.7)38.0 (37.0–39.0)36.2 (2.8)37.0 (34.0–38.0)<0.001
 Year of Norwood2011 (2006–2016)2019 (2013–2020)<0.001
Categorical factors
n (%)n (%)
APVR0.007
 None653 (96.3)73 (89.0)
 Present25 (3.7)9 (11.0)
AVVR<0.001
 No/trace/mild609 (89.8)62 (75.6)
 Moderate/severe69 (10.2)20 (24.4)
Era<0.001
 2004–2008268 (39.5)7 (8.5)
 2009–2014186 (27.4)16 (19.5)
 2015–2018120 (17.7)15 (18.3)
 2019–2022104 (15.3)44 (53.7)
Sex0.292
 Male421 (62.1)46 (56.1)
 Female257 (37.9)36 (43.9)
Genetic anomaly<0.001
 Normal531 (78.3)44 (53.7)
 Confirmed/suspect147 (21.7)38 (46.3)
HLHS subtype0.001
 AA/MA227 (33.5)13 (15.8)
 AA/MS121 (17.8)12 (14.6)
 AS/MA; AS/MS127 (18.7)18 (22.0)
 HLHS variant203 (29.9)39 (47.6)
Atrial septal restriction0.042
 None599 (88.4)66 (80.5)
 Yes79 (11.6)16 (19.5)
Preterm birth<0.001
 Term (37+ weeks)596 (87.9)47 (57.3)
 Preterm (<37 weeks)82 (12.1)35 (42.7)
Race0.266
 Caucasian406 (60.1)46 (57.5)
 African American108 (16.0)9 (11.2)
 Other162 (24.0)25 (31.2)
Weight at surgery<0.001
 ≤2.5 kg90 (13.3)28 (34.2)
 2.5 kg +588 (86.7)54 (65.8)

HLHS subtypes: AA/MA: aortic atresia/mitral atresia; AA/MS: aortic atresia/mitral stenosis; AS/MA: AS/MS: aortic stenosis/mitral atresia and aortic stenosis/mitral stenosis (combined for modelling due to small sample sizes); variant: HLHS variant.

APVR: anomalous pulmonary venous return; AVVR: atrioventricular valve regurgitation; IQR: interquartile range; HLHS: hypoplastic left heart syndrome; SD: standard deviation.

Table 3:
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Comparison of patient characteristics for Norwood versus Hybrid subgroups

Norwood (n = 678)
Hybrid (n = 82)
VariableMean (SD)Median (IQR)Mean (SD)Median (IQR)P-value
Continuous factors
 Ascending aorta (mm)3.6 (1.9)3.2 (2.0–5.0)4.4 (1.9)4.0 (3.0–5.8)<0.001
 Age at Norwood (days)5.5 (9.0)4.0 (2.5–6.0)9.7 (16.2)5.2 (3.4–9.6)0.036
 Birth weight (kg)3.1 (0.6)3.2 (2.8–3.5)2.7 (0.7)2.9 (2.1–3.2)<0.001
 Gestational age (weeks)38.1 (1.7)38.0 (37.0–39.0)36.2 (2.8)37.0 (34.0–38.0)<0.001
 Year of Norwood2011 (2006–2016)2019 (2013–2020)<0.001
Categorical factors
n (%)n (%)
APVR0.007
 None653 (96.3)73 (89.0)
 Present25 (3.7)9 (11.0)
AVVR<0.001
 No/trace/mild609 (89.8)62 (75.6)
 Moderate/severe69 (10.2)20 (24.4)
Era<0.001
 2004–2008268 (39.5)7 (8.5)
 2009–2014186 (27.4)16 (19.5)
 2015–2018120 (17.7)15 (18.3)
 2019–2022104 (15.3)44 (53.7)
Sex0.292
 Male421 (62.1)46 (56.1)
 Female257 (37.9)36 (43.9)
Genetic anomaly<0.001
 Normal531 (78.3)44 (53.7)
 Confirmed/suspect147 (21.7)38 (46.3)
HLHS subtype0.001
 AA/MA227 (33.5)13 (15.8)
 AA/MS121 (17.8)12 (14.6)
 AS/MA; AS/MS127 (18.7)18 (22.0)
 HLHS variant203 (29.9)39 (47.6)
Atrial septal restriction0.042
 None599 (88.4)66 (80.5)
 Yes79 (11.6)16 (19.5)
Preterm birth<0.001
 Term (37+ weeks)596 (87.9)47 (57.3)
 Preterm (<37 weeks)82 (12.1)35 (42.7)
Race0.266
 Caucasian406 (60.1)46 (57.5)
 African American108 (16.0)9 (11.2)
 Other162 (24.0)25 (31.2)
Weight at surgery<0.001
 ≤2.5 kg90 (13.3)28 (34.2)
 2.5 kg +588 (86.7)54 (65.8)
Norwood (n = 678)
Hybrid (n = 82)
VariableMean (SD)Median (IQR)Mean (SD)Median (IQR)P-value
Continuous factors
 Ascending aorta (mm)3.6 (1.9)3.2 (2.0–5.0)4.4 (1.9)4.0 (3.0–5.8)<0.001
 Age at Norwood (days)5.5 (9.0)4.0 (2.5–6.0)9.7 (16.2)5.2 (3.4–9.6)0.036
 Birth weight (kg)3.1 (0.6)3.2 (2.8–3.5)2.7 (0.7)2.9 (2.1–3.2)<0.001
 Gestational age (weeks)38.1 (1.7)38.0 (37.0–39.0)36.2 (2.8)37.0 (34.0–38.0)<0.001
 Year of Norwood2011 (2006–2016)2019 (2013–2020)<0.001
Categorical factors
n (%)n (%)
APVR0.007
 None653 (96.3)73 (89.0)
 Present25 (3.7)9 (11.0)
AVVR<0.001
 No/trace/mild609 (89.8)62 (75.6)
 Moderate/severe69 (10.2)20 (24.4)
Era<0.001
 2004–2008268 (39.5)7 (8.5)
 2009–2014186 (27.4)16 (19.5)
 2015–2018120 (17.7)15 (18.3)
 2019–2022104 (15.3)44 (53.7)
Sex0.292
 Male421 (62.1)46 (56.1)
 Female257 (37.9)36 (43.9)
Genetic anomaly<0.001
 Normal531 (78.3)44 (53.7)
 Confirmed/suspect147 (21.7)38 (46.3)
HLHS subtype0.001
 AA/MA227 (33.5)13 (15.8)
 AA/MS121 (17.8)12 (14.6)
 AS/MA; AS/MS127 (18.7)18 (22.0)
 HLHS variant203 (29.9)39 (47.6)
Atrial septal restriction0.042
 None599 (88.4)66 (80.5)
 Yes79 (11.6)16 (19.5)
Preterm birth<0.001
 Term (37+ weeks)596 (87.9)47 (57.3)
 Preterm (<37 weeks)82 (12.1)35 (42.7)
Race0.266
 Caucasian406 (60.1)46 (57.5)
 African American108 (16.0)9 (11.2)
 Other162 (24.0)25 (31.2)
Weight at surgery<0.001
 ≤2.5 kg90 (13.3)28 (34.2)
 2.5 kg +588 (86.7)54 (65.8)

HLHS subtypes: AA/MA: aortic atresia/mitral atresia; AA/MS: aortic atresia/mitral stenosis; AS/MA: AS/MS: aortic stenosis/mitral atresia and aortic stenosis/mitral stenosis (combined for modelling due to small sample sizes); variant: HLHS variant.

APVR: anomalous pulmonary venous return; AVVR: atrioventricular valve regurgitation; IQR: interquartile range; HLHS: hypoplastic left heart syndrome; SD: standard deviation.

Table 4:
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Morality rate and number of risk factors by eras and surgical procedure (n = 760)

Number of risk factors
Surgical procedure
Era (π, years)		0 (%)1 (%)2 (%)3 or More (%)
Norwood (n = 678)
 Era 5 (11.2, 2004–2008)15 (5.6)167 (62.3)71 (26.5)15 (5.6)
 Era 6 (16.1, 2009–2014)7 (3.8)101 (54.3)56 (30.1)22 (11.8)
 Era 7 (10.8, 2015–2018)0 (0.0)70 (58.3)41 (34.20)9 (7.5)
 Era 8 (11.5, 2019–2022)3 (2.9)37 (35.6)55 (52.9)9 (8.6)
 Eras 5–8 (12.5, 2004–2022)
Hybrid (n = 82)
 Era 5 (28.6, 2004–2008)0 (0.0)1 (14.3)4 (57.1)2 (28.6)
 Era 6 (31.2, 2009–2014)0 (0.0)3 (18.8)11 (68.8)2 (12.5)
 Era 7 (46.7, 2015–2018)0 (0.0)6 (40.0)2 (13.3)7 (46.7)
 Era 8 (27.9, 2019–2022)0 (0.0)8 (18.2)26 (59.1)10 (22.7)
 Eras 5–8 (32.1, 2004–2022)
Number of risk factors
Surgical procedure
Era (π, years)		0 (%)1 (%)2 (%)3 or More (%)
Norwood (n = 678)
 Era 5 (11.2, 2004–2008)15 (5.6)167 (62.3)71 (26.5)15 (5.6)
 Era 6 (16.1, 2009–2014)7 (3.8)101 (54.3)56 (30.1)22 (11.8)
 Era 7 (10.8, 2015–2018)0 (0.0)70 (58.3)41 (34.20)9 (7.5)
 Era 8 (11.5, 2019–2022)3 (2.9)37 (35.6)55 (52.9)9 (8.6)
 Eras 5–8 (12.5, 2004–2022)
Hybrid (n = 82)
 Era 5 (28.6, 2004–2008)0 (0.0)1 (14.3)4 (57.1)2 (28.6)
 Era 6 (31.2, 2009–2014)0 (0.0)3 (18.8)11 (68.8)2 (12.5)
 Era 7 (46.7, 2015–2018)0 (0.0)6 (40.0)2 (13.3)7 (46.7)
 Era 8 (27.9, 2019–2022)0 (0.0)8 (18.2)26 (59.1)10 (22.7)
 Eras 5–8 (32.1, 2004–2022)

For purposes of this analysis, risk factors were presence of anomalous pulmonary venous drainage, moderate to severe atrioventricular valve regurgitation, confirmed/suspected genetical anomaly, intact/highly restrictive atrial septum, preterm birth (dichotomized at 37 weeks) and weight at stage 1 reconstruction (dichotomized at 2.5 kg).

Table 4:
Open in new tab

Morality rate and number of risk factors by eras and surgical procedure (n = 760)

Number of risk factors
Surgical procedure
Era (π, years)		0 (%)1 (%)2 (%)3 or More (%)
Norwood (n = 678)
 Era 5 (11.2, 2004–2008)15 (5.6)167 (62.3)71 (26.5)15 (5.6)
 Era 6 (16.1, 2009–2014)7 (3.8)101 (54.3)56 (30.1)22 (11.8)
 Era 7 (10.8, 2015–2018)0 (0.0)70 (58.3)41 (34.20)9 (7.5)
 Era 8 (11.5, 2019–2022)3 (2.9)37 (35.6)55 (52.9)9 (8.6)
 Eras 5–8 (12.5, 2004–2022)
Hybrid (n = 82)
 Era 5 (28.6, 2004–2008)0 (0.0)1 (14.3)4 (57.1)2 (28.6)
 Era 6 (31.2, 2009–2014)0 (0.0)3 (18.8)11 (68.8)2 (12.5)
 Era 7 (46.7, 2015–2018)0 (0.0)6 (40.0)2 (13.3)7 (46.7)
 Era 8 (27.9, 2019–2022)0 (0.0)8 (18.2)26 (59.1)10 (22.7)
 Eras 5–8 (32.1, 2004–2022)
Number of risk factors
Surgical procedure
Era (π, years)		0 (%)1 (%)2 (%)3 or More (%)
Norwood (n = 678)
 Era 5 (11.2, 2004–2008)15 (5.6)167 (62.3)71 (26.5)15 (5.6)
 Era 6 (16.1, 2009–2014)7 (3.8)101 (54.3)56 (30.1)22 (11.8)
 Era 7 (10.8, 2015–2018)0 (0.0)70 (58.3)41 (34.20)9 (7.5)
 Era 8 (11.5, 2019–2022)3 (2.9)37 (35.6)55 (52.9)9 (8.6)
 Eras 5–8 (12.5, 2004–2022)
Hybrid (n = 82)
 Era 5 (28.6, 2004–2008)0 (0.0)1 (14.3)4 (57.1)2 (28.6)
 Era 6 (31.2, 2009–2014)0 (0.0)3 (18.8)11 (68.8)2 (12.5)
 Era 7 (46.7, 2015–2018)0 (0.0)6 (40.0)2 (13.3)7 (46.7)
 Era 8 (27.9, 2019–2022)0 (0.0)8 (18.2)26 (59.1)10 (22.7)
 Eras 5–8 (32.1, 2004–2022)

For purposes of this analysis, risk factors were presence of anomalous pulmonary venous drainage, moderate to severe atrioventricular valve regurgitation, confirmed/suspected genetical anomaly, intact/highly restrictive atrial septum, preterm birth (dichotomized at 37 weeks) and weight at stage 1 reconstruction (dichotomized at 2.5 kg).

To account for potential confounding factors like selection bias on the part of the surgeon, and the changing nature of both the population and medical care (calendar bias), a separate sensitivity analysis was conducted using the same model as described previously, only now with matched samples based on propensity scores. This analysis yielded a statistically significant result for the testable covariate, with a higher mortality for the Hybrid versus the Norwood procedure (P = 0.033). The other 3 factors were not statistically significant. Hence, the finding of a statistically significant relationship between procedure and mortality observed in the full analysis was also observed in matched sample using propensity scores.

DISCUSSION

As previously reported, operative mortality at our institution for patients undergoing the initial stage of reconstruction for HLHS and variants decreased from the mid-1980s until the mid-2000s [10]. Because of continued early mortality, the Hybrid procedure was 1st used at our institution in 2004 in an attempt to improve early outcomes, mainly in infants deemed high-risk. Use of the Hybrid procedure was at the discretion of the surgeon, not by protocol and its use has steadily increased. Despite increasing use of the Hybrid procedure, hospital mortality for the entire cohort has not decreased in recent years. In general, patients with characteristics considered to increase the risk of mortality were selected for the Hybrid procedure. Even though mortality for the entire cohort of children with HLHS has plateaued, mortality for the Norwood procedure tended to be lower in the later years, potentially due to more high-risk patients undergoing the Hybrid procedure. These data highlight a weakness of procedural-based reporting of outcomes, rather than reporting on outcomes for all patients with the same diagnosis. The outcome may depend on patient factors more so than the therapeutic strategy chosen. Differences in outcome between the treatment strategies may be due to unequal allocation of high-risk patients.

The concept of the Hybrid procedure was introduced in 1993 [5]. By the early 2000s, there were increasing reports of use of the Hybrid procedure as a successful bridge to cardiac transplantation or further staged palliative surgery for patients with HLHS and variants [6, 15]. There was increasing interest in the Hybrid procedure as a less-invasive procedure, which might mitigate some of the mortality in high-risk patients. Bacha and colleagues reported 79% hospital survival in a small cohort of high-risk patients and suggested the Hybrid might become the preferred alternative for these subjects [9].

It is difficult to compare outcomes for the Norwood versus Hybrid procedures without considering the associated patient characteristics. Yerebakan and co-workers reported a hospital mortality of 2.5% for the Hybrid procedure [7]. There were 5 patients with APVR; but data concerning preterm birth, weight at the time of surgery, genetic anomalies and atrial septal restriction were not reported. Baba and associates reported excellent outcomes after the Norwood and Hybrid procedures with hospital mortality of <10% [8]. Data on patient characteristics prior to the Norwood and Hybrid were not reported. Pizarro and associates have reported their early experience with the Hybrid, highlighting the importance of patient characteristics [16]. Operative mortality was 32.4%, and non-modifiable factors (low weight, preterm birth, genetic anomalies, and extracardiac anomalies) had a significant adverse impact on early survival [16]. Sower and colleagues specifically examined the impact of high-risk characteristics on Norwood versus Hybrid outcomes [17]. Use of the Hybrid was not associated with improved midterm outcomes. Wilder and coinvestigators from the Congenital Heart Surgeons’ Society (CHSS) reported outcomes for newborns with critical left ventricular outflow tract obstruction undergoing the Norwood of Hybrid procedure [18]. Risk-adjusted survival was significantly better for the Norwood with a right ventricle to pulmonary artery conduit compared to either the Norwood with a modified Blalock–Taussig–Thomas shunt or the Hybrid procedure.

Limitations

There are limitations to the current study. It is a single-centre cohort study, utilizing retrospective data, much of it transcribed from paper charts with missing data There is a limited amount of data available for the earliest subjects. In addition, it was not possible to assess potentially important factors such as AVVR after intervention, changes in ventricular function, socioeconomic status, etc., which may modify the risk of mortality. However, for the most recent eras, the eras for which outcomes between the Norwood procedure and the Hybrid procedure are being compared, missingness was very low. There are limited echocardiographic data available for the earlier eras and the presence of ventricular dysfunction could not be reliably ascertained. The choice of procedure was at the discretion of the surgeon and not by protocol. Despite increasing use of the Hybrid procedures, the numbers are small compared to the number who underwent the Norwood procedure. In addition, over the almost 40 years of the study, there have been numerous changes in referral patterns, prenatal care, operative and perioperative management, etc. There is no way that all these changes can be quantified and incorporated in the analyses. Our aim was to compare an initial palliative strategy of the Norwood procedure compared to an initial strategy of the Hybrid procedure. Implementation of either strategy is very heterogeneous. For the Norwood, there are differences in choice of shunt, arch reconstruction, bypass strategies, etc., which may impact outcome. For the Hybrid procedure, there are differences in the technique for PA banding, use of a ductal stent or prostaglandin, management of the atrial septum, etc. Evaluation of each of these would result in multiple small subgroups. Therefore, we elected to classify subjects as Norwood or Hybrid without further subcategorization.

CONCLUSIONS

In conclusion, we found that operative mortality for all patients undergoing initial palliation (Norwood or Hybrid) for HLHS and variants has plateaued over the last 20 years at our institution. Over the same time, use of the Hybrid procedure has increased. Based on clinical judgement, the patients selected for the Hybrid procedure were more likely to have multiple high-risk characteristics. However, even after adjustment for the identified risk factors, use of the Hybrid procedure was associated with increased mortality suggesting that use of the Hybrid does not mitigate high-risk patient factors. If high-risk patients are primarily selected for 1 treatment and lower risk subjects for another, observed differences in outcomes may be due to patient characteristics and may not reflect differences in the effectiveness of the surgical strategy. Creation of inception cohorts that are based on diagnosis and include all patients regardless of therapy chosen could provide important information to guide decisions about choice of specific therapies.

Presented at the EACTS Annual Meeting, Vienna, Austria, October 2023.

SUPPLEMENTARY MATERIAL

Supplementary material is available at EJCTS online.

FUNDING

This project was funded by the Mortimer J. Buckley Jr. MD. Endowed Chair in Cardiac Surgery, the Thomas L. Spray, MD Endowed Chair in Paediatric Cardiothoracic Surgery and the Daniel M. Tabas Endowed Chair in Paediatric Cardiothoracic Surgery at the Children’s Hospital of Philadelphia.

Conflict of Interest: none declared.

DATA AVAILABILITY

Reasonable data requests will be considered.

Author contributions

Jonathan M. Chen: Conceptualization; Writing—review and editing. Richard F. Ittenbach: Data curation; Formal analysis; Writing—review and editing. Kendall M. Lawrence: Investigation; Writing—review and editing. Mallory L. Hunt: Investigation; Writing—review and editing. Michelle Kaplinski: Investigation; Writing—review and editing. Marlene Mahle: Data curation; Investigation; Project administration; Writing—review and editing. Stephanie Fuller: Visualization; Writing—review and editing. Katsuhide Maeda: Validation; Writing—review and editing. Muhammad A.K. Nuri: Validation; Writing—review and editing. Monique M. Gardner: Investigation; Validation; Writing—review and editing. Constantine D. Mavroudis: Validation; Writing—review and editing. Christopher E. Mascio: Investigation; Validation; Writing—review and editing. Thomas L. Spray: Conceptualization; Validation; Writing—review and editing. J. William Gaynor: Conceptualization; Data curation; Investigation; Resources; Supervision; Validation; Visualization; Writing—original draft; Writing—review and editing.

Reviewer information

European Journal of Cardio-Thoracic Surgery thanks Nicholas D. Andersen and the other, anonymous reviewers for their contribution to the peer review process of this article.

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ABBREVIATIONS

    ABBREVIATIONS
     
  • APVR

    Anomalous pulmonary venous connection

    •  
  • AVVR

    Atrioventricular valve regurgitation

    •  
  • CHSS

    Congenital Heart Surgeons’ Society

    •  
  • HLHS

    Hypoplastic left heart syndrome

© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://dbpia.nl.go.kr/pages/standard-publication-reuse-rights)
Topic:
Subject
Univentricular Palliation Vessel Anomalies (Congenital)
Issue Section:
CONGENITAL
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