{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T14:08:23Z","timestamp":1779286103809,"version":"3.51.4"},"reference-count":128,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>Background: Hypoplastic left heart syndrome (HLHS) is defined as \u201ca spectrum of congenital cardiovascular malformations with normally aligned great arteries without a common atrioventricular junction, characterized by underdevelopment of the left heart with significant hypoplasia of the left ventricle including atresia, stenosis, or hypoplasia of the aortic or mitral valve, or both valves, and hypoplasia of the ascending aorta and aortic arch\u201d. Without treatment, HLHS is usually lethal in the neonate. Many hypotheses have been advanced to explain the etiology of HLHS; however, no single theory appears to fully explain the phenotypic variability seen in HLHS. Furthermore, many of these theories offer no explanations regarding the precipitating events which lead to the development of HLHS. Objective: This review considers and critically evaluates the strengths and weaknesses of the leading theories proposed to explain the pathogenesis of HLHS\u2014including hemodynamic disturbances, primary myocardial structural defects, valvar malformations, and genetic or epigenetic alterations that may provoke developmental and anatomic abnormalities. After presenting each model, we propose a novel, comprehensive, and data-driven framework which may assist researchers in developing models for the pathogenesis of the various subtypes of HLHS. Methods: Key findings from human fetal imaging, histopathology, genetic studies, and animal models were considered, as well as the hypothetical contribution of each in observed HLHS phenotypes. The rationales for these findings as causal factors initiating individual HLHS patterns, as well as how they might contribute to HLHS in general, were critically analyzed. Results: The flow theory is strongly supported by animal models and in utero interventions that demonstrate the impact of altered hemodynamics on cardiac morphogenesis. However, the flow theory fails to identify initial causes of disturbed flow or related histological features of HLHS like endocardial fibroelastosis. The myocardial and valve-first models suggest an important role in developmental defects, but do not necessarily have a strong experimental basis that provides explanations for how they mediate HLHS. Genetic studies in patients with HLHS have identified several candidate causal mutations. However, such genetic causes of HLHS exhibit incomplete phenotypic penetrance and clinical impact. A multifactorial framework attempts to integrate these diverse mechanisms and may provide the most coherent explanation that can accommodate the heterogeneity and variable presentation of HLHS. Such a framework may identify multiple forces that drive disease but does not provide useful pathways for future research about HLHS. Conclusions: No single hypothesis has fully explained how HLHS is initiated, progresses, and presents with the clinical conditions that are encountered by cardiac surgeons and cardiologists. The most current models suggest that the spectrum of HLHS reflects acomplex interaction between genetic susceptibility, flow-dependent cardiac remodeling, and environmental factors in utero. A multifactorial model integrates these diverse mechanisms and may provide the most coherent explanation for the various phenotypic variations in HLHS. Based on our analysis of the most current data and the strengths and weaknesses of the current theoretical frameworks, we propose a novel research strategy aimed at identifying specific cardiac progenitor cell populations whose dysregulation may represent a unifying explanation for the etiology of the various phenotypes of HLHS. Based on the arguments made throughout this manuscript that evaluate the various genetic, structural, and hemodynamic models of initiation of disease, we believe that the significant phenotypic variability across the spectrum of HLHS (i.e., the different anatomic subtypes for \u201cclassic\u201d HLHS) most likely reflects different underlying etiologies and mechanisms. At the very least, it is very likely that the timing of the insult is critical in determining anatomic subtype. Based on the published data and the arguments within this manuscript, it seems naive to think that there is a single unifying mechanism explain all forms of HLHLS.<\/jats:p>","DOI":"10.3390\/pathophysiology33020033","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T12:30:51Z","timestamp":1779280251000},"page":"33","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Is There a Unified Etiology of Hypoplastic Left Heart Syndrome? Evaluating Genetic, Structural, and Hemodynamic Models of Disease Initiation"],"prefix":"10.3390","volume":"33","author":[{"given":"Reese","family":"Leonhard","sequence":"first","affiliation":[{"name":"Congenital Heart Center, Departments of Surgery and Pediatrics, UF Health Shands Hospital, University of Florida, 1600 SW Archer Rd, Gainesville, FL 32608, USA"},{"name":"Louisiana State University Health Sciences Center at Shreveport, School of Medicine, 1501 Kings Highway, Shreveport, LA 71103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zachary Beau","family":"Phillips","sequence":"additional","affiliation":[{"name":"Congenital Heart Center, Departments of Surgery and Pediatrics, UF Health Shands Hospital, University of Florida, 1600 SW Archer Rd, Gainesville, FL 32608, USA"},{"name":"Louisiana State University Health Sciences Center at Shreveport, School of Medicine, 1501 Kings Highway, Shreveport, LA 71103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamie","family":"Wilson","sequence":"additional","affiliation":[{"name":"Congenital Heart Center, Departments of Surgery and Pediatrics, UF Health Shands Hospital, University of Florida, 1600 SW Archer Rd, Gainesville, FL 32608, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zaid","family":"Abu-Mowis","sequence":"additional","affiliation":[{"name":"Congenital Heart Center, Departments of Surgery and Pediatrics, UF Health Shands Hospital, University of Florida, 1600 SW Archer Rd, Gainesville, FL 32608, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"DiGiorgi","sequence":"additional","affiliation":[{"name":"Congenital Heart Center, Departments of Surgery and Pediatrics, UF Health Shands Hospital, University of Florida, 1600 SW Archer Rd, Gainesville, FL 32608, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Epiphany N.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Congenital Heart Center, Departments of Surgery and Pediatrics, UF Health Shands Hospital, University of Florida, 1600 SW Archer Rd, Gainesville, FL 32608, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0923-1284","authenticated-orcid":false,"given":"Zane","family":"Borenstein","sequence":"additional","affiliation":[{"name":"Congenital Heart Center, Departments of Surgery and Pediatrics, UF Health Shands Hospital, University of Florida, 1600 SW Archer Rd, Gainesville, FL 32608, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Wilson","sequence":"additional","affiliation":[{"name":"Congenital Heart Center, Departments of Surgery and Pediatrics, UF Health Shands Hospital, University of Florida, 1600 SW Archer Rd, Gainesville, FL 32608, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5490-3227","authenticated-orcid":false,"given":"Richard","family":"Tang","sequence":"additional","affiliation":[{"name":"Pediatric Cardiac Surgery, Children\u2019s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth H.","family":"Stephens","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian","family":"Crucean","sequence":"additional","affiliation":[{"name":"Department of Paediatric Cardiac Surgery, Birmingham Women\u2019s and Children\u2019s Hospital, Birmingham B4 6N4, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael S.","family":"Shillingford","sequence":"additional","affiliation":[{"name":"Congenital Heart Center, Departments of Surgery and Pediatrics, UF Health Shands Hospital, University of Florida, 1600 SW Archer Rd, Gainesville, FL 32608, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1313-6498","authenticated-orcid":false,"given":"Giles J.","family":"Peek","sequence":"additional","affiliation":[{"name":"Congenital Heart Center, Departments of Surgery and Pediatrics, UF Health Shands Hospital, University of Florida, 1600 SW Archer Rd, Gainesville, FL 32608, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark Steven","family":"Bleiweis","sequence":"additional","affiliation":[{"name":"Congenital Heart Center, Departments of Surgery and Pediatrics, UF Health Shands Hospital, University of Florida, 1600 SW Archer Rd, Gainesville, FL 32608, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6975-3711","authenticated-orcid":false,"given":"J. Steven","family":"Alexander","sequence":"additional","affiliation":[{"name":"Louisiana State University Health Sciences Center at Shreveport, School of Medicine, 1501 Kings Highway, Shreveport, LA 71103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey Phillip","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Congenital Heart Center, Departments of Surgery and Pediatrics, UF Health Shands Hospital, University of Florida, 1600 SW Archer Rd, Gainesville, FL 32608, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1017\/S104795112100281X","article-title":"Nomenclature for Pediatric and Congenital Cardiac Care: Unification of Clinical and Administrative Nomenclature\u2014The 2021 International Paediatric and Congenital Cardiac Code (IPCCC) and the Eleventh Revision of the International Classification of Diseases (ICD-11)","volume":"31","author":"Jacobs","year":"2021","journal-title":"Cardiol. Young"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1177\/21501351211032919","article-title":"Nomenclature for Pediatric and Congenital Cardiac Care: Unification of Clinical and Administrative Nomenclature\u2014The 2021 International Paediatric and Congenital Cardiac Code (IPCCC) and the Eleventh Revision of the International Classification of Diseases (ICD-11)","volume":"12","author":"Jacobs","year":"2021","journal-title":"World J. Pediatr. Congenit. Heart Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S170","DOI":"10.1016\/S0003-4975(99)01283-7","article-title":"Congenital Heart Surgery Nomenclature and Database Project: Hypoplastic left heart syndrome","volume":"69","author":"Tchervenkov","year":"2000","journal-title":"Ann. Thorac. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1017\/S1047951106000291","article-title":"The nomenclature, definition and classification of hypoplastic left heart syndrome","volume":"16","author":"Tchervenkov","year":"2006","journal-title":"Cardiol. Young"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1177\/21501351221114770","article-title":"Hypoplastic Left Heart Syndrome: Definition, Morphology, and Classification","volume":"13","author":"Jacobs","year":"2022","journal-title":"World J. Pediatr. Congenit. Heart Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1177\/21501351221114775","article-title":"Hypoplastic Left Ventricle: Definition, Morphology, and Classification of the Cardiac Phenotypes","volume":"13","author":"Jacobs","year":"2022","journal-title":"World J. Pediatr. Congenit. Heart Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1177\/21501351221116016","article-title":"Hypoplastic Left Ventricle: Hypoplastic Left Heart Complex","volume":"13","author":"Tchervenkov","year":"2022","journal-title":"World J. Pediatr. Congenit. Heart Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1177\/21501351231189277","article-title":"Defining the Spectrum of Hypoplastic Left Heart Syndrome (HLHS)","volume":"14","author":"Jacobs","year":"2023","journal-title":"World J. Pediatr. Congenit. Heart Surg."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Grossfeld, P., Nie, S., Lin, L., Wang, L., and Anderson, R.H. (2019). Hypoplastic Left Heart Syndrome: A New Paradigm for an Old Disease?. J. Cardiovasc. Dev. Dis., 6.","DOI":"10.3390\/jcdd6010010"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1177\/21501351221088030","article-title":"A Comprehensive Approach to the Management of Patients with HLHS and Related Malformations: An Analysis of 83 Patients (2015-2021)","volume":"13","author":"Bleiweis","year":"2022","journal-title":"World J. Pediatr. Congenit. Heart Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.athoracsur.2024.05.010","article-title":"Comprehensive Approach to the Management of Patients with Hypoplastic Left Heart Syndrome: Analysis of 100 Consecutive Neonates","volume":"119","author":"Bleiweis","year":"2025","journal-title":"Ann. Thorac. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.athoracsur.2021.05.073","article-title":"Combined Hybrid Procedure and VAD Insertion in 9 High-Risk Neonates and Infants with HLHS","volume":"114","author":"Bleiweis","year":"2022","journal-title":"Ann. Thorac. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1016\/j.jtcvs.2009.11.029","article-title":"Center variation and outcomes associated with delayed sternal closure after stage 1 palliation for hypoplastic left heart syndrome","volume":"139","author":"Johnson","year":"2010","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"E428","DOI":"10.1016\/S0735-1097(11)60428-2","article-title":"Variation in perioperative management of Norwood surgery in the Pediatric Heart Network\u2019s Single Ventricle Reconstruction trial","volume":"57","author":"Ohye","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.jtcvs.2012.05.021","article-title":"Variation in perioperative care across centers for infants undergoing the Norwood procedure","volume":"144","author":"Pasquali","year":"2012","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1017\/S1047951118000999","article-title":"Variation in care for infants undergoing the Stage II palliation for hypoplastic left heart syndrome","volume":"28","author":"Eckhauser","year":"2018","journal-title":"Cardiol. Young"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1017\/S1047951119002658","article-title":"Variation in care for children undergoing the Fontan operation for hypoplastic left heart syndrome","volume":"29","author":"Eckhauser","year":"2019","journal-title":"Cardiol. Young"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1056\/NEJM198301063080106","article-title":"Physiologic repair of aortic atresia-hypoplastic left heart syndrome","volume":"308","author":"Norwood","year":"1983","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3321","DOI":"10.1001\/jama.1985.03360230053022","article-title":"Baboon-to-human cardiac xenotransplantation in a neonate","volume":"254","author":"Bailey","year":"1985","journal-title":"JAMA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1161\/hc0902.104709","article-title":"Stenting of the arterial duct and banding of the pulmonary arteries: Basis for combined Norwood stage I and II repair in hypoplastic left heart","volume":"105","author":"Akintuerk","year":"2002","journal-title":"Circulation"},{"key":"ref_21","unstructured":"Jacobs, J.P., Mayer, J.E., Pasquali, S.K., and Kumar, S.R. The Society of Thoracic Surgeons Congenital Heart Surgery Database\u2014Spring 2018 Twenty-Eighth Harvest\u2014(January 1, 2014\u2013December 31, 2017). Table 18, The Society of Thoracic Surgeons (STS) and Duke Clinical Research Institute (DCRI), Duke University Medical Center. Available online: https:\/\/www.annalsthoracicsurgery.org\/article\/S0003-4975(19)30069-4\/fulltext."},{"key":"ref_22","unstructured":"The Society of Thoracic Surgeons Congenital Heart Surgery Database\u2014Spring 2023\u2014(January 1, 2019\u2013December 31, 2022). Table 28, The Society of Thoracic Surgeons (STS)."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1056\/NEJMoa0912461","article-title":"Comparison of shunt types in the Norwood procedure for single-ventricle lesions","volume":"362","author":"Ohye","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1161\/CIRCULATIONAHA.113.006191","article-title":"Transplantation-free survival and interventions at 3 years in the single ventricle reconstruction trial","volume":"129","author":"Newburger","year":"2014","journal-title":"Circulation"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1161\/CIRCULATIONAHA.117.029375","article-title":"Transplant-Free Survival and Interventions at 6 Years in the SVR Trial","volume":"137","author":"Newburger","year":"2018","journal-title":"Circulation"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S1047951104006225","article-title":"Introduction to Cardiology in the Young Hypoplastic Left Heart Syndrome Supplement","volume":"14","author":"Jacobs","year":"2004","journal-title":"Cardiol. Young"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1017\/S1047951104006390","article-title":"Biventricular Repair in the Management of Hypoplastic Left Heart Syndrome","volume":"14","author":"Morell","year":"2004","journal-title":"Cardiol. Young"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1017\/S1047951104006456","article-title":"Achieving a balance in the current approach to the surgical treatment of hypoplastic left heart syndrome","volume":"14","author":"Quintessenza","year":"2004","journal-title":"Cardiol. Young"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1017\/S1047951106001223","article-title":"Rescue Cardiac Transplantation for Failing Staged Palliation in Patients with Hypoplastic Left Heart Syndrome","volume":"16","author":"Jacobs","year":"2006","journal-title":"Cardiol. Young"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1017\/S1047951107001187","article-title":"Hypoplastic left heart syndrome: Consensus and controversies in 2007","volume":"17","author":"Wernovsky","year":"2007","journal-title":"Cardiol. Young"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1016\/j.athoracsur.2008.01.057","article-title":"Management of 239 patients with hypoplastic left heart syndrome and related malformations from 1993 to 2007","volume":"85","author":"Jacobs","year":"2008","journal-title":"Ann. Thorac. Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1016\/j.athoracsur.2010.02.004","article-title":"Impact of noncardiac congenital and genetic abnormalities on outcomes in hypoplastic left heart syndrome","volume":"89","author":"Patel","year":"2010","journal-title":"Ann. Thorac. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1177\/2150135111406942","article-title":"Can Randomized Clinical Trials Impact the Surgical Approach for Hypoplastic Left Heart Syndrome?","volume":"2","author":"Tabbutt","year":"2011","journal-title":"World J. Pediatr. Congenit. Heart Surg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.jtcvs.2010.11.052","article-title":"Reporting adverse events in a surgical trial for complex congenital heart disease: The Pediatric Heart Network experience","volume":"142","author":"Virzi","year":"2011","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.healun.2011.03.020","article-title":"Outcomes after listing for primary transplantation for infants with unoperated-on non-hypoplastic left heart syndrome congenital heart disease: A multi-institutional study","volume":"30","author":"Guleserian","year":"2011","journal-title":"J. Heart Lung Transplant."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1016\/j.athoracsur.2011.05.100","article-title":"Complications After the Norwood Operation: An Analysis of The Society of Thoracic Surgeons Congenital Heart Surgery Database","volume":"92","author":"Hornik","year":"2011","journal-title":"Ann. Thorac. Surg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S1047951111001375","article-title":"Introduction to the supplement: A holistic approach to hypoplastic left heart syndrome and other evolving challenges in paediatric and congenital cardiac disease","volume":"21","author":"Jacobs","year":"2011","journal-title":"Cardiol. Young"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1017\/S1047951111001715","article-title":"Informed consent, bioethical equipoise, and hypoplastic left heart syndrome","volume":"21","author":"Mavroudis","year":"2011","journal-title":"Cardiol. Young"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1161\/CIRCULATIONAHA.111.064113","article-title":"Early developmental outcome in children with hypoplastic left heart syndrome and related anomalies: The single ventricle reconstruction trial","volume":"125","author":"Newburger","year":"2012","journal-title":"Circulation"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1016\/j.athoracsur.2011.07.081","article-title":"The Complex Relationship Between Center Volume and Outcome in Patients Undergoing the Norwood Operation","volume":"93","author":"Pasquali","year":"2012","journal-title":"Ann. Thorac. Surg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1016\/j.athoracsur.2012.01.107","article-title":"Relative impact of surgeon and center volume on early mortality after the Norwood operation","volume":"93","author":"Hornik","year":"2012","journal-title":"Ann. Thorac. Surg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s00246-012-0450-1","article-title":"A predictive model for neurodevelopmental outcome after the Norwood procedure","volume":"34","author":"Mahle","year":"2013","journal-title":"Pediatr. Cardiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1016\/j.jtcvs.2014.05.076","article-title":"Technical performance score is associated with outcomes after the Norwood procedure","volume":"148","author":"Nathan","year":"2014","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.jtcvs.2014.08.020","article-title":"Stage 1 hybrid palliation for hypoplastic left heart syndrome-assessment of contemporary patterns of use: An analysis of The Society of Thoracic Surgeons Congenital Heart Surgery Database","volume":"149","author":"Karamlou","year":"2015","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/j.amjcard.2015.07.044","article-title":"Associations Between Day of Admission and Day of Surgery on Outcome and Resource Utilization in Infants with Hypoplastic Left Heart Syndrome Who Underwent Stage I Palliation (from the Single Ventricle Reconstruction Trial)","volume":"116","author":"Johnson","year":"2015","journal-title":"Am. J. Cardiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1016\/j.jtcvs.2015.06.069","article-title":"Survival and right ventricular performance for matched children after stage-1 Norwood: Modified Blalock-Taussig shunt versus right-ventricle-to-pulmonary-artery conduit","volume":"150","author":"Wilder","year":"2015","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.jtcvs.2016.03.091","article-title":"Maladaptive aortic properties after the Norwood procedure: An angiographic analysis of the Pediatric Heart Network Single Ventricle Reconstruction Trial","volume":"152","author":"Plummer","year":"2016","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.jpeds.2016.09.048","article-title":"Assessment of Growth 6 Years after the Norwood Procedure","volume":"180","author":"Burch","year":"2017","journal-title":"J. Pediatr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.athoracsur.2017.05.041","article-title":"The Optimal Timing of Stage-2-Palliation After the Norwood Operation","volume":"105","author":"Meza","year":"2018","journal-title":"Ann. Thorac. Surg."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1017\/S104795111700169X","article-title":"Utilisation of early intervention services in young children with hypoplastic left heart syndrome","volume":"28","author":"Mussatto","year":"2018","journal-title":"Cardiol. Young"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/j.healun.2018.02.009","article-title":"Heart failure after the Norwood procedure: An analysis of the Single Ventricle Reconstruction Trial","volume":"37","author":"Mahle","year":"2018","journal-title":"J. Heart Lung Transplant."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.jtcvs.2018.09.130","article-title":"Intervention for arch obstruction after the Norwood procedure: Prevalence, associated factors, and practice variability","volume":"157","author":"Devlin","year":"2019","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"E20182577","DOI":"10.1542\/peds.2018-2577","article-title":"Gestational Age, Birth Weight, and Outcomes Six Years After the Norwood Procedure","volume":"143","author":"Miller","year":"2019","journal-title":"Pediatrics"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"E20191010","DOI":"10.1542\/peds.2019-1010","article-title":"Behavior and Quality of Life at 6 Years for Children with Hypoplastic Left Heart Syndrome","volume":"144","author":"Goldberg","year":"2019","journal-title":"Pediatrics"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1093\/ejcts\/ezaa188","article-title":"Guidelines for the management of neonates and infants with hypoplastic left heart syndrome: The European Association for Cardio-Thoracic Surgery (EACTS) and the Association for European Paediatric and Congenital Cardiology (AEPC) Hypoplastic Left Heart Syndrome Guidelines Task Force","volume":"58","author":"Alphonso","year":"2020","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_56","first-page":"6621","article-title":"The Pediatric Heart Network\u2019s Study on Long-term Outcomes of Children with HLHS and the Impact of Norwood Shunt Type in the Single Ventricle Reconstruction Trial Cohort (SVRIII): Design and Adaptations","volume":"14","author":"Goldberg","year":"2022","journal-title":"Am. Heart J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1177\/21501351221076043","article-title":"Biventricular Conversion of Borderline Hypoplastic Left Heart Complex Facilitated by Spontaneous Closure of the Atrial Septum","volume":"13","author":"Zhu","year":"2022","journal-title":"World J. Pediatr. Congenit. Heart Surg."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/j.jtcvs.2023.01.013","article-title":"Norwood operation versus comprehensive stage II after bilateral pulmonary artery banding palliation for infants with critical left heart obstruction","volume":"166","author":"Argo","year":"2023","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.athoracsur.2022.06.046","article-title":"Norwood Operation: Immediate vs Delayed Sternal Closure","volume":"115","author":"Asfari","year":"2023","journal-title":"Ann. Thorac. Surg."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1017\/S1047951123001294","article-title":"Quality analysis of publicly available information about hypoplastic left heart syndrome","volume":"33","author":"Brennan","year":"2023","journal-title":"Cardiol. Young"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0070-2153(10)90001-X","article-title":"How to make a heart: The origin and regulation of cardiac progenitor cells","volume":"90","author":"Vincent","year":"2010","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4165","DOI":"10.1242\/dev.099325","article-title":"Wnt\/\u03b2-catenin signaling directs the regional expansion of first and second heart field-derived ventricular cardiomyocytes","volume":"140","author":"Buikema","year":"2013","journal-title":"Development"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1161\/01.RES.0000141146.95728.da","article-title":"Heart valve development: Endothelial cell signaling and differentiation","volume":"95","author":"Armstrong","year":"2004","journal-title":"Circ. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S0074-7696(05)43005-3","article-title":"Cell biology of cardiac cushion development","volume":"243","author":"Person","year":"2005","journal-title":"Int. Rev. Cytol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1161\/CIRCRESAHA.109.201566","article-title":"Heart valve development: Regulatory networks in development and disease","volume":"105","author":"Combs","year":"2009","journal-title":"Circ. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ydbio.2012.04.020","article-title":"Epicardially derived fibroblasts preferentially contribute to the parietal leaflets of the atrioventricular valves in the murine heart","volume":"366","author":"Wessels","year":"2012","journal-title":"Dev. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1161\/01.RES.0000141429.13560.cb","article-title":"Lineage and morphogenetic analysis of the cardiac valves","volume":"95","author":"Moorman","year":"2004","journal-title":"Circ. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.diff.2012.04.001","article-title":"Atrioventricular valve development: New perspectives on an old theme","volume":"84","author":"Sauls","year":"2012","journal-title":"Differentiation"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1242\/dev.127.8.1607","article-title":"Fate of the mammalian cardiac neural crest","volume":"127","author":"Jiang","year":"2000","journal-title":"Development"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/ajmg.c.31366","article-title":"Embryonic cardiac chamber maturation: Trabeculation, conduction, and cardiomyocyte proliferation","volume":"163","author":"Samsa","year":"2013","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1002\/bies.950180714","article-title":"Trabeculation in the embryonic heart","volume":"18","author":"Sedmera","year":"1996","journal-title":"Bioessays"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1002\/dvdy.22526","article-title":"Dependence of cardiac trabeculation on neuregulin signaling and blood flow in zebrafish","volume":"240","author":"Peshkovsky","year":"2011","journal-title":"Dev. Dyn."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"9","DOI":"10.5802\/crbiol.151","article-title":"On the involvement of the second heart field in congenital heart defects","volume":"347","author":"Guijarro","year":"2024","journal-title":"Comptes Rendus Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0002-9149(73)90810-2","article-title":"Experimental production of hypoplastic left heart syndrome in the chick embryo","volume":"31","author":"Harh","year":"1973","journal-title":"Am. J. Cardiol."},{"key":"ref_75","unstructured":"Abercrombie, M., and Brachet, J. (1962). Experimental Morphology of the Aortic Arches and the Heart Loop in Chick Embryos. Advances in Morphogenesis, Elsevier."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1002\/(SICI)1097-0185(19990201)254:2<238::AID-AR10>3.0.CO;2-V","article-title":"Remodeling of chick embryonic ventricular myoarchitecture under experimentally changed loading conditions","volume":"254","author":"Sedmera","year":"1999","journal-title":"Anat. Rec."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1002\/ar.20885","article-title":"Dependence of aortic arch morphogenesis on intracardiac blood flow in the left atrial ligated chick embryo","volume":"292","author":"Hu","year":"2009","journal-title":"Anat. Rec."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1161\/01.RES.0000266606.88463.cb","article-title":"Increased ventricular preload is compensated by myocyte proliferation in normal and hypoplastic fetal chick left ventricle","volume":"100","author":"deAlmeida","year":"2007","journal-title":"Circ. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/ar.10098","article-title":"Cellular changes in experimental left heart hypoplasia","volume":"267","author":"Sedmera","year":"2002","journal-title":"Anat. Rec."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s10237-020-01413-5","article-title":"Effect of left atrial ligation-driven altered inflow hemodynamics on embryonic heart development: Clues for prenatal progression of hypoplastic left heart syndrome","volume":"20","author":"Salman","year":"2021","journal-title":"Biomech. Model. Mechanobiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"dmm049077","DOI":"10.1242\/dmm.049077","article-title":"A mouse model of hypoplastic left heart syndrome demonstrating left heart hypoplasia and retrograde aortic arch flow","volume":"14","author":"Rahman","year":"2021","journal-title":"Dis. Model. Mech."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Salman, H.E., and Yalcin, H.C. (2021). Computational Modeling of Blood Flow Hemodynamics for Biomechanical Investigation of Cardiac Development and Disease. J. Cardiovasc. Dev. Dis., 8.","DOI":"10.3390\/jcdd8020014"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1161\/01.CIR.0000144357.29279.54","article-title":"Balloon dilation of severe aortic stenosis in the fetus: Potential for prevention of hypoplastic left heart syndrome: Candidate selection, technique, and results of successful intervention","volume":"110","author":"Tworetzky","year":"2004","journal-title":"Circulation"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1002\/pd.6592","article-title":"Transforming congenital heart disease management: Advances in fetal cardiac interventions","volume":"44","author":"Guseh","year":"2024","journal-title":"Prenat. Diagn."},{"key":"ref_85","unstructured":"Fetal Heart Society (2026, April 09). Counseling Sheet: Hypoplastic Left Heart Syndrome (HLHS). Available online: https:\/\/fetalheartsociety.org\/wp-content\/uploads\/2025\/10\/Hypoplastic_Left_Heart_Syndrome.pdf."},{"key":"ref_86","first-page":"392","article-title":"Prospective diagnosis of 1,006 congenital heart defects in the fetus","volume":"17","author":"Allan","year":"2001","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Chaudhry, B., Alqahtani, A., Eley, L., Coats, L., Moldovan, C., Annavarapu, S.R., and Henderson, D.J. (2022). The Left Ventricular Myocardium in Hypoplastic Left Heart Syndrome. J. Cardiovasc. Dev. Dis., 9.","DOI":"10.3390\/jcdd9080279"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.gene.2015.09.008","article-title":"Cardiac myosin-binding protein C (MYBPC3) in cardiac pathophysiology","volume":"573","author":"Carrier","year":"2015","journal-title":"Gene"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"RP97268","DOI":"10.7554\/eLife.97268.3","article-title":"Mechanical forces pattern endocardial Notch activation via mTORC2-PKC pathway","volume":"13","author":"Mu","year":"2024","journal-title":"eLife"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/s41569-018-0100-2","article-title":"Notch and interacting signalling pathways in cardiac development, disease, and regeneration","volume":"15","author":"MacGrogan","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_91","first-page":"e1","article-title":"Endocardial Notch Signaling in Cardiac Development and Disease","volume":"118","author":"MacGrogan","year":"2016","journal-title":"Circ. Res."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Gerede, A., Orgianelis, I., Stavros, S., Potiris, A., Drakaki, E., Tsimpoukis, I., Papasozomenou, P., Domali, E., Nikolettos, N., and Chatzakis, C. (2025). Unmasking the Placenta-Heart Axis: A Comprehensive Review of Placental Abnormalities in Congenital Heart Disease. Diagnostics, 15.","DOI":"10.3390\/diagnostics15172159"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1038\/ng.3870","article-title":"The complex genetics of hypoplastic left heart syndrome","volume":"49","author":"Liu","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_94","unstructured":"Kritzmire, S.M., Thomas, A., Horenstein, M.S., and Cossu, A.E. (2025). Hypoplastic Left Heart Syndrome [Updated 2025 Jan 19]. StatPearls, StatPearls Publishing. Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK554576\/."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1007\/s10741-023-10319-0","article-title":"Endocardial fibroelastosis in infants and young children: A state-of-the-art review","volume":"28","author":"Aldawsari","year":"2023","journal-title":"Heart Fail. Rev."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1017\/S1047951110000181","article-title":"Changing concepts of endocardial fibroelastosis","volume":"20","author":"Lurie","year":"2010","journal-title":"Cardiol. Young"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.stem.2020.07.015","article-title":"Intrinsic Endocardial Defects Contribute to Hypoplastic Left Heart Syndrome","volume":"27","author":"Miao","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1161\/CIRCRESAHA.116.305629","article-title":"Endocardial fibroelastosis is caused by aberrant endothelial to mesenchymal transition","volume":"116","author":"Xu","year":"2015","journal-title":"Circ. Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"416","DOI":"10.5966\/sctm.2013-0105","article-title":"An induced pluripotent stem cell model of hypoplastic left heart syndrome (HLHS) reveals multiple expression and functional differences in HLHS-derived cardiac myocytes","volume":"3","author":"Jiang","year":"2014","journal-title":"Stem Cells Transl. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1152\/physiolgenomics.00091.2016","article-title":"Impact of MYH6 variants in hypoplastic left heart syndrome","volume":"48","author":"Stamm","year":"2016","journal-title":"Physiol. Genom."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e003126","DOI":"10.1161\/CIRCGEN.120.003126","article-title":"Genetic Association Between Hypoplastic Left Heart Syndrome and Cardiomyopathies","volume":"14","author":"Theis","year":"2021","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.jtcvs.2019.09.001","article-title":"Commentary: Why do some patients with hypoplastic left heart syndrome have endocardial fibroelastosis?","volume":"159","author":"Anderson","year":"2020","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1002\/uog.27658","article-title":"Postnatal outcome following fetal aortic valvuloplasty for critical aortic stenosis","volume":"64","author":"Corroenne","year":"2024","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_104","first-page":"43","article-title":"Morphology of the hypoplastic left heart syndrome from the surgical perspective","volume":"37","year":"2001","journal-title":"Cesk Patol."},{"key":"ref_105","first-page":"1923","article-title":"The Perinatal Transition and Early Neonatal Period in Hypoplastic Left Heart Syndrome Is Associated with Reduced Systemic and Cerebral Perfusion","volume":"37","author":"Eckersley","year":"2021","journal-title":"Can. J. Cardiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1007\/s00018-015-1885-3","article-title":"Blood flow mechanics in cardiovascular development","volume":"72","author":"Boselli","year":"2015","journal-title":"Cell Mol. Life Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/uog.1785","article-title":"Impact of congenital heart disease on cerebrovascular blood flow dynamics in the fetus","volume":"25","author":"Kaltman","year":"2005","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Rahman, A., Chaturvedi, R.R., and Sled, J.G. (2022). Flow-Mediated Factors in the Pathogenesis of Hypoplastic Left Heart Syndrome. J. Cardiovasc. Dev. Dis., 9.","DOI":"10.3390\/jcdd9050154"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s13023-017-0683-4","article-title":"Re-evaluation of hypoplastic left heart syndrome from a developmental and morphological perspective","volume":"12","author":"Crucean","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1007\/s00439-015-1582-1","article-title":"Compound heterozygous NOTCH1 mutations underlie impaired cardiogenesis in a patient with hypoplastic left heart syndrome","volume":"134","author":"Theis","year":"2015","journal-title":"Hum. Genet."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1007\/s00246-017-1650-5","article-title":"Hypoplastic Left Heart Syndrome Sequencing Reveals a Novel NOTCH1 Mutation in a Family with Single Ventricle Defects","volume":"38","author":"Durbin","year":"2017","journal-title":"Pediatr. Cardiol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1161\/CIRCRESAHA.122.322353","article-title":"hiPSCs as a Unique Platform to Model Cardiogenesis in NOTCH1-Associated HLHS: hiPSCs to Model Complex Congenital Heart Defects","volume":"132","year":"2023","journal-title":"Circ. Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1002\/humu.20958","article-title":"GJA1 mutations, variants, and connexin 43 dysfunction as it relates to the oculodentodigital dysplasia phenotype","volume":"30","author":"Paznekas","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Chung, I.M., and Rajakumar, G. (2016). Genetics of Congenital Heart Defects: The NKX2-5 Gene, a Key Player. Genes, 7.","DOI":"10.3390\/genes7020006"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.ajhg.2009.05.005","article-title":"Genomic deletions of the FOX gene cluster cause malformations","volume":"84","author":"Stankiewicz","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1161\/CIRCGENETICS.115.001070","article-title":"Recessive MYH6 Mutations in Hypoplastic Left Heart with Reduced Ejection Fraction","volume":"8","author":"Theis","year":"2015","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1161\/CIRCRESAHA.122.321398","article-title":"Impaired Human Cardiac Cell Development due to NOTCH1 Deficiency","volume":"132","author":"Ye","year":"2023","journal-title":"Circ. Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e019006","DOI":"10.1161\/JAHA.120.019006","article-title":"Genetic Etiology of Left-Sided Obstructive Heart Lesions: A Story in Development","volume":"10","author":"Parker","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1378\/chest.101.1.263","article-title":"Hypoplastic left heart syndrome associated with congenital right-sided diaphragmatic hernia and omphalocele","volume":"101","author":"Nishimura","year":"1992","journal-title":"Chest"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Datta, S., Cao, W., Skillman, M., and Wu, M. (2023). Hypoplastic Left Heart Syndrome: Signaling & Molecular Perspectives, and the Road Ahead. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242015249"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1007\/978-3-031-44087-8_61","article-title":"Molecular Pathways and Animal Models of Hypoplastic Left Heart Syndrome","volume":"1441","author":"Yagi","year":"2024","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1161\/CIRCULATIONAHA.114.009032","article-title":"Fetal aortic valvuloplasty for evolving hypoplastic left heart syndrome: Postnatal outcomes of the first 100 patients","volume":"130","author":"Freud","year":"2014","journal-title":"Circulation"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1242\/dev.01094","article-title":"BMP10 is essential for maintaining cardiac growth during murine cardiogenesis","volume":"131","author":"Chen","year":"2004","journal-title":"Development"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"S43","DOI":"10.1016\/j.jacc.2011.04.046","article-title":"Left ventricular hypoplasia: A spectrum of disease involving the left ventricular outflow tract, aortic valve, and aorta","volume":"59","author":"Hickey","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.annepidem.2016.10.003","article-title":"Proportion of selected congenital heart defects attributable to recognized risk factors","volume":"26","author":"Simeone","year":"2016","journal-title":"Ann. Epidemiol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/cvr\/cvv043","article-title":"Dual developmental role of transcriptional regulator Ets1 in Xenopus cardiac neural crest vs. heart mesoderm","volume":"106","author":"Nie","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1016\/j.jpedsurg.2008.11.002","article-title":"Increased incidence of Hirschsprung\u2019s disease in patients with hypoplastic left heart syndrome\u2014A common neural crest-derived etiology?","volume":"44","author":"Ahola","year":"2009","journal-title":"J. Pediatr. Surg."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1053\/j.semtcvs.2020.02.019","article-title":"Pathologic Characteristics of 119 Archived Specimens Showing the Phenotypic Features of Hypoplastic Left Heart Syndrome","volume":"32","author":"Stephens","year":"2020","journal-title":"Semin. Thorac. Cardiovasc. Surg."}],"container-title":["Pathophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1873-149X\/33\/2\/33\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T13:23:53Z","timestamp":1779283433000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1873-149X\/33\/2\/33"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":128,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["pathophysiology33020033"],"URL":"https:\/\/doi.org\/10.3390\/pathophysiology33020033","relation":{},"ISSN":["1873-149X"],"issn-type":[{"value":"1873-149X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]}}}