1. Lipid-Rich Plaque Study
Study Initiation Visit
[Insert SiteName]
[Insert Site ID]
[Insert SIV Date]

2. Agenda Study & Device Overview Protocol Training Study Design
Inclusion/Exclusion Criteria
Procedural Activities
Screening and Informed Consent
Imaging Guidelines
Post Procedure Activities
Submission of Imaging Data
Adverse Event Reporting
Regulatory Document Guidelines

3. TVC Imaging System [NIRS-IVUS]
FDA cleared and CE marked
Identifies cholesterol-rich atherosclerotic plaques known as Lipid-Rich Plaques in coronary arteries
Instrument components: 1
Pullback Device
(Nexus)
Compute 4mm sub segment LCBIs
Console
Catheter

4. TVC Imaging System [NIRS-IVUS]
IVUS cross-sectional image with NIRS (Chemogram) ring (Left)
Chemogram (Top Right)
Longitudinal NIRS and IVUS images (Bottom Right)
No Lipid-Rich Plaque = RED
Lipid-Rich Plaque = YELLOW 1
Compute 4mm sub segment LCBIs

5. Lipid Core Burden Index (LCBI)
Measure of the proportion of Lipid-Rich Plaque in the vessel
Scale of
0 = Fibrotic tissue (RED)
1 to 1000= Lipid-Rich Plaque (YELLOW)
Vessel LCBI: LCBI across entire scan
Regional LCBI: LCBI in a user-selected region (between marks)
Max LCBI4mm: The maximum lipid burden in any 4mm section within a user
defined segment 1
Max LCBI 4mm
Regional LCBI
Vessel LCBI

6. Study Overview Global, multicenter and observational outcomes study
Enroll 9,000 patients in 100 sites within the US, Europe, and Japan
Evaluate the correlation between the presence of non-intervened, non-flow-limiting Lipid-Rich Plaques and the future development of Major Adverse Cardiac Events over 2 years
Screen and enroll patients requiring clinically indicated IVUS interrogation
ClinicalTrials.gov Identifier: NCT
Index
Observe for Events
Follow up
2 Mo.
6 Mo.
12 Mo.
24 Mo.

7. Study Timeline ? Index Procedure: Follow-Up:
Demographics
Medical History
Eligibility
Procedural Data
Angiogram
NIRS-IVUS Imaging
Follow-Up:
2, 6,12, and 24 months
Phone Call to Subject
Inquire about MACE
Follow Up Catheterization Data
Cardiac Symptoms
Angiograms
Chemograms (if performed)
IVUS (if performed)
Blood Labs
Follow Up Catheterization Data
Cardiac Symptoms
Angiograms
Chemograms (if performed)
IVUS (if performed)
Blood Labs
Follow Up Catheterization Data
Cardiac Symptoms
Angiograms
Chemograms (if performed)
IVUS (if performed)
Blood Labs
Follow Up Catheterization Data
Cardiac Symptoms
Angiograms
Chemograms (if performed)
IVUS (if performed)
Blood Labs
Index Contact
Demographics
Cardiac Symptoms
Index Contact )
Blood Labs
Index 2month 6month 12month 24month
Unplanned Catheterizations:
Cardiac Symptoms
Angiograms
NIRS-IVUS imaging
(if performed) ? ?

8. Key Procedural Terms & Definitions
Major Epicardial Arteries – left anterior descending (LAD), left circumflex (LCX), and right coronary arteries (RCA) and the branches associated with each.
Suspected Index Culprit Lesion - lesion or multiple lesions requiring clinically necessary NIRS-IVUS interrogation at the time of the index procedure.
Index Suspected Culprit Artery - artery that contains at least one Suspected Culprit Lesion at the time of the index procedure.
Index Culprit Lesion - lesion responsible for the presenting symptoms during index procedure.
Index Non Culprit Artery - artery that contains no culprit lesions during index procedure.
Follow-Up Culprit Lesion - lesion related to a Major Adverse Cardiac Event (MACE) during the 2 year follow up timeframe.
Large LRP - At least one 4 mm length of artery with a LCBI ≥ 250 as assessed by NIRS-IVUS imaging

9. Study Design BLINDED BLINDED BLINDED Index 2yr Follow-Up 2yr Follow-Up
Non Culprit
Artery
(IVUS is un-blinded)
Suspected
Index Culprit
Lesion
Index
Culprit
Lesion
-or-
Send to Core Lab
BLINDED
BLINDED
Core Lab will
Un-blind NIRS data
N= 3000
Large LRP
(MaxLCBI4mm ≥ 250)
N= 6000
Small/No LRP
(MaxLCBI4mm < 250)
N= 3000
N= 3000
2yr Follow-Up
2yr Follow-Up
Terminate upon
Discharge

10. General Inclusion/Exclusion Criteria
Subject must meet all of the following criteria:
Scheduled for coronary angiography in whom IVUS imaging is likely to be performed for clinical purpose
18 years of age or older
Present with one of the following clinical symptoms:
Stabilized ACS (Elevated cardiac enzymes, ST depression or ST elevation >1mm in 2 or more contiguous leads in the absence of LVH, 24 to 72 hours post STEMI)
Unstable angina pectoris
Stable angina and/or positive functional study
Subjects must not meet the following criteria:
Unstable patient (STEMI <24 hours, cardiogenic shock, hypotension needing, inotropes, hypoxia needing intubation, and IABP)
History of CABG or planned CABG within 6 months following NIRS-IVUS Imaging
Life expectancy is less than 2 years
Ejection fraction (EF) <30%
Pacemaker dependent/paced rhythm
Pregnant and/or lactating patient
Procedural complications during index procedure (coronary dissection, perforation or a complication that would necessitate immediate-unplanned revascularization)
Scheduled staged PCI

11. Imaging Guidelines: Angiogram Acquisition
Angiographic Inclusion Criteria
The following must be imaged with NIRS-IVUS:
≥1 Suspected Index Culprit Lesion clinically indicated for IVUS interrogation
≥2 Native epicardial coronary arteries eligible for NIRS-IVUS imaging – may include the
Index Culprit Vessel
Perform angiographic imaging per standard of care.
Ensure catheters are clearly visualized in the cines with a straight portion of the unfilled catheter.
Obtain at least 2 orthogonal angiographic views of the lesion.
Document the following:
NTG administration
PCI during the procedure
Catheter sizes
Distal and proximal placements of the NIRS-IVUS catheter recorded by fluoroscopy.
Imaging Guidelines: Angiogram Acquisition

12. NIRS-IVUS Imaging Inclusion Criteria
Scan Index Culprit Artery – NIRS and IVUS Unblinded
Scan one or more Non-Culprit Arteries – NIRS Blinded, IVUS Unblinded
NIRS-IVUS Catheter should be placed as far distal as possible in each artery and scan should be performed back into the guide.
Scan a minimum 50 mm of non-culprit segment of coronary artery:
Non-culprit study segment defined as: Non-flow limiting, does not contain
> 50% diameter stenosis by visual estimate
Has not undergone previous PCI and/or does not have a planned PCI
Excluding 5 mm borders of new or existing stent(s)
May include contributions from index culprit artery and non-culprit arteries
NIRS-IVUS Assessment
Suspected Index Culprit Lesion
Index Non-Culprit Artery
IVUS Use
Clinically Indicated
Not Clinically Indicated
Display
NIRS & IVUS
IVUS Only (NIRS Image is Blinded)
BLINDED

13. Scenario 1: Diagnostic No PCI Required
Left Coronary Artery (LCA)
Right Coronary Artery (RCA)
LCX
50mm
RCA
65mm GC GC
Study Segment Qualifications:
At least one Suspected Index Culprit Lesion (LAD)
At least two major epicardial vessels eligible for IVUS-NIRS Imaging (RCA , LAD, LCX)
At least 50mm total pullback (Visually estimated LAD 70mm pullback, LCX 50 mm pullback, RCA 65mm. Approximate total 185mm pullback of scanned coronary artery)
LAD
70mm
Total Eligible Length (excludes stents & borders) = ~185mm
Suspected Index Culprit Lesion: Prox LAD
Unblinded Run: LAD
Index Non-Culprit Artery: RCA, LCX
Blinded Run(s): LCX, RCA
PCI Performed: No PCI performed
= Suspected Index
Culprit Lesion
= Blinded Scan
= Guide Catheter
= Unblinded Scan
= 5mm excluded stent
border
= Treated Segment;
scanned but not
included in analysis
XXXXX= Stent

14. Scenario 2: Single Lesion PCIGC
LCA
RCA
LAD
45mm GC
LCX
60mm
RCA
50mm
Study Segment Qualifications:
At least one Suspected Index Culprit Lesion (RCA)
At least two major epicardial vessels eligible for IVUS-NIRS Imaging (RCA , LAD, LCX)
At least 50mm total pullback (Visually estimated LAD 45mm pullback, LCX 60 mm pullback, RCA 50mm. Approximate total 155mm pullback of scanned coronary artery)
Total Eligible Length (excluding stent & borders) = ~155mm
Suspected Index Culprit Lesion: RCA
Unblinded Run: RCA
Index Non-Culprit Artery: LAD, LCX
Blinded Run(s): LCX, LAD
PCI Performed On: Prox RCA
XXXXX GC
Exclude 5mm borders
= Suspected Index
Culprit Lesion
= Blinded Scan
= Guide Catheter
= Unblinded Scan
= 5mm excluded stent
border
= Treated Segment;
scanned but not
included in analysis
XXXXX = Stent
RCA
50mm

15. Scenario 3: Chronic Total Occlusion
RCA GC
LCA
RCA GC
CTO
LAD
35mm
LCX
55mm
RCA GC
Study Segment Qualifications:
At least one Suspected Index Culprit Lesion (RCA)
At least two major epicardial vessels eligible for IVUS-NIRS Imaging (LAD, LCX)
At least 50mm total pullback (Visually estimated LAD 35mm pullback, LCX 55 mm pullback. Approximate total 90mm pullback of scanned coronary artery)
Total Eligible Legth (exluding stents & borders) = ~90mm
Suspected Index Culprit Lesion: RCA
Unblinded Run: RCA
Index Non-Culprit Artery: LAD, LCX
Blinded Run(s): LCX, LAD
PCI Performed On: Prox RCA
RCA GC
=Suspected Index
Culprit Lesion
= Blinded Scan
XXXXXXXXXXX
= Guide Catheter
= Unblinded Scan
Exclude 5mm borders
= Treated Segment;
scanned but not
included in analysis
= 5mm excluded stent
border
XXXXX = Stent

16. Scenario 4: Ramus Present
LCA
RCA
LAD
45mm GC GC
RCA
70mm
LCX
55mm
Ramus
20mm
Study Segment Qualification:
At least one Suspected Index Culprit Lesion (LCX)
At least two major epicardial vessels eligible for IVUS-NIRS Imaging (RCA , LAD, LCX, Ramus)
At least 50mm total pullback (Visually estimated LAD 45mm pullback, LCX 55 mm pullback, RCA 70mm, Ramus 20mm. Approximate total 190mm pullback of scanned coronary artery)
Total Eligible Length (excluding stent & borders)= ~190mm
Suspected Index Culprit Lesion: Prox LCX
Unblinded Run: LCX
Index Non-Culprit Artery: LAD, RCA, Ramus
Blinded Run: LAD, RCA, Ramus
PCI Performed On: No PCI performed
= Suspected Index
Culprit Lesion
= Blinded Scan
= Guide Catheter
= Unblinded Scan
= 5mm excluded stent
border
= Treated Segment;
scanned but not
included in analysis
XXXXX = Stent

17. Scenario 5: Multi Lesion PCI
LCA
RCA GC GC
Total Eligible Lengh (excluding stent & borders)= ~75mm
Suspected Index Culprit Lesion: LAD, RCA
Unblinded Run: LAD, RCA
Index Non-Culprit Artery: Prox RCA
Blinded Run: N/A
PCI Performed On: Prox RCA and Prox/Mid LAD
LAD
25mm
RCA
50mm
Study Segment Qualifications:
At least one Suspected Index Culprit Lesion (LAD, RCA)
At least two major epicardial vessels eligible for IVUS-NIRS Imaging (RCA , LAD)
At least 50mm total pullback (Visually estimated LAD 25mm pullback, RCA 50mm. Approximate total 75mm pullback of scanned coronary artery)
= Suspected Index
Culprit Lesion
Exclude 5mm
borders
Exclude 5mm borders
= Unblinded Scan
XXXXXX
= Treated Segment;
scanned but not
included in analysis GC
XXXXX
LAD
25mm
= Blinded Scan GC
= Guide Catheter
XXXXXX
= 5mm excluded stent
border
RCA
50mm
XXXXX = Stent
CS0168rA DCR14-172

18. Scenario 6: Prior Stenting
LCA
RCA
XXX GC GC
LAD
35mm
XXXXXXXXXXXXX
Exclude 5mm borders
Study Segment Qualifications:
At least one Suspected Index Culprit Lesion (LAD, RCA)
At least two major epicardial vessels eligible for IVUS-NIRS Imaging (RCA , LAD, LCX)
At least 50mm total pullback (Visually estimated LAD 35mm pullback, RCA 15mm, LCX 40mm. Approximate total 90mm pullback of scanned coronary artery)
RCA
15mm
LCX
40mm
Total Eligible Length (exluding stent & borders) = ~90mm
Suspected Index Culprit Lesion: LAD, RCA
Unblinded Run: LAD, RCA
Index Non-Culprit Artery: LCX
Blinded Run: LCX
PCI Performed On: No PCI
= Suspected Index
Culprit Lesion
= Blinded Scan
= Guide Catheter
= Unblinded Scan
= 5mm excluded stent
border
= Treated Segment;
scanned but not
included in analysis
XXXXX = Stent

19. Scenario 7: Single Lesion PCI and Ramus
LCA
RCA
LAD
Ramus
35mm
RCA
80mm
LCX
40mm
LCX
Study Segment Qualifications:
At least one Suspected Index Culprit Lesion (LAD)
At least two major epicardial vessels eligible for IVUS-NIRS Imaging (RCA , LAC, LCX)
At least 50mm total pullback (Visually estimated LAD 25mm pullback, LCX 40 mm pullback, RCA 80mm, Ramus 35mm. Approximate total 180mm pullback of scanned coronary artery)
Total Eligible Length (excluding stent & borders)= ~180mm
Suspected Index Culprit Lesion: LAD
Unblinded Run: LAD
Index Non-Culprit Artery: LCX, RCA, Ramus
Blinded Run: LCX, RCA, Ramus
PCI Performed On: Prox LAD
Exclude 5mm borders
LAD
25mm
XXXXX
= Suspected Index
Culprit Lesion
= Blinded Scan
Ramus
35mm
= Guide Catheter
= Unblinded Scan
= 5mm excluded stent
border
LCX
40mm
= Treated Segment;
scanned but not
included in analysis
XXXXX= Stent

20. Procedure for Blinding Chemogram * Stand Alone Console
Closing out of unblinded scan is required.
Return to Main Screen
Select
Confidential - Internal Use Only
CS0168rA
DCR14-172

21. Patients Demographics Retrieval
Type first letters of patients last name.
Select (Find) Icon
Confidential - Internal Use Only
CS0168rA
DCR14-172

22. Patients Demographics Retrieval using (Find) Feature
1. Select name in patient list.
2. Select “Select Patient” Icon.
3. Patient demographics auto populate.
Confidential - Internal Use Only
CS0168rA
DCR14-172

23. Patients Demographics-Enabling Blinding Chemogram Feature
Patient Demographics auto populate
2. Select Blinding Feature.
3. Select (Save) Icon
Chemogram blinding NOT ENABLED
Chemogram blinding ENABLED
* If the blinding control is selected, the chemogram blinding will persist throughout the entire TVC procedure.
Confidential - Internal Use Only
CS0168rA
DCR14-172

24. Patient Demographics-Enabling Blinding Chemogram Feature
Select “Continue”Icon
Confidential - Internal Use Only
CS0168rA
DCR14-172

25. Data Acquisition Screen
* Confirmation of Blinded Chemogram Status
Unblinded Scan
2. Blinded scan
(Chemogram Blinding Enabled)
Confidential - Internal Use Only
CS0168rA
DCR14-172

26. Active Scans (Unblinded and Blinded)
Confidential - Internal Use Only
CS0168rA
DCR14-172

27. Completed Scan (Blinded)
Blinded scans, the chemogram will not be displayed. However, IVUS information will continuously be displayed
Chemogram
Data
BLINDED
Block
Chemogram Data BLINDED
Chemogram Ring BLINDED
Confidential - Internal Use Only
CS0168rA
DCR14-172

28. Quality Assessment of Blinded Chemogram
Place two “Marks” in the scan at the distal and proximal locations of the representative segment of your choice. If the system is able to compute an LCBI within that region, “Data Quality Acceptable” will appear.
Good Quality Scan
Marks placed at distal and proximal locations in scan
Confidential - Internal Use Only
CS0168rA
DCR14-172

29. Quality Assessment of Blinded Chemogram
If the quality of the collected chemogram is not sufficient, “Quality Not Acceptable” will appear.
If “Data Quality Unacceptable” continues to appear, repeat the scan in accordance with the protocol.
Quality of chemogram is insufficient
Marks placed at distal and proximal locations in scan
Confidential - Internal Use Only
CS0168rA
DCR14-172

30. Adverse Event Protocol Specific Terms & Definitions
Major Adverse Cardiac Event (MACE)
Cardiac death
Cardiac arrest
Non-fatal myocardial infarction (MI)
Acute coronary syndrome
Revascularization by CABG or PCI
Re-hospitalization for progressive angina, adjudicated to a non-index-culprit lesion secondary to significant fixed, non-reversible (not-spasm related) lesion progression of more than 20% from the baseline study (confirmed by either serial angiography or by necropsy)
Non-Culprit Major Adverse Cardiac Event (NC-MACE)
Event that occurs in the index non-culprit artery at time of follow up.

31. Study Contacts CRA (Primary Contact): [Monitor Name] [Monitor Email]
[Monitor Phone #]
Senior CRA (Secondary Contact): Tania Medeiros
Project Coordinator Sponsor: Priti Shah
Administrative Assistance: Ruth Potwin
Clinical Fax No:
Principal Investigator: Ron Waksman, MD
Project Manager-Core Lab Rebecca Torguson, MPH

32. Questions?