Coronary Artery Disease
Conditions
Brief summary
The purpose of this study is to measure the changes in cardiac function during a Lexiscan pharmacologic stress test using cardiac magnetic resonance imaging test.
Interventions
DRUGRegadenoson
Regadenoson injection is a pharmacologic stress agent indicated for radionuclide myocardial perfusion imaging.
Sponsors
Saint Luke's Health System
Saint Luke's Cardiovascular Consultants
Timothy M. Bateman
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 90 Years
Healthy volunteers
Yes
Inclusion criteria
* Myocardial rest/regadenoson stress perfusion PET study within 60 days * Normal rest LVEF (greater than or equal to 50%) * No change in symptoms or treatment between the PET and the MRI study * Willing to consent to the study * Male or female who is either post-menopausal, surgically sterile, or if has a childbearing potential, a negative pregnancy test within 2 days prior to the MRI study.
Exclusion criteria
* Renal dysfunction (estimated glomerular filtration rate \< 60 mL/min/1.73m2) within 6 months * Metallic implants, pacemaker, blood vessel clip (contra-indicated for MRI) * Patient size exceeds MRI bore/table limits: (Max body diameter \> 60 cm, weight \> 136 kg) * History of gadolinium contrast allergy or intolerance * Second or third degree AV block * Sinus node dysfunction * Acute myocardial infarction (past 3 months) * Actively wheezing or with acute asthma or bronchospastic attacks requiring changes in therapy within the past 30 days * Patients that have experienced a previous hypersensitivity reaction thought to be related to regadenoson
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| RADIAL STRAIN | Day 1 | A measurement of the relative displacement between myocardial points between end-diastole and end-systole along a common ray extending from the center of the left ventricular (LV) cavity (analogous to myocardial thickening). A normal radial strain is indicated by a positive decimal value and can be understood as the percentage change in wall thickness of a myocardial segment. A POSITIVE change in radial strain indicates an increase in wall thickening. Because strain is a measurement in change in length (distance) divided by an original length (distance) it is considered unitless. |
| CIRCUMFERENTIAL STRAIN | Day 1 | A measurement of the relative displacement of myocardial points directed along the circumference of the ventricular wall at a given radial distance from the left ventricular (LV) cavity center (e.g. midline). A normal circumferential strain is indicated by a negative decimal value and can be understood as the percentage shortening along the ventricular wall with a greater negative value indicating greater ventricular shortening along the circumference. A positive change in strain would therefore be interpreted as a decrease in circumferential shortening. Because strain is a measurement in change in length (distance) divided by an original length (distance) it is considered unitless. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Late Gadolinium Enhancement (LGE) and RADIAL Myocardial Strain | Day 1 | For each subject, the 16-segments were visually assessed along the short-axis plane for the presence of LGE. These images were collected post regadenoson stress recovery using an inversion-recovery prepared, fast gradient echo sequence and a delay of at least 8 minutes after administration of a single dose of gadobenate dimeglumine. The presence of LGE within a segment is a separate classification of segment type. The segment classifications in the other outcomes are determined from the prior positron-emission-tomography (PET) examination where the LGE determination is based solely on cardiac magnetic resonance (CMR) imaging collected data. The measurement was performed to determine if the presence of LGE within a particular segment affect the resulting strain? |
| Adverse Events | Day 1 | Adverse events were monitored and recorded on a specific Adverse Event (AE) log. |
| Late Gadolinium Enhancement and CIRCUMFERENTIAL Myocardial Strain | Day 1 | The Effects of the presence of LGE on CIRCUMFERENTIAL myocardial Strain |
Countries
United States
Participant flow
Recruitment details
All subjects were recruited from two groups: a population with coronary artery disease (CAD) of those with low-likelihood-CAD (Control). The myocardial segment perfusion and wall motion scores from the prior clinical positron-emission-tomography (PET) were used to classify segments as one of the following: CONTROL, CAD\_REMOTE, CAD\_REVERSIBLE.
Pre-assignment details
Cardiac Magnetic Resonance (CMR) imaging was performed in the same order for all subjects with rest imaging preceding regadenoson stress imaging. The same prescription for tagged CMR slice locations (basal, mid, and apical) were used at both rest and stress.
Participants by arm
| Arm | Count |
|---|---|
| CONTROL Myocardial strain imaging was performed for all subjects in a similar order. Rest-tag imaging was performed first, then Stress-tag imaging was performed at maximal heart rate following administration of the regadenoson dose.
Strain values were then calculated for each of 16-segments for each subject. Segments are classified based on myocardial perfusion imaging scores.
A control subject is an individual from a low-likelihood CAD population with a prior clinically indicated PET with perfusion and wall motion scores (rest-to-stress). | 13 |
| Coronary Artery Disease Myocardial strain imaging was performed for all subjects in a similar order. Rest-tag imaging was performed first, then Stress-tag imaging was performed at maximal heart rate following administration of the regadenoson dose.
Strain values were then calculated for each of 16-segments for each subject. Segments are classified based on myocardial perfusion imaging scores.
A Coronary artery disease subject is an individual from a CAD population with a prior clinically indicated PET with perfusion and wall motion scores (rest-to-stress). | 23 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Safety Screening | 2 | 2 |
Baseline characteristics
| Characteristic | CONTROL | Coronary Artery Disease | Total |
|---|---|---|---|
| Age, Continuous | 55 years STANDARD_DEVIATION 10 | 72 years STANDARD_DEVIATION 9 | 66 years STANDARD_DEVIATION 12 |
| BMI | 32 kg/m^2 STANDARD_DEVIATION 6 | 31 kg/m^2 STANDARD_DEVIATION 6 | 31 kg/m^2 STANDARD_DEVIATION 6 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 9 Participants | 7 Participants | 16 Participants |
| Sex: Female, Male Male | 4 Participants | 16 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 36 |
| other Total, other adverse events | 29 / 36 |
| serious Total, serious adverse events | 0 / 36 |
Outcome results
Primary
CIRCUMFERENTIAL STRAIN
A measurement of the relative displacement of myocardial points directed along the circumference of the ventricular wall at a given radial distance from the left ventricular (LV) cavity center (e.g. midline). A normal circumferential strain is indicated by a negative decimal value and can be understood as the percentage shortening along the ventricular wall with a greater negative value indicating greater ventricular shortening along the circumference. A positive change in strain would therefore be interpreted as a decrease in circumferential shortening. Because strain is a measurement in change in length (distance) divided by an original length (distance) it is considered unitless.
Time frame: Day 1
Population: Myocardial segments from the population groups according to the AHA 16-segment model and classified according to PET perfusion and wall motion scores.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CONTROL | CIRCUMFERENTIAL STRAIN | REGADENSOSON STRESS | -0.169 strain (unitless) | Standard Deviation 0.059 |
| CONTROL | CIRCUMFERENTIAL STRAIN | REST | -0.181 strain (unitless) | Standard Deviation 0.056 |
| CONTROL | CIRCUMFERENTIAL STRAIN | REST-to-STRESS CHANGE | 0.012 strain (unitless) | Standard Deviation 0.065 |
| CAD_REMOTE | CIRCUMFERENTIAL STRAIN | REGADENSOSON STRESS | -0.150 strain (unitless) | Standard Deviation 0.053 |
| CAD_REMOTE | CIRCUMFERENTIAL STRAIN | REST | -0.140 strain (unitless) | Standard Deviation 0.057 |
| CAD_REMOTE | CIRCUMFERENTIAL STRAIN | REST-to-STRESS CHANGE | -0.013 strain (unitless) | Standard Deviation 0.051 |
| CAD_REVERSIBLE | CIRCUMFERENTIAL STRAIN | REST | -0.121 strain (unitless) | Standard Deviation 0.054 |
| CAD_REVERSIBLE | CIRCUMFERENTIAL STRAIN | REST-to-STRESS CHANGE | -0.006 strain (unitless) | Standard Deviation 0.051 |
| CAD_REVERSIBLE | CIRCUMFERENTIAL STRAIN | REGADENSOSON STRESS | -0.126 strain (unitless) | Standard Deviation 0.066 |
Comparison: Rest VS Regadenoson Stressp-value: 0.011paired, t-test
Comparison: Rest VS Regadenoson Stressp-value: 0.003paired t-test
Comparison: Rest VS Regadenoson Stressp-value: 0.39paired, t-test
Comparison: RESTp-value: <0t-test, 2 sided
Comparison: RESTp-value: <0t-test, 2 sided
Comparison: RESTp-value: 0.022t-test, 2 sided
Comparison: Regadenoson STRESSp-value: 0.001t-test, 2 sided
Comparison: Regadenoson STRESSp-value: <0t-test, 2 sided
Comparison: Regadenoson STRESSp-value: 0.006t-test, 2 sided
Comparison: REST-TO-STRESS Changep-value: <0t-test, 2 sided
Comparison: REST-TO-STRESS Changesp-value: 0.058t-test, 2 sided
Comparison: REST-TO-STRESS Changep-value: 0.31t-test, 2 sided
Primary
RADIAL STRAIN
A measurement of the relative displacement between myocardial points between end-diastole and end-systole along a common ray extending from the center of the left ventricular (LV) cavity (analogous to myocardial thickening). A normal radial strain is indicated by a positive decimal value and can be understood as the percentage change in wall thickness of a myocardial segment. A POSITIVE change in radial strain indicates an increase in wall thickening. Because strain is a measurement in change in length (distance) divided by an original length (distance) it is considered unitless.
Time frame: Day 1
Population: Myocardial segments classified according to subject groups and myocardial perfusion and wall motion scores on prior positron-emission-tomography (PET).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CONTROL | RADIAL STRAIN | REGADENOSON STRESS | 0.190 unitless (strain) | Standard Deviation 0.113 |
| CONTROL | RADIAL STRAIN | REST | 0.158 unitless (strain) | Standard Deviation 0.1 |
| CONTROL | RADIAL STRAIN | REST-to-STRESS CHANGE | 0.033 unitless (strain) | Standard Deviation 0.137 |
| CAD_REMOTE | RADIAL STRAIN | REGADENOSON STRESS | 0.167 unitless (strain) | Standard Deviation 0.104 |
| CAD_REMOTE | RADIAL STRAIN | REST | 0.149 unitless (strain) | Standard Deviation 0.098 |
| CAD_REMOTE | RADIAL STRAIN | REST-to-STRESS CHANGE | 0.022 unitless (strain) | Standard Deviation 0.107 |
| CAD_REVERSIBLE | RADIAL STRAIN | REST | 0.150 unitless (strain) | Standard Deviation 0.094 |
| CAD_REVERSIBLE | RADIAL STRAIN | REST-to-STRESS CHANGE | -0.009 unitless (strain) | Standard Deviation 0.099 |
| CAD_REVERSIBLE | RADIAL STRAIN | REGADENOSON STRESS | 0.141 unitless (strain) | Standard Deviation 0.085 |
Comparison: REST-TO-REGADENOSON STRESSp-value: 0.001paired, t-test
Comparison: REST-TO-REGADENOSON STRESSp-value: 0.017paired, t-test
Comparison: REST-TO-REGADENOSON STRESSp-value: 0.495paired, t-test
Comparison: RESTp-value: 0.365t-test, 2 sided
Comparison: RESTp-value: 0.602t-test, 2 sided
Comparison: RESTp-value: 0.915t-test, 2 sided
Comparison: Regadenoson STRESSp-value: 0.033t-test, 2 sided
Comparison: Regadenoson STRESSp-value: 0.002t-test, 2 sided
Comparison: Regadenoson STRESSp-value: 0.087t-test, 2 sided
Comparison: REST-TO-STRESS CHANGEp-value: 0.399t-test, 2 sided
Comparison: REST-TO-STRESS Changep-value: 0.03t-test, 2 sided
Comparison: REST-TO-STRESS Changep-value: 0.048t-test, 2 sided
Secondary
Adverse Events
Adverse events were monitored and recorded on a specific Adverse Event (AE) log.
Time frame: Day 1
Population: Count of Adverse Events not clinically expect and reportable to IRB.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CONTROL | Adverse Events | No Adverse Events | 7 Participants |
| CONTROL | Adverse Events | Adverse Events | 29 Participants |
| CONTROL | Adverse Events | Serious Adverse Events | 0 Participants |
Secondary
Late Gadolinium Enhancement and CIRCUMFERENTIAL Myocardial Strain
The Effects of the presence of LGE on CIRCUMFERENTIAL myocardial Strain
Time frame: Day 1
Population: LGE as determined by CMR imaging using the AHA 16 segment model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CONTROL | Late Gadolinium Enhancement and CIRCUMFERENTIAL Myocardial Strain | REST-to-STRESS | 0.012 strain (unitless) | Standard Deviation 0.066 |
| CONTROL | Late Gadolinium Enhancement and CIRCUMFERENTIAL Myocardial Strain | REGADENOSON STRESS | -0.169 strain (unitless) | Standard Deviation 0.059 |
| CONTROL | Late Gadolinium Enhancement and CIRCUMFERENTIAL Myocardial Strain | REST | -0.181 strain (unitless) | Standard Deviation 0.057 |
| CAD_REMOTE | Late Gadolinium Enhancement and CIRCUMFERENTIAL Myocardial Strain | REST-to-STRESS | -0.011 strain (unitless) | Standard Deviation 0.046 |
| CAD_REMOTE | Late Gadolinium Enhancement and CIRCUMFERENTIAL Myocardial Strain | REST | -0.139 strain (unitless) | Standard Deviation 0.052 |
| CAD_REMOTE | Late Gadolinium Enhancement and CIRCUMFERENTIAL Myocardial Strain | REGADENOSON STRESS | -0.150 strain (unitless) | Standard Deviation 0.052 |
| CAD_REVERSIBLE | Late Gadolinium Enhancement and CIRCUMFERENTIAL Myocardial Strain | REGADENOSON STRESS | -0.111 strain (unitless) | Standard Deviation 0.051 |
| CAD_REVERSIBLE | Late Gadolinium Enhancement and CIRCUMFERENTIAL Myocardial Strain | REST | -0.101 strain (unitless) | Standard Deviation 0.063 |
| CAD_REVERSIBLE | Late Gadolinium Enhancement and CIRCUMFERENTIAL Myocardial Strain | REST-to-STRESS | -0.010 strain (unitless) | Standard Deviation 0.051 |
Comparison: REST vs STRESSp-value: 0.008paired, t-test
Comparison: REST vs STRESSp-value: 0.006paired, t-test
Comparison: REST vs STRESSp-value: 0.428paired, t-test
Comparison: RESTp-value: <0t-test, 2 sided
Comparison: RESTp-value: <0t-test, 2 sided
Comparison: RESTp-value: 0.006t-test, 2 sided
Comparison: Regadenoson STRESSp-value: 0.002t-test, 2 sided
Comparison: Regadenoson STRESSp-value: <0t-test, 2 sided
Comparison: Regadenoson STRESSp-value: 0.004t-test, 2 sided
Comparison: REST-to-STRESS Changep-value: <0t-test, 2 sided
Comparison: REST-to-STRESS Changep-value: 0.172t-test, 2 sided
Comparison: REST-to-STRESS Changep-value: 0.957t-test, 2 sided
Secondary
Late Gadolinium Enhancement (LGE) and RADIAL Myocardial Strain
For each subject, the 16-segments were visually assessed along the short-axis plane for the presence of LGE. These images were collected post regadenoson stress recovery using an inversion-recovery prepared, fast gradient echo sequence and a delay of at least 8 minutes after administration of a single dose of gadobenate dimeglumine. The presence of LGE within a segment is a separate classification of segment type. The segment classifications in the other outcomes are determined from the prior positron-emission-tomography (PET) examination where the LGE determination is based solely on cardiac magnetic resonance (CMR) imaging collected data. The measurement was performed to determine if the presence of LGE within a particular segment affect the resulting strain?
Time frame: Day 1
Population: LGE imaging by CMR was acquired only in subjects meeting GFR restrictions.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CONTROL | Late Gadolinium Enhancement (LGE) and RADIAL Myocardial Strain | REGADENOSON STRESS | 0.190 strain (unitless) | Standard Deviation 0.113 |
| CONTROL | Late Gadolinium Enhancement (LGE) and RADIAL Myocardial Strain | REST | 0.157 strain (unitless) | Standard Deviation 0.1 |
| CONTROL | Late Gadolinium Enhancement (LGE) and RADIAL Myocardial Strain | REST-to_STRESS | 0.032 strain (unitless) | Standard Deviation 0.136 |
| CAD_REMOTE | Late Gadolinium Enhancement (LGE) and RADIAL Myocardial Strain | REGADENOSON STRESS | 0.185 strain (unitless) | Standard Deviation 0.107 |
| CAD_REMOTE | Late Gadolinium Enhancement (LGE) and RADIAL Myocardial Strain | REST | 0.155 strain (unitless) | Standard Deviation 0.097 |
| CAD_REMOTE | Late Gadolinium Enhancement (LGE) and RADIAL Myocardial Strain | REST-to_STRESS | 0.031 strain (unitless) | Standard Deviation 0.116 |
| CAD_REVERSIBLE | Late Gadolinium Enhancement (LGE) and RADIAL Myocardial Strain | REST | 0.140 strain (unitless) | Standard Deviation 0.074 |
| CAD_REVERSIBLE | Late Gadolinium Enhancement (LGE) and RADIAL Myocardial Strain | REST-to_STRESS | -0.008 strain (unitless) | Standard Deviation 0.089 |
| CAD_REVERSIBLE | Late Gadolinium Enhancement (LGE) and RADIAL Myocardial Strain | REGADENOSON STRESS | 0.132 strain (unitless) | Standard Deviation 0.091 |
Comparison: REST vs STRESSp-value: 0.001paired, t-test
Comparison: REST vs STRESSp-value: 0.002paired, t-test
Comparison: REST vs STRESSp-value: 0.721paired, t-test
Comparison: RESTp-value: 0.797t-test, 2 sided
Comparison: RESTp-value: 0.474t-test, 2 sided
p-value: 0.537t-test, 2 sided
Comparison: Regadenoson STRESSp-value: 0.717t-test, 2 sided
Comparison: Regadenoson STRESSp-value: 0.041t-test, 2 sided
Comparison: Regadenoson STRESSp-value: 0.05t-test, 2 sided
Comparison: REST-to-STRESS Changep-value: 0.908t-test, 2 sided
p-value: 0.233t-test, 2 sided
Comparison: REST-to-STRESS Changep-value: 0.187t-test, 2 sided