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Comprehensive Management of Major Aortopulmonary Collaterals in the Repair of Tetralogy of Fallot
Comprehensive Management of Major Aortopulmonary Collaterals in the Repair of Tetralogy of Fallot Michael Ma, Richard D. Mainwaring, and Frank L. Hanley The heterogenous anatomy of Tetralogy of Fallot with major aortopulmonary collateral arteries has engendered a similar degree of diversity in its management and, ultimately, outcome. We summarize our comprehensive treatment paradigm for this lesion evolved over 15 years of experience through 458 patients and the results obtained. An updated analysis of 307 patients treated primarily at our institution is included. A review of recent literature, comparison of management strategies, and discussion of ongoing controversies are provided. Semin Thorac Cardiovasc Surg Pediatr Card Surg Ann 21:75–82 © 2017 Elsevier Inc. All rights reserved. Keywords: tetralogy of Fallot, major aortopulmonary collateral arteries (MAPCAs), unifocalization, complex congenital heart disease
Introduction Tetralogy of Fallot (ToF) with major aortopulmonary collateral arteries (MAPCAs), has remained an elusive disease to treat. Its anatomic heterogeneity has led to a variety of treatment paradigms; concomitant outcomes have proven similarly diverse.1-14 A summary of our approach to the management of ToF/ MAPCAs, the results obtained, and a comparison to alternate strategies is provided. We hope that this information may be useful in developing a more universally accepted strategy to improve outcomes for these patients.
Anatomic and Physiologic Heterogeneity Anatomic The intracardiac anatomy of ToF/MAPCAs is fairly uniform. Intracardiac admixture occurs at the level of a non-restrictive anteriorly-malaligned ventricular septal defect, often paired with an atrial level shunt. Pulmonary atresia is complete or nearcomplete, and the pulmonary bed receives its input through MAPCAs. Heterogeneity in this lesion occurs with regard to the sources of pulmonary blood flow. The native main and branch pulmonary arteries are absent in 20-25%.15,16 In the 75-80% of patients that do have intrapericardial native pulmonary arteries, these Department of Cardiothoracic Surgery, School of Medicine, Stanford University, Lucile Packard Children’s Hospital, Stanford, CA, USA. Supported in part by: n/a. Address correspondence to: Michael Ma, MD, Department of Cardiothoracic
https://doi.org/10.1053/j.pcsu.2017.11.002 1092-9126/© 2017 Elsevier Inc. All rights reserved.
Lucile Packard Children’s Hospital treatment algorithm for the management of newborns with Tetralogy of Fallot and major aortopulmonary collateral arteries. Central Message A comprehensive management algorithm that appropriately recruits all sources of pulmonary blood flow enables early intracardiac repair of Tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral arteries, in turn yielding excellent hemodynamic and survival outcomes. Surgery, School of Medicine, Stanford University, Lucile Packard Children’s Hospital, 780 Welch Road, Falk Building, CVRB, Mail Code 5407, Stanford, CA 94304, USA. E-mail: [email protected]
PEDIATRIC CARDIAC SURGERY ANNUAL • 2018
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76 vessels are abnormal in several respects. They are qualitatively hypoplastic to varying degrees, since their development presumably occurs through retrograde flow through collateral vessels, given the lack of an antegrade connection to the right ventricular outflow. The arborization pattern of the native pulmonary arteries also varies widely, ranging from completely normal branching in about 10% of patients, with a wide spectrum of reduced branching in the remaining 90%.17 Individual segments of lung parenchyma may be supplied singly by native pulmonary or collateral flow (single-supply), or redundantly by both (dual-supply). MAPCAs may vary in number, origin, course, size, and quality. In our series, the mean number of MAPCAs was 4.1 +- 0.9, with 2.3 +- 0.5 to the right lung, and 1.8 +- 0.4 to the left.15 They derive most commonly from the descending thoracic aorta, but may also arise from neighboring systemic arterial vessels, including the innominate, subclavian, internal mammary, and coronary arteries. These vessels most commonly course within the posterior mediastinum, in close association with the major airways, and may be intimately associated with the esophagus, at times even coursing within the esophageal musculature.18
Physiologic ToF/MAPCAs is a total mixing lesion, with pulmonary blood flow dictated by overall resistance of the pulmonary bed, integrated through these various sources of supply. A spectrum of neonatal presentations exist. 90% of patients are well-balanced, with oxygen saturations between 75-90%. The remaining 10% present with significant over (O2 saturation > 90%) or under (O2 saturation < 75%) circulation. Importantly, regardless of an individual’s overall oxygen saturation, their various lung segments are not receiving a uniform distribution of the overall pulmonary blood flow. MAPCA size and quality, and their physiologic behavior over time, is highly variable, not only from individual to individual, but also within a single individual. Quality of the proximal vessel is subject to continuous systemic arterial sheer force, which may result in varying degrees of MAPCA stenosis and microvascular damage. Those MAPCAs that remain large will overcirculate, damaging distal vessels, and result in elevated distal resistance, while those that stenose will protect the distal microvasculature at the expense of the proximal conduit vessel. As the disease progresses, an infinite spectrum of changes to these vessels may occur, and while the patient may maintain a stable hemodynamic and oxygen saturation profile, individual segments of lung parenchyma may be compromised, either with progression of MAPCA stenosis to atresia, leading to loss of lung segments, or overcirculation with concomitant pulmonary vascular obstructive disease (PVOD).19
Diagnosis An appropriate treatment strategy is highly individualized, and requires detailed understanding of each individual’s heterogenous pulmonary vascular bed. Fetal and neonatal echocardiography may delineate the ventricular septal defect, the presence of pulmonary atresia, and the presence of
aortopulmonary collaterals. Further anatomic delineation requires additional modalities, most commonly computed tomographic angiography and cardiac catheterization. Patients presenting to our institution are evaluated with transthoracic echocardiography and highly specialized computed tomographic angiography, which usually provide enough information in the neonatal period to determine the necessity of an early intervention (see Management below). Most patients are deferred to 3-6 months of age for elective repair, just prior to which a detailed cardiac catheterization is performed to assess the relevant MAPCA and native pulmonary artery anatomy.
Management Principles Our management philosophy17 aims to achieve normal physiology. 1. Minimize pulmonary vascular resistance by maximally preserving and augmenting the pulmonary vascular bed. This is achieved by early and complete unifocalization. Early intervention prevents arterial sheer from damaging distal microvasculature, and prevents loss of lung segments. Recruitment and utilization of all “raw material”, whether native pulmonary artery or MAPCA, is emphasized to provide appropriate inflow and maximize use of living material with growth potential. 2. Complete biventricular repair via atrial and ventricular septal defect closure, and placement of a right ventricular to pulmonary artery valved conduit in those patients in whom the RV:LV pressure ratio is confirmed to be less than 0.5. This is performed at the time of unifocalization in roughly 85% of patients in our primary experience. In the remaining patients, a central shunt is used as the initial source of pulmonary blood flow to the unifocalized pulmonary vascular bed. The intraoperative flow study is critical to determining which patients will receive intracardiac repair and which patients will receive a shunt.14,20-22 Complete biventricular repair in shunted patients is performed as soon as an RV:LV pressure ratio of less than 0.5 is documented at follow up. 3. Assess the adequacy of our interventions.23 Perform interval evaluations and procedures to document and/or promote growth of the pulmonary vascular bed as needed, focusing both on overall pulmonary vascular resistance and on homogeneity of pulmonary blood flow.
Neonates As previously alluded, neonatal diagnosis affords the ability to intervene in this early period in certain unusual circumstances. These circumstances arise in about 15% of all patients.24 Two anatomic and two physiologic etiologies prompt neonatal repair. 1. Anatomic a. Unilateral lung supply by MAPCAs, with contralateral lung supply by a ductus arteriosus. In this
Comprehensive management of major aortopulmonary collaterals in the repair of Tetralogy of Fallot situation, the ductus will close if not recognized in the neonatal period, resulting in loss of the associated lung. Neonatal intervention is thus required, and may range from a primary neonatal unifocalization and intracardiac repair, if the contralateral MAPCAs are favorable, to a ductal stent or surgical shunt into the duct-dependent lung, if the contralateral MAPCAs are unfavorable. The shunt or stent preserves blood supply to the ductdependent lung, enabling eventual reconstruction of the entire pulmonary vascular bed.25 b. Normally arborizing hypoplastic native pulmonary arteries (ie all lung segments supplied by native PA). By definition, all MAPCAs are dual-supply in this situation. If the MAPCAs provide purely redundant flow, these may be ligated, and a surgical aortopulmonary window can be created to promote interval native pulmonary vascular bed growth.26 2. Physiologic a. Profound overcirculation. These individuals typically have a substantial amount of pulmonary blood flow, through MAPCA-derived sources. Candidacy for early unifocalization with complete intracardiac repair is usually excellent given the adequacy of tissue. Surgery is performed early (neonatal period) only if severe failure to thrive is documented; an increased risk of airway and pulmonary morbidity is accepted (see Infancy below).25 b. Profound hypoxia. These patients fall into two further categories. Favorably, a patient may have adequate raw material with aggressive formation of proximal MAPCA stenoses, resulting in reduced pulmonary blood flow. Unfavorably, a patient may have a dearth of raw material altogether. In these latter patients, candidacy for early complete repair is generally poor, and long-term ability to achieve physiologic biventricular repair is also limited.25
Infants The majority (85%) of patients return at age 3-6 months for surgical repair.24 This window is ideal for initial intervention because the inevitable hemodynamic compromise of pulmonary overcirculation is avoided, while enough time has passed to allow the trachea and secondary airways to mature, minimizing airway related post-surgical morbidity. A detailed schematic of our methodology is previously described and reproduced herein (Fig. 1).15,17
Re-Operations A significant portion of our experience derives from late referrals of patients initially operated on at outside institutions.15 Our operations are tailored to the individual problem; however, a similar general philosophy is followed. Any centrally reconstructed pulmonary bed is rehabilitated with extensive reconstruction, residual MAPCAs are unifocalized, and a single source of pulmonary blood flow created. Intracardiac repair
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depends on predicted RV:LV pressure. Selective balloon angioplasty of focal PA stenoses is utilized as well, but stent deployment is avoided, given their limited benefits and inherent difficulties during subsequent re-intervention.
Results Our most recent single-center experience was published in 2017.15 This entailed a retrospective review of all patients with ToF/ MAPCAs who underwent surgical intervention between November 2001 and April 2016, totaling 458 patients, of which 291 (64%) were primarily managed at our center, and 167 (36%) after prior outside surgical intervention. At a median follow-up of 3.0 years (0.6-7.9 years), estimated Kaplan-Meier 5-year survival was 85% +- 2%. To date, 402 patients have undergone complete repair, with one and five year probabilities of achieving complete repair 83 and 93% respectively. The median RV:LV pressure 0.35 (0.300.42), with only four patients persisting with an RV:LV > 0.6. Mortality subsequent to complete repair was influenced by chromosomal abnormalities, age at repair, elevated RV pressure, RV:LV pressure > 0.35, and number of unifocalized MAPCAs. Prior outside interventions and presence/absence of native intrapericardial PAs did not influence survival. To further analyze our strategy, we performed an in-depth analysis of patients managed primarily at our institution.24 This included 307 patients spanning 15 years of treatment, with 280 (91%) achieving complete repair. 241 patients underwent elective infant midline unifocalization, with 204 achieving singlestage complete repair, and an additional 24 achieving secondary intracardiac repair. 66 patients underwent neonatal intervention, with 52 achieving secondary intracardiac repair (Fig. 2). For all patients achieving complete repair, mean RV:LV pressure ratio was 0.36, with 265 of 280 (94.6%) attaining RV:LV pressure ratio < 0.5. Single-stage repair attained a mean RV:LV of 0.36, and secondary intracardiac repair attained 0.40. 196 of 204 (96.1%) single-stage repairs attained RV:LV pressure < 0.5, and 69 of 76 (90.8%) secondary intracardiac repairs attained the same metric (Fig. 3). Actuarial survival was 92% at five years. Patients who were able to undergo single-stage complete repair demonstrated superior survival to those that underwent neonatal palliation (95 v. 82%, p < 0.001) (Fig. 4).
Comparison Several single center series have been published to date.1-14 Comparable results are summarized (Table 1). The early experience with this lesion relied on multiple sternotomy and thoracotomy approaches to gradually address MAPCA vessels, with the eventual goal for complete repair. These series demonstrate modest improvements in hemodynamics (RV:LV pressure ratios of 0.5-0.62) and ability to achieve complete repair (42.5-64.6%). Two diverging management strategies have evolved from these initial results, philosophically divided with regard to the utility of collateral-based sources of pulmonary blood flow. Our
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Figure 1 Lucile Packard Children’s Hospital treatment algorithm for the management of newborns with Tetralogy of Fallot and major aortopulmonary collateral arteries. Qp, pulmonary blood flow; AP, aortopulmonary; PDA, patent ductus arteriosus; PA, pulmonary artery; RV, right ventricle; VSD, ventricular septal defect. (Color version of figure is available online.)
strategy, as aforementioned, attempts to recruit all sources of pulmonary blood flow, and prioritizes early intervention and midline single-stage unifocalization whenever possible. 87.8% achieved complete repair, with an RV:LV pressure ratio 0.35 (0.300.42). 84.1% achieved a combined endpoint of complete repair, operative survival, and RV:LV pressure < 0.5. This contrasts to groups that favor native pulmonary artery rehabilitation,6-10 whereby collateral vessels are thought to be inferior sources of pulmonary blood flow over time, and thus largely ignored in favor of the native pulmonary bed. The native bed is grown in isolation, through a central connection via aortopulmonary shunt or right ventricle-pulmonary artery conduit. This connection provides a direct pathway for interventional techniques to serially balloon dilate and/or stent the native pulmonary tree, in hopes of achieving an acceptable pulmonary vascular resistance to allow eventual septation of the pulmonary and systemic circulations. Hemodynamic improvement (RV:LV pressure ratios of 0.5-0.64) and ability to achieve complete repair (45.9-75%) are reported.
Discussion We demonstrate that our proposed algorithm, one that aggressively unifies all sources of pulmonary blood flow in early infancy, yields an excellent and durable hemodynamic result, with concomitantly high rates of complete repair and long-term survival. Focusing particularly on patients managed through our protocol from the newborn period,24 the majority (85%) did not have completely dual-supply sources of pulmonary blood flow and were thus not candidates for a strategy relying on native pulmonary artery rehabilitation. We emphasize that preserving blood flow to the entire distribution of the pulmonary microvasculature is imperative to achieving low pulmonary vascular resistance. Any strategy that ignores single-supply MAPCAs will invariably result in loss of lung perfusion to segments that are not supplied by native intrapericardial pulmonary arteries. This will result in increasing loss of perfused functional lung parenchyma, and thus elevated pulmonary vascular resistance and pulmonary hypertension.
Comprehensive management of major aortopulmonary collaterals in the repair of Tetralogy of Fallot
Figure 2 15 year single-center experience utilizing LPCH algorithm: complete repair rates. The majority of patients primarily managed were able to undergo midline unifocalization with primary or secondary complete repair (280/307 = 91.2%). LPCH, Lucile Packard Children’s Hospital. (Color version of figure is available online.)
Figure 3 15 year single-center experience utilizing LPCH algorithm: hemodynamic results. (a) Primary (mean RV:LV pressure ratio 0.36) and (b) secondary (mean RV:LV pressure ratio 0.40) repair afforded physiologic hemodynamic results. RV, right ventricle; LV, left ventricle. (Color version of figure is available online.)
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Figure 4 15 year single-center experience utilizing LPCH algorithm: actuarial survival. (a) Overall cohort demonstrates 92% five year actuarial survival. (b) Single-stage complete repair demonstrates improved survival (95%) v. initial neonatal palliation (82%). (Color version of figure is available online.)
In select situations (10%), we do perform native pulmonary artery rehabilitation as the primary management option, but as a subset for a much broader treatment paradigm. In our own algorithm, we utilize this approach when (1) the native intrapericardial pulmonary artery bed exists and (2) this bed
arborizes to all segments of lung parenchyma. By definition, MAPCA-derived sources of pulmonary blood flow are dualsupply, and can be ignored or ligated without unifocalization. An aortopulmonary window is created to promote interval growth of the native bed, and adjunct procedures may be performed
Table 1 Reported single-center outcomes in the management of Tetralogy of Fallot with major aortopulmonary collaterals. CR, complete repair; RV, right ventricle; LV, left ventricle Group
Author
Year
Study Span
Cohort Size
Management
CR
RV/LV if CR
LPCH, California Melbourne, Australia
Hanley Iyers, Mee
2017 1991
2001-2016 1979-1989
458 58
Unifocalization Staged unifocalization
87.8% 44.8%
UCLA Melbourne, Australia Tokyo, Japan South Korea Marseille, France Melbourne, Australia Fuwai Hospital, China Fuwai Hospital, China Melbourne, Australia
Gupta d’Udekem Ishibashi Song Dragulescu Liava’a Zhang Chen Soquet
2003 2005 2006 2008 2011 2012 2013 2015 2017
1983-2000 1975-1995 1982-2004 1998-2006 1991-2010 2003-2008 2009-2012 2009-2014 2003-2014
104 82 113 40 20 25 37 69 40
Staged unifocalization Staged unifocalization Staged unifocalization Staged unifocalization Rehabilitation Rehabilitation Rehabilitation Rehabilitation Rehabilitation
55.8% 64.6% 70.8% 42.5% 75.0% 60.0% 45.9% 49.3% 73.3%
0.35 (0.30-0.42) RV/LV < 0.5 (12 patients), RV/LV 0.7-0.9 (5 patients) 0.5 (0.15-1.0) 0.62 +- 0.32 0.7 +- 0.28 0.57 +- 0.13 0.58 0.64 (0.54-.91) 0.5 +- 0.1 0.57 +- 0.12 0.64 (0.37-0.84)
Comprehensive management of major aortopulmonary collaterals in the repair of Tetralogy of Fallot prior to attempting complete intracardiac repair and placing an RV-PA conduit. This selected management option is consistent with our overall philosophy that blood supply to every lung segment must be maintained. In our experience, MAPCA-based pulmonary blood flow is extremely reliable following unifocalization. An analysis of the subset of our patients with absent native pulmonary arteries who have undergone repair relying solely on MAPCAs as their source of pulmonary blood flow after unifocalization, has demonstrated equivalent early and late results relative to the entire cohort.16,23 Thus, our data strongly contradicts the position that MAPCAs should not be utilized in reconstruction because they are an unreliable long-term source of pulmonary blood flow. Historical analyses of MAPCA-based circulations have shown less favorable outcomes,1-5 which we hypothesize may be related to both surgical technique of unifocalization, and to older age of unifocalization and repair, which likely subjects such vessels to a prolonged period of systemic arterial sheer and subsequent damage. With regard to early conduit placement and ventricular septal defect fenestration,2,13 this is a recognized practice that we have avoided. The intraoperative flow study allows reliable prediction of post-operative RV:LV pressure, helping to avoid a scenario where conduit placement and intracardiac septation fails and requires fenestration. Additionally, in situations where the flow study predicts a high RV pressure, a shunt is preferred to a conduit with VSD unaddressed, because it (1) avoids any surgical manipulation of the right ventricle and (2) does not permit high pressure to cause mid-term pseudoaneurysm formation in the conduit.15
4.
5.
6.
7.
8.
9.
10.
11.
12.
Conclusion Our 15-year single center experience with ToF/MAPCAs has helped define a comprehensive management algorithm that attempts to maximize all sources of pulmonary blood flow, protects the distal microvasculature from systemic arterial sheer force, recruits all functional lung parenchyma, and restores septated intracardiac anatomy, with low-pressure, high output, rightsided physiology. Our recently summarized results provide a retrospective assessment of our efforts, and demonstrate that this proposed algorithm can provide durable improvements in the natural history of this disease process. We highlight other recent experiences to continue to stimulate dialogue in reaching a consensus in the most appropriate method for treating patients afflicted by this complex lesion.
13.
14.
15.
16.
17.
References 1. Iyer KS, Mee RBB. Staged repair of pulmonary atresia with ventricular septal defect and major systemic to pulmonary artery collaterals. Ann Thorac Surg 1991;51:65-72 2. Duncan BW, Mee RB, Prieto LR, et al: Staged repair of tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral arteries. J Thorac Cardiovasc Surg 2003;126:694-702 3. Song SW, Park HK, Park YH, et al: Pulmonary atresia with ventricular septal defects and major aortopulmonary collaterals:
18.
19.
20.
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18-year clinical experience and angiographic follow-up of major aortopulmonary collateral arteries. Circ J 2009;73:516-522 Ishibashi N, Shin’oka T, Ishiyama M, et al: Clinical results of staged repair with complete unifocalization for pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. Eur J Cardiothorac Surg 2007;32:202-208 Gupta A, Odim J, Levi D, et al: Staged repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries: experience with 104 patients. J Thorac Cardiovasc Surg 2003;126:1746-1752 d’Udekem Y, Alphonso N, Norgaard MA, et al: Pulmonary atresia with ventricular septal defects and major aortopulmonary collateral arteries: unifocalization brings no long-term benefits. J Thorac Cardiovasc Surg 2005;130:1496-1502 Dragulescu A, Kammache I, Fouilloux V, et al: Long-term results of pulmonary artery rehabilitation in patients with pulmonary atresia, ventricular septal defect, pulmonary artery hypoplasia, and major aortopulmonary collaterals. J Thorac Cardiovasc Surg 2011;142:1274-1280 Liava’a M, Brizard CP, Konstantinov IE, et al: Pulmonary atresia, ventricular septal defect, and major aortopulmonary collaterals: neonatal pulmonary artery rehabilitation without unifocalization. Ann Thorac Surg 2012;93:185-192 Soquet J, Liava’a M, Eastaugh L, et al: Achievements and limitations of a strategy of rehabilitation of native pulmonary vessels in pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries. Ann Thorac Surg 2017;103: 1519-1526 Zhang Y, Hua Z, Yang K, et al: Outcomes of the rehabilitative procedure for patients with pulmonary atresia, ventricular septal defect and hypoplastic pulmonary arteries beyond the infant period. Eur J Cardiothorac Surg 2014;46:297-303 Chen Q, Ma K, Hua Z, et al: Multistage pulmonary artery rehabilitation in patients with pulmonary atresia, ventricular septal defect and hypoplastic pulmonary artery. Eur J Cardiothorac Surg 2016;50: 160-166 Carotti A, Albanese SB, Filippelli 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;140:1092-1103 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;138:1269-1275 Zhu J, Meza J, Kato A, et al: Pulmonary flow study predicts survival in pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. J Thorac Cardiovasc Surg 2016;152:1494-1503 Bauser-Heaton H, Borquez A, Han B, et al: Programmatic approach to management of Tetralogy of Fallot with major aortopulmonary collateral arteries: a 15-year experience with 458 patients. Circ Cardiovasc Interv 2017;10:e004952 Carrillo SA, Mainwaring RD, Patrick WL, et al: Surgical repair of pulmonary atresia/ventricular septal defect/major aortopulmonary collaterals with absent intra-pericardial pulmonary arteries. Ann Thorac Surg 2015;100:606-614 Malhotra SP, Hanley FL. Surgical management of pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals: a protocol-based approach. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2009;12:145-151 Mainwaring RD, Patrick WL, Carrillo SA, et al: Prevalence and anatomy of retro-esophageal major aortopulmonary collateral arteries. Ann Thorac Surg 2016;102:877-883 Kirklin JW, Blackstone EH, Shumazaki Y, et al: Survival, functional status, and reoperations after repair of tetralogy of Fallot with pulmonary atresia. J Thorac Cardiovasc Surg 1988;96:102-116 Mainwaring RD, Sheikh AY, Reddy VM, et al: Surgical results in patients with pulmonary atresia/major aortopulmonary collaterals
82 and Alagille syndrome. Eur J Cardiothorac Surg 2012;42:235241 21. Honjo O, Al-Radi OO, MacDonald C, et al: The functional intraoperative pulmonary blood flow study is a more sensitive predictor than preoperative anatomy for right ventricular pressure and physiologic tolerance of ventricular septal defect closure after complete unifocalization in patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collaterals. Circulation 2009;120: 546-552 22. Grosse-Wortmann L, Yoo S-J, van Arsdell G, et al: Preoperative total pulmonary blood flow predicts right ventricular pressure in patients early after complete repair of tetralogy of Fallot and pulmonary atresia with major aortopulmonary collateral arteries. J Thorac Cardiovasc Surg 2013;146:1185-1190
M. Ma et al 23. Mainwaring RD, Reddy VM, Peng L, et al: Hemodynamic assessment after complete repair of pulmonary atresia/major aortopulmonary collaterals. Ann Thorac Surg 2013;95:1397-1402 24. Hanley FL, Mainwaring RD, Patrick WL, et al: Surgical algorithm and results for repair of pulmonary atresia/ventricular septal defect/major aortopulmonary collaterals. Presented at the American Association for Thoracic Surgery Centennial (2017) 25. Watanabe N, Mainwaring RD, Reddy VM, et al: Early complete repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals. Ann Thorac Surg 2014;97:909-915 26. Mainwaring RD, Reddy VM, Perry SB, et al: Late outcomes in patients undergoing aortopulmonary window for pulmonary atresia/ stenosis and major aortopulmonary collaterals. Ann Thorac Surg 2012;94:842-848
Introduction Tetralogy of Fallot (ToF) with major aortopulmonary collateral arteries (MAPCAs), has remained an elusive disease to treat. Its anatomic heterogeneity has led to a variety of treatment paradigms; concomitant outcomes have proven similarly diverse.1-14 A summary of our approach to the management of ToF/ MAPCAs, the results obtained, and a comparison to alternate strategies is provided. We hope that this information may be useful in developing a more universally accepted strategy to improve outcomes for these patients.
Anatomic and Physiologic Heterogeneity Anatomic The intracardiac anatomy of ToF/MAPCAs is fairly uniform. Intracardiac admixture occurs at the level of a non-restrictive anteriorly-malaligned ventricular septal defect, often paired with an atrial level shunt. Pulmonary atresia is complete or nearcomplete, and the pulmonary bed receives its input through MAPCAs. Heterogeneity in this lesion occurs with regard to the sources of pulmonary blood flow. The native main and branch pulmonary arteries are absent in 20-25%.15,16 In the 75-80% of patients that do have intrapericardial native pulmonary arteries, these Department of Cardiothoracic Surgery, School of Medicine, Stanford University, Lucile Packard Children’s Hospital, Stanford, CA, USA. Supported in part by: n/a. Address correspondence to: Michael Ma, MD, Department of Cardiothoracic
https://doi.org/10.1053/j.pcsu.2017.11.002 1092-9126/© 2017 Elsevier Inc. All rights reserved.
Lucile Packard Children’s Hospital treatment algorithm for the management of newborns with Tetralogy of Fallot and major aortopulmonary collateral arteries. Central Message A comprehensive management algorithm that appropriately recruits all sources of pulmonary blood flow enables early intracardiac repair of Tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral arteries, in turn yielding excellent hemodynamic and survival outcomes. Surgery, School of Medicine, Stanford University, Lucile Packard Children’s Hospital, 780 Welch Road, Falk Building, CVRB, Mail Code 5407, Stanford, CA 94304, USA. E-mail: [email protected]
PEDIATRIC CARDIAC SURGERY ANNUAL • 2018
75
M. Ma et al
76 vessels are abnormal in several respects. They are qualitatively hypoplastic to varying degrees, since their development presumably occurs through retrograde flow through collateral vessels, given the lack of an antegrade connection to the right ventricular outflow. The arborization pattern of the native pulmonary arteries also varies widely, ranging from completely normal branching in about 10% of patients, with a wide spectrum of reduced branching in the remaining 90%.17 Individual segments of lung parenchyma may be supplied singly by native pulmonary or collateral flow (single-supply), or redundantly by both (dual-supply). MAPCAs may vary in number, origin, course, size, and quality. In our series, the mean number of MAPCAs was 4.1 +- 0.9, with 2.3 +- 0.5 to the right lung, and 1.8 +- 0.4 to the left.15 They derive most commonly from the descending thoracic aorta, but may also arise from neighboring systemic arterial vessels, including the innominate, subclavian, internal mammary, and coronary arteries. These vessels most commonly course within the posterior mediastinum, in close association with the major airways, and may be intimately associated with the esophagus, at times even coursing within the esophageal musculature.18
Physiologic ToF/MAPCAs is a total mixing lesion, with pulmonary blood flow dictated by overall resistance of the pulmonary bed, integrated through these various sources of supply. A spectrum of neonatal presentations exist. 90% of patients are well-balanced, with oxygen saturations between 75-90%. The remaining 10% present with significant over (O2 saturation > 90%) or under (O2 saturation < 75%) circulation. Importantly, regardless of an individual’s overall oxygen saturation, their various lung segments are not receiving a uniform distribution of the overall pulmonary blood flow. MAPCA size and quality, and their physiologic behavior over time, is highly variable, not only from individual to individual, but also within a single individual. Quality of the proximal vessel is subject to continuous systemic arterial sheer force, which may result in varying degrees of MAPCA stenosis and microvascular damage. Those MAPCAs that remain large will overcirculate, damaging distal vessels, and result in elevated distal resistance, while those that stenose will protect the distal microvasculature at the expense of the proximal conduit vessel. As the disease progresses, an infinite spectrum of changes to these vessels may occur, and while the patient may maintain a stable hemodynamic and oxygen saturation profile, individual segments of lung parenchyma may be compromised, either with progression of MAPCA stenosis to atresia, leading to loss of lung segments, or overcirculation with concomitant pulmonary vascular obstructive disease (PVOD).19
Diagnosis An appropriate treatment strategy is highly individualized, and requires detailed understanding of each individual’s heterogenous pulmonary vascular bed. Fetal and neonatal echocardiography may delineate the ventricular septal defect, the presence of pulmonary atresia, and the presence of
aortopulmonary collaterals. Further anatomic delineation requires additional modalities, most commonly computed tomographic angiography and cardiac catheterization. Patients presenting to our institution are evaluated with transthoracic echocardiography and highly specialized computed tomographic angiography, which usually provide enough information in the neonatal period to determine the necessity of an early intervention (see Management below). Most patients are deferred to 3-6 months of age for elective repair, just prior to which a detailed cardiac catheterization is performed to assess the relevant MAPCA and native pulmonary artery anatomy.
Management Principles Our management philosophy17 aims to achieve normal physiology. 1. Minimize pulmonary vascular resistance by maximally preserving and augmenting the pulmonary vascular bed. This is achieved by early and complete unifocalization. Early intervention prevents arterial sheer from damaging distal microvasculature, and prevents loss of lung segments. Recruitment and utilization of all “raw material”, whether native pulmonary artery or MAPCA, is emphasized to provide appropriate inflow and maximize use of living material with growth potential. 2. Complete biventricular repair via atrial and ventricular septal defect closure, and placement of a right ventricular to pulmonary artery valved conduit in those patients in whom the RV:LV pressure ratio is confirmed to be less than 0.5. This is performed at the time of unifocalization in roughly 85% of patients in our primary experience. In the remaining patients, a central shunt is used as the initial source of pulmonary blood flow to the unifocalized pulmonary vascular bed. The intraoperative flow study is critical to determining which patients will receive intracardiac repair and which patients will receive a shunt.14,20-22 Complete biventricular repair in shunted patients is performed as soon as an RV:LV pressure ratio of less than 0.5 is documented at follow up. 3. Assess the adequacy of our interventions.23 Perform interval evaluations and procedures to document and/or promote growth of the pulmonary vascular bed as needed, focusing both on overall pulmonary vascular resistance and on homogeneity of pulmonary blood flow.
Neonates As previously alluded, neonatal diagnosis affords the ability to intervene in this early period in certain unusual circumstances. These circumstances arise in about 15% of all patients.24 Two anatomic and two physiologic etiologies prompt neonatal repair. 1. Anatomic a. Unilateral lung supply by MAPCAs, with contralateral lung supply by a ductus arteriosus. In this
Comprehensive management of major aortopulmonary collaterals in the repair of Tetralogy of Fallot situation, the ductus will close if not recognized in the neonatal period, resulting in loss of the associated lung. Neonatal intervention is thus required, and may range from a primary neonatal unifocalization and intracardiac repair, if the contralateral MAPCAs are favorable, to a ductal stent or surgical shunt into the duct-dependent lung, if the contralateral MAPCAs are unfavorable. The shunt or stent preserves blood supply to the ductdependent lung, enabling eventual reconstruction of the entire pulmonary vascular bed.25 b. Normally arborizing hypoplastic native pulmonary arteries (ie all lung segments supplied by native PA). By definition, all MAPCAs are dual-supply in this situation. If the MAPCAs provide purely redundant flow, these may be ligated, and a surgical aortopulmonary window can be created to promote interval native pulmonary vascular bed growth.26 2. Physiologic a. Profound overcirculation. These individuals typically have a substantial amount of pulmonary blood flow, through MAPCA-derived sources. Candidacy for early unifocalization with complete intracardiac repair is usually excellent given the adequacy of tissue. Surgery is performed early (neonatal period) only if severe failure to thrive is documented; an increased risk of airway and pulmonary morbidity is accepted (see Infancy below).25 b. Profound hypoxia. These patients fall into two further categories. Favorably, a patient may have adequate raw material with aggressive formation of proximal MAPCA stenoses, resulting in reduced pulmonary blood flow. Unfavorably, a patient may have a dearth of raw material altogether. In these latter patients, candidacy for early complete repair is generally poor, and long-term ability to achieve physiologic biventricular repair is also limited.25
Infants The majority (85%) of patients return at age 3-6 months for surgical repair.24 This window is ideal for initial intervention because the inevitable hemodynamic compromise of pulmonary overcirculation is avoided, while enough time has passed to allow the trachea and secondary airways to mature, minimizing airway related post-surgical morbidity. A detailed schematic of our methodology is previously described and reproduced herein (Fig. 1).15,17
Re-Operations A significant portion of our experience derives from late referrals of patients initially operated on at outside institutions.15 Our operations are tailored to the individual problem; however, a similar general philosophy is followed. Any centrally reconstructed pulmonary bed is rehabilitated with extensive reconstruction, residual MAPCAs are unifocalized, and a single source of pulmonary blood flow created. Intracardiac repair
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depends on predicted RV:LV pressure. Selective balloon angioplasty of focal PA stenoses is utilized as well, but stent deployment is avoided, given their limited benefits and inherent difficulties during subsequent re-intervention.
Results Our most recent single-center experience was published in 2017.15 This entailed a retrospective review of all patients with ToF/ MAPCAs who underwent surgical intervention between November 2001 and April 2016, totaling 458 patients, of which 291 (64%) were primarily managed at our center, and 167 (36%) after prior outside surgical intervention. At a median follow-up of 3.0 years (0.6-7.9 years), estimated Kaplan-Meier 5-year survival was 85% +- 2%. To date, 402 patients have undergone complete repair, with one and five year probabilities of achieving complete repair 83 and 93% respectively. The median RV:LV pressure 0.35 (0.300.42), with only four patients persisting with an RV:LV > 0.6. Mortality subsequent to complete repair was influenced by chromosomal abnormalities, age at repair, elevated RV pressure, RV:LV pressure > 0.35, and number of unifocalized MAPCAs. Prior outside interventions and presence/absence of native intrapericardial PAs did not influence survival. To further analyze our strategy, we performed an in-depth analysis of patients managed primarily at our institution.24 This included 307 patients spanning 15 years of treatment, with 280 (91%) achieving complete repair. 241 patients underwent elective infant midline unifocalization, with 204 achieving singlestage complete repair, and an additional 24 achieving secondary intracardiac repair. 66 patients underwent neonatal intervention, with 52 achieving secondary intracardiac repair (Fig. 2). For all patients achieving complete repair, mean RV:LV pressure ratio was 0.36, with 265 of 280 (94.6%) attaining RV:LV pressure ratio < 0.5. Single-stage repair attained a mean RV:LV of 0.36, and secondary intracardiac repair attained 0.40. 196 of 204 (96.1%) single-stage repairs attained RV:LV pressure < 0.5, and 69 of 76 (90.8%) secondary intracardiac repairs attained the same metric (Fig. 3). Actuarial survival was 92% at five years. Patients who were able to undergo single-stage complete repair demonstrated superior survival to those that underwent neonatal palliation (95 v. 82%, p < 0.001) (Fig. 4).
Comparison Several single center series have been published to date.1-14 Comparable results are summarized (Table 1). The early experience with this lesion relied on multiple sternotomy and thoracotomy approaches to gradually address MAPCA vessels, with the eventual goal for complete repair. These series demonstrate modest improvements in hemodynamics (RV:LV pressure ratios of 0.5-0.62) and ability to achieve complete repair (42.5-64.6%). Two diverging management strategies have evolved from these initial results, philosophically divided with regard to the utility of collateral-based sources of pulmonary blood flow. Our
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Figure 1 Lucile Packard Children’s Hospital treatment algorithm for the management of newborns with Tetralogy of Fallot and major aortopulmonary collateral arteries. Qp, pulmonary blood flow; AP, aortopulmonary; PDA, patent ductus arteriosus; PA, pulmonary artery; RV, right ventricle; VSD, ventricular septal defect. (Color version of figure is available online.)
strategy, as aforementioned, attempts to recruit all sources of pulmonary blood flow, and prioritizes early intervention and midline single-stage unifocalization whenever possible. 87.8% achieved complete repair, with an RV:LV pressure ratio 0.35 (0.300.42). 84.1% achieved a combined endpoint of complete repair, operative survival, and RV:LV pressure < 0.5. This contrasts to groups that favor native pulmonary artery rehabilitation,6-10 whereby collateral vessels are thought to be inferior sources of pulmonary blood flow over time, and thus largely ignored in favor of the native pulmonary bed. The native bed is grown in isolation, through a central connection via aortopulmonary shunt or right ventricle-pulmonary artery conduit. This connection provides a direct pathway for interventional techniques to serially balloon dilate and/or stent the native pulmonary tree, in hopes of achieving an acceptable pulmonary vascular resistance to allow eventual septation of the pulmonary and systemic circulations. Hemodynamic improvement (RV:LV pressure ratios of 0.5-0.64) and ability to achieve complete repair (45.9-75%) are reported.
Discussion We demonstrate that our proposed algorithm, one that aggressively unifies all sources of pulmonary blood flow in early infancy, yields an excellent and durable hemodynamic result, with concomitantly high rates of complete repair and long-term survival. Focusing particularly on patients managed through our protocol from the newborn period,24 the majority (85%) did not have completely dual-supply sources of pulmonary blood flow and were thus not candidates for a strategy relying on native pulmonary artery rehabilitation. We emphasize that preserving blood flow to the entire distribution of the pulmonary microvasculature is imperative to achieving low pulmonary vascular resistance. Any strategy that ignores single-supply MAPCAs will invariably result in loss of lung perfusion to segments that are not supplied by native intrapericardial pulmonary arteries. This will result in increasing loss of perfused functional lung parenchyma, and thus elevated pulmonary vascular resistance and pulmonary hypertension.
Comprehensive management of major aortopulmonary collaterals in the repair of Tetralogy of Fallot
Figure 2 15 year single-center experience utilizing LPCH algorithm: complete repair rates. The majority of patients primarily managed were able to undergo midline unifocalization with primary or secondary complete repair (280/307 = 91.2%). LPCH, Lucile Packard Children’s Hospital. (Color version of figure is available online.)
Figure 3 15 year single-center experience utilizing LPCH algorithm: hemodynamic results. (a) Primary (mean RV:LV pressure ratio 0.36) and (b) secondary (mean RV:LV pressure ratio 0.40) repair afforded physiologic hemodynamic results. RV, right ventricle; LV, left ventricle. (Color version of figure is available online.)
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Figure 4 15 year single-center experience utilizing LPCH algorithm: actuarial survival. (a) Overall cohort demonstrates 92% five year actuarial survival. (b) Single-stage complete repair demonstrates improved survival (95%) v. initial neonatal palliation (82%). (Color version of figure is available online.)
In select situations (10%), we do perform native pulmonary artery rehabilitation as the primary management option, but as a subset for a much broader treatment paradigm. In our own algorithm, we utilize this approach when (1) the native intrapericardial pulmonary artery bed exists and (2) this bed
arborizes to all segments of lung parenchyma. By definition, MAPCA-derived sources of pulmonary blood flow are dualsupply, and can be ignored or ligated without unifocalization. An aortopulmonary window is created to promote interval growth of the native bed, and adjunct procedures may be performed
Table 1 Reported single-center outcomes in the management of Tetralogy of Fallot with major aortopulmonary collaterals. CR, complete repair; RV, right ventricle; LV, left ventricle Group
Author
Year
Study Span
Cohort Size
Management
CR
RV/LV if CR
LPCH, California Melbourne, Australia
Hanley Iyers, Mee
2017 1991
2001-2016 1979-1989
458 58
Unifocalization Staged unifocalization
87.8% 44.8%
UCLA Melbourne, Australia Tokyo, Japan South Korea Marseille, France Melbourne, Australia Fuwai Hospital, China Fuwai Hospital, China Melbourne, Australia
Gupta d’Udekem Ishibashi Song Dragulescu Liava’a Zhang Chen Soquet
2003 2005 2006 2008 2011 2012 2013 2015 2017
1983-2000 1975-1995 1982-2004 1998-2006 1991-2010 2003-2008 2009-2012 2009-2014 2003-2014
104 82 113 40 20 25 37 69 40
Staged unifocalization Staged unifocalization Staged unifocalization Staged unifocalization Rehabilitation Rehabilitation Rehabilitation Rehabilitation Rehabilitation
55.8% 64.6% 70.8% 42.5% 75.0% 60.0% 45.9% 49.3% 73.3%
0.35 (0.30-0.42) RV/LV < 0.5 (12 patients), RV/LV 0.7-0.9 (5 patients) 0.5 (0.15-1.0) 0.62 +- 0.32 0.7 +- 0.28 0.57 +- 0.13 0.58 0.64 (0.54-.91) 0.5 +- 0.1 0.57 +- 0.12 0.64 (0.37-0.84)
Comprehensive management of major aortopulmonary collaterals in the repair of Tetralogy of Fallot prior to attempting complete intracardiac repair and placing an RV-PA conduit. This selected management option is consistent with our overall philosophy that blood supply to every lung segment must be maintained. In our experience, MAPCA-based pulmonary blood flow is extremely reliable following unifocalization. An analysis of the subset of our patients with absent native pulmonary arteries who have undergone repair relying solely on MAPCAs as their source of pulmonary blood flow after unifocalization, has demonstrated equivalent early and late results relative to the entire cohort.16,23 Thus, our data strongly contradicts the position that MAPCAs should not be utilized in reconstruction because they are an unreliable long-term source of pulmonary blood flow. Historical analyses of MAPCA-based circulations have shown less favorable outcomes,1-5 which we hypothesize may be related to both surgical technique of unifocalization, and to older age of unifocalization and repair, which likely subjects such vessels to a prolonged period of systemic arterial sheer and subsequent damage. With regard to early conduit placement and ventricular septal defect fenestration,2,13 this is a recognized practice that we have avoided. The intraoperative flow study allows reliable prediction of post-operative RV:LV pressure, helping to avoid a scenario where conduit placement and intracardiac septation fails and requires fenestration. Additionally, in situations where the flow study predicts a high RV pressure, a shunt is preferred to a conduit with VSD unaddressed, because it (1) avoids any surgical manipulation of the right ventricle and (2) does not permit high pressure to cause mid-term pseudoaneurysm formation in the conduit.15
4.
5.
6.
7.
8.
9.
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Conclusion Our 15-year single center experience with ToF/MAPCAs has helped define a comprehensive management algorithm that attempts to maximize all sources of pulmonary blood flow, protects the distal microvasculature from systemic arterial sheer force, recruits all functional lung parenchyma, and restores septated intracardiac anatomy, with low-pressure, high output, rightsided physiology. Our recently summarized results provide a retrospective assessment of our efforts, and demonstrate that this proposed algorithm can provide durable improvements in the natural history of this disease process. We highlight other recent experiences to continue to stimulate dialogue in reaching a consensus in the most appropriate method for treating patients afflicted by this complex lesion.
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18-year clinical experience and angiographic follow-up of major aortopulmonary collateral arteries. Circ J 2009;73:516-522 Ishibashi N, Shin’oka T, Ishiyama M, et al: Clinical results of staged repair with complete unifocalization for pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. Eur J Cardiothorac Surg 2007;32:202-208 Gupta A, Odim J, Levi D, et al: Staged repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries: experience with 104 patients. J Thorac Cardiovasc Surg 2003;126:1746-1752 d’Udekem Y, Alphonso N, Norgaard MA, et al: Pulmonary atresia with ventricular septal defects and major aortopulmonary collateral arteries: unifocalization brings no long-term benefits. J Thorac Cardiovasc Surg 2005;130:1496-1502 Dragulescu A, Kammache I, Fouilloux V, et al: Long-term results of pulmonary artery rehabilitation in patients with pulmonary atresia, ventricular septal defect, pulmonary artery hypoplasia, and major aortopulmonary collaterals. J Thorac Cardiovasc Surg 2011;142:1274-1280 Liava’a M, Brizard CP, Konstantinov IE, et al: Pulmonary atresia, ventricular septal defect, and major aortopulmonary collaterals: neonatal pulmonary artery rehabilitation without unifocalization. Ann Thorac Surg 2012;93:185-192 Soquet J, Liava’a M, Eastaugh L, et al: Achievements and limitations of a strategy of rehabilitation of native pulmonary vessels in pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries. Ann Thorac Surg 2017;103: 1519-1526 Zhang Y, Hua Z, Yang K, et al: Outcomes of the rehabilitative procedure for patients with pulmonary atresia, ventricular septal defect and hypoplastic pulmonary arteries beyond the infant period. Eur J Cardiothorac Surg 2014;46:297-303 Chen Q, Ma K, Hua Z, et al: Multistage pulmonary artery rehabilitation in patients with pulmonary atresia, ventricular septal defect and hypoplastic pulmonary artery. Eur J Cardiothorac Surg 2016;50: 160-166 Carotti A, Albanese SB, Filippelli 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;140:1092-1103 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;138:1269-1275 Zhu J, Meza J, Kato A, et al: Pulmonary flow study predicts survival in pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. J Thorac Cardiovasc Surg 2016;152:1494-1503 Bauser-Heaton H, Borquez A, Han B, et al: Programmatic approach to management of Tetralogy of Fallot with major aortopulmonary collateral arteries: a 15-year experience with 458 patients. Circ Cardiovasc Interv 2017;10:e004952 Carrillo SA, Mainwaring RD, Patrick WL, et al: Surgical repair of pulmonary atresia/ventricular septal defect/major aortopulmonary collaterals with absent intra-pericardial pulmonary arteries. Ann Thorac Surg 2015;100:606-614 Malhotra SP, Hanley FL. Surgical management of pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals: a protocol-based approach. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2009;12:145-151 Mainwaring RD, Patrick WL, Carrillo SA, et al: Prevalence and anatomy of retro-esophageal major aortopulmonary collateral arteries. Ann Thorac Surg 2016;102:877-883 Kirklin JW, Blackstone EH, Shumazaki Y, et al: Survival, functional status, and reoperations after repair of tetralogy of Fallot with pulmonary atresia. J Thorac Cardiovasc Surg 1988;96:102-116 Mainwaring RD, Sheikh AY, Reddy VM, et al: Surgical results in patients with pulmonary atresia/major aortopulmonary collaterals
82 and Alagille syndrome. Eur J Cardiothorac Surg 2012;42:235241 21. Honjo O, Al-Radi OO, MacDonald C, et al: The functional intraoperative pulmonary blood flow study is a more sensitive predictor than preoperative anatomy for right ventricular pressure and physiologic tolerance of ventricular septal defect closure after complete unifocalization in patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collaterals. Circulation 2009;120: 546-552 22. Grosse-Wortmann L, Yoo S-J, van Arsdell G, et al: Preoperative total pulmonary blood flow predicts right ventricular pressure in patients early after complete repair of tetralogy of Fallot and pulmonary atresia with major aortopulmonary collateral arteries. J Thorac Cardiovasc Surg 2013;146:1185-1190
M. Ma et al 23. Mainwaring RD, Reddy VM, Peng L, et al: Hemodynamic assessment after complete repair of pulmonary atresia/major aortopulmonary collaterals. Ann Thorac Surg 2013;95:1397-1402 24. Hanley FL, Mainwaring RD, Patrick WL, et al: Surgical algorithm and results for repair of pulmonary atresia/ventricular septal defect/major aortopulmonary collaterals. Presented at the American Association for Thoracic Surgery Centennial (2017) 25. Watanabe N, Mainwaring RD, Reddy VM, et al: Early complete repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals. Ann Thorac Surg 2014;97:909-915 26. Mainwaring RD, Reddy VM, Perry SB, et al: Late outcomes in patients undergoing aortopulmonary window for pulmonary atresia/ stenosis and major aortopulmonary collaterals. Ann Thorac Surg 2012;94:842-848