<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/NCT03280433</url>
  </required_header>
  <id_info>
    <org_study_id>SFRH/BD/104369/2014</org_study_id>
    <nct_id>NCT03280433</nct_id>
  </id_info>
  <brief_title>Influence of EPICardial Adipose Tissue in HEART Diseases: EPICHEART Study</brief_title>
  <acronym>EPICHEART</acronym>
  <official_title>Association of the Volume and Proteome of Epicardial Adipose Tissue With Coronary Artery Disease, Left Atrial Remodelling and Atrial Fibrillation in Severe Aortic Stenosis Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Universidade do Porto</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.</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>
      This translational study was designed to explore the association of the quantity and quality&#xD;
      of epicardial adipose tissue (EAT) with coronary artery disease (CAD), left atrial remodeling&#xD;
      and postoperative atrial fibrillation in a high cardiovascular disease-risk population. The&#xD;
      investigators expect to identify new biochemical factors and biomarkers in the crosstalk&#xD;
      between the epicardial adipocytes, coronary plaques and atrial cardiomyocytes that are&#xD;
      involved in the pathogenesis of atherosclerosis and atrial fibrillation, respectively.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: EAT has emerged as a new independent, and, potentially, modifiable cardiovascular&#xD;
      risk factor for CAD. EAT volume assessed by computed tomography (CT) was independently&#xD;
      associated with the presence of coronary stenosis, coronary calcification and myocardial&#xD;
      ischemia in cross-sectional studies, and, prospectively, with major adverse cardiovascular&#xD;
      events. Most of these clinical studies were, however, derived from community-based patients&#xD;
      with low-to intermediate-risk profile and the role of EAT in high-risk patients is currently&#xD;
      unclear. Accumulation of EAT has been also associated with left atrial (LA) dilation,&#xD;
      presence, chronicity, and recurrence of atrial fibrillation (AF). Although there is evidence&#xD;
      suggesting that EAT may be a major determinant of the LA vulnerable substrate of AF, the&#xD;
      mechanisms in the causal pathway between the EAT and LA remodeling are not completely&#xD;
      elucidated.&#xD;
&#xD;
      Aims: The main aims are to investigate if the volume of the EAT on CT and EAT proteome&#xD;
      assessed by SWATH-mass spectrometry are associated with extent, distribution and complexity&#xD;
      of coronary stenosis and coronary artery calcification, left atrial strain and incidence of&#xD;
      postoperative atrial fibrillation in patients with symptomatic severe aortic stenosis.&#xD;
&#xD;
      Methods: This a prospective study enrolling symptomatic severe aortic stenosis patients&#xD;
      referred to aortic valve replacement. The protocol includes preoperative detailed clinical&#xD;
      and nutritional evaluations, echocardiography, CT, cardiac magnetic resonance imaging and&#xD;
      invasive coronary angiography. During cardiac surgery, biopsies from the EAT, mediastinal and&#xD;
      subcutaneous thoracic adipose tissues will be performed to undergo analysis of proteome using&#xD;
      SWAT-mass spectrometry. Samples from the pericardial fluid, circulating and coronary sinus&#xD;
      blood samples will be collected as well in order to find local and peripheral adipose&#xD;
      tissue-derived biomarkers of the disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">September 1, 2014</start_date>
  <completion_date type="Anticipated">November 25, 2018</completion_date>
  <primary_completion_date type="Actual">November 25, 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>New onset atrial fibrillation</measure>
    <time_frame>Intra-hospital (i.e. from surgery until hospital discharge which means 7 days on average)</time_frame>
    <description>Incidence of atrial fibrillation after aortic valve replacement</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Left atrial remodelling by transthoracic echocardiography and magnetic resonance imaging</measure>
    <time_frame>6-month following aortic valve replacement</time_frame>
    <description>Change in left atrial strain and volumes</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Frailty syndrome according to Fried et al. scale</measure>
    <time_frame>6-month following aortic valve replacement</time_frame>
    <description>Change in frailty syndrome classification</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Coronary artery disease according to the presence of coronary stenosis and/or calcification</measure>
    <time_frame>Baseline</time_frame>
    <description>Prevalent coronary artery stenosis and coronary calcification</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Left ventricular hypertrophy by transthoracic echocardiography and magnetic resonance imaging</measure>
    <time_frame>6-month following aortic valve replacement</time_frame>
    <description>Regression of left ventricular mass after aortic valve replacement</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Right ventricular structure and function by transthoracic echocardiography and magnetic resonance imaging</measure>
    <time_frame>6-month following aortic valve replacement</time_frame>
    <description>Changes in right ventricular structure and function after aortic valve replacement</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Mortality</measure>
    <time_frame>3- to 5-year after aortic valve replacement</time_frame>
    <description>Incidence of all-cause death after aortic valve replacement</description>
  </other_outcome>
  <enrollment type="Anticipated">500</enrollment>
  <condition>Coronary Artery Disease</condition>
  <condition>Coronary Arteriosclerosis</condition>
  <condition>Atrial Fibrillation</condition>
  <condition>Left Atrial Abnormality</condition>
  <condition>Severe Aortic Stenosis</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Aortic valve replacement</intervention_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Fat samples (Epicardial fat, mediastinal fat, and subcutaneous fat), blood samples,&#xD;
      pericardial fluid samples, right atrial appendage sample.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Symptomatic severe aortic stenosis referred to aortic valve replacement.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  symptomatic severe aortic stenosis patients (defined as aortic valve area of &lt; 1 cm2&#xD;
             or 0.6 cm2/m2 by transthoracic echocardiography) referred to aortic valve replacement.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  diagnosis of acute coronary syndrome in the last 3 months.&#xD;
&#xD;
          -  prior history of persistent or permanent atrial or flutter fibrillation.&#xD;
&#xD;
          -  coexisting moderate to severe aortic valve regurgitation or moderate to severe mitral&#xD;
             valve disease, bicuspid aortic valve.&#xD;
&#xD;
          -  left ventricular dilatation [end-diastolic volume index &gt;75 mL/m²].&#xD;
&#xD;
          -  left ventricular ejection fraction &lt;55%.&#xD;
&#xD;
          -  chronic renal failure stage 3 to 5 defined as glomerular filtration rate GFR estimated&#xD;
             by Cockcroft-Gault formula adjusted for body surface area &lt; 30 mL/min/1.73m².&#xD;
&#xD;
          -  moderate to severe chronic obstructive pulmonary disease defined as forced expiratory&#xD;
             volume in one second &lt;50% according to the 2011 Global Initiative for Chronic&#xD;
             Obstructive Pulmonary Disease guidelines.&#xD;
&#xD;
          -  active malignancy (i.e. With no evidence of recurrence and no longer receiving active&#xD;
             treatment).&#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_contact>
    <last_name>Jennifer Mancio, MD, PhD candidate</last_name>
    <phone>00351961529516</phone>
    <email>jennifer.mancio@cardiov.ox.ac.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Nuno Bettencourt, MD, PhD</last_name>
    <phone>00351934258281</phone>
    <email>bettencourt.n@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Centro Hospitalar de Vila Nova de Gaia/Espinho</name>
      <address>
        <city>Vila Nova de Gaia</city>
        <state>Porto</state>
        <zip>4430-502</zip>
        <country>Portugal</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jennifer Mancio, MD, PhD candidate</last_name>
      <phone>00351 961529516</phone>
      <email>jennifer.mancio@cardiov.ox.ac.uk</email>
    </contact>
    <contact_backup>
      <last_name>Nuno Bettencourt, MD, PhD</last_name>
      <phone>00351 934258281</phone>
      <email>bettencourt.n@gmail.com</email>
    </contact_backup>
    <investigator>
      <last_name>Vasco Gama Ribeiro, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Luis Vouga, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Faculty of Medicine of Porto</name>
      <address>
        <city>Porto</city>
        <zip>4200-319</zip>
        <country>Portugal</country>
      </address>
    </facility>
    <status>Enrolling by invitation</status>
  </location>
  <location_countries>
    <country>Portugal</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 8, 2017</study_first_submitted>
  <study_first_submitted_qc>September 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <last_update_submitted>September 13, 2017</last_update_submitted>
  <last_update_submitted_qc>September 13, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 14, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.</investigator_affiliation>
    <investigator_full_name>Jennifer Mancio</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Epicardial adipose tissue</keyword>
  <keyword>Coronary artery disease</keyword>
  <keyword>Atrial fibrillation</keyword>
  <keyword>Severe aortic stenosis</keyword>
  <keyword>Proteome</keyword>
  <keyword>Mass spectrometry</keyword>
  <keyword>Computed tomography</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Myocardial Ischemia</mesh_term>
    <mesh_term>Coronary Disease</mesh_term>
    <mesh_term>Aortic Valve Stenosis</mesh_term>
    <mesh_term>Arteriosclerosis</mesh_term>
    <mesh_term>Constriction, Pathologic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03280433
org study id: SFRH/BD/104369/2014
nct id: NCT03280433
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This translational study was designed to explore the association of the quantity and quality
      of epicardial adipose tissue (EAT) with coronary artery disease (CAD), left atrial remodeling
      and postoperative atrial fibrillation in a high cardiovascular disease-risk population. The
      investigators expect to identify new biochemical factors and biomarkers in the crosstalk
      between the epicardial adipocytes, coronary plaques and atrial cardiomyocytes that are
      involved in the pathogenesis of atherosclerosis and atrial fibrillation, respectively.
Background: EAT has emerged as a new independent, and, potentially, modifiable cardiovascular
      risk factor for CAD. EAT volume assessed by computed tomography (CT) was independently
      associated with the presence of coronary stenosis, coronary calcification and myocardial
      ischemia in cross-sectional studies, and, prospectively, with major adverse cardiovascular
      events. Most of these clinical studies were, however, derived from community-based patients
      with low-to intermediate-risk profile and the role of EAT in high-risk patients is currently
      unclear. Accumulation of EAT has been also associated with left atrial (LA) dilation,
      presence, chronicity, and recurrence of atrial fibrillation (AF). Although there is evidence
      suggesting that EAT may be a major determinant of the LA vulnerable substrate of AF, the
      mechanisms in the causal pathway between the EAT and LA remodeling are not completely
      elucidated.

      Aims: The main aims are to investigate if the volume of the EAT on CT and EAT proteome
      assessed by SWATH-mass spectrometry are associated with extent, distribution and complexity
      of coronary stenosis and coronary artery calcification, left atrial strain and incidence of
      postoperative atrial fibrillation in patients with symptomatic severe aortic stenosis.

      Methods: This a prospective study enrolling symptomatic severe aortic stenosis patients
      referred to aortic valve replacement. The protocol includes preoperative detailed clinical
      and nutritional evaluations, echocardiography, CT, cardiac magnetic resonance imaging and
      invasive coronary angiography. During cardiac surgery, biopsies from the EAT, mediastinal and
      subcutaneous thoracic adipose tissues will be performed to undergo analysis of proteome using
      SWAT-mass spectrometry. Samples from the pericardial fluid, circulating and coronary sinus
      blood samples will be collected as well in order to find local and peripheral adipose
      tissue-derived biomarkers of the disease.
observational model: Cohort
time perspective: Prospective
measure: New onset atrial fibrillation
time frame: Intra-hospital (i.e. from surgery until hospital discharge which means 7 days on average)
description: Incidence of atrial fibrillation after aortic valve replacement
measure: Left atrial remodelling by transthoracic echocardiography and magnetic resonance imaging
time frame: 6-month following aortic valve replacement
description: Change in left atrial strain and volumes
measure: Frailty syndrome according to Fried et al. scale
time frame: 6-month following aortic valve replacement
description: Change in frailty syndrome classification
measure: Coronary artery disease according to the presence of coronary stenosis and/or calcification
time frame: Baseline
description: Prevalent coronary artery stenosis and coronary calcification
measure: Left ventricular hypertrophy by transthoracic echocardiography and magnetic resonance imaging
time frame: 6-month following aortic valve replacement
description: Regression of left ventricular mass after aortic valve replacement
measure: Right ventricular structure and function by transthoracic echocardiography and magnetic resonance imaging
time frame: 6-month following aortic valve replacement
description: Changes in right ventricular structure and function after aortic valve replacement
measure: Mortality
time frame: 3- to 5-year after aortic valve replacement
description: Incidence of all-cause death after aortic valve replacement
intervention type: Other
intervention name: Aortic valve replacement
Fat samples (Epicardial fat, mediastinal fat, and subcutaneous fat), blood samples,
      pericardial fluid samples, right atrial appendage sample.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jennifer Mancio, MD, PhD candidate
phone: 00351961529516
email: jennifer.mancio@cardiov.ox.ac.uk
last name: Nuno Bettencourt, MD, PhD
phone: 00351934258281
email: bettencourt.n@gmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
facility: 
status: Enrolling by invitation
country: Portugal
responsible party type: Principal Investigator
investigator affiliation: Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.
investigator full name: Jennifer Mancio
investigator title: Principal Investigator
mesh term: Atrial Fibrillation
mesh term: Coronary Artery Disease
mesh term: Myocardial Ischemia
mesh term: Coronary Disease
mesh term: Aortic Valve Stenosis
mesh term: Arteriosclerosis
mesh term: Constriction, Pathologic
sharing ipd: No