Postoperative Ascending Aortic Aneurysm in Pulmonary Atresia with Ventricular Septal Defect: Report of 3 Adult Cases

Postoperative Ascending Aortic Aneurysm in Pulmonary Atresia with Ventricular Septal Defect: Report of 3 Adult Cases | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Postoperative Ascending Aortic Aneurysm in Pulmonary Atresia with Ventricular Septal Defect: Report of 3 Adult Cases Zhengjie Zhang, Mingkui Zhang, Hui Xue, Lixin Fan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4571906/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 15 Jan, 2025 Read the published version in Journal of Cardiothoracic Surgery → Version 1 posted 31 You are reading this latest preprint version Abstract Background: Progressive dilation of the ascending aorta is prone to lead to aortic dissection in patients with pulmonary artery atresia and ventricular septal defect. However, reports of long-term complications such as aortic aneurysm or aortic dissection in adults with pulmonary artery atresia are relatively rare. Case presentation: Case 1: A 38-year-old male patient diagnosed with "pulmonary artery atresia, ventricular septal defect, bicuspid aortic valve deformity" underwent ventricular septal defect repair, aortic valve replacement, and correction of pulmonary artery atresia at the age of 21. Seventeen years postoperatively, he developed aortic dissection and underwent Bentall surgery. Case 2: A 33-year-old male patient diagnosed with "pulmonary artery atresia, ventricular septal defect" underwent Blalock-Taussig shunt surgery at the age of 17. Sixteen years postoperatively, he developed aortic root aneurysm and ascending aortic dilation. Case 3: A 42-year-old female patient diagnosed with "pulmonary artery atresia, ventricular septal defect" underwent pulmonary artery atresia corrective surgery and ventricular septal defect repair at the age of 14. Twenty-eight years postoperatively, she developed aortic root aneurysm and ascending aortic dilation. Conclusions: Following corrective surgery for pulmonary artery atresia with ventricular septal defect, long-term follow-up monitoring is necessary. Progressive dilation of the aorta should be promptly intervened to prevent the occurrence of aortic dissection. Pulmonary Atresia Aortic Sinus Aneurysm Aortic Dissection Ascending Aorta Dilation Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Congenital pulmonary atresia with ventricular septal defect (PA/VSD) is a rare congenital cardiovascular disease. According to reports, there are seven cases of PA/VSD among 100,000 live births, accounting for approximately 1–2% of children with congenital heart disease( 1 ). In patients with pulmonary atresia, pulmonary blood flow is supplied via extracardiac pathways, most commonly through the ductus arteriosus (ductal-dependent), major aortopulmonary collateral arteries (MAPCAs, MAPCA-dependent), or a combination of both ( 2 ).There is limited literature reporting on the long-term progressive dilation of the ascending aorta or aortic dissection following corrective or shunting surgery for pulmonary atresia with ventricular septal defect, and the underlying mechanisms remain unclear. We present three cases of adult patients with congenital pulmonary artery atresia who underwent surgical correction and developed varying degrees of aortic root and ascending aortic dilation in the long term, with one case progressing to a rare giant ascending aortic aneurysm and aortic dissection. Case Presentation Case 1 A 38-year-old middle-aged male patient presented with heart murmurs detected at 8 months old, accompanied by mild cyanosis of the lips and face, which worsened over time along with decreased exercise tolerance. He sought medical attention at our hospital at the age of 21. Physical examination revealed chronic illness appearance, cyanosis of the lips and skin, cardiomegaly, grade III/6 diastolic murmur at the aortic valve auscultation area, and systolic murmur audible at the left sternal border between the third and fourth ribs. Color Doppler echocardiography indicated aortic root diameter of 34mm, ascending aorta diameter of 43mm, right ventricular hypertrophy of 11mm, a 30mm subaortic ventricular septal defect with bidirectional shunting, aortic override of the ventricular septum, predominantly originating from the right ventricle with an override rate of approximately 75%, and no visible right ventricular outflow tract, pulmonary valve, or main pulmonary artery structure(Figure 1 A and B). Cardiac catheterization revealed formation of systemic-to-pulmonary collaterals (Fig. 1 C). The diagnosis was pulmonary atresia with ventricular septal defect, moderate aortic valve regurgitation, bicuspid aortic valve deformity, systemic-to-pulmonary collateral formation, tricuspid valve insufficiency, and patent foramen ovale. Intraoperative exploration revealed right ventricular hypertrophy, aortic override of the ventricular septum with an override rate of approximately 70%, a 3.0 cm subaortic ventricular septal defect, pulmonary artery atresia, hypoplastic left and right pulmonary arteries, tricuspid valve incompetence, bicuspid aortic valve deformity with calcification and severe regurgitation, and patent foramen ovale with a diameter of 5 mm, along with systemic-to-pulmonary collateral formation. The patient underwent corrective surgery for pulmonary atresia with ventricular septal defect, tricuspid valve repair, patent foramen ovale closure, and ligation of systemic-to-pulmonary collaterals. Postoperative Doppler echocardiography revealed no residual shunt at the ventricular septal defect repair site, normal reconstruction of the right ventricular outflow tract after pulmonary artery atresia closure, and normal function of the prosthetic aortic valve with minimal tricuspid valve regurgitation (Fig. 1 D and E). The patient recovered smoothly postoperatively, with significant improvement in symptoms. Regular follow-up examinations after discharge showed no abnormalities. Seventeen years postoperatively, in January 2023, the patient developed chest pain and dyspnea after exertion. Color Doppler echocardiography revealed an aneurysmal-like dilation of the sinus and ascending aorta, with a 1.6cm echo defect in the posterior wall of the aorta approximately 5.3cm above the aortic valve, communicating with a larger cavity, indicating aortic dissection. Further examination with chest CTA confirmed the diagnosis of aortic dissection and aneurysmal-like dilation of the ascending aorta (Fig. 2 A and B). There was a risk of imminent rupture of the aneurysm leading to sudden death. Emergency surgical intervention was performed, revealing severe dilation of the ascending aorta with a diameter of 15cm, extending from the ascending aorta to the aortic root, with a rupture located 10cm above the aortic valve on the right side of the ascending aorta (Fig. 2 C and D). Additionally, a residual leak of 6mm was observed at the site of the repaired ventricular septal defect. A Bentall procedure (replacement of the ascending aorta with a composite graft containing a prosthetic aortic valve) along with ventricular septal defect repair was performed. The surgery proceeded smoothly. Postoperatively, follow-up ultrasound showed successful reconstruction of the ventricular septal defect and right ventricular outflow tract, normal function of the prosthetic aortic valve with minimal regurgitation after the Bentall procedure, and significant improvement in the patient's symptoms. Case 2 A 33-year-old male patient presented with cyanosis of the lips, heart murmurs, chest tightness, shortness of breath, and a preference for squatting after exertion since birth. He sought outpatient consultation at our hospital at the age of 17. Cardiac ultrasound examination revealed aortic root diameter of 42mm, ascending aorta diameter of 36mm, 30mm subaortic ventricular septal defect with bidirectional shunting, aortic override of the ventricular septum with an override rate of approximately 50%, absence of pulmonary valve opening on multi-angle exploration, and a 12mm diameter in the right pulmonary artery with visible systemic-to-pulmonary collateral vessels. Cardiac catheterization revealed formation of prominent systemic-to-pulmonary collateral vessels (Fig. 3 A and B). Based on the medical history, physical examination, and auxiliary examinations, the diagnosis was pulmonary atresia with ventricular septal defect, aortic override, and systemic-to-pulmonary collateral formation. Due to poor development of the pulmonary artery, the patient underwent a Blalock-Taussig shunt procedure. Postoperative ultrasound showed aortic root diameter of 42mm, ascending aorta diameter of 35mm, pulmonary atresia, membranous perimembranous ventricular septal defect of 31mm, aortic override, and smooth blood flow after the Blalock-Taussig shunt procedure. The patient recovered well postoperatively but did not attend regular follow-up appointments. Sixteen years postoperatively, the patient experienced chest tightness and shortness of breath without obvious triggers after exertion. Subsequently, the symptoms worsened, with chest tightness occurring at rest and an inability to lie flat at night. He presented at our hospital outpatient clinic with cyanosis, grade IV/6 systolic murmur at the left third and fourth intercostal spaces, and grade III/6 diastolic murmur at the aortic auscultation area. Cardiac ultrasound examination revealed aortic root diameter of 74mm, ascending aorta diameter of 48mm, pulmonary atresia with ventricular septal defect, aortic override, post-Blalock-Taussig shunt, significant aneurysmal-like dilation of the aortic sinus, ascending aortic dilation, moderate to severe aortic valve regurgitation, global cardiac enlargement, and impaired left ventricular systolic function (Fig. 3 C). Further confirmation of ascending aortic dilation and aneurysmal-like dilation of the aortic sinus was provided by aortic CTA (Fig. 3 D and E). Case 3 A 42-year-old female patient, diagnosed with congenital heart disease since childhood, underwent corrective surgery for pulmonary atresia with ventricular septal defect at the age of 14 at an outside hospital, but did not attend regular follow-up appointments postoperatively. In March 2022, the patient experienced dyspnea, palpitations, and cough without apparent triggers, with intermittent exacerbations of symptoms that gradually worsened over time. In March 2023, she sought outpatient consultation at our hospital. Physical examination revealed coarse breath sounds in both lungs without obvious crackles or wheezing. Cardiac auscultation revealed a grade III/6 systolic murmur at the left third and fourth intercostal spaces and a grade III/6 diastolic sigh-like murmur at the aortic auscultation area. Echocardiography showed global cardiac enlargement, aortic sinus diameter of 55mm, ascending aorta diameter of 51mm, main pulmonary artery diameter of 33mm, residual shunting at the ventricular septal defect level post-corrective surgery for aortic override and pulmonary atresia, patent foramen ovale, aneurysmal-like dilation of the aortic sinus, ascending aortic dilation, and severe aortic valve regurgitation (Fig. 4 A). Whole aortic CTA confirmed the ascending aortic dilation and aneurysmal-like dilation of the aortic sinus (Fig. 4 B-D). Discussion and Conclusion We report three cases of adults with pulmonary atresia with ventricular septal defect (PA/VSD), all diagnosed with congenital heart disease since childhood. Two patients underwent definitive corrective surgery, while one patient underwent palliative surgery. Several years postoperatively, all three patients developed varying degrees of aortic root aneurysms and ascending aortic dilation. In one case, this progression led to the development of a massive aortic root aneurysm and aortic dissection(The clinical characteristics of the three patients are summarized in Table 1.( 2 , 3 )). PA/VSD is a complex cyanotic congenital heart disease, also known as Tetralogy of Fallot (TOF) with pulmonary atresia ( 4 – 6 ).It accounts for 20% of all TOF cases and 2% of all congenital heart diseases (CHD). Niwa et al.'s study found that approximately 15% of adult cases after TOF corrective surgery exhibited significant aortic dilation( 7 ). There are very few reports in the current literature of aortic root aneurysms, dissections, or ruptures in patients with TOF. Furthermore, there are even fewer reported cases documenting the postoperative outcomes specifically in patients with PA/VSD. The potential mechanisms for the occurrence of aortic root aneurysms, ascending aortic dilation, and aortic dissection in PA/VSD patients include alterations in aortic histopathology, hemodynamic changes, and genetic susceptibility. Studies in the congenital heart disease (CHD) population have found that abnormalities in smooth muscle, elastic fibers, collagen, and matrix in the media layer of the ascending aorta are commonly present in all CHD patients, predisposing them to aortic dilation. Chowdhury et al. analyzed aortic wall tissues from 74 patients undergoing corrective surgery for TOF. The results showed that 78.4% of aortic tissue specimens exhibited significant medial layer loss, and 96% showed abnormal histopathological changes. Patients with histopathological changes had an 8.83 times higher risk of developing aortic dilation compared to those without histopathological changes( 7 ). The hemodynamic changes in PA/VSD also play a significant role in the development of aortic abnormalities. Pulmonary artery atresia combined with a large ventricular septal defect leads to abnormal right-to-left shunting, resulting in increased blood flow to the aorta. Additionally, in three cases, there was prolonged overriding of the aorta over both ventricles, leading to aortic valve insufficiency and volume overload. This volume overload exerts maximum shear force on the aortic root and ascending aorta ( 7 ). Francois et al.'s retrospective study of 88 TOF patients found a significant regression in indexed aortic root dimensions over time, highlighting the necessity of early stage correction in TOF cases( 7 ). There is a significant familial tendency in the occurrence of PA/VSD, although the coexistence with non-chromosomal anomalies is not common. PA/VSD combined with chromosomal microdeletions, particularly 22q11.2 microdeletion syndrome, is frequent. Furthermore, studies have indicated a significantly increased probability of PA/VSD patients with associated MAPCAs or right-sided aortic arch having 22q11.2 microdeletion syndrome ( 8 , 9 )。In addition, age and gender are also risk factors for aortic dilation in patients with congenital heart disease. Patient Sex Age (year) Castaneda /Tchervenkov Surgery type at age (year) Postoperative aortic root/ascending aorta diameter (mm) Aortic valve leaflets Follow-up aortic root/ascending aorta diameter (mm) Treatment Case1 m 38 Ⅲ/B Corrective surgery (21) 34/43 2 59/48 Bentall operation + VSD repair Case2 m 32 Ⅲ/B B-T shunt (17) 42/35 3 75/48 Follow-up Case3 f 42 Ⅲ/B Corrective surgery (14) - 3 55/51 Follow-up Among the three cases, one was diagnosed with bicuspid aortic valve (BAV), and this was the only case that progressed to aortic dissection. Research on bicuspid aortic valve has found that BAV increases the risk of aortic dilation and aortic dissection in patients( 10 ). Bissell et al( 11 ) Research shows that up to 80% of young patients with bicuspid aortic valve (BAV) have concomitant ascending aortic dilatation (AAD), with a risk of aortic dissection or rupture 5 to 10 times higher than the general population. The pathogenic factors associated with AAD in BAV patients include genetic inheritance, hemodynamics, metalloproteinases, age, and other factors( 12 – 14 ). Bicuspid aortic valve (BAV) disease exhibits familial aggregation, and its inheritance pattern is autosomal dominant ( 15 , 16 ). Moreover, current clinical research results have confirmed that mutations in multiple genes such as KCNJ2, NOS3, NOTCH1, and SMAD6 are associated with the occurrence of bicuspid aortic valve (BAV)( 17 – 19 ). The BAV patient reported by us underwent aortic valve replacement surgery due to severe aortic valve regurgitation during the first operation. However, they still progressed to a dissecting aortic aneurysm. Currently, there are studies suggesting that early aortic replacement surgery in BAV patients, restoring normal hemodynamics, may reduce the incidence of aortic dissection ( 20 ), This suggests the necessity of early surgical intervention. Michelena et al ( 21 ) Research has found that BAV patients without valvular dysfunction can still develop AAD. Pathological findings suggest cystic medial necrosis and elastic fiber fragmentation in the aortic media, indicating that structural developmental abnormalities are important factors in ascending aortic damage. Rueda-Martinez et al." and "Navarrete et al. ( 22 , 23 ) Research indicates that BAV patients exhibit upregulation of aortic extracellular matrix proteins, leading to increased susceptibility of the aortic medial layer elastic fibers to damage, thereby contributing to the development of AAD.Table 1 The Clinical Characteristics of Three Patients. The three cases of adults we report who underwent corrective surgery for PA/VSD and subsequently developed complications such as aortic root aneurysms, ascending aortic dilation, and even aortic dissection rupture serve as clinical examples. While this constitutes a small sample size from a single center, it serves as a warning to clinicians dealing with such patients to fully consider the risk factors associated with aortic pathology. Additionally, regular follow-up and imaging examinations are crucial for early detection and intervention of aortic-related complications. When determining surgical treatment, a comprehensive evaluation of the patient's overall condition and the characteristics of the aneurysm should be conducted, and appropriate treatment strategies should be implemented. Abbreviations PV pulmonary atresia VSD ventricular septal defect MAPCAs major aortopulmonary collateral arteries TOF tetralogy of fallot CHD congenital heart disease BAV bicuspid aortic valve AAD ascending aortic dilatation Declarations Acknowledgements The author would like to thank Dr. Tang Xiujie and Dr. Niu Yonghong for their support in radiological diagnosis. Author contributions ZJ and MK wrote the main manuscript text. ZJ collected and prepared the clinical data of the patients.H.X. and LX participated in patients care. MZ revised the manuscript. All authors reviewed the manuscript. All authors read and approved the fnal manuscript. Funding This work was supported by Beijing Natural Science Foundation（2024G101） and Tsinghua Precision Medicine Foundation (No. 10001020132 and No. 100010714 No. 100020104). Availability of data and materials The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate This work has received approval from the Ethics Committee of the First Hospital of Tsinghua University. Consent for publication Not applicable. Competing interests We declare that the research was conducted in the absence of any commercial or fnancial relationships that could be construed as a potential confict of interest. References Chan KC, Fyfe DA, McKay CA, Sade RM, Crawford FA. Right ventricular outflow reconstruction with cryopreserved homografts in pediatric patients: intermediate-term follow-up with serial echocardiographic assessment. J Am Coll Cardiol. 1994;24(2):483–9. Tchervenkov CI, Roy N. Congenital Heart Surgery Nomenclature and Database Project: pulmonary atresia–ventricular septal defect. Ann Thorac Surg. 2000;69(4 Suppl):S97–105. Castañeda AR. Cardiac surgery of the neonate and infant. Cardiac surgery of the neonate and infant; 1994. Meinel FG, Huda W, Schoepf UJ, Rao AG, Cho YJ, Baker GH, et al. Diagnostic accuracy of CT angiography in infants with tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral arteries. J Cardiovasc Comput Tomogr. 2013;7(6):367–75. Mackie AS, Gauvreau K, Perry SB, del Nido PJ, Geva T. Echocardiographic predictors of aortopulmonary collaterals in infants with tetralogy of fallot and pulmonary atresia. J Am Coll Cardiol. 2003;41(5):852–7. Asija R, Roth SJ, Hanley FL, Peng L, Liu K, Abbott J, et al. Reperfusion pulmonary edema in children with tetralogy of Fallot, pulmonary atresia, and major aortopulmonary collateral arteries undergoing unifocalization procedures: A pilot study examining potential pathophysiologic mechanisms and clinical significance. J Thorac Cardiovasc Surg. 2014;148(4):1560–5. Ramaprabhu K, Idhrees M, Velayudhan B. Aortopathy in tetralogy of Fallot-a collective review. Indian J Thorac Cardiovasc Surg. 2019;35(4):575–8. Gómez O, Soveral I, Bennasar M, Crispi F, Masoller N, Marimon E, et al. Accuracy of Fetal Echocardiography in the Differential Diagnosis between Truncus Arteriosus and Pulmonary Atresia with Ventricular Septal Defect. Fetal Diagn Ther. 2016;39(2):90–9. Peyvandi S, Lupo PJ, Garbarini J, Woyciechowski S, Edman S, Emanuel BS, et al. 22q11.2 deletions in patients with conotruncal defects: data from 1,610 consecutive cases. Pediatr Cardiol. 2013;34(7):1687–94. !!! INVALID CITATION !!! [10]. Bissell MM, Hess AT, Biasiolli L, Glaze SJ, Loudon M, Pitcher A, et al. Aortic dilation in bicuspid aortic valve disease: flow pattern is a major contributor and differs with valve fusion type. Circ Cardiovasc Imaging. 2013;6(4):499–507. McKellar SH, Michelena HI, Li Z, Schaff HV, Sundt TM 3. Long-term risk of aortic events following aortic valve replacement in patients with bicuspid aortic valves. Am J Cardiol. 2010;106(11):1626–33. Henn D, Bandner-Risch D, Perttunen H, Schmied W, Porras C, Ceballos F, et al. Identification of reference genes for quantitative RT-PCR in ascending aortic aneurysms. PLoS ONE. 2013;8(1):e54132. Wang H, Zhu Y, Zhao M, Wu C, Zhang P, Tang L, et al. miRNA-29c suppresses lung cancer cell adhesion to extracellular matrix and metastasis by targeting integrin β1 and matrix metalloproteinase2 (MMP2). PLoS ONE. 2013;8(8):e70192. Aboulhosn J, Child JS. Left ventricular outflow obstruction: subaortic stenosis, bicuspid aortic valve, supravalvar aortic stenosis, and coarctation of the aorta. Circulation. 2006;114(22):2412–22. Martín M, Pichel IA, Flórez Muñoz JP, Naves-Díaz M, Palacín M, Cannata-Andía JB, et al. Low transcriptional activity haplotype of matrix metalloproteinase 1 is less frequent in bicuspid aortic valve patients. Gene. 2013;524(2):304–8. Bravo-Jaimes K, Prakash SK. Genetics in bicuspid aortic valve disease: Where are we? Prog Cardiovasc Dis. 2020;63(4):398–406. Gould RA, Aziz H, Woods CE, Seman-Senderos MA, Sparks E, Preuss C, et al. ROBO4 variants predispose individuals to bicuspid aortic valve and thoracic aortic aneurysm. Nat Genet. 2019;51(1):42–50. Wünnemann F, Ta-Shma A, Preuss C, Leclerc S, van Vliet PP, Oneglia A, et al. Loss of ADAMTS19 causes progressive non-syndromic heart valve disease. Nat Genet. 2020;52(1):40–7. Girdauskas E, Disha K, Borger MA, Kuntze T. Risk of proximal aortic dissection in patients with bicuspid aortic valve: how to address this controversy? Interactive cardiovascular and thoracic surgery. 2014;18(3):355–9. Michelena HI, Della Corte A, Prakash SK, Milewicz DM, Evangelista A, Enriquez-Sarano M. Bicuspid aortic valve aortopathy in adults: Incidence, etiology, and clinical significance. Int J Cardiol. 2015;201:400–7. Rueda-Martínez C, Lamas O, Mataró MJ, Robledo-Carmona J, Sánchez-Espín G, Moreno-Santos I, et al. Fibrillin 2 is upregulated in the ascending aorta of patients with bicuspid aortic valve. Eur J Cardiothorac Surg. 2017;51(1):104–11. Navarrete Santos A, Yan J, Lochmann P, Pfeil H, Petersen M, Simm A, et al. Collagen analysis of the ascending aortic dilatation associated with bicuspid aortic valve disease compared with tricuspid aortic valve. Arch Physiol Biochem. 2016;122(5):289–94. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 15 Jan, 2025 Read the published version in Journal of Cardiothoracic Surgery → Version 1 posted Editorial decision: Revision requested 29 Jul, 2024 Reviewers agreed at journal 20 Jul, 2024 Reviews received at journal 17 Jul, 2024 Reviews received at journal 16 Jul, 2024 Reviews received at journal 12 Jul, 2024 Reviews received at journal 11 Jul, 2024 Reviews received at journal 11 Jul, 2024 Reviews received at journal 11 Jul, 2024 Reviews received at journal 10 Jul, 2024 Reviews received at journal 10 Jul, 2024 Reviews received at journal 08 Jul, 2024 Reviewers agreed at journal 07 Jul, 2024 Reviewers agreed at journal 06 Jul, 2024 Reviewers agreed at journal 06 Jul, 2024 Reviewers agreed at journal 06 Jul, 2024 Reviewers agreed at journal 03 Jul, 2024 Reviewers agreed at journal 03 Jul, 2024 Reviewers agreed at journal 03 Jul, 2024 Reviews received at journal 02 Jul, 2024 Reviewers agreed at journal 01 Jul, 2024 Reviewers agreed at journal 01 Jul, 2024 Reviewers agreed at journal 01 Jul, 2024 Reviewers agreed at journal 01 Jul, 2024 Reviewers agreed at journal 01 Jul, 2024 Reviewers agreed at journal 01 Jul, 2024 Reviewers agreed at journal 01 Jul, 2024 Reviewers agreed at journal 01 Jul, 2024 Reviewers invited by journal 01 Jul, 2024 Editor assigned by journal 17 Jun, 2024 Submission checks completed at journal 17 Jun, 2024 First submitted to journal 12 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4571906","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":321783989,"identity":"141e4908-4c1b-4629-8557-ef5e6dc22114","order_by":0,"name":"Zhengjie Zhang","email":"","orcid":"","institution":"Tsinghua University","correspondingAuthor":false,"prefix":"","firstName":"Zhengjie","middleName":"","lastName":"Zhang","suffix":""},{"id":321783992,"identity":"02bc9790-a48f-4dd3-963a-f52ff0aa1a81","order_by":1,"name":"Mingkui Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3UlEQVRIie3PMQrCMBSA4RcC7RJ1zSWEJ4GoWOphhExBnBzFqS49gN5Cb1AMOqldO7iIIIgOdXNwsLrp0NbNId/0HuQnCYBl/SMKQMbAAV9Lip7/W0KmA9UrdVGWwDuhLF2+l1z1ScWcZ0Gr23S35uJhRME1q3leIk1VtRcBp+2wrzoa91VgSiX5CZONQ8AdjLQUGk8UOJOlEobxVYoWGjIukYhD9jCOiRZHKJlIMt1xxOQqSYiq5xT+Jd6IWzgcdTHWIr0/PL/mmnVuknH4x+AUHH+h6fdgWZZlfXgCmPpJCf2yrw8AAAAASUVORK5CYII=","orcid":"","institution":"Tsinghua University","correspondingAuthor":true,"prefix":"","firstName":"Mingkui","middleName":"","lastName":"Zhang","suffix":""},{"id":321783994,"identity":"30a9e311-816e-45dc-a6c3-9da444e5195c","order_by":2,"name":"Hui Xue","email":"","orcid":"","institution":"The First Affiliated Hospital of Tsinghua University","correspondingAuthor":false,"prefix":"","firstName":"Hui","middleName":"","lastName":"Xue","suffix":""},{"id":321783995,"identity":"be64e057-4b3c-436c-9582-15e628e48a0b","order_by":3,"name":"Lixin Fan","email":"","orcid":"","institution":"The First Affiliated Hospital of Tsinghua University","correspondingAuthor":false,"prefix":"","firstName":"Lixin","middleName":"","lastName":"Fan","suffix":""}],"badges":[],"createdAt":"2024-06-12 17:50:58","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4571906/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4571906/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13019-024-03293-7","type":"published","date":"2025-01-15T15:56:51+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":60435735,"identity":"4c30ace2-dea8-449a-8928-01095e3beecb","added_by":"auto","created_at":"2024-07-16 17:25:24","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":221630,"visible":true,"origin":"","legend":"\u003cp\u003ePanel A and B: Preoperative echocardiography of PA/VSD, showing subaortic ventricular septal defect with absence of right ventricular outflow tract, pulmonary valve, and main pulmonary artery structure. The red arrows in Panel A indicate the area of the ventricular septal defect, while the red arrows in Panel B indicate the same area. Panel C: Preoperative right ventricular and aortic root angiography demonstrating prominent systemic-to-pulmonary collateral vessels originating from the aorta, indicated by the red arrows. Panels D and E: Postoperative echocardiography following pulmonary atresia with ventricular septal defect corrective surgery. Panel D shows reconstruction of the right ventricular outflow tract with bidirectional flow in the reconstructed pulmonary artery. Panel E indicates the repaired area of the ventricular septal defect, as highlighted by the red arrows.\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-4571906/v1/e6ebd147f23983873389d915.png"},{"id":60435736,"identity":"9159a242-626f-4f27-85fe-e6d878c7b57a","added_by":"auto","created_at":"2024-07-16 17:25:24","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":313070,"visible":true,"origin":"","legend":"\u003cp\u003ePanel A and B: Preoperative CT and three-dimensional reconstruction of the aortic dissection. The red arrows in Panel A indicate the area of the aortic dissection defect, while the red arrows in Panel B indicate the dilated ascending aorta. Panel C and D: Intraoperative exploration of the ascending aortic aneurysm and dissection rupture site. The white arrow in Panel D indicates the area where the aortic dissection defect was discovered during the intraoperative exploration.\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-4571906/v1/cf4b4012cc87bb8a448d9978.png"},{"id":60435734,"identity":"17bf1c7e-1691-4755-a59b-aa072137b3ce","added_by":"auto","created_at":"2024-07-16 17:25:24","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":204413,"visible":true,"origin":"","legend":"\u003cp\u003ePanel A and B: Preoperative cardiac catheterization for pulmonary atresia, showing no sequential filling of the pulmonary artery in right ventricular angiography, with two prominent branches originating from the descending aorta. The red arrow in Panel B indicates the prominent branch vessel. Panel C: Echocardiography showing significant aneurysmal-like dilation of the aortic sinus. Panel D-F: Congenital heart disease-enhanced CTA and three-dimensional reconstruction, demonstrating ascending aortic dilation and aneurysmal-like dilation of the aortic sinus. The left side of the ascending aortic wall is connected to the pulmonary artery by an artificial conduit, as indicated by the red arrows in Panel D (B-T shunt conduit) and Panel E (dilated ascending aortic root and ascending aorta).\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-4571906/v1/a5966449907c8b2e66407be4.png"},{"id":60436410,"identity":"2dd003b0-5f36-4ed4-831b-ca8b6f2f8767","added_by":"auto","created_at":"2024-07-16 17:33:24","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":285982,"visible":true,"origin":"","legend":"\u003cp\u003ePanel A: Echocardiography showing global cardiac enlargement. Post-repair residual shunt at the right ventricular end of the patch, indicated by the red arrow. Panels B-D: Congenital heart disease-enhanced CTA and three-dimensional reconstruction, depicting changes post-corrective surgery for pulmonary atresia. There is widening of the ascending aorta and aneurysmal-like dilation of the aortic sinus. Panels C and D: The red arrows indicate the dilated ascending aortic sinus and ascending aorta.\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-4571906/v1/ee23d805dcd4fadd19d0b552.png"},{"id":74284438,"identity":"9ddca12a-7527-411f-bb61-e4fe6351495c","added_by":"auto","created_at":"2025-01-20 16:05:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1781634,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4571906/v1/a720a43d-7117-4946-879d-c8268440491b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Postoperative Ascending Aortic Aneurysm in Pulmonary Atresia with Ventricular Septal Defect: Report of 3 Adult Cases","fulltext":[{"header":"Background","content":"\u003cp\u003eCongenital pulmonary atresia with ventricular septal defect (PA/VSD) is a rare congenital cardiovascular disease. According to reports, there are seven cases of PA/VSD among 100,000 live births, accounting for approximately 1\u0026ndash;2% of children with congenital heart disease(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). In patients with pulmonary atresia, pulmonary blood flow is supplied via extracardiac pathways, most commonly through the ductus arteriosus (ductal-dependent), major aortopulmonary collateral arteries (MAPCAs, MAPCA-dependent), or a combination of both (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).There is limited literature reporting on the long-term progressive dilation of the ascending aorta or aortic dissection following corrective or shunting surgery for pulmonary atresia with ventricular septal defect, and the underlying mechanisms remain unclear. We present three cases of adult patients with congenital pulmonary artery atresia who underwent surgical correction and developed varying degrees of aortic root and ascending aortic dilation in the long term, with one case progressing to a rare giant ascending aortic aneurysm and aortic dissection.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003e\u003cb\u003eCase\u003c/b\u003e 1\u003c/p\u003e\u003cp\u003eA 38-year-old middle-aged male patient presented with heart murmurs detected at 8 months old, accompanied by mild cyanosis of the lips and face, which worsened over time along with decreased exercise tolerance. He sought medical attention at our hospital at the age of 21. Physical examination revealed chronic illness appearance, cyanosis of the lips and skin, cardiomegaly, grade III/6 diastolic murmur at the aortic valve auscultation area, and systolic murmur audible at the left sternal border between the third and fourth ribs. Color Doppler echocardiography indicated aortic root diameter of 34mm, ascending aorta diameter of 43mm, right ventricular hypertrophy of 11mm, a 30mm subaortic ventricular septal defect with bidirectional shunting, aortic override of the ventricular septum, predominantly originating from the right ventricle with an override rate of approximately 75%, and no visible right ventricular outflow tract, pulmonary valve, or main pulmonary artery structure(Figure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA and B). Cardiac catheterization revealed formation of systemic-to-pulmonary collaterals (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). The diagnosis was pulmonary atresia with ventricular septal defect, moderate aortic valve regurgitation, bicuspid aortic valve deformity, systemic-to-pulmonary collateral formation, tricuspid valve insufficiency, and patent foramen ovale. Intraoperative exploration revealed right ventricular hypertrophy, aortic override of the ventricular septum with an override rate of approximately 70%, a 3.0 cm subaortic ventricular septal defect, pulmonary artery atresia, hypoplastic left and right pulmonary arteries, tricuspid valve incompetence, bicuspid aortic valve deformity with calcification and severe regurgitation, and patent foramen ovale with a diameter of 5 mm, along with systemic-to-pulmonary collateral formation. The patient underwent corrective surgery for pulmonary atresia with ventricular septal defect, tricuspid valve repair, patent foramen ovale closure, and ligation of systemic-to-pulmonary collaterals. Postoperative Doppler echocardiography revealed no residual shunt at the ventricular septal defect repair site, normal reconstruction of the right ventricular outflow tract after pulmonary artery atresia closure, and normal function of the prosthetic aortic valve with minimal tricuspid valve regurgitation (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD and E). The patient recovered smoothly postoperatively, with significant improvement in symptoms. Regular follow-up examinations after discharge showed no abnormalities.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eSeventeen years postoperatively, in January 2023, the patient developed chest pain and dyspnea after exertion. Color Doppler echocardiography revealed an aneurysmal-like dilation of the sinus and ascending aorta, with a 1.6cm echo defect in the posterior wall of the aorta approximately 5.3cm above the aortic valve, communicating with a larger cavity, indicating aortic dissection. Further examination with chest CTA confirmed the diagnosis of aortic dissection and aneurysmal-like dilation of the ascending aorta (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA and B). There was a risk of imminent rupture of the aneurysm leading to sudden death. Emergency surgical intervention was performed, revealing severe dilation of the ascending aorta with a diameter of 15cm, extending from the ascending aorta to the aortic root, with a rupture located 10cm above the aortic valve on the right side of the ascending aorta (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC and D). Additionally, a residual leak of 6mm was observed at the site of the repaired ventricular septal defect. A Bentall procedure (replacement of the ascending aorta with a composite graft containing a prosthetic aortic valve) along with ventricular septal defect repair was performed. The surgery proceeded smoothly. Postoperatively, follow-up ultrasound showed successful reconstruction of the ventricular septal defect and right ventricular outflow tract, normal function of the prosthetic aortic valve with minimal regurgitation after the Bentall procedure, and significant improvement in the patient's symptoms.\u003c/p\u003e\u003cp\u003eCase 2\u003c/p\u003e\u003cp\u003eA 33-year-old male patient presented with cyanosis of the lips, heart murmurs, chest tightness, shortness of breath, and a preference for squatting after exertion since birth. He sought outpatient consultation at our hospital at the age of 17. Cardiac ultrasound examination revealed aortic root diameter of 42mm, ascending aorta diameter of 36mm, 30mm subaortic ventricular septal defect with bidirectional shunting, aortic override of the ventricular septum with an override rate of approximately 50%, absence of pulmonary valve opening on multi-angle exploration, and a 12mm diameter in the right pulmonary artery with visible systemic-to-pulmonary collateral vessels. Cardiac catheterization revealed formation of prominent systemic-to-pulmonary collateral vessels (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA and B). Based on the medical history, physical examination, and auxiliary examinations, the diagnosis was pulmonary atresia with ventricular septal defect, aortic override, and systemic-to-pulmonary collateral formation. Due to poor development of the pulmonary artery, the patient underwent a Blalock-Taussig shunt procedure. Postoperative ultrasound showed aortic root diameter of 42mm, ascending aorta diameter of 35mm, pulmonary atresia, membranous perimembranous ventricular septal defect of 31mm, aortic override, and smooth blood flow after the Blalock-Taussig shunt procedure. The patient recovered well postoperatively but did not attend regular follow-up appointments. Sixteen years postoperatively, the patient experienced chest tightness and shortness of breath without obvious triggers after exertion. Subsequently, the symptoms worsened, with chest tightness occurring at rest and an inability to lie flat at night. He presented at our hospital outpatient clinic with cyanosis, grade IV/6 systolic murmur at the left third and fourth intercostal spaces, and grade III/6 diastolic murmur at the aortic auscultation area. Cardiac ultrasound examination revealed aortic root diameter of 74mm, ascending aorta diameter of 48mm, pulmonary atresia with ventricular septal defect, aortic override, post-Blalock-Taussig shunt, significant aneurysmal-like dilation of the aortic sinus, ascending aortic dilation, moderate to severe aortic valve regurgitation, global cardiac enlargement, and impaired left ventricular systolic function (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC). Further confirmation of ascending aortic dilation and aneurysmal-like dilation of the aortic sinus was provided by aortic CTA (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eD and E).\u003c/p\u003e\u003cp\u003eCase 3\u003c/p\u003e\u003cp\u003eA 42-year-old female patient, diagnosed with congenital heart disease since childhood, underwent corrective surgery for pulmonary atresia with ventricular septal defect at the age of 14 at an outside hospital, but did not attend regular follow-up appointments postoperatively. In March 2022, the patient experienced dyspnea, palpitations, and cough without apparent triggers, with intermittent exacerbations of symptoms that gradually worsened over time. In March 2023, she sought outpatient consultation at our hospital. Physical examination revealed coarse breath sounds in both lungs without obvious crackles or wheezing. Cardiac auscultation revealed a grade III/6 systolic murmur at the left third and fourth intercostal spaces and a grade III/6 diastolic sigh-like murmur at the aortic auscultation area. Echocardiography showed global cardiac enlargement, aortic sinus diameter of 55mm, ascending aorta diameter of 51mm, main pulmonary artery diameter of 33mm, residual shunting at the ventricular septal defect level post-corrective surgery for aortic override and pulmonary atresia, patent foramen ovale, aneurysmal-like dilation of the aortic sinus, ascending aortic dilation, and severe aortic valve regurgitation (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA). Whole aortic CTA confirmed the ascending aortic dilation and aneurysmal-like dilation of the aortic sinus (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB-D).\u003c/p\u003e"},{"header":"Discussion and Conclusion","content":"\u003cp\u003eWe report three cases of adults with pulmonary atresia with ventricular septal defect (PA/VSD), all diagnosed with congenital heart disease since childhood. Two patients underwent definitive corrective surgery, while one patient underwent palliative surgery. Several years postoperatively, all three patients developed varying degrees of aortic root aneurysms and ascending aortic dilation. In one case, this progression led to the development of a massive aortic root aneurysm and aortic dissection(The clinical characteristics of the three patients are summarized in Table\u0026nbsp;1.(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)). PA/VSD is a complex cyanotic congenital heart disease, also known as Tetralogy of Fallot (TOF) with pulmonary atresia (\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).It accounts for 20% of all TOF cases and 2% of all congenital heart diseases (CHD). Niwa et al.'s study found that approximately 15% of adult cases after TOF corrective surgery exhibited significant aortic dilation(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). There are very few reports in the current literature of aortic root aneurysms, dissections, or ruptures in patients with TOF. Furthermore, there are even fewer reported cases documenting the postoperative outcomes specifically in patients with PA/VSD.\u003c/p\u003e\u003cp\u003eThe potential mechanisms for the occurrence of aortic root aneurysms, ascending aortic dilation, and aortic dissection in PA/VSD patients include alterations in aortic histopathology, hemodynamic changes, and genetic susceptibility. Studies in the congenital heart disease (CHD) population have found that abnormalities in smooth muscle, elastic fibers, collagen, and matrix in the media layer of the ascending aorta are commonly present in all CHD patients, predisposing them to aortic dilation. Chowdhury et al. analyzed aortic wall tissues from 74 patients undergoing corrective surgery for TOF. The results showed that 78.4% of aortic tissue specimens exhibited significant medial layer loss, and 96% showed abnormal histopathological changes. Patients with histopathological changes had an 8.83 times higher risk of developing aortic dilation compared to those without histopathological changes(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). The hemodynamic changes in PA/VSD also play a significant role in the development of aortic abnormalities. Pulmonary artery atresia combined with a large ventricular septal defect leads to abnormal right-to-left shunting, resulting in increased blood flow to the aorta. Additionally, in three cases, there was prolonged overriding of the aorta over both ventricles, leading to aortic valve insufficiency and volume overload. This volume overload exerts maximum shear force on the aortic root and ascending aorta (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Francois et al.'s retrospective study of 88 TOF patients found a significant regression in indexed aortic root dimensions over time, highlighting the necessity of early stage correction in TOF cases(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). There is a significant familial tendency in the occurrence of PA/VSD, although the coexistence with non-chromosomal anomalies is not common. PA/VSD combined with chromosomal microdeletions, particularly 22q11.2 microdeletion syndrome, is frequent. Furthermore, studies have indicated a significantly increased probability of PA/VSD patients with associated MAPCAs or right-sided aortic arch having 22q11.2 microdeletion syndrome (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)。In addition, age and gender are also risk factors for aortic dilation in patients with congenital heart disease.\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"546\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.424908424908425%\" valign=\"top\"\u003e\n \u003cp\u003ePatient\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.677655677655678%\" valign=\"top\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.509157509157509%\" valign=\"top\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003cp\u003e(year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003eCastaneda\u003c/p\u003e\n \u003cp\u003e/Tchervenkov\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.89010989010989%\" valign=\"top\"\u003e\n \u003cp\u003eSurgery type at age (year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.384615384615385%\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative aortic root/ascending aorta diameter (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.058608058608058%\" valign=\"top\"\u003e\n \u003cp\u003eAortic valve leaflets\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3003663003663%\" valign=\"top\"\u003e\n \u003cp\u003eFollow-up aortic root/ascending aorta diameter (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.087912087912088%\" valign=\"top\"\u003e\n \u003cp\u003eTreatment\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.424908424908425%\" valign=\"top\"\u003e\n \u003cp\u003eCase1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.677655677655678%\" valign=\"top\"\u003e\n \u003cp\u003em\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.509157509157509%\" valign=\"top\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003eⅢ/B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.89010989010989%\" valign=\"top\"\u003e\n \u003cp\u003eCorrective surgery (21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.384615384615385%\" valign=\"top\"\u003e\n \u003cp\u003e34/43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.058608058608058%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3003663003663%\" valign=\"top\"\u003e\n \u003cp\u003e59/48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.087912087912088%\" valign=\"top\"\u003e\n \u003cp\u003eBentall operation + VSD repair\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.424908424908425%\" valign=\"top\"\u003e\n \u003cp\u003eCase2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.677655677655678%\" valign=\"top\"\u003e\n \u003cp\u003em\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.509157509157509%\" valign=\"top\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003eⅢ/B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.89010989010989%\" valign=\"top\"\u003e\n \u003cp\u003eB-T shunt (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.384615384615385%\" valign=\"top\"\u003e\n \u003cp\u003e42/35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.058608058608058%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3003663003663%\" valign=\"top\"\u003e\n \u003cp\u003e75/48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.087912087912088%\" valign=\"top\"\u003e\n \u003cp\u003eFollow-up\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.424908424908425%\" valign=\"top\"\u003e\n \u003cp\u003eCase3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.677655677655678%\" valign=\"top\"\u003e\n \u003cp\u003ef\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.509157509157509%\" valign=\"top\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"top\"\u003e\n \u003cp\u003eⅢ/B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.89010989010989%\" valign=\"top\"\u003e\n \u003cp\u003eCorrective surgery (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.384615384615385%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.058608058608058%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.3003663003663%\" valign=\"top\"\u003e\n \u003cp\u003e55/51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.087912087912088%\" valign=\"top\"\u003e\n \u003cp\u003eFollow-up\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\u003c/br\u003e\n\u003cp\u003eAmong the three cases, one was diagnosed with bicuspid aortic valve (BAV), and this was the only case that progressed to aortic dissection. Research on bicuspid aortic valve has found that BAV increases the risk of aortic dilation and aortic dissection in patients(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Bissell et al(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) Research shows that up to 80% of young patients with bicuspid aortic valve (BAV) have concomitant ascending aortic dilatation (AAD), with a risk of aortic dissection or rupture 5 to 10 times higher than the general population. The pathogenic factors associated with AAD in BAV patients include genetic inheritance, hemodynamics, metalloproteinases, age, and other factors(\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Bicuspid aortic valve (BAV) disease exhibits familial aggregation, and its inheritance pattern is autosomal dominant (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Moreover, current clinical research results have confirmed that mutations in multiple genes such as KCNJ2, NOS3, NOTCH1, and SMAD6 are associated with the occurrence of bicuspid aortic valve (BAV)(\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). The BAV patient reported by us underwent aortic valve replacement surgery due to severe aortic valve regurgitation during the first operation. However, they still progressed to a dissecting aortic aneurysm. Currently, there are studies suggesting that early aortic replacement surgery in BAV patients, restoring normal hemodynamics, may reduce the incidence of aortic dissection (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), This suggests the necessity of early surgical intervention. Michelena et al (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) Research has found that BAV patients without valvular dysfunction can still develop AAD. Pathological findings suggest cystic medial necrosis and elastic fiber fragmentation in the aortic media, indicating that structural developmental abnormalities are important factors in ascending aortic damage. Rueda-Martinez et al.\" and \"Navarrete et al. (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) Research indicates that BAV patients exhibit upregulation of aortic extracellular matrix proteins, leading to increased susceptibility of the aortic medial layer elastic fibers to damage, thereby contributing to the development of AAD.Table\u0026nbsp;1 The Clinical Characteristics of Three Patients.\u003c/p\u003e\u003cp\u003eThe three cases of adults we report who underwent corrective surgery for PA/VSD and subsequently developed complications such as aortic root aneurysms, ascending aortic dilation, and even aortic dissection rupture serve as clinical examples. While this constitutes a small sample size from a single center, it serves as a warning to clinicians dealing with such patients to fully consider the risk factors associated with aortic pathology. Additionally, regular follow-up and imaging examinations are crucial for early detection and intervention of aortic-related complications. When determining surgical treatment, a comprehensive evaluation of the patient's overall condition and the characteristics of the aneurysm should be conducted, and appropriate treatment strategies should be implemented.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003ePV pulmonary atresia\u003c/p\u003e \u003cp\u003eVSD ventricular septal defect\u003c/p\u003e \u003cp\u003eMAPCAs major aortopulmonary collateral arteries\u003c/p\u003e \u003cp\u003eTOF tetralogy of fallot\u003c/p\u003e \u003cp\u003eCHD congenital heart disease\u003c/p\u003e \u003cp\u003eBAV bicuspid aortic valve\u003c/p\u003e \u003cp\u003eAAD ascending aortic dilatation\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author would like to thank Dr. Tang Xiujie and Dr. Niu Yonghong for their support in radiological diagnosis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZJ and MK wrote the main manuscript text. ZJ collected and prepared the clinical data of the patients.H.X. and LX participated in patients care. MZ revised the manuscript. All authors reviewed the manuscript. All authors read and approved the fnal manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by\u0026nbsp;Beijing Natural Science Foundation（2024G101）\u0026nbsp;and\u0026nbsp;Tsinghua Precision Medicine Foundation (No. 10001020132 and No. 100010714 No. 100020104).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work has received approval from the Ethics Committee of the First Hospital of Tsinghua University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe declare that the research was conducted in the absence of any commercial or fnancial relationships that could be construed as a potential confict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eChan KC, Fyfe DA, McKay CA, Sade RM, Crawford FA. Right ventricular outflow reconstruction with cryopreserved homografts in pediatric patients: intermediate-term follow-up with serial echocardiographic assessment. J Am Coll Cardiol. 1994;24(2):483\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTchervenkov CI, Roy N. Congenital Heart Surgery Nomenclature and Database Project: pulmonary atresia\u0026ndash;ventricular septal defect. Ann Thorac Surg. 2000;69(4 Suppl):S97\u0026ndash;105.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCasta\u0026ntilde;eda AR. Cardiac surgery of the neonate and infant. Cardiac surgery of the neonate and infant; 1994.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeinel FG, Huda W, Schoepf UJ, Rao AG, Cho YJ, Baker GH, et al. Diagnostic accuracy of CT angiography in infants with tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral arteries. J Cardiovasc Comput Tomogr. 2013;7(6):367\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMackie AS, Gauvreau K, Perry SB, del Nido PJ, Geva T. Echocardiographic predictors of aortopulmonary collaterals in infants with tetralogy of fallot and pulmonary atresia. J Am Coll Cardiol. 2003;41(5):852\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAsija R, Roth SJ, Hanley FL, Peng L, Liu K, Abbott J, et al. Reperfusion pulmonary edema in children with tetralogy of Fallot, pulmonary atresia, and major aortopulmonary collateral arteries undergoing unifocalization procedures: A pilot study examining potential pathophysiologic mechanisms and clinical significance. J Thorac Cardiovasc Surg. 2014;148(4):1560\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRamaprabhu K, Idhrees M, Velayudhan B. Aortopathy in tetralogy of Fallot-a collective review. Indian J Thorac Cardiovasc Surg. 2019;35(4):575\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eG\u0026oacute;mez O, Soveral I, Bennasar M, Crispi F, Masoller N, Marimon E, et al. Accuracy of Fetal Echocardiography in the Differential Diagnosis between Truncus Arteriosus and Pulmonary Atresia with Ventricular Septal Defect. Fetal Diagn Ther. 2016;39(2):90\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeyvandi S, Lupo PJ, Garbarini J, Woyciechowski S, Edman S, Emanuel BS, et al. 22q11.2 deletions in patients with conotruncal defects: data from 1,610 consecutive cases. Pediatr Cardiol. 2013;34(7):1687\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e!!! INVALID CITATION !!! [10].\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBissell MM, Hess AT, Biasiolli L, Glaze SJ, Loudon M, Pitcher A, et al. Aortic dilation in bicuspid aortic valve disease: flow pattern is a major contributor and differs with valve fusion type. Circ Cardiovasc Imaging. 2013;6(4):499\u0026ndash;507.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcKellar SH, Michelena HI, Li Z, Schaff HV, Sundt TM 3. Long-term risk of aortic events following aortic valve replacement in patients with bicuspid aortic valves. Am J Cardiol. 2010;106(11):1626\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHenn D, Bandner-Risch D, Perttunen H, Schmied W, Porras C, Ceballos F, et al. Identification of reference genes for quantitative RT-PCR in ascending aortic aneurysms. PLoS ONE. 2013;8(1):e54132.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang H, Zhu Y, Zhao M, Wu C, Zhang P, Tang L, et al. miRNA-29c suppresses lung cancer cell adhesion to extracellular matrix and metastasis by targeting integrin β1 and matrix metalloproteinase2 (MMP2). PLoS ONE. 2013;8(8):e70192.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAboulhosn J, Child JS. Left ventricular outflow obstruction: subaortic stenosis, bicuspid aortic valve, supravalvar aortic stenosis, and coarctation of the aorta. Circulation. 2006;114(22):2412\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMart\u0026iacute;n M, Pichel IA, Fl\u0026oacute;rez Mu\u0026ntilde;oz JP, Naves-D\u0026iacute;az M, Palac\u0026iacute;n M, Cannata-And\u0026iacute;a JB, et al. Low transcriptional activity haplotype of matrix metalloproteinase 1 is less frequent in bicuspid aortic valve patients. Gene. 2013;524(2):304\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBravo-Jaimes K, Prakash SK. Genetics in bicuspid aortic valve disease: Where are we? Prog Cardiovasc Dis. 2020;63(4):398\u0026ndash;406.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGould RA, Aziz H, Woods CE, Seman-Senderos MA, Sparks E, Preuss C, et al. ROBO4 variants predispose individuals to bicuspid aortic valve and thoracic aortic aneurysm. Nat Genet. 2019;51(1):42\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eW\u0026uuml;nnemann F, Ta-Shma A, Preuss C, Leclerc S, van Vliet PP, Oneglia A, et al. Loss of ADAMTS19 causes progressive non-syndromic heart valve disease. Nat Genet. 2020;52(1):40\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGirdauskas E, Disha K, Borger MA, Kuntze T. Risk of proximal aortic dissection in patients with bicuspid aortic valve: how to address this controversy? Interactive cardiovascular and thoracic surgery. 2014;18(3):355\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMichelena HI, Della Corte A, Prakash SK, Milewicz DM, Evangelista A, Enriquez-Sarano M. Bicuspid aortic valve aortopathy in adults: Incidence, etiology, and clinical significance. Int J Cardiol. 2015;201:400\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRueda-Mart\u0026iacute;nez C, Lamas O, Matar\u0026oacute; MJ, Robledo-Carmona J, S\u0026aacute;nchez-Esp\u0026iacute;n G, Moreno-Santos I, et al. Fibrillin 2 is upregulated in the ascending aorta of patients with bicuspid aortic valve. Eur J Cardiothorac Surg. 2017;51(1):104\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNavarrete Santos A, Yan J, Lochmann P, Pfeil H, Petersen M, Simm A, et al. Collagen analysis of the ascending aortic dilatation associated with bicuspid aortic valve disease compared with tricuspid aortic valve. Arch Physiol Biochem. 2016;122(5):289\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-cardiothoracic-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jcts","sideBox":"Learn more about [Journal of Cardiothoracic Surgery](http://cardiothoracicsurgery.biomedcentral.com)","snPcode":"13019","submissionUrl":"https://submission.nature.com/new-submission/13019/3","title":"Journal of Cardiothoracic Surgery","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Pulmonary Atresia, Aortic Sinus Aneurysm, Aortic Dissection, Ascending Aorta Dilation","lastPublishedDoi":"10.21203/rs.3.rs-4571906/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4571906/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Progressive dilation of the ascending aorta is prone to lead to aortic dissection in patients with pulmonary artery atresia and ventricular septal defect. However, reports of long-term complications such as aortic aneurysm or aortic dissection in adults with pulmonary artery atresia are relatively rare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation: \u003c/strong\u003eCase 1: A 38-year-old male patient diagnosed with \"pulmonary artery atresia, ventricular septal defect, bicuspid aortic valve deformity\" underwent ventricular septal defect repair, aortic valve replacement, and correction of pulmonary artery atresia at the age of 21. Seventeen years postoperatively, he developed aortic dissection and underwent Bentall surgery.\u003c/p\u003e\n\u003cp\u003eCase 2: A 33-year-old male patient diagnosed with \"pulmonary artery atresia, ventricular septal defect\" underwent Blalock-Taussig shunt surgery at the age of 17. Sixteen years postoperatively, he developed aortic root aneurysm and ascending aortic dilation.\u003c/p\u003e\n\u003cp\u003eCase 3: A 42-year-old female patient diagnosed with \"pulmonary artery atresia, ventricular septal defect\" underwent pulmonary artery atresia corrective surgery and ventricular septal defect repair at the age of 14. Twenty-eight years postoperatively, she developed aortic root aneurysm and ascending aortic dilation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Following corrective surgery for pulmonary artery atresia with ventricular septal defect, long-term follow-up monitoring is necessary. Progressive dilation of the aorta should be promptly intervened to prevent the occurrence of aortic dissection.\u003c/p\u003e","manuscriptTitle":"Postoperative Ascending Aortic Aneurysm in Pulmonary Atresia with Ventricular Septal Defect: Report of 3 Adult Cases","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-16 17:25:19","doi":"10.21203/rs.3.rs-4571906/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision 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