<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04475289</url>
  </required_header>
  <id_info>
    <org_study_id>2020-00841</org_study_id>
    <nct_id>NCT04475289</nct_id>
  </id_info>
  <brief_title>Registry for Invasive and Non-invasive Anatomical Assessment and Outcome of Coronary Artery Anomalies</brief_title>
  <acronym>NARCO</acronym>
  <official_title>Registry for Invasive and Non-invasive Anatomical Assessment and Outcome of Coronary Artery Anomalies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Insel Gruppe AG, University Hospital Bern</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University Hospital, Zürich</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Insel Gruppe AG, University Hospital Bern</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      An anomalous coronary artery from the opposite sinus of Valsalva (ACAOS) represents a&#xD;
      congenital disorder with an anomalous location and/or course of the coronary vessel. The&#xD;
      prevalence of ACAOS in the general population is around 1 % and they are mostly clinically&#xD;
      insignificant and remain often undetected. However, some variants of ACAOS are associated&#xD;
      with adverse cardiac events. The possible presence of an interarterial/intramural course is&#xD;
      the primary cause for an oval proximal vessel shape and/or proximal vessel narrowing, which&#xD;
      may lead under stress conditions to a &quot;dynamic compression&quot; of the vessel (compared to&#xD;
      &quot;fixed&quot; stenosis in coronary artery disease). To mimic these conditions, dobutamine and&#xD;
      volume challenge is used to invasively measure fractional flow reserve (FFR) during coronary&#xD;
      angiography and is seen as the gold standard in assessing the hemodynamic relevance of ACAOS.&#xD;
      We established a specialized interdisciplinary clinic for coronary artery anomalies including&#xD;
      imaging specialists, invasive cardiologists and congenital heart disease surgeons as correct&#xD;
      downstream testing and treatment decision is highly challenging in these patients. Thus,&#xD;
      systematic collecting of all available diagnostic methods (invasive and non-invasive) is&#xD;
      required to assess the optimal diagnostic procedure and treatment for these patients.&#xD;
      Coronary computed tomography angiography (CCTA) is the method of choice to characterize the&#xD;
      exact anatomy of ACAOS. However, how functional invasive FFR is associated with anatomical&#xD;
      CCTA findings is unknown. Further, diagnostic accuracy of a novel independent research&#xD;
      algorithm with computational fluid dynamics (ctFFR) as well as functional imaging (i.e.&#xD;
      stress single photon emission computed tomography) in this specific setting is unknown.&#xD;
&#xD;
      The presented project will help to understand the pathophysiology of CAAs with particular&#xD;
      focus on ACAOS-IC and improve risk stratification based on non-invasive imaging.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Anomalous coronary arteries (CAA) represent a congenital disorder hallmarked by an anomalous&#xD;
      location of the coronary ostium and/or vessel course. Based on the largest study assessing&#xD;
      the prevalence and characteristics of CAA detected by coronary computer tomography&#xD;
      angiography (CCTA) in Switzerland, the overall prevalence of CAA is 2.6%. However, depending&#xD;
      of the type of CAA and its course in relation to the big vessels (aorta and pulmonary&#xD;
      artery), not every CAA is accompanied by an increased cardiovascular risk.&#xD;
&#xD;
      Of particular interests are anomalous coronary arteries from the opposite sinus of Valsalva&#xD;
      with an interarterial course (ACAOS-IC). Those CAAs represents a congenital disorder with an&#xD;
      anomalous location of the coronary ostium and a course of the anomalous vessel between the&#xD;
      aorta and the pulmonary artery. The prevalence of ACAOS-IC in the general population is&#xD;
      around 1 % and even they are mostly clinically insignificant and remain often undetected.&#xD;
&#xD;
      However, some variants of ACAOS-IC are associated with adverse cardiac events (e.g. sudden&#xD;
      cardiac death in young athletes). The possible presence of an intramural course, a course&#xD;
      within the aortic wall is the primary cause for an oval proximal vessel shape and proximal&#xD;
      vessel narrowing and is suggested to be the primary cause for ischemia. These features may&#xD;
      lead under stress conditions to a &quot;dynamic compression&quot; of the vessel (compared to &quot;fixed&quot;&#xD;
      stenosis in coronary artery disease). Therefore, to mimic these conditions, dobutamine and&#xD;
      volume challenge is used to invasively measure fractional flow reserve (FFRDobutamine) during&#xD;
      coronary angiography and is seen as the gold standard in assessing the hemodynamic relevance&#xD;
      of ACAOS-IC. Presence of an abnormal FFRDobutamine is one of the most important factors in&#xD;
      the decision-making towards surgical repair in ACAOS-IC.&#xD;
&#xD;
      With the frequent use of invasive and non-invasive imaging to rule out coronary artery&#xD;
      disease, an increase in absolute numbers of ACAOS-IC is seen and physicians are more&#xD;
      confronted with the dilemma of how to manage these patients. Usually the question is whether&#xD;
      the ACAOS-IC is a coincidental finding or if the anomaly is causative for the patients'&#xD;
      symptoms. Thus, systematic acquisition of all available diagnostic methods (invasive and&#xD;
      non-invasive) is required to assess the optimal diagnostic procedure for this patients.&#xD;
&#xD;
      The presented project will help to understand the pathophysiology of CAAs with particular&#xD;
      focus on ACAOS-IC and improve risk stratification based on non-invasive imaging.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 1, 2000</start_date>
  <completion_date type="Anticipated">June 30, 2030</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2030</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>5 Years</target_duration>
  <primary_outcome>
    <measure>Frequency of revascularization</measure>
    <time_frame>5 years</time_frame>
    <description>Frequency of revascularizations (i.e. unroofing, re-implantation of the coronary artery, percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) etc.) of the anomalous vessel in patients with CAA.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quantitative assessment (in SI-Units) of the anatomical features in the coronary computed tomography angiography (CCTA)</measure>
    <time_frame>5 years</time_frame>
    <description>The correlation between anatomical features in the CCTA and the primary outcome (frequency of revascularization)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Invasive assessment of hemodynamic relevance</measure>
    <time_frame>Through clinically indicated diagnostic evaluation, an average of 2 months</time_frame>
    <description>The correlation of invasive assessement under pharmacologic inotropic stress and volume challenge (intravascular ultrasound and fractional flow reserve) with the quantitative determined anatomical features assessed in the CCTA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Computational fluid dynamics</measure>
    <time_frame>Through clinically indicated diagnostic evaluation, an average of 2 months</time_frame>
    <description>The correlation between FFR-CT and the invasively measured FFR-values</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>IVUS</measure>
    <time_frame>Through clinically indicated diagnostic evaluation, an average of 2 months</time_frame>
    <description>The alternation of intravascular ultrasound (IVUS) minimum lumen area at rest and under pharmacologic inotropic stress + volume challenge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sports</measure>
    <time_frame>at baseline, one year and 5 year after diagnosis</time_frame>
    <description>Sports behaviour survey</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">1000</enrollment>
  <condition>Anomalous Coronary Artery Origin</condition>
  <condition>Anomalous Coronary Artery Course</condition>
  <condition>Anomalous Coronary Artery With Aortic Origin and Course Between the Great Arteries</condition>
  <arm_group>
    <arm_group_label>Patients with an coronary artery anomaly (focus on ACAOS)</arm_group_label>
    <description>Patients eligible for study participation have a CAA and a prior, clinically indicated testing (noninvasive and/or invasive measurement) at our institution to evaluate the hemodynamic significance of this coronary anomaly. They will be approach either after start of this study (retrospective inclusion) or before their testing (prospective inclusion).</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patients eligible for study participation have a CAA and a prior, clinically indicated&#xD;
        testing (noninvasive and/or invasive measurement) at our institution to evaluate the&#xD;
        hemodynamic significance of this coronary anomaly.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥18 years.&#xD;
&#xD;
          -  CAA with a clinically indicated testing (noninvasive and/or invasive measurement) at&#xD;
             our institution&#xD;
&#xD;
          -  Informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        - None&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christoph Gräni, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Inselspital, Bern University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Christoph Gräni, MD PhD</last_name>
    <phone>+41 31 632 4508</phone>
    <email>christoph.graeni@insel.ch</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Marius R Bigler, MD</last_name>
    <phone>+41 31 632 8030</phone>
    <email>mariusreto.bigler@insel.ch</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University Hospital Inselspital, Bern</name>
      <address>
        <city>Bern</city>
        <zip>3010</zip>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christoph Gräni, MD PhD</last_name>
      <phone>+41316324508</phone>
      <email>christoph.graeni@insel.ch</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University Hospital, Zürich</name>
      <address>
        <city>Zürich</city>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ronny R Büchel, Prof.</last_name>
      <phone>+41 43 253 87 89</phone>
    </contact>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <reference>
    <citation>Grani C, Buechel RR, Kaufmann PA, Kwong RY. Multimodality Imaging in Individuals With Anomalous Coronary Arteries. JACC Cardiovasc Imaging. 2017 Apr;10(4):471-481. doi: 10.1016/j.jcmg.2017.02.004.</citation>
    <PMID>28385257</PMID>
  </reference>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>July 10, 2020</study_first_submitted>
  <study_first_submitted_qc>July 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 17, 2020</study_first_posted>
  <last_update_submitted>December 19, 2022</last_update_submitted>
  <last_update_submitted_qc>December 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Congenital Abnormalities</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04475289
org study id: 2020-00841
nct id: NCT04475289
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
An anomalous coronary artery from the opposite sinus of Valsalva (ACAOS) represents a
      congenital disorder with an anomalous location and/or course of the coronary vessel. The
      prevalence of ACAOS in the general population is around 1 % and they are mostly clinically
      insignificant and remain often undetected. However, some variants of ACAOS are associated
      with adverse cardiac events. The possible presence of an interarterial/intramural course is
      the primary cause for an oval proximal vessel shape and/or proximal vessel narrowing, which
      may lead under stress conditions to a "dynamic compression" of the vessel (compared to
      "fixed" stenosis in coronary artery disease). To mimic these conditions, dobutamine and
      volume challenge is used to invasively measure fractional flow reserve (FFR) during coronary
      angiography and is seen as the gold standard in assessing the hemodynamic relevance of ACAOS.
      We established a specialized interdisciplinary clinic for coronary artery anomalies including
      imaging specialists, invasive cardiologists and congenital heart disease surgeons as correct
      downstream testing and treatment decision is highly challenging in these patients. Thus,
      systematic collecting of all available diagnostic methods (invasive and non-invasive) is
      required to assess the optimal diagnostic procedure and treatment for these patients.
      Coronary computed tomography angiography (CCTA) is the method of choice to characterize the
      exact anatomy of ACAOS. However, how functional invasive FFR is associated with anatomical
      CCTA findings is unknown. Further, diagnostic accuracy of a novel independent research
      algorithm with computational fluid dynamics (ctFFR) as well as functional imaging (i.e.
      stress single photon emission computed tomography) in this specific setting is unknown.

      The presented project will help to understand the pathophysiology of CAAs with particular
      focus on ACAOS-IC and improve risk stratification based on non-invasive imaging.
Anomalous coronary arteries (CAA) represent a congenital disorder hallmarked by an anomalous
      location of the coronary ostium and/or vessel course. Based on the largest study assessing
      the prevalence and characteristics of CAA detected by coronary computer tomography
      angiography (CCTA) in Switzerland, the overall prevalence of CAA is 2.6%. However, depending
      of the type of CAA and its course in relation to the big vessels (aorta and pulmonary
      artery), not every CAA is accompanied by an increased cardiovascular risk.

      Of particular interests are anomalous coronary arteries from the opposite sinus of Valsalva
      with an interarterial course (ACAOS-IC). Those CAAs represents a congenital disorder with an
      anomalous location of the coronary ostium and a course of the anomalous vessel between the
      aorta and the pulmonary artery. The prevalence of ACAOS-IC in the general population is
      around 1 % and even they are mostly clinically insignificant and remain often undetected.

      However, some variants of ACAOS-IC are associated with adverse cardiac events (e.g. sudden
      cardiac death in young athletes). The possible presence of an intramural course, a course
      within the aortic wall is the primary cause for an oval proximal vessel shape and proximal
      vessel narrowing and is suggested to be the primary cause for ischemia. These features may
      lead under stress conditions to a "dynamic compression" of the vessel (compared to "fixed"
      stenosis in coronary artery disease). Therefore, to mimic these conditions, dobutamine and
      volume challenge is used to invasively measure fractional flow reserve (FFRDobutamine) during
      coronary angiography and is seen as the gold standard in assessing the hemodynamic relevance
      of ACAOS-IC. Presence of an abnormal FFRDobutamine is one of the most important factors in
      the decision-making towards surgical repair in ACAOS-IC.

      With the frequent use of invasive and non-invasive imaging to rule out coronary artery
      disease, an increase in absolute numbers of ACAOS-IC is seen and physicians are more
      confronted with the dilemma of how to manage these patients. Usually the question is whether
      the ACAOS-IC is a coincidental finding or if the anomaly is causative for the patients'
      symptoms. Thus, systematic acquisition of all available diagnostic methods (invasive and
      non-invasive) is required to assess the optimal diagnostic procedure for this patients.

      The presented project will help to understand the pathophysiology of CAAs with particular
      focus on ACAOS-IC and improve risk stratification based on non-invasive imaging.
observational model: Case-Only
time perspective: Prospective
measure: Frequency of revascularization
time frame: 5 years
description: Frequency of revascularizations (i.e. unroofing, re-implantation of the coronary artery, percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) etc.) of the anomalous vessel in patients with CAA.
measure: Quantitative assessment (in SI-Units) of the anatomical features in the coronary computed tomography angiography (CCTA)
time frame: 5 years
description: The correlation between anatomical features in the CCTA and the primary outcome (frequency of revascularization)
measure: Invasive assessment of hemodynamic relevance
time frame: Through clinically indicated diagnostic evaluation, an average of 2 months
description: The correlation of invasive assessement under pharmacologic inotropic stress and volume challenge (intravascular ultrasound and fractional flow reserve) with the quantitative determined anatomical features assessed in the CCTA
measure: Computational fluid dynamics
time frame: Through clinically indicated diagnostic evaluation, an average of 2 months
description: The correlation between FFR-CT and the invasively measured FFR-values
measure: IVUS
time frame: Through clinically indicated diagnostic evaluation, an average of 2 months
description: The alternation of intravascular ultrasound (IVUS) minimum lumen area at rest and under pharmacologic inotropic stress + volume challenge
measure: Sports
time frame: at baseline, one year and 5 year after diagnosis
description: Sports behaviour survey
arm group label: Patients with an coronary artery anomaly (focus on ACAOS)
description: Patients eligible for study participation have a CAA and a prior, clinically indicated testing (noninvasive and/or invasive measurement) at our institution to evaluate the hemodynamic significance of this coronary anomaly. They will be approach either after start of this study (retrospective inclusion) or before their testing (prospective inclusion).
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Christoph Gräni, MD PhD
role: Principal Investigator
affiliation: Inselspital, Bern University Hospital
last name: Christoph Gräni, MD PhD
phone: +41 31 632 4508
email: christoph.graeni@insel.ch
last name: Marius R Bigler, MD
phone: +41 31 632 8030
email: mariusreto.bigler@insel.ch
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Switzerland
citation: Grani C, Buechel RR, Kaufmann PA, Kwong RY. Multimodality Imaging in Individuals With Anomalous Coronary Arteries. JACC Cardiovasc Imaging. 2017 Apr;10(4):471-481. doi: 10.1016/j.jcmg.2017.02.004.
PMID: 28385257
responsible party type: Sponsor
mesh term: Congenital Abnormalities