Rapid Stress/Rest Single-Day Tc-99m Sestamibi Myocardial Single Photon Emission Computed Tomography
Study Details
Study Description
Brief Summary
This protocol details a novel myocardial perfusion Single Photon Emission Computed Tomography (SPECT) protocol wherein patients receive a low-dose (6 mCi) of Tc-99m sestamibi during exercise or regadenoson pharmacologic stress and undergo a full-time SPECT acquisition processed with Wide Beam Reconstruction (WBR). Immediately thereafter patients receive a high-dose (30-35 mCi) of Tc-99m sestamibi at rest and undergo a half-time rest scan, also processed with WBR. All enrolled research subjects will undergo both the initial stress and subsequent rest scan.
The radiation exposure associated with this new stress/rest protocol is equivalent to that of the conventional rest/stress protocol presently in routine clinical uses at SLRHC.
Eventually, when and if this novel stress/rest protocol is adopted in routine clinical practice, patients with normal stress scans would receive only 6 mCi of Tc-99m sestamibi (331 mSv in men, 241 mSv in women) and spend only approximately one hour in the Nuclear Medicine Laboratory.
All patients presenting to the Nuclear Medicine Laboratory for evaluation of known or suspected coronary artery disease will be candidates for enrollment. Fifty patients undergoing treadmill exercise stress and 50 patients undergoing regadenoson pharmacologic stress will be enrolled. Pregnant and breast-feeding patients will not be eligible.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
Specific Aims:
To validate acceptable image quality and the stress/rest myocardial count density ratio (as defined below) of the Rapid Stress/Rest Protocol
Experimental Design and Methods:
Validation of the stress/rest myocardial count density ratio achieved using a standard rest/stress protocol incorporating a conventional 3:1 stress/rest Tc-99m radiopharmaceutical dose ratio.
Human subjects:
To determine the stress/rest myocardial count density ratio encountered using existing rest/stress imaging protocols in routine clinical practice, 100 consecutive patients undergoing either exercise or pharmacologic stress (dipyridamole or regadenoson) myocardial perfusion SPECT were included. The stress/rest Tc-99m sestamibi/Tc-99m tetrofosmin radiopharmaceutical dose ratio was 3:1 in all patients. Stress and rest maximal myocardial counts were determined from reconstructed tomograms using Evolution software (GE Healthcare).
The Investigational, novel stress/rest protocol:
Human Subjects: Characteristics and Plans for Recruitment 100 patients, who give their consent, presenting for myocardial perfusion SPECT in whom exercise or pharmacologic stress is clinically indicated will be enrolled prospectively. There will be no bias in selection of patients with regard to gender or racial/ethnic composition. 50 patients will be stressed with exercise. 50 additional patients will receive pharmacologic stress with the on-label dose of Regadenoson. All patients will receive the appropriate dose of radiotracer according to their size and weight. Pregnant women and those who are breast feeding will not be enrolled.
Patient Informed Consent:
Written informed consent will be obtained by either the Principal Investigator, the PI's research assistant (a physician), a Nuclear Medicine resident, or a Cardiology fellow (who will supervise and monitor the stress testing).
Methods - Imaging and Data Analysis:
The rapid stress/rest protocol, as described above, will be performed using the GE Ventri, MG or Maxxus dual-head supine scintillation camera and UltraSPECT Wide Beam Reconstruction (WBR) software. Both stress and rest SPECT will be performed in all patients, even if the initial stress images are normal.
Images will be interpreted and reported in the standard fashion for clinical patient management, characterizing perfusion defects in terms of location, extent, severity, reversibility, and function in terms of volume, regional wall motion and wall thickening.
Patient flow:
-
Upon arrival in the Nuclear Medicine Laboratory, patients will be interviewed regarding their medical history and a limited physical examination will be performed (as routinely performed for all clinically-indicated myocardial perfusion scans), and informed consent will be obtained for enrollment in this research study.
-
Patients able to perform treadmill exercise to 85% of their age-predicted maximum heart rate will undergo treadmill exercise stress. In the remainder of patients pharmacologic stress will be achieved with intravenous regadenoson. A stress dose of 5-7 mCi (adjusted for patient weight and chest circumference) Tc-99m sestamibi will be administered intravenously.
-
Post-stress gated SPECT will be acquired 30-60 min. thereafter using a full-time stress (12 min.) acquisition protocol, and processed using "half-time" Wide Beam Reconstruction software (i.e."half-dose" WBR protocol).
-
Within 60 minutes thereafter patients will receive an additional intravenous dose of 35-42 mCi (adjusted for patient weight and chest circumference) Tc-99m sestamibi at rest.
-
Resting gated SPECT will be acquired 40-60 minutes thereafter using a half-time resting (7.5 min.) acquisition protocol, and processed using "half-time" Wide Beam Reconstruction software (i.e. half-time" WBR protocol).
-
The estimated time for the entire study is approximately 3 hrs, which is slightly less than the time fro the standard rest/stress protocol the investigators now use.
Scans will be assessed for image quality using a 5-point subjective scale used in several reports the investigators have published previously (in references #2 and #3 below):
The image quality of the stress and rest perfusion tomograms and the gated tomograms is graded visually using a 5-point scale: 1 (poor) - 5 (excellent). Myocardial count density and uniformity, endocardial and epicardial edge definition, visualization and definition of the right ventricle, and background noise are parameters considered subjectively when grading image quality. In addition to those same attributes considered when grading the summed perfusion tomograms, the definition of the left ventricular cavity at end-systole and the temporal smoothness of the gated frames are also considered when grading the post-stress and rest gated images.
Stress and rest absolute myocardial count density and the stress:rest myocardial count density ratio will be determined from processed tomograms using General Electric Xeleris computer software. Count density is basically the "information density" of the scan. In general, as for all of nuclear imaging, the higher the count density, the better the image quality, the lower the incidence of scan artifacts, and the greater the clinical value of the scan.
The rest/stress myocardial count density ratio achieved using the novel low-dose stress/high-dose rest protocol will be compared to the stress/rest ratios achieved using conventional rest/stress protocols (described above). The unpaired Student's t-test will be used. In addition rest/stress count densities achieved using exercise (50 patients) and regadenoson (50 patients) with the novel protocol will be compared with stress/rest ratios achieved using standard rest/stress imaging in the exercise (59 patients) and regadenoson (29 patients) subgroups.
Primary Endpoint 1: Comparison of the myocardial count density ratio of the test group using the Rapid Protocol vs. the myocardial count density ratio of the Traditional protocol in the control group.
Secondary Endpoints
-
Image quality
-
of patients with normal stress studies that may have had a stress-only study.
-
Reduction in radiation exposure between Test (Rapid) and Control (Traditional) groups
-
Comparison of absolute stress and rest myocardial count densities in Test and Control groups 5. Start to finish time, and potential cost savings between the two groups 6. Comparison of total radiopharmaceutical dose between the two groups
Study Duration:
1 year
Statistical Plan:
Primary endpoint: The individual stress and rest, as well as the stress:rest myocardial count density ratio will be determined from test group processed tomograms and compared with control group using UNPAIRED T TEST
Secondary: The image quality of the test group stress and rest perfusion tomograms and the gated tomograms will be graded visually using a 5-point scale: 1 (poor) - 5 (excellent), and compared with the control group using the UNPAIRED T TEST.
The overall reduction in radiation exposure to the test group will be analyzed using, as a comparator, the patient size and weight based radiopharmaceutical dose and imaging time used in a standard Stress/Rest Protocol.
The time and cost savings associated with forgoing the resting study in those patients with a normal stress scan will be calculated.
Based on a control group mean maximum contrast dose (MCD) of 4.4 and standard deviation of 9.5, this study will have greater than 80% power to detect a 0.3 difference in the MCD ratio. (Alpha=5%)
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: low-dose stress MPI SPECT Patients will receive a low-dose stress/high-dose rest protocol. Subject results are compared to archived patients undergoing a standard protocol./ |
Other: low-dose stress MPI SPECT
novel low-dose rest/high-dose Tc-99m sestamibi SPECT protocol with wide beam reconstruction SPECT processing
|
Outcome Measures
Primary Outcome Measures
- Myocardial Perfusion SPECT Image Quality 12 Minutes [at 12 minutes]
SPECT image quality realized using the stress/rest single-day protocol: 12- minute post-stress acquisitions If myocardial image quality is equivalent or superior to that encountered with standard myocardial perfusion SPECT performed using a standard low-dose rest/high-dose SPECT protocol and OSEM processing and if the rest/stress myocardial count density ratio is > 3.5 the outcome of a particular patient is judged to be favorable (acceptable).If either image quality is "poor" or if the rest/stress count density ratio is less than 3.5, the outcome is judged unfavorable.
- Myocardial Perfusion SPECT Image Quality 16 Minutes [at 16 minutes]
SPECT image quality realized using the stress/rest single-day protocol: 16- minute post-stress acquisitions If myocardial image quality is equivalent or superior to that encountered with standard myocardial perfusion SPECT performed using a standard low-dose rest/high-dose SPECT protocol and OSEM processing and if the rest/stress myocardial count density ratio is > 3.5 the outcome of a particular patient is judged to be favorable (acceptable).If either image quality is "poor" or if the rest/stress count density ratio is less than 3.5, the outcome is judged unfavorable.
Secondary Outcome Measures
- Rest/Stress Myocardial Count Density Ratio [immediately following SPECT image processing (1 hour after the test)]
The rest and stress myocardial count densities are determined automatically using Evolution software on the GE Healthcare Xeleris Nuclear Medicine computer workstation. The ratio is calculated by simple division. Please not that patient outcomes are NOT measured in this research protocol.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
adult
-
not pregnant
-
suspected coronary artery disease
Exclusion Criteria:
-
pregnant
-
under 18 years of age
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 'St. Luke's-Roosevelt Hospital | New York | New York | United States | 10025 |
Sponsors and Collaborators
- St. Luke's-Roosevelt Hospital Center
Investigators
- Principal Investigator: Ernest G DePuey, M.D., St. Luke's-Roosevelt Hospital Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- REGA-10K09
Study Results
Participant Flow
| Recruitment Details | 102 consecutive patients referred for clinically indicated myocardial perfusion SPECT were recruited. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Stress/Rest Myocardial Perfusion SPECT Patients |
|---|---|
| Arm/Group Description | All patients referred for clinically indicated myocardial perfusion SPECT are eligible candidates for this protocol. Low-dose stress/high-dose rest myocardial perfusion SPECT is performed according to the protocol and image quality and rest/stress myocardial count density ratios are assessed. |
| Period Title: Overall Study | |
| STARTED | 102 |
| COMPLETED | 102 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Myocardial Perfusion SPECT |
|---|---|
| Arm/Group Description | The 102 study patients underwent a very low-activity stress/high-activity rest, single-day myocardial perfusion SPECT ith a conventional sodium iodide camera and wide beam reconstruction processing. |
| Overall Participants | 102 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
70
68.6%
|
| >=65 years |
32
31.4%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
55
(15)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
53
52%
|
| Male |
49
48%
|
| Region of Enrollment (participants) [Number] | |
| United States |
102
100%
|
| Weight (pounds) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [pounds] |
178
(41)
|
| Chest circumference (inches) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [inches] |
41.5
(4.0)
|
| Coronary Artery Disease (participants) [Number] | |
| yes |
53
52%
|
| no |
49
48%
|
| Risk of Coronary Artery Disease (participants) [Number] | |
| yes |
37
36.3%
|
| no |
65
63.7%
|
| Non-cardiac surgery (participants) [Number] | |
| yes |
12
11.8%
|
| no |
90
88.2%
|
Outcome Measures
| Title | Myocardial Perfusion SPECT Image Quality 12 Minutes |
|---|---|
| Description | SPECT image quality realized using the stress/rest single-day protocol: 12- minute post-stress acquisitions If myocardial image quality is equivalent or superior to that encountered with standard myocardial perfusion SPECT performed using a standard low-dose rest/high-dose SPECT protocol and OSEM processing and if the rest/stress myocardial count density ratio is > 3.5 the outcome of a particular patient is judged to be favorable (acceptable).If either image quality is "poor" or if the rest/stress count density ratio is less than 3.5, the outcome is judged unfavorable. |
| Time Frame | at 12 minutes |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Myocardial Perfusion SPECT |
|---|---|
| Arm/Group Description | Participants underwent novel low-dose rest/high-dose Tc-99m sestamibi SPECT protocol with wide beam reconstruction SPECT processing |
| Measure Participants | 102 |
| Stress non-gated Poor |
1
1%
|
| Stress gated Poor |
0
0%
|
| Stress non-gated Fair |
8
7.8%
|
| Stress gated Fair |
3
2.9%
|
| Stress non-gated Good |
30
29.4%
|
| Stress gated Good |
20
19.6%
|
| Stress non-gated Excellent |
63
61.8%
|
| Stress gated |
79
77.5%
|
| Title | Myocardial Perfusion SPECT Image Quality 16 Minutes |
|---|---|
| Description | SPECT image quality realized using the stress/rest single-day protocol: 16- minute post-stress acquisitions If myocardial image quality is equivalent or superior to that encountered with standard myocardial perfusion SPECT performed using a standard low-dose rest/high-dose SPECT protocol and OSEM processing and if the rest/stress myocardial count density ratio is > 3.5 the outcome of a particular patient is judged to be favorable (acceptable).If either image quality is "poor" or if the rest/stress count density ratio is less than 3.5, the outcome is judged unfavorable. |
| Time Frame | at 16 minutes |
Outcome Measure Data
| Analysis Population Description |
|---|
| Of the total 102 patients enrolled, additional 16-minute post-stress SPECT was performed on 37 patients. |
| Arm/Group Title | Myocardial Perfusion SPECT |
|---|---|
| Arm/Group Description | Participants underwent novel low-dose rest/high-dose Tc-99m sestamibi SPECT protocol with wide beam reconstruction SPECT processing |
| Measure Participants | 37 |
| Stress non-gated Poor |
0
0%
|
| Stress gated Poor |
0
0%
|
| Stress non-gated Fair |
1
1%
|
| Stress gated Fair |
1
1%
|
| Stress non-gated Good |
7
6.9%
|
| Stress gated Good |
7
6.9%
|
| Stress non-gated Excellent |
29
28.4%
|
| Stress gated Excellent |
30
29.4%
|
| Title | Rest/Stress Myocardial Count Density Ratio |
|---|---|
| Description | The rest and stress myocardial count densities are determined automatically using Evolution software on the GE Healthcare Xeleris Nuclear Medicine computer workstation. The ratio is calculated by simple division. Please not that patient outcomes are NOT measured in this research protocol. |
| Time Frame | immediately following SPECT image processing (1 hour after the test) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | Adverse Events information not collected for this study. | |
| Arm/Group Title | Myocardial Perfusion SPECT | |
| Arm/Group Description | ||
All Cause Mortality |
||
| Myocardial Perfusion SPECT | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Myocardial Perfusion SPECT | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/0 (NaN) | |
Other (Not Including Serious) Adverse Events |
||
| Myocardial Perfusion SPECT | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/0 (NaN) | |
Limitations/Caveats
More Information
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
| Name/Title | E. Gordon DePuey, M.D. |
|---|---|
| Organization | St. Luke's-Roosevelt Hospital |
| Phone | 212-523-3400 |
| edepuey@chpnet.org |
- REGA-10K09