<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/NCT03238690</url>
  </required_header>
  <id_info>
    <org_study_id>IRB_00095106</org_study_id>
    <nct_id>NCT03238690</nct_id>
  </id_info>
  <brief_title>LVAD Conditioning for Cardiac Recovery</brief_title>
  <official_title>Sequential Left Ventricular Assist Device (LVAD) Unloading and Conditioning to Induce Sustained Cardiac Recovery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>STAVROS G DRAKOS</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>American Heart Association</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Utah</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to investigate the potential recovery of heart function in&#xD;
      end-stage heart failure patients supported with a Left Ventricular Assist Device (LVAD)&#xD;
      through applying a myocardial conditioning protocol. During myocardial conditioning, LVAD&#xD;
      speed is reduced gradually in order to increase the work load of the heart. Multiple previous&#xD;
      studies have shown that interventions like this may improve heart function and give patients&#xD;
      the opportunity for a better quality of life.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Heart failure can be caused by various disorders, such as myocardial infarction,&#xD;
      hypertension, viral infection, exposure to toxins, chemotherapy, or genetically transmitted&#xD;
      muscular diseases. Regardless of the etiology, these disorders initiate ventricular&#xD;
      remodeling, an adaptive, compensatory process which becomes progressively maladaptive and the&#xD;
      cause of functional and clinical deterioration, eventually leading to heart failure. Local&#xD;
      and systemic compensatory responses that initially allow surviving muscle to maintain&#xD;
      hemodynamic function continue over time and due to this persistent compensatory over-activity&#xD;
      the initially unaffected myocardium becomes dysfunctional. These compensatory responses to an&#xD;
      abnormal cardiac load or myocardial injury involve several pathophysiological adaptations in&#xD;
      the cardiac structure at the genetic, molecular, cellular, and tissue levels. Furthermore,&#xD;
      left ventricular pressure and volume overload has shown to alter metabolic substrate&#xD;
      utilization, decrease mitochondrial function and reduce energy production in the failing&#xD;
      heart.&#xD;
&#xD;
      Mechanical circulatory support with LVAD has become a standard bridge to cardiac&#xD;
      transplantation, and has also been approved in the United States as permanent (destination)&#xD;
      therapy for selected patients presenting with end-stage heart failure. Clinical experience&#xD;
      with LVAD support has shown that it can reverse the complex process of chronic left&#xD;
      ventricular remodeling to a point where a subset of patients could be weaned from the device&#xD;
      after restoration of basic cardiac function. LVAD-induced mechanical unloading of the failing&#xD;
      heart leads to reduced mitochondrial density, structure and function, and interventions that&#xD;
      enhance mitochondrial biogenesis, function and structure, such as controlled cardiac&#xD;
      reloading may enhance LVAD-induced myocardial reverse remodeling and cardiac recovery. This&#xD;
      study is designed to investigate gradual reduction in LVAD speed within the range defined by&#xD;
      the assist device manufacturer's manual as appropriate for regular clinic use, to determine&#xD;
      the effect on reverse remodeling and myocardial recovery in end-stage heart failure patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 23, 2017</start_date>
  <completion_date type="Anticipated">June 30, 2026</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2024</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Left Ventricular Ejection Fraction (LVEF)</measure>
    <time_frame>Baseline (prior to LVAD implantation) and 12 months post-LVAD implantation, or at time of LVAD explantation/heart transplant</time_frame>
    <description>LVEF is measured by echocardiography. The average change in LVEF from baseline to 12 months or transplant in the study participant arm will be compared to results from an historical control group.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Left Ventricular End Diastolic Diameter (LVEDD)</measure>
    <time_frame>Baseline (prior to LVAD implantation) and 12 months post-LVAD implantation, or at time of LVAD explantation/heart transplant</time_frame>
    <description>LVEDD is measured by echocardiography. The average change in LVEDD from baseline to 12 months or transplant in the study participant arm will be compared to results from an historical control group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Left Ventricular End Systolic Diameter (LVESD)</measure>
    <time_frame>Baseline (prior to LVAD implantation) and 12 months post-LVAD implantation, or at time of LVAD explantation/heart transplant</time_frame>
    <description>LVESD is measured by echocardiography. The average change in LVESD from baseline to 12 months or transplant in the study participant arm will be compared to results from an historical control group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Left Ventricular End Diastolic Volume (LVEDV)</measure>
    <time_frame>Baseline (prior to LVAD implantation) and 12 months post-LVAD implantation, or at time of LVAD explantation/heart transplant</time_frame>
    <description>LVEDV is measured by echocardiography. The average change in LVEDV from baseline to 12 months or transplant in the study participant arm will be compared to results from an historical control group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Left Ventricular End Systolic Volume (LVESV)</measure>
    <time_frame>Baseline (prior to LVAD implantation) and 12 months post-LVAD implantation, or at time of LVAD explantation/heart transplant</time_frame>
    <description>LVESV is measured by echocardiography. The average change in LVESV from baseline to 12 months or transplant in the study participant arm will be compared to results from an historical control group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in heart tissue Glucose 1-phosphate levels</measure>
    <time_frame>Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)</time_frame>
    <description>Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for Glucose 1-phosphate levels. The average change in Glucose 1-phosphate from baseline to transplant in the study participant arm will be compared to results from an historical control group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in heart tissue Glucose 6-phosphate levels</measure>
    <time_frame>Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)</time_frame>
    <description>Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for Glucose 6-phosphate levels. The average change in Glucose 6-phosphate from baseline to transplant in the study participant arm will be compared to results from an historical control group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in heart tissue Pyruvate levels</measure>
    <time_frame>Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)</time_frame>
    <description>Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for Pyruvate levels. The average change in Pyruvate from baseline to transplant in the study participant arm will be compared to results from an historical control group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in heart tissue Lactic Acid levels</measure>
    <time_frame>Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)</time_frame>
    <description>Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for Lactic Acid levels. The average change in Lactic Acid from baseline to transplant in the study participant arm will be compared to results from an historical control group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in heart tissue Acetyl Coenzyme A levels</measure>
    <time_frame>Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)</time_frame>
    <description>Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for Acetyl Coenzyme A levels. The average change in Acetyl Coenzyme A from baseline to transplant in the study participant arm will be compared to results from an historical control group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in heart tissue Glucose Transporter 1 (GLUT1) levels</measure>
    <time_frame>Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)</time_frame>
    <description>Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for GLUT1 levels. The average change in GLUT1 from baseline to transplant in the study participant arm will be compared to results from an historical control group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in heart tissue Glucose Transporter 1 (GLUT1) messenger ribonucleic acid (mRNA) levels</measure>
    <time_frame>Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)</time_frame>
    <description>Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for GLUT1 mRNA levels. The average change in GLUT1 mRNA from baseline to transplant in the study participant arm will be compared to results from an historical control group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in heart tissue Glucose Transporter 4 (GLUT4) levels</measure>
    <time_frame>Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)</time_frame>
    <description>Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for GLUT4 levels. The average change in GLUT4 from baseline to transplant in the study participant arm will be compared to results from an historical control group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in heart tissue Glucose Transporter 4 (GLUT4) messenger ribonucleic acid (mRNA) levels</measure>
    <time_frame>Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)</time_frame>
    <description>Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for GLUT4 mRNA levels. The average change in GLUT4 mRNA from baseline to transplant in the study participant arm will be compared to results from an historical control group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in heart tissue Mitochondrial Pyruvate Carrier 1 (MPC1) levels</measure>
    <time_frame>Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)</time_frame>
    <description>Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for MPC1 levels. The average change in MPC1 from baseline to transplant in the study participant arm will be compared to results from an historical control group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in heart tissue Mitochondrial Pyruvate Carrier 2 (MPC2) levels</measure>
    <time_frame>Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)</time_frame>
    <description>Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for MPC2 levels. The average change in MPC2 from baseline to transplant in the study participant arm will be compared to results from an historical control group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in heart tissue Mitochondrial Density</measure>
    <time_frame>Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)</time_frame>
    <description>Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for mitochondrial density by electron microscopy. The average change in mitochondrial density from baseline to transplant in the study participant arm will be compared to results from an historical control group.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Heart Failure</condition>
  <arm_group>
    <arm_group_label>Controlled Cardiac Reloading</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Heart failure patients with recent LVAD implantation after an optimum unloading phase, will undergo controlled cardiac reloading through LVAD speed adjustment reductions in a controlled reloading phase</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Controlled Cardiac Reloading through LVAD Speed Adjustment</intervention_name>
    <description>LVAD speed is reduced at a fixed rate according to the particular LVAD device model implanted. LVAD speed reduction adjustments will be performed at visits occurring every 2 - 3 weeks, up to a total of 8 visits. Reduction of LVAD speed will continue until the soonest of: minimum operating setting as recommended in the LVAD Operator's manual is reached; the minimum setting tolerated by the subject is reached; the subject completes 8 visits; or until the subject receives a heart transplant.</description>
    <arm_group_label>Controlled Cardiac Reloading</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosed with heart failure undergoing LVAD implantation as a bridge to transplant&#xD;
&#xD;
          -  Enrolled in the Effects of Mechanical Unloading on Myocardial Function and Structure&#xD;
             study (IRB 30622)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Neither the subject nor the subject's representative is willing to provide written&#xD;
             consent for participation&#xD;
&#xD;
          -  Neither the subject nor the subject's representative understands spoken English&#xD;
&#xD;
          -  Subjects with adverse events leading to hospitalization during the optimum unloading&#xD;
             phase are excluded from participation in the controlled reloading phase&#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>Stavros Drakos, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Utah</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>John Kirk</last_name>
    <phone>801-585-2944</phone>
    <email>john.kirk@hsc.utah.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stavros Drakos, MD</last_name>
      <phone>801-585-2340</phone>
      <email>stavros.drakos@hsc.utah.edu</email>
    </contact>
    <investigator>
      <last_name>Stavros Drakos, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>George RS, Sabharwal NK, Webb C, Yacoub MH, Bowles CT, Hedger M, Khaghani A, Birks EJ. Echocardiographic assessment of flow across continuous-flow ventricular assist devices at low speeds. J Heart Lung Transplant. 2010 Nov;29(11):1245-52. doi: 10.1016/j.healun.2010.05.032. Epub 2010 Aug 5.</citation>
    <PMID>20688540</PMID>
  </reference>
  <reference>
    <citation>Healy AH, Koliopoulou A, Drakos SG, McKellar SH, Stehlik J, Selzman CH. Patient-controlled conditioning for left ventricular assist device-induced myocardial recovery. Ann Thorac Surg. 2015 May;99(5):1794-6. doi: 10.1016/j.athoracsur.2014.07.058.</citation>
    <PMID>25952209</PMID>
  </reference>
  <reference>
    <citation>Frazier OH, Baldwin AC, Demirozu ZT, Segura AM, Hernandez R, Taegtmeyer H, Mallidi H, Cohn WE. Ventricular reconditioning and pump explantation in patients supported by continuous-flow left ventricular assist devices. J Heart Lung Transplant. 2015 Jun;34(6):766-72. doi: 10.1016/j.healun.2014.09.015. Epub 2014 Sep 28.</citation>
    <PMID>25447571</PMID>
  </reference>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 31, 2017</study_first_submitted>
  <study_first_submitted_qc>July 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2017</study_first_posted>
  <last_update_submitted>June 22, 2023</last_update_submitted>
  <last_update_submitted_qc>June 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Utah</investigator_affiliation>
    <investigator_full_name>STAVROS G DRAKOS</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>LVAD</keyword>
  <keyword>Cardiac Recovery</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</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/NCT03238690
org study id: IRB_00095106
nct id: NCT03238690
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
The purpose of this study is to investigate the potential recovery of heart function in
      end-stage heart failure patients supported with a Left Ventricular Assist Device (LVAD)
      through applying a myocardial conditioning protocol. During myocardial conditioning, LVAD
      speed is reduced gradually in order to increase the work load of the heart. Multiple previous
      studies have shown that interventions like this may improve heart function and give patients
      the opportunity for a better quality of life.
Heart failure can be caused by various disorders, such as myocardial infarction,
      hypertension, viral infection, exposure to toxins, chemotherapy, or genetically transmitted
      muscular diseases. Regardless of the etiology, these disorders initiate ventricular
      remodeling, an adaptive, compensatory process which becomes progressively maladaptive and the
      cause of functional and clinical deterioration, eventually leading to heart failure. Local
      and systemic compensatory responses that initially allow surviving muscle to maintain
      hemodynamic function continue over time and due to this persistent compensatory over-activity
      the initially unaffected myocardium becomes dysfunctional. These compensatory responses to an
      abnormal cardiac load or myocardial injury involve several pathophysiological adaptations in
      the cardiac structure at the genetic, molecular, cellular, and tissue levels. Furthermore,
      left ventricular pressure and volume overload has shown to alter metabolic substrate
      utilization, decrease mitochondrial function and reduce energy production in the failing
      heart.

      Mechanical circulatory support with LVAD has become a standard bridge to cardiac
      transplantation, and has also been approved in the United States as permanent (destination)
      therapy for selected patients presenting with end-stage heart failure. Clinical experience
      with LVAD support has shown that it can reverse the complex process of chronic left
      ventricular remodeling to a point where a subset of patients could be weaned from the device
      after restoration of basic cardiac function. LVAD-induced mechanical unloading of the failing
      heart leads to reduced mitochondrial density, structure and function, and interventions that
      enhance mitochondrial biogenesis, function and structure, such as controlled cardiac
      reloading may enhance LVAD-induced myocardial reverse remodeling and cardiac recovery. This
      study is designed to investigate gradual reduction in LVAD speed within the range defined by
      the assist device manufacturer's manual as appropriate for regular clinic use, to determine
      the effect on reverse remodeling and myocardial recovery in end-stage heart failure patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Left Ventricular Ejection Fraction (LVEF)
time frame: Baseline (prior to LVAD implantation) and 12 months post-LVAD implantation, or at time of LVAD explantation/heart transplant
description: LVEF is measured by echocardiography. The average change in LVEF from baseline to 12 months or transplant in the study participant arm will be compared to results from an historical control group.
measure: Change in Left Ventricular End Diastolic Diameter (LVEDD)
time frame: Baseline (prior to LVAD implantation) and 12 months post-LVAD implantation, or at time of LVAD explantation/heart transplant
description: LVEDD is measured by echocardiography. The average change in LVEDD from baseline to 12 months or transplant in the study participant arm will be compared to results from an historical control group.
measure: Change in Left Ventricular End Systolic Diameter (LVESD)
time frame: Baseline (prior to LVAD implantation) and 12 months post-LVAD implantation, or at time of LVAD explantation/heart transplant
description: LVESD is measured by echocardiography. The average change in LVESD from baseline to 12 months or transplant in the study participant arm will be compared to results from an historical control group.
measure: Change in Left Ventricular End Diastolic Volume (LVEDV)
time frame: Baseline (prior to LVAD implantation) and 12 months post-LVAD implantation, or at time of LVAD explantation/heart transplant
description: LVEDV is measured by echocardiography. The average change in LVEDV from baseline to 12 months or transplant in the study participant arm will be compared to results from an historical control group.
measure: Change in Left Ventricular End Systolic Volume (LVESV)
time frame: Baseline (prior to LVAD implantation) and 12 months post-LVAD implantation, or at time of LVAD explantation/heart transplant
description: LVESV is measured by echocardiography. The average change in LVESV from baseline to 12 months or transplant in the study participant arm will be compared to results from an historical control group.
measure: Change in heart tissue Glucose 1-phosphate levels
time frame: Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)
description: Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for Glucose 1-phosphate levels. The average change in Glucose 1-phosphate from baseline to transplant in the study participant arm will be compared to results from an historical control group.
measure: Change in heart tissue Glucose 6-phosphate levels
time frame: Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)
description: Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for Glucose 6-phosphate levels. The average change in Glucose 6-phosphate from baseline to transplant in the study participant arm will be compared to results from an historical control group.
measure: Change in heart tissue Pyruvate levels
time frame: Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)
description: Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for Pyruvate levels. The average change in Pyruvate from baseline to transplant in the study participant arm will be compared to results from an historical control group.
measure: Change in heart tissue Lactic Acid levels
time frame: Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)
description: Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for Lactic Acid levels. The average change in Lactic Acid from baseline to transplant in the study participant arm will be compared to results from an historical control group.
measure: Change in heart tissue Acetyl Coenzyme A levels
time frame: Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)
description: Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for Acetyl Coenzyme A levels. The average change in Acetyl Coenzyme A from baseline to transplant in the study participant arm will be compared to results from an historical control group.
measure: Change in heart tissue Glucose Transporter 1 (GLUT1) levels
time frame: Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)
description: Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for GLUT1 levels. The average change in GLUT1 from baseline to transplant in the study participant arm will be compared to results from an historical control group.
measure: Change in heart tissue Glucose Transporter 1 (GLUT1) messenger ribonucleic acid (mRNA) levels
time frame: Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)
description: Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for GLUT1 mRNA levels. The average change in GLUT1 mRNA from baseline to transplant in the study participant arm will be compared to results from an historical control group.
measure: Change in heart tissue Glucose Transporter 4 (GLUT4) levels
time frame: Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)
description: Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for GLUT4 levels. The average change in GLUT4 from baseline to transplant in the study participant arm will be compared to results from an historical control group.
measure: Change in heart tissue Glucose Transporter 4 (GLUT4) messenger ribonucleic acid (mRNA) levels
time frame: Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)
description: Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for GLUT4 mRNA levels. The average change in GLUT4 mRNA from baseline to transplant in the study participant arm will be compared to results from an historical control group.
measure: Change in heart tissue Mitochondrial Pyruvate Carrier 1 (MPC1) levels
time frame: Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)
description: Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for MPC1 levels. The average change in MPC1 from baseline to transplant in the study participant arm will be compared to results from an historical control group.
measure: Change in heart tissue Mitochondrial Pyruvate Carrier 2 (MPC2) levels
time frame: Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)
description: Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for MPC2 levels. The average change in MPC2 from baseline to transplant in the study participant arm will be compared to results from an historical control group.
measure: Change in heart tissue Mitochondrial Density
time frame: Baseline (LVAD implantation) and at time of LVAD explantation/heart transplantation (up to 12 months)
description: Heart tissue samples will be collected at LVAD implantation when the tissue from the core becomes available and then at explant when the whole heart becomes available, and will be analyzed for mitochondrial density by electron microscopy. The average change in mitochondrial density from baseline to transplant in the study participant arm will be compared to results from an historical control group.
arm group label: Controlled Cardiac Reloading
arm group type: Experimental
description: Heart failure patients with recent LVAD implantation after an optimum unloading phase, will undergo controlled cardiac reloading through LVAD speed adjustment reductions in a controlled reloading phase
intervention type: Device
intervention name: Controlled Cardiac Reloading through LVAD Speed Adjustment
description: LVAD speed is reduced at a fixed rate according to the particular LVAD device model implanted. LVAD speed reduction adjustments will be performed at visits occurring every 2 - 3 weeks, up to a total of 8 visits. Reduction of LVAD speed will continue until the soonest of: minimum operating setting as recommended in the LVAD Operator's manual is reached; the minimum setting tolerated by the subject is reached; the subject completes 8 visits; or until the subject receives a heart transplant.
arm group label: Controlled Cardiac Reloading
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Stavros Drakos, MD
role: Principal Investigator
affiliation: University of Utah
last name: John Kirk
phone: 801-585-2944
email: john.kirk@hsc.utah.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
citation: George RS, Sabharwal NK, Webb C, Yacoub MH, Bowles CT, Hedger M, Khaghani A, Birks EJ. Echocardiographic assessment of flow across continuous-flow ventricular assist devices at low speeds. J Heart Lung Transplant. 2010 Nov;29(11):1245-52. doi: 10.1016/j.healun.2010.05.032. Epub 2010 Aug 5.
PMID: 20688540
citation: Healy AH, Koliopoulou A, Drakos SG, McKellar SH, Stehlik J, Selzman CH. Patient-controlled conditioning for left ventricular assist device-induced myocardial recovery. Ann Thorac Surg. 2015 May;99(5):1794-6. doi: 10.1016/j.athoracsur.2014.07.058.
PMID: 25952209
citation: Frazier OH, Baldwin AC, Demirozu ZT, Segura AM, Hernandez R, Taegtmeyer H, Mallidi H, Cohn WE. Ventricular reconditioning and pump explantation in patients supported by continuous-flow left ventricular assist devices. J Heart Lung Transplant. 2015 Jun;34(6):766-72. doi: 10.1016/j.healun.2014.09.015. Epub 2014 Sep 28.
PMID: 25447571
responsible party type: Sponsor-Investigator
investigator affiliation: University of Utah
investigator full name: STAVROS G DRAKOS
investigator title: Principal Investigator
mesh term: Heart Failure
sharing ipd: No