Trial Outcomes & Findings for Characterization of Changes in Ventricular Mechanics in Response to Lexiscan Stress Using Tagged Cine Cardiac Magnetic Resonance Imaging (NCT NCT02115308)

NCT ID: NCT02115308

Last Updated: 2018-09-19

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

40 participants

Primary outcome timeframe

Day 1

Results posted on

2018-09-19

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure
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 population of low-likelihood CAD exhibiting both normal perfusion score and normal wall motion score rest-to-stress as indicated on a clinically indicated PET.
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 (CAD) subject is an individual from a population with CAD exhibiting both normal perfusion and normal wall motion scores (rest-to-stress) on a prior clinically indicated PET.
Overall Study
STARTED
15
25
Overall Study
COMPLETED
13
23
Overall Study
NOT COMPLETED
2
2

Reasons for withdrawal

Reasons for withdrawal
Measure
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 population of low-likelihood CAD exhibiting both normal perfusion score and normal wall motion score rest-to-stress as indicated on a clinically indicated PET.
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 (CAD) subject is an individual from a population with CAD exhibiting both normal perfusion and normal wall motion scores (rest-to-stress) on a prior clinically indicated PET.
Overall Study
Safety Screening
2
2

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
CONTROL
n=13 Participants
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).
Coronary Artery Disease
n=23 Participants
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).
Total
n=36 Participants
Total of all reporting groups
Age, Continuous
55 years
STANDARD_DEVIATION 10 • n=13 Participants
72 years
STANDARD_DEVIATION 9 • n=23 Participants
66 years
STANDARD_DEVIATION 12 • n=36 Participants
Sex: Female, Male
Female
9 Participants
n=13 Participants
7 Participants
n=23 Participants
16 Participants
n=36 Participants
Sex: Female, Male
Male
4 Participants
n=13 Participants
16 Participants
n=23 Participants
20 Participants
n=36 Participants
Race and Ethnicity Not Collected
0 Participants
Race and Ethnicity were not collected from any participant.
BMI
32 kg/m^2
STANDARD_DEVIATION 6 • n=13 Participants
31 kg/m^2
STANDARD_DEVIATION 6 • n=23 Participants
31 kg/m^2
STANDARD_DEVIATION 6 • n=36 Participants

PRIMARY outcome

Timeframe: Day 1

Population: Myocardial segments classified according to subject groups and myocardial perfusion and wall motion scores on prior positron-emission-tomography (PET).

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.

Outcome measures

Outcome measures
Measure
CONTROL
n=203 myocardial segments
A myocardial segment from an individual from a low-likelihood coronary-artery-disease (CAD) population exhibiting both normal perfusion and normal wall motion scores (rest-to-stress) on a prior clinically indicated PET.
CAD_REMOTE
n=159 myocardial segments
A myocardial segment from an individual from a population with CAD exhibiting normal perfusion scores and normal wall motion scores (rest-to-stress) on a prior clinically indicated PET.
CAD_REVERSIBLE
n=60 myocardial segments
A myocardial segment from an individual from a population with CAD exhibiting a change in perfusion scores and a change in wall motion scores (rest-to-stress) on a prior clinically indicated PET.
RADIAL STRAIN
REST
0.158 unitless (strain)
Standard Deviation 0.100
0.149 unitless (strain)
Standard Deviation 0.098
0.150 unitless (strain)
Standard Deviation 0.094
RADIAL STRAIN
REGADENOSON STRESS
0.190 unitless (strain)
Standard Deviation 0.113
0.167 unitless (strain)
Standard Deviation 0.104
0.141 unitless (strain)
Standard Deviation 0.085
RADIAL STRAIN
REST-to-STRESS CHANGE
0.033 unitless (strain)
Standard Deviation 0.137
0.022 unitless (strain)
Standard Deviation 0.107
-0.009 unitless (strain)
Standard Deviation 0.099

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
CONTROL
n=203 myocardial segments
A myocardial segment from an individual from a low-likelihood coronary-artery-disease (CAD) population exhibiting both normal perfusion and normal wall motion scores (rest-to-stress) on a prior clinically indicated PET.
CAD_REMOTE
n=159 myocardial segments
A myocardial segment from an individual from a population with CAD exhibiting normal perfusion scores and normal wall motion scores (rest-to-stress) on a prior clinically indicated PET.
CAD_REVERSIBLE
n=60 myocardial segments
A myocardial segment from an individual from a population with CAD exhibiting a change in perfusion scores and a change in wall motion scores (rest-to-stress) on a prior clinically indicated PET.
CIRCUMFERENTIAL STRAIN
REST
-0.181 strain (unitless)
Standard Deviation 0.056
-0.140 strain (unitless)
Standard Deviation 0.057
-0.121 strain (unitless)
Standard Deviation 0.054
CIRCUMFERENTIAL STRAIN
REGADENSOSON STRESS
-0.169 strain (unitless)
Standard Deviation 0.059
-0.150 strain (unitless)
Standard Deviation 0.053
-0.126 strain (unitless)
Standard Deviation 0.066
CIRCUMFERENTIAL STRAIN
REST-to-STRESS CHANGE
0.012 strain (unitless)
Standard Deviation 0.065
-0.013 strain (unitless)
Standard Deviation 0.051
-0.006 strain (unitless)
Standard Deviation 0.051

SECONDARY outcome

Timeframe: Day 1

Population: LGE imaging by CMR was acquired only in subjects meeting GFR restrictions.

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?

Outcome measures

Outcome measures
Measure
CONTROL
n=208 Myocardial Segments
A myocardial segment from an individual from a low-likelihood coronary-artery-disease (CAD) population exhibiting both normal perfusion and normal wall motion scores (rest-to-stress) on a prior clinically indicated PET.
CAD_REMOTE
n=143 Myocardial Segments
A myocardial segment from an individual from a population with CAD exhibiting normal perfusion scores and normal wall motion scores (rest-to-stress) on a prior clinically indicated PET.
CAD_REVERSIBLE
n=17 Myocardial Segments
A myocardial segment from an individual from a population with CAD exhibiting a change in perfusion scores and a change in wall motion scores (rest-to-stress) on a prior clinically indicated PET.
Late Gadolinium Enhancement (LGE) and RADIAL Myocardial Strain
REST
0.157 strain (unitless)
Standard Deviation 0.100
0.155 strain (unitless)
Standard Deviation 0.097
0.140 strain (unitless)
Standard Deviation 0.074
Late Gadolinium Enhancement (LGE) and RADIAL Myocardial Strain
REGADENOSON STRESS
0.190 strain (unitless)
Standard Deviation 0.113
0.185 strain (unitless)
Standard Deviation 0.107
0.132 strain (unitless)
Standard Deviation 0.091
Late Gadolinium Enhancement (LGE) and RADIAL Myocardial Strain
REST-to_STRESS
0.032 strain (unitless)
Standard Deviation 0.136
0.031 strain (unitless)
Standard Deviation 0.116
-0.008 strain (unitless)
Standard Deviation 0.089

SECONDARY outcome

Timeframe: Day 1

Population: Count of Adverse Events not clinically expect and reportable to IRB.

Adverse events were monitored and recorded on a specific Adverse Event (AE) log.

Outcome measures

Outcome measures
Measure
CONTROL
n=36 Participants
A myocardial segment from an individual from a low-likelihood coronary-artery-disease (CAD) population exhibiting both normal perfusion and normal wall motion scores (rest-to-stress) on a prior clinically indicated PET.
CAD_REMOTE
A myocardial segment from an individual from a population with CAD exhibiting normal perfusion scores and normal wall motion scores (rest-to-stress) on a prior clinically indicated PET.
CAD_REVERSIBLE
A myocardial segment from an individual from a population with CAD exhibiting a change in perfusion scores and a change in wall motion scores (rest-to-stress) on a prior clinically indicated PET.
Adverse Events
No Adverse Events
7 Participants
Adverse Events
Adverse Events
29 Participants
Adverse Events
Serious Adverse Events
0 Participants

SECONDARY outcome

Timeframe: Day 1

Population: LGE as determined by CMR imaging using the AHA 16 segment model.

The Effects of the presence of LGE on CIRCUMFERENTIAL myocardial Strain

Outcome measures

Outcome measures
Measure
CONTROL
n=208 Myocardial Segments
A myocardial segment from an individual from a low-likelihood coronary-artery-disease (CAD) population exhibiting both normal perfusion and normal wall motion scores (rest-to-stress) on a prior clinically indicated PET.
CAD_REMOTE
n=143 Myocardial Segments
A myocardial segment from an individual from a population with CAD exhibiting normal perfusion scores and normal wall motion scores (rest-to-stress) on a prior clinically indicated PET.
CAD_REVERSIBLE
n=17 Myocardial Segments
A myocardial segment from an individual from a population with CAD exhibiting a change in perfusion scores and a change in wall motion scores (rest-to-stress) on a prior clinically indicated PET.
Late Gadolinium Enhancement and CIRCUMFERENTIAL Myocardial Strain
REST
-0.181 strain (unitless)
Standard Deviation 0.057
-0.139 strain (unitless)
Standard Deviation 0.052
-0.101 strain (unitless)
Standard Deviation 0.063
Late Gadolinium Enhancement and CIRCUMFERENTIAL Myocardial Strain
REGADENOSON STRESS
-0.169 strain (unitless)
Standard Deviation 0.059
-0.150 strain (unitless)
Standard Deviation 0.052
-0.111 strain (unitless)
Standard Deviation 0.051
Late Gadolinium Enhancement and CIRCUMFERENTIAL Myocardial Strain
REST-to-STRESS
0.012 strain (unitless)
Standard Deviation 0.066
-0.011 strain (unitless)
Standard Deviation 0.046
-0.010 strain (unitless)
Standard Deviation 0.051

Adverse Events

Regadenoson

Serious events: 0 serious events
Other events: 29 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Regadenoson
n=36 participants at risk
Regadenoson is a single-use, pre-filled syringe containing 0.4 mg/5 mL of regadenoson. Regadenoson: Regadenoson injection is a pharmacologic stress agent indicated for radionuclide myocardial perfusion imaging. Strain imaging was performed on ALL subjects in the same order with resting strain preceding regadenoson stress strain. Myocardial segments were classified based on prior clinical positron-emission-tomography (PET) results so that segmental strain response to regadenoson could be observed.
General disorders
Dyspnea
30.6%
11/36 • Day 1
General disorders
Chest Discomfort
27.8%
10/36 • Day 1
General disorders
Headache
22.2%
8/36 • Day 1
General disorders
Flushing
19.4%
7/36 • Day 1
Gastrointestinal disorders
Abdominal: ache/discomfort
16.7%
6/36 • Day 1
Gastrointestinal disorders
Nausea
13.9%
5/36 • Day 1
General disorders
Numbness: Jaw/shoulder
11.1%
4/36 • Day 1
General disorders
Anxiety
8.3%
3/36 • Day 1
Cardiac disorders
Palpitations
5.6%
2/36 • Day 1

Additional Information

Joseph Soltys, PhD

Cardiovascular Imaging Technologies, LLC

Phone: 816-531-2842

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place