Aortic Angulation Distribution and Effects on the Outcome and Complications of Self-expanding Transcatheter Aortic Valve Replacement

Aortic Angulation Distribution and Effects on the Outcome and Complications of Self-expanding Transcatheter Aortic Valve Replacement | 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 Research Article Aortic Angulation Distribution and Effects on the Outcome and Complications of Self-expanding Transcatheter Aortic Valve Replacement Ruitao Li, Yuanyuan Yu, Tianyuan Xiong, Fei Chen, Zhengang Zhao, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4884787/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Aims To investigate the effect of aortic angulation (AA) on clinical outcomes and related complications in patients with severe aortic valve stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) with self-expanding (SE) valve. Background AA is defined as the angle between the horizontal plane on the coronal plane and the plane of the aortic valve annulus, and is an important anatomical factor in TAVR. Whether AA affects the early clinical outcomes and complications in SE-TAVR procedure is still controversial. Methods and Results This was a retrospective cohort study of 519 consecutive patients who underwent SE-TAVR in our center from January 2016 to January 2021.The range of AA in patients undergoing SE-TAVR in this study was 25°~ 93°, with an average angle of 55.4 ± 9.7°. There was a statistically significant difference in technique success between AA ≤ 55° and AA > 55° group (87.3% vs. 79.1%, P = 0.011), which was mainly due to the proportion of second-valve implantation was implanted during TAVR (8.8% vs. 19.6%, P 55°were more likely to require second-valve implantation compared to those with an AA ≤ 55° (8.8% vs. 29.8%, P < 0.001), whereas this trend did not show significant statistical differences among patients with BAV (9.6% vs. 7.3%, P = 0.345). Conclusions Larger angulation of aortic valve has significant lower technique success of TAVR which was mainly due to increasing of second-valve implantation events in SE-TAVR patients. AA mainly affects the incidence of second-valve implantation during SE-TAVR in TAV group, rather than BAV group. Transcatheter aortic valve replacement aortic angulation self-expanding valve Figures Figure 1 Introduction Aortic valve stenosis (AS) refers to a slowly progressive disease in which the aortic valve begins to thicken and harden due to congenital or acquired factors, gradually leading to valve movement disorders and restricted valve opening. Symptomatic severe AS patients may have a poor prognosis if valve replacement surgery is not performed[ 1 , 2 , 3 ]. Based on several landmark clinical trials, transcatheter aortic valve replacement (TAVR) has become an established therapy for patients with symptomatic severe AS[ 4 , 5 , 6 ]. The use of computed tomography angiography (CTA) has become an important preoperative assessment for TAVR[ 7 ]. The anatomical characteristics of the aortic root determines the implantation strategies, including pre-dilation balloon size, valve sizes, and the precise releasing of valve, etc. Aortic angulation (AA) is one of the measurement index before TAVR. AA is defined as the angle between the horizontal plane on the coronal plane and the plane of the aortic valve annulus. Because of the low frame height and coaxiality of delivery system, AA does not affect the occurrence of various adverse events on TAVR patients who used balloon-expandable (BE) valves[ 8 , 9 , 10 ]. However, there is still controversy over whether AA affects the outcomes and complications after self-expanding TAVR (SE-TAVR)[ 8 , 11 , 12 , 13 ]. This article selects AA as an indicator, and try to explores the relationship of outcomes and complications between AA and SE-TAVR. Methods We retrospectively enrolled 519 consecutive patients who underwent SE-TAVR in our center from January 2016 to January 2021. The cardiac CT was performed using a German Siemens dual source 64-detector-row scanner (Siemens Medical Solutions USA Inc, Malvern, Pennsylvania). CTA was analyzed through Fluoro CT 3.0 (Circle Cardiovascular Imaging Inc, Calgary, Canada). The type of aortic valve was classified according to Sievers classification. Transthoracic echocardiography (TTE) was performed by experienced echocardiographers. AS severity was evaluated through peak velocity, mean gradient, and effective orifice area (EOA). Severe AS is defined as peak aortic velocity ≥ 4.0m/s, pressure gradient ≥ 40mmHg, or EOA ≤ 1.0m 2 . In this study, self-expanding transcatheter prosthetic valves were implanted. Prosthetic valve size was selected based on preoperative cardiac CT. All vascular access approaches were femoral arteries. General baseline, 12-lead electrocardiogram, TTE was recorded. The definition of successful implantation is based on valve academic research consortium-3 (VARC-3)[ 14 ]. The trial was conducted according to the Helsinki Declaration and was approved by the Clinical Trials and Biomedical Ethics Committee of West China Hospital, Sichuan University. It was registered on http://www.chictr.org.cn/ (ChiCTR2000033419) on May 31, 2020, in West China Hospital, Sichuan University. The informed consent was exempted due to the retrospective design of this study, which was approved by the ethics committee. Statistical analysis All data were statistically tested using SPSS 26.0 software. Perform independent sample normality tests on continuous variables using Shapiro Wilk (sample size ≤ 50) or Kolmogorov-Smirnov test (sample size > 50). If the distribution is normal, use mean ± standard deviation. When the variance is homogeneous, use t-test for comparison between the two groups. When the variance is uneven, use t-test for comparison between two groups. If it does not follow a normal distribution, use the median [IQR] and the Wilcoxon rank-sum non parametric test. The categorical variables are described using frequency and percentage, and Pearson chi-square test or Fisher's exact test is used. All statistical tests are two tailed tests, with p < 0.05 indicating statistical significance. Results A total of 519 patients who underwent TAVR were included in this research. The range of AA in patients undergoing SE-TAVR in this study was 25°~ 93°, with an average angle of 55.4 ± 9.7°. Patients were divided into AA ≤ 55° and AA > 55° groups based on the average angle of 55°. There were 47 patients with AA > 70 °, accounting for approximately 9.1%. Among all patients, there are 285 cases in the AA ≤ 55° group and 234 cases in the AA > 55° group. The baseline characteristics were presented in Table 1 . Compared with patients in AA ≤ 55° group, patients in AA > 55° group have a higher BMI, higher comorbidities burden of hypertension and diabetes, but with a better cardiac function, fewer patients with NYHA class III/IV, and fewer patients with LVEF 50° group (87.3% vs. 79.1%, P = 0.011). This difference was primarily attributed to a lower proportion of second-valve implantation events occurred during TAVR in the AA ≤ 55° group (8.8% vs. 19.6%, P < 0.001). There were no statistically significant differences between the two groups of patients in terms of perioperative complications, although there was a trend towards statistical significance for permanent pacemaker implantation after SE-TAVR (20.7% (59/285) vs. 27.8% (65/234), P = 0 .060). Table 1 Baseline characteristics AA ≤ 55° (n = 285) AA>55° (n = 234) P value Age, years 73.1 ± 7.0 74.4 ± 6.9 0.030 Male 175(61.4) 124(53.0) 0.054 BMI (kg/m 2 ) 22.1 ± 3.4 23.4 ± 3.2 0.000 STS (%) 5.9 ± 5.2 5.8 ± 4.4 0.774 NYHA III/IV 232(81.4) 173(73.9) 0.041 Hypertension 107(37.5) 128(54.7) 0.000 CAD 59(20.7) 55(23.5) 0.443 Previous PCI 19(6.7) 15(6.4) 0.906 Diabetes 39(13.7) 50(21.4) 0.021 CKD 19(6.7) 27(11.5) 0.052 COPD 117(41.1) 82(35.0) 0.161 Cerebrovascular disease 79(27.7) 63(26.9) 0.804 AV peak velocity (m/s) 4.6 ± 0.9 4.5 ± 1.2 0.367 AV mean gradient (mmHg) 54.5 ± 20.7 52.9 ± 24.5 0.558 LVEF<50% 113(39.7) 66(28.2) 0.006 BAV 125(43.9) 110(47.0) 0.480 Values are mean ± SD or n (%). BMI = body mass index; STS = Society of Thoracic Surgeons; CAD = coronary artery disease; PCI = percutaneous coronary intervention; CKD = chronic kidney disease; COPD = chronic obstructive pulmonary disease; AV = aortic valve; LVEF = left ventricular ejection fraction; BAV = bicuspid aortic valve. Table 2 Procedure details and clinical outcomes AA ≤ 55° (n = 285) AA>55° (n = 234) P value Post-dilation 150 (52.6) 106 (45.3) 0.096 Technique success 249 (87.3) 185 (79.1) 0.011 Freedom from mortality 285 (100) 232 (99.2) 0.203 Correction positioning of a single valve 260 (91.2) 189 (80.4) 0.000 Freedom from surgery or intervention 274 (96.1) 229 (97.9) 0.314 Perioperative complications Permanent pacemaker Implantation (%) 59 (20.7) 65 (27.8) 0.060 Major vascular complication (%) 5 (1.8) 2 (0.9) 0.466 Minor vascular complication (%) 17 (6.0) 16 (6.8) 0.685 Severe bleeding events (%) 4 (1.4) 3 (1.3) 1.000 Coronary artery obstruction (%) 10 (3.5) 3 (1.3) 0.106 Stroke (%) Mild or server perivalvular leakage 3 (1.1) 5 (1.8) 3 (1.3) 8 (3.5) 1.000 0.215 At both 30 days and six months after procedure, there were no statistically significant differences in cardiac and all-cause mortality rates between two groups (Supplementary materials 1). Kaplan Meier survival curves for both groups at one-year post-TAVR showed a higher survival rate for patients with an AA ≤ 55° compared to those with an AA > 55°, but this difference was not statistically significant (P = 0.846) (Fig. 1 ). Subgroup analysis was conducted between bicuspid aortic valve (BAV) (n = 235, 45.3%) and tricuspid aortic valve (TAV) (n = 284, 54.7%), of which the baseline was summarized in Supplementary materials 2 and outcomes in Table 3 . Among patients with TAV, those with an AA > 55°were more likely to require second-valve implantation compared to those with an AA ≤ 55° (8.8% vs. 29.8%, P < 0.001), whereas this trend did not show significant statistical differences among patients with BAV (9.6% vs. 7.3%, P = 0.345). Table 3 Procedure details and clinical outcomes of BAV and TAV BAV (n = 235) TAV (n = 284) AA ≤ 55° (n = 125) AA>55° (n = 110) P value AA ≤ 55° (n = 160) AA>55° (n = 124) P value Post-dilation 80 (64.0) 63 (57.3) 0.292 70 (43.8) 43 (34.7) 0.121 Technique success 118 (94.4) 104 (94.5) 1.000 138 (86.3) 99 (79.8) 0.197 Freedom from mortality 125 (100) 108 (98.2) 0.218 160 (1) 124 (1) - Correction positioning of a single valve 113 (90.4) 102 (92.7) 0.345 147 (91.2) 87 (70.2) 0.000 Freedom from surgery or intervention 122 (97.6) 109 (99.1) 0.625 152 (95.0) 120 (96.8) 0.560 Perioperative complications Permanent pacemaker Implantation (%) 23 (18.4) 29 (26.4) 0.142 36 (22.5) 36 (29.0) 0.209 Major vascular complication (%) 1 (0.8) 1 (0.9) 1.000 4 (2.5) 1 (0.8) 0.391 Minor vascular complication (%) 12 (9.6) 12 (10.9) 0.741 5 (3.1) 4 (3.2) 1.000 Severe bleeding events (%) 2 (1.6) 2 (1.8) 1.000 2 (1.3) 1 (0.8) 1.000 Coronary artery obstruction (%) 2 (1.6) 1 (0.9) 1.000 8 (5.0) 2 (1.6) 0.194 Stroke (%) 2 (1.6) 2 (1.8) 1.000 1 (0.6) 1 (0.8) 1.000 Discuss The aortic angulation is a crucial factor in the preoperative CT assessment of TAVR, and larger AA lead to challenging TAVR procedures. The size of the AA didn’t significantly impact intraoperative, 30-day, 6-month, and 1-year mortality rates, except for the rate of second-valve implantation occurrences. Subgroup analysis revealed that AA mainly affects the incidence of second-valve implantation during SE-TAVR in TAV group, rather than BAV group. Previous studies have reported that European patients undergoing TAVR had an AA range of 18° to 90° with an average angle of 49.4 ± 9.4°, while another study involving 582 patients showed an average angle of AA at 47.3°±8.7°[ 8 , 15 ]. The average angle of AA in this study was higher than that observed in Western TAVR patients, which may be attributed to the inclusion of more BAV patients in this study. Previous research has indicated that BAV patients are more likely to have larger AA, and the proportion of BAV patients among Chinese TAVR recipients is significantly higher than that seen in Western countries[ 16 ]. Additionally, our study found that patients with larger AAs were older, had higher BMI values and a higher incidence of hypertension, findings consistent with previous studies[ 13 , 15 , 17 ]. With the increase of age, the ascending aorta begins to elongate, undergo structural changes, and ultimately leads to an increase in AA, which is due to fracture and breakdown of elastin fibres[ 18 ]. The previous study proved that the strong correlation between the clockwise rotation and dilation of aorta, which serves as a bridge between risk factors following and the increase in AA[ 19 ]. The association between hypertension and aortic root dilation has been well-established for a long time[ 20 , 21 ]. Canciello’s study revealed the revealed that hypertension and obesity contributes to the development of aortic dilation[ 22 ]. In addition, this study found that patients with smaller AA had worse cardiac function. It may be one of the reasons why younger patients received TAVR compared to AA > 55°group. Furthermore, there was no significant difference in 1-year postoperative survival between two groups. In previous studies, the patients with AA > 70° were excluded for TAVR[ 13 , 23 ]. However, in our study there were approximately 47 patients with AA > 70°accounting for around 9.1%, although still a relatively small sample size, but it offers better generalizability compared to previous research. Larger AA size is associated with increased difficulty in TAVR. This may be attributed to the lack of coaxiality of the SE valve delivery system, as well as the tendency for a more perpendicular orientation of the aortic annulus with decreasing AA size. These factors significantly contribute to the challenges encountered in crossing the aortic valve and accurately positioning and releasing the valve coaxially. A retrospective study involving a small sample of TAVR patients indicated that larger AA size is correlated with higher likelihood of perivalvular leakage[ 24 ]. Previous studies have suggested that for patients with larger AA, alternative transcatheter approaches such as subclavian artery, carotid artery, aorta, or apex approach could be considered as viable options[ 25 , 26 , 27 ]. There was a statistically significant difference in technique success between AA ≤ 55° and AA > 55° group, primarily due to the proportion of second-valve implantation. The SE valve features a longer valve support frame (49 to 52 millimeters) and its delivery system cannot be flexed or extended, potentially leading to challenges in precise valve positioning when dealing with large AAs. This can result in the release position of the valve being too high or low, leading to procedure-related complications. However, this study found that the incidence of other TAVR complications, intraoperative adverse events, mortality rates, and 1-year survival rates were similar in both groups. Popma et al. noted that among patients receiving first-generation SE-TAVR, those with larger AAs experienced slightly longer procedure times but did not exhibit any impact on clinical outcomes[ 13 ]. Additionally, both Abramowitz and Sherif observed that larger AAs are associated with an increased risk of perivalvular leakage following TAVR[ 8 , 24 ]. Although our study revealed a higher incidence of severe perivalvular leakage in patients with AA > 55° group compared to those with smaller AAs, this difference did not reach statistical significance and may require a larger sample size for validation. It is possible that post-dilation or emergency placement of a second valve during angiography could reduce perivalvular regurgitation in cases of significant leakage. The outer skirt design and recapturing/repositioning capabilities of second-generation SE valves have contributed to decreased incidences of perivalvular leakage[ 28 ]. Subsequently, Ancona and Stefano reported in their study on second-generation SE valves that enlargement of the AA was not correlated with TAVR outcomes or related adverse events[ 9 , 29 ]. In subgroup analysis, similar conclusions were obtained in patients with TAV, but there was no difference in the incidence of TAVR complications and intraoperative adverse events between the two groups of patients with BAV. The TAV patients with AA > 55°have a higher incidence of second-valve implantation during TAVR. Compared to TAV patients, we found that the incidence of second-valve implantation in BAV patients was lower at 8.5%, and the size of AA had no effect on its incidence in BAV patients. The asymmetric structure of BAV may cause uneven tension and radial forces on the SE valve, making it difficult to migration. When significant perivalvular leakage occurs due to insufficient expansion of the first implanted valve during TAVR, balloon dilation can be performed to reduce regurgitation. In this study, 60.9% of BAV patients underwent postoperative balloon dilation compared to 39.8% in TAV patients. This suggests that evaluating valve leakage and ensuring adequate valve dilation during surgery may contribute to reducing intraoperative second-valve implantation leakage in BAV patients. The incidence of second-valve implantation was most associated with malposition of the primary valve[ 30 ]. Patients with BAV often have more complex anatomical structures and receive more accurate and rigorous preoperative evaluations, which may reduce the influences of AA. Meanwhile, BAV are more likely to calcification, which could provide outer support and anchoring sites[ 31 , 32 ]. The above reasons have led to a greater influence of AA in the TAV group patients. As the new generation prosthetic aortic valve is applied in TAVR, this proportion will further decrease. Limitation This study is a retrospective single center study with poor extrapolation and certain limitations. More valve types and longer follow-up can further deepen our research findings. Besides, we are one of the most experienced centers of BAV-TAVR, so there may be a single center bias in these outcomes, which also limits the scalability of this study. Conclusion The size of the AA has significant effects on the technique success of SE-TAVR, especially in the proportion of second-valve implantation and patients with TAV. The size of the AA has no significant effects on 30-day postoperative mortality rate, half year postoperative mortality rate, and 1-year postoperative survival rate in SE-TAVR patients. More researches are required to further our outcomes. Declarations Availability of data and materials The data generated or analyzed during this study are available from Yuan Feng and Yijian Li (corresponding authors) on reasonable request. Competing interests All authors declare no conflict of interest for this contribution. Funding The work was supported by Sichuan Provincial Cadre Health Research Program (grant number ZH2024-103) and 1· 3· 5 project for disciplines of excellence - Clinical Research Fund, West China Hospital, Sichuan University (grant number 2024HXFH038). Authors' contributions Ruitao Li and Yuanyuan Yu wrote the main manuscript and measurements of the aortic angulation. Tianyuan Xiong and Fei Chen completed tables and the figure. Zhengang Zhao instructed the methodology. Zhicheng Chen, Qianbei He, and Zhixiang Yu completed data collection. Yijian Li and Yuan Feng were responsible for review and editing. 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Incidence, Causes, and Outcomes Associated With Urgent Implantation of a Supplementary Valve During Transcatheter Aortic Valve Replacement. JAMA Cardiol. 2021;6(8):936–44. Mayfield JJ, Otto CM. Stroke and Noninfective Native Valvular Disease. Curr Cardiol Rep. 2023;25(5):333–48. Coffey S, Roberts-Thomson R, Brown A, Carapetis J, Chen M, Enriquez-Sarano M, et al. Global epidemiology of valvular heart disease. Nat Rev Cardiol. 2021;18(12):853–64. Additional Declarations No competing interests reported. Supplementary Files Supplementarymaterials.docx Cite Share Download PDF Status: Posted Version 1 posted 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-4884787","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":354203377,"identity":"6ea17c35-82b1-4801-a855-1da7f17aaabf","order_by":0,"name":"Ruitao Li","email":"","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Ruitao","middleName":"","lastName":"Li","suffix":""},{"id":354203378,"identity":"b0399457-c127-4aa4-be46-4b0b5d13a5f8","order_by":1,"name":"Yuanyuan Yu","email":"","orcid":"","institution":"Ningxia Hui Autonomous Region Peoples Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuanyuan","middleName":"","lastName":"Yu","suffix":""},{"id":354203379,"identity":"6a1009f9-590d-4bf9-af9f-19815b5eea99","order_by":2,"name":"Tianyuan Xiong","email":"","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Tianyuan","middleName":"","lastName":"Xiong","suffix":""},{"id":354203380,"identity":"5036ab6e-690e-44f4-a870-3f4c9be02d6f","order_by":3,"name":"Fei Chen","email":"","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Fei","middleName":"","lastName":"Chen","suffix":""},{"id":354203381,"identity":"24ff7160-050a-4b46-b07a-2999c440129a","order_by":4,"name":"Zhengang Zhao","email":"","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Zhengang","middleName":"","lastName":"Zhao","suffix":""},{"id":354203382,"identity":"31a720dd-c476-48c0-a1a7-9fac7814abb3","order_by":5,"name":"Zhicheng Chen","email":"","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Zhicheng","middleName":"","lastName":"Chen","suffix":""},{"id":354203383,"identity":"496a693e-3fdf-4acf-ac12-2978c78ae5c5","order_by":6,"name":"Qianbei He","email":"","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Qianbei","middleName":"","lastName":"He","suffix":""},{"id":354203384,"identity":"c0712547-eb18-4f27-95fc-c80f60b5166d","order_by":7,"name":"Zhixiang Yu","email":"","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Zhixiang","middleName":"","lastName":"Yu","suffix":""},{"id":354203385,"identity":"7004fe14-6fcb-4d62-a527-22a8a584e4d2","order_by":8,"name":"Yijian Li","email":"","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Yijian","middleName":"","lastName":"Li","suffix":""},{"id":354203386,"identity":"dd699f73-9b4e-46ae-81fe-23c9e311e3ba","order_by":9,"name":"Yuan Feng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6UlEQVRIiWNgGAWjYBAC9gYwdYCBgYf5GJjJxk5AC88BsAaQFrY0BoYEoBZm4rXwmIG1MBDUIpF78PGHijty/Dxnvj34+GObPB8zA+OHjzn4tOQlGxw488xYsrd3u+GMhNuGbcwMzJIzt+HWYi+RYyZxsO1w4obzvNukeRJuMwK1sDHz4tHCA9byD6SF5xlIiz2RWhqAWs72sIG0JBLWwvPG2ODMMaBfeo6ZSc5Iu53cxszYjNcvPOw5hg8qakAhlvxM4oPNbdv57c0HP3zEo4VBIAFDiLEBj3og4D+AX34UjIJRMApGAQMAf+NRJpekfI8AAAAASUVORK5CYII=","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":true,"prefix":"","firstName":"Yuan","middleName":"","lastName":"Feng","suffix":""}],"badges":[],"createdAt":"2024-08-09 06:29:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4884787/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4884787/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":66630234,"identity":"2a4696ab-2532-4775-b36c-bd73055936a2","added_by":"auto","created_at":"2024-10-15 04:45:10","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":87371,"visible":true,"origin":"","legend":"\u003cp\u003eAnalysis of Kaplan-Meier curves for the AA≤55° and AA\u0026gt;55° group after 1 year of TAVR (P=0.846).\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4884787/v1/602218d7d8b721526474e869.jpg"},{"id":66631121,"identity":"17e315c7-d050-48da-89cd-f3353ca644a9","added_by":"auto","created_at":"2024-10-15 04:53:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":555375,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4884787/v1/54a8d0b5-9393-4e0c-872f-bdc984da69b7.pdf"},{"id":66630235,"identity":"7684a3f5-3cc3-4ebd-b4e9-a20edf1b60df","added_by":"auto","created_at":"2024-10-15 04:45:10","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":15934,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterials.docx","url":"https://assets-eu.researchsquare.com/files/rs-4884787/v1/68a68d728b39046b08c3fcf5.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Aortic Angulation Distribution and Effects on the Outcome and Complications of Self-expanding Transcatheter Aortic Valve Replacement","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAortic valve stenosis (AS) refers to a slowly progressive disease in which the aortic valve begins to thicken and harden due to congenital or acquired factors, gradually leading to valve movement disorders and restricted valve opening. Symptomatic severe AS patients may have a poor prognosis if valve replacement surgery is not performed[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Based on several landmark clinical trials, transcatheter aortic valve replacement (TAVR) has become an established therapy for patients with symptomatic severe AS[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The use of computed tomography angiography (CTA) has become an important preoperative assessment for TAVR[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The anatomical characteristics of the aortic root determines the implantation strategies, including pre-dilation balloon size, valve sizes, and the precise releasing of valve, etc. Aortic angulation (AA) is one of the measurement index before TAVR. AA is defined as the angle between the horizontal plane on the coronal plane and the plane of the aortic valve annulus. Because of the low frame height and coaxiality of delivery system, AA does not affect the occurrence of various adverse events on TAVR patients who used balloon-expandable (BE) valves[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, there is still controversy over whether AA affects the outcomes and complications after self-expanding TAVR (SE-TAVR)[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. This article selects AA as an indicator, and try to explores the relationship of outcomes and complications between AA and SE-TAVR.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eWe retrospectively enrolled 519 consecutive patients who underwent SE-TAVR in our center from January 2016 to January 2021. The cardiac CT was performed using a German Siemens dual source 64-detector-row scanner (Siemens Medical Solutions USA Inc, Malvern, Pennsylvania). CTA was analyzed through Fluoro CT 3.0 (Circle Cardiovascular Imaging Inc, Calgary, Canada). The type of aortic valve was classified according to Sievers classification. Transthoracic echocardiography (TTE) was performed by experienced echocardiographers. AS severity was evaluated through peak velocity, mean gradient, and effective orifice area (EOA). Severe AS is defined as peak aortic velocity\u0026thinsp;\u0026ge;\u0026thinsp;4.0m/s, pressure gradient\u0026thinsp;\u0026ge;\u0026thinsp;40mmHg, or EOA\u0026thinsp;\u0026le;\u0026thinsp;1.0m\u003csup\u003e2\u003c/sup\u003e. In this study, self-expanding transcatheter prosthetic valves were implanted. Prosthetic valve size was selected based on preoperative cardiac CT. All vascular access approaches were femoral arteries. General baseline, 12-lead electrocardiogram, TTE was recorded. The definition of successful implantation is based on valve academic research consortium-3 (VARC-3)[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The trial was conducted according to the Helsinki Declaration and was approved by the Clinical Trials and Biomedical Ethics Committee of West China Hospital, Sichuan University. It was registered on \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.chictr.org.cn/\u003c/span\u003e\u003cspan address=\"http://www.chictr.org.cn/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (ChiCTR2000033419) on May 31, 2020, in West China Hospital, Sichuan University. The informed consent was exempted due to the retrospective design of this study, which was approved by the ethics committee.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll data were statistically tested using SPSS 26.0 software. Perform independent sample normality tests on continuous variables using Shapiro Wilk (sample size\u0026thinsp;\u0026le;\u0026thinsp;50) or Kolmogorov-Smirnov test (sample size\u0026thinsp;\u0026gt;\u0026thinsp;50). If the distribution is normal, use mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. When the variance is homogeneous, use t-test for comparison between the two groups. When the variance is uneven, use t-test for comparison between two groups. If it does not follow a normal distribution, use the median [IQR] and the Wilcoxon rank-sum non parametric test. The categorical variables are described using frequency and percentage, and Pearson chi-square test or Fisher's exact test is used. All statistical tests are two tailed tests, with p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicating statistical significance.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 519 patients who underwent TAVR were included in this research. The range of AA in patients undergoing SE-TAVR in this study was 25\u0026deg;~ 93\u0026deg;, with an average angle of 55.4\u0026thinsp;\u0026plusmn;\u0026thinsp;9.7\u0026deg;. Patients were divided into AA\u0026thinsp;\u0026le;\u0026thinsp;55\u0026deg; and AA\u0026thinsp;\u0026gt;\u0026thinsp;55\u0026deg; groups based on the average angle of 55\u0026deg;. There were 47 patients with AA\u0026thinsp;\u0026gt;\u0026thinsp;70 \u0026deg;, accounting for approximately 9.1%. Among all patients, there are 285 cases in the AA\u0026thinsp;\u0026le;\u0026thinsp;55\u0026deg; group and 234 cases in the AA\u0026thinsp;\u0026gt;\u0026thinsp;55\u0026deg; group. The baseline characteristics were presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Compared with patients in AA\u0026thinsp;\u0026le;\u0026thinsp;55\u0026deg; group, patients in AA\u0026thinsp;\u0026gt;\u0026thinsp;55\u0026deg; group have a higher BMI, higher comorbidities burden of hypertension and diabetes, but with a better cardiac function, fewer patients with NYHA class III/IV, and fewer patients with LVEF\u0026thinsp;\u0026lt;\u0026thinsp;50%. But there was no significant difference in STS scores finally. Intraoperative data were presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The technique success in AA\u0026thinsp;\u0026le;\u0026thinsp;55\u0026deg; group was statistically higher than that in AA\u0026thinsp;\u0026gt;\u0026thinsp;50\u0026deg; group (87.3% vs. 79.1%, P\u0026thinsp;=\u0026thinsp;0.011). This difference was primarily attributed to a lower proportion of second-valve implantation events occurred during TAVR in the AA\u0026thinsp;\u0026le;\u0026thinsp;55\u0026deg; group (8.8% vs. 19.6%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). There were no statistically significant differences between the two groups of patients in terms of perioperative complications, although there was a trend towards statistical significance for permanent pacemaker implantation after SE-TAVR (20.7% (59/285) vs. 27.8% (65/234), P\u0026thinsp;=\u0026thinsp;0 .060).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAA\u0026thinsp;\u0026le;\u0026thinsp;55\u0026deg;\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;285)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAA\u0026gt;55\u0026deg;\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;234)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73.1\u0026thinsp;\u0026plusmn;\u0026thinsp;7.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e 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colname=\"c4\"\u003e \u003cp\u003e0.443\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious PCI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19(6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15(6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.906\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39(13.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50(21.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCKD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19(6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27(11.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.052\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOPD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e117(41.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e82(35.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.161\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebrovascular disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79(27.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63(26.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.804\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAV peak velocity (m/s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.367\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAV mean gradient (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54.5\u0026thinsp;\u0026plusmn;\u0026thinsp;20.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52.9\u0026thinsp;\u0026plusmn;\u0026thinsp;24.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.558\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVEF\u0026lt;50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e113(39.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66(28.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.006\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBAV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e125(43.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e110(47.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.480\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eValues are mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or n (%).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eBMI\u0026thinsp;=\u0026thinsp;body mass index; STS\u0026thinsp;=\u0026thinsp;Society of Thoracic Surgeons; CAD\u0026thinsp;=\u0026thinsp;coronary artery disease; PCI\u0026thinsp;=\u0026thinsp;percutaneous coronary intervention; CKD\u0026thinsp;=\u0026thinsp;chronic kidney disease; COPD\u0026thinsp;=\u0026thinsp;chronic obstructive pulmonary disease; AV\u0026thinsp;=\u0026thinsp;aortic valve; LVEF\u0026thinsp;=\u0026thinsp;left ventricular ejection fraction; BAV\u0026thinsp;=\u0026thinsp;bicuspid aortic valve.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eProcedure details and clinical outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAA\u0026thinsp;\u0026le;\u0026thinsp;55\u0026deg;\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;285)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAA\u0026gt;55\u0026deg; (n\u0026thinsp;=\u0026thinsp;234)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-dilation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e150 (52.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e106 (45.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.096\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTechnique success\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e249 (87.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e185 (79.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFreedom from mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e285 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e232 (99.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.203\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorrection positioning of a single valve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e260 (91.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e189 (80.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFreedom from surgery or intervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e274 (96.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e229 (97.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.314\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerioperative complications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePermanent pacemaker Implantation (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59 (20.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e65 (27.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.060\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMajor vascular complication (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.466\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMinor vascular complication (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.685\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere bleeding events (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoronary artery obstruction (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.106\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStroke (%)\u003c/p\u003e \u003cp\u003eMild or server perivalvular leakage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (1.1)\u003c/p\u003e \u003cp\u003e5 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (1.3)\u003c/p\u003e \u003cp\u003e8 (3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003cp\u003e0.215\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAt both 30 days and six months after procedure, there were no statistically significant differences in cardiac and all-cause mortality rates between two groups (Supplementary materials 1). Kaplan Meier survival curves for both groups at one-year post-TAVR showed a higher survival rate for patients with an AA\u0026thinsp;\u0026le;\u0026thinsp;55\u0026deg; compared to those with an AA\u0026thinsp;\u0026gt;\u0026thinsp;55\u0026deg;, but this difference was not statistically significant (P\u0026thinsp;=\u0026thinsp;0.846) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSubgroup analysis was conducted between bicuspid aortic valve (BAV) (n\u0026thinsp;=\u0026thinsp;235, 45.3%) and tricuspid aortic valve (TAV) (n\u0026thinsp;=\u0026thinsp;284, 54.7%), of which the baseline was summarized in Supplementary materials 2 and outcomes in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Among patients with TAV, those with an AA\u0026thinsp;\u0026gt;\u0026thinsp;55\u0026deg;were more likely to require second-valve implantation compared to those with an AA\u0026thinsp;\u0026le;\u0026thinsp;55\u0026deg; (8.8% vs. 29.8%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), whereas this trend did not show significant statistical differences among patients with BAV (9.6% vs. 7.3%, P\u0026thinsp;=\u0026thinsp;0.345).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eProcedure details and clinical outcomes of BAV and TAV\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eBAV (n\u0026thinsp;=\u0026thinsp;235)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eTAV (n\u0026thinsp;=\u0026thinsp;284)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAA\u0026thinsp;\u0026le;\u0026thinsp;55\u0026deg;\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;125)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAA\u0026gt;55\u0026deg; (n\u0026thinsp;=\u0026thinsp;110)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAA\u0026thinsp;\u0026le;\u0026thinsp;55\u0026deg;\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;160)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAA\u0026gt;55\u0026deg; (n\u0026thinsp;=\u0026thinsp;124)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-dilation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80 (64.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63 (57.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.292\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e70 (43.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e43 (34.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.121\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTechnique success\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e118 (94.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e104 (94.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e138 (86.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e99 (79.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.197\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFreedom from mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e125 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e108 (98.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.218\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e160 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e124 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorrection positioning of a single valve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e113 (90.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e102 (92.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.345\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e147 (91.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e87 (70.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.000\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFreedom from surgery or intervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e122 (97.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e109 (99.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.625\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e152 (95.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e120 (96.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.560\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003ePerioperative complications\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePermanent pacemaker Implantation (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (18.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (26.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.142\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36 (22.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e36 (29.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.209\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMajor vascular complication (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.391\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMinor vascular complication (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (10.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.741\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere bleeding events (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoronary artery obstruction (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.194\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStroke (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discuss","content":"\u003cp\u003eThe aortic angulation is a crucial factor in the preoperative CT assessment of TAVR, and larger AA lead to challenging TAVR procedures. The size of the AA didn\u0026rsquo;t significantly impact intraoperative, 30-day, 6-month, and 1-year mortality rates, except for the rate of second-valve implantation occurrences. Subgroup analysis revealed that AA mainly affects the incidence of second-valve implantation during SE-TAVR in TAV group, rather than BAV group.\u003c/p\u003e \u003cp\u003ePrevious studies have reported that European patients undergoing TAVR had an AA range of 18\u0026deg; to 90\u0026deg; with an average angle of 49.4\u0026thinsp;\u0026plusmn;\u0026thinsp;9.4\u0026deg;, while another study involving 582 patients showed an average angle of AA at 47.3\u0026deg;\u0026plusmn;8.7\u0026deg;[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The average angle of AA in this study was higher than that observed in Western TAVR patients, which may be attributed to the inclusion of more BAV patients in this study. Previous research has indicated that BAV patients are more likely to have larger AA, and the proportion of BAV patients among Chinese TAVR recipients is significantly higher than that seen in Western countries[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Additionally, our study found that patients with larger AAs were older, had higher BMI values and a higher incidence of hypertension, findings consistent with previous studies[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. With the increase of age, the ascending aorta begins to elongate, undergo structural changes, and ultimately leads to an increase in AA, which is due to fracture and breakdown of elastin fibres[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The previous study proved that the strong correlation between the clockwise rotation and dilation of aorta, which serves as a bridge between risk factors following and the increase in AA[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The association between hypertension and aortic root dilation has been well-established for a long time[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Canciello\u0026rsquo;s study revealed the revealed that hypertension and obesity contributes to the development of aortic dilation[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In addition, this study found that patients with smaller AA had worse cardiac function. It may be one of the reasons why younger patients received TAVR compared to AA\u0026thinsp;\u0026gt;\u0026thinsp;55\u0026deg;group. Furthermore, there was no significant difference in 1-year postoperative survival between two groups. In previous studies, the patients with AA\u0026thinsp;\u0026gt;\u0026thinsp;70\u0026deg; were excluded for TAVR[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. However, in our study there were approximately 47 patients with AA\u0026thinsp;\u0026gt;\u0026thinsp;70\u0026deg;accounting for around 9.1%, although still a relatively small sample size, but it offers better generalizability compared to previous research.\u003c/p\u003e \u003cp\u003eLarger AA size is associated with increased difficulty in TAVR. This may be attributed to the lack of coaxiality of the SE valve delivery system, as well as the tendency for a more perpendicular orientation of the aortic annulus with decreasing AA size. These factors significantly contribute to the challenges encountered in crossing the aortic valve and accurately positioning and releasing the valve coaxially. A retrospective study involving a small sample of TAVR patients indicated that larger AA size is correlated with higher likelihood of perivalvular leakage[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Previous studies have suggested that for patients with larger AA, alternative transcatheter approaches such as subclavian artery, carotid artery, aorta, or apex approach could be considered as viable options[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThere was a statistically significant difference in technique success between AA\u0026thinsp;\u0026le;\u0026thinsp;55\u0026deg; and AA\u0026thinsp;\u0026gt;\u0026thinsp;55\u0026deg; group, primarily due to the proportion of second-valve implantation. The SE valve features a longer valve support frame (49 to 52 millimeters) and its delivery system cannot be flexed or extended, potentially leading to challenges in precise valve positioning when dealing with large AAs. This can result in the release position of the valve being too high or low, leading to procedure-related complications. However, this study found that the incidence of other TAVR complications, intraoperative adverse events, mortality rates, and 1-year survival rates were similar in both groups. Popma et al. noted that among patients receiving first-generation SE-TAVR, those with larger AAs experienced slightly longer procedure times but did not exhibit any impact on clinical outcomes[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Additionally, both Abramowitz and Sherif observed that larger AAs are associated with an increased risk of perivalvular leakage following TAVR[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Although our study revealed a higher incidence of severe perivalvular leakage in patients with AA\u0026thinsp;\u0026gt;\u0026thinsp;55\u0026deg; group compared to those with smaller AAs, this difference did not reach statistical significance and may require a larger sample size for validation. It is possible that post-dilation or emergency placement of a second valve during angiography could reduce perivalvular regurgitation in cases of significant leakage. The outer skirt design and recapturing/repositioning capabilities of second-generation SE valves have contributed to decreased incidences of perivalvular leakage[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Subsequently, Ancona and Stefano reported in their study on second-generation SE valves that enlargement of the AA was not correlated with TAVR outcomes or related adverse events[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn subgroup analysis, similar conclusions were obtained in patients with TAV, but there was no difference in the incidence of TAVR complications and intraoperative adverse events between the two groups of patients with BAV. The TAV patients with AA\u0026thinsp;\u0026gt;\u0026thinsp;55\u0026deg;have a higher incidence of second-valve implantation during TAVR. Compared to TAV patients, we found that the incidence of second-valve implantation in BAV patients was lower at 8.5%, and the size of AA had no effect on its incidence in BAV patients. The asymmetric structure of BAV may cause uneven tension and radial forces on the SE valve, making it difficult to migration. When significant perivalvular leakage occurs due to insufficient expansion of the first implanted valve during TAVR, balloon dilation can be performed to reduce regurgitation. In this study, 60.9% of BAV patients underwent postoperative balloon dilation compared to 39.8% in TAV patients. This suggests that evaluating valve leakage and ensuring adequate valve dilation during surgery may contribute to reducing intraoperative second-valve implantation leakage in BAV patients. The incidence of second-valve implantation was most associated with malposition of the primary valve[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Patients with BAV often have more complex anatomical structures and receive more accurate and rigorous preoperative evaluations, which may reduce the influences of AA. Meanwhile, BAV are more likely to calcification, which could provide outer support and anchoring sites[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. The above reasons have led to a greater influence of AA in the TAV group patients. As the new generation prosthetic aortic valve is applied in TAVR, this proportion will further decrease.\u003c/p\u003e\n\u003ch3\u003eLimitation\u003c/h3\u003e\n\u003cp\u003eThis study is a retrospective single center study with poor extrapolation and certain limitations. More valve types and longer follow-up can further deepen our research findings. Besides, we are one of the most experienced centers of BAV-TAVR, so there may be a single center bias in these outcomes, which also limits the scalability of this study.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe size of the AA has significant effects on the technique success of SE-TAVR, especially in the proportion of second-valve implantation and patients with TAV. The size of the AA has no significant effects on 30-day postoperative mortality rate, half year postoperative mortality rate, and 1-year postoperative survival rate in SE-TAVR patients. More researches are required to further our outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data generated or analyzed during this study are available from Yuan Feng and Yijian Li (corresponding authors) on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare no conflict of interest for this contribution.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe work was supported by Sichuan Provincial Cadre Health Research Program (grant number ZH2024-103) and 1\u0026middot;\u0026nbsp;3\u0026middot;\u0026nbsp;5 project for disciplines of excellence - Clinical Research Fund, West China Hospital, Sichuan University (grant number 2024HXFH038).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRuitao Li and Yuanyuan Yu wrote the main manuscript and measurements of the aortic angulation. Tianyuan Xiong and Fei Chen completed tables and the figure. Zhengang Zhao instructed the methodology. Zhicheng Chen, Qianbei He, and Zhixiang Yu completed data collection. Yijian Li and Yuan Feng were responsible for review and editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to express our gratitude to Yanbiao Liao and Mao Chen for their contributions to this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBen-Dor I, Pichard AD, Gonzalez MA, Weissman G, Li Y, Goldstein SA, et al. Correlates and causes of death in patients with severe symptomatic aortic stenosis who are not eligible to participate in a clinical trial of transcatheter aortic valve implantation. Circulation. 2010;122(11 Suppl):S37\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChizner MA, Pearle DL, deLeon AC Jr.. The natural history of aortic stenosis in adults. Am Heart J. 1980;99(4):419\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchwarz F, Baumann P, Manthey J, Hoffmann M, Schuler G, Mehmel HC, et al. The effect of aortic valve replacement on survival. Circulation. 1982;66(5):1105\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCribier A, Eltchaninoff H, Bash A, Borenstein N, Tron C, Bauer F, et al. Percutaneous transcatheter implantation of an aortic valve prosthesis for calcific aortic stenosis: first human case description. Circulation. 2002;106(24):3006\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSiontis GCM, Overtchouk P, Cahill TJ, Modine T, Prendergast B, Praz F, et al. Transcatheter aortic valve implantation vs. surgical aortic valve replacement for treatment of symptomatic severe aortic stenosis: an updated meta-analysis. 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Curr Probl Cardiol. 2021;46(2):100415.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eElmously A, Gray KD, Truong QA, Burshtein A, Wong SC, de Biasi AR, et al. Aortic Angulation Does Not Impact Outcomes in Self-Expandable or Balloon-Expandable Transcatheter Aortic Valve Replacement. Cardiology. 2018;140(2):96\u0026ndash;102.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaneko U, Hachinohe D, Kobayashi K, Shitan H, Mitsube K, Furugen A, et al. Evolut Self-Expanding Transcatheter Aortic Valve Replacement in Patients with Extremely Horizontal Aorta (Aortic Root Angle\u0026thinsp;\u0026ge;\u0026thinsp;70\u0026deg;). Int Heart J. 2020;61(5):1059\u0026ndash;69.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePopma JJ, Reardon MJ, Yakubov SJ, Hermiller JB Jr., Harrison JK, Gleason TG, et al. Safety and Efficacy of Self-Expanding TAVR in Patients With Aortoventricular Angulation. JACC Cardiovasc Imaging. 2016;9(8):973\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eG\u0026eacute;n\u0026eacute;reux P, Piazza N, Alu MC, Nazif T, Hahn RT, Pibarot P, et al. Valve Academic Research Consortium 3: updated endpoint definitions for aortic valve clinical research. Eur Heart J. 2021;42(19):1825\u0026ndash;57.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoscarelli M, Gallo F, Gallone G, Kim WK, Reifart J, Veulemans V, et al. Aortic angle distribution and predictors of horizontal aorta in patients undergoing transcatheter aortic valve replacement. Int J Cardiol. 2021;338:58\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJilaihawi H, Wu Y, Yang Y, Xu L, Chen M, Wang J, et al. Morphological characteristics of severe aortic stenosis in China: imaging corelab observations from the first Chinese transcatheter aortic valve trial. 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Clin Anat. 2020;33(8):1240\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKatsi V, Georgiopoulos G, Oikonomou D, Aggeli C, Grassos C, Papadopoulos DP, et al. Aortic Stenosis, Aortic Regurgitation and Arterial Hypertension. Curr Vasc Pharmacol. 2019;17(2):180\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eObel LM, Diederichsen AC, Steffensen FH, Frost L, Lambrechtsen J, Busk M, et al. Population-Based Risk Factors for Ascending, Arch, Descending, and Abdominal Aortic Dilations for 60-74-Year-Old Individuals. J Am Coll Cardiol. 2021;78(3):201\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCanciello G, Mancusi C, Izzo R, Morisco C, Strisciuglio T, Barbato E, et al. Determinants of aortic root dilatation over time in patients with essential hypertension: The Campania Salute Network. Eur J Prev Cardiol. 2021;28(13):1508\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMedranda GA, Musallam A, Zhang C, Rappaport H, Gallino PE, Case BC, et al. The Impact of Aortic Angulation on Contemporary Transcatheter Aortic Valve Replacement Outcomes. JACC Cardiovasc Interv. 2021;14(11):1209\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSherif MA, Abdel-Wahab M, St\u0026ouml;cker B, Geist V, Richardt D, T\u0026ouml;lg R, et al. Anatomic and procedural predictors of paravalvular aortic regurgitation after implantation of the Medtronic CoreValve bioprosthesis. J Am Coll Cardiol. 2010;56(20):1623\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChan PH, Alegria-Barrero E, Di Mario C. Difficulties with horizontal aortic root in transcatheter aortic valve implantation. Catheter Cardiovasc Interv. 2013;81(4):630\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNoble S, Roffi M. Retrograde aortic valve crossing of the CoreValve prosthesis using the buddy balloon technique. Catheter Cardiovasc Interv. 2014;84(6):897\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRod\u0026eacute;s-Cabau J. Transcatheter aortic valve implantation: current and future approaches. Nat Rev Cardiol. 2011;9(1):15\u0026ndash;29.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarkham R, Ghodsian M, Sharma R. TAVR in Patients with Pure Aortic Regurgitation: Ready to Use? Curr Cardiol Rep. 2020;22(9):98.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eD'Ancona G, Kische S, El-Mawardy M, Di\u0026szlig;mann M, Heinze H, Zohlnh\u0026ouml;fer-Momm D, et al. Aortic annulus angulation does not attenuate procedural success of transcatheter aortic valve replacement using a novel self-expanding bioprosthesis. Heart Vessels. 2019;34(12):1969\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLandes U, Witberg G, Sathananthan J, Kim WK, Codner P, Buzzatti N, et al. Incidence, Causes, and Outcomes Associated With Urgent Implantation of a Supplementary Valve During Transcatheter Aortic Valve Replacement. JAMA Cardiol. 2021;6(8):936\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMayfield JJ, Otto CM. Stroke and Noninfective Native Valvular Disease. Curr Cardiol Rep. 2023;25(5):333\u0026ndash;48.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCoffey S, Roberts-Thomson R, Brown A, Carapetis J, Chen M, Enriquez-Sarano M, et al. Global epidemiology of valvular heart disease. Nat Rev Cardiol. 2021;18(12):853\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Transcatheter aortic valve replacement, aortic angulation, self-expanding valve","lastPublishedDoi":"10.21203/rs.3.rs-4884787/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4884787/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eAims\u003c/h2\u003e \u003cp\u003eTo investigate the effect of aortic angulation (AA) on clinical outcomes and related complications in patients with severe aortic valve stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) with self-expanding (SE) valve.\u003c/p\u003e\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAA is defined as the angle between the horizontal plane on the coronal plane and the plane of the aortic valve annulus, and is an important anatomical factor in TAVR. Whether AA affects the early clinical outcomes and complications in SE-TAVR procedure is still controversial.\u003c/p\u003e\u003ch2\u003eMethods and Results\u003c/h2\u003e \u003cp\u003eThis was a retrospective cohort study of 519 consecutive patients who underwent SE-TAVR in our center from January 2016 to January 2021.The range of AA in patients undergoing SE-TAVR in this study was 25\u0026deg;~ 93\u0026deg;, with an average angle of 55.4\u0026thinsp;\u0026plusmn;\u0026thinsp;9.7\u0026deg;. There was a statistically significant difference in technique success between AA\u0026thinsp;\u0026le;\u0026thinsp;55\u0026deg; and AA\u0026thinsp;\u0026gt;\u0026thinsp;55\u0026deg; group (87.3% vs. 79.1%, P\u0026thinsp;=\u0026thinsp;0.011), which was mainly due to the proportion of second-valve implantation was implanted during TAVR (8.8% vs. 19.6%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Among patients with TAV, those with an AA\u0026thinsp;\u0026gt;\u0026thinsp;55\u0026deg;were more likely to require second-valve implantation compared to those with an AA\u0026thinsp;\u0026le;\u0026thinsp;55\u0026deg; (8.8% vs. 29.8%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), whereas this trend did not show significant statistical differences among patients with BAV (9.6% vs. 7.3%, P\u0026thinsp;=\u0026thinsp;0.345).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eLarger angulation of aortic valve has significant lower technique success of TAVR which was mainly due to increasing of second-valve implantation events in SE-TAVR patients. AA mainly affects the incidence of second-valve implantation during SE-TAVR in TAV group, rather than BAV group.\u003c/p\u003e","manuscriptTitle":"Aortic Angulation Distribution and Effects on the Outcome and Complications of Self-expanding Transcatheter Aortic Valve Replacement","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-15 04:45:05","doi":"10.21203/rs.3.rs-4884787/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1c32138d-c70f-4559-b151-153dc3d5d251","owner":[],"postedDate":"October 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-10-15T04:45:07+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-15 04:45:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4884787","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4884787","identity":"rs-4884787","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}