Apples to oranges: Making sense of hybrid palliation for hypoplastic left heart syndrome

Abstract

Central MessageHybrid palliation is a niche treatment strategy for neonates with hypoplastic left heart syndrome. Uniform terminology for intent and risk stratification will help compare outcomes, leading to improved clinical decision making.See Commentaries on pages 55 and 56. Hybrid palliation is a niche treatment strategy for neonates with hypoplastic left heart syndrome. Uniform terminology for intent and risk stratification will help compare outcomes, leading to improved clinical decision making. See Commentaries on pages 55 and 56. Feature Editor's Introduction—Hypoplastic left heart syndrome (HLHS) remains one of the most challenging anomalies for the surgical repertoire. Despite initial nearly overwhelming enthusiasm for a hybrid strategy as the first surgical step in single-ventricle palliation, the hybrid procedure did not show convincing superiority over conventional stage 1 surgical palliation. Here, experts discuss the role, pitfalls, potential benefits, and outcomes of the hybrid procedure. Igor E. Konstantinov, MD, PhD, FRACS In the early 1980s, the Norwood operation revolutionized treatment for children with hypoplastic left heart syndrome (HLHS) and related variants.1Norwood W.I. Lang P. Casteneda A.R. Campbell D.N. Experience with operations for hypoplastic left heart syndrome.J Thorac Cardiovasc Surg. 1981; 82: 511-519Abstract Full Text PDF PubMed Google Scholar Although survival among children with HLHS has continued to improve, outcomes for patients with HLHS remain comparatively poor compared with outcomes in patients with less severe congenital heart defects.2Newburger J.W. Sleeper L.A. Frommelt P.C. Pearson G.D. Mahle W.T. Chen S. et al.Transplantation-free survival and interventions at 3 years in the single ventricle reconstruction trial.Circulation. 2014; 129: 2013-2020Crossref PubMed Scopus (145) Google Scholar In the early 1990s, the hybrid strategy for single-ventricle palliation was developed as an alternative management approach, initially aimed at improving outcomes among neonates with HLHS by providing a bridge to heart transplantation.3Gibbs J.L. Wren C. Watterson K.G. Hunter S. Hamilton J.R. Stenting of the arterial duct combined with banding of the pulmonary arteries and atrial septectomy or septostomy: a new approach to palliation for the hypoplastic left heart syndrome.Br Heart J. 1993; 69: 551-555Crossref PubMed Scopus (191) Google Scholar Hybrid strategies subsequently became a stage 1 alternative with the objective of achieving Fontan completion. Enthusiasm for hybrid strategies was based on the expectation that avoiding cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) or antegrade cerebral perfusion (ACP) during the neonatal period would provide superior long-term outcomes. The objectives of any stage 1 palliation strategy for neonates with HLHS are to achieve (1) unobstructed systemic outflow, (2) balanced pulmonary blood flow (PBF), (3) unrestricted pulmonary venous egress, and (4) unobstructed coronary artery perfusion.4Norwood W.I. Lang P. Hansen D.D. Physiologic repair of aortic atresia-hypoplastic left heart syndrome.N Engl J Med. 1983; 308: 23-26Crossref PubMed Scopus (594) Google Scholar The hybrid stage 1 procedure as initially described achieved these objectives via catheter-based stenting of the patent ductus arteriosus (PDA) combined with surgically placed bilateral pulmonary artery (PA) bands and, if needed, balloon atrial septostomy.3Gibbs J.L. Wren C. Watterson K.G. Hunter S. Hamilton J.R. Stenting of the arterial duct combined with banding of the pulmonary arteries and atrial septectomy or septostomy: a new approach to palliation for the hypoplastic left heart syndrome.Br Heart J. 1993; 69: 551-555Crossref PubMed Scopus (191) Google Scholar,5Ruiz C.E. Gamra H. Zhang H.P. García E.J. Boucek M.M. Brief report: stenting of the ductus arteriosus as a bridge to cardiac transplantation in infants with the hypoplastic left-heart syndrome.N Engl J Med. 1993; 328: 1605-1608Crossref PubMed Scopus (103) Google Scholar,6Gibbs J.L. Rothman M.T. Rees M.R. Parsons J.M. Blackburn M.E. Ruiz C.E. Stenting of the arterial duct: a new approach to palliation for pulmonary atresia.Br Heart J. 1992; 67: 240-245Crossref PubMed Scopus (195) Google Scholar In the “conventional” hybrid approach, a comprehensive stage 2 (CS2) operation is performed 4 to 6 months after hybrid stage 1 palliation. The CS2 operation consists of PA band and ductal stent removal, atrial septectomy, aortic arch reconstruction, and creation of a bidirectional superior cavopulmonary connection (SCPC).7Galantowicz M. Yates A.R. Improved outcomes with the comprehensive stage 2 procedure after an initial hybrid stage 1.J Thorac Cardiovasc Surg. 2016; 151: 424-429Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar The objective following second-stage palliation, either Norwood or hybrid, is for children to undergo Fontan palliation (total cavopulmonary connection) at around 3 years of age. Since the introduction of hybrid strategies in the early 1990s, variations of the conventional technique involving surgical PA banding and ductal stent placement have emerged.3Gibbs J.L. Wren C. Watterson K.G. Hunter S. Hamilton J.R. Stenting of the arterial duct combined with banding of the pulmonary arteries and atrial septectomy or septostomy: a new approach to palliation for the hypoplastic left heart syndrome.Br Heart J. 1993; 69: 551-555Crossref PubMed Scopus (191) Google Scholar Innovative strategies for hybrid palliation have evolved for application in a number of clinical scenarios. Unfortunately, however, as palliative strategies and technical details associated with the hybrid procedure have evolved, the intention of the clinicians using the hybrid approach is not always clearly articulated. For example, clinical intent might be to palliate for planned cardiac transplantation, salvage for a patient who presents with shock or organ dysfunction, or as an intentional alternative to the Norwood procedure because of patient/family preference. Consequently, a retrospective analysis of hybrid strategy outcomes is challenging. Standardized definitions of palliative intent and details of the variations in procedural techniques are important to permit risk stratification and comparison of outcomes between the hybrid and Norwood strategies and permit comparisons across institutions. In this review, we summarize the contemporary hybrid strategy literature, emphasizing patterns of hybrid use, in an effort to promote clarification and standardization of terms of clinical intention and thereby allow more refined assessment of outcomes. Although hybrid palliation offers several theoretical advantages compared with the Norwood strategy, understanding outcomes and potential limitations of the hybrid strategy is important to identify the optimal clinical scenario for hybrid strategies. Overall survival for patients after hybrid palliation has been studied independently as well as in comparison to recipients of a Norwood procedure. Although reports evaluating outcomes after hybrid palliation are often confounded by biased patient selection or heterogeneous patient populations, in the aggregate, overall survival is similar after the hybrid and Norwood stage 1 procedures.7Galantowicz M. Yates A.R. Improved outcomes with the comprehensive stage 2 procedure after an initial hybrid stage 1.J Thorac Cardiovasc Surg. 2016; 151: 424-429Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar, 8Schranz D. Bauer A. Reich B. Steinbrenner B. Recla S. Schmidt D. et al.Fifteen-year single center experience with the “Giessen Hybrid” approach for hypoplastic left heart and variants: current strategies and outcomes.Pediatr Cardiol. 2015; 36: 365-373Crossref PubMed Scopus (100) Google Scholar, 9Kobayashi D. Natarajan G. Turner D.R. Forbes T.J. Delius R.E. Walters H.L. et al.Effect of hybrid stage 1 procedure on ventricular function in infants with hypoplastic left heart syndrome.Cardiol Young. 2016; 26: 867-875Crossref Scopus (4) Google Scholar, 10Newburger J.W. Sleeper L.A. Gaynor J.W. Hollenbeck-Pringle D. Frommelt P.C. Li J.S. et al.Transplant-free survival and interventions at 6 years in the SVR trial.Circulation. 2018; 137: 2246-2253Crossref PubMed Scopus (129) Google Scholar, 11Yerebakan C. Valeske K. Elmontaser H. Yörüker U. Mueller M. Thul J. et al.Hybrid therapy for hypoplastic left heart syndrome: Myth, alternative, or standard?.J Thorac Cardiovasc Surg. 2016; 151 (1123.e1-5): 1112-1121Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar An important difference between hybrid and Norwood stage 1 palliation strategies is the complexity of the second-stage operation. That is, the CS2 operation is more complex than the typical SCPC after Norwood procedures. Importantly, aortic arch reconstruction during the CS2 requires either DHCA or ACP and their attendant risks. The relative complexity of the CS2 operation after hybrid stage 1 is considered a potential limitation of hybrid strategies. As such, evaluating outcomes after the CS2 is important. Compared with the stage 2 SCPC after a Norwood operation, which does not require cardiac arrest in most situations, the CS2 after a hybrid procedure is associated with worse outcomes.12Cua C.L. McConnell P.I. Meza J.M. Hill K.D. Zhang S. Hersey D. et al.Hybrid palliation: outcomes after the comprehensive stage 2 procedure.Ann Thorac Surg. 2018; 105: 1455-1460Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar,13Jacobs J.P. Mayer Jr., J.E. Mavroudis C. O'Brien S.M. Austin III, E.H. Pasquali S.K. et al.The Society of Thoracic Surgeons congenital heart surgery database: 2017 update on outcomes and quality.Ann Thorac Surg. 2017; 103: 699-709Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar However, centers experienced with hybrid palliation are able to achieve mortality rates of 5% to 7% after CS2.7Galantowicz M. Yates A.R. Improved outcomes with the comprehensive stage 2 procedure after an initial hybrid stage 1.J Thorac Cardiovasc Surg. 2016; 151: 424-429Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar,11Yerebakan C. Valeske K. Elmontaser H. Yörüker U. Mueller M. Thul J. et al.Hybrid therapy for hypoplastic left heart syndrome: Myth, alternative, or standard?.J Thorac Cardiovasc Surg. 2016; 151 (1123.e1-5): 1112-1121Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar Despite these favorable results, the hospital mortality associated with the CS2 operation remains higher than that with the SCPC after the Norwood procedure.11Yerebakan C. Valeske K. Elmontaser H. Yörüker U. Mueller M. Thul J. et al.Hybrid therapy for hypoplastic left heart syndrome: Myth, alternative, or standard?.J Thorac Cardiovasc Surg. 2016; 151 (1123.e1-5): 1112-1121Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar,14Baba K. Kotani Y. Chetan D. Chaturvedi R.R. Lee K.J. Benson L.N. et al.Hybrid versus Norwood strategies for single-ventricle palliation.Circulation. 2012; 126: S123-S131Crossref PubMed Scopus (82) Google Scholar A recent review of the Society of Thoracic Surgeons (STS) Congenital Heart Surgery Database reported a 12.4% operative mortality after CS2,12Cua C.L. McConnell P.I. Meza J.M. Hill K.D. Zhang S. Hersey D. et al.Hybrid palliation: outcomes after the comprehensive stage 2 procedure.Ann Thorac Surg. 2018; 105: 1455-1460Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar considerably higher than the STS-reported hospital mortality of 2.5% for SCPC.13Jacobs J.P. Mayer Jr., J.E. Mavroudis C. O'Brien S.M. Austin III, E.H. Pasquali S.K. et al.The Society of Thoracic Surgeons congenital heart surgery database: 2017 update on outcomes and quality.Ann Thorac Surg. 2017; 103: 699-709Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar PA reintervention, particularly on the left PA (LPA), is an important consideration after either hybrid or Norwood stage-1 palliation.15Davies R.R. Radtke W. Bhat M.A. Baffa J.M. Woodford E. Pizarro C. Hybrid palliation for critical systemic outflow obstruction: neither rapid stage 1 Norwood nor comprehensive stage 2 mitigate consequences of early risk factors.J Thorac Cardiovasc Surg. 2015; 149: 182-191Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar, 16Davies R.R. Radtke W.A. Klenk D. Pizarro C. Bilateral pulmonary arterial banding results in an increased need for subsequent pulmonary artery interventions.J Thorac Cardiovasc Surg. 2014; 147: 706-712Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar, 17Rahkonen O. Chaturvedi R.R. Benson L. Honjo O. Caldarone C.A. Lee K.J. Pulmonary artery stenosis in hybrid single-ventricle palliation: high incidence of left pulmonary artery intervention.J Thorac Cardiovasc Surg. 2015; 149: 1102-1110.e2Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar, 18Yörüker U. Akintürk H. Giessen procedure as comprehensive stage II palliation with aortic arch reconstruction after hybrid bilateral pulmonary artery banding and ductal stenting for hypoplastic left heart syndrome.Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2018; 21: 19-27Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar Repeated PA intervention may negatively impact PA growth, which is a critical factor in determining Fontan candidacy and post-Fontan outcomes. PA interventions before stage 2 are uncommon for both hybrid and Norwood strategies.17Rahkonen O. Chaturvedi R.R. Benson L. Honjo O. Caldarone C.A. Lee K.J. Pulmonary artery stenosis in hybrid single-ventricle palliation: high incidence of left pulmonary artery intervention.J Thorac Cardiovasc Surg. 2015; 149: 1102-1110.e2Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar However, patients undergoing hybrid palliation are at increased risk for PA reintervention compared with patients undergoing Norwood procedures.16Davies R.R. Radtke W.A. Klenk D. Pizarro C. Bilateral pulmonary arterial banding results in an increased need for subsequent pulmonary artery interventions.J Thorac Cardiovasc Surg. 2014; 147: 706-712Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar,17Rahkonen O. Chaturvedi R.R. Benson L. Honjo O. Caldarone C.A. Lee K.J. Pulmonary artery stenosis in hybrid single-ventricle palliation: high incidence of left pulmonary artery intervention.J Thorac Cardiovasc Surg. 2015; 149: 1102-1110.e2Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar,19Latus H. Nassar M.S. Wong J. Hachmann P. Bellsham-Revell H. Hussain T. et al.Ventricular function and vascular dimensions after Norwood and hybrid palliation of hypoplastic left heart syndrome.Heart. 2018; 104: 244-252Crossref PubMed Scopus (14) Google Scholar PA reintervention rates after CS2 range between 46%11Yerebakan C. Valeske K. Elmontaser H. Yörüker U. Mueller M. Thul J. et al.Hybrid therapy for hypoplastic left heart syndrome: Myth, alternative, or standard?.J Thorac Cardiovasc Surg. 2016; 151 (1123.e1-5): 1112-1121Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar and 50%17Rahkonen O. Chaturvedi R.R. Benson L. Honjo O. Caldarone C.A. Lee K.J. Pulmonary artery stenosis in hybrid single-ventricle palliation: high incidence of left pulmonary artery intervention.J Thorac Cardiovasc Surg. 2015; 149: 1102-1110.e2Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar at experienced hybrid centers but can be as high as 86% in low-volume centers.20Dave H. Rosser B. Knirsch W. Hübler M. Prêtre R. Kretschmar O. Hybrid approach for hypoplastic left heart syndrome and its variants: the fate of the pulmonary arteries.Eur J Cardiothorac Surg. 2014; 46: 14-19Crossref PubMed Scopus (35) Google Scholar Most PA reinterventions are directed at the LPA and include catheter-based balloon dilation with or without PA stent placement.11Yerebakan C. Valeske K. Elmontaser H. Yörüker U. Mueller M. Thul J. et al.Hybrid therapy for hypoplastic left heart syndrome: Myth, alternative, or standard?.J Thorac Cardiovasc Surg. 2016; 151 (1123.e1-5): 1112-1121Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar,15Davies R.R. Radtke W. Bhat M.A. Baffa J.M. Woodford E. Pizarro C. Hybrid palliation for critical systemic outflow obstruction: neither rapid stage 1 Norwood nor comprehensive stage 2 mitigate consequences of early risk factors.J Thorac Cardiovasc Surg. 2015; 149: 182-191Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar,17Rahkonen O. Chaturvedi R.R. Benson L. Honjo O. Caldarone C.A. Lee K.J. Pulmonary artery stenosis in hybrid single-ventricle palliation: high incidence of left pulmonary artery intervention.J Thorac Cardiovasc Surg. 2015; 149: 1102-1110.e2Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar,18Yörüker U. Akintürk H. Giessen procedure as comprehensive stage II palliation with aortic arch reconstruction after hybrid bilateral pulmonary artery banding and ductal stenting for hypoplastic left heart syndrome.Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2018; 21: 19-27Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar PA size at the time of Fontan palliation is smaller following hybrid stage 1 than after a Norwood procedure.15Davies R.R. Radtke W. Bhat M.A. Baffa J.M. Woodford E. Pizarro C. Hybrid palliation for critical systemic outflow obstruction: neither rapid stage 1 Norwood nor comprehensive stage 2 mitigate consequences of early risk factors.J Thorac Cardiovasc Surg. 2015; 149: 182-191Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar,17Rahkonen O. Chaturvedi R.R. Benson L. Honjo O. Caldarone C.A. Lee K.J. Pulmonary artery stenosis in hybrid single-ventricle palliation: high incidence of left pulmonary artery intervention.J Thorac Cardiovasc Surg. 2015; 149: 1102-1110.e2Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar,19Latus H. Nassar M.S. Wong J. Hachmann P. Bellsham-Revell H. Hussain T. et al.Ventricular function and vascular dimensions after Norwood and hybrid palliation of hypoplastic left heart syndrome.Heart. 2018; 104: 244-252Crossref PubMed Scopus (14) Google Scholar Even though hybrid palliation is associated with increased rates of PA reintervention, in high-volume centers, PA reinterventions did not impact survival or Fontan candidacy.17Rahkonen O. Chaturvedi R.R. Benson L. Honjo O. Caldarone C.A. Lee K.J. Pulmonary artery stenosis in hybrid single-ventricle palliation: high incidence of left pulmonary artery intervention.J Thorac Cardiovasc Surg. 2015; 149: 1102-1110.e2Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar,18Yörüker U. Akintürk H. Giessen procedure as comprehensive stage II palliation with aortic arch reconstruction after hybrid bilateral pulmonary artery banding and ductal stenting for hypoplastic left heart syndrome.Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2018; 21: 19-27Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar In aggregate, the data on the fate of PA growth after stage 1 palliation suggest that PA stenosis occurs more frequently following hybrid palliation than after Norwood palliation, occurs most commonly after stage 2, and usually involves the LPA. Importantly, PA stenosis is largely treatable and does not seem to have a lasting impact on survival, Fontan completion, or successful palliation. Although the objectives for stage 1 palliation can be achieved with both the hybrid approach and the Norwood procedure, there are important differences in cardiovascular physiology between the 2 strategies. Following a Norwood procedure, systemic arterial blood flow—including cerebral and coronary circulation—is delivered via the reconstructed neoaorta. In contrast, circulation after hybrid palliation relies on retrograde arch perfusion of the brachiocephalic and coronary arteries. Consequently, arch obstruction secondary to narrowing of the isthmus by the ductal stent or delayed coarctation can result in cerebral and coronary malperfusion.21Michel-Behnke I. Akintuerk H. Marquardt I. Mueller M. Thul J. Bauer J. et al.Stenting of the ductus arteriosus and banding of the pulmonary arteries: basis for various surgical strategies in newborns with multiple left heart obstructive lesions.Heart. 2003; 89: 645-650Crossref PubMed Scopus (88) Google Scholar,22Pizarro C. Murdison K.A. Off pump palliation for hypoplastic left heart syndrome: surgical approach.Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2005; : 66-71Abstract Full Text Full Text PDF Scopus (31) Google Scholar Risk factors for retrograde arch obstruction include aortic atresia, small aortic root, increased angle between the ductus arteriosus and aortic isthmus, and increased peak Doppler velocities in the retrograde arch.23Stoica S.C. Philips A.B. Egan M. Rodeman R. Chisolm J. Hill S. et al.The retrograde aortic arch in the hybrid approach to hypoplastic left heart syndrome.Ann Thorac Surg. 2009; 88 (discussion 1946-7): 1939-1946Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar For patients at risk of retrograde arch obstruction, a prophylactic main PA–to–innominate artery (reverse modified Blalock–Taussig [BT]) shunt may help mitigate the effects of retrograde arch obstruction.24Caldarone C.A. Benson L.N. Holtby H. Van Arsdell G.S. Main pulmonary artery to innominate artery shunt during hybrid palliation of hypoplastic left heart syndrome.J Thorac Cardiovasc Surg. 2005; 130: e1-e2Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar Although the Toronto group demonstrated the feasibility of using a reverse BT shunt,25Baba K. Honjo O. Chaturvedi R. Lee K.J. Van Arsdell G. Caldarone C.A. et al.“Reverse Blalock-Taussig shunt”: application in single ventricle hybrid palliation.J Thorac Cardiovasc Surg. 2013; 146: 352-357Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar current data supporting use of a reverse BT shunt are limited. Placement of an aortic isthmus stent is an alternative strategy to secure retrograde arch perfusion in patients with obstruction due to “jailing” of the isthmus from the ductal stent.23Stoica S.C. Philips A.B. Egan M. Rodeman R. Chisolm J. Hill S. et al.The retrograde aortic arch in the hybrid approach to hypoplastic left heart syndrome.Ann Thorac Surg. 2009; 88 (discussion 1946-7): 1939-1946Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar However, more common strategies to avoid ductal stenting (and potential retrograde arch obstruction) among high-risk neonates for retrograde arch obstruction include the use of continuous prostaglandin infusion to maintain the ductal patency and avoidance of ductal stenting or abandonment of the hybrid strategy with a Norwood procedure.26Austin III, E.H. Management of retrograde aortic arch malperfusion after hybrid stage I palliation: good save. Learn anything?.J Thorac Cardiovasc Surg. 2015; 150: e89-e90Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar Diastolic runoff occurs when blood is shunted away from the systemic and coronary arterial systems in favor of the pulmonary circulation. A potential consequence of diastolic runoff is poor coronary perfusion or “coronary steal,” which in severe cases causes decreased myocardial reserve and hemodynamic compromise. The arterial source of PBF makes the physiology after Norwood-BT and hybrid stage 1 susceptible to diastolic runoff, which can lead to hemodynamic instability in the early postoperative period.4Norwood W.I. Lang P. Hansen D.D. Physiologic repair of aortic atresia-hypoplastic left heart syndrome.N Engl J Med. 1983; 308: 23-26Crossref PubMed Scopus (594) Google Scholar,27Feinstein J.A. Benson D.W. Dubin A.M. Cohen M.S. Maxey D.M. Mahle W.T. et al.Hypoplastic left heart syndrome: current considerations and expectations.J Am Coll Cardiol. 2012; 59: S1-S42Crossref PubMed Scopus (358) Google Scholar, 28Ohye R.G. Sleeper L.A. Mahony L. Newburger J.W. Pearson G.D. Lu M. et al.Comparison of shunt types in the Norwood procedure for single-ventricle lesions.N Engl J Med. 2010; 362: 1980-1992Crossref PubMed Scopus (684) Google Scholar, 29Wilder T.J. McCrindle B.W. Hickey E.J. Ziemer G. Tchervenkov C.I. Jacobs M.L. et al.Is a hybrid strategy a lower-risk alternative to stage 1 Norwood operation?.J Thorac Cardiovasc Surg. 2017; 153: 163-172.e6Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar, 30DeCampli W.M. Tsai F.W. Argueta-Morales I.R. Smith C. Munro H.M. The effect of epinephrine on coronary flow in the setting of a systemic-to-pulmonary artery shunt.World J Pediatr Congenit Heart Surg. 2013; 4: 373-379Crossref PubMed Scopus (5) Google Scholar Creating bilateral PA bands that precisely balance systemic and PA blood flow while also allowing for equal distribution of blood flow to each lung is technically challenging. Although there are various physiological parameters to help guide PA band placement, this is an inexact process. In addition, the early period after hybrid stage 1 tends to be associated with increased systemic vascular resistance, decreased cardiac efficiency, and lower cardiac output compared with the Norwood procedure,9Kobayashi D. Natarajan G. Turner D.R. Forbes T.J. Delius R.E. Walters H.L. et al.Effect of hybrid stage 1 procedure on ventricular function in infants with hypoplastic left heart syndrome.Cardiol Young. 2016; 26: 867-875Crossref Scopus (4) Google Scholar,31Li J. Zhang G. Benson L. Holtby H. Cai S. Humpl T. et al.Comparison of the profiles of postoperative systemic hemodynamics and oxygen transport in neonates after the hybrid or the Norwood procedure: a pilot study.Circulation. 2007; 116: I179-I187Crossref PubMed Scopus (70) Google Scholar with higher oxygen extraction ratios despite lower oxygen consumption.31Li J. Zhang G. Benson L. Holtby H. Cai S. Humpl T. et al.Comparison of the profiles of postoperative systemic hemodynamics and oxygen transport in neonates after the hybrid or the Norwood procedure: a pilot study.Circulation. 2007; 116: I179-I187Crossref PubMed Scopus (70) Google Scholar Typically, the hemodynamic discrepancy between patients undergoing a Norwood procedure and those undergoing a hybrid procedure resolves within 48 hours. During this period, strategies to reduce afterload help improve cardiac efficiency, especially in those neonates with marginal myocardial reserve.31Li J. Zhang G. Benson L. Holtby H. Cai S. Humpl T. et al.Comparison of the profiles of postoperative systemic hemodynamics and oxygen transport in neonates after the hybrid or the Norwood procedure: a pilot study.Circulation. 2007; 116: I179-I187Crossref PubMed Scopus (70) Google Scholar For neonates with HLHS, brain development is delayed by an average of 5 weeks at birth compared with normal controls.32Licht D.J. Shera D.M. Clancy R.R. Wernovsky G. Montenegro L.M. Nicolson S.C. et al.Brain maturation is delayed in infants with complex congenital heart defects.J Thorac Cardiovasc Surg. 2009; 137 (discussion 536-7): 529-536Abstract Full Text Full Text PDF PubMed Scopus (463) Google Scholar,33Limperopoulos C. Tworetzky W. McElhinney D.B. Newburger J.W. Brown D.W. Robertson Jr., R.L. et al.Brain volume and metabolism in fetuses with congenital heart disease: evaluation with quantitative magnetic resonance imaging and spectroscopy.Circulation. 2010; 121: 26-33Crossref PubMed Scopus (482) Google Scholar Not surprisingly, immature brain development increases the risk for compromised neurodevelopment when exposed to CPB.34Back S.A. Gan X. Li Y. Rosenberg P.A. Volpe J.J. Maturation-dependent vulnerability of oligodendrocytes to oxidative stress-induced death caused by glutathione depletion.J Neurosci. 1998; 18: 6241-6253Crossref PubMed Google Scholar,35Beca J. Gunn J.K. Coleman L. Hope A. Reed P.W. Hunt R.W. et al.New white matter brain injury after infant heart surgery is associated with diagnostic group and the use of circulatory arrest.Circulation. 2013; 127: 971-979Crossref PubMed Scopus (202) Google Scholar Early adoption of hybrid procedures was driven by the presumed benefit of avoiding CPB and arch reconstruction in the neonate; however, skeptics argue that important physiological considerations regarding persistent retrograde aortic arch perfusion diminish the benefits gained by avoiding neonatal CPB.19Latus H. Nassar M.S. Wong J. Hachmann P. Bellsham-Revell H. Hussain T. et al.Ventricular function and vascular dimensions after Norwood and hybrid palliation of hypoplastic left heart syndrome.Heart. 2018; 104: 244-252Crossref PubMed Scopus (14) Google Scholar,36Knirsch W. Mayer K.N. Scheer I. Tuura R. Schranz D. Hahn A. et al.Structural cerebral abnormalities and neurodevelopmental status in single ventricle congenital heart disease before Fontan procedure.Eur J Cardiothorac Surg. 2017; 51: 740-746PubMed Google Scholar A recent study evaluating brain magnetic resonance imaging results in children age 2 to 3 years found that patients who underwent hybrid palliation had comparable total gray matter as age-matched controls, but children who underwent Norwood palliation had persistent gray matter loss.37Knirsch W. Heye K.N. Tuura R.O. Hahn A. Wetterling K. Latal B. et al.Smaller brain volumes at two years of age in patients with hypoplastic left heart syndrome—impact of surgical approach.Int J Cardiol. 2019; 291: 42-44Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar The clinical significance of reduced brain volume on functional neurologic outcomes is unknown, however. Furthermore, these findings are confounded by results showing no difference in neurocognitive outcomes among toddlers who underwent hybrid or Norwood palliation when assessed by the Bayley-III standardized neuromotor examination.38Durán-Carabali L.E. Arcego D.M. Odorcyk F.K. Reichert L. Cordeiro J.L. Sanches E.F. et al.Prenatal and early postnatal environmen