Major Aortopulmonary Collateral Arteries With Anatomy Other Than Pulmonary Atresia/Ventricular Septal Defect

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1 Major Aortopulmonary Collateral Arteries With Anatomy Other Than Pulmonary Atresia/Ventricular Septal Defect William L. Patrick, BS,* Richard D. Mainwaring, MD, Olaf Reinhartz, MD, Rajesh Punn, MD, Theresa Tacy, MD, and Frank L. Hanley, MD Divisions of Pediatric Cardiac Surgery and Pediatric Cardiology, Lucile Packard Children s Hospital/Stanford University, Stanford, California Background. Major aortopulmonary collateral arteries (MAPCAs) are frequently found in association with pulmonary atresia with ventricular septal defect (PA/ VSD). However, some patients with MAPCAs do not have PA/VSD but have a variety of other atypical anatomic diagnoses. Methods. This was a retrospective review of patients with MAPCAs and atypical anatomy. The 50 patients with MAPCAs could be divided into two subgroups: (1) single ventricle anatomy (n [ 33) and (2) two ventricle anatomy (n [ 17). Results. The 33 patients with MAPCAs and single ventricle included 15 with unbalanced complete atrioventricular canal (CAVC), 6 with pulmonary atresia-intact ventricular septum, and 12 with other forms of single ventricle. The initial cardiac operation included unifocalization/shunt in 24 patients and creation of aortopulmonary window or central shunt in 9 patients. There were seven operative and eight late deaths. Sixteen patients have had a bidirectional Glenn procedure and 6 had a Fontan procedure. The 17 patients with MAPCAs and two ventricles included 5 with CAVC, 4 with corrected transposition, 3 with double outlet right ventricle, 3 with scimitar syndrome, and 2 with complex D-transposition. The initial cardiac operation included single-stage complete repair in 5 patients, unifocalization/shunt in 10 patients, and aortopulmonary window in 2 patients. There were two operative and two late deaths. Thirteen patients have achieved complete repair status. Conclusions. The data demonstrate the wide diversity of anatomy seen in patients with MAPCAs when evaluating diagnoses other than PA/VSD. Two-thirds of the patients had single ventricle and was associated with a relatively high mortality. (Ann Thorac Surg 2017;104:907 16) Ó 2017 by The Society of Thoracic Surgeons Major aortopulmonary collateral arteries (MAP- CAs) are a relatively rare component of congenital heart defects that are embryologically linked with pulmonary valve atresia or near atresia [1, 2]. Most patients with MAPCAs have the intracardiac anatomy of pulmonary atresia with ventricular septal defect (PA/ VSD) [3, 4]. As a consequence, most of the existing literature has focused on the surgical techniques for repair of PA/VSD/MAPCAs and the attendant results [5, 6]. There is a smaller subset of patients with MAPCAs that do not have PA/VSD but instead have a variety of other atypical anatomic diagnoses [7, 8]. It is not surprising that there is a limited amount of literature Accepted for publication Feb 7, *Mr Patrick is the recipient of the 2016 Southern Thoracic Surgical Association George Daicoff President s Award. Presented at the Sixty-third Annual Meeting of the Southern Thoracic Surgical Association, Naples, FL, Nov 9 12, Address correspondence to Dr Mainwaring, Stanford University School of Medicine, 300 Pasteur Dr, Falk CVRC, Stanford, CA 94305; mainwaring@stanford.edu. on this subject, because atypical anatomy represents a small fraction of an already rare condition of MAPCAs. ThefewreportsonpatientswithMAPCAsandatypical anatomy would suggest that they may have a wide array of intracardiac anatomy, including many patients with complex single ventricle [9 13] or total anomalous pulmonary venous connection (TAPVC) [14]. These prior reports have focused on specific subsets of patients with atypical anatomy and MAPCAs; therefore, this subset is certainly not representative of the group as a whole. The previous reports do highlight the complex nature of the intracardiac anatomy of the atypical patients and the unique challenge of addressing this surgically in addition to the management of the MAPCAs. Our surgical group has acquired an extensive experience in the management of patients with the intracardiac anatomy of PA/VSD in association with MAPCAs [15, 16]. Given the lack of a comprehensive analysis of patients with atypical anatomy and MAPCAs, the purpose of the present study was to evaluate the surgical experience with MAPCAs in patients with anatomy other than PA/VSD. Ó 2017 by The Society of Thoracic Surgeons /$36.00 Published by Elsevier Inc.

2 908 PATRICK ET AL Ann Thorac Surg MAPCAS WITH ATYPICAL ANATOMY 2017;104: Material and Methods This study was approved by the institutional review board at Stanford University. Patients included in the study underwent surgical treatment for MAPCAs in association with atypical intracardiac anatomy (ie, something other than PA/VSD). There were a total of 50 patients who fulfilled these criteria for inclusion over the 20-year time period from 1996 to Forty-seven of the 50 patients in this study had pulmonary atresia with MAPCA-dependent pulmonary blood flow. Forty-five patients had MAPCAs supplying both lungs, whereas 2 patients had a ductus arteriosus to one lung with MAPCAs supplying the contralateral lung. The remaining 3 patients included in this study did not have pulmonary atresia but had a single MAPCA to the lower lobe as part of scimitar syndrome. For the 45 patients with MAPCAs supplying both lungs, there was a mean of total MAPCAs, divided into MAPCAs to the right lung (with a range of 1 to 5) and MAPCAs to the left lung (with a range of 1 to 4). Thirty-six of the 45 patients were deemed to have primarily single supply MAPCAs, whereas 9 patients had primarily dual supply MAPCAs. The 2 patients who had a ductus to the left lung and MAPCAs to the right lung had one and three MAPCAs on the right side. Thirty-six of the 47 patients (77%) with MAPCAdependent pulmonary circulation had native, intrapericardial pulmonary arteries identified by catheterization and confirmed at operation. This included (by definition) all 9 patients with dual-supply MAPCAs and 27 of 36 patients with single-supply MAPCAs. Eleven of the 47 patients (23%) had a complete absence of native, intrapericardial pulmonary arteries, including 9 patients with single-supply MAPCAs and both patients with a ductus to one lung and MAPCAs to the contralateral lung. Thirty-three of the 50 patients (66%) had single ventricle anatomy. The anatomic diagnoses of these 33 patients are shown in Table 1. Fifteen of the 33 patients with single ventricle had heterotaxy with an unbalanced complete atrioventricular canal (CAVC). The remaining 18 patients with single ventricle had a variety of other anatomic diagnoses. An example of a patient with single ventricle and MAPCAs is shown in Figures 1 and 2. Table 1. Diagnoses of the 33 Patients With MAPCAs and Single-Ventricle Anatomy Diagnosis Number Heterotaxy, unbalanced atrioventricular canal, TAPVC 8 Heterotaxy, unbalanced atrioventricular canal 7 Pulmonary atresia-intact ventricular septum 6 Tricuspid atresia 4 Complex transposition 4 Single left ventricle 3 Double outlet right ventricle 1 MAPCA ¼ major aortopulmonary collateral artery; anomalous pulmonary venous connection. TAPVC ¼ total Fig 1. Echocardiogram of a patient with tricuspid atresia, pulmonary atresia, transposition, and major aortopulmonary collateral arteries (MAPCAs). The right atrium (RA), left atrium (LA), right ventricle (RV), left ventricle (LV), and atretic tricuspid valve (TV) are labeled. (bpm ¼ beats/min; VSD ¼ ventricular septal defect.) Twelve of the 33 single ventricle patients (37%) had total anomalous pulmonary venous connection (TAPVC). The anatomy of TAPVC was supracardiac in 5 patients, infradiaphragmatic in 2 patients, intracardiac in 4 patients, and mixed in 1 patient. Eight of the 12 patients presented with or subsequently had signs of pulmonary vein obstruction. For these 8 patients, the timing of operation was frequently dictated by the degree of pulmonary venous obstruction. Two patients (both with infradiaphragmatic TAPVC) had obstructed pulmonary veins at birth and required emergency operation within hours of birth. Six patients initially did not have evidence of pulmonary venous obstruction at birth but had clinical signs of obstruction between 2 weeks and 2.5 months of age. Four patients with TAPVC never did have pulmonary venous obstruction and underwent elective operation at 3, 3, and 4 months, and 8yearsofage. Seventeen of the 50 patients (34%) in this study had two ventricle intracardiac anatomy. The diagnoses of these 17 patients are shown in Table 2. An example of a patient with MAPCAs and two ventricle anatomy is shown in Figures 3 and 4. Four of the 17 two ventricle patients were born with TAPVC. One of these 4 patients required surgical treatment at 10 days of age because of increasing obstruction of the pulmonary venous drainage. The other 3 patients underwent operation at 8, 10, and 12 weeks of age. There were 28 males and 22 females in the study. Two patients had Alagille syndrome, both of whom were in the single ventricle subgroup. The median age at the time of the first operation was 3.0 months, with a range of 3 hours to 8.5 years. The median weight at the time of operation was 5.1 kg (range, 1.1 to 41.8 kg). Results are reported as medians with ranges and means standard errors where appropriate. Follow-up evaluation was performed through a combination of the

3 Ann Thorac Surg PATRICK ET AL 2017;104: MAPCAS WITH ATYPICAL ANATOMY 909 Fig 2. (A,B,C,D) Angiogram demonstrating the four major aortopulmonary collateral arteries (MAPCAs) in the above patient with tricuspid atresia. There were three MAPCAs to the right and one to the left. This patient underwent complete unifocalization of the four MAPCAs and placement of a central shunt at 3 months of age. available medical records, contacting referring physicians offices, and searching the Social Security death registry. There were seven operative deaths (21%) in the 33 patients with single ventricle. Four patients sustained sudden cardiac-related events, were placed on extracorporeal membrane oxygenation (ECMO), but did not Results For the 33 patients with MAPCAs and single ventricle, the initial cardiac procedure was a complete unifocalization and placement of a central shunt in 24 patients and creation of aortopulmonary window or placement of a central shunt in 9 patients. The mean number of MAPCAs was in the 24 patients who underwent unifocalization. Table 2. Diagnoses of the 17 Patients With MAPCAs and Two-Ventricle Anatomy Diagnosis Number Complete atrioventricular canal 5 Corrected transposition of the great arteries 4 Double outlet right ventricle 3 Scimitar syndrome 3 Complex D-transposition 2 MAPCA ¼ major aortopulmonary collateral artery. Fig 3. Echocardiogram of a patient with congenitally corrected transposition of the great arteries and major aortopulmonary collateral arteries (MAPCAs). The left ventricle (LV) is to the right and right ventricle (RV) is to the left. (bpm ¼ beats/min; VSD ¼ ventricular septal defect.)

4 910 PATRICK ET AL Ann Thorac Surg MAPCAS WITH ATYPICAL ANATOMY 2017;104: Fig 4. (A,B,C,D) Angiogram of the patient with corrected transposition. There are four major aortopulmonary collateral arteries (MAPCAs), with two to the right and two to the left. This patient underwent complete unifocalization of the four MAPCAs and a concomitant double switch operation. survive. Two operative deaths occurred in patients with heterotaxy, unbalanced CAVC, and obstructed TAPVC (one with a birth weight of 1.1 kg). The final operative death occurred 1 day after operation in a patient with pulmonary atresia with intact ventricular septum and right ventricular dependent coronary circulation. There have been eight interim deaths among the 26 operative survivors with single ventricle. Two of these interim deaths occurred in patients with heterotaxy, unbalanced CAVC, and TAPVC. One of the 2 patients with Alagille syndrome and single ventricle died in the interim after the initial operation. One death occurred in a patient with pulmonary atresia and intact ventricular septum and right ventricular dependent coronary circulation, and 1 patient with known tracheobronchial malacia died after an acute respiratory-related event. Two deaths occurred as the result of infectious causes in an outpatient setting, and the final death was related to recurrent pulmonary venous obstruction. Sixteen of the 18 surviving patients in the single ventricle group have undergone a bidirectional Glenn procedure. Six of these 16 patients have subsequently undergone a nonfenestrated Fontan procedure. Of the 10 patients who have had a bidirectional Glenn but not a Fontan procedure, 6 are considered potential candidates for a Fontan procedure and are awaiting future evaluation. Three patients are not considered candidates for a Fontan procedure because of elevated pulmonary vascular resistance, and there was one late death. Thus, for the entire single ventricle cohort, the combined early and late mortality has been 45%, with a mean duration of follow-up of years for the survivors. The flow diagram for the single ventricle cohort is shown in Figure 5. For the 17 patients with MAPCAs and two ventricles, the initial cardiac procedure was a single-stage complete repair in 5 patients. This included bilateral unifocalization and repair of CAVC in 1 patient, bilateral unifocalization and repair of corrected transposition in 1 patient, and unilateral unifocalization and repair of scimitar syndrome (including repair of the anomalous pulmonary venous drainage of the right lung) in 3 patients. Twelve of the 17 patients with MAPCAs and two ventricles underwent a staged approach. Ten of these patients underwent a bilateral unifocalization and placement of a central shunt. These patients had a mean of MAPCAs unifocalized. Two patients with MAPCAs and two ventricles underwent an initial aortopulmonary window.

5 Ann Thorac Surg PATRICK ET AL 2017;104: MAPCAS WITH ATYPICAL ANATOMY 911 Fig 5. Flow diagram for the 33 patients with major aortopulmonary collateral arteries (MAPCAs) and single ventricle anatomy. (APW ¼ aortopulmonary window; BDG ¼ bidirectional Glenn.) There were two operative deaths (12%) in this cohort of 17 patients. One patient was born with double outlet right ventricle in association with obstructed TAPVC and underwent an operation at 10 days of age. This patient had persistent pulmonary hypertension postoperatively and died of hypoxemia and respiratory failure. The second patient was born with CAVC, severe AV valve regurgitation, and partial anomalous pulmonary venous drainage. This patient underwent unifocalization and complete repair of CAVC but did not survive. Eight of the 11 operative survivors of these initial palliative procedures have subsequently undergone complete biventricular repair, including repair of CAVC in 3 patients, double outlet right ventricle in 1 patient, and corrected transposition in 3 patients. Two of the remaining 3 patients are viable candidates for eventual complete repair. One patient was undergoing a follow-up operation and sustained a cardiopulmonary arrest, was placed on ECMO, but did not survive. There was a second late death in a patient who had been fully repaired but experienced respiratory failure secondary to a viral infection, was placed on ECMO, and did not survive. Thus, there have been two early and two late deaths in this subgroup, with a mean duration of follow-up of years. The flow diagram for the two ventricle patients is shown in Figure 6. The actuarial survival curves for the 33 single ventricle patients and the 17 two ventricle patients are shown in Figure 7. The 5-year survival for the two groups was 56% and 66%, respectively. There were 16 patients (12 with single ventricle and 4 with two ventricle anatomy) who were born with TAPVC. The actuarial survival curves for patients with and without TAPVC are shown in Figure 8A. Eleven of the 16 patients were born with or experienced signs of pulmonary venous obstruction, which then dictated the timing of surgical intervention. The actuarial curve for the 11 patients with obstructed TAPVC compared with the 5 patients with nonobstructed TAPVC are shown in Figure 8B. Eleven of the 50 patients in this study were placed on ECMO at some time during their clinical course. Six (of 33) patients with single ventricle and MAPCAs were placed on ECMO for cardiac support. Four of these 6 patients had sudden events in the intensive care unit, precipitating the need for ECMO, and the remaining 2 patients had deterioration in their hemodynamics to an unsustainable level. Three of these 6 patients were eventually weaned from ECMO, but there were only two hospital survivors in this group. Five (of 17) patients with two ventricle anatomy were placed on ECMO, including 3 patients in the postoperative period because of sudden cardiac-related events or hemodynamic instability. Two of these 3 patients did survive, but 1 patient did not. One patient was undergoing a subsequent reoperation and sustained a cardiopulmonary arrest before the beginning of the operation, was placed emergently on ECMO, but did not survive. The final 2 ventricle patients who required ECMO were doing well until they experienced respiratory failure due to a viral infection, was placed on ECMO for respiratory support, but did not survive. Thus,

6 912 PATRICK ET AL Ann Thorac Surg MAPCAS WITH ATYPICAL ANATOMY 2017;104: Fig 6. Flow diagram for the 17 patients with major aortopulmonary collateral arteries (MAPCAs) and two ventricle anatomy. (APW ¼ aortopulmonary window.) only 4 of the 11 patients who were placed on ECMO were successfully weaned and are long-term survivors. These data are depicted in Figure 8C. There were 47 patients with MAPCA-dependent circulation, and all 19 deaths occurred in this cohort of patients. For the 36 patients with single-supply MAPCAs, there were a total of 16 deaths (eight early and eight late). Nine patients had dual-supply MAPCAs, with three deaths. There were no deaths in the subset of 2 patients with a ductus to one lung and MAPCAs to the other lung. The mean number of MAPCAs for patients who survived was compared with for patients who did not survive (not significant). The 16 patients in the single ventricle group who achieved a bidirectional Glenn Fig 7. Actuarial survival curves for the single ventricle and two ventricle cohorts. The 5-year survival was 56% and 66%, respectively. procedure had a mean of MAPCAs compared with MAPCAs (not significant) for patients who did not survive. There were just 6 patients who have achieved a Fontan procedure to date, and these patients had a mean of MAPCAs. Presence of central, intrapericardial pulmonary arteries had no substantial influence on survival (85% versus 70%), achieving a bidirectional Glenn procedure (87% versus 70%) or Fontan procedure (67% versus 100%). Comment This study was performed to evaluate the surgical results in patients with MAPCAs and intracardiac anatomy other than PA/VSD. Approximately two-thirds of the patients included in this study had single ventricle anatomy. Nearly half of these single ventricle patients had the entity of heterotaxy with an unbalanced CAVC (both with and without TAPVC). This finding suggests that there may be a genetic or developmental link between heterotaxy/cavc/ pulmonary atresia and the formation of MAPCAs. The remainder of the single ventricle patients had a diverse mixture of anatomy. One-third of the patients with atypical anatomy had two ventricles, with most falling under the broad categories of conotruncal or CAVC abnormalities. The data demonstrate the wide heterogeneity of anatomy that is seen in cases other than PA/VSD. For the single ventricle cohort of 33 patients, there were seven operative deaths at the initial procedure, representing an overall mortality of 21%. All of these patients had pulmonary atresia and underwent shunt procedures

7 Ann Thorac Surg PATRICK ET AL 2017;104: MAPCAS WITH ATYPICAL ANATOMY 913 Fig 8. (A) Actuarial survival curves for the 16 patients with total anomalous pulmonary venous connection (TAPVC) compared with the 34 patients who did not have TAPVC. The 5-year survival was 56% and 61%, respectively. (B) Actuarial survival curves for the 11 patients with obstructed TAPVC compared with the 5 patients with nonobstructed TAPVC. The 5-year survival was 58% and 60%, respectively. (C) Actuarial survival curves for the 11 patients who were placed on extracorporeal membrane oxygenation (ECMO) compared with the 39 patients who did not require ECMO. The 5-year survival was 30% and 69%, respectively. resulting in parallel physiologic process. Twenty-four of the 33 patients also underwent unifocalization of MAP- CAs, and 8 patients underwent concomitant repair of TAPVC. The Society of Thoracic Surgeons (STS) Congenital Cardiac Surgery Database provides an important context to evaluate these results. These data demonstrate an 8% operative mortality for a systemic-topulmonary artery shunt procedure and does not differentiate between single versus two ventricle anatomy (presumably patients with single ventricle would have a higher mortality than their two ventricle counterparts). Patients undergoing TAPVC with two ventricles had an operative mortality of 8.9%, whereas patients undergoing repair of TAPVC in combination with a systemic-topulmonary artery shunt (a marker for total veins in combination with single ventricle) had a 36.3% operative mortality. Thus, the results described in this report demonstrate an operative mortality similar to The STS Congenital Database, with the caveat that most patients in our study also underwent a concomitant unifocalization procedure. Sixteen patients in this series have had a bidirectional Glenn procedure, and there are 2 additional patients who are potential candidates for this procedure. The bidirectional Glenn procedure results in a reduction in volume load and eliminates the potential for substantial changes in the distribution of cardiac output. There have been no deaths related to the bidirectional Glenn procedure and a single death subsequent to this procedure. Thus, it is evident that the vulnerable period for patients with single ventricle and MAPCAs is the time when they are palliated with a shunt, and this risk is largely alleviated after the bidirectional Glenn procedure. Six patients in this series have undergone a Fontan procedure. In addition, there are 6 patients who are potential candidates for a Fontan procedure. This result can be viewed in a variety of ways. On the one hand, it is somewhat surprising that any single ventricle patient with pulmonary atresia and MAPCAs can achieve a low enough pulmonary vascular resistance to reach the Fontan procedure. On the other hand, 6 of the 33 patients have reached this goal of complete separation of the systemic and pulmonary circulations. In 2006, we reported the results of unifocalization of MAPCAs in 14 single ventricle patients [13]. Over the past 10 years, we have performed operations in an additional 19 patients, or 2 patients per year. The results of the operation in the second half of the series are improved incrementally compared with the first half. We would attribute this trend to a combination of the learning curve, using smaller shunts, and leaving patients with shunted physiologic process for the shortest possible duration. To date, we have not extended this concept to combine a unifocalization with concomitant bidirectional Glenn procedure. There are many risk factors that are difficult to mitigate, including obstructed TAPVC [14], low birth weight, Alagille syndrome [17], and right ventricular dependent coronary circulation in pulmonary atresia with intact ventricular septum. Five of the 17 patients with two ventricles underwent a single-stage complete repair, including unifocalization of MAPCAs and repair of the intracardiac anatomy. There was one operative death in this cohort. The remaining 12 patients underwent unifocalization of MAPCAs, and a shunt in 10 patients and an aortopulmonary window in 2 patients. There was one operative death in this cohort.

8 914 PATRICK ET AL Ann Thorac Surg MAPCAS WITH ATYPICAL ANATOMY 2017;104: For the 11 operative survivors, 8 patients have subsequently been repaired and 2 are good candidates for repair. There were two late deaths, one of whom was in a palliated state and one who underwent complete repair and died after the development of a viral pneumonia. The 17 patients with MAPCAs, atypical anatomy, and two ventricles had a wide variety of intracardiac anatomy. Twelve of the 17 patients had either a CAVC or conotruncal defect. However, we also had 3 patients with scimitar syndrome and a MAPCA supplying a large portion of the right lower lobe that was aerated and therefore functional (ie, an intralobar sequestration). Two of these 3 patients had symptoms of congestive heart failure related to the extent of left-to-right shunt from the MAPCA. The conventional management of this condition historically has been either coil embolization of the MAPCA or surgical resection in the presence of chronic or recurrent infections. However, in the absence of infection, there is no theoretical reason why this otherwise functional lung should not be incorporated into the pulmonary circulation at the time of repair of the anomalous pulmonary venous drainage. This is a report of such an approach to scimitar syndrome. Sixteen of the 19 deaths in this series occurred during the time frame when the patients had shunted physiologic process. There were 9 patients who sustained sudden cardiac-related events postoperatively, accounting for eight of the nine early deaths. Many of these patients were placed emergently on ECMO, but with only a few survivors. These data highlight the tenuous physiologic process created through the combination of lengthy surgical procedures and shunted physiologic process. Anatomic factors that one might reasonably assume would influence survival include the presence of TAPVC and particularly obstructed TAPVC. There were 16 patients with TAPVC, and 11 of these experienced obstruction. However, our data do not demonstrate that TAPVC, whether it was obstructed or not, was a risk factor for poorer outcome. One might also speculate that MAPCA or central pulmonary artery anatomy might have an influence on outcome. The data demonstrate that patients had a similar number of MAPCAs and prevalence of central pulmonary arteries compared with previously published reports on PA/VSD/MAPCAs [15]. Thus, the nature of the MAPCAs and central pulmonary arteries does not appear to be substantively different, comparing atypical and typical intracardiac anatomy. Our data demonstrate that MAPCA and central pulmonary artery anatomy did not influence outcome, with the caveat that the numbers of patients in this study were relatively small and thus rendering statistical analyses less meaningful. Our surgical approach to the two ventricle patients with MAPCAs has become more aggressive over years, aiming to perform a complete repair at the time of unifocalization. This is in response to the recognition that the unifocalization/shunt patients are the subgroup that remain vulnerable to early and late demise. We provided an example of a recent patient in whom we performed a combined unifocalization and double switch procedure for corrected transposition. Although this operation requires a lengthy surgical procedure, the establishment of completely corrected cardiac physiologic process readily offsets the additional time spent on cardiopulmonary bypass. In summary, the results of this study demonstrate the wide diversity of anatomy that can be seen in patients with MAPCAs without PA/VSD. Most patients have complex forms of single ventricle, and these patients are at high risk because of the inherent need for shunted (parallel) physiologic process. The two ventricle group also had a wide variety of complex intracardiac anatomy, and we would advocate an aggressive approach to achieve complete repair whenever feasible in these patients. These data comprise a comprehensive evaluation of both single and two ventricle patients with MAPCAs and intracardiac anatomy other than PA/VSD. References 1. Griselli M, McGuirk SP, Winslaw DS, et al. The influence of pulmonary artery morphology on the results of operations for major aortopulmonary collateral arteries and complex congenital heart defects. J Thorac Cardiovasc Surg 2004;127: Mainwaring RD, Punn R, Reddy VM, Hanley FL. Surgical reconstruction of pulmonary stenosis with ventricular septal defect and major aortopulmonary collaterals. Ann Thorac Surg 2013;95: Carotti A, Albanese SB, Filleppelli S, et al. Determinants of outcome after surgical treatment of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. J Thorac Cardiovasc Surg 2010;140: Davies B, Mussa S, Davies P, et al. Unifocalization of major aortopulmonary collateral arteries in pulmonary atresia with ventricular septal defect is essential to achieve excellent outcomes irrespective of native pulmonary artery morphology. J Thorac Cardiovasc Surg 2009;138: Amark KM, Karamlou T, O Connell A, et al. Independent risk factors associated with mortality, reintervention, and achievement of complete repair in children with pulmonary atresia with ventricular septal defect. J Am Coll Cardiol 2006;47: Song SW, Park HK, Park YH, Cho BK. Pulmonary atresia with ventricular septal defects and major aortopulmonary collateral arteries. Circ J 2009;73: Hsu J-Y, Wang J-K, Lin M-T, et al. Clinical implications of major aortopulmonary collateral arteries in patients with right isomerism. Ann Thorac Surg 2006;82: Uemura H, Yagihara T, Kawahira Y, Yoshikawa Y. Staged unifocalization and anatomic repair in a patient with right isomerism. Ann Thorac Surg 2001;71: Miyagi K, Nagata N, Matsui H, Miyamoto T, Kitahori K. Successful Fontan procedure for asplenia with pulmonary atresia and major aortopulmonary collateral arteries. J Thorac Cardiovasc Surg 2003;126: Shinkawa T, Yamagishi M, Shuntoh K, Yaku H. One-stage unifocalization followed by staged Fontan operation. Interact Cardiovasc Thorac Surg 2007;6: Nagashima M, Hibino N, Yamamato E, Higaki T. Total cavopulmonary connection for functionally single ventricle with pulmonary atresia and abnormal arborization of pulmonary arteries exclusion of overwhelmed area by collateral arteries from Fontan circulation. Interact Cardiovasc Thorac Surg 2008;7: Ban Y, Noma M, Horigome H, et al. Kawashima procedure after staged unifocalizations in aplenia with major aortopulmonary collateral arteries. Ann Thorac Surg 2010;89:

9 Ann Thorac Surg PATRICK ET AL 2017;104: MAPCAS WITH ATYPICAL ANATOMY Reinhartz O, Reddy VM, Petrossian E, et al. Unifocalization of major aortopulmonary collaterals in single-ventricle patients. Ann Thorac Surg 2006;82:934 9; discussion Mainwaring RD, Reddy VM, Reinhartz O, Punn R, Tacy T, Hanley FL. Surgical results in patients with pulmonary atresia-major aortopulmonary collaterals in association with total anomalous pulmonary venous connection. Ann Thorac Surg 2011;92: Mainwaring RD, Reddy VM, Peng L, Kuan C, Palmon M, Hanley FL. Hemodynamic assessment after complete repair DISCUSSION DR JEFFREY JACOBS (St. Petersburg, FL): Great job. I would like to congratulate soon-to-be Dr Patrick, Dr Mainwaring, Dr Hanley, and his colleagues for their excellent and important analysis. I would also like to congratulate soon-to-be Dr Patrick for a very nice presentation. I am going to go off script. This is probably the first presentation ever at the Southern Thoracic presented by two walk-on Division 1 athletes from Duke University, because Dr Mainwaring was a walk-on basketball player at Duke and you were a walk-on football player at Duke. So this is definitely a first, and I think that is pretty cool, and that s a lot coming from a University of Miami guy. Back to the script. The work of Dr Mainwaring and Dr Hanley in improving the care of patients with pulmonary atresia, VSD, and MAPCAs is certainly legendary. Under the leadership of Dr Hanley, the team has developed a protocol-based approach to care for these patients. Under the leadership of Dr Mainwaring, The STS Congenital Heart Surgery Database has modified the nomenclature and classification for these patients with pulmonary atresia, VSD, and MAPCAs. In the analysis that you presented today, your team has demonstrated the wide diversity of anatomy that can be seen in patients with MAPCAs when evaluating diagnoses other than pulmonary atresia/vsd/mapcas. More than two-thirds of the patients with this atypical anatomy had single ventricle, and single ventricle anatomy was clearly associated with a relatively high mortality. As demonstrated by your team from Stanford, although the patients with pulmonary atresia/vsd/mapcas have remarkable uniformity in the intracardiac anatomy, there is a wide diversity seen in this series. The patients with pulmonary atresia/vsd are almost universally two ventricle patients, whereas two-thirds of this series have functionally univentricular hearts. Most patients with pulmonary atresia/vsd and MAPCAs are candidates for complete repair, which results in normalization of the circulation. In contrast, patients in this series are not candidates for complete repair and thus are obligated to have an operation that results in some type of shunted physiology. And finally, this study infers that the major difference in outcomes between the standard pulmonary atresia/vsd/ MAPCAs and patients with the atypical anatomy is related to the fact that the former group can have a complete repair, whereas the latter group heads toward staged palliation quite often. Congratulations for your excellent presentation, and I have three questions that I will ask sequentially. First of all, it looks like the patients in this study underwent a variety of different initial operations. Could you just comment a little bit on the algorithm that you used to make the decisions for which operation would be done? of pulmonary atresia/major aortopulmonary collaterals. Ann Thorac Surg 2013;95: Watanabe N, Mainwaring RD, Reddy VM, Palmon M, Hanley FL. Early complete repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals. Ann Thorac Surg 2014;97:909 15; discussion Mainwaring RD, Sheikh AY, Punn R, Reddy VM, Hanley FL. Surgical outcomes for patients with pulmonary atresia/major aortopulmonary collaterals and Alagille syndrome. Eur J Cardiothorac Surg 2012;42:235 40; discussion MR WILLIAM L. PATRICK (Stanford, CA): Thank you for your kind comments and a great question. Which of the two primary procedures we perform, that is a unifocalization or aortopulmonary (AP) window, is determined by both the anatomy and the physiology of the MAPCAs, which is determined by a neonatal catheterization. If a single-supply MAPCA is demonstrated on the catheterization, the patient will be sent home and brought back in 3 to 6 months, at which time they will undergo a unifocalization. If it is determined that there is a dual-supply MAPCA, the patient will undergo an AP window in the neonatal period before leaving the hospital. One caveat that we have noted in this particular series of patients is a relatively high prevalence of total veins. We had 16 patients with total veins, which is an anatomy that often dictates earlier surgical intervention. When putting together this data, we assumed this would be a risk factor for poor mid- and long-term outcomes, but as you can see from this Kaplan-Meier survival curve, that turned out not to be true. DR JACOBS: The second question is, there were a total of 19 early and late mortalities, or 38% of the entire cohort. Recognizing that these are very complex patients, can you comment on the causes of mortality in these patients? MR PATRICK: Certainly. As you point out, we did have a very high relative mortality in this cohort, 19 patients or 38%. There were nine early deaths. These are very long operations, they are very complex operations, and, as you pointed out in your commentary, the patients often come out of the operating room with shunted physiology, which is known to be more tenuous. We discovered in putting together this data that there were 11 patients who had a sudden cardiac-related event in the intensive care unit that required them to be placed on ECMO, and of those 11 patients, 4 of them survived and 7 did not. So of the nine operative deaths, 7 were patients who had been placed on ECMO. Here is a Kaplan-Meier curve showing this stark difference, and clearly ECMO is a risk factor for poor mid- and lateterm survival. There were 10 late mortalities. Of those 10, eight were in patients who had a shunted physiology. So when you add up a total of eight from the early operative mortality group and eight from the late operative mortality group, 16 of our 19 patients died in the period of time when they were in a shunted physiologic state. DR JACOBS: One last question. What lessons can you learn from this series? MR PATRICK: As probably is clear from what I was alluding to earlier, the critical time period for these patients is that window when they are in a shunted physiologic state. We cannot control the complexity of this anatomy, but we can do some things to

10 916 PATRICK ET AL Ann Thorac Surg MAPCAS WITH ATYPICAL ANATOMY 2017;104: address the risk that these patients face during that time period when they are shunted. We have gradually started moving toward smaller and smaller shunts; we also try to limit and decrease the amount of time that the patient will spend in a shunted state; and then finally, when possible, obviously in the two ventricle group, perform an early complete repair. DR JACOBS: I just want to congratulate you for a great presentation. For a fourth-year medical student to stand up with that kind of poise and just do a beautiful job like this, you have a lot to be proud of. You represented Stanford and I guess Duke well. MR PATRICK: Thank you. DR S. RAM KUMAR (Los Angeles, CA): Great presentation. In that subgroup, the heterotaxy, unbalanced AV canal, single ventricle, total anomalous pulmonary venous return with MAPCA, I think we have all had 1 or 2 of these patients and they particularly do poorly. I think Dallas has already shown that not too many people make it to the final stage. Did you in that cohort have any patients that made it to Fontan procedure, and if they did, did you learn any lessons that you can teach us how to get this difficult subset through the stages of palliation? MR PATRICK: I could not answer honestly that I could tell you. Looking at the overall Kaplan-Meier survival for that group with total veins, you would think that the mid- and long-term survival is pretty equivalent, so you would think maybe. But I could not tell you. I would have to go back and perform that specific subgroup analysis. DR JOHN E. MAYER JR (Boston, MA): You showed us some pictures that looked like there were pretty nice distal pulmonary arteries once the MAPCA joined the pulmonary parenchyma, but I suspect there is a spectrum of how well developed those peripheral pulmonary arteries are, and there may also be distal pulmonary artery stenoses. Did you look at that at all as a predictor of the outcome? That is question one. MR PATRICK: We did not, but I do agree that would be worthwhile to look at. DR MAYER: The second question is whether or not you have data on the actual pressures that were measured in those distal arteries once you were past the AP collateral part, or the systemic arterial part, and whether or not that in any way had an impact on outcomes. My guess, particularly in the single ventricle group, is that that is going to be probably the major determinant of whether or not you ever get those patients to a Fontan procedure. So those two, both anatomic as well as physiologic abnormalities, would probably be things that might be worth looking at. MR PATRICK: I agree, and we did not look at them in this particular cohort of patients with MAPCAs. DR CHARLES HUDDLESTON (St. Louis, MO): You may not have this information because you just reviewed the patients that had operations, but, sort of getting at what Dr Mayer was driving at to some degree, were there any patients that were ever turned down, and if so, what are the criteria for accepting patients or criteria for excluding them? MR PATRICK: It is a good point. Obviously, this was a retrospective review, so we did only look at patients who received an operation and consequently did not look at all the patients who were consulted for an operation. And frankly, I was not part of those consults, and I would not be able to tell you how many or the percentage that are turned down and for what exact reasons, but it is duly noted. DR HUDDLESTON: Because I suspect some of your patients were turned down at other places. MR PATRICK: I would have to assume that you are probably correct, yes.