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Ann Thorac Surg 2004;78:1696-1702
© 2004 The Society of Thoracic Surgeons

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Original article: cardiovascular

Associated Factors and Trends in Outcomes of Interrupted Aortic Arch

^a Department of Pediatrics, Division of CardiologyToronto, Ontario, Canada
^b Department of Surgery, Division of Cardiothoracic Surgery, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada

Accepted for publication May 14, 2004.

^* Address reprint requests to Dr McCrindle, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario M5G 1X8, Canada
brian.mccrindle{at}sickkids.ca

	Abstract

Top Abstract Introduction Material and Methods Results Comment References

 
BACKGROUND: Interrupted aortic arch (IAA) continues to be associated with important mortality, both before and immediately after repair, with ongoing morbidity during follow-up. We sought to determine trends in presentation, management, outcomes and associated factors.

METHODS: We reviewed all consecutive patients (n = 119) presenting from 1975 to 1999, and data were collected regarding demographics, anatomy, management and outcomes.

RESULTS: Significant trends over time for patients born in three consecutive periods (1975 to 1984, 1985 to 1993, and 1994 to 1999) demonstrated a smaller proportion of patients with presentation with circulatory collapse (65%, 51%, and 25%, respectively), greater use of prostaglandins (72%, 90%, 100%), fewer deaths without IAA repair (49%, 15%, 13%) and greater use of one-stage repair (68%, 75%, 100%). Independent risk factors for death without IAA repair (p < 0.001) included absence of ventricular septal defect, and the presence of noncardiac anomaly, complex cardiac anomaly, episode of acidosis and earlier birth cohort. Overall survival after repair was 50% at age 1 month, 35% at 1 year, and 34% at 5 years. Early and constant-hazard phases were noted, with incremental risk factors for early phase mortality being cyanosis at presentation, presence of truncus arteriosus or aortic stenosis, an episode of circulatory collapse before repair, earlier date of repair, and lower weight at repair. Greatest survival occurred in those patients with uncomplicated IAA who had repair since 1993 (5 year survival, 83%). Freedom from reintervention for arch obstruction was 60% at 5 years.

CONCLUSIONS: While improving, outcomes of IAA remain of concern, especially in patients with associated lesions.

	Introduction

Top Abstract Introduction Material and Methods Results Comment References

 
The management and outcomes of interrupted aortic arch (IAA), a rare and complex form of congenital heart disease, have changed dramatically since the first repair (including direct arch anastomosis) performed by Trusler in 1975 [1]. Improvements in preoperative management, surgical technique and postoperative care have contributed to the overall favorable outcomes in the current era [2–11]. However, IAA continues to be associated with mortality, both before and immediately after repair, and with ongoing morbidity during follow-up [6]. Trends in management, outcomes, and associated factors have been suboptimally defined, in that the focus has been on outcomes only in patients who have had surgical repair. We, therefore, sought to determine the presurgical outcomes, the evolution and impact of preoperative care, surgical technique and associated complex lesions had on outcomes for all (surgical and nonsurgical) patients presenting with IAA to a single institution.

	Material and Methods

Top Abstract Introduction Material and Methods Results Comment References

 
Study Subjects
All patients with the diagnosis of IAA were identified from the databases of both the Divisions of Cardiology and Cardiovascular Surgery, The Hospital for Sick Children, Toronto, Canada. All presenting patients born between 1975 and 1999 were included in the present study. The diagnosis was verified from the medical record by echocardiography, angiography, surgery or autopsy where available. Patients who had their initial IAA repair performed at another institution were excluded from this study.

Measurements
The medical records for all patients were reviewed. When there were incomplete or discrepant data in the cardiology records, the hospital records were also reviewed. Data collected included patient demographics, anatomical diagnoses, clinical status at presentation, echocardiographic and cardiac catheterization assessments and procedures, operations, and follow-up clinical status. If no recent follow-up was performed in our institution or if the initial surgical procedure (non-IAA repair) was performed in another hospital, the responsible physician was contacted and the missing data obtained.

Data Analysis
Data are described as frequencies, medians with ranges and means with standard deviations as appropriate. Where data are missing, the number of nonmissing values is given. Patients were divided into three approximately equal groups based on their date of birth as follows: 1975 to 1984, 1985 to 1993, and 1994 to 1999. The three groups were compared to identify the changing patterns in characteristics, management and outcomes using ² tests, Kruskal-Wallis analysis of variance, and analysis of variance. Factors associated with mortality before IAA repair were sought using ², Student's t tests, Kruskal-Wallis analysis of variance, and multiple logistic regression analysis. Associated factors for time-related death and reintervention after IAA repair were sought by parametric modeling of the hazard function as described by Blackstone and coworkers [12]. All data analyses were performed using SAS Statistical Software Version 7 (SAS Institute, Inc., Cary, NC) using default settings.

	Results

Top Abstract Introduction Material and Methods Results Comment References

 
Demographics
From the patient databases, 126 patients were identified with a diagnosis of IAA and a date of birth from 1975 to 1999. The initial IAA repair had been performed at another institution for 7 patients, who were then excluded from the analysis, leaving 119 patients in the final cohort. Patients were grouped into the three birth cohorts as follows: 1975 to 1984, n = 41; 1985 to 1993, n = 48; and 1994 to 1999 and n = 30. There were 55 males and 64 females.

Presentation
The median age at first presentation to our institution was 3 days (range, birth to 7.2 months), and did not change significantly in consecutive birth cohorts (Table 1). Clinical signs at presentation (n = 117) included congestive heart failure in 43 patients (37%), murmur in 36 (31%), circulatory collapse in 33 (28%), cyanosis in 29 (24%), tachypnea in 14 (12%), weak femoral pulses in 5 (4%), and respiratory distress in 3 patients (3%). Significantly fewer patients in the more recent cohort presented in circulatory collapse, with all patients receiving prostaglandin infusion (Table 1). An echocardiogram was performed in 103 patients (87%) before IAA repair, and a catheterization was performed in 51 patients (43%). In 2 patients neither an echocardiogram nor a cardiac catheterization were performed. In these cases the diagnosis was confirmed by autopsy. The diagnosis was made antenatally by fetal ultrasound in 2 patients.

From all available data, qualitative assessment of the left ventricular outflow structures was used to define those with grade mild or greater stenosis or hypoplasia. Subaortic stenosis was noted in 51 patients (43%), a hypoplastic or stenotic aortic valve annulus in 16 patients (13%), and a hypoplastic left ventricle in 3 patients (3%). The presence of a hypoplastic aorta was noted in 8 patients (7%). In total 60 patients (50%) had an obstructive lesion or hypoplasia within the left heart complex. Other associated cardiac anomalies are listed in (Table 2). No significant changes in the prevalence of the different cardiac anomalies were noted in consecutive birth cohorts (Table 1).

Management and Outcomes
The management and survival for the patients are illustrated in Figure 1.

View larger version (25K): [in this window] [in a new window]   Fig 1. Management and outcomes for all patients. (IAA = interrupted aortic arch; OR = operating room; PA = pulmonary artery; VSD = ventricular septal defect.)

Three patients (all with associated VSD) died intraoperatively during IAA repair. One of these patients had been initially deemed inoperable, but was reviewed again at 3 months of age and underwent attempted complete repair, but did not survive the procedure. Another patient had repair of associated truncus arteriosus the day before attempting IAA repair; the IAA had been missed on preoperative cardiac catheterization and detected on postoperative cardiac catherization the next day. This patient died on the operating room during attempted IAA repair. The final patient died of unknown reasons shortly after sternotomy.

The remaining 14 patients with VSD underwent repair of IAA only as the initial procedure, with 10 having concomitant banding of the main pulmonary artery. There were 4 deaths and 1 patient was lost to follow-up. Subsequent VSD closure was performed at a later procedure in 9 patients, with 1 hospital death and 1 late death.

At the time of IAA repair, the mean duration of cardiopulmonary bypass (n = 66) was 123 ± 45 minutes, with a mean duration of aortic cross-clamping (n = 50) of 74 ± 27 minutes and a mean duration of circulatory arrest (n = 69) of 55 ± 16 minutes. The repair of the aortic arch (n = 85) was achieved with direct anastomosis in 60 patients (68%), an interposition graft in 11 (13%), a direct anastomosis with patch augmentation of the arch in 12 (14%), and a direct anastomosis with a modified Norwood arch augmentation in 2 patients (2%). At the time of repair of the IAA, 14 patients (16%) had truncus arteriosus repair, 16 (18%) had atrial septal defect closure, 11 (13%) had subaortic myectomy or myotomy, and 3 patients (3%) had a Damus-Kaye-Stansel procedure. There was a significant increase in the proportion of patients with concommitant VSD who had initial complete IAA repair with consecutive birth cohorts, as described in Table 1.

Mortality After IAA Repair
Overall, Kaplan Meier estimates of survival after IAA repair were 50% at age 1 month, 35% at 1 year, and 34% at 5 years, and are illustrated in Figure 2 with the estimates from the parametric modeling. There were 46 deaths (52%) before hospital discharge after IAA repair, with 16 of these deaths (35%) occurring either in the operating room or within the first 24 hours after repair. Causes of death included a myocardial infarction before surgery in one patient, a pulmonary thromboembolism after surgery in one patient and intensive primary pulmonary vascular obstructive disease with lung parenchymal damage in one patient. The remainder of the patients who died had circulatory failure with a cardiac arrest and multiple organ failure.

View larger version (18K): [in this window] [in a new window]   Fig 2. Survival after repair of interrupted aortic arch. Circles represent the Kaplan-Meier estimate for survival at each death; solid line represents the parametric determination of continuous point estimates, with the dashed lines enclosing the 70% confidence interval; numbers in parentheses represent the number of patients remaining at risk at that time. (IAA = interrupted aortic arch.)

View larger version (17K): [in this window] [in a new window]   Fig 3. Time-related mortality after repair of IAA stratified by birth cohort. From parametric multivariable model, predicted for a patient without any other incremental risk factors and weight at repair of 3.5 kg, as noted in Table 4. (IAA = interrupted aortic arch.)

View larger version (17K): [in this window] [in a new window]   Fig 4. Management and outcomes for patients with associated TA. (IAA = interrupted aortic arch; TA = truncus arteriosus.)

Subsequent Procedures
Reintervention for residual or recurrent aortic arch obstruction after IAA repair was required in 17 patients, occurring during the initial hospitalization in 2 of these patients. Parametric modeling of time-related arch reintervention showed a single hazard phase characterized by a gradual tapering of risk (Fig 5), with a freedom from reintervention at 5 years after repair of 60%. Initial reintervention was surgical in 6 patients and transcatheter balloon dilation in 11 patients. A second reintervention was required in 4 patients, in 2 of these patients after an unsuccessful balloon dilation. In multivariable modeling, patient and repair characteristics were not significantly related to time-related reintervention for aortic arch obstruction, particularly the type of arch repair.

View larger version (21K): [in this window] [in a new window]   Fig 5. Freedom from time-related intervention for residual or recurrent aortic arch obstruction after repair of interrupted aortic arch. Circles represent the Kaplan-Meier estimate for reintervention at each event; solid line represents the parametric determination of continuous point estimates, with the dashed lines enclosing the 70% confidence interval; numbers in parentheses represent the number of patients remaining at risk at that time. (IAA = interrupted aortic arch.)

	Comment

Top Abstract Introduction Material and Methods Results Comment References

 
Prerepair Management and Outcomes
Complete resuscitation of the neonate with IAA is necessary for optimal surgical management and outcomes [2]. Early in our experience, a significantly higher proportion of infants presented with circulatory collapse, and a significantly lower percentage received prostaglandins. As a result, more patients died before repair, and for patients who received repair for IAA, the incremental risk of death after repair was increased by poor preoperative condition (cyanosis, circulatory collapse). Thus, adequate resuscitation with prostaglandin infusion, avoidance of hyperventilation and pulmonary over-circulation, inotropic myocardial support and aggressive treatment of acidosis of the neonate who presents with IAA shoud be provided to ensure optimal outcomes of subsequent surgical reconstruction. While these preoperative variables predominated in the analysis of our data, it is likely that with greater numbers of subjects additional and specific surgical factors would be identified.

Repair of IAA
Complete one-stage repair of IAA (and associated cardiac anomalies, ie, VSD, truncus arteriosus) through a midline sternotomy is the current standard of care [6], and was instituted in all patients in the most recent birth cohort of this study. Arch reconstruction in the entire cohort was performed by either interposition grafting, direct anastomosis, extended end-to-end anastomosis, patch augmentation of the ascending aorta/aortic arch, and Norwood type reconstruction with a gusset of homograft material. Currently, the favored surgical technique includes extended direct anastomosis, patch augmentation of the ascending aorta or arch, or Norwood type reconstruction for patients with associated truncus arteriosus. All cases in this report were completed using circulatory arrest. Direct cannulation of the innominate artery, or perfusion through a graft anastomosis to the innominate-subclavian arterial junction, allows for avoidance or marked reduction of circulatory arrest during arch reconstruction 13.

Survival After IAA Repair
In the Congenital Heart Surgeons Society report on outcomes of neonates with IAA and VSD (between 1987 and 1992) survival was 73% at 1 month, 65% at 1 year, and 63% at 4 years [6]. Survival after IAA repair in the current series over a greater time period was lower, 50% at 1 month, 35% at 1 year, and 34% at 5 years. In both studies, the risk of death was greatest in the early (less than 1 month) postoperative period. Earlier date of repair was an incremental risk factor for early phase mortality after IAA repair. The relatively lower survival in this series compared to the Congenital Heart Surgeons Society report may be explained by the inclusion of the high risk subset of patients operated on early in the experience (1976 to 1984), and the inclusion of patients with complex anomalies. Since 1993, 5-year survival following repair of uncomplicated IAA is 93%. It should be noted that 50% of the patients in this series had associated obstructive lesions of the left heart complex, compared with only 20% of patients in the Congenital Heart Surgeons Society study [6]. The definitions of subaortic stenosis were somewhat different in the two studies. Our study used all available sources of data and relied on largely qualitative assessments, whereas the Congenital Heart Surgeons Society studies rely on submission of selected documents within the medical record and used available but limited measurement data. Our definition is likely to include many more patients with mild degrees of obstruction.

Impact of Associated Truncus Arteriosus
The presence of associated truncus arteriosus was an independent risk factor for early phase mortality, and this finding is not corroborated by other reports. The association between the two lesions with respect to adverse outcomes was demonstrated by Hanley and coworkers [14] in a report on a cohort of patients with truncus arteriosus as the primary diagnosis. A recent study [15] from the same institution suggests that, with increased experience, the presence of IAA is not currently a predictor of mortality following repair of truncus arteriosus with associated IAA. In a recent report from our institution [16] of outcomes following repair of truncus arteriosus, IAA was not a significant predictor of postoperative mortality. This suggests that it is the diagnosis of truncus arteriosus that primarily acts as the driving force for mortality following repair of hearts in which both lesions are present.

Impact of LV Outflow Obstructive Lesions
Hypoplasia or stenosis of the aortic valve or its annulus [17], present in 13% of patients in this series, acted as the only other (in addition to truncus arteriosus) morphologic feature predictive of adverse outcome. Subaortic stenosis was present in 43% of patients undergoing repair in the current series, but was not an independent risk factor for early phase mortality. In a recent study from the Royal Children's Hospital in Melbourne [9], actuarial survival following repair of IAA was not different between patients with or without left ventricular outflow tract obstruction.

In the Congenital Heart Surgeons Society study, subaortic narrowing was an independent predictor of postrepair mortality [6]. One-stage repair plus augmentation of the ascending aorta or aortic arch afforded best survival outcomes for patients with IAA, VSD, and left heart obstructions. Patients who had the procedural addition of subaortic myectomy or myotomy, in fact, had worse survival outcomes (50% at 5 years). Bove and colleagues [4] and DeLeon and associates [3] have observed lower mortality rates following repair of IAA, VSD, and subaortic stenosis in infants where infundibular/conal muscle excision was performed. However, the morbidity of myotomy/myectomy was significant, and included injury to aortic valve and complete heart block. The inference from the Congenital Heart Surgeons Society data are that repair of IAA and VSD with aortic arch/ascending aorta augmentation in patients who have associated subaortic stenosis is sufficient to allow for optimal outcome in terms of mortality and reoperation.

Luciani and associates [8] add that the perimembranous VSD with a posteriorly malaligned infundibular septum should be closed with a downsized patch sewn to the left ventricular side of the infundibular septum. Such maneuvers should deflect the conal septum anteriorly [18], prevent patch bulging into the left ventricular outflow tract and optimize laminar flow in the subaortic region, theoretically reducing risk of hypertrophy, and persistent or recurrent subaortic stenosis.

We did not observe an obvious relationship between preoperative subaortic stenosis and need for later reoperation against subaortic stenosis or the development of a significant gradient across the left ventricular outflow tract. Likewise, Fulton and colleagues [9] suggest that the presence of left ventricular outflow tract obstruction before repair does not predict need for future reoperations. In the Congenital Heart Surgeons Society study [6], complete repair of IAA and VSD and associated arch augmentation allowed for a relatively low risk of later reintervention for left heart obstructive lesions.

Residual or Recurrent Aortic Arch Obstruction
Reoperation for recurrent or persistent aortic arch obstruction was performed during follow-up in 31% of patients in the current series. Although most aortic arch reoperations were performed in patients in the earlier birth cohort, multivariable analysis did not identify predictors of reoperation for recurrent or persistent arch obstruction, including the type of arch repair. However, arch reconstruction should include augmentation of the ascending aorta and aortic arch or extended primary anastomosis. Twenty (17%) of the 116 patients receiving one-stage repair in the Congenital Heart Surgeons Society study required reintervention for arch obstruction. The risk is reduced (about 6%) if arch augmentation is incorporated into the initial complete repair. In the majority of patients who suffer recurrent obstruction of the aortic arch, percutaneous catheter-based balloon dilatation is effective.

Study Limitations
The results of this study are limited by the retrospective nature of the data collection, and the reliance on the medical record over a relatively long period of time. Also, follow-up was incomplete for some patients. Uniform definitions of risk factors and outcomes, such as subaortic stenosis, were not available or could not be applied to our data.

Conclusions
Although there are significant trends towards improving morbidity and mortality related to IAA, patients with associated truncus arteriosus continue to have suboptimal outcomes. While late intervention for subaortic stenosis was not frequent in our study, this remains controversial. Residual or recurrent aortic arch obstruction is common, and requires careful surveillance.

	References

Top Abstract Introduction Material and Methods Results Comment 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 Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Anthony Azakie William G. Williams Brian W. McCrindle Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Oosterhof, T. Articles by McCrindle, B. W. Search for Related Content PubMed PubMed Citation Articles by Oosterhof, T. Articles by McCrindle, B. W. Related Collections Congenital - cyanotic