Intravascular Near Infrared Spectroscopy (NIRS) Bifurcation - Lipid Core Plaque Shift Study

Coronary artery bifurcations (branching areas) are predisposed to atherosclerosis from
turbulent flow and increased shear stress. Dilating lesions that involve a branch vessel is
associated with the risk of closure of the side branch. Plaque redistribution or 'plaque
shift' across the carina of the bifurcation is regarded as the responsible mechanism for the
side branch stenosis and occlusion after angioplasty and stenting. Modern techniques of side
branch protection require positioning of a second wire into the side branch before starting
the treatment of the main branch. Placing an additional wire in the side branch is more
laborious and complex than the wiring of the main branch only, is associated with additional
use of contrast media and radiation, and may associated with additional risk of
complications. Being able to determine which side branches require wiring for protection
while treating the main vessel stenosis may make the procedure simpler and safer.

Lipid core plaque (LCP) in the coronary arteries is very common in acute coronary syndrome,
but can often be found also in patients with stable angina. Lipid core plaque cannot be
detected by angiography or intra-vascular ultrasound. Near infrared spectroscopy (NIRS) has
the ability to identify chemicals in mixture. LipiScan, a catheter based NIRS coronary
imaging system can detect intra-vascular LCP. This catheter has been shown to be able to
identify LCP through blood in a prospective autopsy study, and that the LCP detection
algorithm developed and validated on ex vivo data is applicable in vivo. The image generated
by this system is called 'chemogram'. The catheter has also been tested successfully in a
clinical study in the United States and Canada. Based on these studies the FDA approved the
use of the LipiScan coronary imaging system. In CUMC, we have started to use this catheter
to identify LCP, and have gained experience with its simple use.

This study is intended as a pilot study to identify angioplasty related redistribution or
shift of lipid core plaque (LCP) lesions that are located at sites of artery bifurcation. We
hypothesize that during angioplasty and stenting, soft plaque that contains lipid cores may
be prone to shift more than (hard) fibrotic or calcified lesions. This pilot study may help
to better characterize lesions likely to shift and to provide imaging-based information like
NIRS that will improve the interventional treatment of bifurcation lesions.

A total of 20 patients with significant coronary artery disease with a bifurcation lesion
suitable for angioplasty and stenting will be studied. The lesions that will be studied
contain significant stenosis (≥50% stenosis) located in proximity (less than 2 mm) to a side
branch. Prior to angioplasty, the main vessel involved in the bifurcation will be imaged
using the LipiScan Coronary Imaging System. Angioplasty and stenting will be performed in
the usual conventional way, and then re-imaged with the LipiScan system. Intravascular
ultrasound will be done as standard interventional imaging procedure, when directed by the
treating interventional cardiologist. Angiographic and Chemographic data will be
qualitatively and quantitatively analyzed to assess LCP and plaque shift into the side
branch. Subjects that have intravascular ultrasound as part of routine care, will have this
data analyzed and compared to the chemogram data.

Improved understanding of how plaques and lipid cores redistribute and under what conditions
redistribution occurs could assist interventional cardiologists to better plan and perform
complex procedures that involve bifurcation plaques. Improved procedural planning and
prediction of shift can reduce instances of difficult side branch rescue and reduce
occurrence of peri-procedural events, such as myocardial infarction. This may in turn lead
to a reduction in overall complexity of treatment procedures, complication, and procedure
recovery times.

The catheter-based interventional treatment of branching points in blocked heart blood
vessels is complex and prone to higher rate of complications. This study is intended to
better understand why and under what conditions coronary blockages move during balloon
angioplasty and stenting. The movement of coronary artery blockages during the standard
treatment of coronary disease often leads to blocking of small artery branches near the
treatment site. The blocking of these small branches does not occur at all times, but when
it does occur it often results in small myocardial infarctions or residual chest pain.

All patients in this study will undergo standard cardiac catheterization and intervention as
directed by their treating physician. In this research, the researchers will analyze imaging
data that will be collected during the procedure. This includes the angiography (all
patients), intravascular ultrasound (in the patients that the operator determines its need
for use as part of the procedure), and imaging from the LipiScan catheter (all patients).
The LipiScan catheter is approved by the FDA for intravascular detection of fat in the blood
vessel, and will be used to detect the fat composition of the blockage. This catheter,
detects whether the blockage is composed of fat and is soft, or is fibrous and hard. In this
study we are going to try to identify the type of blockages that are associated with
branching points, and to learn whether soft and fat containing blockages are associated with
shifting or movement of the blockage material into the side branch. The information learned
from this study may help interventional cardiologists in the future to better plan their
interventional techniques and strategy and to perform safer and more successful procedures.

Coronary artery bifurcations (branching areas) are predisposed to atherosclerosis from
turbulent flow and increased shear stress. Lesions situated at a bifurcation segment account
for up to 16% of the interventional procedures (1). Stenoses at a bifurcation remains one of
the most technically challenging lesion subsets to treat by coronary angioplasty and
stenting (2- 5). Dilating lesions that involve a branch vessel is associated with the risk
of stenosis or complete closure of the side branch. In the past, bifurcation lesions were
considered a contraindication to PTCA due to the significantly increased risk of side-branch
occlusion. In various series, the rates of side branch stenosis or occlusion post
angioplasty and stenting is in the range of 9-67% (6-11) of threatened side branches.
Salvage of an occluded side-branch may be difficult, and unsuccessful in around 50% of
rescues, especially when the ostium of the side branch contains stenosis prior to occlusion
(12, 13). In other cases, the side branch is not occluded, but may be severely narrowed,
mainly because of plaque shift. Over the years, with the improved experience, techniques,
and technology, it is common practice now to treat bifurcation lesions percutaneously, with
high success and acceptable complication rates. Nevertheless bifurcation lesion pose higher
technical demand and more use of interventional devices.

Using IVUS imaging, plaque redistribution was described during stenting (14, 15). Plaque
redistribution or 'plaque shift' across the carina of the bifurcation is regarded as the
responsible mechanism that compromises the side branch lumen. Other predictors of side
branch occlusion include significant branch-ostial stenosis, main vessel dissection, and
acute coronary syndrome including acute MI (16). The later are important situations in which
there may be a combination of thrombus on top of a lipid containing plaque.

Modern techniques of side branch protection entails positioning of a second wire into the
side branch before starting the treatment of the main branch (1,16, 17). The decision to
protect the side branch depends on the estimated risk of closure while treating the main
branch. Unfortunately, it is impossible to predict whether or not a specific side branch
will be compromised. Advancing an additional wire in the side branch is more laborious and
complex than the wiring of the main branch, mandating the use of larger caliber guiding
catheters, prolongs the overall procedure time, associated with larger volume of contrast
media and x-ray radiation, and may be associated with increased risk of complications like
coronary dissection, perforation, bleeding and contrast induced nephropathy (1). The
ability to identify which side branches need to be wired and protected while working on the
main vessel will make the procedure simpler and safer.