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Eur J Cardiothorac Surg 2006;29:675-681
© 2006 Elsevier Science NL
a Department of Cardiac Surgery, Birmingham Children's Hospital, United Kingdom
b Department of Cardiology, Birmingham Children's Hospital, United Kingdom
Received 13 September 2005; received in revised form 20 January 2006; accepted 26 January 2006.
* Corresponding author. Address: Department of Paediatric Cardiac Surgery, Birmingham Children's Hospital, Steelhouse Lane, Birmingham B4 6NH, United Kingdom. Tel.: +44 121 333 9435; fax: +44 121 333 9441. (Email: dr_mcguirk{at}dsl.pipex.com).
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Abstract |
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 Top Abstract 1. Introduction2. Materials and methods3. Results4. Discussion5. Study limitations6. ConclusionReferences |
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Key Words: Hypoplastic left heart syndrome • Norwood procedure • Risk factors • Heart defects, congenital • Paediatrics
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1. Introduction |
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TopAbstract1. Introduction2. Materials and methods3. Results4. Discussion5. Study limitations6. ConclusionReferences |
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There has been a substantial improvement in the surgical outcome in patients with HLHS since the Norwood procedure was introduced. Early survival following the Norwood procedure in contemporary series ranges between 73 and 80% [2–4], although an increasing number of centres have reported hospital survival rates of more than 90% [5,6]. Nevertheless, the Norwood procedure remains one of the highest risk procedures in paediatric cardiac surgery [7].
This study was undertaken to identify the anatomic and technical factors that influenced early outcome following the modified Norwood procedure, based on our 12-year single-institution experience. We sought to develop a simple predictive risk model to account for differences in case mix and surgical technique, which could be used to monitor the on-going clinical performance.
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2. Materials and methods |
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TopAbstract1. Introduction2. Materials and methods3. Results4. Discussion5. Study limitations6. ConclusionReferences |
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The median diameter of the ascending aorta was 3.0 mm (range, 1.0–10.0 mm), and was 
2.0 mm in 82 patients (25%). Fifty-four patients (16.2%) had additional cardiac abnormalities including interrupted aortic arch, abnormal systemic or venous drainage, or congenital heart block. Fourteen patients (4.2%) were premature (gestational age < 37 weeks) and 18 patients (5.4%) were originally diagnosed with additional major structural abnormalities or genetic anomalies. Ninety-two patients (28%) had impaired right ventricular function on preoperative echocardiography.
The Norwood procedure was performed at a median age of 4 days (range, 0–217 days). The majority (n = 265, 80%) were operated within the first 7 days and only 13 patients (3.9%) were operated at >30 days of age. The median weight at operation was 3.1 kg (range, 1.7–6.6 kg). The weight at operation Z score was –1.17 ± 1.22, based on the British 1990 reference population [9]. The median body surface area (BSA) at operation was 0.20 m2 (range, 0.14–0.33 m2).
All operations were performed by one of the three surgeons using deep hypothermic cardiopulmonary bypass (CPB) with periods of circulatory arrest (DHCA) for arch reconstruction [8]. Antegrade cerebral perfusion was introduced in September 2002 and used during arch reconstruction in 72 patients (22%). The median duration of CPB, aortic cross-clamp and DHCA were 71 min (range, 17–323 min), 51 min (range, 0–109 min) and 55 min (range, 0–121 min), respectively. The median period of cardiopulmonary support (the cumulative duration of CPB and DHCA) was 121 min (range, 20–414 min).
The arch was reconstructed using one of the two established techniques [8]. The original technique involved arch reconstruction without additional patch material (n = 129, 39%). The second technique, used exclusively since April 1999, involved arch reconstruction with a pulmonary homograft patch (n = 204, 61%).
Pulmonary blood flow was established using a systemic to pulmonary artery (systemic–pulmonary) shunt (n = 260, 78%) or a right ventricle to pulmonary artery (RV–PA) conduit (n = 73, 22%) [8]. The systemic–pulmonary shunt generally consisted of a right modified Blalock–Taussig shunt (RMBTS; n = 258, 99.2%). The median diameter of the RMBTS was 3.5 mm (range, 3–5 mm) and the mean shunt diameter indexed to body weight was 1.07 ± 0.18 mm kg–1. Two patients had an anomalous right subclavian artery arising from the descending thoracic aorta. In these cases, the systemic–pulmonary shunt was created using a 3-mm tube conduit between the proximal main pulmonary artery or the aortic arch and the right pulmonary artery. The RV–PA conduit was introduced in March 2002 and involved a tube conduit that passed to the left (n = 17, 5.1%) or right (n = 56, 17%) of the neo-aortic reconstruction. The median diameter of the RV–PA conduit was 5 mm (range, 4–5 mm) and the mean indexed shunt diameter was 1.65 ± 0.30 mm kg–1.
Three epochs were defined based on the techniques used to reconstruct the aortic arch and establish pulmonary blood flow. Between December 1992 and April 1999 (Epoch 1, n = 168), the aortic arch was reconstructed without additional material and pulmonary blood flow was supplied by a systemic–pulmonary shunt. Between April 1999 and March 2002 (Epoch 2, n = 86), the aortic arch was reconstructed with a pulmonary homograft patch and pulmonary blood flow was supplied by a systemic–pulmonary shunt. Finally, between March 2002 and June 2004 (Epoch 3, n = 79), the aortic arch was reconstructed with a pulmonary homograft patch and pulmonary blood flow was established using a RV–PA conduit.
2.1 Data analysis
This was a retrospective study based on the review of hospital records and operation notes. Early mortality (in-patient or 30-day) following the Norwood procedure was the primary outcome measure. This was evaluated with reference to a series of morphologic, preoperative and operative variables (Table 1
). Complete data were available for 332 patients. Follow-up was complete with a median interval of 3.7 years (range, 32 days to 11.3 years).
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2-test, two-sided Fisher exact test or binomial logistic regression. A non-linear relationship has been reported between certain continuous variables, such as age and duration of CPB, and early mortality [10]. In this study, continuous variables were analysed as fractional polynomials of the data. Variables with a univariable probability value, P
0.1, were included in a stepwise logistic regression model. The results of these multivariable analyses have been expressed as logistic coefficients ± standard error for variables with a probability value, P
< 0.05.
Two separate risk models were developed to predict the early outcome following the Norwood procedure for HLHS. A preoperative risk model, Model 1, evaluated the influence of the preoperative variables on early outcome. The techniques used to reconstruct the aortic arch and establish pulmonary blood flow were included in this model, as these factors were primarily influenced by surgical epoch rather than intraoperative findings. An operative risk model, Model 2, assessed the additional influence of intraoperative events on early outcome. Model 2 used all available preoperative and operative data. Model 1 and Model 2 were used to predict the individual patient risk, based on a logistic transformation of the coefficients (Eq. (1)).
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| (1) |
; B
0 is the constant, X
1 to X
n
are independent predictors and B
1 to B
n
represent logistic coefficients for the respective parameters. The performance of each risk model was evaluated using goodness-of-fit analyses. Calibration was assessed using the standardised mortality rate (SMR) and the Hosmer–Lemeshow (H–L) test. Discrimination was assessed using the receiver operating characteristic (ROC) curve.
An estimate of early mortality over time was calculated using an exponentially weighted moving average (EWMA), in which previous observations were systematically down-weighted by 5% per case [11]. The EWMA was originally applied by de Leval et al. [11] to illustrate changes in early mortality during a series of neonatal arterial switch operations for transposition of the great arteries. This technique discounts more remote results and emphasises current experience. With a 5% memory loss, the experience with the 14th previous patient carries about half the weight of the last patient seen. The 95% confidence intervals (CI) for each estimate were calculated using the method (Method 3) described by Newcombe [12].
Changes in early mortality were analysed using two cumulative sum (CUSUM) charts, the cumulative observed minus expected (O–E) plot [13], and the two-sided log-likelihood ratio CUSUM (LLR-CUSUM) [14,15]. The expected outcome was defined as the average 30-day mortality or risk-adjusted 30-day mortality, calculated using Model 1 or Model 2.
Exact estimates for the probabilities of occurrence have been calculated for the cumulative O–E plots, using the method described by Sherlaw-Johnson et al. [16]. The percentile ranges corresponding with these estimates have been plotted in a continuous fashion to provide a guide for the interpretation of these CUSUM charts.
The two-sided LLR-CUSUM consists of two separate one-sided charts, which are plotted jointly [14,15]. The upper chart is designed to determine whether the outcome has deteriorated, which we defined as a doubling in the odds of death. The lower chart is designed to detect an improvement in outcome, which we defined as a halving in the odds of death. Each chart is similar to a sequential probability ratio test (SPRT), which Spiegelhalter et al. [17] used to illustrate how relatively poor performance at Bristol Royal Infirmary might have been identified earlier.
The two-sided LLR-CUSUM is designed to monitor a process sequentially until sufficient evidence of change in outcome has been acquired. This is the point when the chart crosses the upper (b) or lower (a) horizontal boundary threshold. These thresholds were calculated from pre-specified values for notional type I (
*) and type II (ß
*) error rates [14,17]. Separate alert and alarm thresholds were calculated to reflect different degrees of clinical importance. The alert threshold was set at
*
=
ß
*
= 0.05 and the alarm threshold at
*
=
ß
*
= 0.01.
The upper and lower charts are constrained to lie above and below zero in order to make each chart more sensitive to changes in outcome [14,15]. However, strict interpretation of type I and type II error rates is lost. The performance of the LLR-CUSUM is measured in terms of the average run length (ARL) before a conclusion can be drawn when the process is in control or out of control. The in-control and out-of-control ARL are analogous to the type I and type II error rates, respectively [14,15]. The ARL for upper (ARL+) and lower (ARL–) alarm thresholds were estimated using the Markov chain methodology with a multiplier of 300 [14,15]. This multiplier was chosen, using the method illustrated by Grigg et al. [14], to minimise the error associated with the ARL calculation. The in-control ARL for the two-sided LLR-CUSUM (ARLc) was approximated from ARL+ and ARL– [14].
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3. Results |
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TopAbstract1. Introduction2. Materials and methods3. Results4. Discussion5. Study limitations6. ConclusionReferences |
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) during which there was a relative deterioration in early outcome.
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), at which point there were 12.7 excess deaths. This point lay within the upper 1–5% tail of the O–E plot. During the subsequent phase, the observed mortality was less than the expected mortality and the O–E score returned to zero. The decline in observed mortality was more rapid and consistent in Epoch 3.
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). This alarm threshold was first crossed in May 2002 (operation 290) and the chart has remained below this threshold since August 2003 (operation 323). This finding represents a substantial, sustained and real improvement in early outcome during the latter part of the series. The in-control ARLc was 1302. The out-of-control ARL+ and ARL– were 70 and 100, respectively.
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Goodness-of-fit analyses demonstrated that both models were well calibrated. The SMR was 1.00 and 1.03 and the H–L test statistic was 6.03 (P = 0.64) and 4.84 (P = 0.77), respectively. The calibration remained consistent across all deciles. Both models had moderate discrimination characteristics with an area under the ROC curve (95% CI) of 0.71 (0.65–0.77) for Model 1 and 0.75 (0.69–0.81) for Model 2.
3.3 Risk-adjusted data
Risk adjustment broadly accounted for the changes in outcome observed in the unadjusted data. The risk-adjusted cumulative O–E plot for Model 1 is illustrated in Fig. 4
. The risk-adjusted scores were closer to the expected, ranging between –2.4 and 4.9 excess deaths. These scores lay primarily between the upper and lower 25% tails of the plot. Comparable findings were also evident with Model 2.
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4. Discussion |
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TopAbstract1. Introduction2. Materials and methods3. Results4. Discussion5. Study limitations6. ConclusionReferences |
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A number of authors have reported a similar improvement in the outcome following the Norwood procedure over time [2,3,18]. A variety of reasons have been postulated to explain this ‘era effect’, including increasing antenatal diagnosis, improved perioperative management and modifications in surgical technique [2,3]. In our experience, the improvement in early mortality was primarily attributable to the introduction of the RV–PA conduit as the source of pulmonary blood flow.
The Norwood procedure with RV–PA conduit represents one of the most important recent developments in the management of HLHS [19]. The principle advantage of this modification is that it abolishes the diastolic ‘runoff’ from the systemic to the pulmonary circulation, which characterises the systemic–pulmonary shunt. This raises diastolic pressure, increases coronary perfusion pressure and may ensure a more stable balance between the systemic and pulmonary circulations [20]. Pizarro et al. [6] demonstrated that the RV–PA conduit was associated with a better early outcome following the Norwood procedure. In this series, the odds of death halved following the introduction of the RV–PA conduit. Multivariable analyses also demonstrated that the RV–PA conduit was associated with a substantial improvement in early outcome, which was independent of other risk factors.
Several other risk factors for mortality following the Norwood procedure have been reported. These include prematurity, lower weight, older age, anatomic subtype, inadequate preoperative resuscitation or the presence of additional cardiac, extra-cardiac or chromosomal abnormalities [2–4,18,21,22]. In our experience, early outcome was independently associated with the patient's BSA or weight, the size of the ascending aorta and the preoperative right ventricular function.
Low birth weight is a risk factor for death after many cardiac surgical procedures, including the Norwood procedure [2,3,18,21,22]. Weinstein et al. [21] reported that the operative mortality following the Norwood procedure for patients weighing 2.5 kg was 51% compared with an overall early mortality of 26% at their institution. More recent reports suggest that the outlook for these patients may have improved [3], especially following the introduction of the RV–PA conduit [19].
There is contradictory evidence about the influence of morphologic variables on outcome following the Norwood procedure. The size of the ascending aorta has been the subject of considerable debate [2–4,18,22]. In this study, a diminutive ascending aorta was associated with an increased risk of early mortality, which was not influenced by the technique used to reconstruct the neo-aortic arch. These findings probably reflect the continued difficulty in establishing an unobstructed coronary blood flow in patients with a small ascending aorta [18,22].
The preoperative condition of patients has a profound effect on surgical outcome. Abnormal preoperative right ventricular function, in particular, is associated with an increased risk of early mortality [2,3,21]. We were not able to determine the cause of right ventricular dysfunction in this series. It might have reflected inadequate or incomplete preoperative resuscitation or diminished coronary perfusion. Nevertheless, this finding emphasises the importance of aggressive and complete resuscitation before the Norwood procedure is performed.
The duration of DHCA has also been associated with an increased mortality after the Norwood procedure [5,22]. Modified perfusion techniques, such as antegrade cerebral perfusion, might improve the outcome by reducing the duration of ischaemia. However, perfusion technique did not influence early mortality in this series. By contrast, the duration of cardiopulmonary support was an independent risk factor. This is in keeping with previous reports and probably reflects the increased risk associated with longer and more complex procedures [3,10].
Routine monitoring of results has an increasingly important role to play in the provision of safe and effective medical care. In paediatric cardiac surgery performance monitoring might improve the likelihood of survival and reduce the risk of serious complications. However, performance monitoring in paediatric cardiac surgery is intrinsically difficult because of the wide variation in case mix. A variety of methods have been advocated to overcome this problem, including reporting benchmark procedures [23]; stratifying procedures into risk groups [7]; or adjusting for the complexity of the procedure [24]. Fundamental objections have been raised about the validity of each of these methods [25].
This study has established that a limited number of preoperative and known operative variables can reliably predict the early outcome following the Norwood procedure for HLHS. The outcome predicted using the preoperative model varied markedly between individual patients. For example, the expected early mortality for patients with BSA of 0.24 m2, 5 mm ascending aorta, good ventricular function and undergoing a Norwood procedure with RV–PA conduit is 11%. In contrast, the expected early mortality for a patient with BSA of 0.16 m2, 1.5 mm ascending aorta, impaired ventricular function and undergoing a Norwood procedure with systemic–pulmonary shunt is 47%. This is clinically important information, which could help counsel parents about the likely risk of death. Nevertheless, the patient's preoperative risk is modified by intraoperative events [3]. The inclusion of the duration of cardiopulmonary support in the operative risk model improved the ability of the risk model to discriminate between patients who died and survived.
The preoperative and operative risk models were incorporated into a system to monitor the clinical effectiveness of the Norwood procedure for HLHS, which could account for differences in case mix and surgical technique. This monitoring system used separate and complementary CUSUM charts to sequentially monitor the cumulative performance over time. We believe that this risk-adjusted performance-monitoring system could be prospectively applied to identify problems early, evaluate the effectiveness of new procedures or compare practice within a single institution or amongst a number of institutions.
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5. Study limitations |
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TopAbstract1. Introduction2. Materials and methods3. Results4. Discussion5. Study limitations6. ConclusionReferences |
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The risk models described in this study reflect the population from which they were derived. Although internally consistent, they are speculative and have not been validated on an independent population. Internal and external validation studies are required to clarify the predictive abilities of these models. It would be advantageous to omit subjective risk factors, such as impaired right ventricular function, from the model in order to eliminate the potential for gaming. Great care should be exercised when considering the application of this information for patient prognostication because there is a substantial variation in the early mortality risk for each individual patient.
The Norwood procedure for HLHS remains a relatively infrequent procedure. Consequently, a monitoring system could run for a considerable period before a conclusion is reached. Nevertheless, we believe that this caveat should not preclude their application as part of routine clinical monitoring. We would advocate the inclusion of ‘alert’ thresholds that might be used to identify apparent changes in practice that merit more systematic evaluation.
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6. Conclusion |
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TopAbstract1. Introduction2. Materials and methods3. Results4. Discussion5. Study limitations6. ConclusionReferences |
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Acknowledgments |
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Simon McGuirk was supported by a British Heart Foundation Junior Research Fellowship (FS/03/102).
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References |
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TopAbstract1. Introduction2. Materials and methods3. Results4. Discussion5. Study limitations6. ConclusionReferences |
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