Atherosclerosis, Coronary Artery Disease
Conditions
Keywords
Lipid, Vulnerable Plaque, Plaque, Cholesterol, Near Infrared Spectroscopy, NIRS-IVUS, Intravascular Ultrasound, Angiography, Coronary Imaging
Brief summary
The purpose of this study is to enhance medical knowledge of the causes of future coronary problems. Many studies in patients who have already experienced a coronary problem point to the danger associated with plaques that are rich in cholesterol. This study determines if the near-infrared method of detection of these fatty plaques can predict future events. If dangerous plaques can be identified, there are many treatments already available that could be tested for their ability to prevent coronary events.
Interventions
DEVICENIRS-IVUS Imaging (TVC Imaging System)
Diagnostic Imaging Catheter
Sponsors
Medstar Health Research Institute
Infraredx
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
General Inclusion Criteria: * Subjects presenting for coronary angiography in whom IVUS imaging is likely to be performed for clinical purposes. * Greater than 18 years of age. * Clinical presenting symptoms meeting one of the three criteria below: 1. Subjects presenting with an acute coronary syndrome (ACS) including at least one of the following: 1. Elevated cardiac biomarkers with CK-MB or troponin greater than upper limits of normal; 2. ST depression or ST elevation \>1mm in 2 or more contiguous leads in the absence of LVH, paced rhythm, BBB or early repolarization; 3. A stabilized patient 24 to 72 hours post STEMI; 2. Unstable angina pectoris; 3. Stable angina pectoris and/or a positive functional study with evidence of ischemia. Angiographic Inclusion Criteria * At least one Suspected Index Culprit Lesion requiring imaging with IVUS and/or NIRS for clinical indications. * At least two native epicardial coronary arteries (which may include the Suspected Index Culprit Artery) eligible for imaging with NIRS-IVUS. IVUS/NIRS Imaging Inclusion Criterion * A minimum of a total 50 mm of coronary artery not involved in a prior or Index Procedure PCI (including the 5mm borders on either edge of the site receiving PCI) must be scanned. This 50mm total length may include contributions from the Suspected Index Culprit Arteries and from Index Non-Culprit Arteries. This total length must include contributions from two or more native imaged arteries.
Exclusion criteria
* Unstable patients (STEMI within the prior 24 hours; cardiogenic shock, hypotension needing inotropes, hypoxia needing intubation, and IABP) and patients that had a procedural complication (coronary dissection, perforation or a complication that would necessitate immediate-unplanned revascularization) during index PCI procedure. * History of CABG or planned CABG within 6 months following NIRS-IVUS imaging. * Patient has additional lesion(s) that needs a staged PCI. * Subject life expectancy is less than 2 years at time of index catheterization. * Subject with ejection fraction (EF) \<30%. * Subject pacemaker dependent/paced rhythm. * Subject pregnant and lactating. * Any other factor that the investigator feels would put the patient at increased risk or otherwise make the patient unsuitable for participation in the protocol * Patients undergoing performance of PCI in all three major vessels during the index PCI.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Stratified as Non-Index Culprit Lesion Related Major Adverse Cardiac Events (NC-MACE) or No NC-MACE and Association With maxLCBI4mm as a Continuous Variable | 2 years | Association of maximum 4 mm Lipid Core Burden Index (maxLCBI4mm) as a continuous value in 100 unit increments in all imaged arteries and NC-MACE at both (1) Patient Level and (2) Plaque Level Non-Index Culprit Lesion related Major Adverse Cardiac Events (NC-MACE) is defined as a composite of: * cardiac death * cardiac arrest * non-fatal myocardial infarction (MI) * acute coronary syndrome * revascularization by coronary artery bypass graft (CABG) or percutaneous intervention (PCI) * rehospitalization for progressive angina, related to a non-index culprit lesion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Stratified as NC-MACE or No NC-MACE and Association With maxLCBI4mm More Than a Threshold of 400 | 2 years | Association of maxLCBI4mm more than and less than a threshold of 400 in all imaged arteries and NC-MACE at both (1) Patient Level and (2) Plaque Level Non-Index Culprit Lesion related Major Adverse Cardiac Events (NC-MACE) is defined as a composite of: * cardiac death * cardiac arrest * non-fatal myocardial infarction (MI) * acute coronary syndrome * revascularization by coronary artery bypass graft (CABG) or percutaneous intervention (PCI) * rehospitalization for progressive angina, related to a non-index culprit lesion |
Countries
Italy, Latvia, Netherlands, Slovakia, United Kingdom, United States
Participant flow
Recruitment details
Enrolled patients with a large LRP (Maximum Lipid Core Burden Index\>250 in 4 mm or maxLCBI4mm\>=250) were assigned to 2 year follow up to determine if a new coronary event had occurred. A randomly selected half of the patients with a small or no LRP (MaxLCBI4mm\<250) had 2 year follow up.
Pre-assignment details
A randomly selected half of the patients with a small or no LRP (MaxLCBI4mm\<250) did not have 2 year follow up and were not included in the primary analyses. This reduced the total number of patients followed for two years to 1271 patients.
Participants by arm
| Arm | Count |
|---|---|
| Participants With 2 Year Follow up Participants with NIRS-IVUS imaging at baseline and assigned to follow up for Non-Index Culprit Lesion related Major Adverse Cardiac Events (NC-MACE) for 2 years | 1,271 |
| Total | 1,271 |
Baseline characteristics
| Characteristic | Participants With 2 Year Follow up |
|---|---|
| Age, Continuous | 64 years STANDARD_DEVIATION 10.3 |
| Race/Ethnicity, Customized African American | 158 Participants |
| Race/Ethnicity, Customized Asian Pacific | 44 Participants |
| Race/Ethnicity, Customized Caucasian | 942 Participants |
| Race/Ethnicity, Customized Hispanic | 101 Participants |
| Race/Ethnicity, Customized Native American | 0 Participants |
| Race/Ethnicity, Customized Other | 128 Participants |
| Region of Enrollment Italy | 10 Participants |
| Region of Enrollment Latvia | 10 Participants |
| Region of Enrollment Netherlands | 187 Participants |
| Region of Enrollment Slovakia | 17 Participants |
| Region of Enrollment United Kingdom | 46 Participants |
| Region of Enrollment United States | 1001 Participants |
| Sex: Female, Male Female | 388 Participants |
| Sex: Female, Male Male | 883 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1,563 |
| other Total, other adverse events | 0 / 1,563 |
| serious Total, serious adverse events | 6 / 1,563 |
Outcome results
Primary
Number of Participants Stratified as Non-Index Culprit Lesion Related Major Adverse Cardiac Events (NC-MACE) or No NC-MACE and Association With maxLCBI4mm as a Continuous Variable
Association of maximum 4 mm Lipid Core Burden Index (maxLCBI4mm) as a continuous value in 100 unit increments in all imaged arteries and NC-MACE at both (1) Patient Level and (2) Plaque Level Non-Index Culprit Lesion related Major Adverse Cardiac Events (NC-MACE) is defined as a composite of: * cardiac death * cardiac arrest * non-fatal myocardial infarction (MI) * acute coronary syndrome * revascularization by coronary artery bypass graft (CABG) or percutaneous intervention (PCI) * rehospitalization for progressive angina, related to a non-index culprit lesion
Time frame: 2 years
Population: Patients assigned to 2 year follow up were analyzed, at the patient and plaque level, to test the association between maximum 4 mm Lipid Core Burden Index (maxLCBI4mm) and Non-Index Culprit Lesion related Major Adverse Cardiac Events (NC-MACE).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants With 2 Year Follow up | Number of Participants Stratified as Non-Index Culprit Lesion Related Major Adverse Cardiac Events (NC-MACE) or No NC-MACE and Association With maxLCBI4mm as a Continuous Variable | Participants with NC-MACE | 104 Participants |
| Participants With 2 Year Follow up | Number of Participants Stratified as Non-Index Culprit Lesion Related Major Adverse Cardiac Events (NC-MACE) or No NC-MACE and Association With maxLCBI4mm as a Continuous Variable | Participants with No NC-MACE | 1167 Participants |
Comparison: Hypothesis 1 (Vulnerable Patient Hypothesis) first fit a univariate proportional hazards regression model in which maxLCBI4mm is the only independent variable and NC-MACE during 2 years is the outcome. The null hypothesis tested by the Wald test that the regression coefficient in a proportional hazards regression model is significantly different from 0. This analysis determined whether maxLCBI4mmI is a risk factor for NC-MACE.p-value: 0.000495% CI: [1.09, 1.35]Regression, Cox
Comparison: Hypothesis 2 (Vulnerable Plaque Hypothesis) first fit a univariate proportional hazards regression model in which maxLCBI4mm in the coronary artery segment is the measure of exposure and NC-MACE during 2 years caused by a new culprit lesion in that segment is the outcome. This analysis was performed with adjustment for the potential clustering effect within patient utilizing the Wei, Lin and Weissfeld (WLW) methodology. This analysis determined whether maxLCBI4mm is a risk factor NC-MACE.p-value: <0.000195% CI: [1.3, 1.6]Regression, Cox
Secondary
Number of Participants Stratified as NC-MACE or No NC-MACE and Association With maxLCBI4mm More Than a Threshold of 400
Association of maxLCBI4mm more than and less than a threshold of 400 in all imaged arteries and NC-MACE at both (1) Patient Level and (2) Plaque Level Non-Index Culprit Lesion related Major Adverse Cardiac Events (NC-MACE) is defined as a composite of: * cardiac death * cardiac arrest * non-fatal myocardial infarction (MI) * acute coronary syndrome * revascularization by coronary artery bypass graft (CABG) or percutaneous intervention (PCI) * rehospitalization for progressive angina, related to a non-index culprit lesion
Time frame: 2 years
Population: Patients assigned to 2 year follow up were analyzed, at the patient and plaque level to test the association between maximum 4mm Lipid Core Burden index (maxLCBI4mm) \>400 and Non-Index Culprit Lesion related Major Cardiac Events (NC-MACE)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants With 2 Year Follow up | Number of Participants Stratified as NC-MACE or No NC-MACE and Association With maxLCBI4mm More Than a Threshold of 400 | Participants with NC-MACE | 104 Participants |
| Participants With 2 Year Follow up | Number of Participants Stratified as NC-MACE or No NC-MACE and Association With maxLCBI4mm More Than a Threshold of 400 | Participants with No NC-MACE | 1167 Participants |
Comparison: Secondary Hypothesis 1 (Vulnerable Patient)- Cox proportional hazards regression model to assess a threshold of maxLCBI4mm \> 400 as the independent variable and NC-MACE during 2 years as the outcome.p-value: <0.000195% CI: [1.48, 3.22]Regression, Cox
Comparison: Secondary Hypothesis 2 (Vulnerable Plaque)- Cox proportional hazards regression model to assess a threshold of maxLCBI4mm \> 400 in the coronary artery segment as the independent variable and NC-MACE during 2 years caused by a new culprit lesion in that segment is the outcome.p-value: <0.000195% CI: [2.39, 7.45]Regression, Cox