<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" "journalpublishing.dtd">
<article article-type="research-article" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xml:lang="EN">
<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Cardiovasc. Med.</journal-id>
<journal-title>Frontiers in Cardiovascular Medicine</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Cardiovasc. Med.</abbrev-journal-title>
<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.2023.1256420</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Cardiovascular Medicine</subject>
<subj-group>
<subject>Original Research</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Valvular and ascending aortic hemodynamics of the On-X aortic valved conduit by same-day echocardiography and 4D flow MRI</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes"><name><surname>Lee</surname><given-names>Jeesoo</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/2335533/overview"/><role content-type="https://credit.niso.org/contributor-roles/formal-analysis/"/><role content-type="https://credit.niso.org/contributor-roles/investigation/"/><role content-type="https://credit.niso.org/contributor-roles/methodology/"/><role content-type="https://credit.niso.org/contributor-roles/validation/"/><role content-type="https://credit.niso.org/contributor-roles/visualization/"/><role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/><role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/></contrib>
<contrib contrib-type="author"><name><surname>Huh</surname><given-names>Hyungkyu</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref><role content-type="https://credit.niso.org/contributor-roles/data-curation/"/><role content-type="https://credit.niso.org/contributor-roles/formal-analysis/"/><role content-type="https://credit.niso.org/contributor-roles/methodology/"/><role content-type="https://credit.niso.org/contributor-roles/visualization/"/><role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/></contrib>
<contrib contrib-type="author"><name><surname>Scott</surname><given-names>Michael B.</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref><role content-type="https://credit.niso.org/contributor-roles/methodology/"/><role content-type="https://credit.niso.org/contributor-roles/resources/"/><role content-type="https://credit.niso.org/contributor-roles/software/"/><role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/></contrib>
<contrib contrib-type="author"><name><surname>Elbaz</surname><given-names>Mohammed S. M.</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref><role content-type="https://credit.niso.org/contributor-roles/formal-analysis/"/><role content-type="https://credit.niso.org/contributor-roles/software/"/><role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/></contrib>
<contrib contrib-type="author"><name><surname>Puthumana</surname><given-names>Jyothy J.</given-names></name>
<xref ref-type="aff" rid="aff4"><sup>4</sup></xref><role content-type="https://credit.niso.org/contributor-roles/investigation/"/><role content-type="https://credit.niso.org/contributor-roles/methodology/"/><role content-type="https://credit.niso.org/contributor-roles/validation/"/><role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/></contrib>
<contrib contrib-type="author"><name><surname>McCarthy</surname><given-names>Patrick</given-names></name>
<xref ref-type="aff" rid="aff5"><sup>5</sup></xref><role content-type="https://credit.niso.org/contributor-roles/methodology/"/><role content-type="https://credit.niso.org/contributor-roles/validation/"/><role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/></contrib>
<contrib contrib-type="author"><name><surname>Malaisrie</surname><given-names>S. Christopher</given-names></name>
<xref ref-type="aff" rid="aff5"><sup>5</sup></xref><role content-type="https://credit.niso.org/contributor-roles/conceptualization/"/><role content-type="https://credit.niso.org/contributor-roles/resources/"/><role content-type="https://credit.niso.org/contributor-roles/validation/"/><role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/></contrib>
<contrib contrib-type="author"><name><surname>Markl</surname><given-names>Michael</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref><uri xlink:href="https://loop.frontiersin.org/people/105806/overview" /><role content-type="https://credit.niso.org/contributor-roles/conceptualization/"/><role content-type="https://credit.niso.org/contributor-roles/funding-acquisition/"/><role content-type="https://credit.niso.org/contributor-roles/project-administration/"/><role content-type="https://credit.niso.org/contributor-roles/resources/"/><role content-type="https://credit.niso.org/contributor-roles/supervision/"/><role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/></contrib>
<contrib contrib-type="author"><name><surname>Thomas</surname><given-names>James D.</given-names></name>
<xref ref-type="aff" rid="aff4"><sup>4</sup></xref><role content-type="https://credit.niso.org/contributor-roles/conceptualization/"/><role content-type="https://credit.niso.org/contributor-roles/funding-acquisition/"/><role content-type="https://credit.niso.org/contributor-roles/supervision/"/><role content-type="https://credit.niso.org/contributor-roles/validation/"/><role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/></contrib>
<contrib contrib-type="author"><name><surname>Barker</surname><given-names>Alex J.</given-names></name>
<xref ref-type="aff" rid="aff6"><sup>6</sup></xref><role content-type="https://credit.niso.org/contributor-roles/conceptualization/"/><role content-type="https://credit.niso.org/contributor-roles/funding-acquisition/"/><role content-type="https://credit.niso.org/contributor-roles/methodology/"/><role content-type="https://credit.niso.org/contributor-roles/supervision/"/><role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/></contrib>
</contrib-group>
<aff id="aff1"><label><sup>1</sup></label><institution>Department of Radiology, Feinberg School of Medicine, Northwestern University</institution>, <addr-line>Chicago, IL</addr-line>, <country>United States</country></aff>
<aff id="aff2"><label><sup>2</sup></label><institution>Medical Device Development Center</institution>, <institution>Daegu-Gyeongbuk Medical Innovation Foundation</institution>, <addr-line>Daegu</addr-line>, <country>Republic of Korea</country></aff>
<aff id="aff3"><label><sup>3</sup></label><institution>Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University</institution>, <addr-line>Evanston, IL</addr-line>, <country>United States</country></aff>
<aff id="aff4"><label><sup>4</sup></label><institution>Department of Cardiology, Feinberg School of Medicine, Northwestern University</institution>, <addr-line>Chicago, IL</addr-line>, <country>United States</country></aff>
<aff id="aff5"><label><sup>5</sup></label><institution>Division of Cardiac Surgery, Feinberg School of Medicine, Northwestern University</institution>, <addr-line>Chicago, IL</addr-line>, <country>United States</country></aff>
<aff id="aff6"><label><sup>6</sup></label><institution>Department of Radiology, University of Colorado Anschutz Medical Campus</institution>, <addr-line>Aurora, CO</addr-line>, <country>United States</country></aff>
<author-notes>
<fn fn-type="edited-by"><p><bold>Edited by:</bold> Attila Kardos, Milton Keynes University Hospital, United Kingdom</p></fn>
<fn fn-type="edited-by"><p><bold>Reviewed by:</bold> Gerald Marx, Boston Children&#x0027;s Hospital and Harvard Medical School, United States Francesco Sturla, IRCCS San Donato Polyclinic, Italy</p></fn>
<corresp id="cor1"><label>&#x002A;</label><bold>Correspondence:</bold> Jeesoo Lee <email>jeesoolee@northwestern.edu</email></corresp>
</author-notes>
<pub-date pub-type="epub"><day>14</day><month>11</month><year>2023</year></pub-date>
<pub-date pub-type="collection"><year>2023</year></pub-date>
<volume>10</volume><elocation-id>1256420</elocation-id>
<history>
<date date-type="received"><day>10</day><month>07</month><year>2023</year></date>
<date date-type="accepted"><day>17</day><month>10</month><year>2023</year></date>
</history>
<permissions>
<copyright-statement>&#x00A9; 2023 Lee, Huh, Scott, Elbaz, Puthumana, McCarthy, Malaisrie, Markl, Thomas and Barker.</copyright-statement>
<copyright-year>2023</copyright-year><copyright-holder>Lee, Huh, Scott, Elbaz, Puthumana, McCarthy, Malaisrie, Markl, Thomas and Barker</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://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.</p></license>
</permissions>
<abstract>
<p>This study aims to assess whether the On-X aortic valved conduit better restores normal valvular and ascending aortic hemodynamics than other commonly used bileaflet mechanical valved conduit prostheses from St. Jude Medical and Carbomedics by using same-day transthoracic echocardiography (TTE) and 4D flow magnetic resonance imaging (MRI) examinations. TTE and 4D flow MRI were performed back-to-back in 10 patients with On-X, six patients with St. Jude (two) and Carbomedics (four) prostheses, and 36 healthy volunteers. TTE evaluated valvular hemodynamic parameters: transvalvular peak velocity (TPV), mean and peak transvalvular pressure gradient (TPG), and effective orifice area (EOA). 4D flow MRI evaluated the peak systolic 3D viscous energy loss rate (VELR) density and mean vorticity magnitude in the ascending aorta (AAo). While higher TPV and mean and peak TPG were recorded in all patients compared to healthy subjects, the values in On-X patients were closer to those in healthy subjects (TPV 1.9&#x2009;&#x00B1;&#x2009;0.3 vs. 2.2&#x2009;&#x00B1;&#x2009;0.3 vs. 1.2&#x2009;&#x00B1;&#x2009;0.2&#x2005;m/s, mean TPG 7.4&#x2009;&#x00B1;&#x2009;1.9 vs. 9.2&#x2009;&#x00B1;&#x2009;2.3 vs. 3.1&#x2009;&#x00B1;&#x2009;0.9&#x2005;mmHg, peak TPG 15.3&#x2009;&#x00B1;&#x2009;5.2 vs. 18.9&#x2009;&#x00B1;&#x2009;5.2 vs. 6.1&#x2009;&#x00B1;&#x2009;1.8&#x2005;mmHg, <italic>p</italic>&#x2009;&#x003C;&#x2009;0.001). Likewise, while higher VELR density and mean vorticity magnitude were recorded in all patients than in healthy subjects, the values in On-X patients were closer to those in healthy subjects (VELR: 50.6&#x2009;&#x00B1;&#x2009;20.1 vs. 89.8&#x2009;&#x00B1;&#x2009;35.2 vs. 21.4&#x2009;&#x00B1;&#x2009;9.2&#x2005;W/m<sup>3</sup>, <italic>p</italic>&#x2009;&#x003C;&#x2009;0.001) and vorticity (147.6&#x2009;&#x00B1;&#x2009;30.0 vs. 191.2&#x2009;&#x00B1;&#x2009;26.0 vs. 84.6&#x2009;&#x00B1;&#x2009;20.5 s-1, <italic>p</italic>&#x2009;&#x003C;&#x2009;0.001). This study demonstrates that the On-X aortic valved conduit may produce less aberrant hemodynamics in the AAo while maintaining similar valvular hemodynamics to St. Jude Medical and Carbomedics alternatives.</p>
</abstract>
<kwd-group>
<kwd>bileaflet mechanical aortic valved conduit</kwd>
<kwd>valvular hemodynamics</kwd>
<kwd>ascending aortic hemodynamics</kwd>
<kwd>4D flow MRI</kwd>
<kwd>echocardiography</kwd>
</kwd-group>
<contract-num rid="cn001">&#x00A0;</contract-num>
<contract-sponsor id="cn001">CryoLife, Inc</contract-sponsor>
<counts>
<fig-count count="2"/>
<table-count count="2"/><equation-count count="0"/><ref-count count="27"/><page-count count="0"/><word-count count="0"/></counts><custom-meta-wrap><custom-meta><meta-name>section-at-acceptance</meta-name><meta-value>Cardiovascular Imaging</meta-value></custom-meta></custom-meta-wrap>
</article-meta>
</front>
<body>
<sec id="s1" sec-type="intro"><label>1.</label><title>Introduction</title>
<p>Bileaflet mechanical aortic valves are commonly recommended for aortic valve replacement (AVR) in patients with a longer life expectancy [age &#x2264;50 (<xref ref-type="bibr" rid="B1">1</xref>) or 60 years (<xref ref-type="bibr" rid="B2">2</xref>)] due to their long-lasting structural durability over bioprosthetic valves (<xref ref-type="bibr" rid="B1">1</xref>&#x2013;<xref ref-type="bibr" rid="B3">3</xref>). However, mechanical valves are more prone to thrombus formation, which requires patients to undergo a lifelong anticoagulation therapy, subsequently increasing the risk of bleeding events compared to bioprosthetic valves (35.1&#x0025; vs. 23.3&#x0025; in patients 45&#x2013;54 years of age) (<xref ref-type="bibr" rid="B3">3</xref>&#x2013;<xref ref-type="bibr" rid="B6">6</xref>). The On-X aortic valve (On-X Life Technologies, Kennesaw, GA) is currently the only mechanical heart valve approved by the FDA for a lower international normalized ratio target of 1.5&#x2013;2.0 (cf., standard range&#x2009;&#x003D;&#x2009;2.0&#x2013;3.0) (<xref ref-type="bibr" rid="B7">7</xref>). Further, improved valvular hemodynamics has been reported for the On-X valve compared to other bileaflet mechanical valves, as marked by reduced transvalvular peak velocity (TPV), transvalvular pressure gradient (TPG), and increased effective orifice area (EOA) (<xref ref-type="bibr" rid="B8">8</xref>&#x2013;<xref ref-type="bibr" rid="B10">10</xref>). However, the hemodynamic impact of AVR with a valved conduit is unclear since the changes in Windkessel performance of a stiff conduit vs. native elastic aortic tissue may impact cardiac afterload and downstream hemodynamics (<xref ref-type="bibr" rid="B11">11</xref>).</p>
<p>Time-resolved three-dimensional (3D) phase-contrast magnetic resonance imaging (MRI), commonly referred to as 4D flow MRI (<xref ref-type="bibr" rid="B12">12</xref>), is capable of visualizing 3D aortic flow behavior and has been utilized to assess the impact of different aortic valve prostheses on aortic hemodynamics (<xref ref-type="bibr" rid="B13">13</xref>&#x2013;<xref ref-type="bibr" rid="B15">15</xref>). For example, von Knobelsdorff-Brenkenhoff et al. observed aberrant vortical and helical ascending aorta (AAo) flow patterns in AVR patients with autograft, mechanical, and bioprosthetic valves, including those with bileaflet mechanical valves (<xref ref-type="bibr" rid="B14">14</xref>). In particular to the On-X valved conduit, Keller et al. reported similar helical and vortical flow patterns in AAo between patients and healthy controls (<xref ref-type="bibr" rid="B15">15</xref>). However, prior studies have only evaluated qualitative 3D aortic flow patterns using semi-quantitative scoring, limiting the data reproducibility. Further, valvular hemodynamics was not evaluated due to susceptibility image artifacts induced by the valve.</p>
<p>This pilot study conducted a comprehensive and quantitative evaluation of valvular and ascending aorta (AAo) hemodynamics of the On-X aortic valved conduit in comparison to healthy subjects and other commonly used prostheses, namely, St. Jude Medical (SJM) and Carbomedics (CM), using same-day transthoracic echocardiography (TTE) and 4D flow MRI examinations. Valvular hemodynamics was characterized by clinical standard TTE measures (TPV, mean and peak TPG, and EOA). AAo hemodynamics was characterized by computing viscous energy loss and vorticity at peak systole. This study aims to examine whether the On-X aortic valved conduit restores normal valvular and AAo hemodynamics better than the other prostheses.</p>
</sec>
<sec id="s2" sec-type="methods"><label>2.</label><title>Materials and methods</title>
<sec id="s2a"><label>2.1.</label><title>Study cohort</title>
<p>This study was approved by the Institutional Review Board, and written informed consent was obtained from all subjects. Inclusion criteria were adult patients (age 18&#x2013;89 years) who underwent Bentall procedure on or after 1 January 2001 using the following bileaflet mechanical aortic valved conduit prostheses: On-X Ascending Aortic Prosthesis with Vascutek Gelweave Valsalva Graft (On-X), SJM Masters HP Valved Graft with Gelweave Valsalva Technology, or CM Carbo-seal Valsalva. Seventeen patients were prospectively enrolled between October 2017 and June 2020 and divided into two groups: (1) On-X (<italic>n</italic>&#x2009;&#x003D;&#x2009;11) and (2) SJM (<italic>n</italic>&#x2009;&#x003D;&#x2009;2) or CM (<italic>n</italic>&#x2009;&#x003D;&#x2009;4). Thirty-six healthy subjects with a tricuspid aortic valve who underwent same-day TTE and 4D flow MRI examinations for another study were retrospectively recruited.</p>
</sec>
<sec id="s2b"><label>2.2.</label><title>Echocardiography</title>
<p>A standard-of-care TTE was performed using a Vivid E95 echocardiography scanner (General Electric Healthcare, Waukesha, WI, USA). TPV, mean and peak TPG, EOA, and EOA index (EOAi) were evaluated based on continuous-wave Doppler and 2D color Doppler echocardiography following the American Society of Echocardiography guidelines (<xref ref-type="bibr" rid="B16">16</xref>). To briefly explain how EOA was measured, first, the left ventricle stroke volume at the left ventricle outflow tract was obtained by multiplying the velocity-time-integral of forward flow (toward the aortic valve) by the cross-sectional area, which are measured using pulsed-wave Doppler and parasternal long-axis B-mode echocardiography, respectively. Given the principle of mass conservation, the stroke volume at the left ventricle outflow tract should be equal to that at the aortic valve. The stroke volume at the left ventricle outflow tract was divided by the velocity-time-integral of the forward transaortic valvular flow, which is measured using aortic valve continuous-wave Doppler echocardiography, giving EOA. In addition, a discharge coefficient, defined as EOA normalized by a geometrical orifice area (i.e., the area when a valve is fully opened), was introduced to account for valve label size differences in patients. The geometrical orifice area was obtained from the valve specification sheet provided by the respective valve manufacturers. The discharge coefficient indicates the ability of the valve to distribute blood flow effectively across the valve.</p>
</sec>
<sec id="s2c"><label>2.3.</label><title>4D flow MRI</title>
<p>All MRI examinations were conducted on a 1.5-T system (Aera, Siemens Healthineers, Erlangen, Germany). A retrospective electrocardiogram and respiratory-gated, free-breathing 4D flow MRI examination was performed with the following parameters; echo time&#x2009;&#x003D;&#x2009;2.1&#x2013;2.3&#x2005;ms, repetition time&#x2009;&#x003D;&#x2009;4.8&#x2013;5.1&#x2005;ms, flip angle&#x2009;&#x003D;&#x2009;7&#x00B0;, temporal resolution&#x2009;&#x003D;&#x2009;38.8&#x2013;40.6&#x2005;ms, bandwidth&#x2009;&#x003D;&#x2009;455&#x2005;Hz/pixel, field of view&#x2009;&#x003D;&#x2009;285&#x2013;345&#x2009;&#x00D7;&#x2009;380&#x2013;460&#x2009;&#x00D7;&#x2009;72&#x2013;96&#x2005;mm<sup>3</sup>, matrix size&#x2009;&#x003D;&#x2009;120&#x2009;&#x00D7;&#x2009;160&#x2009;&#x00D7;&#x2009;30&#x2013;32, voxel size&#x2009;&#x003D;&#x2009;3.4&#x2013;4.1&#x2009;&#x00D7;&#x2009;2.4&#x2013;2.9&#x2009;&#x00D7;&#x2009;2.4&#x2013;3&#x2005;mm<sup>3</sup>, and encoding velocity&#x2009;&#x003D;&#x2009;150&#x2013;275&#x2005;cm/s. All 4D flow MRI datasets were corrected for background phase offset and velocity aliasing using previously described methods (<xref ref-type="bibr" rid="B17">17</xref>). The entire thoracic aorta was segmented using a deep learning technique described previously (<xref ref-type="bibr" rid="B18">18</xref>). The AAo was then defined manually from the sinotubular junction to the first brachiocephalic branch (<xref ref-type="fig" rid="F1">Figure&#x00A0;1</xref>, white line). The peak systole time point is defined as the frame at which the average velocity magnitude of the blood in the aorta is at its maximum. At peak systole, the viscous energy loss rate (VELR) and a vorticity vector were computed per voxel, providing a 3D map, as shown in <xref ref-type="fig" rid="F1">Figure&#x00A0;1</xref>, columns 2 and 3, respectively. VELR represents the rate of flow mechanical energy loss due to friction between two adjacent fluid layers moving at a different velocity (i.e., fluid shear) (<xref ref-type="bibr" rid="B19">19</xref>). Vorticity represents the angular velocity vector of a fluid element under rotation. The magnitude of vorticity increases in regions of large velocity gradient, which indicates a spatially non-uniform flow field (i.e., less organized or chaotic). Mathematical definitions of VELR and vorticity are provided in the <xref ref-type="sec" rid="s10">Supplementary Material</xref>. Total VELR, which is the sum of all voxelwise VELR values in the AAo, VELR density (total VELR divided by AAo volume), and mean vorticity, which is the sum of vorticity magnitude in the AAo divided by AAo volume, were computed. In addition, time-resolved 3D flow patterns in the aorta were visualized by generating 3D flow pathlines using Ensight (2022 R1, Ansys, Canonsburg, PA, USA). Each pathline represents a trajectory of a zero-mass particle seeded in the aorta segmentation over a 40&#x2005;ms time window. A total of 400 zero-mass particles were continuously seeded in the entire aorta with a 40&#x2005;ms interval. The aortic flow pathlines of the subjects presented in <xref ref-type="fig" rid="F1">Figure&#x00A0;1</xref> are included as <xref ref-type="sec" rid="s10">Supplementary Videos S1</xref>&#x2013;<xref ref-type="sec" rid="s10">S4</xref>.</p>
<fig id="F1" position="float"><label>Figure 1</label>
<caption><p>Example images showing the peak systolic aortic flow field quantified by 4D flow MRI in patients with the on-X aortic valve conduit (column 1), St. Jude Medical (column 2), Carbomedics (column 3), and healthy subjects (column 4). The velocity magnitude (row 1) and vorticity magnitude (row 3) are shown as the maximum intensity projection, and VELR (row 2) indicates the viscous energy loss rate. The white polygons indicate the ascending aortic region of interest. Note that the yellow arrows indicate the region of susceptibility artifact due to the presence of a mechanical aortic valve. The temporal evolution of 3D aortic flow in the subjects presented in this figure is visualized using pathlines and is available as <xref ref-type="sec" rid="s10">Supplementary Videos</xref>.</p></caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-10-1256420-g001.tif"/>
</fig>
</sec>
<sec id="s2d"><label>2.4.</label><title>Statistical analysis</title>
<p>Average statistics are reported using the mean and standard deviation or median and interquartile range depending on data normality determined by the Lilliefors test. One-way analysis of variance or the Kruskal&#x2013;Wallis test was used for evaluating differences between all three groups (On-X vs. SJM/CM vs. healthy controls) with a significance level of <italic>p</italic>&#x2009;&#x003C;&#x2009;0.05. Pairwise differences between the two groups were tested using a two-tailed unpaired <italic>t</italic>-test or the Wilcoxon rank-sum test with a significance level of <italic>p</italic>&#x2009;&#x003C;&#x2009;0.017 adjusted using the Bonferroni correction.</p>
</sec>
</sec>
<sec id="s3" sec-type="results"><label>3.</label><title>Results</title>
<sec id="s3a"><label>3.1.</label><title>Study cohort characteristics</title>
<p>One On-X patient could not complete an MRI exam due to claustrophobia and thus was excluded from the study. Baseline characteristics of the patients (<italic>n</italic>&#x2009;&#x003D;&#x2009;10 On-X, <italic>n</italic>&#x2009;&#x003D;&#x2009;6 SJM/CM) and healthy subjects (<italic>n</italic>&#x2009;&#x003D;&#x2009;36) are listed in <xref ref-type="table" rid="T1">Table&#x00A0;1</xref>. The age and body surface area were not statistically different between the three groups. The left ventricle end-diastolic volume (131&#x2009;&#x00B1;&#x2009;25 vs. 161&#x2009;&#x00B1;&#x2009;56&#x2005;ml) and end-systolic volume (55&#x2009;&#x00B1;&#x2009;7 vs. 69&#x2009;&#x00B1;&#x2009;22&#x2005;ml) were not different between the On-X and SJM/CM patients but were larger than those of healthy subjects (end-diastolic volume 97&#x2009;&#x00B1;&#x2009;33&#x2005;ml and end-systolic volume 36&#x2009;&#x00B1;&#x2009;16&#x2005;ml). The left ventricle ejection fraction in both patient groups was lower than in healthy subjects but within the normal range (52&#x0025;&#x2013;72&#x0025;). At the time of imaging, all patients had undergone surgery more than 1 year ago, but On-X patients had a shorter postoperative period than SJM/CM patients [1,561 (1,198&#x2013;1,629) days vs. 2,283 (1,797&#x2013;2,747) days].</p>
<table-wrap id="T1" position="float"><label>Table 1</label>
<caption><p>Study cohort characteristics.</p></caption>
<table frame="hsides" rules="groups">
<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>
<tbody>
<tr>
<th valign="top" align="left">Characteristics</th>
<th valign="top" align="center">On-X (<italic>n</italic>&#x2009;&#x003D;&#x2009;10)</th>
<th valign="top" align="center">SJM/CM (<italic>n</italic>&#x2009;&#x003D;&#x2009;6)</th>
<th valign="top" align="center">Healthy control (<italic>n</italic>&#x2009;&#x003D;&#x2009;36)</th>
<th valign="top" align="center"><italic>p</italic>-value On-X vs. SJM/CM</th>
<th valign="top" align="center"><italic>p</italic>-value On-X vs. healthy</th>
<th valign="top" align="center"><italic>p</italic>-value SJM/CM vs. healthy</th>
<th valign="top" align="center"><italic>p</italic>-value ANOVA</th>
</tr>
<tr>
<td valign="top" align="left">Gender</td>
<td valign="top" align="center">M 9/F 1</td>
<td valign="top" align="center">M 4/F 2</td>
<td valign="top" align="center">M 15/F 21</td>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left">Age</td>
<td valign="top" align="center">49&#x2009;&#x00B1;&#x2009;14</td>
<td valign="top" align="center">45&#x2009;&#x00B1;&#x2009;12</td>
<td valign="top" align="center">52&#x2009;&#x00B1;&#x2009;10</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
</tr>
<tr>
<td valign="top" align="left">BSA (m<sup>2</sup>)</td>
<td valign="top" align="center">2.1&#x2009;&#x00B1;&#x2009;0.2</td>
<td valign="top" align="center">2.2&#x2009;&#x00B1;&#x2009;0.3</td>
<td valign="top" align="center">1.9&#x2009;&#x00B1;&#x2009;0.2</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">0.023</td>
<td valign="top" align="center">0.03</td>
<td valign="top" align="center">&#x2014;</td>
</tr>
<tr>
<td valign="top" align="left">End-diastolic LV volume (ml)&#x002A;<sup>,</sup>&#x002A;&#x002A;</td>
<td valign="top" align="center">131&#x2009;&#x00B1;&#x2009;25</td>
<td valign="top" align="center">161&#x2009;&#x00B1;&#x2009;56</td>
<td valign="top" align="center">97&#x2009;&#x00B1;&#x2009;33</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">0.004</td>
<td valign="top" align="center">&#x003C;0.001</td>
<td valign="top" align="center">&#x003C;0.001</td>
</tr>
<tr>
<td valign="top" align="left">End-systolic LV volume (ml)&#x002A;<sup>,</sup>&#x002A;&#x002A;</td>
<td valign="top" align="center">55&#x2009;&#x00B1;&#x2009;7</td>
<td valign="top" align="center">69&#x2009;&#x00B1;&#x2009;22</td>
<td valign="top" align="center">36&#x2009;&#x00B1;&#x2009;16</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x003C;0.001</td>
<td valign="top" align="center">0.001</td>
<td valign="top" align="center">&#x003C;0.001</td>
</tr>
<tr>
<td valign="top" align="left">EF (&#x0025;)&#x002A;<sup>,</sup>&#x002A;&#x002A;</td>
<td valign="top" align="center">57&#x2009;&#x00B1;&#x2009;6</td>
<td valign="top" align="center">57&#x2009;&#x00B1;&#x2009;5</td>
<td valign="top" align="center">64&#x2009;&#x00B1;&#x2009;10</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">0.002</td>
<td valign="top" align="center">0.003</td>
<td valign="top" align="center">&#x003C;0.001</td>
</tr>
<tr>
<td valign="top" align="left">Graft diameter (mm)</td>
<td valign="top" align="center">26 (26&#x2013;26)</td>
<td valign="top" align="center">30 (26&#x2013;30)</td>
<td valign="top" align="center">n.a.</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
</tr>
<tr>
<td valign="top" align="left">Valve label size (mm)</td>
<td valign="top" align="center">25 (25&#x2013;25)</td>
<td valign="top" align="center">28 (25&#x2013;31)</td>
<td valign="top" align="center">n.a.</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
</tr>
<tr>
<td valign="top" align="left">Geometric orifice area (cm<sup>2</sup>)</td>
<td valign="top" align="center">3.73 (3.73&#x2013;3.73)</td>
<td valign="top" align="center">4.14 (3.16&#x2013;5.18)</td>
<td valign="top" align="center">n.a.</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
</tr>
<tr>
<td valign="top" align="left">Days after surgery&#x002A;&#x002A;&#x002A;</td>
<td valign="top" align="center">1,561 (1,198&#x2013;1,629)</td>
<td valign="top" align="center">2,283 (1,797&#x2013;2,747)</td>
<td valign="top" align="center">n.a.</td>
<td valign="top" align="center">0.016</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="table-fn1"><p>LV, left ventricle; BSA, body surface area; EF, ejection fraction.</p></fn>
<fn id="table-fn2"><p>The listed <italic>p</italic>-values are three-group comparison results. Significant differences between the two groups are denoted as follows: &#x002A;On-X vs. healthy controls; &#x002A;&#x002A;SJM/CM vs. healthy controls; &#x002A;&#x002A;&#x002A;On-X vs. SJM/CM.</p></fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="s3b"><label>3.2.</label><title>Hemodynamic assessment</title>
<p>Hemodynamic assessment results are listed in <xref ref-type="table" rid="T2">Table&#x00A0;2</xref>. Valvular hemodynamic assessments showed that On-X patients had elevated TPV (1.9&#x2009;&#x00B1;&#x2009;0.3 vs. 1.2&#x2009;&#x00B1;&#x2009;0.2&#x2005;m/s, <italic>p</italic>&#x2009;&#x003C;&#x2009;0.001), mean TPG (7.4&#x2009;&#x00B1;&#x2009;1.9 vs. 3.1&#x2009;&#x00B1;&#x2009;0.9&#x2005;mmHg, <italic>p</italic>&#x2009;&#x003C;&#x2009;0.001), and peak TPG (15.3&#x2009;&#x00B1;&#x2009;5.2 vs. 6.1&#x2009;&#x00B1;&#x2009;1.8&#x2005;mmHg, <italic>p</italic>&#x2009;&#x003C;&#x2009;0.001) compared to healthy subjects, while SJM/CM patients had even higher values (TPV 2.2&#x2009;&#x00B1;&#x2009;0.3&#x2005;m/s, mean TPG 9.2&#x2009;&#x00B1;&#x2009;1.9&#x2005;mmHg and peak TPG 18.9&#x2009;&#x00B1;&#x2009;5.2&#x2005;mmHg, all <italic>p</italic>&#x2019;s&#x2009;&#x003C;&#x2009;0.001). However, the difference between On-X and SJM/CM patients was not statistically significant. The EOA and EOA indexes in On-X and SJM/CM patients were not different from each other or healthy subjects. The discharge coefficient was also not different between the On-X and SJM/CM patients.</p>
<table-wrap id="T2" position="float"><label>Table 2</label>
<caption><p>Hemodynamic assessment.</p></caption>
<table frame="hsides" rules="groups">
<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>
<tbody>
<tr>
<th valign="top" align="left">Measurements</th>
<th valign="top" align="center">On-X (<italic>n</italic>&#x2009;&#x003D;&#x2009;10)</th>
<th valign="top" align="center">SJM/CM (<italic>n</italic>&#x2009;&#x003D;&#x2009;6)</th>
<th valign="top" align="center">Healthy controls (<italic>n</italic>&#x2009;&#x003D;&#x2009;36)</th>
<th valign="top" align="center"><italic>p</italic>-value On-X vs. SJM/CM</th>
<th valign="top" align="center"><italic>p</italic>-value On-X vs. healthy</th>
<th valign="top" align="center"><italic>p</italic>-value SJM/CM vs. healthy</th>
<th valign="top" align="center"><italic>p</italic>-value ANOVA</th>
</tr>
<tr>
<td valign="top" align="left" colspan="8">Valvular hemodynamics</td>
</tr>
<tr>
<td valign="top" align="left">TPV (m/s)&#x002A;<sup>,</sup>&#x002A;&#x002A;</td>
<td valign="top" align="center">1.9&#x2009;&#x00B1;&#x2009;0.3</td>
<td valign="top" align="center">2.2&#x2009;&#x00B1;&#x2009;0.3</td>
<td valign="top" align="center">1.2&#x2009;&#x00B1;&#x2009;0.2</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x003C;0.001</td>
<td valign="top" align="center">&#x003C;0.001</td>
<td valign="top" align="center">&#x003C;0.001</td>
</tr>
<tr>
<td valign="top" align="left">Mean TPG (mmHg)&#x002A;<sup>,</sup>&#x002A;&#x002A;</td>
<td valign="top" align="center">7.4&#x2009;&#x00B1;&#x2009;1.9</td>
<td valign="top" align="center">9.2&#x2009;&#x00B1;&#x2009;2.3</td>
<td valign="top" align="center">3.1&#x2009;&#x00B1;&#x2009;0.9</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x003C;0.001</td>
<td valign="top" align="center">&#x003C;0.001</td>
<td valign="top" align="center">&#x003C;0.001</td>
</tr>
<tr>
<td valign="top" align="left">Peak TPG (mmHg)&#x002A;<sup>,</sup>&#x002A;&#x002A;</td>
<td valign="top" align="center">15.3&#x2009;&#x00B1;&#x2009;5.2</td>
<td valign="top" align="center">18.9&#x2009;&#x00B1;&#x2009;5.2</td>
<td valign="top" align="center">6.1&#x2009;&#x00B1;&#x2009;1.8</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x003C;0.001</td>
<td valign="top" align="center">&#x003C;0.001</td>
<td valign="top" align="center">&#x003C;0.001</td>
</tr>
<tr>
<td valign="top" align="left">EOA (cm<sup>2</sup>)</td>
<td valign="top" align="center">2.51&#x2009;&#x00B1;&#x2009;0.58</td>
<td valign="top" align="center">2.53&#x2009;&#x00B1;&#x2009;0.64</td>
<td valign="top" align="center">2.3(2.1&#x2013;2.8)</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
</tr>
<tr>
<td valign="top" align="left">EOAi (cm<sup>2</sup>/m<sup>2</sup>)</td>
<td valign="top" align="center">1.21&#x2009;&#x00B1;&#x2009;0.34</td>
<td valign="top" align="center">1.18&#x2009;&#x00B1;&#x2009;0.30</td>
<td valign="top" align="center">1.3&#x2009;&#x00B1;&#x2009;0.30</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
</tr>
<tr>
<td valign="top" align="left">Discharge coefficient</td>
<td valign="top" align="center">0.69&#x2009;&#x00B1;&#x2009;0.14</td>
<td valign="top" align="center">0.65&#x2009;&#x00B1;&#x2009;0.20</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
<td valign="top" align="center">&#x2014;</td>
</tr>
<tr>
<td valign="top" align="left" colspan="8">Ascending aortic hemodynamics</td>
</tr>
<tr>
<td valign="top" align="left">Total VELR (mW)&#x002A;<sup>,</sup>&#x002A;&#x002A;<sup>,</sup>&#x002A;&#x002A;&#x002A;</td>
<td valign="top" align="center">3.1&#x2009;&#x00B1;&#x2009;1.0</td>
<td valign="top" align="center">6.0&#x2009;&#x00B1;&#x2009;4.1</td>
<td valign="top" align="center">1.6&#x2009;&#x00B1;&#x2009;0.7</td>
<td valign="top" align="center">0.009</td>
<td valign="top" align="center">&#x003C;0.001</td>
<td valign="top" align="center">&#x003C;0.001</td>
<td valign="top" align="center">&#x003C;0.001</td>
</tr>
<tr>
<td valign="top" align="left">VELR density (W/m<sup>3</sup>)&#x002A;<sup>,</sup>&#x002A;&#x002A;<sup>,</sup>&#x002A;&#x002A;&#x002A;</td>
<td valign="top" align="center">50.6&#x2009;&#x00B1;&#x2009;20.1</td>
<td valign="top" align="center">89.8&#x2009;&#x00B1;&#x2009;35.2</td>
<td valign="top" align="center">21.4&#x2009;&#x00B1;&#x2009;9.2</td>
<td valign="top" align="center">0.013</td>
<td valign="top" align="center">&#x003C;0.001</td>
<td valign="top" align="center">&#x003C;0.001</td>
<td valign="top" align="center">&#x003C;0.001</td>
</tr>
<tr>
<td valign="top" align="left">Mean vorticity (s<sup>&#x2212;1</sup>)&#x002A;<sup>,</sup>&#x002A;&#x002A;<sup>,</sup>&#x002A;&#x002A;&#x002A;</td>
<td valign="top" align="center">147.6&#x2009;&#x00B1;&#x2009;30.0</td>
<td valign="top" align="center">191.2&#x2009;&#x00B1;&#x2009;26.0</td>
<td valign="top" align="center">84.6&#x2009;&#x00B1;&#x2009;20.5</td>
<td valign="top" align="center">0.011</td>
<td valign="top" align="center">&#x003C;0.001</td>
<td valign="top" align="center">&#x003C;0.001</td>
<td valign="top" align="center">&#x003C;0.001</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="table-fn3"><p>TPV, transvalular peak velocity; TPG, transvalvular pressure gradient; EOA, effective orifice area, EOAi, effective orifice area index; VELR, viscous energy loss rate.</p></fn>
<fn id="table-fn4"><p>The listed <italic>p</italic>-values are three-group comparison results. Significant differences between the two groups are denoted as follows: &#x002A;On-X vs. healthy controls; &#x002A;&#x002A;SJM/CM vs. healthy controls; &#x002A;&#x002A;&#x002A;On-X vs. SJM/CM.</p></fn>
</table-wrap-foot>
</table-wrap>
<p>Ascending aortic hemodynamic assessments demonstrated similar trends to valvular hemodynamics. Compared to healthy subjects, On-X patients had significantly higher total VELR (3.1&#x2009;&#x00B1;&#x2009;1.0 vs. 1.6&#x2009;&#x00B1;&#x2009;0.7&#x2005;mW, <italic>p</italic>&#x2009;&#x003C;&#x2009;0.001), VELR density (50.6&#x2009;&#x00B1;&#x2009;20.1 vs. 89.8&#x2009;&#x00B1;&#x2009;35.2&#x2005;W/m<sup>3</sup>, <italic>p</italic>&#x2009;&#x003C;&#x2009;0.001), and mean vorticity (147.6&#x2009;&#x00B1;&#x2009;30.0 vs. 84.6&#x2009;&#x00B1;&#x2009;20.5&#x2005;s<sup>&#x2212;1</sup>, <italic>p</italic>&#x2009;&#x003C;&#x2009;0.001), while SJM/CM patients had even higher values (total VELR 6.0&#x2009;&#x00B1;&#x2009;4.1&#x2005;mW, VELR density 89.8&#x2009;&#x00B1;&#x2009;35.2&#x2005;W/m<sup>3</sup>, and mean vorticity 191.2&#x2009;&#x00B1;&#x2009;26.0&#x2005;s<sup>&#x2212;1</sup>, all <italic>p</italic>&#x2019;s&#x2009;&#x003C;&#x2009;0.001 vs. healthy subjects). The differences in VELR density and mean vorticity between On-X and SJM/CM patients were statistically significant (<italic>p</italic>&#x2009;&#x003C;&#x2009;0.017), as shown in <xref ref-type="fig" rid="F2">Figure&#x00A0;2</xref>.</p>
<fig id="F2" position="float"><label>Figure 2</label>
<caption><p>Boxplots showing the distribution of (<bold>A</bold>) viscous energy loss rate (VELR) density and (<bold>B</bold>) mean vorticity magnitude within each group.</p></caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-10-1256420-g002.tif"/>
</fig>
</sec>
</sec>
<sec id="s4" sec-type="discussion"><label>4.</label><title>Discussion</title>
<p>This is a pilot study that utilized same-day TTE and 4D flow MRI examinations for a comprehensive assessment of valvular and AAo hemodynamics of the On-X aortic valved conduit compared with similar aortic valved conduits from SJM and CM and with healthy subjects. Our study suggests that while there may be no significant improvements in valvular hemodynamics, the On-X prosthesis may produce less aberrant flow in the AAo as indicated by lower viscous energy loss and vorticity magnitude that are closer to those of healthy subjects compared to the SJM and CM alternatives.</p>
<p>Elevated VELR and vorticity have been associated with aberrant ascending aortic flow patterns such as helical flow, vortical flow, and flow jets, which are frequently observed in patients with aortic valve disease, including aortic stenosis and bicuspid aortic valve (<xref ref-type="bibr" rid="B20">20</xref>, <xref ref-type="bibr" rid="B21">21</xref>). Previous studies have reported abnormal helical and vortical flow patterns in patients with various types of AVR, including SJM and CM bileaflet mechanical aortic valves (<xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B14">14</xref>). In contrast, patients with the On-X valved conduit showed flow patterns similar to healthy volunteers (<xref ref-type="bibr" rid="B15">15</xref>). Our study found lower VELR and vorticity in patients with the On-X valved conduit than those with alternative SJM and CM bileaflet mechanical aortic valved conduits, but the values were still higher than those of healthy subjects who demonstrated the most aligned ascending aortic flow patterns compared to patients based on qualitative assessment (<xref ref-type="sec" rid="s10">Supplementary Video S1</xref>&#x2013;<xref ref-type="sec" rid="s10">S4</xref>). Considering our results in conjunction with previous studies, the On-X aortic valved conduit may perform better in mitigating aberrant flow patterns in the aorta compared to other SJM and CM alternatives but may not completely restore normal flow patterns.</p>
<p>Since all three prostheses share the same Gelweave graft with preserved sinuses of Valsalva, the valve design is likely the major factor responsible for hemodynamic differences between the two patient groups. The On-X valve has a flared inlet, while the other two have a straight inlet. This tapered inlet may have facilitated the smooth entry of blood flow from the left ventricle outflow tract, promoting organized flow stream and thus preventing complex flow formation in the aorta (<xref ref-type="bibr" rid="B22">22</xref>). Another design feature of the On-X valve is the 90&#x00B0; valve leaflet opening angle, which is higher than those of SJM (85&#x00B0;) and CM (78&#x00B0;). The ability to fully open may be more beneficial in terms of forming coherent centrally aligned flows, while valves with an opening angle of less than 90&#x00B0; create flows directed toward the aortic wall that may initiate secondary helical and vortical flow patterns, as observed in a previous study (<xref ref-type="bibr" rid="B14">14</xref>). In addition to the differences in valve design, individual variation in the graft curvature may also alter downstream flow formation as it affects the impact angle of transaortic valvular flow on the graft wall. However, within our limited patient cohort, there was no noticeable relationship between the graft curvature and VELR or mean vorticity magnitude among patients with the same prosthesis (<xref ref-type="sec" rid="s10">Supplementary Figure S1</xref> and <xref ref-type="sec" rid="s10">S2</xref>).</p>
<p>Given that peak and mean TPG were not significantly different between the two patient groups, the lower VELR density in the On-X patients may indicate that the On-X prosthesis provides a more energy-efficient AAo flow since viscous energy loss is one of the irreversible pressure energy losses that occur in the downstream of the valve. A reduction in irreversible energy loss leads to higher pressure recovery (<xref ref-type="bibr" rid="B23">23</xref>, <xref ref-type="bibr" rid="B24">24</xref>) in the aorta; thus reducing the work the left ventricle must produce to push blood into the aorta. It is also worth noting that VELR in the AAo was analyzable and not limited by the presence of a mechanical aortic valve. The size of the magnetic susceptibility artifact (i.e., signal void region), as depicted in <xref ref-type="fig" rid="F1">Figure&#x00A0;1</xref>, measured approximately 1.5&#x2005;cm along the aorta. Velocities in the AAo, defined as the sinotubular junction to the brachiocephalic artery, remained unaffected by the artifact. Another significant source of irreversible energy loss is turbulent dissipation, which requires high temporal resolution measurement of random velocity fluctuations (i.e., turbulence). The 4D flow MRI technique used in this study does not have sufficient temporal resolution for direct turbulence measurement and only acquires blood velocities averaged over multiple heartbeats. A special 4D flow MRI sequence such as ICOSA6 (<xref ref-type="bibr" rid="B25">25</xref>) designed to quantify average turbulent kinetic energy may be utilized; however, it requires further validation in <italic>in vivo</italic> pulsatile flow scenarios.</p>
<p>While a similar to or higher EOA has been reported for the On-X valve than the SJM or CM valve for the same valve label size (<xref ref-type="bibr" rid="B8">8</xref>, <xref ref-type="bibr" rid="B10">10</xref>, <xref ref-type="bibr" rid="B26">26</xref>), our results showed no significant difference between On-X and SJM/CM patients. However, the size of the implanted valve widely varied in the SJM/CM patients (ranging from 23 to 31&#x2005;mm), while the On-X patients only had two sizes: 23 or 25&#x2005;mm. To eliminate the confounding effects of size heterogeneity, we computed the discharge coefficient, which is the ratio of EOA to the geometrical orifice area. The discharge coefficient provides an indication of the valve design&#x0027;s effectiveness in constricting blood flow. Our results showed that the discharge coefficient was similar between the two patient groups (0.69&#x2009;&#x00B1;&#x2009;0.14 vs. 0.65&#x2009;&#x00B1;&#x2009;0.20, <italic>P</italic>&#x2009;&#x003D;&#x2009;0.65). This suggests that the unique design features of the On-X valve did not provide any significant valvular hemodynamic advantage over the other two valves. A previous <italic>in vitro</italic> study observed that the On-X valve leaflets experienced fluctuation during systole, which may affect the valve&#x0027;s ability to remain fully open, while the SJM valve leaflets remained stable (<xref ref-type="bibr" rid="B27">27</xref>). This could be due to the leaflets opening at 90&#x00B0;, which results in the absence of supporting force compared to leaflets that fully open at &#x003C;90&#x00B0;, which experience a constant pressure force from the incoming flow. This leaflet instability may cause flow separation at the valve, blocking blood flow through the valve and reducing EOA.</p>
<p>There are several limitations in this study. First, the small patient sample size critically limits the statistical power of the study. Second, the comparison group consisted of two different mechanical valves, which may introduce confounding variables that could affect the results. However, the patient cohort in this study presented a significant recruitment challenge due to the low prevalence of mechanical AVR, which is only performed in about 10&#x0025; of AVR patients, and the even lower frequency of Bentall procedures. Third, the valve label size and graft size were not controlled between the On-X and SJM/CM groups, where the sizes varied more widely in SJM/CM patients. We compensated for these size discrepancies by introducing the discharge coefficient and normalizing total VELR and vorticity by the AAo volume. Finally, downstream flow turbulence was not examined due to technical limitations, and thus, the downstream energetic efficiency was not fully investigated. A carefully designed <italic>in vitro</italic> experiment with a high-resolution velocity imaging technique such as particle image velocimetry may be a valuable approach to analyzing detailed turbulent flow structures and identifying sources of turbulence. Nonetheless, this study provides a valuable three-dimensional assessment of the hemodynamic performance of the On-X aortic valved conduit compared to other mechanical valves.</p>
</sec>
</body>
<back>
<sec id="s5" 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 per request, without undue reservation.</p>
</sec>
<sec id="s6" sec-type="ethics-statement"><title>Ethics statement</title>
<p>The studies involving humans were approved by Northwestern University Institutional Review Board. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.</p>
</sec>
<sec id="s7" sec-type="author-contributions"><title>Author contributions</title>
<p>JL: Formal analysis, Investigation, Methodology, Validation, Visualization, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. HH: Data curation, Formal analysis, Methodology, Visualization, Writing &#x2013; review &#x0026; editing. MS: Methodology, Resources, Software, Writing &#x2013; review &#x0026; editing. ME: Formal analysis, Software, Writing &#x2013; review &#x0026; editing. JP: Investigation, Methodology, Validation, Writing &#x2013; review &#x0026; editing. PM: Methodology, Validation, Writing &#x2013; review &#x0026; editing. CM: Conceptualization, Resources, Validation, Writing &#x2013; review &#x0026; editing. MM: Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Writing &#x2013; review &#x0026; editing. JT: Conceptualization, Funding acquisition, Supervision, Validation, Writing &#x2013; review &#x0026; editing. AB: Conceptualization, Funding acquisition, Methodology, Supervision, Writing &#x2013; review &#x0026; editing.</p>
</sec>
<sec id="s8" sec-type="funding-information"><title>Funding</title>
<p>The authors declare financial support was received for the research, authorship, and/or publication of this article.</p>
<p>This study received funding from CryoLife, Inc. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.</p>
</sec>
<ack><title>Acknowledgments</title>
<p>The authors acknowledge support from the Irene D. Pritzker Foundation and General Electric Medical Services.</p>
</ack>
<sec id="s9" sec-type="COI-statement"><title>Conflict of interest</title>
<p>The authors declare that the research 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="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="s10" 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.2023.1256420/full#supplementary-material">https://www.frontiersin.org/articles/10.3389/fcvm.2023.1256420/full&#x0023;supplementary-material</ext-link></p>
<supplementary-material id="SD1" content-type="local-data"><label>Supplementary Figure S1</label>
<caption><p>Maximum intensity projection of the viscous energy loss rate (VELR) at peak systole in all patients. The diameter of the implanted graft is indicated below each image.</p></caption>
<media mimetype="image" mime-subtype="jpeg" xlink:href="Image1.jpeg"/>
</supplementary-material>
<supplementary-material id="SD2" content-type="local-data"><label>Supplementary Figure S2</label>
<caption><p>Maximum intensity projection of vorticity magnitude at peak systole in all patients. The diameter of the implanted graft is indicated below each image.</p></caption>
<media mimetype="image" mime-subtype="jpeg" xlink:href="Image2.jpeg"/>
</supplementary-material>
<supplementary-material id="SD3" content-type="local-data"><label>Supplementary Video S1</label>
<caption><p>Time-resolved 3D aortic blood flow pattern in a patient with On-X prosthesis.</p></caption>
<media mimetype="video" mime-subtype="mpeg" xlink:href="Video1.mp4"/>
</supplementary-material>
<supplementary-material id="SD4" content-type="local-data"><label>Supplementary Video S2</label>
<caption><p>Time-resolved 3D aortic blood flow pattern in a patient with St. Jude Medical Masters prosthesis.</p></caption>
<media mimetype="video" mime-subtype="mpeg" xlink:href="Video2.mp4"/>
</supplementary-material>
<supplementary-material id="SD5" content-type="local-data"><label>Supplementary Video S3</label>
<caption><p>Time-resolved 3D aortic blood flow pattern in a patient with Carbomedic prosthesis.</p></caption>
<media mimetype="video" mime-subtype="mpeg" xlink:href="Video3.mp4"/>
</supplementary-material>
<supplementary-material id="SD6" content-type="local-data"><label>Supplementary Video S4</label>
<caption><p>Time-resolved 3D aortic blood flow pattern in a healthy volunteer.</p></caption>
<media mimetype="video" mime-subtype="mpeg" xlink:href="Video4.mp4"/>
</supplementary-material>
<supplementary-material id="SD7" content-type="local-data">
<media mimetype="application" mime-subtype="vnd.openxmlformats-officedocument.wordprocessingml.document" xlink:href="Datasheet1.docx"/>
</supplementary-material>
</sec>
<ref-list><title>References</title>
<ref id="B1"><label>1.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Otto</surname><given-names>CM</given-names></name><name><surname>Nishimura</surname><given-names>RA</given-names></name><name><surname>Bonow</surname><given-names>RO</given-names></name><name><surname>Carabello</surname><given-names>BA</given-names></name><name><surname>Erwin</surname><given-names>JP</given-names><suffix>III</suffix></name><name><surname>Gentile</surname><given-names>F</given-names></name><etal/></person-group> <article-title>2020 ACC/AHA guideline for the management of patients with valvular heart disease: executive summary: a report of the American college of cardiology/American heart association joint committee on clinical practice guidelines</article-title>. <source>Circulation</source>. (<year>2021</year>) <volume>143</volume>(<issue>5</issue>):<fpage>e35</fpage>&#x2013;<lpage>71</lpage>. <pub-id pub-id-type="doi">10.1161/CIR.0000000000000932</pub-id>. <comment>Erratum in</comment>: <source>Circulation</source>. (<year>2021</year>) <volume>143</volume>(<issue>5</issue>):<fpage>e228</fpage>. <comment>Erratum in</comment>: <source>Circulation</source>. (<year>2021</year>) <volume>143</volume>(<issue>10</issue>):<fpage>e784</fpage>. PMID: <pub-id pub-id-type="pmid">33332149</pub-id><pub-id pub-id-type="pmid">33332149</pub-id></citation></ref>
<ref id="B2"><label>2.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Falk</surname><given-names>V</given-names></name><name><surname>Baumgartner</surname><given-names>H</given-names></name><name><surname>Bax</surname><given-names>JJ</given-names></name><name><surname>De Bonis</surname><given-names>M</given-names></name><name><surname>Hamm</surname><given-names>C</given-names></name><name><surname>Holm</surname><given-names>PJ</given-names></name><etal/></person-group> <article-title>2017 ESC/EACTS guidelines for the management of valvular heart disease</article-title>. <source>Eur J Cardiothorac Surg</source>. (<year>2017</year>) <volume>52</volume>(<issue>4</issue>):<fpage>616</fpage>&#x2013;<lpage>64</lpage>. <pub-id pub-id-type="doi">10.1093/ejcts/ezx324</pub-id><pub-id pub-id-type="pmid">29156023</pub-id></citation></ref>
<ref id="B3"><label>3.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Head</surname><given-names>SJ</given-names></name><name><surname>&#x00C7;elik</surname><given-names>M</given-names></name><name><surname>Kappetein</surname><given-names>AP</given-names></name></person-group>. <article-title>Mechanical versus bioprosthetic aortic valve replacement</article-title>. <source>Eur Heart J</source>. (<year>2017</year>) <volume>38</volume>(<issue>28</issue>):<fpage>2183</fpage>&#x2013;<lpage>91</lpage>. <pub-id pub-id-type="doi">10.1093/eurheartj/ehx141</pub-id><pub-id pub-id-type="pmid">28444168</pub-id></citation></ref>
<ref id="B4"><label>4.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Goldstone</surname><given-names>AB</given-names></name><name><surname>Chiu</surname><given-names>P</given-names></name><name><surname>Baiocchi</surname><given-names>M</given-names></name><name><surname>Lingala</surname><given-names>B</given-names></name><name><surname>Patrick</surname><given-names>WL</given-names></name><name><surname>Fischbein</surname><given-names>MP</given-names></name><etal/></person-group> <article-title>Mechanical or biologic prostheses for aortic-valve and mitral-valve replacement</article-title>. <source>N Engl J Med</source>. (<year>2017</year>) <volume>377</volume>(<issue>19</issue>):<fpage>1847</fpage>&#x2013;<lpage>57</lpage>. <pub-id pub-id-type="doi">10.1056/NEJMoa1613792</pub-id><pub-id pub-id-type="pmid">29117490</pub-id></citation></ref>
<ref id="B5"><label>5.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Hammermeister</surname><given-names>K</given-names></name><name><surname>Sethi</surname><given-names>GK</given-names></name><name><surname>Henderson</surname><given-names>WG</given-names></name><name><surname>Grover</surname><given-names>FL</given-names></name><name><surname>Oprian</surname><given-names>C</given-names></name><name><surname>Rahimtoola</surname><given-names>SH</given-names></name></person-group>. <article-title>Outcomes 15 years after valve replacement with a mechanical versus a bioprosthetic valve: final report of the veterans affairs randomized trial</article-title>. <source>J Am Coll Cardiol</source>. (<year>2000</year>) <volume>36</volume>(<issue>4</issue>):<fpage>1152</fpage>&#x2013;<lpage>8</lpage>. <pub-id pub-id-type="doi">10.1016/S0735-1097(00)00834-2</pub-id><pub-id pub-id-type="pmid">11028464</pub-id></citation></ref>
<ref id="B6"><label>6.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Cannegieter</surname><given-names>S</given-names></name><name><surname>Rosendaal</surname><given-names>F</given-names></name><name><surname>Briet</surname><given-names>E</given-names></name></person-group>. <article-title>Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses</article-title>. <source>Circulation</source>. (<year>1994</year>) <volume>89</volume>(<issue>2</issue>):<fpage>635</fpage>&#x2013;<lpage>41</lpage>. <pub-id pub-id-type="doi">10.1161/01.CIR.89.2.635</pub-id><pub-id pub-id-type="pmid">8313552</pub-id></citation></ref>
<ref id="B7"><label>7.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Puskas</surname><given-names>JD</given-names></name><name><surname>Gerdisch</surname><given-names>M</given-names></name><name><surname>Nichols</surname><given-names>D</given-names></name><name><surname>Fermin</surname><given-names>L</given-names></name><name><surname>Rhenman</surname><given-names>B</given-names></name><name><surname>Kapoor</surname><given-names>D</given-names></name><etal/></person-group> <article-title>Anticoagulation and antiplatelet strategies after On-X mechanical aortic valve replacement</article-title>. <source>J Am Coll Cardiol</source>. (<year>2018</year>) <volume>71</volume>(<issue>24</issue>):<fpage>2717</fpage>&#x2013;<lpage>26</lpage>. <pub-id pub-id-type="doi">10.1016/j.jacc.2018.03.535</pub-id><pub-id pub-id-type="pmid">29903344</pub-id></citation></ref>
<ref id="B8"><label>8.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Chambers</surname><given-names>J</given-names></name><name><surname>Roxburgh</surname><given-names>J</given-names></name><name><surname>Blauth</surname><given-names>C</given-names></name><name><surname>O&#x2019;Riordan</surname><given-names>J</given-names></name><name><surname>Hodson</surname><given-names>F</given-names></name><name><surname>Rimington</surname><given-names>H</given-names></name></person-group>. <article-title>A randomized comparison of the MCRI On-X and CarboMedics top hat bileaflet mechanical replacement aortic valves: early postoperative hemodynamic function and clinical events</article-title>. <source>J Thorac Cardiovasc Surg</source>. (<year>2005</year>) <volume>130</volume>(<issue>3</issue>):<fpage>759</fpage>&#x2013;<lpage>64</lpage>. <pub-id pub-id-type="doi">10.1016/j.jtcvs.2005.02.057</pub-id><pub-id pub-id-type="pmid">16153925</pub-id></citation></ref>
<ref id="B9"><label>9.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Walther</surname><given-names>T</given-names></name><name><surname>Falk</surname><given-names>V</given-names></name><name><surname>Tigges</surname><given-names>R</given-names></name><name><surname>Kr&#x00FC;ger</surname><given-names>M</given-names></name><name><surname>Langebartels</surname><given-names>G</given-names></name><name><surname>Diegeler</surname><given-names>A</given-names></name><etal/></person-group> <article-title>Comparison of on-X and SJM HP bileaflet aortic valves</article-title>. <source>J Heart Valve Dis</source>. (<year>2000</year>) <volume>9</volume>(<issue>3</issue>):<fpage>403</fpage>&#x2013;<lpage>7</lpage>. PMID: <pub-id pub-id-type="pmid">10888098</pub-id><pub-id pub-id-type="pmid">10888098</pub-id></citation></ref>
<ref id="B10"><label>10.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Xu</surname><given-names>R</given-names></name><name><surname>Rahnavardi</surname><given-names>M</given-names></name><name><surname>Pitman</surname><given-names>B</given-names></name><name><surname>Shirazi</surname><given-names>M</given-names></name><name><surname>Stuklis</surname><given-names>R</given-names></name><name><surname>Edwards</surname><given-names>J</given-names></name><etal/></person-group> <article-title>On-X versus St Jude medical regent mechanical aortic valve prostheses: early haemodynamics</article-title>. <source>Open Heart</source>. (<year>2017</year>) <volume>4</volume>(<issue>1</issue>):<fpage>e000539</fpage>. <pub-id pub-id-type="doi">10.1136/openhrt-2016-000539</pub-id><pub-id pub-id-type="pmid">28674619</pub-id></citation></ref>
<ref id="B11"><label>11.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Bargiotas</surname><given-names>I</given-names></name><name><surname>Bollache</surname><given-names>E</given-names></name><name><surname>Mousseaux</surname><given-names>E</given-names></name><name><surname>Giron</surname><given-names>A</given-names></name><name><surname>de Cesare</surname><given-names>A</given-names></name><name><surname>Redheuil</surname><given-names>A</given-names></name><etal/></person-group> <article-title>MR and applanation tonometry derived aortic impedance: association with aging and left ventricular remodeling</article-title>. <source>J Magn Reson Imaging</source>. (<year>2015</year>) <volume>41</volume>(<issue>3</issue>):<fpage>781</fpage>&#x2013;<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1002/jmri.24620</pub-id><pub-id pub-id-type="pmid">24616151</pub-id></citation></ref>
<ref id="B12"><label>12.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Markl</surname><given-names>M</given-names></name><name><surname>Schnell</surname><given-names>S</given-names></name><name><surname>Wu</surname><given-names>C</given-names></name><name><surname>Bollache</surname><given-names>E</given-names></name><name><surname>Jarvis</surname><given-names>K</given-names></name><name><surname>Barker</surname><given-names>AJ</given-names></name><etal/></person-group> <article-title>Advanced flow MRI: emerging techniques and applications</article-title>. <source>Clin Radiol</source>. (<year>2016</year>) <volume>71</volume>(<issue>8</issue>):<fpage>779</fpage>&#x2013;<lpage>95</lpage>. <pub-id pub-id-type="doi">10.1016/j.crad.2016.01.011</pub-id><pub-id pub-id-type="pmid">26944696</pub-id></citation></ref>
<ref id="B13"><label>13.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Collins</surname><given-names>JD</given-names></name><name><surname>Semaan</surname><given-names>E</given-names></name><name><surname>Barker</surname><given-names>A</given-names></name><name><surname>McCarthy</surname><given-names>PM</given-names></name><name><surname>Carr</surname><given-names>JC</given-names></name><name><surname>Markl</surname><given-names>M</given-names></name><etal/></person-group> <article-title>Comparison of hemodynamics after aortic root replacement using valve-sparing or bioprosthetic valved conduit</article-title>. <source>Ann Thorac Surg</source>. (<year>2015</year>) <volume>100</volume>(<issue>5</issue>):<fpage>1556</fpage>&#x2013;<lpage>62</lpage>. <pub-id pub-id-type="doi">10.1016/j.athoracsur.2015.04.109</pub-id><pub-id pub-id-type="pmid">26212514</pub-id></citation></ref>
<ref id="B14"><label>14.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>von Knobelsdorff-Brenkenhoff</surname><given-names>F</given-names></name><name><surname>Trauzeddel</surname><given-names>RF</given-names></name><name><surname>Barker</surname><given-names>AJ</given-names></name><name><surname>Gruettner</surname><given-names>H</given-names></name><name><surname>Markl</surname><given-names>M</given-names></name><name><surname>Schulz-Menger</surname><given-names>J</given-names></name></person-group>. <article-title>Blood flow characteristics in the ascending aorta after aortic valve replacement&#x2014;a pilot study using 4D-flow MRI</article-title>. <source>Int J Cardiol</source>. (<year>2014</year>) <volume>170</volume>(<issue>3</issue>):<fpage>426</fpage>&#x2013;<lpage>33</lpage>. <pub-id pub-id-type="doi">10.1016/j.ijcard.2013.11.034</pub-id><pub-id pub-id-type="pmid">24315151</pub-id></citation></ref>
<ref id="B15"><label>15.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Keller</surname><given-names>EJ</given-names></name><name><surname>Malaisrie</surname><given-names>SC</given-names></name><name><surname>Kruse</surname><given-names>J</given-names></name><name><surname>McCarthy</surname><given-names>PM</given-names></name><name><surname>Carr</surname><given-names>JC</given-names></name><name><surname>Markl</surname><given-names>M</given-names></name><etal/></person-group> <article-title>Reduction of aberrant aortic haemodynamics following aortic root replacement with a mechanical valved conduit</article-title>. <source>Interact Cardiovasc Thorac Surg</source>. (<year>2016</year>) <volume>23</volume>(<issue>3</issue>):<fpage>416</fpage>&#x2013;<lpage>23</lpage>. <pub-id pub-id-type="doi">10.1093/icvts/ivw173</pub-id><pub-id pub-id-type="pmid">27245620</pub-id></citation></ref>
<ref id="B16"><label>16.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Zoghbi</surname><given-names>WA</given-names></name><name><surname>Chambers</surname><given-names>JB</given-names></name><name><surname>Dumesnil</surname><given-names>JG</given-names></name><name><surname>Foster</surname><given-names>E</given-names></name><name><surname>Gottdiener</surname><given-names>JS</given-names></name><name><surname>Grayburn</surname><given-names>PA</given-names></name><etal/></person-group> <article-title>Recommendations for evaluation of prosthetic valves with echocardiography and Doppler ultrasound</article-title>. <source>J Am Soc Echocardiogr</source>. (<year>2009</year>) <volume>22</volume>(<issue>9</issue>):<fpage>975</fpage>&#x2013;<lpage>1014</lpage>. <pub-id pub-id-type="doi">10.1016/j.echo.2009.07.013</pub-id><pub-id pub-id-type="pmid">19733789</pub-id></citation></ref>
<ref id="B17"><label>17.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Walker</surname><given-names>PG</given-names></name><name><surname>Cranney</surname><given-names>GB</given-names></name><name><surname>Scheidegger</surname><given-names>MB</given-names></name><name><surname>Waseleski</surname><given-names>G</given-names></name><name><surname>Pohost</surname><given-names>GM</given-names></name><name><surname>Yoganathan</surname><given-names>AP</given-names></name></person-group>. <article-title>Semiautomated method for noise reduction and background phase error correction in MR phase velocity data</article-title>. <source>J Magn Reson Imaging</source>. (<year>1993</year>) <volume>3</volume>(<issue>3</issue>):<fpage>521</fpage>&#x2013;<lpage>30</lpage>. <pub-id pub-id-type="doi">10.1002/jmri.1880030315</pub-id><pub-id pub-id-type="pmid">8324312</pub-id></citation></ref>
<ref id="B18"><label>18.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Berhane</surname><given-names>H</given-names></name><name><surname>Scott</surname><given-names>M</given-names></name><name><surname>Elbaz</surname><given-names>M</given-names></name><name><surname>Jarvis</surname><given-names>K</given-names></name><name><surname>McCarthy</surname><given-names>P</given-names></name><name><surname>Carr</surname><given-names>J</given-names></name><etal/></person-group> <article-title>Fully automated 3D aortic segmentation of 4D flow MRI for hemodynamic analysis using deep learning</article-title>. <source>Magn Reson Med</source>. (<year>2020</year>) <volume>84</volume>(<issue>4</issue>):<fpage>2204</fpage>&#x2013;<lpage>18</lpage>. <pub-id pub-id-type="doi">10.1002/mrm.28257</pub-id><pub-id pub-id-type="pmid">32167203</pub-id></citation></ref>
<ref id="B19"><label>19.</label><citation citation-type="book"><person-group person-group-type="author"><name><surname>Kundu</surname><given-names>PK</given-names></name><name><surname>Cohen</surname><given-names>IM.</given-names></name></person-group> <source>Fluid mechanics</source>, <edition>4th ed</edition>. <publisher-loc>Burlington, MA, USA</publisher-loc>: <publisher-name>Elsevier</publisher-name> (<year>2008</year>). p. <fpage>112</fpage>&#x2013;<lpage>3</lpage>.</citation></ref>
<ref id="B20"><label>20.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Barker</surname><given-names>AJ</given-names></name><name><surname>van Ooij</surname><given-names>P</given-names></name><name><surname>Bandi</surname><given-names>K</given-names></name><name><surname>Garcia</surname><given-names>J</given-names></name><name><surname>Albaghdadi</surname><given-names>M</given-names></name><name><surname>McCarthy</surname><given-names>P</given-names></name><etal/></person-group> <article-title>Viscous energy loss in the presence of abnormal aortic flow</article-title>. <source>Magn Reson Med</source>. (<year>2014</year>) <volume>72</volume>(<issue>3</issue>):<fpage>620</fpage>&#x2013;<lpage>8</lpage>. <pub-id pub-id-type="doi">10.1002/mrm.24962</pub-id><pub-id pub-id-type="pmid">24122967</pub-id></citation></ref>
<ref id="B21"><label>21.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Elbaz</surname><given-names>MS</given-names></name><name><surname>Scott</surname><given-names>MB</given-names></name><name><surname>Barker</surname><given-names>AJ</given-names></name><name><surname>McCarthy</surname><given-names>P</given-names></name><name><surname>Malaisrie</surname><given-names>C</given-names></name><name><surname>Collins</surname><given-names>JD</given-names></name><etal/></person-group> <article-title>Four-dimensional virtual catheter: noninvasive assessment of intra-aortic hemodynamics in bicuspid aortic valve disease</article-title>. <source>Radiology</source>. (<year>2019</year>) <volume>293</volume>(<issue>3</issue>):<fpage>541</fpage>&#x2013;<lpage>50</lpage>. <pub-id pub-id-type="doi">10.1148/radiol.2019190411</pub-id><pub-id pub-id-type="pmid">31592729</pub-id></citation></ref>
<ref id="B22"><label>22.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Akutsu</surname><given-names>T</given-names></name><name><surname>Matsumoto</surname><given-names>A</given-names></name></person-group>. <article-title>Influence of three mechanical bileaflet prosthetic valve designs on the three-dimensional flow field inside a simulated aorta</article-title>. <source>J Artif Organs</source>. (<year>2010</year>) <volume>13</volume>(<issue>4</issue>):<fpage>207</fpage>&#x2013;<lpage>17</lpage>. <pub-id pub-id-type="doi">10.1007/s10047-010-0519-7</pub-id><pub-id pub-id-type="pmid">20924771</pub-id></citation></ref>
<ref id="B23"><label>23.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Bech-Hanssen</surname><given-names>O</given-names></name><name><surname>Caidahl</surname><given-names>K</given-names></name><name><surname>Wallentin</surname><given-names>I</given-names></name><name><surname>Brandberg</surname><given-names>J</given-names></name><name><surname>Wranne</surname><given-names>B</given-names></name><name><surname>Ask</surname><given-names>P</given-names></name></person-group>. <article-title>Aortic prosthetic valve design and size: relation to Doppler echocardiographic findings and pressure recovery&#x2014;an in vitro study</article-title>. <source>J Am Soc Echocardiogr</source>. (<year>2000</year>) <volume>13</volume>(<issue>1</issue>):<fpage>39</fpage>&#x2013;<lpage>50</lpage>. PMID: <pub-id pub-id-type="pmid">10625830</pub-id><pub-id pub-id-type="pmid">10625830</pub-id></citation></ref>
<ref id="B24"><label>24.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Vandervoort</surname><given-names>PM</given-names></name><name><surname>Greenberg</surname><given-names>NL</given-names></name><name><surname>Pu</surname><given-names>M</given-names></name><name><surname>Powell</surname><given-names>KA</given-names></name><name><surname>Cosgrove</surname><given-names>DM</given-names></name><name><surname>Thomas</surname><given-names>JD</given-names></name></person-group>. <article-title>Pressure recovery in bileaflet heart valve prostheses: localized high velocities and gradients in central and side orifices with implications for Doppler-catheter gradient relation in aortic and mitral position</article-title>. <source>Circulation</source>. (<year>1995</year>) <volume>92</volume>(<issue>12</issue>):<fpage>3464</fpage>&#x2013;<lpage>72</lpage>. <pub-id pub-id-type="doi">10.1161/01.CIR.92.12.3464</pub-id><pub-id pub-id-type="pmid">8521568</pub-id></citation></ref>
<ref id="B25"><label>25.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Ha</surname><given-names>H</given-names></name><name><surname>Kvitting</surname><given-names>JP</given-names></name><name><surname>Dyverfeldt</surname><given-names>P</given-names></name><name><surname>Ebbers</surname><given-names>T</given-names></name></person-group>. <article-title>Validation of pressure drop assessment using 4D flow MRI-based turbulence production in various shapes of aortic stenoses</article-title>. <source>Magn Reson Med</source>. (<year>2019</year>) <volume>81</volume>(<issue>2</issue>):<fpage>893</fpage>&#x2013;<lpage>906</lpage>. <pub-id pub-id-type="doi">10.1002/mrm.27437</pub-id><pub-id pub-id-type="pmid">30252155</pub-id></citation></ref>
<ref id="B26"><label>26.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Rajani</surname><given-names>R</given-names></name><name><surname>Mukherjee</surname><given-names>D</given-names></name><name><surname>Chambers</surname><given-names>JB</given-names></name></person-group>. <article-title>Doppler Echocardiography in normally functioning replacement aortic valves: a review of 129 studies</article-title>. <source>J Heart Valve Dis</source>. (<year>2007</year>) <volume>16</volume>(<issue>5</issue>):<fpage>519</fpage>&#x2013;<lpage>35</lpage>. PMID: <pub-id pub-id-type="pmid">17944125</pub-id><pub-id pub-id-type="pmid">17944125</pub-id></citation></ref>
<ref id="B27"><label>27.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Hatoum</surname><given-names>H</given-names></name><name><surname>Maureira</surname><given-names>P</given-names></name><name><surname>Dasi</surname><given-names>LP</given-names></name></person-group>. <article-title>A turbulence in vitro assessment of On-X and St Jude medical prostheses</article-title>. <source>J Thorac Cardiovasc Surg</source>. (<year>2020</year>) <volume>159</volume>(<issue>1</issue>):<fpage>88</fpage>&#x2013;<lpage>97</lpage>. <pub-id pub-id-type="doi">10.1016/j.jtcvs.2019.02.046</pub-id><pub-id pub-id-type="pmid">30905419</pub-id></citation></ref></ref-list>
</back>
</article>