1. Near-Infrared Spectroscopy: Lipid-Rich Plaque Study Update
Ron Waksman, MD, FACC, FSCAI Professor of Medicine, (Cardiology) Georgetown University Director, Cardiovascular Research Advanced Education,
MedStar Heart & Vascular Institute, Washington DC

2. Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship
Company
Boston Scientific
Biotronik
Biosensors
Astra Zeneca
Medtronic Vascular
Abbott Vascular
Symetis
Med Alliance
LifeTech
Amgen
Grant/Research Support
Consulting Fees/Honoraria

3. Detection by Intracoronary Near-Infrared Spectroscopy of LipidCore Plaque at Culprit Sites in Survivors of Cardiac Arrest
Ryan D. Madder, David H. Wohns, James E. Muller,
J INVASIVE CARDIOL 2014;26(2)

4. Cardiac Arrest in 5K Race associated with LAD Stenosis and a Circular Lipid Core Plaque
Ventricular Fibrillation
Courtesy Dr. Madder et al, JIC, In pressR

5. Near Infrared Spectroscopy Can Differentiate
Lipid Core Plaque From Fibrotic And Calcified Plaque
A yellow spot on the chemogram shows lipid core plaque has been detected

6. Combination NIRS-IVUS Instrument
TVC Imaging System™
Laser
Computer with algorithms
Pull-back and rotation device
TVC Insight™ Catheter
Single use, 3.2 Fr
Dual modality
Spectroscopy – lipid core plaque
IVUS – plaque structure

7. Chemogram Findings in a Coronary Autopsy Specimen: Comparison with Histology
40 mm
36 mm
20 mm
26 mm

8. Five Anecdotal NIRS Event Cases with Chemogram Pre or Post
Five Anecdotal NIRS Event Cases with Chemogram Pre or Post. All have yellow chemogram.
Chemogram
Pre event
Chemograms
Post event

9. LCBI in Non-culprit Artery Identifies: Vulnerable Patients
Above the Median
Median
LCBI = 43
Rohit M. Oemrawsingh, MD, ET AL. JACC VOL , NO. 2 3 ,2014

10. Identification of Vulnerable Patients by Intra-coronary NIRS
121 Patients Post PCI with single vessel chemogram.
maxLCBI4mm ≥500 at a non-stented site in 9.9% of patients.
MACCE in 58.3%
of patients
with a maxLCBI4mm ≥500
compared to
only 6.4% of those
with a maxLCBI4mm <500
(p<0.001;
relative risk=9.1).
maxLCBI4mm ≥500
Madder et al, 2014

11. The Lipid-rich Plaque (LRP) Study
Dr. Ron Waksman, PI
2 year MACE from a new lesion at patient and coronary segment level
1,562 PCI
patients
with ACS or SA
with
NIRS-IVUS
imaging of
2 or more
vessels

12. Terminate upon Discharge
Study Flow
Index
N~1500
BLINDED
Index
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= 1260
Large LRP
(MaxLCBI4mm ≥ 250)
N= 240
Small/No LRP
(MaxLCBI4mm < 250)
N= 120
N= 120
2 Year Follow-Up
2 Year Follow-Up
Terminate upon Discharge

13. LRP Study Endpoints For the Test of the Vulnerable Patient Hypothesis
The primary endpoint for the test of the vulnerable patient hypothesis will be the increased incidence of NC-MACE within 24 months in patients with increased max 4mm LCBI in all scanned arteries as opposed to those without increased max 4mm LCBI
For the Test of the Vulnerable Plaque Hypothesis
The primary endpoint for the test of the vulnerable plaque hypothesis will be the increased incidence of NC-MACE within 24 months in coronary artery segments with increased max 4mm LCBI as opposed to those without increased max 4mm LCBI

14. Endpoint Assessment Flow
Follow Up Patients
N ~ 1563
Reported Patient-Level Event
Reported by the site via EDC
Cleveland Clinic will identify, if imaging is available, follow up event location
Send to Cleveland Clinic Adjudication Team
Collaborative Effort: Feedback Between Both Teams at Each Step
Adjudicated Patient-Level Non-Event
Adjudicated Patient-Level Endpoint Event
The provided follow up event location guides and drives MCRN Plaque Adjudication Team
Send to MCRN Plaque Adjudication Team
Adjudicated Plaque-Level Non-Event
Adjudicated Plaque-Level Endpoint Event

15. Plaque Adjudication Flow
Plaque adjudication is triggered upon adjudication of a patient level endpoint event if an angiogram or cardiac CT is available
Cleveland Clinic Physician Adjudication team provides the following information:
Culprit Lesion CASS Code
Culprit Lesion Location
Ex: proximal, mid, distal, ostial, etc.
Here is a visual representation of how we have defined segments and subsegments for both the purposes of index procedure analysis and event adjudication. For a given vessel, in this example the LCX, we divide the pullback into 30 mm segments with a maximum of 4 segments. These segments, the proximal, mid, distal, and distal distal, comprise a possible total 120 mm of scanned vessel. Each of these segments are further divided into 10mm segments that we refer to as subsegments. As visualized in this blue proximal segment, we have the three 10mm subsegments denoted with the nomenclautre prox 1, prox 2, and prox 3. The same nomenclature with use of numbers would be used to describe the subsegments of the mid, distal, or distal distal segments. In order to adjudicate a plaque level event, the adjudicator will need to identify the event culprit lesion and determine its location on a segment and subsegment level. A MCRN Plaque Coordinator will create still images of the index and event angiograms and indicate segment borders for ease of adjudication by a separate, blinded Plaque Adjudicator. As we move through the steps of a plaque level adjudication we will provide an example.

16. Ware Segments: A Standardized Method of Plaque Adjudication
The MCRN Plaque Adjudication Team confirms the culprit lesion provided by Cleveland Clinic and translates the culprit vessel into standardized Ware Segments and Subsegments
Ware Segments
30 mm each; 120 mm total
Proximal, Mid, Distal, and Distal Distal
Ware Subsegments
10 mm; 3 per segment
Ex: prox 1, prox 2, prox 3 1 2 3
Proximal
Mid
Distal
Distal Distal
Prox 3
Prox 2
Prox 1
Here is a visual representation of how we have defined segments and subsegments for both the purposes of index procedure analysis and event adjudication. For a given vessel, in this example the LCX, we divide the pullback into 30 mm segments with a maximum of 4 segments. These segments, the proximal, mid, distal, and distal distal, comprise a possible total 120 mm of scanned vessel. Each of these segments are further divided into 10mm segments that we refer to as subsegments. As visualized in this blue proximal segment, we have the three 10mm subsegments denoted with the nomenclautre prox 1, prox 2, and prox 3. The same nomenclature with use of numbers would be used to describe the subsegments of the mid, distal, or distal distal segments. In order to adjudicate a plaque level event, the adjudicator will need to identify the event culprit lesion and determine its location on a segment and subsegment level. A MCRN Plaque Coordinator will create still images of the index and event angiograms and indicate segment borders for ease of adjudication by a separate, blinded Plaque Adjudicator. As we move through the steps of a plaque level adjudication we will provide an example.

17. Final Plaque Adjudication
The MCRN Plaque Adjudicator identifies the Ware Segments and Subsegments that contain the endpoint event culprit lesion based off of the adjudicated lesion information provided by Cleveland Clinic
MCRN Plaque Adjudicator is blinded to all NIRS data
Cleveland Clinic Physician Adjudication team confirms adjudication 1 2 3
Plaque-Level Endpoint Event: Adjudicated Ware Segments and Subsegments
Here is a visual representation of how we have defined segments and subsegments for both the purposes of index procedure analysis and event adjudication. For a given vessel, in this example the LCX, we divide the pullback into 30 mm segments with a maximum of 4 segments. These segments, the proximal, mid, distal, and distal distal, comprise a possible total 120 mm of scanned vessel. Each of these segments are further divided into 10mm segments that we refer to as subsegments. As visualized in this blue proximal segment, we have the three 10mm subsegments denoted with the nomenclautre prox 1, prox 2, and prox 3. The same nomenclature with use of numbers would be used to describe the subsegments of the mid, distal, or distal distal segments. In order to adjudicate a plaque level event, the adjudicator will need to identify the event culprit lesion and determine its location on a segment and subsegment level. A MCRN Plaque Coordinator will create still images of the index and event angiograms and indicate segment borders for ease of adjudication by a separate, blinded Plaque Adjudicator. As we move through the steps of a plaque level adjudication we will provide an example.

18. Methodology for the Vulnerable Plaque Endpoint
Ware Segment containing Endpoint Event Culprit Lesion
Developed a standardized method of determining location of plaques using Ware Segments and Subsegments
Utilizing systematic, blinded adjudication process guided by Cleveland Clinic
Suspected
Vulnerable plaque in non-culprit artery scanned at index
Cause of Index Procedure
Cause of Follow Up Endpoint Event

19. LRP Enrollment Complete
1563 patients
Completed 2 years follow up
Currently, 1518 pt years of follow up
Subjects
Sites

20. Conclusions Detection of vulnerable plaque is a priority
Near-Infrared Spectroscopy of lipid core plaque is detected in patients with ACS and post cardiac arrest
Preliminary studies support the predictability of lipid core findings of future events
The Lipid Rich Plaque (LRP) Study is the largest trial to detect vulnerable plaque, Complete enrollment and detect evaluable events
Expected presentation in 2017
If the LRP study meets the co-primary hypotheses then target technology will be applied for the treatment of vulnerable plaques

21. Thank You for Your Attention