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Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve

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ClinicalTrials.gov Identifier: NCT03249272
Recruitment Status : Terminated (Sponsor withdrew funding)
First Posted : August 15, 2017
Results First Posted : September 16, 2020
Last Update Posted : September 16, 2020
Sponsor:
Information provided by (Responsible Party):
Duke University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Basic Science
Conditions Hypertrophic Cardiomyopathy
Non-ischemic Dilated Cardiomyopathy
Microvascular Ischaemia of Myocardium
Interventions Drug: Regadenoson
Drug: Adenosine
Enrollment 31
Recruitment Details  
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.
Arm/Group Title Hypertrophic Cardiomyopathy Non-ischemic Dilated Cardiomyopathy Control
Hide Arm/Group Description

Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:

  1. Global perfusion reserve (GPR) < 2.0.

    • 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.
  2. The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.

For the analysis of the global perfusion ratio, the regadenson and adenosine groups were combined.

The prevalence will be calculated by dividing the number of hypertrophic cardiomyopathy patients with MVD by the total number of patients with hypertrophic cardiomyopathy.

Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:

  1. Global perfusion reserve (GPR) < 2.0.

    • 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.
  2. The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.

For the analysis of the global perfusion ratio, the regadenson and adenosine groups were combined.

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.

Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:

  1. Global perfusion reserve (GPR) < 2.0.

    • 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.
  2. The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.

For the analysis of the global perfusion ratio, the regadenson and adenosine groups were combined.

The prevalence will be calculated by dividing the number of control patients with MVD by the total number of control patients.

Period Title: Overall Study
Started 19 6 6
Completed 19 6 6
Not Completed 0 0 0
Arm/Group Title Hypertrophic Cardiomyopathy Non-ischemic Dilated Cardiomyopathy Control Patients Total
Hide Arm/Group Description

Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:

  1. Global perfusion reserve (GPR) < 2.0.

    • 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.
  2. The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.

The prevalence will be calculated by dividing the number of hypertrophic cardiomyopathy patients with MVD by the total number of patients with hypertrophic cardiomyopathy.

Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:

  1. Global perfusion reserve (GPR) < 2.0.

    • 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.
  2. The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.

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.

Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:

  1. Global perfusion reserve (GPR) < 2.0.

    • 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.
  2. The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.

The prevalence will be calculated by dividing the number of control patients with MVD by the total number of control patients.

Total of all reporting groups
Overall Number of Baseline Participants 19 6 6 31
Hide Baseline Analysis Population Description
As was pre-specified, the regadenoson and adenosine groups were combined for analysis as these interventions are interchangeable.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants 6 participants 6 participants 31 participants
46.1  (17.7) 60.6  (12.2) 53.2  (5.7) 50.3  (15.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 6 participants 6 participants 31 participants
Female
5
  26.3%
2
  33.3%
5
  83.3%
12
  38.7%
Male
14
  73.7%
4
  66.7%
1
  16.7%
19
  61.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 6 participants 6 participants 31 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   5.3%
0
   0.0%
0
   0.0%
1
   3.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
  10.5%
1
  16.7%
1
  16.7%
4
  12.9%
White
16
  84.2%
5
  83.3%
5
  83.3%
26
  83.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 19 participants 6 participants 6 participants 31 participants
19
 100.0%
5
  83.3%
6
 100.0%
30
  96.8%
1.Primary Outcome
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.
Hide 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:

  1. prior to the the administration of adenosine/regadenoson
  2. 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.

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.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Hypertrophic Cardiomyopathy Non-ischemic Dilated Cardiomyopathy Control
Hide Arm/Group Description:

Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:

  1. Global perfusion reserve (GPR) < 2.0.

    • 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.
  2. The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.

The prevalence will be calculated by dividing the number of hypertrophic cardiomyopathy patients with MVD by the total number of patients with hypertrophic cardiomyopathy.

Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:

  1. Global perfusion reserve (GPR) < 2.0.

    • 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.
  2. The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.

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.

Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:

  1. Global perfusion reserve (GPR) < 2.0.

    • 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.
  2. The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.

The prevalence will be calculated by dividing the number of control patients with MVD by the total number of control patients.

Overall Number of Participants Analyzed 19 6 5
Measure Type: Number
Unit of Measure: Percentage of group with MVD
79 33.3 20
2.Secondary Outcome
Title CMR Measurement of Global Perfusion Reserve Ratio
Hide 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:

  1. prior to the the administration of adenosine/regadenoson
  2. during the administration of adenosine/regadenoson
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.
Hide Outcome Measure Data
Hide Analysis Population Description
As was pre-specified, the regadenoson and adenosine groups were combined for analysis as these interventions are interchangeable.
Arm/Group Title Hypertrophic Cardiomyopathy Non-ischemic Dilated Cardiomyopathy Control
Hide Arm/Group Description:
Global perfusion reserve
Global perfusion reserve
Global perfusion reserve
Overall Number of Participants Analyzed 19 6 5
Median (Inter-Quartile Range)
Unit of Measure: ratio
2.99
(1.87 to 4.65)
3.04
(2.64 to 3.61)
3.83
(2.42 to 4.34)
3.Secondary Outcome
Title The Association Between Global Perfusion Reserve (GPR) Ratio and Regional Myocardial Scarring.
Hide Description Relationship between global perfusion reserve 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.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Hypertrophic Cardiomyopathy - Scarring Hypertrophic Cardiomyopathy - Without Scarring Non-ischemic Dilated Cardiomyopathy - Scarring Non-ischemic Dilated Cardiomyopathy - Without Scarring Control - Scarring Control - Without Scarring
Hide Arm/Group Description:
Mean value of all patients with Hypertrophic cardiomyopathy with scarring.
Mean value of all patients with Hypertrophic cardiomyopathy without scarring.
Mean value of all patients with Non-ischemic Dilated cardiomyopathy with scarring.
Mean value of all patients with Non-ischemic Dilated cardiomyopathy without scarring.
Mean value of all control patients with scarring.
Mean value of all control patients without scarring.
Overall Number of Participants Analyzed 15 4 6 0 0 5
Mean (Standard Deviation)
Unit of Measure: Global perfusion reserve ratio
3.19  (1.71) 5.91  (4.09) 3.16  (0.65) 3.53  (1.26)
Time Frame Adverse events were assessed during the time of the MR scan.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Hypertrophic Cardiomyopathy - Adenosine Hypertrophic Cardiomyopathy - Regadenoson Non-ischemic Dilated Cardiomyopathy - Adenosine Non-ischemic Dilated Cardiomyopathy - Regadenoson Control - Adenosine Control - Regadenoson
Hide Arm/Group Description

Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:

  1. Global perfusion reserve (GPR) < 2.0.

    • 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.
  2. The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.

The prevalence will be calculated by dividing the number of hypertrophic cardiomyopathy patients with MVD by the total number of patients with hypertrophic cardiomyopathy.

Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:

  1. Global perfusion reserve (GPR) < 2.0.

    • 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.
  2. The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.

The prevalence will be calculated by dividing the number of hypertrophic cardiomyopathy patients with MVD by the total number of patients with hypertrophic cardiomyopathy.

Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:

  1. Global perfusion reserve (GPR) < 2.0.

    • 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.
  2. The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.

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.

Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:

  1. Global perfusion reserve (GPR) < 2.0.

    • 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.
  2. The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.

The prevalence will be calculated by dividing the number of hypertrophic cardiomyopathy patients with MVD by the total number of patients with hypertrophic cardiomyopathy.

Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:

  1. Global perfusion reserve (GPR) < 2.0.

    • 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.
  2. The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.

The prevalence will be calculated by dividing the number of control patients with MVD by the total number of control patients.

Microvascular dysfunction (MVD) will be categorized as present based upon the presence of one of the following:

  1. Global perfusion reserve (GPR) < 2.0.

    • 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.
  2. The presence of regional perfusion abnormalities on visual assessment of first pass perfusion images.

The prevalence will be calculated by dividing the number of hypertrophic cardiomyopathy patients with MVD by the total number of patients with hypertrophic cardiomyopathy.

All-Cause Mortality
Hypertrophic Cardiomyopathy - Adenosine Hypertrophic Cardiomyopathy - Regadenoson Non-ischemic Dilated Cardiomyopathy - Adenosine Non-ischemic Dilated Cardiomyopathy - Regadenoson Control - Adenosine Control - Regadenoson
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/9 (0.00%)   0/2 (0.00%)   0/4 (0.00%)   0/3 (0.00%)   0/3 (0.00%) 
Hide Serious Adverse Events
Hypertrophic Cardiomyopathy - Adenosine Hypertrophic Cardiomyopathy - Regadenoson Non-ischemic Dilated Cardiomyopathy - Adenosine Non-ischemic Dilated Cardiomyopathy - Regadenoson Control - Adenosine Control - Regadenoson
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/9 (0.00%)   0/2 (0.00%)   0/4 (0.00%)   0/3 (0.00%)   0/3 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Hypertrophic Cardiomyopathy - Adenosine Hypertrophic Cardiomyopathy - Regadenoson Non-ischemic Dilated Cardiomyopathy - Adenosine Non-ischemic Dilated Cardiomyopathy - Regadenoson Control - Adenosine Control - Regadenoson
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/9 (0.00%)   0/2 (0.00%)   0/4 (0.00%)   0/3 (0.00%)   0/3 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Han Kim, MD
Organization: Duke Cardiovascular Magnetic Resonance Center
Phone: 9196683539
EMail: han.kim@duke.edu
Layout table for additonal information
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT03249272    
Other Study ID Numbers: Pro00082447
First Submitted: August 8, 2017
First Posted: August 15, 2017
Results First Submitted: March 6, 2020
Results First Posted: September 16, 2020
Last Update Posted: September 16, 2020