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J Thorac Cardiovasc Surg 2009;137:347-354
© 2009 The American Association for Thoracic Surgery

Congenital Heart Disease

Improvement in long-term survival after hospital discharge but not in freedom from reoperation after the change from atrial to arterial switch for transposition of the great arteries

^a Department of Cardiovascular Surgery, German Heart Center Munich, Technical University Munich, Munich, Germany
^b Department of Pediatric Cardiology and Congenital Heart Disease, German Heart Center Munich, Technical University Munich, Munich, Germany
^c Institute of Medical Statistics and Epidemiology, Technical University Munich, Munich, Germany

Received for publication April 24, 2008; revisions received July 22, 2008; accepted for publication September 12, 2008.

^_* Address for reprints: Jürgen Hörer, MD, Lazarettstrasse 36, D-80636 Munich, Germany. (Email: hoerer{at}dhm.mhn.de).

	Abstract

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Objective: To compare survival, freedom from reoperation, and functional status between atrial switch and arterial switch operations for transposition of the great arteries.

Methods: Data from 88, 329, and 512 patients who underwent Mustard, Senning, and arterial switch operations between 1974 and 2006 were analyzed.

Results: In-hospital mortalities were 8.0% for Mustard, 4.6% for Senning, and 6.4% for arterial switch. Presence of ventricular septal defect (hazard ratio 3.3, P < .001) was the only risk factor for in-hospital mortality in multivariate analysis. Follow-up for Mustard was 22.6 ± 8.1 years, for Senning was 18.2 ± 5.7 years, and for arterial switch was 9.5 ± 5.7 years. Highest survival at 20 years was after arterial switch (96.6% ± 1.3%), followed by Senning (92.6% ± 1.5%) and Mustard (82.4% ± 4.3%). Transposition with ventricular septal defect (hazard ratio 3.1, P < .001), transposition with ventricular septal defect and left ventricular outflow tract obstruction (hazard ratio 3.0, P = .029), and Mustard operation (hazard ratio 2.1, P = .011) emerged as risk factors for late death, with arterial switch a protective factor (hazard ratio 0.3, P = .010). Highest freedom from reoperation at 20 years was after Senning (88.7% ± 1.9%), followed by arterial switch (75.0% ± 6.4%) and Mustard (70.6% ± 5.4%). Presence of complex transposition (hazard ratio 2.1, P < .001), previous palliative operation (hazard ratio 1.8, P = .016), surgery between 1985 and 1995 (hazard ratio 2.6, P = .002), surgery after 1995 (hazard ratio 3.5, P < .001), and Mustard operation (hazard ratio 3.3, P < .001) emerged as risk factors for reoperation.

Conclusion: Change from atrial to arterial switch led to improved long-term survival after hospital discharge but not to lower incidence of reoperation. Survival and freedom from reoperation are determined by morphology.

	Introduction

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Transposition of the great arteries (TGA) is the most common cyanotic heart defect in infancy and accounts for almost 10% of all cases of congenital heart disease.¹ Successful therapy for TGA was first possible with the introduction of the surgical atrial septectomy in 1950.² This procedure, which created an atrial septal defect and thus allowed intra-atrial mixing of the pulmonary and systemic circulations, was the first to permit survival of neonates with TGA and intact ventricular septum (IVS).

In the mid 1950s, early attempts at arterial switch operations failed. This failure was mainly due to difficulties with coronary transfer in small children.^3-5 Therefore patients with TGA and IVS or with TGA and ventricular septal defect (VSD) were treated by means of an atrial switch operation, such as the Senning operation⁶ (since 1957) or the Mustard operation⁷ (since 1963). For more than 2 decades, these atrial switch operations were the treatment of choice for patients with TGA, with or without VSD.

In 1975, Jatene and colleagues⁸ reported the first successful arterial switch operation. Despite the initially higher early mortality of the arterial switch relative to atrial switch operations,⁹ the move in surgical strategy from the atrial switch toward the arterial switch operation was mainly completed by the early 1990s. Concerns about the function of the systemic right ventricle in the long term after any atrial baffle procedure spurred this change in operative strategy. In addition, an increasing number of complications of those newly constructed venous pathways was observed.¹⁰

Because patients who have undergone arterial switch operations have now reached follow-up intervals as long as 30 years, it now seems reasonable to compare the long-term outcomes of patients after different types of repair for TGA. We therefore sought to determine the outcomes in terms of early and late survivals and freedom from reoperation for 929 patients treated for TGA at a single center.

	Materials and Methods

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Patients
All patients who had undergone correction of TGA by means of an atrial or arterial switch operation between 1974 and 2006 were included in a follow-up study. The study included 929 patients (Table 1 ). The Mustard operation was performed in 88 cases from 1974 until 1982, the Senning operation was performed in 329 cases from 1977 until 1993 (except for 3 patients), and the arterial switch operation was performed from 1983 onward (Figure 1 ). The surgical techniques are described elsewhere.^11,12

View larger version (16K): [in this window] [in a new window]   Figure 1. Number of operations stratified by type of operation and year between 1974 and 2006.

Data Collection
All data were collected from medical records and from follow-up examinations at the outpatient facilities. Records were retrospectively reviewed for demographic, morphologic, clinical, echocardiographic, and hemodynamic details. The congenital heart lesion was classified as simple TGA if the interventricular septum was intact and as TGA with VSD if there was a VSD. In cases of left ventricular outflow tract obstruction (LVOTO), the classifications were TGA with LVOTO versus TGA with VSD and LVOTO. Patients with a small, restrictive VSD that was not closed were also classified as having TGA with VSD.

Follow-up data were obtained by a written questionnaire or by telephone. The functional status was determined according to the New York Heart Association (NYHA) functional class. Patients or their parents were asked about the occurrence of cardiovascular events, such as arrhythmia, stroke, thrombosis, and reoperation, and also about previous cardiac catheterization, pacemaker implantation, hospital admissions, concomitant diseases, and medication. For patients who had died, their relatives and their general physicians were contacted to determine the cause of death.

Follow-up was conducted between 2003 and 2007. The numbers of patients who could not be contacted within this interval were 6 for the Mustard operation, 15 for the Senning operation, and 34 for the arterial switch operation. Follow-up of survivors of the initial hospitalization was 92.6% complete for the Mustard group, 95.2% for the Senning group, and 92.9% for the arterial switch group. Mean follow-up times were 22.6 ± 8.1 years for the Mustard, 18.2 ± 5.7 years for the Senning, and 9.5 ± 5.7 years for the arterial switch. Mean follow-up times of patients unavailable for final follow-up were 16.4 ± 10.5 years for the Mustard, 10.2 ± 7.8 years for the Senning, and 6.9 ± 6.3 years for the arterial switch. Mean follow-up time for the whole study population was 13.6 ± 7.8 years (12,417 patient-years).

During long-term follow-up, patients underwent routine examinations, including echocardiography and electrocardiography. Data from echocardiographic examinations from the outpatient clinics were evaluated according to written notes by one of the authors (JH). Systemic ventricular function was graded as normal or as mildly, moderately, or severely impaired. Insufficiency of the tricuspid valve for patients after an atrial switch operation and of the neoaortic valve for patients after an arterial switch were graded as none, mild, moderate, or severe. Twelve-lead resting and 24-hour ambulatory electrocardiography were used for evaluation of cardiac rhythm.

Statistical Analysis
Descriptive data for continuous variables are presented as mean ± SD, and categoric variables are presented as relative frequencies. The Fisher exact test was performed to detect significant differences between groups. For comparison of continuous variables between two groups, the t test was used (2-tailed tests were used for all analyses). The probability of freedom from events was estimated according to the Kaplan–Meier method. The time of the Senning, Mustard, or arterial switch operation was designated as time zero. Freedom-from-event curves were compared with the log-rank test. Hazard ratios were estimated according to the Cox proportional model. Multivariate analyses were performed by means of a logistic regression model for the end point of in-hospital mortality and by means of a Cox proportional hazard model for the end points of late mortality and reoperation. Variables with P values less than .1 in univariate analysis were entered into the multivariate models. Patients were assigned to 3 groups according to when surgery was performed (<1985, 1985–1995, and >1995). Analyses were performed with SPSS 16.0 for Windows (SPSS Inc, Chicago, Ill).

	Results

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Perioperative Data
Patients who underwent the atrial type of repair significantly more often had LVOTO (P < .001) and significantly less often had VSD (P = .038) than did patients who underwent the arterial type of repair. Patients who underwent the atrial type of repair significantly more often underwent balloon atrial septostomy (P < .001) than did patients who underwent the arterial type of repair, and they were significantly older at the time of correction (P < .001). In-hospital mortalities were 8.0% for the Mustard operation, 4.6% for the Senning operation, and 6.4% for the arterial switch operation. Among morphology, previous operations, age, and type of correction, presence of a VSD (hazard ratio 3.3, P < .001) was the only risk factor for in-hospital mortality in multivariate analysis (Table 2 ). Between 1983 and 1993, there was a change in surgical strategy from the Senning operation (n = 202) to the arterial switch operation (n = 168). In that decade, significantly more patients who had TGA with VSD underwent an arterial switch operation (P < .001). In-hospital mortality was approximately twice as high after the arterial switch operation (4.8%) as after the Senning operation (2.5%, P = .264).

View larger version (16K): [in this window] [in a new window]   Figure 2. Estimated survival among survivors of initial hospitalization after correction stratified by type of operation.

Late Reoperations
Reoperations after hospital discharge were required in 30 Mustard, 33 Senning, and 52 arterial switch patients. Frequently, several procedures had to be performed during a single reoperative event, resulting in 67, 66, and 91 procedures performed in 37, 38, and 69 reoperations in the Mustard, Senning, and arterial switch groups, respectively (Table 4 ). The procedures most frequently performed in both atrial repair groups were relief of baffle stenosis, closure of baffle leaks, and procedures for systemic right ventricular dysfunction (arterial switch and Senning takedown, banding without conversion, tricuspid valve repair, cardiac transplantation). The most frequent procedures performed in the arterial switch group were relief of stenosis in the right ventricular outflow tract (including enlargement of pulmonary artery stenosis), relief of stenosis in the left ventricular outflow tract, and neoaortic valve replacement. The highest freedom from reoperation at 20 years was observed after the Senning operation (88.7% ± 1.9%), followed by the arterial switch operation (75.0% ± 6.4%) and the Mustard operation (70.6% ± 5.4%) (Figure 3 ). Among morphology, previous operations, timing of correction, age, and type of correction, presence of a complex transposition (hazard ratio 2.1, P < .001), previous palliative operation (hazard ratio 1.8, P = .016), surgery between 1985 and 1995 (hazard ratio 2.6, P = .002), surgery after 1995 (hazard ratio 3.5, P < .001), and the Mustard operation (hazard ratio 3.3, P < .001) emerged as risk factors for reoperation (Table 5 ).

View larger version (18K): [in this window] [in a new window]   Figure 3. Estimated freedom from reoperation among survivors of initial hospitalization after correction stratified by type of operation.

Rhythm disturbances
Pacemaker implantation was required after discharge from the hospital in 12, 22, and 12 patients in the Mustard, Senning, and arterial switch groups, respectively. Freedoms from pacemaker implantation at 20 years were 89.3% ± 3.6% for the Mustard group, 94.4% ± 1.4% for the Senning group, and 92.0% ± 4.1% for the arterial switch group. Differences between groups were not statistically significant. Presence of a VSD at the time of repair emerged as a risk factor for shorter time to pacemaker implantation in multivariate analysis (hazard ratio 2.4, 95% confidence interval 1.2–4.6, P = .012).

Functional status
Information concerning the functional status at the time of final follow-up could be obtained for 789 patients (95.9% of long-term survivors). Accordingly, 47.9% of the patients in the Senning group could be assigned to NYHA functional class I. The same percentage of patients (47.9%) could be assigned to NYHA functional class II, with 4.1% assigned to NYHA functional class III. In the Mustard group, 44.6%, 48.2%, and 7.1% of the patients were assigned to NYHA functional classes I, II, and III, respectively. Almost all patients in the arterial switch group could be assigned to NYHA functional class I (98.3%), with only 1.7% in NYHA functional class II.

	Discussion

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From the historical point of view, the atrial switch operation preceded the arterial switch operation. Despite the age-related incidence of baffle stenosis,¹³ however, the main disadvantage of the atrial switch operation is the incorporation of the right ventricle into the systemic circulation. With time, increasing numbers of patients with diminished exercise tolerance¹⁴ and impaired systemic right ventricular function¹⁵ have been reported. The arterial switch operation was introduced because of its potential advantage in incorporating the left ventricle into the systemic circulation. Although the first successful arterial switch operation was performed as early as 1975 by Jatene and colleagues,¹⁶ it was not until the 1990s that the transition from the atrial switch operation to the arterial switch took place. The main reason for this long transition was the concern with abandoning a well-established procedure with an early mortality below 5%^17-19 in favor of a demanding procedure with unknown early mortality.

In fact, during the transition from the atrial to the arterial repair, early mortality of the arterial switch operation was reported to be higher than that of the atrial switch operation. In a series of 829 patients treated for TGA between 1985 and 1989, Williams and coworkers⁹ reported an early mortality of 14.9% after the arterial switch operation, compared with 3.6% after the Mustard operation. In our study population, early mortalities during the transition from the Senning to the arterial switch were 2.5% and 4.8%, respectively. This difference, however, was not statistically significant. In addition, in our study population, type of repair had no impact in multivariate analysis on early mortality calculated for the whole study period. Presence of a VSD was the only risk factor for in-hospital mortality in multivariate analysis. In our analysis early mortality of patients undergoing repair of TGA was determined by the presence of a VSD, not by the type of correction or by the surgical period. The higher early mortality among patients after arterial switch operations during the transitional era thus may be explained by the fact that significantly more patients who underwent arterial switch operations had TGA with VSD.

It is of major interest whether the arterial switch operation has fulfilled our expectations with regard to improvements in long-term functional outcome and mortality. Losay and associates²⁰ reported a survival of 88% at 15 years after an arterial switch operation in a group of 1095 survivors of initial hospitalization, with no late deaths beyond 5 years after initial repair. Other authors have also reported low incidences of late death after the arterial switch operation.^9,21 In contrast, survival after atrial switch operations has been reported to be as low as 77% at 15 years,²² although reports range as high as 94% at 15 years.^9,10,22,23

Comparisons between the atrial and the arterial types of repair with regard to mortality in the long-term are biased by the different follow-up intervals for the 2 groups of patients. To overcome this error, Williams and coworkers⁹ performed a study that included only patients operated on during the transition from the atrial switch to the arterial switch operation (between 1985 and 1989). The methodologic problem of that study, however, consisted in comparing the well-established surgical technique of atrial switch with the newly introduced technique of arterial switch. The effect was the previously mentioned difference in early mortality (14.9% after arterial switch vs 3.6% after atrial switch). We therefore included all patients, irrespective of the time of initial repair. To reveal the potential effect of the time of repair, the surgical period (<1985, 1985–1995, and >1995) was included as a covariable in the multivariate model. The surgical period was found to have no statistical influence on late mortality.

Because of the higher early mortality with the arterial repair relative to the atrial repair and the higher late mortality with the atrial repair relative to the arterial repair, there is a crossover of the survival curves in favor of the arterial repair. In the study reported by Williams and coworkers,⁹ this crossover was observed at 17 years after the initial repair. In our study population, this crossover took place within the first year after repair. This earlier crossover was due to the lower early mortality of the arterial switch operation in our cohort than the cohort studied by Williams and coworkers.⁹ Thus with regard to overall survival, there was a benefit of the arterial switch operation as soon as 1 year after initial repair. This finding was confirmed by multivariate testing in our study population. The type of repair had no statistically significant influence on early mortality, whereas the hazard for late death among patients after an arterial repair was less than a third that among patients after an atrial repair. In this context, it is noteworthy that preoperative mortality among neonates scheduled for an atrial repair was reported to be higher than that among patients scheduled for an arterial repair (4.7% vs 2.5%)⁹ as a result of the longer time of palliation and older age of the children at the time of atrial switch repair. Thus the benefit of the arterial switch with respect to overall mortality from birth may even be more evident.

According to many previously published series,^20,22-24 survival in the long term was found to be determined by the complexity of the heart defect. Patients who had TGA with VSD, or TGA with VSD and LVOTO had a 3-fold greater risk for late death than did patients who had TGA with IVS. Finally, survival in our study population was higher after the Senning operation than after the Mustard operation. Interestingly, this finding is in line with other reports from Europe,²² whereas the experiences in North America seem to be contrary.²⁴

Freedom from reoperation has been reported to vary between 60% and 90% 20 years after an atrial switch operation.^9,10,22 The main indications for reoperation were stenoses and leaks of the venous pathways, which seem to be more frequent after the Mustard operation than after the Senning operation.^10,22 As expected, with the transition from the atrial repair to the arterial repair, the main location of complications requiring reoperation shifted from the inflow to the outflow of the ventricles. Stenoses of the pulmonary arteries therefore accounted for most of the more than 100 reoperations necessary in the large study population reported on by Losay and associates.²⁰ Accordingly, freedom from reoperation at 15 years was 82% in their study population.

These findings could be confirmed in our study. The main indications for reoperation after the arterial switch operation were stenoses of the right ventricular outflow tract and the pulmonary arteries, which were corrected in 46% of the 52 patients who required reoperation. The main indications for reoperation after the atrial switch operations were complications of the venous pathway, which were corrected in 63% of the 63 patients who required reoperation. In our study population, freedoms from reoperation at 20 years were 75.0% ± 6.4% after arterial switch operations and 84.5% ± 2.0% after atrial switch operations. This difference, however, was not statistically significant, although freedom from reoperation after the Senning operation was significantly higher than that after the arterial switch operation. In our experience, there was no improvement with regard to freedom from reoperation after the introduction of the arterial switch operation.

Functional status appeared to be superior after the arterial switch relative to the atrial switch operations. According to different studies, 66% to 93% of the patients after atrial switch are in NYHA functional class I,^10,23,25 versus almost all patients after arterial switch,²⁶ a finding confirmed in our investigation (98% in NYHA functional class I after arterial switch). These subjective findings in functional status were reflected in the objective measurements of the cardiac function. At echocardiographic examination during follow-up, only 0.4% of the patients after arterial switch showed at least moderately impaired left ventricular function, whereas 9.1% of the patients after atrial switch showed at least moderately impaired right ventricular function. The significant differences in follow-up time between the atrial and the arterial types of repair, however, must be kept in mind.

Study Limitations
This was a retrospective follow-up study covering a long period of patient inclusion. Changes in preoperative, operative, and postoperative management may have affected the outcome parameters in ways not covered by our analysis. The comparability of the echocardiographic findings and NYHA functional status at the time of final follow-up between the repair technique groups is also limited by the differences in follow-up time.

	Conclusions

Top Abstract Introduction Materials and Methods Results Discussion Conclusions References

 
The change from the atrial to the arterial switch led to improved long-term survival and improved functional status but not to lower incidence of reoperation. Both survival and freedom from reoperation are determined by the presence of a VSD at the time of correction.

	Footnotes

 
Read at the Eighty-eighth Annual Meeting of The American Association for Thoracic Surgery, San Diego, Calif, May 10–14, 2008.

	References

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Christian Schreiber Julie Cleuziou Zsolt Prodan Klaus Holper Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hörer, J. Articles by Lange, R. Search for Related Content PubMed Articles by Hörer, J. Articles by Lange, R. Related Collections Congenital - cyanotic Great vessels