<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/NCT02260466</url>
  </required_header>
  <id_info>
    <org_study_id>2013-02</org_study_id>
    <nct_id>NCT02260466</nct_id>
  </id_info>
  <brief_title>Prevalence and Post-surgical Outcomes of CARdiac Wild-type TransthyrEtin amyloidoSIs in Elderly Patients With Aortic steNosis Referred for Valvular Replacement.</brief_title>
  <acronym>AMYLOCARTESIAN</acronym>
  <official_title>AMYLO-CARTESIAN Study :Prevalence and Post-surgical Outcomes of CARdiac Wild-type TransthyrEtin amyloidoSIs in Elderly Patients With Aortic steNosis Referred for Valvular Replacement.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>French Cardiology Society</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Henri Mondor University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>French Cardiology Society</source>
  <brief_summary>
    <textblock>
      Background: The prevalence of both senile cardiac amyloidosis (CA) and aortic stenosis (AS)&#xD;
      markedly increases with age. Aortic stenosis increases left ventricular pressure overload.&#xD;
      Cardiac deposits have been observed in AS and the amount of these deposits has been&#xD;
      correlated to post-surgical outcome. As they are strong echocardiographic and cardiac MRI&#xD;
      imaging similarities between CA and AS, the investigators hypothesized that the deposit&#xD;
      observed in AS is transthyretin amyloid deposit. The investigators objective is to&#xD;
      demonstrate that amyloid deposit is associated with poor outcomes following aortic stenosis&#xD;
      surgical valve replacement.&#xD;
&#xD;
      Materiel and methods: 180 patients with indication for surgical aortic valve replacement will&#xD;
      be recruited prospectively and consecutively in 5 French centers. A replicative study will be&#xD;
      performed in one Austrian center. Echocardiography, cardiac MRI and bone scintigraphy will be&#xD;
      performed prior to surgery. During surgery, a basal LV septum biopsy will be collected for&#xD;
      determination and quantification of interstitial deposits using specific staining which will&#xD;
      be performed in a blind fashion. Clinical outcomes will be recorded during the&#xD;
      hospitalization period following the surgery and at 1 year. Alive and re-hospitalization&#xD;
      status will be determined. Patients will be classified according to the presence or not of&#xD;
      amyloid deposits.&#xD;
&#xD;
      Expected results and impact: This study will emphasize how pressure overload stress&#xD;
      accelerates and magnifies amyloid deposition usually known to be related to cardiac aging&#xD;
      process. It will develop reliable imaging tools and markers to detect cardiac amyloid&#xD;
      deposition. Correlation between anatomopathologic analyses and the three different imaging&#xD;
      technics will identify accurate imaging markers of CA. A risk stratification model based on&#xD;
      amyloid deposits level for the clinical management of these patients will be created&#xD;
      combining imaging and biological markers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cardiovascular diseases remain the major cause of mortality and morbidity in industrialised&#xD;
      countries. Their prevalence increases steeply as consequence of the aging of the population&#xD;
      in these countries. Curiously, cardiovascular and neurodegenerative diseases share common&#xD;
      aging pathological pathways involving abnormal accumulation of insoluble amyloid proteins in&#xD;
      the extracellular matrix disrupting normal organ function. Whereas neurological amyloid&#xD;
      diseases has been considerably investigated, little attention has been paid to the&#xD;
      aggregation of amyloid proteins in cardiovascular diseases. Post-mortem studies have&#xD;
      identified cardiac wild-type transthyretin amyloidosis deposition in 25% of individuals over&#xD;
      the age of 80 years leading to the concept of &quot;senile cardiac amyloidosis&quot; (CA) (Cornwell, Am&#xD;
      j Med 1984; Pitkanen, Am J Pathol 1984). The cause of this deposition is not yet known but&#xD;
      might be related primarily to aging process and enhanced by cardiac mechanical stress&#xD;
      (overload), hypoxia, oxidative stress and inflammation. Since patients with transthyretin CA&#xD;
      develop severe heart failure with poor prognosis, it is crucial to identify them especially&#xD;
      among population at risk such those with aortic stenosis (AS). Indeed this common valvular&#xD;
      heart disease affects mainly senescent subjects and combines so the adverse effects on&#xD;
      myocardial function of both pressure overload and myocardial aging.&#xD;
&#xD;
      Interestingly, some elderly patients with severe AS exhibit similar echocardiographic and&#xD;
      cardiac MRI patterns as those reported in CA including increased cardiac wall thickness and&#xD;
      progressive left ventricular dysfunction starting with alteration of basal LV-2D strain. They&#xD;
      also exhibit increased late gadolinium enhancement (LGE) at cardiac MRI. This has been&#xD;
      interpreted as related to interstitial myocardial &quot;fibrosis&quot; and has been correlated with&#xD;
      poor prognosis after aortic valve replacement i.e.; high mortality, persistence of heart&#xD;
      failure symptoms and LV dysfunction (Weidemann Circ 2009; Dweck, JACC 2011; Hermann JACC&#xD;
      2011). However none of these patients have benefited from a detailed histology analysis with&#xD;
      aiming at identifying amyloid deposits. The investigators have recently found similar&#xD;
      clinical observations in the investigators AS cohort. Using specific staining, the&#xD;
      investigators were able to unmask the association of severe AS and CA in these patients.&#xD;
      These preliminary findings raise the question of a potential pathophysiological link between&#xD;
      CA and AS and might explain why some patients with AS may not benefit from cardiac surgery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Anticipated">July 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Screening</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical composite criterion: All causes of death and cardiovascular hospitalization at 1 year after surgery</measure>
    <time_frame>1 year</time_frame>
    <description>All causes of death and cardiovascular hospitalization at 1 year after surgery</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">186</enrollment>
  <condition>Heart Disease</condition>
  <condition>Aging</condition>
  <condition>Amyloidosis</condition>
  <condition>Aortic Valve Stenosis</condition>
  <arm_group>
    <arm_group_label>elderly patients with Aortic steNosis valvular replacement</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>a basal LV septum biopsy</intervention_name>
    <description>During surgery, a basal LV septum biopsy will be collected for determination and quantification of interstitial deposits using specific staining which will be performed in a blind fashion</description>
    <arm_group_label>elderly patients with Aortic steNosis valvular replacement</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Significant aortic stenosis. The aortic stenosis severity (aortic area : &lt;1cm² or&#xD;
             &lt;0.6cm²/m² measured by echocardiography&#xD;
&#xD;
          -  Indication of surgical aortic valve replacement for AS: will be defined in each center&#xD;
             in accordance with ESC guidelines.&#xD;
&#xD;
          -  Patient ≥ 70 years old and NYHA class ≥2 and LVEF &lt;60% or global LV strain more than&#xD;
             &quot;-17%&quot;.&#xD;
&#xD;
          -  Written consent prior to surgery.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Other severe disease with a life prognosis below than 1 year.&#xD;
&#xD;
          -  Already known other causes of amyloidosis than senile amyloidosis will be excluded.&#xD;
&#xD;
          -  Patients unsuitable for AS surgery as defined by ESC guidelines 2012.&#xD;
&#xD;
          -  Significant mitral valve disease needing a surgical treatment.&#xD;
&#xD;
          -  Significant aortic regurgitation (class &gt;III).&#xD;
&#xD;
        NB: Patients with pacemaker will be included but will not perform the cardiac MRI.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thibaud DAMY, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU Henri Mondor, Paris</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hôpital Henri Mondor</name>
      <address>
        <city>Creteil</city>
        <zip>94010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Limoges</name>
      <address>
        <city>Limoges</city>
        <zip>87000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU LYON</name>
      <address>
        <city>Lyon</city>
        <zip>69000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu Rennes</name>
      <address>
        <city>Rennes</city>
        <zip>35000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Cardiologique du Nord</name>
      <address>
        <city>Saint-Denis</city>
        <zip>93200</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Toulouse</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>October 6, 2014</study_first_submitted>
  <study_first_submitted_qc>October 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 9, 2014</study_first_posted>
  <last_update_submitted>September 30, 2022</last_update_submitted>
  <last_update_submitted_qc>September 30, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Amyloidosis</keyword>
  <keyword>echocardiography</keyword>
  <keyword>magnetic resonance imaging</keyword>
  <keyword>radionuclide imaging</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Aortic Valve Stenosis</mesh_term>
    <mesh_term>Amyloidosis</mesh_term>
    <mesh_term>Constriction, Pathologic</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/NCT02260466
org study id: 2013-02
nct id: NCT02260466
lead sponsor: 
collaborator: 
collaborator: 
Background: The prevalence of both senile cardiac amyloidosis (CA) and aortic stenosis (AS)
      markedly increases with age. Aortic stenosis increases left ventricular pressure overload.
      Cardiac deposits have been observed in AS and the amount of these deposits has been
      correlated to post-surgical outcome. As they are strong echocardiographic and cardiac MRI
      imaging similarities between CA and AS, the investigators hypothesized that the deposit
      observed in AS is transthyretin amyloid deposit. The investigators objective is to
      demonstrate that amyloid deposit is associated with poor outcomes following aortic stenosis
      surgical valve replacement.

      Materiel and methods: 180 patients with indication for surgical aortic valve replacement will
      be recruited prospectively and consecutively in 5 French centers. A replicative study will be
      performed in one Austrian center. Echocardiography, cardiac MRI and bone scintigraphy will be
      performed prior to surgery. During surgery, a basal LV septum biopsy will be collected for
      determination and quantification of interstitial deposits using specific staining which will
      be performed in a blind fashion. Clinical outcomes will be recorded during the
      hospitalization period following the surgery and at 1 year. Alive and re-hospitalization
      status will be determined. Patients will be classified according to the presence or not of
      amyloid deposits.

      Expected results and impact: This study will emphasize how pressure overload stress
      accelerates and magnifies amyloid deposition usually known to be related to cardiac aging
      process. It will develop reliable imaging tools and markers to detect cardiac amyloid
      deposition. Correlation between anatomopathologic analyses and the three different imaging
      technics will identify accurate imaging markers of CA. A risk stratification model based on
      amyloid deposits level for the clinical management of these patients will be created
      combining imaging and biological markers.
Cardiovascular diseases remain the major cause of mortality and morbidity in industrialised
      countries. Their prevalence increases steeply as consequence of the aging of the population
      in these countries. Curiously, cardiovascular and neurodegenerative diseases share common
      aging pathological pathways involving abnormal accumulation of insoluble amyloid proteins in
      the extracellular matrix disrupting normal organ function. Whereas neurological amyloid
      diseases has been considerably investigated, little attention has been paid to the
      aggregation of amyloid proteins in cardiovascular diseases. Post-mortem studies have
      identified cardiac wild-type transthyretin amyloidosis deposition in 25% of individuals over
      the age of 80 years leading to the concept of "senile cardiac amyloidosis" (CA) (Cornwell, Am
      j Med 1984; Pitkanen, Am J Pathol 1984). The cause of this deposition is not yet known but
      might be related primarily to aging process and enhanced by cardiac mechanical stress
      (overload), hypoxia, oxidative stress and inflammation. Since patients with transthyretin CA
      develop severe heart failure with poor prognosis, it is crucial to identify them especially
      among population at risk such those with aortic stenosis (AS). Indeed this common valvular
      heart disease affects mainly senescent subjects and combines so the adverse effects on
      myocardial function of both pressure overload and myocardial aging.

      Interestingly, some elderly patients with severe AS exhibit similar echocardiographic and
      cardiac MRI patterns as those reported in CA including increased cardiac wall thickness and
      progressive left ventricular dysfunction starting with alteration of basal LV-2D strain. They
      also exhibit increased late gadolinium enhancement (LGE) at cardiac MRI. This has been
      interpreted as related to interstitial myocardial "fibrosis" and has been correlated with
      poor prognosis after aortic valve replacement i.e.; high mortality, persistence of heart
      failure symptoms and LV dysfunction (Weidemann Circ 2009; Dweck, JACC 2011; Hermann JACC
      2011). However none of these patients have benefited from a detailed histology analysis with
      aiming at identifying amyloid deposits. The investigators have recently found similar
      clinical observations in the investigators AS cohort. Using specific staining, the
      investigators were able to unmask the association of severe AS and CA in these patients.
      These preliminary findings raise the question of a potential pathophysiological link between
      CA and AS and might explain why some patients with AS may not benefit from cardiac surgery.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Screening
masking: None (Open Label)
measure: Clinical composite criterion: All causes of death and cardiovascular hospitalization at 1 year after surgery
time frame: 1 year
description: All causes of death and cardiovascular hospitalization at 1 year after surgery
arm group label: elderly patients with Aortic steNosis valvular replacement
arm group type: Other
intervention type: Other
intervention name: a basal LV septum biopsy
description: During surgery, a basal LV septum biopsy will be collected for determination and quantification of interstitial deposits using specific staining which will be performed in a blind fashion
arm group label: elderly patients with Aortic steNosis valvular replacement
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Thibaud DAMY, MD PhD
role: Principal Investigator
affiliation: CHU Henri Mondor, Paris
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Heart Diseases
mesh term: Aortic Valve Stenosis
mesh term: Amyloidosis
mesh term: Constriction, Pathologic