<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3-mathml3.dtd">
<article article-type="research-article" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" dtd-version="1.3" xml:lang="EN">
<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Cardiovasc. Med.</journal-id><journal-title-group>
<journal-title>Frontiers in Cardiovascular Medicine</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Cardiovasc. Med.</abbrev-journal-title></journal-title-group>
<issn pub-type="epub">2297-055X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fcvm.2026.1755835</article-id>
<article-version article-version-type="Version of Record" vocab="NISO-RP-8-2008"/>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Original Research</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Methods for improved bileaflet aortic valve detection prior to transcatheter aortic valve replacement</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes"><name><surname>Tretter</surname><given-names>Justin T.</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="corresp" rid="cor1">&#x002A;</xref><uri xlink:href="https://loop.frontiersin.org/people/3296905/overview"/><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="conceptualization" vocab-term-identifier="https://credit.niso.org/contributor-roles/conceptualization/">Conceptualization</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Formal analysis" vocab-term-identifier="https://credit.niso.org/contributor-roles/formal-analysis/">Formal analysis</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="investigation" vocab-term-identifier="https://credit.niso.org/contributor-roles/investigation/">Investigation</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="methodology" vocab-term-identifier="https://credit.niso.org/contributor-roles/methodology/">Methodology</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; original draft" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-original-draft/">Writing &#x2013; original draft</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; review &#x0026; editing" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing &#x2013; review &#x0026; editing</role></contrib>
<contrib contrib-type="author"><name><surname>Eleid</surname><given-names>Mackram F.</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref><uri xlink:href="https://loop.frontiersin.org/people/1092963/overview" /><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; review &#x0026; editing" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing &#x2013; review &#x0026; editing</role></contrib>
<contrib contrib-type="author"><name><surname>Bedogni</surname><given-names>Francesco</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref><uri xlink:href="https://loop.frontiersin.org/people/1171009/overview" /><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; review &#x0026; editing" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing &#x2013; review &#x0026; editing</role></contrib>
<contrib contrib-type="author"><name><surname>Rod&#x00E9;s-Cabau</surname><given-names>Josep</given-names></name>
<xref ref-type="aff" rid="aff4"><sup>4</sup></xref><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; review &#x0026; editing" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing &#x2013; review &#x0026; editing</role></contrib>
<contrib contrib-type="author"><name><surname>Regueiro</surname><given-names>Ander</given-names></name>
<xref ref-type="aff" rid="aff5"><sup>5</sup></xref><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; review &#x0026; editing" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing &#x2013; review &#x0026; editing</role></contrib>
<contrib contrib-type="author"><name><surname>Testa</surname><given-names>Luca</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; review &#x0026; editing" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing &#x2013; review &#x0026; editing</role></contrib>
<contrib contrib-type="author"><name><surname>Chen</surname><given-names>Shmuel</given-names></name>
<xref ref-type="aff" rid="aff6"><sup>6</sup></xref><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; review &#x0026; editing" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing &#x2013; review &#x0026; editing</role></contrib>
<contrib contrib-type="author"><name><surname>Galhardo</surname><given-names>Attilio</given-names></name>
<xref ref-type="aff" rid="aff4"><sup>4</sup></xref><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; review &#x0026; editing" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing &#x2013; review &#x0026; editing</role></contrib>
<contrib contrib-type="author"><name><surname>Ellenbogen</surname><given-names>Kenneth A.</given-names></name>
<xref ref-type="aff" rid="aff7"><sup>7</sup></xref><uri xlink:href="https://loop.frontiersin.org/people/2801722/overview" /><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; review &#x0026; editing" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing &#x2013; review &#x0026; editing</role></contrib>
<contrib contrib-type="author"><name><surname>Leon</surname><given-names>Martin B.</given-names></name>
<xref ref-type="aff" rid="aff8"><sup>8</sup></xref>
<xref ref-type="aff" rid="aff9"><sup>9</sup></xref><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; review &#x0026; editing" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing &#x2013; review &#x0026; editing</role></contrib>
<contrib contrib-type="author"><name><surname>Ben-Haim</surname><given-names>Shlomo</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; review &#x0026; editing" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing &#x2013; review &#x0026; editing</role></contrib>
</contrib-group>
<aff id="aff1"><label>1</label><institution>Hobart Healthcare Research Institute</institution>, <city>London</city>, <country country="gb">United Kingdom</country></aff>
<aff id="aff2"><label>2</label><institution>Department of Cardiovascular Medicine, Mayo Clinic</institution>, <city>Rochester</city>, <state>MN</state>, <country country="us">United States</country></aff>
<aff id="aff3"><label>3</label><institution>Department of Cardiology, Policlinico San Donato</institution>, <city>Milan</city>, <country country="it">Italy</country></aff>
<aff id="aff4"><label>4</label><institution>Department of Cardiology, Quebec Heart and Lung Institute, Laval University</institution>, <city>Quebec City</city>, <state>QC</state>, <country country="ca">Canada</country></aff>
<aff id="aff5"><label>5</label><institution>Cardiology Department, Hospital Cl&#x00ED;nic de Barcelona</institution>, <city>Barcelona</city>, <country country="es">Spain</country></aff>
<aff id="aff6"><label>6</label><institution>Division of Cardiology, NewYork-Presbyterian/Weill Cornell Medical Center</institution>, <city>New York</city>, <state>NY</state>, <country country="us">United States</country></aff>
<aff id="aff7"><label>7</label><institution>Division of Cardiology, Virginia Commonwealth University School of Medicine</institution>, <city>Richmond</city>, <state>VA</state>, <country country="us">United States</country></aff>
<aff id="aff8"><label>8</label><institution>Division of Cardiovascular Medicine, Columbia University Irving Medical Center/New York-Presbyterian Hospital</institution>, <city>New York</city>, <state>NY</state>, <country country="us">United States</country></aff>
<aff id="aff9"><label>9</label><institution>Cardiovascular Research Foundation</institution>, <city>New York</city>, <state>NY</state>, <country country="us">United States</country></aff>
<author-notes>
<corresp id="cor1"><label>&#x002A;</label><bold>Correspondence:</bold> Justin T. Tretter, <email xlink:href="mailto:trettej3@ccf.org">trettej3@ccf.org</email></corresp>
</author-notes>
<pub-date publication-format="electronic" date-type="pub" iso-8601-date="2026-02-23"><day>23</day><month>02</month><year>2026</year></pub-date>
<pub-date publication-format="electronic" date-type="collection"><year>2026</year></pub-date>
<volume>13</volume><elocation-id>1755835</elocation-id>
<history>
<date date-type="received"><day>27</day><month>11</month><year>2025</year></date>
<date date-type="rev-recd"><day>29</day><month>01</month><year>2026</year></date>
<date date-type="accepted"><day>05</day><month>02</month><year>2026</year></date>
</history>
<permissions>
<copyright-statement>&#x00A9; 2026 Tretter, Eleid, Bedogni, Rod&#x00E9;s-Cabau, Regueiro, Testa, Chen, Galhardo, Ellenbogen, Leon and Ben-Haim.</copyright-statement>
<copyright-year>2026</copyright-year><copyright-holder>Tretter, Eleid, Bedogni, Rod&#x00E9;s-Cabau, Regueiro, Testa, Chen, Galhardo, Ellenbogen, Leon and Ben-Haim</copyright-holder><license><ali:license_ref start_date="2026-02-23">https://creativecommons.org/licenses/by/4.0/</ali:license_ref><license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License (CC BY)</ext-link>. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p></license>
</permissions>
<abstract><sec><title>Background</title>
<p>Bileaflet aortic valve prevalence in transcatheter aortic valve replacement (TAVR) patients is poorly defined. We evaluated a TAVR cohort to determine the bileaflet aortic valve prevalence and understand features which may improve detection. In addition, we related valvar morphology to the occurrence of permanent pacemaker implantation (PPI) following TAVR.</p>
</sec><sec><title>Methods</title>
<p>Aortic valvar morphology diagnosis was recorded from the pre-procedural cardiac CTA reports prior to TAVR. Commissural angles, comparison of commissural heights, and dynamic visual inspection of the aortic valve were subsequently evaluated on pre-procedural cardiac CTA by an expert cardiac anatomist and imager, methods previously validated in a surgical cohort, to determine aortic valvar morphology and compared to the historical diagnosis. Relationships between valvar morphological characteristics with the need for PPM within 30-days post-TAVR were determined.</p>
</sec><sec><title>Results</title>
<p>Four-hundred and thirty-three (mean age 81.3&#x2009;&#x00B1;&#x2009;6.6 years, 53.8&#x0025; female) underwent TAVR [corrected diagnosis: 393 (90.8&#x0025;) trileaflet vs. 40 (9.2&#x0025;) bileaflet valves]. Bileaflet valves were historically misdiagnosed in 80&#x0025; of pre-procedural cardiac CTA reports. Thirty-four (85.0&#x0025;) had intercoronary leaflet fusion [mean commissural angle&#x2009;&#x003D;&#x2009;148.1 (18.3) degrees]. A commissural angle threshold of 141.1 degrees had a sensitivity of 0.73 and specificity of 0.86 for identifying a bileaflet valve. PPI post-TAVR occurred in 38&#x0025; bileaflet vs. 19&#x0025; trileaflet patients (<italic>p</italic>&#x2009;<italic>&#x003D;</italic>&#x2009;<italic>0.0114</italic>) [unadjusted OR for bileaflet valve requiring PPI&#x2009;&#x003D;&#x2009;2.54, 95&#x0025; CI (1.25&#x2013;5.01)].</p>
</sec><sec><title>Conclusions</title>
<p>Bileaflet aortic valves are commonly misdiagnosed. Assessment of the commissural angle and comparison of commissural heights may improve CTA-based diagnostic accuracy prior to TAVR. Improved detection may guide improved outcomes in this higher risk population.</p>
</sec>
</abstract>
<abstract abstract-type="graphical"><title>Graphical Abstract</title>
<p>
<fig>
<caption><p>Improved bileaflet aortic valve detection can be achieved by cardiac computed tomography prior to transcatheter aortic valve replacement.</p></caption>
<graphic xlink:href="fcvm-13-1755835-ga001.tif" position="anchor"/>
</fig></p>
</abstract>
<kwd-group>
<kwd>bicuspid aortic valve</kwd>
<kwd>calcific aortic valve disease</kwd>
<kwd>complete heart block</kwd>
<kwd>computed tomography</kwd>
<kwd>permanent pacemaker implantation</kwd>
<kwd>transcatheter aortic valve replacement</kwd>
</kwd-group><funding-group><funding-statement>The author(s) declared that financial support was not received for this work and/or its publication.</funding-statement></funding-group><counts>
<fig-count count="2"/>
<table-count count="5"/><equation-count count="0"/><ref-count count="25"/><page-count count="9"/><word-count count="0"/></counts><custom-meta-group><custom-meta><meta-name>section-at-acceptance</meta-name><meta-value>Cardiovascular Imaging</meta-value></custom-meta></custom-meta-group>
</article-meta>
</front>
<body><sec id="s1" sec-type="intro"><title>Introduction</title>
<p>A bileaflet (bicuspid) aortic valve accounts for up to 10&#x0025; of elderly patients currently treated by transcatheter aortic valve replacement (TAVR) (<xref ref-type="bibr" rid="B1">1</xref>&#x2013;<xref ref-type="bibr" rid="B4">4</xref>). Related to TAVR, these congenitally malformed valves, commonly compounded with calcific disease, are more technically demanding with increased risks (<xref ref-type="bibr" rid="B5">5</xref>). However, various retrospective and observational studies have reported discrepant findings (<xref ref-type="bibr" rid="B6">6</xref>). For example, the rate of need for permanent pacemaker implantation (PPI) following TAVR with newer-generation prostheses in those with a bileaflet aortic valve has been reported between 15&#x0025;, to over 40&#x0025; (<xref ref-type="bibr" rid="B5">5</xref>, <xref ref-type="bibr" rid="B6">6</xref>). This may partly be influenced by institutional volume and experience (<xref ref-type="bibr" rid="B5">5</xref>, <xref ref-type="bibr" rid="B7">7</xref>). These discrepancies may also relate to the high misdiagnosis rate of bileaflet valves prior to the TAVR procedure. In fact, a single center study reported misdiagnoses of bileaflet valves in up to 90&#x0025; of elderly patients considered for TAVR when relying on transthoracic echocardiogram (<xref ref-type="bibr" rid="B8">8</xref>). While the use of cardiac computed tomography angiography (CTA), magnetic resonance angiography, or transesophageal echocardiogram may approximately double the detection rate, a large proportion of these patients remain misclassified going into the TAVR procedure (<xref ref-type="bibr" rid="B8">8</xref>, <xref ref-type="bibr" rid="B9">9</xref>).</p>
<p>Advancements in the imaging interrogation and surgical strategies towards repairing the bileaflet aortic valve have necessitated improved descriptions and classification schemes (<xref ref-type="bibr" rid="B10">10</xref>&#x2013;<xref ref-type="bibr" rid="B12">12</xref>). Historical classification schemes solely focused on the number of leaflets and presence or absence of leaflet fusion with corresponding raphe (<xref ref-type="bibr" rid="B13">13</xref>). Newer classification schemes hold in common the additional description of the commissural angle between the two normal commissures in the more prevalent functionally bileaflet aortic valve which retains three sinuses (<xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B14">14</xref>). In this form of the bileaflet valve, the commissural angle has a predictable relationship to both the degree of leaflet fusion and the height of the corresponding fused commissure and its underlying hypoplastic interleaflet triangle (<xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B15">15</xref>). Furthermore, morphologic and surgical observational studies suggest that over 80&#x0025; of those with a functionally bileaflet aortic valve may have abnormal commissural angles with resulting leaflet and sinus asymmetries when compared to a normal trileaflet valve (<xref ref-type="bibr" rid="B16">16</xref>). This feature alone may aid the clinician in detecting a bileaflet aortic valve (<xref ref-type="bibr" rid="B12">12</xref>). The remaining 10&#x0025;, however, may appear indistinguishable from a trileaflet valve with commissural angles approximating 120 degrees (<xref ref-type="bibr" rid="B15">15</xref>). Interrogation of the commissural height of the suspected fused leaflet will aid in properly diagnosing these rarer subtypes of functionally bileaflet aortic valves (<xref ref-type="bibr" rid="B10">10</xref>&#x2013;<xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B17">17</xref>). This understanding may be used to improve the detection rate of bileaflet aortic valves (<xref ref-type="bibr" rid="B10">10</xref>, <xref ref-type="bibr" rid="B17">17</xref>). In fact, in a recent report utilizing CTA for personalized surgical planning and execution in children and adults with congenitally malformed aortic valves, this approach was validated by intraoperative inspection, reporting approximately two-thirds of patients with a functionally unileaflet aortic valve had been misclassified prior to this pre-surgical imaging evaluation (<xref ref-type="bibr" rid="B18">18</xref>). Understanding both commissural angles and commissure height has also proven to be an important variable to dictate the surgical repair strategy and predict subsequent repair durability (<xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B19">19</xref>).</p>
<p>While these described nuances have become common place in interrogation and surgical planning for those with a bileaflet aortic valve (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B18">18</xref>), little attention has been given to those considered for TAVR. In the current study we aimed to retrospectively assess these previously validated features by cardiac CTA in a large population considered for TAVR to the proportion of patients with a bileaflet aortic valve. Furthermore, we aimed to assess these morphological valvar features which may aid in the detection rate of these congenitally malformed valves and related valvar morphology to the occurrence of need for PPI following TAVR.</p>
</sec>
<sec id="s2" sec-type="methods"><title>Methods</title>
<sec id="s2a"><title>Study population</title>
<p>This study included patients who underwent TAVR from five institutions between November 2021 and May 2024 and were evaluated prior to the procedure by gated cardiac CTA. Patient selection for TAVR was performed per local standard practice. Study exclusion criteria included: low-quality images related to cardiac motion or respiratory artifact, scans which did not utilize cardiac gating, and valve-in-valve procedures. Patient demographics, medical history and comorbidities were recorded. This study was approved by the institutional review boards of the participating centers with informed consent required for patient involvement.</p>
</sec>
<sec id="s2b"><title>Pre-procedural cardiac computed tomography acquisition and assessment</title>
<p>Routine preprocedural cardiac CTA for TAVR was obtained per clinical guidelines at the discretion of the acquiring institution (<xref ref-type="bibr" rid="B20">20</xref>). Scan acquisition included a cardiac retrospective ECG-gated contrast-enhanced data set acquired throughout the cardiac cycle or ECG-gated dataset acquired in peak systole of the aortic root and heart.</p>
<p>The cardiac CTA was retrospectively assessed by an expert cardiac anatomist and imager (J.T.T), the same individual who had previously validated this approach compared to direct intraoperative surgical inspection in a cohort of children and adults undergoing congenital aortic valvar surgery (<xref ref-type="bibr" rid="B18">18</xref>). The valvar morphology was categorized based on recent expert consensus of the normal and congenitally malformed aortic root (<xref ref-type="bibr" rid="B12">12</xref>). Each of the three aortic valvar commissures were marked in the short axis of the aortic root. Mid-diastolic measurements (70&#x0025; R-R) were preferred when available, however, in the minority of cases involving only a peak systolic gated acquisition, measurements were performed in peak systole. The phase of the cardiac cycle where measurements were obtained was recorded. Angles were measured between each of the three sets of commissures with reference to the centroid of the trisinuate aortic root (X, right and non-coronary leaflet commissure; Y, right and left coronary leaflet commissure; Z, left and non-coronary leaflet commissure) (<xref ref-type="fig" rid="F1">Figure&#x00A0;1A</xref>). In the short axis of the aortic virtual basal ring and sinus of Valsalva planes, a center bisecting plane cutting across the midline of one leaflet and continuing across the zone of apposition between the other two leaflets was obtained. The commissural height of this zone of apposition, which represents the height of the intervening interleaflet triangle, was qualitatively compared both to the plane of the sinutubular junction and to the other two commissural heights (<xref ref-type="fig" rid="F1">Figures&#x00A0;1B&#x2013;F</xref>) (<xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B17">17</xref>). When available, the short axis cine of the aortic valve was visualized from the four-dimensional CTA cine to further assess the valvar morphology. The combined assessment of the commissural angles, comparison between the commissural heights, and visual dynamic assessment of the valve were used to distinguish the morphology of the aortic root and its valve (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B12">12</xref>).</p>
<fig id="F1" position="float"><label>Figure&#x00A0;1</label>
<caption><p>Cardiac computed tomographic assessment of the commissural angle and commissural heights are demonstrated. <bold>(A)</bold> Short axis of the aortic root is obtained to measure the commissural angle (angulated white double-headed arrow). In this functionally bileaflet aortic valve with fusion between the coronary leaflets it measures approximately 170 degrees. The black hashed line represents the center bisecting plane, which cuts from the interrogated commissure across to the midline of the opposite leaflet. <bold>(B)</bold> In the center bisecting plane, the height of the fused commissure (white arrow with black outline) above the plane of the virtual basal ring (green lines and hashed lines) will be short relative to the sinutubular junction (blue lines and hashed lines) and relative to interrogation of the normal commissures. <bold>(C)</bold> The long axis of the center bisecting plane is demonstrated in a normal trileaflet valve depicting a double shadow of the interrogated zone of apposition, leading up to the normal commissure (white arrow). <bold>(D&#x2013;F)</bold> Three-dimensional reconstructions of the depicted bileaflet valve demonstrate three sinuses, with a shortened interleaflet triangle (white arrow with black outline) and commissural height of the fused coronary leaflets relative to the other two normal commissures (white arrow).</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-13-1755835-g001.tif"><alt-text content-type="machine-generated">Six-panel composite image displaying cross-sectional CT scans and 3D reconstructions of a heart valve. Panels A&#x2013;C show grayscale CT slices with colored lines, arrows, and \"zone of apposition\" label marking anatomical features. Panels D&#x2013;F present orange 3D-rendered views with dashed lines and arrows indicating corresponding planes and regions of interest.</alt-text>
</graphic>
</fig>
<p>To assess for variability in the rotational position of the aortic root relative to the base of the left ventricle, a midline point was marked at the base of the inferoseptal recess roof (Point i), in line with the atrial septum, and compared to the angle with the non-coronary leaflet nadir. The aorto-ventricular angle was assessed from the coronal view as the angle between a horizontal line at the level of the basal left ventricle and the aortic valve annulus (<xref ref-type="bibr" rid="B21">21</xref>).</p>
</sec>
<sec id="s2c"><title>Morphological method for diagnosing a bileaflet aortic valve</title>
<p>In those suspected to have leaflet fusion with leaflet and sinus asymmetry, the following findings supported the diagnosis of a congenital functionally bileaflet aortic valve:
<list list-type="simple">
<list-item>
<p>the two suspected normal commissures deviating from their normal commissural angle of approximately 120&#x2013;130 degrees,</p></list-item>
<list-item>
<p>and a commissural height of the suspected fused commissure significantly shorter than the two normal commissures, and significantly below the plane of the sinutubular junction (<xref ref-type="fig" rid="F1">Figure&#x00A0;1</xref>) (<xref ref-type="bibr" rid="B12">12</xref>).</p></list-item>
</list></p>
</sec>
<sec id="s2d"><title>Procedural details and outcomes</title>
<p>The type of transcatheter heart valve deployed was recorded. Requirement for PPI within 30-days following the procedure was recorded. Other common complications which were not consistently recorded and available in this retrospective chart review, such as paravalvar leak, were not assessed.</p>
</sec>
<sec id="s2e"><title>Statistical analysis</title>
<p>Continuous variables were summarized as mean (standard deviation), and categorical variables as frequencies (percentages). Student&#x0027;s <italic>t</italic>-test and Pearson&#x0027;s Chi-squared test with continuity correction (where applicable) were performed to compare continuous and categorical variables across groups of interest, respectively. Linear models adjusted for CTA assessment phase and commissural angle width were regressed on anatomical variables to assess the difference between valve types. The receiver-operator characteristics (ROC) of the commissural angle were examined using a simple binary logistic model by regressing the angle of non-fused commissures on the judgement of the valve being bileaflet. To account for the potential differences in measurements made in systolic and diastolic phases, the assessed relationships were additionally adjusted for CTA assessment phase. A simple (unadjusted) binary logistic model was regressed to assess aortic leaflet morphology related to the occurrence of PPI, with adjusted and unadjusted models assessing the impact of prosthetic valve type.</p>
<p>An alpha level &#x003C;0.05 was assessed to identify statistical relationships not due to chance. All statistical analyses were performed in R (<xref ref-type="bibr" rid="B22">22</xref>), and with the help of packages <italic>pROC</italic> (<xref ref-type="bibr" rid="B23">23</xref>) and <italic>emmeans</italic> package (<xref ref-type="bibr" rid="B24">24</xref>).</p>
</sec>
</sec>
<sec id="s3" sec-type="results"><title>Results</title>
<p>Four-hundred and thirty-three patients were included in the analysis with a mean (SD) age of 81.3 years (6.6), 53.8&#x0025; female. Due to retrospective, multicenter design of the study, the quantitative CTA assessments were carried out in either diastole or systole as described in the methods: 270 cases were analyzed in diastole (62&#x0025;), and another 163 (38&#x0025;) were analyzed in systole. Utilizing our morphological method for diagnosis, 393 (90.8&#x0025;) were determined to have trileaflet and 40 (9.2&#x0025;) functionally bileaflet aortic valves with trisinuate aortic roots. No patient had a bileaflet valve with bisinuate aortic root. Based on the pre-procedural cardiac CT report, bileaflet aortic valves had been prospectively misdiagnosed as having a trileaflet valve in 32 of 40 cases (80&#x0025;), while 4&#x0025; of those with a trileaflet aortic valve were incorrectly classified as having a bileaflet valve. The baseline demographics, pre-procedural aortic virtual basal ring dimensions and prosthetic device type and size compared between these two groups are summarized in <xref ref-type="table" rid="T1">Table&#x00A0;1</xref>.</p>
<table-wrap id="T1" position="float"><label>Table&#x00A0;1</label>
<caption><p>Baseline demographics, pre-procedural rhythm electrocardiographic findings, aortic virtual basal ring dimensions and device selection.</p></caption>
<table>
<colgroup>
<col align="left"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left" rowspan="2">Variable</th>
<th valign="top" align="center" colspan="2">Trileaflet aortic (<italic>n</italic>&#x2009;&#x003D;&#x2009;393)</th>
<th valign="top" align="center" colspan="2">Bileaflet aortic (<italic>n</italic>&#x2009;&#x003D;&#x2009;40)</th>
<th valign="top" align="center" rowspan="2"><italic>p</italic>-value</th>
</tr>
<tr>
<th valign="top" align="center">Mean/N</th>
<th valign="top" align="center">STD/&#x0025;</th>
<th valign="top" align="center">Mean/N</th>
<th valign="top" align="center">STD/&#x0025;</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Age (years)</td>
<td valign="top" align="center">81.5</td>
<td valign="top" align="center">6.6</td>
<td valign="top" align="center">79.5</td>
<td valign="top" align="center">6.0</td>
<td valign="top" align="center">0.0449</td>
</tr>
<tr>
<td valign="top" align="left">Sex (female)</td>
<td valign="top" align="center">215</td>
<td valign="top" align="center">55&#x0025;</td>
<td valign="top" align="center">16</td>
<td valign="top" align="center">40&#x0025;</td>
<td valign="top" align="center">0.1769</td>
</tr>
<tr>
<td valign="top" align="left">Atrial Fibrillation</td>
<td valign="top" align="center">81</td>
<td valign="top" align="center">21&#x0025;</td>
<td valign="top" align="center">8</td>
<td valign="top" align="center">20&#x0025;</td>
<td valign="top" align="center">1.0000</td>
</tr>
<tr>
<td valign="top" align="left">Diabetes Mellitus</td>
<td valign="top" align="center">101</td>
<td valign="top" align="center">26&#x0025;</td>
<td valign="top" align="center">10</td>
<td valign="top" align="center">25&#x0025;</td>
<td valign="top" align="center">1.0000</td>
</tr>
<tr>
<td valign="top" align="left">Chronic Kidney Disease</td>
<td valign="top" align="center">42</td>
<td valign="top" align="center">11&#x0025;</td>
<td valign="top" align="center">6</td>
<td valign="top" align="center">15&#x0025;</td>
<td valign="top" align="center">0.1671</td>
</tr>
<tr>
<td valign="top" align="left">Hypertension</td>
<td valign="top" align="center">273</td>
<td valign="top" align="center">69&#x0025;</td>
<td valign="top" align="center">23</td>
<td valign="top" align="center">58&#x0025;</td>
<td valign="top" align="center">0.2395</td>
</tr>
<tr>
<td valign="top" align="left">Right bundle branch block</td>
<td valign="top" align="center">36</td>
<td valign="top" align="center">9&#x0025;</td>
<td valign="top" align="center">4</td>
<td valign="top" align="center">10&#x0025;</td>
<td valign="top" align="center">1.0000</td>
</tr>
<tr>
<td valign="top" align="left">Left bundle branch block</td>
<td valign="top" align="center">25</td>
<td valign="top" align="center">6&#x0025;</td>
<td valign="top" align="center">8</td>
<td valign="top" align="center">20&#x0025;</td>
<td valign="top" align="center">0.0051</td>
</tr>
<tr>
<td valign="top" align="left">1st degree AV block</td>
<td valign="top" align="center">116</td>
<td valign="top" align="center">30&#x0025;</td>
<td valign="top" align="center">19</td>
<td valign="top" align="center">48&#x0025;</td>
<td valign="top" align="center">0.0282</td>
</tr>
<tr>
<td valign="top" align="left">Aortic VBR perimeter (mm)</td>
<td valign="top" align="center">75.1</td>
<td valign="top" align="center">7.3</td>
<td valign="top" align="center">81.2</td>
<td valign="top" align="center">9.9</td>
<td valign="top" align="center">0.0005</td>
</tr>
<tr>
<td valign="top" align="left">Aortic VBR major axis diameter (mm)</td>
<td valign="top" align="center">26.5</td>
<td valign="top" align="center">2.7</td>
<td valign="top" align="center">28.5</td>
<td valign="top" align="center">3.5</td>
<td valign="top" align="center">0.0010</td>
</tr>
<tr>
<td valign="top" align="left">Aortic VBR minor axis diameter (mm)</td>
<td valign="top" align="center">21.1</td>
<td valign="top" align="center">2.6</td>
<td valign="top" align="center">22.8</td>
<td valign="top" align="center">3.1</td>
<td valign="top" align="center">0.0015</td>
</tr>
<tr>
<td valign="top" align="left">Device (self-expanding valve)</td>
<td valign="top" align="center">240</td>
<td valign="top" align="center">61&#x0025;</td>
<td valign="top" align="center">23</td>
<td valign="top" align="center">58&#x0025;</td>
<td valign="top" align="center">0.7869</td>
</tr>
<tr>
<td valign="top" align="left">Device Type</td>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
<td valign="top" align="center">0.1017</td>
</tr>
<tr>
<td valign="top" align="left">&#x2003;Acurate&#x2122;</td>
<td valign="top" align="center">65</td>
<td valign="top" align="center">17&#x0025;</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">5&#x0025;</td>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">&#x2003;Evolut&#x2122;</td>
<td valign="top" align="center">93</td>
<td valign="top" align="center">24&#x0025;</td>
<td valign="top" align="center">15</td>
<td valign="top" align="center">38&#x0025;</td>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">&#x2003;JenaValve&#x2122;</td>
<td valign="top" align="center">5</td>
<td valign="top" align="center">1&#x0025;</td>
<td valign="top" align="center">0</td>
<td valign="top" align="center">0&#x0025;</td>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">&#x2003;Myval&#x2122;</td>
<td valign="top" align="center">17</td>
<td valign="top" align="center">4&#x0025;</td>
<td valign="top" align="center">0</td>
<td valign="top" align="center">0&#x0025;</td>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">&#x2003;Navitor&#x2122;</td>
<td valign="top" align="center">77</td>
<td valign="top" align="center">20&#x0025;</td>
<td valign="top" align="center">6</td>
<td valign="top" align="center">15&#x0025;</td>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">&#x2003;Sapien&#x2122;</td>
<td valign="top" align="center">136</td>
<td valign="top" align="center">35&#x0025;</td>
<td valign="top" align="center">17</td>
<td valign="top" align="center">43&#x0025;</td>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">Device size (mm)</td>
<td valign="top" align="center">26.3</td>
<td valign="top" align="center">2.5</td>
<td valign="top" align="center">27.5</td>
<td valign="top" align="center">2.8</td>
<td valign="top" align="center">0.0181</td>
</tr>
<tr>
<td valign="top" align="left">CTA Assessment Phase</td>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
<td valign="top" align="center">0.3809</td>
</tr>
<tr>
<td valign="top" align="left">&#x2003;Systolic</td>
<td valign="top" align="center">151</td>
<td valign="top" align="center">38&#x0025;</td>
<td valign="top" align="center">12</td>
<td valign="top" align="center">30&#x0025;</td>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">&#x2003;Diastolic</td>
<td valign="top" align="center">242</td>
<td valign="top" align="center">62&#x0025;</td>
<td valign="top" align="center">28</td>
<td valign="top" align="center">70&#x0025;</td>
<td valign="top" align="center"/>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="TF1"><p>AV, atrioventricular block; CTA, computed tomography angiography; VBR, virtual basal ring.</p></fn>
<fn id="TF2"><p>Percentages may not add up to 100&#x0025; due to rounding effect.</p></fn>
</table-wrap-foot>
</table-wrap>
<p>Thirty-four of the 40 patients (85&#x0025;) with a bileaflet aortic valve had fusion between the right and left coronary leaflets, and the remaining 6 patients (17.5&#x0025;) had fusion between the right and non-coronary leaflets. The mean (SD) commissural angle between the two normal commissures was 148.1 (18.3) degrees, with no significant difference related to fusion phenotype (<italic>p</italic>&#x2009;&#x003D;&#x2009;0.8656). This compared to a mean (SD) commissural angle in the trileaflet aortic valve (average of angles between X&#x2013;Z and Z&#x2013;Y commissures to correspond to the bileaflet valve phenotypes) of 126.0 degrees (13.3) (<italic>p</italic>&#x2009;<italic>&#x003C;</italic>&#x2009;<italic>0.0001</italic>) (<xref ref-type="table" rid="T2">Table&#x00A0;2</xref>). The commissural angle demonstrated an area-under-the-curve of 0.83 [95&#x0025; CI (0.74&#x2013;0.91)] for identifying a functionally bileaflet aortic valve. A diagnostic angle threshold of 141.1 degrees had a sensitivity&#x2009;&#x003D;&#x2009;0.73 [95&#x0025; CI (0.57&#x2013;0.92)] and specificity&#x2009;&#x003D;&#x2009;0.86 [95&#x0025; CI (0.66&#x2013;0.94)] in identifying a bileaflet aortic valve (<xref ref-type="fig" rid="F2">Figure&#x00A0;2</xref>). The angle between the non-coronary leaflet nadir and Point I and the aorto-ventricular angle (both adjusted for CTA assessment phase and commissural angle width) are reported in <xref ref-type="table" rid="T3">Table&#x00A0;3</xref>.</p>
<table-wrap id="T2" position="float"><label>Table&#x00A0;2</label>
<caption><p>Morphological characteristics of aortic valves.</p></caption>
<table>
<colgroup>
<col align="left"/>
<col align="left"/>
<col align="left"/>
<col align="left"/>
<col align="left"/>
<col align="left"/>
<col align="left"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left" rowspan="2">Angle (degrees)</th>
<th valign="top" align="center" colspan="2">Trileaflet valves (<italic>N</italic>&#x2009;&#x003D;&#x2009;393)</th>
<th valign="top" align="center" colspan="4">Bileaflet valves (<italic>N</italic>&#x2009;&#x003D;&#x2009;40)</th>
<th valign="top" align="center"/>
</tr>
<tr>
<th valign="top" align="center"><italic>&#x00B5;</italic></th>
<th valign="top" align="center">sd</th>
<th valign="top" align="center" colspan="2"><italic>&#x00B5;</italic></th>
<th valign="top" align="center" colspan="2">sd</th>
<th valign="top" align="center"><italic>p</italic>-value</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">X-Y</td>
<td valign="top" align="left">110.4</td>
<td valign="top" align="left">11.7</td>
<td valign="top" align="left" style="background-color:#d9d9d9" colspan="2">99.0</td>
<td valign="top" align="left" style="background-color:#d9d9d9" colspan="2">13.1</td>
<td valign="top" align="left">&#x003C;0.0001</td>
</tr>
<tr>
<td valign="top" align="left">Y-Z</td>
<td valign="top" align="left">123.7</td>
<td valign="top" align="left">11.8</td>
<td valign="top" align="left" style="background-color:#d9d9d9" colspan="2">116.6</td>
<td valign="top" align="left" style="background-color:#d9d9d9" colspan="2">18.5</td>
<td valign="top" align="left">0.0283</td>
</tr>
<tr>
<td valign="top" align="left">X&#x2013;Z</td>
<td valign="top" align="left">126.0</td>
<td valign="top" align="left">13.3</td>
<td valign="top" align="left" style="background-color:#d9d9d9" colspan="2">144.4</td>
<td valign="top" align="left" style="background-color:#d9d9d9" colspan="2">21.3</td>
<td valign="top" align="left">&#x003C;0.0001</td>
</tr>
<tr>
<td valign="top" align="left">Commissural<xref ref-type="table-fn" rid="TF4"><sup>&#x2020;</sup></xref></td>
<td valign="top" align="left"><italic>126</italic>.<italic>0</italic></td>
<td valign="top" align="left"><italic>13</italic>.<italic>3</italic></td>
<td valign="top" align="left" style="background-color:#d9d9d9" colspan="2"><italic>148</italic>.<italic>1</italic></td>
<td valign="top" align="left" style="background-color:#d9d9d9" colspan="2"><italic>18</italic>.<italic>3</italic></td>
<td valign="top" align="left">&#x003C;0.0001</td>
</tr>
<tr>
<th valign="top" align="left" colspan="1">Angle (degrees)</th>
<th valign="top" align="left" colspan="2">Trileaflet valves</th>
<th valign="top" align="left" colspan="2">Right/left coronary (<italic>N</italic>&#x2009;&#x003D;&#x2009;34)</th>
<th valign="top" align="left" colspan="2">Right/non-coronary (<italic>N</italic>&#x2009;&#x003D;&#x2009;6)</th>
<th valign="top" align="left"/>
</tr>
<tr>
<th valign="top" align="left"/>
<th valign="top" align="left" colspan="2"></th>
<th valign="top" align="left"><italic>&#x00B5;</italic></th>
<th valign="top" align="left">sd</th>
<th valign="top" align="left"><italic>&#x00B5;</italic></th>
<th valign="top" align="left">sd</th>
<th valign="top" align="left"><italic>p</italic>-value</th>
</tr>
<tr>
<td valign="top" align="left">X&#x2013;Y</td>
<td valign="top" align="left" rowspan="4" style="background-color:#d9d9d9" colspan="2">Not Applicable</td>
<td valign="top" align="left">99.8</td>
<td valign="top" align="left">13.7</td>
<td valign="top" align="left">93.7</td>
<td valign="top" align="left">7.8</td>
<td valign="top" align="left">&#x2014;</td>
</tr>
<tr>
<td valign="top" align="left">Y&#x2013;Z</td>
<td valign="top" align="left">111.9</td>
<td valign="top" align="left">13.6</td>
<td valign="top" align="left">146.7</td>
<td valign="top" align="left">18.8</td>
<td valign="top" align="left">&#x2014;</td>
</tr>
<tr>
<td valign="top" align="left">Z&#x2013;X</td>
<td valign="top" align="left">148.3</td>
<td valign="top" align="left">18.6</td>
<td valign="top" align="left">119.6</td>
<td valign="top" align="left">22.4</td>
<td valign="top" align="left">&#x2014;</td>
</tr>
<tr>
<td valign="top" align="left">Commissural<xref ref-type="table-fn" rid="TF4"><sup>&#x2020;</sup></xref></td>
<td valign="top" align="left">148.3</td>
<td valign="top" align="left">18.6</td>
<td valign="top" align="left">146.7</td>
<td valign="top" align="left">18.8</td>
<td valign="top" align="left">0.8656</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="TF3"><p>X, right and non-coronary leaflet commissure; Y, right and left coronary leaflet commissure; Z, left and non-coronary leaflet commissure.</p></fn>
<fn id="TF4"><label>&#x2020;</label>
<p>For trileaflet valves, the <italic>commissural angle</italic> was defined as the average of X&#x2013;Z and Z&#x2013;Y angles; for bileaflet valves with right/left coronary leaflet fusion the angle corresponds to X&#x2013;Z, and for right/non-coronary leaflet fusion it corresponds to Y&#x2013;Z.</p></fn>
<fn id="TF5"><p>X, right and non-coronary leaflet commissure; Y, right and left coronary leaflet commissure; Z, left and non-coronary leaflet commissure.</p></fn>
</table-wrap-foot>
</table-wrap>
<fig id="F2" position="float"><label>Figure&#x00A0;2</label>
<caption><p>Left panel: receiver operator characteristics of the commissural angle in detecting the bileaflet aortic valve (AUC confidence intervals shaded in blue). Right panel: Confusion matrix for the same.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-13-1755835-g002.tif"><alt-text content-type="machine-generated">Receiver operating characteristic (ROC) curve on the left shows sensitivity versus one minus specificity with area under the curve of zero point eight three, diagnostic threshold greater than one hundred forty-one point one degrees, sensitivity zero point seven three, specificity zero point eight six. Confusion matrix on the right compares actual and predicted valve types: twenty-six true bileaflet, eleven bileaflet misclassified as trileaflet, fifty-three trileaflet misclassified as bileaflet, and three hundred thirty-eight true trileaflet.</alt-text>
</graphic>
</fig>
<table-wrap id="T3" position="float"><label>Table&#x00A0;3</label>
<caption><p>Relationship of the aortic root to the left ventricle.</p></caption>
<table>
<colgroup>
<col align="left"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left" rowspan="3">Variable</th>
<th valign="top" align="center" colspan="2">Trileaflet aortic valve</th>
<th valign="top" align="center" colspan="2">Bileaflet aortic valve</th>
<th valign="top" align="center" rowspan="3">Adjusted difference</th>
<th valign="top" align="center" rowspan="3">SE</th>
<th valign="top" align="center" rowspan="3"><italic>p</italic>-value</th>
</tr>
<tr>
<th valign="top" align="center" colspan="2">(<italic>n</italic>&#x2009;&#x003D;&#x2009;393)</th>
<th valign="top" align="center" colspan="2">(<italic>n</italic>&#x2009;&#x003D;&#x2009;40)</th>
</tr>
<tr>
<th valign="top" align="center">Mean</th>
<th valign="top" align="center">SD</th>
<th valign="top" align="center">Mean</th>
<th valign="top" align="center">SD</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Point I to non-coronary leaflet nadir angle (degrees)</td>
<td valign="top" align="center">&#x2212;1.4</td>
<td valign="top" align="center">13.6</td>
<td valign="top" align="center">5.4</td>
<td valign="top" align="center">15.0</td>
<td valign="top" align="center">6.80</td>
<td valign="top" align="center">2.74</td>
<td valign="top" align="center">0.0064</td>
</tr>
<tr>
<td valign="top" align="left">Left ventricle to aortic angle (degrees)</td>
<td valign="top" align="center">49.2</td>
<td valign="top" align="center">10.3</td>
<td valign="top" align="center">52.4</td>
<td valign="top" align="center">12.0</td>
<td valign="top" align="center">3.19</td>
<td valign="top" align="center">1.60</td>
<td valign="top" align="center">0.1102</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="TF6"><p>Means, standard deviations and difference of means (SE) are adjusted for CTA phase and commissural angle width; <italic>p</italic>-values are from the respective multiple linear models.</p></fn>
</table-wrap-foot>
</table-wrap>
<sec id="s3a"><title>Procedural outcomes</title>
<p>Fifteen of 40 patients (38&#x0025;) with a bileaflet valve compared to 75 of 393 patients (19&#x0025;) with a trileaflet valve had PPI requirement following TAVR (<italic>p</italic>&#x2009;&#x003D;&#x2009;0.0114) (<xref ref-type="table" rid="T4">Table&#x00A0;4</xref>). The unadjusted odds ratio for a bileaflet aortic valve requiring PPI was 2.54, 95&#x0025; CI [1.25&#x2013;5.01]). There was no relationship between balloon- vs. self-expanding device mechanism or size and the occurrence of PPI (<xref ref-type="table" rid="T5">Table&#x00A0;5</xref>). However, among specific devices, odds were lower for Acurate&#x2122; vs. Sapien&#x2122; [OR: 0.27, 95&#x0025; CI (0.09&#x2013;0.67), <italic>p</italic>&#x2009;&#x003D;&#x2009;0.0096], and comparable across remaining devices (<xref ref-type="sec" rid="s12">Supplementary Table 1</xref>). This relationship remained significant after adjusting for the effect of the bileaflet valve [aOR: 0.29, 95&#x0025; CI (0.10&#x2013;0.73), <italic>p</italic>&#x2009;&#x003D;&#x2009;0.0157] (<xref ref-type="sec" rid="s12">Supplementary Table 2</xref>).</p>
<table-wrap id="T4" position="float"><label>Table&#x00A0;4</label>
<caption><p>Comparative outcomes following transcatheter aortic valve replacement.</p></caption>
<table>
<colgroup>
<col align="left"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left" rowspan="3">Outcome</th>
<th valign="top" align="center" colspan="2">Trileaflet aortic valve</th>
<th valign="top" align="center" colspan="2">Bileaflet aortic valve</th>
<th valign="top" align="center" rowspan="3">Pearson&#x0027;s 
chi-squared 
<italic>p</italic>-value</th>
</tr>
<tr>
<th valign="top" align="center" colspan="2">(<italic>n</italic>&#x2009;&#x003D;&#x2009;393)</th>
<th valign="top" align="center" colspan="2">(<italic>n</italic>&#x2009;&#x003D;&#x2009;40)</th>
</tr>
<tr>
<th valign="top" align="center">N</th>
<th valign="top" align="center">&#x0025;</th>
<th valign="top" align="center">N</th>
<th valign="top" align="center">&#x0025;</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Permanent pacemaker</td>
<td valign="top" align="center">75</td>
<td valign="top" align="center">19&#x0025;</td>
<td valign="top" align="center">15</td>
<td valign="top" align="center">38&#x0025;</td>
<td valign="top" align="center">0.0114</td>
</tr>
<tr>
<td valign="top" align="left">Left bundle branch block at discharge</td>
<td valign="top" align="center">75</td>
<td valign="top" align="center">19&#x0025;</td>
<td valign="top" align="center">9</td>
<td valign="top" align="center">23&#x0025;</td>
<td valign="top" align="center">0.3457</td>
</tr>
<tr>
<td valign="top" align="left">Left bundle branch block at 30-day post-op</td>
<td valign="top" align="center">37</td>
<td valign="top" align="center">9&#x0025;</td>
<td valign="top" align="center">6</td>
<td valign="top" align="center">15&#x0025;</td>
<td valign="top" align="center">0.1330</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="T5" position="float"><label>Table&#x00A0;5</label>
<caption><p>Simple binary logistic regression on PPI occurrence in trileaflet and functionally bileaflet valves.</p></caption>
<table>
<colgroup>
<col align="left"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left" rowspan="2">Predictor</th>
<th valign="top" align="center" colspan="2">Trileaflet aortic valve (<italic>n</italic>&#x2009;&#x003D;&#x2009;393)</th>
<th valign="top" align="center" colspan="2">Bileaflet aortic valve (<italic>n</italic>&#x2009;&#x003D;&#x2009;40)</th>
</tr>
<tr>
<th valign="top" align="center">OR</th>
<th valign="top" align="center">95&#x0025; CI</th>
<th valign="top" align="center">OR</th>
<th valign="top" align="center">95&#x0025; CI</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Commissural angle (degrees)</td>
<td valign="top" align="center">1.00</td>
<td valign="top" align="center">[0.98&#x2013;1.02]</td>
<td valign="top" align="center">1.02</td>
<td valign="top" align="center">[0.98&#x2013;1.07]</td>
</tr>
<tr>
<td valign="top" align="left">Age (years)</td>
<td valign="top" align="center">1.00</td>
<td valign="top" align="center">[0.96&#x2013;1.04]</td>
<td valign="top" align="center">1.10</td>
<td valign="top" align="center">[0.98&#x2013;1.27]</td>
</tr>
<tr>
<td valign="top" align="left">Gender (Female)</td>
<td valign="top" align="center">0.62</td>
<td valign="top" align="center">[0.37&#x2013;1.02]</td>
<td valign="top" align="center">1.29</td>
<td valign="top" align="center">[0.33&#x2013;5.04]</td>
</tr>
<tr>
<td valign="top" align="left">Device type (self-expandible)</td>
<td valign="top" align="center">0.95</td>
<td valign="top" align="center">[0.57&#x2013;1.59]</td>
<td valign="top" align="center">0.76</td>
<td valign="top" align="center">[0.21&#x2013;2.81]</td>
</tr>
<tr>
<td valign="top" align="left">Device size (mm)</td>
<td valign="top" align="center">1.06</td>
<td valign="top" align="center">[0.96&#x2013;1.17]</td>
<td valign="top" align="center">0.95</td>
<td valign="top" align="center">[0.72&#x2013;1.21]</td>
</tr>
<tr>
<td valign="top" align="left">Major axis VBR diameter (mm)</td>
<td valign="top" align="center">1.08</td>
<td valign="top" align="center">[0.98&#x2013;1.19]</td>
<td valign="top" align="center">0.92</td>
<td valign="top" align="center">[0.75&#x2013;1.10]</td>
</tr>
<tr>
<td valign="top" align="left">Minor axis VBR diameter (mm)</td>
<td valign="top" align="center">1.05</td>
<td valign="top" align="center">[0.95&#x2013;1.16]</td>
<td valign="top" align="center">0.87</td>
<td valign="top" align="center">[0.67&#x2013;1.07]</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="TF7"><p>PPI, permanent pacemaker implantation; VBR, virtual basal ring.</p></fn>
</table-wrap-foot>
</table-wrap>
<p>There were no significant differences in data missingness between trileaflet and bileaflet valves, with the exception of device size, leaflet angle measurements, and gender, all of which were missing slightly more often in cases with bileaflet valves (<xref ref-type="sec" rid="s12">Supplementary Table 3</xref>).</p>
</sec>
</sec>
<sec id="s4" sec-type="discussion"><title>Discussion</title>
<p>This is the first systematic multi-center study to retrospectively utilize established cardiac CTA-based morphological assessment of the aortic root and its valve (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B12">12</xref>) to accurately determine the true prevalence of congenital bileaflet (bicuspid) aortic valves in a population of patients with aortic stenosis who underwent TAVR. The applied approach has recently been validated in a surgical cohort and compared to intraoperative assessment (<xref ref-type="bibr" rid="B18">18</xref>), based on detailed CTA evaluation and morphological classification (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B18">18</xref>). In addition, this study provides a reliable understanding towards the relationship between a bileaflet valve with the post-TAVR requirement for PPI. The major findings are: 1) a poor diagnostic rate of detecting bileaflet aortic valves when utilizing standard CTA-based visual assessment; 2) an improved diagnostic rate of a bileaflet valve when quantitatively assessing the commissural angle; and 3) a significantly higher rate of PPI following TAVR in those with a bileaflet valve.</p>
<p>Those with a bileaflet aortic valve comprised almost one-tenth of patients undergoing TAVR. Of concern, over three-quarters of these patients were not identified by those reporting the cardiac CTA. Whether or not the performing interventionalist properly identified the valvar morphology prior to the procedure is not clear with the retrospective design of the current study. Over one-third of those with a bileaflet aortic valve required PPI following TAVR, which was over double the incidence of the larger cohort with trileaflet valves (39&#x0025; vs. 19&#x0025;, respectively). The current study was not able to properly assess for other common post-procedural complications, such as paravalvar leak, due to its retrospective design. This study, however, emphasizes the need for the improved delineation of aortic valvar morphology preceding TAVR in order to properly determine related procedural risks and complications. This understanding will in turn guide procedural and technological improvements specific to patients with these not uncommon valvar phenotypes referred for TAVR.</p>
<p>While comparison could be made to other studies which have investigated this same outcome in bileaflet valves, this multi-center study raises concern towards the current real-world detection rate in prospectively identifying these relatively common congenitally malformed aortic valves prior to any TAVR procedure, questioning the accuracy in prior reports. A similar experience in the common misdiagnosis of adults with congenitally malformed aortic valves prior to referral into an international congenital aortic valvar surgical referral center has been reported with validation on direct intraoperative inspection (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B18">18</xref>). In those undergoing TAVR, detection may further be hindered in the setting of concomitant calcific aortic valvar disease, where calcifications may actually cause acquired fusion between leaflets. Quantitative assessment of the angle between the two normal commissures may improve the detection rate of congenital functionally bileaflet aortic valves. Specifically, a diagnostic angle greater than approximately 140 degrees has a sensitivity of 0.73 and specificity of 0.86. This diagnostic method may further be improved by assessing the commissural height of the suspected fused commissure with comparison to that of the normal commissures (<xref ref-type="bibr" rid="B10">10</xref>&#x2013;<xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B17">17</xref>, <xref ref-type="bibr" rid="B25">25</xref>), in combination to visual inspection of the suspected fused zone of apposition in systole (see <xref ref-type="fig" rid="F1">Figure&#x00A0;1</xref>). Depending solely on the latter, which presumably was the primary method used by those prospectively assessing the cardiac CTA prior to the TAVR procedure, is limited by the issue of through-plane motion of a three-dimensional structure through a two-dimensional plane of imaging and the difficulties mentioned in the valve with significant calcific disease (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B18">18</xref>).</p>
<p>In those with a bileaflet valve, there were significant differences in how the aortic root is positioned relative to the base of the left ventricle. This was reflected in a measurement of its rotational position (Point I to non-coronary leaflet nadir angle) and the angle of the long axis of the left ventricle relative to the aortic root. These findings support that the congenital aberration underyling the bileaflet aortic valve not only impacts the leaflets, but also how the aortic root itself is positioned relative the left ventricular outflow tract. These anatomical differences may contribute towards the increased post-procedural risks seen following TAVR, including both the increased risks for conduction damage and paravalvar leak (<xref ref-type="bibr" rid="B5">5</xref>).</p>
<sec id="s4a"><title>Limitations</title>
<p>The current study is limited by the smaller subset of patients with bileaflet valves. In addition, a fair number of patients in both trileaflet and bileaflet cohorts had missing data (reported in <xref ref-type="sec" rid="s12">Supplementary Table 1</xref>) with no significant differences between trileaflet and bileaflet cohorts, with the exception of device size and the angle between the left ventricle and aortic root. This same limitation prohibited the ability to assess for other post-procedural risk factors which were not consistently documented. Furthermore, future studies incorporating assessment of commissural angles should aim to determine the reproducibility of these proposed methods aiding in morphological assessment of the aortic valve.</p>
</sec>
</sec>
<sec id="s5" sec-type="conclusions"><title>Conclusion</title>
<p>Bileaflet aortic valves are common in older adults undergoing TAVR, though often misdiagnosed by traditional methods of dynamic short axis visualization. The diagnostic accuracy may be improved with assessment of the commissural angle and comparison of commissural heights. In those with a bileaflet valve, the rate of PPI following TAVR is almost doubled when compared to trileaflet aortic valves. Significant differences are seen in the position of aortic root relative to the left ventricle between these trileaflet and bileaflet aortic leaflet morphologies. These anatomical differences may contribute towards the increased risks for conduction damage and other complications following TAVR in those with a bileaflet aortic valve. Future studies using this morphological diagnostic method as a starting point in the proper assessment of procedural risk factors in this higher risk TAVR population are required to further validate this approach.</p>
</sec>
</body>
<back>
<sec id="s6" sec-type="data-availability"><title>Data availability statement</title>
<p>The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.</p>
</sec>
<sec id="s7" sec-type="ethics-statement"><title>Ethics statement</title>
<p>The studies involving humans were approved by Justin T. Tretter, Hobart Healthcare Research Institute, and institutional review boards for each participating center. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required from the participants or the participants&#x0027; legal guardians/next of kin in accordance with the national legislation and institutional requirements.</p>
</sec>
<sec id="s8" sec-type="author-contributions"><title>Author contributions</title>
<p>JT: Conceptualization, Formal analysis, Investigation, Methodology, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. ME: Writing &#x2013; review &#x0026; editing. FB: Writing &#x2013; review &#x0026; editing. JR-C: Writing &#x2013; review &#x0026; editing. AR: Writing &#x2013; review &#x0026; editing. LT: Writing &#x2013; review &#x0026; editing. SC: Writing &#x2013; review &#x0026; editing. AG: Writing &#x2013; review &#x0026; editing. KE: Writing &#x2013; review &#x0026; editing. ML: Writing &#x2013; review &#x0026; editing. SB-H: Writing &#x2013; review &#x0026; editing.</p>
</sec>
<sec id="s10" sec-type="COI-statement"><title>Conflict of interest</title>
<p>JT is a consultant for Cara Medical, Ltd.; AR is a consultant for Cara Medical, Ltd. and has received speaker/consultant fees from Abbott, Edwards Lifesciences and Meril. JR-C has received institutional research grants and speaker/consultant fees from Edwards Lifesciences and Medtronic; SB-H is the founder of Cara Medical, Ltd.</p>
<p>The remaining author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec id="s11" sec-type="ai-statement"><title>Generative AI statement</title>
<p>The author(s) declared that generative AI was not used in the creation of this manuscript.</p>
<p>Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.</p>
</sec>
<sec id="s13" sec-type="disclaimer"><title>Publisher&#x0027;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<sec id="s12" sec-type="supplementary-material"><title>Supplementary material</title>
<p>The Supplementary Material for this article can be found online at: <ext-link ext-link-type="uri" xlink:href="https://www.frontiersin.org/articles/10.3389/fcvm.2026.1755835/full#supplementary-material">https://www.frontiersin.org/articles/10.3389/fcvm.2026.1755835/full&#x0023;supplementary-material</ext-link></p>
<supplementary-material xlink:href="Datasheet1.docx" id="SM1" mimetype="application/vnd.openxmlformats-officedocument.wordprocessingml.document"/>
</sec>
<ref-list><title>References</title>
<ref id="B1"><label>1.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Halim</surname> <given-names>SA</given-names></name> <name><surname>Edwards</surname> <given-names>FH</given-names></name> <name><surname>Dai</surname> <given-names>D</given-names></name> <name><surname>Li</surname> <given-names>Z</given-names></name> <name><surname>Mack</surname> <given-names>MJ</given-names></name> <name><surname>Holmes</surname> <given-names>DR</given-names></name><etal/></person-group> <article-title>Outcomes of transcatheter aortic valve replacement in patients with bicuspid aortic valve disease: a report from the society of thoracic surgeons/American College of Cardiology transcatheter valve therapy registry</article-title>. <source>Circulation</source>. (<year>2020</year>) <volume>141</volume>:<fpage>1071</fpage>&#x2013;<lpage>9</lpage>. <pub-id pub-id-type="doi">10.1161/CIRCULATIONAHA.119.040333</pub-id><pub-id pub-id-type="pmid">32098500</pub-id></mixed-citation></ref>
<ref id="B2"><label>2.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Makkar</surname> <given-names>RR</given-names></name> <name><surname>Yoon</surname> <given-names>SH</given-names></name> <name><surname>Leon</surname> <given-names>MB</given-names></name> <name><surname>Chakravarty</surname> <given-names>T</given-names></name> <name><surname>Rinaldi</surname> <given-names>M</given-names></name> <name><surname>Shah</surname> <given-names>PB</given-names></name><etal/></person-group> <article-title>Association between transcatheter aortic valve replacement for bicuspid vs tricuspid aortic stenosis and mortality or stroke</article-title>. <source>Jama</source>. (<year>2019</year>) <volume>321</volume>:<fpage>2193</fpage>&#x2013;<lpage>202</lpage>. <pub-id pub-id-type="doi">10.1001/jama.2019.7108</pub-id><pub-id pub-id-type="pmid">31184741</pub-id></mixed-citation></ref>
<ref id="B3"><label>3.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Forrest</surname> <given-names>JK</given-names></name> <name><surname>Kaple</surname> <given-names>RK</given-names></name> <name><surname>Ramlawi</surname> <given-names>B</given-names></name> <name><surname>Gleason</surname> <given-names>TG</given-names></name> <name><surname>Meduri</surname> <given-names>CU</given-names></name> <name><surname>Yakubov</surname> <given-names>SJ</given-names></name><etal/></person-group> <article-title>Transcatheter aortic valve replacement in bicuspid versus tricuspid aortic valves from the STS/ACC TVT registry</article-title>. <source>JACC Cardiovasc Interv</source>. (<year>2020</year>) <volume>13</volume>:<fpage>1749</fpage>&#x2013;<lpage>59</lpage>. <pub-id pub-id-type="doi">10.1016/j.jcin.2020.03.022</pub-id><pub-id pub-id-type="pmid">32473890</pub-id></mixed-citation></ref>
<ref id="B4"><label>4.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vincent</surname> <given-names>F</given-names></name> <name><surname>Ternacle</surname> <given-names>J</given-names></name> <name><surname>Denimal</surname> <given-names>T</given-names></name> <name><surname>Shen</surname> <given-names>M</given-names></name> <name><surname>Redfors</surname> <given-names>B</given-names></name> <name><surname>Delhaye</surname> <given-names>C</given-names></name><etal/></person-group> <article-title>Transcatheter aortic valve replacement in bicuspid aortic valve stenosis</article-title>. <source>Circulation</source>. (<year>2021</year>) <volume>143</volume>:<fpage>1043</fpage>&#x2013;<lpage>61</lpage>. <pub-id pub-id-type="doi">10.1161/CIRCULATIONAHA.120.048048</pub-id><pub-id pub-id-type="pmid">33683945</pub-id></mixed-citation></ref>
<ref id="B5"><label>5.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Windecker</surname> <given-names>S</given-names></name> <name><surname>Okuno</surname> <given-names>T</given-names></name> <name><surname>Unbehaun</surname> <given-names>A</given-names></name> <name><surname>Mack</surname> <given-names>M</given-names></name> <name><surname>Kapadia</surname> <given-names>S</given-names></name> <name><surname>Falk</surname> <given-names>V</given-names></name></person-group>. <article-title>Which patients with aortic stenosis should be referred to surgery rather than transcatheter aortic valve implantation?</article-title> <source>Eur Heart J</source>. (<year>2022</year>) <volume>43</volume>:<fpage>2729</fpage>&#x2013;<lpage>50</lpage>. <pub-id pub-id-type="doi">10.1093/eurheartj/ehac105</pub-id><pub-id pub-id-type="pmid">35466382</pub-id></mixed-citation></ref>
<ref id="B6"><label>6.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jahangiri</surname> <given-names>M</given-names></name> <name><surname>Prendergast</surname> <given-names>B</given-names></name></person-group>. <article-title>Management of bicuspid aortic valve disease in the transcatheter aortic valve implantation era</article-title>. <source>Heart</source>. (<year>2024</year>) <volume>110</volume>:<fpage>1291</fpage>&#x2013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1136/heartjnl-2024-324054</pub-id><pub-id pub-id-type="pmid">39117383</pub-id></mixed-citation></ref>
<ref id="B7"><label>7.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vora</surname> <given-names>AN</given-names></name> <name><surname>Gada</surname> <given-names>H</given-names></name> <name><surname>Manandhar</surname> <given-names>P</given-names></name> <name><surname>Kosinski</surname> <given-names>A</given-names></name> <name><surname>Kirtane</surname> <given-names>A</given-names></name> <name><surname>Nazif</surname> <given-names>T</given-names></name><etal/></person-group> <article-title>National variability in pacemaker implantation rate following TAVR: insights from the STS/ACC TVT registry</article-title>. <source>JACC Cardiovasc Interv</source>. (<year>2024</year>) <volume>17</volume>:<fpage>391</fpage>&#x2013;<lpage>401</lpage>. <pub-id pub-id-type="doi">10.1016/j.jcin.2023.12.005</pub-id><pub-id pub-id-type="pmid">38355267</pub-id></mixed-citation></ref>
<ref id="B8"><label>8.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname> <given-names>WK</given-names></name> <name><surname>Liebetrau</surname> <given-names>C</given-names></name> <name><surname>Fischer-Rasokat</surname> <given-names>U</given-names></name> <name><surname>Renker</surname> <given-names>M</given-names></name> <name><surname>Rolf</surname> <given-names>A</given-names></name> <name><surname>Doss</surname> <given-names>M</given-names></name><etal/></person-group> <article-title>Challenges of recognizing bicuspid aortic valve in elderly patients undergoing TAVR</article-title>. <source>Int J Cardiovasc Imaging</source>. (<year>2020</year>) <volume>36</volume>:<fpage>251</fpage>&#x2013;<lpage>6</lpage>. <pub-id pub-id-type="doi">10.1007/s10554-019-01704-8</pub-id><pub-id pub-id-type="pmid">31587128</pub-id></mixed-citation></ref>
<ref id="B9"><label>9.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cramer</surname> <given-names>PM</given-names></name> <name><surname>Prakash</surname> <given-names>SK</given-names></name></person-group>. <article-title>Misclassification of bicuspid aortic valves is common and varies by imaging modality and patient characteristics</article-title>. <source>Echocardiography</source>. (<year>2019</year>) <volume>36</volume>:<fpage>761</fpage>&#x2013;<lpage>5</lpage>. <pub-id pub-id-type="doi">10.1111/echo.14295</pub-id><pub-id pub-id-type="pmid">30834578</pub-id></mixed-citation></ref>
<ref id="B10"><label>10.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tretter</surname> <given-names>JT</given-names></name> <name><surname>Izawa</surname> <given-names>Y</given-names></name> <name><surname>Spicer</surname> <given-names>DE</given-names></name> <name><surname>Okada</surname> <given-names>K</given-names></name> <name><surname>Anderson</surname> <given-names>RH</given-names></name> <name><surname>Quintessenza</surname> <given-names>JA</given-names></name><etal/></person-group> <article-title>Understanding the aortic root using computed tomographic assessment: a potential pathway to improved customized surgical repair</article-title>. <source>Circ Cardiovasc Imaging</source>. (<year>2021</year>) <volume>14</volume>:<fpage>e013134</fpage>. <pub-id pub-id-type="doi">10.1161/CIRCIMAGING.121.013134</pub-id><pub-id pub-id-type="pmid">34743527</pub-id></mixed-citation></ref>
<ref id="B11"><label>11.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tretter</surname> <given-names>JT</given-names></name> <name><surname>Burbano-Vera</surname> <given-names>NH</given-names></name> <name><surname>Najm</surname> <given-names>HK</given-names></name></person-group>. <article-title>Multi-modality imaging evaluation and pre-surgical planning for aortic valve-sparing operations in patients with aortic root aneurysm</article-title>. <source>Ann Cardiothorac Surg</source>. (<year>2023</year>) <volume>12</volume>:<fpage>295</fpage>&#x2013;<lpage>317</lpage>. <pub-id pub-id-type="doi">10.21037/acs-2023-avs2-0040</pub-id><pub-id pub-id-type="pmid">37554720</pub-id></mixed-citation></ref>
<ref id="B12"><label>12.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tretter</surname> <given-names>JT</given-names></name> <name><surname>Spicer</surname> <given-names>DE</given-names></name> <name><surname>Franklin</surname> <given-names>RCG</given-names></name> <name><surname>B&#x00E9;land</surname> <given-names>MJ</given-names></name> <name><surname>Aiello</surname> <given-names>VD</given-names></name> <name><surname>Cook</surname> <given-names>AC</given-names></name><etal/></person-group> <article-title>Expert consensus statement: anatomy, imaging, and Nomenclature of congenital aortic root malformations</article-title>. <source>Ann Thorac Surg</source>. (<year>2023</year>) <volume>116</volume>:<fpage>6</fpage>&#x2013;<lpage>16</lpage>. <pub-id pub-id-type="doi">10.1016/j.athoracsur.2023.03.023</pub-id><pub-id pub-id-type="pmid">37294261</pub-id></mixed-citation></ref>
<ref id="B13"><label>13.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sievers</surname> <given-names>HH</given-names></name> <name><surname>Schmidtke</surname> <given-names>C</given-names></name></person-group>. <article-title>A classification system for the bicuspid aortic valve from 304 surgical specimens</article-title>. <source>J Thorac Cardiovasc Surg</source>. (<year>2007</year>) <volume>133</volume>:<fpage>1226</fpage>&#x2013;<lpage>33</lpage>. <pub-id pub-id-type="doi">10.1016/j.jtcvs.2007.01.039</pub-id><pub-id pub-id-type="pmid">17467434</pub-id></mixed-citation></ref>
<ref id="B14"><label>14.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Michelena</surname> <given-names>HI</given-names></name> <name><surname>Della Corte</surname> <given-names>A</given-names></name> <name><surname>Evangelista</surname> <given-names>A</given-names></name> <name><surname>Maleszewski</surname> <given-names>JJ</given-names></name> <name><surname>Edwards</surname> <given-names>WD</given-names></name> <name><surname>Roman</surname> <given-names>MJ</given-names></name><etal/></person-group> <article-title>International consensus statement on Nomenclature and classification of the congenital bicuspid aortic valve and its aortopathy, for clinical, surgical, interventional and research purposes</article-title>. <source>Ann Thorac Surg</source>. (<year>2021</year>) <volume>112</volume>:<fpage>e203</fpage>&#x2013;<lpage>35</lpage>. <pub-id pub-id-type="doi">10.1016/j.athoracsur.2020.08.119</pub-id><pub-id pub-id-type="pmid">34304860</pub-id></mixed-citation></ref>
<ref id="B15"><label>15.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jahanyar</surname> <given-names>J</given-names></name> <name><surname>El Khoury</surname> <given-names>G</given-names></name> <name><surname>de Kerchove</surname> <given-names>L</given-names></name></person-group>. <article-title>Commissural geometry and cusp fusion insights to guide bicuspid aortic valve repair</article-title>. <source>JTCVS Tech</source>. (<year>2021</year>) <volume>7</volume>:<fpage>83</fpage>&#x2013;<lpage>92</lpage>. <pub-id pub-id-type="doi">10.1016/j.xjtc.2020.12.043</pub-id><pub-id pub-id-type="pmid">34319302</pub-id></mixed-citation></ref>
<ref id="B16"><label>16.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>de Kerchove</surname> <given-names>L</given-names></name> <name><surname>Mastrobuoni</surname> <given-names>S</given-names></name> <name><surname>Froede</surname> <given-names>L</given-names></name> <name><surname>Tamer</surname> <given-names>S</given-names></name> <name><surname>Boodhwani</surname> <given-names>M</given-names></name> <name><surname>van Dyck</surname> <given-names>M</given-names></name><etal/></person-group> <article-title>Variability of repairable bicuspid aortic valve phenotypes: towards an anatomical and repair-oriented classification</article-title>. <source>Eur J Cardiothorac Surg</source>. (<year>2019</year>):<fpage>ezz033</fpage>. <pub-id pub-id-type="doi">10.1093/ejcts/ezz033</pub-id><pub-id pub-id-type="pmid">30789231</pub-id></mixed-citation></ref>
<ref id="B17"><label>17.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tretter</surname> <given-names>JT</given-names></name> <name><surname>Spicer</surname> <given-names>DE</given-names></name> <name><surname>Mori</surname> <given-names>S</given-names></name> <name><surname>Chikkabyrappa</surname> <given-names>S</given-names></name> <name><surname>Redington</surname> <given-names>AN</given-names></name> <name><surname>Anderson</surname> <given-names>RH</given-names></name></person-group>. <article-title>The significance of the interleaflet triangles in determining the morphology of congenitally abnormal aortic valves: implications for noninvasive imaging and surgical management</article-title>. <source>J Am Soc Echocardiogr</source>. (<year>2016</year>) <volume>29</volume>:<fpage>1131</fpage>&#x2013;<lpage>43</lpage>. <pub-id pub-id-type="doi">10.1016/j.echo.2016.08.017</pub-id><pub-id pub-id-type="pmid">27742239</pub-id></mixed-citation></ref>
<ref id="B18"><label>18.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tretter</surname> <given-names>JT</given-names></name> <name><surname>Dakik</surname> <given-names>L</given-names></name> <name><surname>Ahmad</surname> <given-names>M</given-names></name> <name><surname>Costello</surname> <given-names>JP</given-names></name> <name><surname>Burbano-Vera</surname> <given-names>N</given-names></name> <name><surname>Fuchs</surname> <given-names>M</given-names></name><etal/></person-group> <article-title>Standardising cardiac CT-based personalised surgical planning and execution in congenital aortic valvar disease</article-title>. <source>Cardiol Young</source>. (<year>2025</year>) <volume>35</volume>:<fpage>2044</fpage>&#x2013;<lpage>52</lpage>. <pub-id pub-id-type="doi">10.1017/S1047951125109475</pub-id><pub-id pub-id-type="pmid">40931677</pub-id></mixed-citation></ref>
<ref id="B19"><label>19.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ehrlich</surname> <given-names>T</given-names></name> <name><surname>Abeln</surname> <given-names>KB</given-names></name> <name><surname>Froede</surname> <given-names>L</given-names></name> <name><surname>Schmitt</surname> <given-names>F</given-names></name> <name><surname>Giebels</surname> <given-names>C</given-names></name> <name><surname>Sch&#x00E4;fers</surname> <given-names>HJ</given-names></name></person-group>. <article-title>Twenty-five years&#x2019; experience with isolated bicuspid aortic valve repair: impact of commissural orientation</article-title>. <source>Eur J Cardiothorac Surg</source>. (<year>2024</year>) <volume>65</volume>:<fpage>ezae163</fpage>. <pub-id pub-id-type="doi">10.1093/ejcts/ezae163</pub-id><pub-id pub-id-type="pmid">38608189</pub-id></mixed-citation></ref>
<ref id="B20"><label>20.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Blanke</surname> <given-names>P</given-names></name> <name><surname>Weir-McCall</surname> <given-names>JR</given-names></name> <name><surname>Achenbach</surname> <given-names>S</given-names></name> <name><surname>Delgado</surname> <given-names>V</given-names></name> <name><surname>Hausleiter</surname> <given-names>J</given-names></name> <name><surname>Jilaihawi</surname> <given-names>H</given-names></name><etal/></person-group> <article-title>Computed tomography imaging in the context of transcatheter aortic valve implantation (TAVI)/transcatheter aortic valve replacement (TAVR): an expert consensus document of the society of cardiovascular computed tomography</article-title>. <source>JACC Cardiovasc Imaging</source>. (<year>2019</year>) <volume>12</volume>:<fpage>1</fpage>&#x2013;<lpage>24</lpage>. <pub-id pub-id-type="doi">10.1016/j.jcmg.2018.12.003</pub-id><pub-id pub-id-type="pmid">30621986</pub-id></mixed-citation></ref>
<ref id="B21"><label>21.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tretter</surname> <given-names>JT</given-names></name> <name><surname>Bedogni</surname> <given-names>F</given-names></name> <name><surname>Rod&#x00E9;s-Cabau</surname> <given-names>J</given-names></name> <name><surname>Regueiro</surname> <given-names>A</given-names></name> <name><surname>Testa</surname> <given-names>L</given-names></name> <name><surname>Eleid</surname> <given-names>MF</given-names></name><etal/></person-group> <article-title>Novel cardiac CT method for identifying the atrioventricular conduction axis by anatomic landmarks</article-title>. <source>Heart Rhythm</source>. (<year>2025</year>) <volume>22</volume>:<fpage>776</fpage>&#x2013;<lpage>85</lpage>. <pub-id pub-id-type="doi">10.1016/j.hrthm.2024.12.022</pub-id><pub-id pub-id-type="pmid">39706459</pub-id></mixed-citation></ref>
<ref id="B22"><label>22.</label><mixed-citation publication-type="book"><collab>R Core Team</collab>. <source>R: A Language and Environment for Statistical Computing</source>. <publisher-loc>Vienna, Austria</publisher-loc>: <publisher-name>R Foundation for Statistical Computing</publisher-name> (<year>2024</year>). <comment>Available online at:</comment> <ext-link ext-link-type="uri" xlink:href="https://www.R-project.org/">https://www.R-project.org/</ext-link></mixed-citation></ref>
<ref id="B23"><label>23.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Robin</surname> <given-names>X</given-names></name> <name><surname>Turck</surname> <given-names>N</given-names></name> <name><surname>Hainard</surname> <given-names>A</given-names></name> <name><surname>Tiberti</surname> <given-names>N</given-names></name> <name><surname>Lisacek</surname> <given-names>F</given-names></name> <name><surname>Sanchez</surname> <given-names>JC</given-names></name><etal/></person-group> <article-title>pROC: an open-source package for R and S&#x002B; to analyze and compare ROC curves</article-title>. <source>BMC Bioinformatics</source>. (<year>2011</year>) <volume>12</volume>:<fpage>77</fpage>. <pub-id pub-id-type="doi">10.1186/1471-2105-12-77</pub-id><pub-id pub-id-type="pmid">21414208</pub-id></mixed-citation></ref>
<ref id="B24"><label>24.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Searle</surname> <given-names>SR</given-names></name> <name><surname>Speed</surname> <given-names>FM</given-names></name> <name><surname>Milliken</surname> <given-names>GA</given-names></name></person-group>. <article-title>Population marginal means in the linear model: an alternative to least squares means</article-title>. <source>Am Stat</source>. (<year>1980</year>) <volume>34</volume>:<fpage>216</fpage>&#x2013;<lpage>21</lpage>. <pub-id pub-id-type="doi">10.1080/00031305.1980.10483031</pub-id></mixed-citation></ref>
<ref id="B25"><label>25.</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Izawa</surname> <given-names>Y</given-names></name> <name><surname>Mori</surname> <given-names>S</given-names></name> <name><surname>Tretter</surname> <given-names>JT</given-names></name> <name><surname>Quintessenza</surname> <given-names>JA</given-names></name> <name><surname>Toh</surname> <given-names>H</given-names></name> <name><surname>Toba</surname> <given-names>T</given-names></name><etal/></person-group> <article-title>Normative aortic valvar measurements in adults using cardiac computed tomography&#x2014;a potential guide to further sophisticate aortic valve-sparing surgery</article-title>. <source>Circ J</source>. (<year>2021</year>) <volume>85</volume>:<fpage>1059</fpage>&#x2013;<lpage>67</lpage>. <pub-id pub-id-type="doi">10.1253/circj.CJ-20-0938</pub-id><pub-id pub-id-type="pmid">33408304</pub-id></mixed-citation></ref></ref-list>
<fn-group>
<fn id="n1" fn-type="custom" custom-type="edited-by"><p>Edited by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1659805/overview">Marco Guglielmo</ext-link>, University Medical Center Utrecht, Netherlands</p></fn>
<fn id="n2" fn-type="custom" custom-type="reviewed-by"><p>Reviewed by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/2122721/overview">Didem Oguz</ext-link>, University of Health Sciences, T&#x00FC;rkiye</p>
<p><ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/3248011/overview">Ramiz Emini</ext-link>, King Salman bin Abdulaziz Hospital, Saudi Arabia</p></fn>
<fn fn-type="abbr" id="abbrev1"><p><bold>Abbreviations</bold> CI, confidence interval; CTA, computed tomography angiography; PPI, permanent pacemaker implantation; ROC, receiver-operator characteristics; TAVR, transcatheter aortic valve replacement.</p></fn>
</fn-group>
</back>
</article>