<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/NCT03249272</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00082447</org_study_id>
    <nct_id>NCT03249272</nct_id>
  </id_info>
  <brief_title>Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve</brief_title>
  <official_title>Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to assess microvascular function as determined by a cardiovascular&#xD;
      magnetic resonance measurement of whole-heart (global) perfusion reserve. The goal is to&#xD;
      determine the prevalence of MVD in two common forms of non-ischemic cardiomyopathy,&#xD;
      hypertrophic cardiomyopathy (HCM) and idiopathic dilated cardiomyopathy (IDCM). The&#xD;
      hypothesis that an optimized technique will provide robust detection of MVD and that a&#xD;
      multifaceted approach will provide new insights into the pathophysiology of MVD, including&#xD;
      the influence of myocardial scarring upon the presence and severity of MVD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Coronary microvascular dysfunction (MVD) has been implicated as an important marker of&#xD;
      cardiac risk and has been thought to directly contribute to the pathogenesis of a wide&#xD;
      variety of cardiomyopathies. For instance, MVD is believed to cause ischemia (with reduction&#xD;
      in coronary flow reserve) in patients with hypertrophic cardiomyopathy (HCM) despite the&#xD;
      presence of angiographically normal epicardial coronary arteries. The implication is that MVD&#xD;
      in HCM may lead to the ventricular arrhythmias, sudden death, and heart failure. Similarly,&#xD;
      patients with idiopathic dilated cardiomyopathy (IDCM) have blunted coronary flow reserve,&#xD;
      which appears to be independently associated with poor prognosis.&#xD;
&#xD;
      Several etiologic mechanisms have been proposed to explain the occurrence of MVD, including&#xD;
      structural and functional abnormalities1:&#xD;
&#xD;
        1. increased microvascular resistance due to reduced vascular luminal caliber.&#xD;
&#xD;
        2. reduced density of microvessels associated with replacement scarring.&#xD;
&#xD;
        3. inappropriate vasoconstrictor responses.&#xD;
&#xD;
        4. inadequate vasodilator responses.&#xD;
&#xD;
      Unfortunately, these mechanisms are difficult to study in humans since no technique currently&#xD;
      allows the direct visualization of the coronary microcirculation in vivo. Thus, MVD has been&#xD;
      largely studied using non-invasive imaging techniques, such as positron emission tomography&#xD;
      (PET) or single photon emitted computed tomography (SPECT).&#xD;
&#xD;
      Although these methods have provided insight into MVD, much remains unknown. For example,&#xD;
      even the prevalence of MVD in patients with various types of cardiomyopathy is unclear, with&#xD;
      different studies showing widely different rates.&#xD;
&#xD;
      Cardiovascular magnetic resonance (CMR) is increasingly being used in clinical practice to&#xD;
      evaluate cardiac disease. CMR employs a multifaceted imaging approach with separate&#xD;
      techniques used to acquire separate sets of raw data, providing information on cardiac&#xD;
      morphology, function, regional myocardial ischemia, scarring, and global myocardial perfusion&#xD;
      reserve. The advantage of this approach is that image artifacts in one set of data will not&#xD;
      affect the quality of the other datasets, and the datasets in combination can be used to&#xD;
      distinguish separate pathophysiologies that could confound image interpretation. For example,&#xD;
      perfusion defects could be due to ischemia or scar tissue, but since the investigators will&#xD;
      obtain both perfusion images and scar images, the investigators will be able to resolve the&#xD;
      etiology. Additionally, CMR provides high spatial resolution (over 10-fold higher than PET),&#xD;
      and hence partial volume affects will be kept to a minimum and variability in measurements&#xD;
      will be reduced.&#xD;
&#xD;
      The aim of this study is to assess microvascular function as determined by a cardiovascular&#xD;
      magnetic resonance measurement of whole-heart (global) perfusion reserve. The goal is to&#xD;
      determine the prevalence of MVD in two common forms of non-ischemic cardiomyopathy,&#xD;
      hypertrophic cardiomyopathy (HCM) and idiopathic dilated cardiomyopathy (IDCM). The&#xD;
      hypothesis that an optimized technique will provide robust detection of MVD and that a&#xD;
      multifaceted approach will provide new insights into the pathophysiology of MVD, including&#xD;
      the influence of myocardial scarring upon the presence and severity of MVD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Sponsor withdrew funding&#xD;
  </why_stopped>
  <start_date type="Actual">September 5, 2017</start_date>
  <completion_date type="Actual">March 31, 2019</completion_date>
  <primary_completion_date type="Actual">March 31, 2019</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Participants undergoing cardiovascular magnetic resonance stress testing will be recruited and randomized to receive either regadenoson or adenosine.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>The reader of the CMR scan will be blinded to the stress agent used.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Prevalence of Microvascular Dysfunction (MVD) by a CMR Measurement of Whole-heart (Global) Perfusion Reserve Ratio in Patients With Hypertrophic Cardiomyopathy, Non-ischemic Cardiomyopathy, and Controls.</measure>
    <time_frame>The prevalence of MVD will be determined based on the findings at the time of the scan on Day 1 of the study.</time_frame>
    <description>Prevalence of microvascular dysfunction as determined by the CMR measure of global perfusion reserve ratio (GPR) in each these patient groups. MVD was considered present when either GPR was &lt;2.0 or regional stress perfusion abnormalities were present.&#xD;
In order to calculate this ratio, coronary sinus flow was measured twice:&#xD;
prior to the the administration of adenosine/regadenoson&#xD;
during the administration of adenosine/regadenoson&#xD;
GPR is a ratio of coronary sinus flow during the administration adenosine/regadenoson divided by the baseline coronary sinus flow measured prior to the administration.&#xD;
Regional perfusion abnormalities will be assessed at the time of adenosine/regadenoson administration.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>CMR Measurement of Global Perfusion Reserve Ratio</measure>
    <time_frame>The global perfusion ratio will be calculated from the measurements obtained at the time of the scan on Day 1 of the study.</time_frame>
    <description>Comparison of the CMR measure of global perfusion reserve ratio (GPR) in each these patient groups.&#xD;
In order to calculate this ratio, coronary sinus flow was measured twice:&#xD;
prior to the the administration of adenosine/regadenoson&#xD;
during the administration of adenosine/regadenoson</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Association Between Global Perfusion Reserve (GPR) Ratio and Regional Myocardial Scarring.</measure>
    <time_frame>Both global perfusion ratio and the presence of regional scarring will be determined/measured from the images obtained during the scan on Day 1 of the study.</time_frame>
    <description>Relationship between global perfusion reserve ratio and regional myocardial scarring.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Hypertrophic Cardiomyopathy</condition>
  <condition>Non-ischemic Dilated Cardiomyopathy</condition>
  <condition>Microvascular Ischaemia of Myocardium</condition>
  <arm_group>
    <arm_group_label>Hypertrophic cardiomyopathy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-ischemic dilated cardiomyopathy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Regadenoson</intervention_name>
    <description>Microvascular disease will be considered present if regional perfusion defects are observed or global perfusion reserve is reduced. For the assessment of microvascular disease, the adenosine and regadenoson groups will be combined, as the medications are considered interchangeable.</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Hypertrophic cardiomyopathy</arm_group_label>
    <arm_group_label>Non-ischemic dilated cardiomyopathy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Adenosine</intervention_name>
    <description>Microvascular disease will be considered present if regional perfusion defects are observed or global perfusion reserve is reduced. For the assessment of microvascular disease, the adenosine and regadenoson groups will be combined, as the medications are considered interchangeable.</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Hypertrophic cardiomyopathy</arm_group_label>
    <arm_group_label>Non-ischemic dilated cardiomyopathy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men or women aged 18 years or older&#xD;
&#xD;
        Cardiomyopathy patients&#xD;
&#xD;
          -  Patients presenting for CMR with the clinical diagnosis of hypertrophic cardiomyopathy&#xD;
             based on left ventricular wall thickness of at least ≥15 mm in the absence of any&#xD;
             other cardiac or systemic cause of hypertrophy&#xD;
&#xD;
          -  Patients presenting for CMR with the clinical diagnosis of idiopathic dilated&#xD;
             cardiomyopathy based upon left ventricular ejection fraction ≤40%, LV end-diastolic&#xD;
             diameter ≥55 mm or left ventricular end-systolic diameter ≤45 mm, and the absence of&#xD;
             coronary stenoses on angiography.&#xD;
&#xD;
        Control patients&#xD;
&#xD;
          -  Patients presenting for CMR without evidence of obstructive coronary artery disease&#xD;
             either by coronary angiography or stress testing.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Decompensated heart failure or hemodynamic instability&#xD;
&#xD;
          -  Prior coronary revascularization (PCI or CABG) or myocardial infarction (as evidenced&#xD;
             by previously elevated CPK-MB or troponin levels)&#xD;
&#xD;
          -  Accelerating angina or unstable angina&#xD;
&#xD;
          -  Inability to physically tolerate MRI or implanted objects that are MRI incompatible&#xD;
&#xD;
          -  Inability to provide written informed consent obtained at time of study enrollment.&#xD;
&#xD;
          -  Severe claustrophobia&#xD;
&#xD;
          -  Advanced heart block or sinus node dysfunction&#xD;
&#xD;
          -  Hypersensitivity or allergic reaction to regadenoson or adenosine&#xD;
&#xD;
          -  Hypotension&#xD;
&#xD;
          -  Active bronchospasm or history of hospitalization due to bronchospasm&#xD;
&#xD;
          -  History of seizures&#xD;
&#xD;
          -  Recent cerebrovascular accident&#xD;
&#xD;
          -  Use of dipyridamole within the last 5 days&#xD;
&#xD;
          -  Contraindication to aminophylline&#xD;
&#xD;
          -  Severe renal insufficiency with estimated glomerular filtration rate &lt;30 ml/min/ 1.73&#xD;
             m2&#xD;
&#xD;
          -  Pregnant or nursing&#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>Han Kim</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Duke Cardiovascular Magnetic Resonance Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Camici PG, d'Amati G, Rimoldi O. Coronary microvascular dysfunction: mechanisms and functional assessment. Nat Rev Cardiol. 2015 Jan;12(1):48-62. doi: 10.1038/nrcardio.2014.160. Epub 2014 Oct 14.</citation>
    <PMID>25311229</PMID>
  </reference>
  <reference>
    <citation>Klem I, Heitner JF, Shah DJ, Sketch MH Jr, Behar V, Weinsaft J, Cawley P, Parker M, Elliott M, Judd RM, Kim RJ. Improved detection of coronary artery disease by stress perfusion cardiovascular magnetic resonance with the use of delayed enhancement infarction imaging. J Am Coll Cardiol. 2006 Apr 18;47(8):1630-8. doi: 10.1016/j.jacc.2005.10.074. Epub 2006 Mar 27.</citation>
    <PMID>16631001</PMID>
  </reference>
  <reference>
    <citation>Klem I, Greulich S, Heitner JF, Kim H, Vogelsberg H, Kispert EM, Ambati SR, Bruch C, Parker M, Judd RM, Kim RJ, Sechtem U. Value of cardiovascular magnetic resonance stress perfusion testing for the detection of coronary artery disease in women. JACC Cardiovasc Imaging. 2008 Jul;1(4):436-45. doi: 10.1016/j.jcmg.2008.03.010.</citation>
    <PMID>19356464</PMID>
  </reference>
  <reference>
    <citation>Camici PG, Crea F. Coronary microvascular dysfunction. N Engl J Med. 2007 Feb 22;356(8):830-40. doi: 10.1056/NEJMra061889. No abstract available.</citation>
    <PMID>17314342</PMID>
  </reference>
  <reference>
    <citation>Choudhury L, Mahrholdt H, Wagner A, Choi KM, Elliott MD, Klocke FJ, Bonow RO, Judd RM, Kim RJ. Myocardial scarring in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2002 Dec 18;40(12):2156-64. doi: 10.1016/s0735-1097(02)02602-5.</citation>
    <PMID>12505229</PMID>
  </reference>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>August 8, 2017</study_first_submitted>
  <study_first_submitted_qc>August 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <results_first_submitted>March 6, 2020</results_first_submitted>
  <results_first_submitted_qc>August 26, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">September 16, 2020</results_first_posted>
  <last_update_submitted>August 26, 2020</last_update_submitted>
  <last_update_submitted_qc>August 26, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 16, 2020</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>Cardiomyopathies</mesh_term>
    <mesh_term>Cardiomyopathy, Hypertrophic</mesh_term>
    <mesh_term>Cardiomyopathy, Dilated</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenosine</mesh_term>
    <mesh_term>Regadenoson</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 1, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/72/NCT03249272/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Due to the slow pace of recruitment, the sponsor withdrew funding for the study. Of the expected 75 participants, 31 were recruited. As was pre-specified, the regadenoson and adenosine groups were combined for analysis as these interventions are interchangeable.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Hypertrophic Cardiomyopathy</title>
          <description>Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:&#xD;
Global perfusion reserve (GPR) &lt; 2.0.&#xD;
Coronary sinus blood flow (CS) with velocity-encoded CMR will be measured during maximal vasodilation and at rest. GPR was calculated as the ratio of stress CS to rest CS blood flow.&#xD;
The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.&#xD;
For the analysis of the global perfusion ratio, the regadenson and adenosine groups were combined.&#xD;
The prevalence will be calculated by dividing the number of hypertrophic cardiomyopathy patients with MVD by the total number of patients with hypertrophic cardiomyopathy.</description>
        </group>
        <group group_id="P2">
          <title>Non-ischemic Dilated Cardiomyopathy</title>
          <description>Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:&#xD;
Global perfusion reserve (GPR) &lt; 2.0.&#xD;
Coronary sinus blood flow (CS) with velocity-encoded CMR will be measured during maximal vasodilation and at rest. GPR was calculated as the ratio of stress CS to rest CS blood flow.&#xD;
The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.&#xD;
For the analysis of the global perfusion ratio, the regadenson and adenosine groups were combined.&#xD;
The prevalence will be calculated by dividing the number of non-ischemic dilated cardiomyopathy patients with MVD by the total number of patients with non-ischemic dilated cardiomyopathy.</description>
        </group>
        <group group_id="P3">
          <title>Control</title>
          <description>Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:&#xD;
Global perfusion reserve (GPR) &lt; 2.0.&#xD;
Coronary sinus blood flow (CS) with velocity-encoded CMR will be measured during maximal vasodilation and at rest. GPR was calculated as the ratio of stress CS to rest CS blood flow.&#xD;
The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.&#xD;
For the analysis of the global perfusion ratio, the regadenson and adenosine groups were combined.&#xD;
The prevalence will be calculated by dividing the number of control patients with MVD by the total number of control patients.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>As was pre-specified, the regadenoson and adenosine groups were combined for analysis as these interventions are interchangeable.</population>
      <group_list>
        <group group_id="B1">
          <title>Hypertrophic Cardiomyopathy</title>
          <description>Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:&#xD;
Global perfusion reserve (GPR) &lt; 2.0.&#xD;
Coronary sinus blood flow (CS) with velocity-encoded CMR will be measured during maximal vasodilation and at rest. GPR was calculated as the ratio of stress CS to rest CS blood flow.&#xD;
The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.&#xD;
The prevalence will be calculated by dividing the number of hypertrophic cardiomyopathy patients with MVD by the total number of patients with hypertrophic cardiomyopathy.</description>
        </group>
        <group group_id="B2">
          <title>Non-ischemic Dilated Cardiomyopathy</title>
          <description>Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:&#xD;
Global perfusion reserve (GPR) &lt; 2.0.&#xD;
Coronary sinus blood flow (CS) with velocity-encoded CMR will be measured during maximal vasodilation and at rest. GPR was calculated as the ratio of stress CS to rest CS blood flow.&#xD;
The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.&#xD;
The prevalence will be calculated by dividing the number of non-ischemic dilated cardiomyopathy patients with MVD by the total number of patients with non-ischemic dilated cardiomyopathy.</description>
        </group>
        <group group_id="B3">
          <title>Control Patients</title>
          <description>Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:&#xD;
Global perfusion reserve (GPR) &lt; 2.0.&#xD;
Coronary sinus blood flow (CS) with velocity-encoded CMR will be measured during maximal vasodilation and at rest. GPR was calculated as the ratio of stress CS to rest CS blood flow.&#xD;
The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.&#xD;
The prevalence will be calculated by dividing the number of control patients with MVD by the total number of control patients.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="19"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="6"/>
            <count group_id="B4" value="31"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="46.1" spread="17.7"/>
                    <measurement group_id="B2" value="60.6" spread="12.2"/>
                    <measurement group_id="B3" value="53.2" spread="5.7"/>
                    <measurement group_id="B4" value="50.3" spread="15.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Prevalence of Microvascular Dysfunction (MVD) by a CMR Measurement of Whole-heart (Global) Perfusion Reserve Ratio in Patients With Hypertrophic Cardiomyopathy, Non-ischemic Cardiomyopathy, and Controls.</title>
        <description>Prevalence of microvascular dysfunction as determined by the CMR measure of global perfusion reserve ratio (GPR) in each these patient groups. MVD was considered present when either GPR was &lt;2.0 or regional stress perfusion abnormalities were present.&#xD;
In order to calculate this ratio, coronary sinus flow was measured twice:&#xD;
prior to the the administration of adenosine/regadenoson&#xD;
during the administration of adenosine/regadenoson&#xD;
GPR is a ratio of coronary sinus flow during the administration adenosine/regadenoson divided by the baseline coronary sinus flow measured prior to the administration.&#xD;
Regional perfusion abnormalities will be assessed at the time of adenosine/regadenoson administration.</description>
        <time_frame>The prevalence of MVD will be determined based on the findings at the time of the scan on Day 1 of the study.</time_frame>
        <population>Due to the slow pace of recruitment, the sponsor withdrew funding for the study. Of the expected 75 participants, 31 were recruited. As was pre-specified, the regadenoson and adenosine groups were combined for analysis as these interventions are interchangeable.</population>
        <group_list>
          <group group_id="O1">
            <title>Hypertrophic Cardiomyopathy</title>
            <description>Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:&#xD;
Global perfusion reserve (GPR) &lt; 2.0.&#xD;
Coronary sinus blood flow (CS) with velocity-encoded CMR will be measured during maximal vasodilation and at rest. GPR was calculated as the ratio of stress CS to rest CS blood flow.&#xD;
The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.&#xD;
The prevalence will be calculated by dividing the number of hypertrophic cardiomyopathy patients with MVD by the total number of patients with hypertrophic cardiomyopathy.</description>
          </group>
          <group group_id="O2">
            <title>Non-ischemic Dilated Cardiomyopathy</title>
            <description>Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:&#xD;
Global perfusion reserve (GPR) &lt; 2.0.&#xD;
Coronary sinus blood flow (CS) with velocity-encoded CMR will be measured during maximal vasodilation and at rest. GPR was calculated as the ratio of stress CS to rest CS blood flow.&#xD;
The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.&#xD;
The prevalence will be calculated by dividing the number of non-ischemic dilated cardiomyopathy patients with MVD by the total number of patients with non-ischemic dilated cardiomyopathy.</description>
          </group>
          <group group_id="O3">
            <title>Control</title>
            <description>Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:&#xD;
Global perfusion reserve (GPR) &lt; 2.0.&#xD;
Coronary sinus blood flow (CS) with velocity-encoded CMR will be measured during maximal vasodilation and at rest. GPR was calculated as the ratio of stress CS to rest CS blood flow.&#xD;
The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.&#xD;
The prevalence will be calculated by dividing the number of control patients with MVD by the total number of control patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Prevalence of Microvascular Dysfunction (MVD) by a CMR Measurement of Whole-heart (Global) Perfusion Reserve Ratio in Patients With Hypertrophic Cardiomyopathy, Non-ischemic Cardiomyopathy, and Controls.</title>
          <description>Prevalence of microvascular dysfunction as determined by the CMR measure of global perfusion reserve ratio (GPR) in each these patient groups. MVD was considered present when either GPR was &lt;2.0 or regional stress perfusion abnormalities were present.&#xD;
In order to calculate this ratio, coronary sinus flow was measured twice:&#xD;
prior to the the administration of adenosine/regadenoson&#xD;
during the administration of adenosine/regadenoson&#xD;
GPR is a ratio of coronary sinus flow during the administration adenosine/regadenoson divided by the baseline coronary sinus flow measured prior to the administration.&#xD;
Regional perfusion abnormalities will be assessed at the time of adenosine/regadenoson administration.</description>
          <population>Due to the slow pace of recruitment, the sponsor withdrew funding for the study. Of the expected 75 participants, 31 were recruited. As was pre-specified, the regadenoson and adenosine groups were combined for analysis as these interventions are interchangeable.</population>
          <units>Percentage of group with MVD</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="79"/>
                    <measurement group_id="O2" value="33.3"/>
                    <measurement group_id="O3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CMR Measurement of Global Perfusion Reserve Ratio</title>
        <description>Comparison of the CMR measure of global perfusion reserve ratio (GPR) in each these patient groups.&#xD;
In order to calculate this ratio, coronary sinus flow was measured twice:&#xD;
prior to the the administration of adenosine/regadenoson&#xD;
during the administration of adenosine/regadenoson</description>
        <time_frame>The global perfusion ratio will be calculated from the measurements obtained at the time of the scan on Day 1 of the study.</time_frame>
        <population>As was pre-specified, the regadenoson and adenosine groups were combined for analysis as these interventions are interchangeable.</population>
        <group_list>
          <group group_id="O1">
            <title>Hypertrophic Cardiomyopathy</title>
            <description>Global perfusion reserve</description>
          </group>
          <group group_id="O2">
            <title>Non-ischemic Dilated Cardiomyopathy</title>
            <description>Global perfusion reserve</description>
          </group>
          <group group_id="O3">
            <title>Control</title>
            <description>Global perfusion reserve</description>
          </group>
        </group_list>
        <measure>
          <title>CMR Measurement of Global Perfusion Reserve Ratio</title>
          <description>Comparison of the CMR measure of global perfusion reserve ratio (GPR) in each these patient groups.&#xD;
In order to calculate this ratio, coronary sinus flow was measured twice:&#xD;
prior to the the administration of adenosine/regadenoson&#xD;
during the administration of adenosine/regadenoson</description>
          <population>As was pre-specified, the regadenoson and adenosine groups were combined for analysis as these interventions are interchangeable.</population>
          <units>ratio</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.99" lower_limit="1.87" upper_limit="4.65"/>
                    <measurement group_id="O2" value="3.04" lower_limit="2.64" upper_limit="3.61"/>
                    <measurement group_id="O3" value="3.83" lower_limit="2.42" upper_limit="4.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Association Between Global Perfusion Reserve (GPR) Ratio and Regional Myocardial Scarring.</title>
        <description>Relationship between global perfusion reserve ratio and regional myocardial scarring.</description>
        <time_frame>Both global perfusion ratio and the presence of regional scarring will be determined/measured from the images obtained during the scan on Day 1 of the study.</time_frame>
        <population>As was pre-specified, the regadenoson and adenosine groups were combined for analysis as these interventions are interchangeable. One of the control patients was not able to hold his/her breath, and no image was acquired for stress perfusion myocardial flow. Thus, global perfusion reserve could not be calculated.</population>
        <group_list>
          <group group_id="O1">
            <title>Hypertrophic Cardiomyopathy - Scarring</title>
            <description>Mean value of all patients with Hypertrophic cardiomyopathy with scarring.</description>
          </group>
          <group group_id="O2">
            <title>Hypertrophic Cardiomyopathy - Without Scarring</title>
            <description>Mean value of all patients with Hypertrophic cardiomyopathy without scarring.</description>
          </group>
          <group group_id="O3">
            <title>Non-ischemic Dilated Cardiomyopathy - Scarring</title>
            <description>Mean value of all patients with Non-ischemic Dilated cardiomyopathy with scarring.</description>
          </group>
          <group group_id="O4">
            <title>Non-ischemic Dilated Cardiomyopathy - Without Scarring</title>
            <description>Mean value of all patients with Non-ischemic Dilated cardiomyopathy without scarring.</description>
          </group>
          <group group_id="O5">
            <title>Control - Scarring</title>
            <description>Mean value of all control patients with scarring.</description>
          </group>
          <group group_id="O6">
            <title>Control - Without Scarring</title>
            <description>Mean value of all control patients without scarring.</description>
          </group>
        </group_list>
        <measure>
          <title>The Association Between Global Perfusion Reserve (GPR) Ratio and Regional Myocardial Scarring.</title>
          <description>Relationship between global perfusion reserve ratio and regional myocardial scarring.</description>
          <population>As was pre-specified, the regadenoson and adenosine groups were combined for analysis as these interventions are interchangeable. One of the control patients was not able to hold his/her breath, and no image was acquired for stress perfusion myocardial flow. Thus, global perfusion reserve could not be calculated.</population>
          <units>Global perfusion reserve ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="0"/>
                <count group_id="O5" value="0"/>
                <count group_id="O6" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.19" spread="1.71"/>
                    <measurement group_id="O2" value="5.91" spread="4.09"/>
                    <measurement group_id="O3" value="3.16" spread="0.65"/>
                    <measurement group_id="O6" value="3.53" spread="1.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were assessed during the time of the MR scan.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Hypertrophic Cardiomyopathy - Adenosine</title>
          <description>Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:&#xD;
Global perfusion reserve (GPR) &lt; 2.0.&#xD;
Coronary sinus blood flow (CS) with velocity-encoded CMR will be measured during maximal vasodilation and at rest. GPR was calculated as the ratio of stress CS to rest CS blood flow.&#xD;
The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.&#xD;
The prevalence will be calculated by dividing the number of hypertrophic cardiomyopathy patients with MVD by the total number of patients with hypertrophic cardiomyopathy.</description>
        </group>
        <group group_id="E2">
          <title>Hypertrophic Cardiomyopathy - Regadenoson</title>
          <description>Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:&#xD;
Global perfusion reserve (GPR) &lt; 2.0.&#xD;
Coronary sinus blood flow (CS) with velocity-encoded CMR will be measured during maximal vasodilation and at rest. GPR was calculated as the ratio of stress CS to rest CS blood flow.&#xD;
The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.&#xD;
The prevalence will be calculated by dividing the number of hypertrophic cardiomyopathy patients with MVD by the total number of patients with hypertrophic cardiomyopathy.</description>
        </group>
        <group group_id="E3">
          <title>Non-ischemic Dilated Cardiomyopathy - Adenosine</title>
          <description>Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:&#xD;
Global perfusion reserve (GPR) &lt; 2.0.&#xD;
Coronary sinus blood flow (CS) with velocity-encoded CMR will be measured during maximal vasodilation and at rest. GPR was calculated as the ratio of stress CS to rest CS blood flow.&#xD;
The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.&#xD;
The prevalence will be calculated by dividing the number of non-ischemic dilated cardiomyopathy patients with MVD by the total number of patients with non-ischemic dilated cardiomyopathy.</description>
        </group>
        <group group_id="E4">
          <title>Non-ischemic Dilated Cardiomyopathy - Regadenoson</title>
          <description>Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:&#xD;
Global perfusion reserve (GPR) &lt; 2.0.&#xD;
Coronary sinus blood flow (CS) with velocity-encoded CMR will be measured during maximal vasodilation and at rest. GPR was calculated as the ratio of stress CS to rest CS blood flow.&#xD;
The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.&#xD;
The prevalence will be calculated by dividing the number of hypertrophic cardiomyopathy patients with MVD by the total number of patients with hypertrophic cardiomyopathy.</description>
        </group>
        <group group_id="E5">
          <title>Control - Adenosine</title>
          <description>Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:&#xD;
Global perfusion reserve (GPR) &lt; 2.0.&#xD;
Coronary sinus blood flow (CS) with velocity-encoded CMR will be measured during maximal vasodilation and at rest. GPR was calculated as the ratio of stress CS to rest CS blood flow.&#xD;
The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.&#xD;
The prevalence will be calculated by dividing the number of control patients with MVD by the total number of control patients.</description>
        </group>
        <group group_id="E6">
          <title>Control - Regadenoson</title>
          <description>Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:&#xD;
Global perfusion reserve (GPR) &lt; 2.0.&#xD;
Coronary sinus blood flow (CS) with velocity-encoded CMR will be measured during maximal vasodilation and at rest. GPR was calculated as the ratio of stress CS to rest CS blood flow.&#xD;
The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.&#xD;
The prevalence will be calculated by dividing the number of hypertrophic cardiomyopathy patients with MVD by the total number of patients with hypertrophic cardiomyopathy.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Slow recruitment led to the end of the study.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Han Kim, MD</name_or_title>
      <organization>Duke Cardiovascular Magnetic Resonance Center</organization>
      <phone>9196683539</phone>
      <email>han.kim@duke.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03249272
org study id: Pro00082447
nct id: NCT03249272
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The aim of this study is to assess microvascular function as determined by a cardiovascular
      magnetic resonance measurement of whole-heart (global) perfusion reserve. The goal is to
      determine the prevalence of MVD in two common forms of non-ischemic cardiomyopathy,
      hypertrophic cardiomyopathy (HCM) and idiopathic dilated cardiomyopathy (IDCM). The
      hypothesis that an optimized technique will provide robust detection of MVD and that a
      multifaceted approach will provide new insights into the pathophysiology of MVD, including
      the influence of myocardial scarring upon the presence and severity of MVD.
Coronary microvascular dysfunction (MVD) has been implicated as an important marker of
      cardiac risk and has been thought to directly contribute to the pathogenesis of a wide
      variety of cardiomyopathies. For instance, MVD is believed to cause ischemia (with reduction
      in coronary flow reserve) in patients with hypertrophic cardiomyopathy (HCM) despite the
      presence of angiographically normal epicardial coronary arteries. The implication is that MVD
      in HCM may lead to the ventricular arrhythmias, sudden death, and heart failure. Similarly,
      patients with idiopathic dilated cardiomyopathy (IDCM) have blunted coronary flow reserve,
      which appears to be independently associated with poor prognosis.

      Several etiologic mechanisms have been proposed to explain the occurrence of MVD, including
      structural and functional abnormalities1:

        1. increased microvascular resistance due to reduced vascular luminal caliber.

        2. reduced density of microvessels associated with replacement scarring.

        3. inappropriate vasoconstrictor responses.

        4. inadequate vasodilator responses.

      Unfortunately, these mechanisms are difficult to study in humans since no technique currently
      allows the direct visualization of the coronary microcirculation in vivo. Thus, MVD has been
      largely studied using non-invasive imaging techniques, such as positron emission tomography
      (PET) or single photon emitted computed tomography (SPECT).

      Although these methods have provided insight into MVD, much remains unknown. For example,
      even the prevalence of MVD in patients with various types of cardiomyopathy is unclear, with
      different studies showing widely different rates.

      Cardiovascular magnetic resonance (CMR) is increasingly being used in clinical practice to
      evaluate cardiac disease. CMR employs a multifaceted imaging approach with separate
      techniques used to acquire separate sets of raw data, providing information on cardiac
      morphology, function, regional myocardial ischemia, scarring, and global myocardial perfusion
      reserve. The advantage of this approach is that image artifacts in one set of data will not
      affect the quality of the other datasets, and the datasets in combination can be used to
      distinguish separate pathophysiologies that could confound image interpretation. For example,
      perfusion defects could be due to ischemia or scar tissue, but since the investigators will
      obtain both perfusion images and scar images, the investigators will be able to resolve the
      etiology. Additionally, CMR provides high spatial resolution (over 10-fold higher than PET),
      and hence partial volume affects will be kept to a minimum and variability in measurements
      will be reduced.

      The aim of this study is to assess microvascular function as determined by a cardiovascular
      magnetic resonance measurement of whole-heart (global) perfusion reserve. The goal is to
      determine the prevalence of MVD in two common forms of non-ischemic cardiomyopathy,
      hypertrophic cardiomyopathy (HCM) and idiopathic dilated cardiomyopathy (IDCM). The
      hypothesis that an optimized technique will provide robust detection of MVD and that a
      multifaceted approach will provide new insights into the pathophysiology of MVD, including
      the influence of myocardial scarring upon the presence and severity of MVD.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants undergoing cardiovascular magnetic resonance stress testing will be recruited and randomized to receive either regadenoson or adenosine.
primary purpose: Basic Science
masking: Single (Outcomes Assessor)
masking description: The reader of the CMR scan will be blinded to the stress agent used.
measure: Prevalence of Microvascular Dysfunction (MVD) by a CMR Measurement of Whole-heart (Global) Perfusion Reserve Ratio in Patients With Hypertrophic Cardiomyopathy, Non-ischemic Cardiomyopathy, and Controls.
time frame: The prevalence of MVD will be determined based on the findings at the time of the scan on Day 1 of the study.
description: Prevalence of microvascular dysfunction as determined by the CMR measure of global perfusion reserve ratio (GPR) in each these patient groups. MVD was considered present when either GPR was <2.0 or regional stress perfusion abnormalities were present.
In order to calculate this ratio, coronary sinus flow was measured twice:
prior to the the administration of adenosine/regadenoson
during the administration of adenosine/regadenoson
GPR is a ratio of coronary sinus flow during the administration adenosine/regadenoson divided by the baseline coronary sinus flow measured prior to the administration.
Regional perfusion abnormalities will be assessed at the time of adenosine/regadenoson administration.
measure: CMR Measurement of Global Perfusion Reserve Ratio
time frame: The global perfusion ratio will be calculated from the measurements obtained at the time of the scan on Day 1 of the study.
description: Comparison of the CMR measure of global perfusion reserve ratio (GPR) in each these patient groups.
In order to calculate this ratio, coronary sinus flow was measured twice:
prior to the the administration of adenosine/regadenoson
during the administration of adenosine/regadenoson
measure: The Association Between Global Perfusion Reserve (GPR) Ratio and Regional Myocardial Scarring.
time frame: Both global perfusion ratio and the presence of regional scarring will be determined/measured from the images obtained during the scan on Day 1 of the study.
description: Relationship between global perfusion reserve ratio and regional myocardial scarring.
arm group label: Hypertrophic cardiomyopathy
arm group type: Active Comparator
arm group label: Non-ischemic dilated cardiomyopathy
arm group type: Active Comparator
arm group label: Control
arm group type: Active Comparator
intervention type: Drug
intervention name: Regadenoson
description: Microvascular disease will be considered present if regional perfusion defects are observed or global perfusion reserve is reduced. For the assessment of microvascular disease, the adenosine and regadenoson groups will be combined, as the medications are considered interchangeable.
arm group label: Control
arm group label: Hypertrophic cardiomyopathy
arm group label: Non-ischemic dilated cardiomyopathy
intervention type: Drug
intervention name: Adenosine
description: Microvascular disease will be considered present if regional perfusion defects are observed or global perfusion reserve is reduced. For the assessment of microvascular disease, the adenosine and regadenoson groups will be combined, as the medications are considered interchangeable.
arm group label: Control
arm group label: Hypertrophic cardiomyopathy
arm group label: Non-ischemic dilated cardiomyopathy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Han Kim
role: Principal Investigator
affiliation: Duke University
facility: 
country: United States
citation: Camici PG, d'Amati G, Rimoldi O. Coronary microvascular dysfunction: mechanisms and functional assessment. Nat Rev Cardiol. 2015 Jan;12(1):48-62. doi: 10.1038/nrcardio.2014.160. Epub 2014 Oct 14.
PMID: 25311229
citation: Klem I, Heitner JF, Shah DJ, Sketch MH Jr, Behar V, Weinsaft J, Cawley P, Parker M, Elliott M, Judd RM, Kim RJ. Improved detection of coronary artery disease by stress perfusion cardiovascular magnetic resonance with the use of delayed enhancement infarction imaging. J Am Coll Cardiol. 2006 Apr 18;47(8):1630-8. doi: 10.1016/j.jacc.2005.10.074. Epub 2006 Mar 27.
PMID: 16631001
citation: Klem I, Greulich S, Heitner JF, Kim H, Vogelsberg H, Kispert EM, Ambati SR, Bruch C, Parker M, Judd RM, Kim RJ, Sechtem U. Value of cardiovascular magnetic resonance stress perfusion testing for the detection of coronary artery disease in women. JACC Cardiovasc Imaging. 2008 Jul;1(4):436-45. doi: 10.1016/j.jcmg.2008.03.010.
PMID: 19356464
citation: Camici PG, Crea F. Coronary microvascular dysfunction. N Engl J Med. 2007 Feb 22;356(8):830-40. doi: 10.1056/NEJMra061889. No abstract available.
PMID: 17314342
citation: Choudhury L, Mahrholdt H, Wagner A, Choi KM, Elliott MD, Klocke FJ, Bonow RO, Judd RM, Kim RJ. Myocardial scarring in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2002 Dec 18;40(12):2156-64. doi: 10.1016/s0735-1097(02)02602-5.
PMID: 12505229
responsible party type: Sponsor
mesh term: Cardiomyopathies
mesh term: Cardiomyopathy, Hypertrophic
mesh term: Cardiomyopathy, Dilated
mesh term: Ischemia
mesh term: Adenosine
mesh term: Regadenoson
sharing ipd: Undecided
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Slow recruitment led to the end of the study.
point of contact: 