Trial Outcomes & Findings for Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve (NCT NCT03249272)

Last Updated: 2020-09-16

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

31 participants

Primary outcome timeframe

The prevalence of MVD will be determined based on the findings at the time of the scan on Day 1 of the study.

Results posted on

2020-09-16

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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 hypertrophic cardiomyopathy patients with MVD by the total number of patients with hypertrophic cardiomyopathy.	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 non-ischemic dilated cardiomyopathy patients with MVD by the total number of patients with non-ischemic dilated cardiomyopathy.	Control 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.
Overall Study STARTED	19	6	6
Overall Study COMPLETED	19	6	6
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Hypertrophic Cardiomyopathy n=19 Participants 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.	Non-ischemic Dilated Cardiomyopathy n=6 Participants 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.	Control Patients n=6 Participants 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 n=31 Participants Total of all reporting groups
Race (NIH/OMB) White	16 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	26 Participants n=4 Participants
Age, Continuous	46.1 years STANDARD_DEVIATION 17.7 • n=5 Participants	60.6 years STANDARD_DEVIATION 12.2 • n=7 Participants	53.2 years STANDARD_DEVIATION 5.7 • n=5 Participants	50.3 years STANDARD_DEVIATION 15.9 • n=4 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	12 Participants n=4 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	19 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	19 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	30 Participants n=4 Participants

PRIMARY outcome

Timeframe: The prevalence of MVD will be determined based on the findings at the time of the scan on Day 1 of the study.

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.

Outcome measures

Outcome measures
Measure	Hypertrophic Cardiomyopathy n=19 Participants 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.	Non-ischemic Dilated Cardiomyopathy n=6 Participants 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.	Control n=5 Participants 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.	Non-ischemic Dilated Cardiomyopathy - Without Scarring Mean value of all patients with Non-ischemic Dilated cardiomyopathy without scarring.	Control - Scarring Mean value of all control patients with scarring.	Control - Without Scarring Mean value of all control patients without scarring.
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.	79 Percentage of group with MVD	33.3 Percentage of group with MVD	20 Percentage of group with MVD	—	—	—

SECONDARY outcome

Timeframe: The global perfusion ratio will be calculated from the measurements obtained at the time of the scan on Day 1 of the study.

Population: As was pre-specified, the regadenoson and adenosine groups were combined for analysis as these interventions are interchangeable.

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

Outcome measures

Outcome measures
Measure	Hypertrophic Cardiomyopathy n=19 Participants 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.	Non-ischemic Dilated Cardiomyopathy n=6 Participants 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.	Control n=5 Participants 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.	Non-ischemic Dilated Cardiomyopathy - Without Scarring Mean value of all patients with Non-ischemic Dilated cardiomyopathy without scarring.	Control - Scarring Mean value of all control patients with scarring.	Control - Without Scarring Mean value of all control patients without scarring.
CMR Measurement of Global Perfusion Reserve Ratio	2.99 ratio Interval 1.87 to 4.65	3.04 ratio Interval 2.64 to 3.61	3.83 ratio Interval 2.42 to 4.34	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Relationship between global perfusion reserve ratio and regional myocardial scarring.