Acute Coronary Syndrome, Acute Myocardial Infarction, Chest Pain, Coronary Artery Disease
Conditions
Keywords
Computed Tomography, CT Angiography (CTA), Cardiac CT, CT, Cardiac CTA (CCTA), Chest Pain, Heart Attack, Emergency Department, Myocardial Infarction, Cost Effectiveness, Acute Coronary Event, Heart Imaging
Brief summary
This multi-center, randomized, controlled trial conducted in Emergency Departments (ED) compares computed tomography (CT) coronary angiography with the traditional approach (usual care) for low- to intermediate-risk chest pain patients. The primary objective is to estimate the rate of major cardiac events (heart attack or cardiac death) within 30 days in trial participants in Group B who were not found to have significant coronary artery disease by CT coronary angiography. Additional evaluations will comprise health care utilization assessments, including length of hospital stay and re-admissions, cost analysis, and 1-year post-triage/presentation major cardiac event rates.
Detailed description
In this study, participants with potential ACS will be randomized to traditional rule out care (Group A) or to traditional care plus CT coronary angiography (Group B) in a ratio of 1:2 traditional versus traditional plus CT coronary angiography. In Group A, all management and disposition decisions will be made by the healthcare providers caring for the participant. Participants will be admitted to hospital, admitted to cardiac diagnostic unit, or discharged to home. Diagnostic testing and treatment will be decided by the team caring for the participant. Follow up will comprise telephone interviews after 30 days and 1 year from triage/presentation. In Group B, participants will receive initial cardiac troponin and creatinine blood tests. Upon return of normal laboratory values, the participants will receive a CT coronary angiography an estimated 90 minutes after the initial values assessment or as soon as the CT scanner is available. Participants with negative test results will be discharged; follow up will comprise telephone interviews after 30 days and 1 year from triage/presentation. Participants with positive test results will be admitted to the hospital for further management dictated by the admitting team.
Interventions
DIAGNOSTIC_TESTCT Coronary Angiography (CTCA)
CT coronary angiography will be performed without and with contrast in participants randomized to receive imaging as well as traditional care. (For applicable purposes, the decision to perform contrast-enhanced imaging in the presence of a large amount of calcium should be made according to procedures at each individual site.) The imaging test will be considered positive if the participant has a greater than 50% stenosis of the right coronary, left main, left anterior descending, or circumflex arteries or of their branches in contrast-enhanced CT coronary angiography. Results will be communicated to the responsible ED and treating staff immediately upon interpretation; ED staff will determine appropriate course of management. Negative results will result in patient discharge.
PROCEDURETraditional Strategy
Participants randomized to traditional care will be assessed and discharged/treated according to routine standard-of-care procedures in the institution's emergency department.
Sponsors
Pennsylvania Department of Health
American College of Radiology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant is 30 years of age or older * Participant presents with complaints consistent with potential ACS (e.g., chest pain, shortness of breath, other) * Participant requires admission or objective testing to exclude ACS * Participant with initial ECG result without acute ischemia * Participant with an initial Thrombolysis in Myocardial Infarction (TIMI) Risk Score of 0 to 2 * Participant is willing to provide a written informed consent
Exclusion criteria
* Patients who present with symptoms that are clearly not cardiac in origin (e.g., chest pain secondary to herpes zoster, obvious pneumonia, or recent trauma); * Patients with no initial ECG performed in the ED * Patients with ST-elevation myocardial infarction (STEMI) * Patients with existing co-morbidity that requires admission regardless of presence of ACS (e.g., uncontrolled diabetes) * Patients with known contraindications to CT coronary angiography: Iodinated contrast allergic-like reaction * Patients who are known to have had CT coronary angiography in the year prior to presentation * Patients who are known to have normal catheterization results (no or minimal, \< 25%, stenosis) in the year prior to presentation * Patients who are pregnant * Patients with known renal insufficiency (e.g., creatinine clearance \< 60 mL/min/1.73 m2) * Patients with no telephone or cell phone numbers (preventing follow up) * Patients unwilling to provide a written informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rates of Major Cardiac Events (AMI or Cardiac Death) Within 30 Days | up to 30 days of discharge from the ED | To estimate the rate of major cardiac events (AMI or cardiac death) within 30 days of discharge from Emergency Department (ED) - patient follow-up included telephone interviews 30 days and 1 year after triage/presentation. Participants in Group B who were found not to have stenosis of the main or first order coronary branches greater than or equal to 50% by CT coronary angiography were considered negative and considered discharged if they were not designated to receive an inpatient bed or formal observation status. All myocardial infarctions were reviewed by an Adjudication Committee to confirm diagnosis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Significant Coronary Artery Disease Detected Within Index Hospitalization as Assessed by Medical Record Review. | baseline | The algorithm used for diagnosis of Significant coronary artery disease is provided in the Appendix of the protocol. |
| Mean Length of Hospital Stay After Initial Visit | 1-7 days | Compare the length of hospital stay in hours between the groups |
| Health Care Utilization During the Index Hospitalization. | 1-7 Days | Downstream diagnostic test during the index visit including Hospital admission or observation. |
| Cardiac Health Care Utilization 1 Year Post Triage/Presentation. | Through 1-yr study follow up | — |
| Major Adverse Cardiac Event (MACE, Including Myocardial Infarction & Cardiac Death) and Revascularization for Participants Within 1 Year Post Triage/Presentation | Through 1-yr study follow up | MACE at 1 year was determined by Patient telephone contact Medical record review Records at the presenting and neighboring hospitals were reviewed for repeat visits When these methods failed to provide survival information, we searched the Social Security Death Master File |
Countries
United States
Participant flow
Recruitment details
The study recruited patients presenting to the emergency department (ED) with potential acute coronary syndromes. After the initial electrocardiogram, consenting subjects were randomization to CCTA or traditional care (2:1ratio). Subjects subsequently found to have a creatinine clearance less than 60 ml/minute or who received a pulmonary embolism protocol CT rather than a CCTA were removed from the study.
Participants by arm
| Arm | Count |
|---|---|
| CT Coronary Angiography-based Rapid Rule Out Arm (Group B) Participants receive initial cardiac troponin/creatinine tests. Upon return of normal laboratory values (including a calculated creatinine clearance), participants receive a CT coronary angiography an estimated 90 minutes or as soon as the CT scanner is available following the initial values assessment. Participants with negative test results will be discharged unless other indications for admission per standard of care and follow up will comprise telephone interviews 30 days and 1 year after triage/presentation. Participants with positive test results will be admitted to the hospital for further management as dictated by the admitting team.
CT Coronary Angiography(CTCA): CT coronary angiography will be performed without and with contrast in participants randomized to receive imaging as well as traditional care. (For applicable purposes, the decision to perform contrast-enhanced imaging in the presence of a large amount of calcium should be made according to procedures at each individual site.) The imaging test will be considered positive if the participant has a greater than 50% stenosis of the right coronary, left main, left anterior descending, or circumflex arteries or of their branches in contrast-enhanced CT coronary angiography. Results will be communicated to the responsible Emergency Department (ED) and treating staff immediately upon interpretation; ED staff will determine appropriate course of management. Negative results will result in patient discharge. | 908 |
| Traditional Strategy (Group A) In the traditional-care arm (Group A), all management and disposition decisions will be made by the healthcare providers caring for the participant. Participants will receive disposition (admit to hospital, admit to cardiac diagnostic unit, or discharge to home), diagnostic testing (none, stress testing, or cardiac catheterization), and treatment according to the team caring for the participant.
Traditional Strategy: Participants randomized to traditional care will be assessed and discharged/treated according to routine standard-of-care (SOC) procedures in the institution's emergency department (ED). | 462 |
| Total | 1,370 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 21 | 1 |
Baseline characteristics
| Characteristic | CT Coronary Angiography-based Rapid Rule Out Arm (Group B) | Total | Traditional Strategy (Group A) |
|---|---|---|---|
| Age, Continuous | 49 years STANDARD_DEVIATION 8.9 | 49 years STANDARD_DEVIATION 9.11 | 50 years STANDARD_DEVIATION 9.5 |
| Cardiac history and risk factors Cocaine use in last week | 49 Participants | 69 Participants | 20 Participants |
| Cardiac history and risk factors Current Tobacco use | 291 Participants | 447 Participants | 156 Participants |
| Cardiac history and risk factors Diabetes Mellitus | 130 Participants | 194 Participants | 64 Participants |
| Cardiac history and risk factors Family History of CAD | 268 Participants | 394 Participants | 126 Participants |
| Cardiac history and risk factors Heart failure | 10 Participants | 19 Participants | 9 Participants |
| Cardiac history and risk factors Hypercholesterolemia | 249 Participants | 367 Participants | 118 Participants |
| Cardiac history and risk factors Hypertension | 463 Participants | 695 Participants | 232 Participants |
| Cardiac history and risk factors Myocardial infarction | 10 Participants | 16 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 21 Participants | 32 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 867 Participants | 1306 Participants | 439 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 20 Participants | 32 Participants | 12 Participants |
| Presenting electrocardiogram Early repolarization | 24 Participants | 38 Participants | 14 Participants |
| Presenting electrocardiogram Ischemia (inadequate blood supply) known to be old | 11 Participants | 17 Participants | 6 Participants |
| Presenting electrocardiogram Ischemia (inadequate blood supply) not known to be old | 10 Participants | 17 Participants | 7 Participants |
| Presenting electrocardiogram Non-diagnostic | 68 Participants | 92 Participants | 24 Participants |
| Presenting electrocardiogram Nonspecific | 208 Participants | 319 Participants | 111 Participants |
| Presenting electrocardiogram Normal | 584 Participants | 883 Participants | 299 Participants |
| Presenting electrocardiogram Other/Unknown | 1 Participants | 2 Participants | 1 Participants |
| Presenting electrocardiogram ST Elevation consistent with Acute Myocardial Infarction (AMI)-old | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 18 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 520 Participants | 806 Participants | 286 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 9 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 13 Participants | 4 Participants |
| Race (NIH/OMB) White | 359 Participants | 517 Participants | 158 Participants |
| Sex: Female, Male Female | 443 Participants | 645 Participants | 202 Participants |
| Sex: Female, Male Male | 465 Participants | 725 Participants | 260 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 929 | 3 / 463 |
| other Total, other adverse events | 0 / 929 | 0 / 463 |
| serious Total, serious adverse events | 0 / 929 | 2 / 463 |
Outcome results
Primary
Rates of Major Cardiac Events (AMI or Cardiac Death) Within 30 Days
To estimate the rate of major cardiac events (AMI or cardiac death) within 30 days of discharge from Emergency Department (ED) - patient follow-up included telephone interviews 30 days and 1 year after triage/presentation. Participants in Group B who were found not to have stenosis of the main or first order coronary branches greater than or equal to 50% by CT coronary angiography were considered negative and considered discharged if they were not designated to receive an inpatient bed or formal observation status. All myocardial infarctions were reviewed by an Adjudication Committee to confirm diagnosis.
Time frame: up to 30 days of discharge from the ED
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CT Coronary Angiography (Group B) | Rates of Major Cardiac Events (AMI or Cardiac Death) Within 30 Days | Death | 0 Participants |
| CT Coronary Angiography (Group B) | Rates of Major Cardiac Events (AMI or Cardiac Death) Within 30 Days | AMI | 10 Participants |
| Traditional Strategy (Group A) | Rates of Major Cardiac Events (AMI or Cardiac Death) Within 30 Days | Death | 0 Participants |
| Traditional Strategy (Group A) | Rates of Major Cardiac Events (AMI or Cardiac Death) Within 30 Days | AMI | 5 Participants |
| Negative CT Coronary Angiography-based Rapid Rule Out (Group B) | Rates of Major Cardiac Events (AMI or Cardiac Death) Within 30 Days | Death | 0 Participants |
| Negative CT Coronary Angiography-based Rapid Rule Out (Group B) | Rates of Major Cardiac Events (AMI or Cardiac Death) Within 30 Days | AMI | 0 Participants |
Comparison: Difference in AMI rate. NULL: equal rates of AMI in both Groups.95% CI: [-5.6, 5.7]
Secondary
Cardiac Health Care Utilization 1 Year Post Triage/Presentation.
Time frame: Through 1-yr study follow up
Population: Subjects with index visit and know outcome at 1-yr post ED triage
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CT Coronary Angiography (Group B) | Cardiac Health Care Utilization 1 Year Post Triage/Presentation. | Hospital admission | 137 Participants |
| CT Coronary Angiography (Group B) | Cardiac Health Care Utilization 1 Year Post Triage/Presentation. | Emergency department visit | 305 Participants |
| CT Coronary Angiography (Group B) | Cardiac Health Care Utilization 1 Year Post Triage/Presentation. | Cardiologist office visit | 148 Participants |
| CT Coronary Angiography (Group B) | Cardiac Health Care Utilization 1 Year Post Triage/Presentation. | CCTA | 2 Participants |
| CT Coronary Angiography (Group B) | Cardiac Health Care Utilization 1 Year Post Triage/Presentation. | Stress testing without imaging | 19 Participants |
| CT Coronary Angiography (Group B) | Cardiac Health Care Utilization 1 Year Post Triage/Presentation. | Stress testing with imaging | 60 Participants |
| CT Coronary Angiography (Group B) | Cardiac Health Care Utilization 1 Year Post Triage/Presentation. | Catheterization | 24 Participants |
| CT Coronary Angiography (Group B) | Cardiac Health Care Utilization 1 Year Post Triage/Presentation. | Echocardiogram | 49 Participants |
| Traditional Strategy (Group A) | Cardiac Health Care Utilization 1 Year Post Triage/Presentation. | Echocardiogram | 26 Participants |
| Traditional Strategy (Group A) | Cardiac Health Care Utilization 1 Year Post Triage/Presentation. | Hospital admission | 74 Participants |
| Traditional Strategy (Group A) | Cardiac Health Care Utilization 1 Year Post Triage/Presentation. | Stress testing without imaging | 2 Participants |
| Traditional Strategy (Group A) | Cardiac Health Care Utilization 1 Year Post Triage/Presentation. | Emergency department visit | 166 Participants |
| Traditional Strategy (Group A) | Cardiac Health Care Utilization 1 Year Post Triage/Presentation. | Catheterization | 13 Participants |
| Traditional Strategy (Group A) | Cardiac Health Care Utilization 1 Year Post Triage/Presentation. | Cardiologist office visit | 53 Participants |
| Traditional Strategy (Group A) | Cardiac Health Care Utilization 1 Year Post Triage/Presentation. | Stress testing with imaging | 33 Participants |
| Traditional Strategy (Group A) | Cardiac Health Care Utilization 1 Year Post Triage/Presentation. | CCTA | 5 Participants |
Secondary
Health Care Utilization During the Index Hospitalization.
Downstream diagnostic test during the index visit including Hospital admission or observation.
Time frame: 1-7 Days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CT Coronary Angiography (Group B) | Health Care Utilization During the Index Hospitalization. | Stress testing, with or without imaging | 124 Participants |
| CT Coronary Angiography (Group B) | Health Care Utilization During the Index Hospitalization. | No additional Diagnostic tests | 80 Participants |
| CT Coronary Angiography (Group B) | Health Care Utilization During the Index Hospitalization. | Cardiac catheterization | 37 Participants |
| CT Coronary Angiography (Group B) | Health Care Utilization During the Index Hospitalization. | Hosp. Admission or observation | 458 Participants |
| CT Coronary Angiography (Group B) | Health Care Utilization During the Index Hospitalization. | CCTA | 767 Participants |
| Traditional Strategy (Group A) | Health Care Utilization During the Index Hospitalization. | Hosp. Admission or observation | 357 Participants |
| Traditional Strategy (Group A) | Health Care Utilization During the Index Hospitalization. | CCTA | 26 Participants |
| Traditional Strategy (Group A) | Health Care Utilization During the Index Hospitalization. | Stress testing, with or without imaging | 267 Participants |
| Traditional Strategy (Group A) | Health Care Utilization During the Index Hospitalization. | Cardiac catheterization | 18 Participants |
| Traditional Strategy (Group A) | Health Care Utilization During the Index Hospitalization. | No additional Diagnostic tests | 167 Participants |
Comparison: H0: no difference in Patient disposition (Discharge) rates between arms95% CI: [21.4, 32.2]
Secondary
Major Adverse Cardiac Event (MACE, Including Myocardial Infarction & Cardiac Death) and Revascularization for Participants Within 1 Year Post Triage/Presentation
MACE at 1 year was determined by Patient telephone contact Medical record review Records at the presenting and neighboring hospitals were reviewed for repeat visits When these methods failed to provide survival information, we searched the Social Security Death Master File
Time frame: Through 1-yr study follow up
Population: Subject with index visit, Vital status available at 1-yr post ED triage, and known outcome
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CT Coronary Angiography (Group B) | Major Adverse Cardiac Event (MACE, Including Myocardial Infarction & Cardiac Death) and Revascularization for Participants Within 1 Year Post Triage/Presentation | Cardiac Death | 1 Participants |
| CT Coronary Angiography (Group B) | Major Adverse Cardiac Event (MACE, Including Myocardial Infarction & Cardiac Death) and Revascularization for Participants Within 1 Year Post Triage/Presentation | MACE | 12 Participants |
| CT Coronary Angiography (Group B) | Major Adverse Cardiac Event (MACE, Including Myocardial Infarction & Cardiac Death) and Revascularization for Participants Within 1 Year Post Triage/Presentation | AMI | 11 Participants |
| CT Coronary Angiography (Group B) | Major Adverse Cardiac Event (MACE, Including Myocardial Infarction & Cardiac Death) and Revascularization for Participants Within 1 Year Post Triage/Presentation | Revascularization | 25 Participants |
| CT Coronary Angiography (Group B) | Major Adverse Cardiac Event (MACE, Including Myocardial Infarction & Cardiac Death) and Revascularization for Participants Within 1 Year Post Triage/Presentation | All-Cause Mortality | 2 Participants |
| Traditional Strategy (Group A) | Major Adverse Cardiac Event (MACE, Including Myocardial Infarction & Cardiac Death) and Revascularization for Participants Within 1 Year Post Triage/Presentation | Revascularization | 7 Participants |
| Traditional Strategy (Group A) | Major Adverse Cardiac Event (MACE, Including Myocardial Infarction & Cardiac Death) and Revascularization for Participants Within 1 Year Post Triage/Presentation | All-Cause Mortality | 3 Participants |
| Traditional Strategy (Group A) | Major Adverse Cardiac Event (MACE, Including Myocardial Infarction & Cardiac Death) and Revascularization for Participants Within 1 Year Post Triage/Presentation | Cardiac Death | 0 Participants |
| Traditional Strategy (Group A) | Major Adverse Cardiac Event (MACE, Including Myocardial Infarction & Cardiac Death) and Revascularization for Participants Within 1 Year Post Triage/Presentation | AMI | 5 Participants |
| Traditional Strategy (Group A) | Major Adverse Cardiac Event (MACE, Including Myocardial Infarction & Cardiac Death) and Revascularization for Participants Within 1 Year Post Triage/Presentation | MACE | 5 Participants |
Comparison: Compare all cause mortality between groups95% CI: [-6, 5.2]
Comparison: Compare Cardiac Death between groups95% CI: [-5.5, 5.7]
Comparison: Compare AMI between groups95% CI: [-5.6, 5.9]
Comparison: Compare MACE between groups95% CI: [-5.5, 6]
Comparison: Compare Revascularization between groups95% CI: [-4.4, 7]
Secondary
Mean Length of Hospital Stay After Initial Visit
Compare the length of hospital stay in hours between the groups
Time frame: 1-7 days
Population: Results report for all patient and for those with a negative index visit assessment.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CT Coronary Angiography (Group B) | Mean Length of Hospital Stay After Initial Visit | Overall | 18.0 hours |
| CT Coronary Angiography (Group B) | Mean Length of Hospital Stay After Initial Visit | Subjects with negative test | 12.3 hours |
| Traditional Strategy (Group A) | Mean Length of Hospital Stay After Initial Visit | Overall | 24.8 hours |
| Traditional Strategy (Group A) | Mean Length of Hospital Stay After Initial Visit | Subjects with negative test | 24.7 hours |
Secondary
Significant Coronary Artery Disease Detected Within Index Hospitalization as Assessed by Medical Record Review.
The algorithm used for diagnosis of Significant coronary artery disease is provided in the Appendix of the protocol.
Time frame: baseline
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CT Coronary Angiography (Group B) | Significant Coronary Artery Disease Detected Within Index Hospitalization as Assessed by Medical Record Review. | Discharge from ED | 450 Participants |
| CT Coronary Angiography (Group B) | Significant Coronary Artery Disease Detected Within Index Hospitalization as Assessed by Medical Record Review. | Admission/observation to ED | 458 Participants |
| CT Coronary Angiography (Group B) | Significant Coronary Artery Disease Detected Within Index Hospitalization as Assessed by Medical Record Review. | Significant coronary disease | 82 Participants |
| Traditional Strategy (Group A) | Significant Coronary Artery Disease Detected Within Index Hospitalization as Assessed by Medical Record Review. | Discharge from ED | 105 Participants |
| Traditional Strategy (Group A) | Significant Coronary Artery Disease Detected Within Index Hospitalization as Assessed by Medical Record Review. | Admission/observation to ED | 357 Participants |
| Traditional Strategy (Group A) | Significant Coronary Artery Disease Detected Within Index Hospitalization as Assessed by Medical Record Review. | Significant coronary disease | 16 Participants |
Comparison: Difference in Discharge rates. H0: equal rates of Discharge in both Groups.95% CI: [21.4, 32.2]
Comparison: Difference in diagnosis rate of Significant coronary disease at index visit. H0: equal rates in both Groups.95% CI: [0, 11.2]