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CARDIAC INTERVENTIONS SCAI 2004
Intravascular atheroma
monitoring: Past, present,
and future of identifying
vulnerable plaques
Suzanne A. Sorof, MD
rotic plaque progresses, the plaque begins
There are approximately 2 million cases of acute coronary syndromes per to encroach on the lumen. This remodel-
year, with medical costs of $100 billion. Aggressive medical therapy with ing, known as the Glagov phenomenon,
3-hydroxyl-3-methylglutyaryl coenzyme A reductase inhibitors, beta-blockers, causes intimal hyperplasia, dilation of the
aspirin, platelet inhibitors, and angiotensin-converting enzyme inhibitors are entire vessel with atherosclerosis, and,
part of the treatment for this ever-growing problem of coronary atherosclero- ultimately, obstruction of the vessel.7 As
sis. As technology continues to evolve, there will be new techniques to assist reported in a recent paper by Pasterkamp
the interventional cardiologist in identifying a plaque and determining its et al,8 3 major interrelated determinants of
primary composition. a plaque’s vulnerability to rupture include
the thickness of the fibrous cap, the size
C
oronary artery stenosis is gener- tory cells, especially macrophages, take up and composition of the atheromatous lipid
ally asymptomatic until a lesion lipids and oxidize them, resulting in the core, and inflammation within or adjacent
exceeds 70% to 80% of the vessel formation of unstable plaques. When this to the fibrous cap.
lumen. An acute coronary syndrome, vulnerable or unstable plaque ruptures,
however, is often due to the rupture of a platelets adhere to the endothelium and Current interventional techniques
40% to 50% soft, lipid-laden plaque.1,2 activate such factors as endothelin-derived Angiography and intravascular ultra-
When a plaque ruptures, a cascade of relaxing factor, prostacyclin, tissue plas- sound (IVUS) are routinely used to assess
clotting factors occurs at the site, causing minogen activator, and other factors, which coronary vessels. With coronary angiog-
the formation of a thrombus.3 This review are prothrombotic in nature.4 raphy, atheroma monitoring is difficult
will discuss atheroma monitoring with because the contrast fills the lumen and
conventional interventional techniques Vulnerable plaques the 2-dimensional (2D) images are only a
and new transcatheter techniques, as well The fibrous collagen cap provides sta- rough estimate of the lesion underneath.
as other adjunctive technology that could bility to the atherosclerotic plaque and Often, a complex plaque is an eccentric
aid in the identification of soft, lipid-laden extracellular matrix below. The unstable lesion and is associated with thrombosis.
lesions. In addition, the combination of plaque has a thin fibrous cab and thrombus In addition, the lesion’s length, diameter,
interventional and molecular biological at the shoulder, many inflammatory cells, and composition are difficult to accurately
techniques used to label and identify and a large lipid core.5 The atheromatous characterize. Lastly, angiography is ap-
inflammatory proteins involved in plaque core makes up >40% of the plaque and is proximately 50% sensitive in identifying
formation will also be discussed. Identifi- rich in cholesterol. The softer the core, the calcium deposition.
cation and treatment of these plaques more vulnerable it is to rupture. Moreover, angiography does not deter-
before rupture may prevent loss of myo- Because there is a significant amount of mine if the lesion is a calcified plaque, a
cardium and sudden cardiac death. circumferential sheering stress on the fibrocalcific lesion, a fibrofatty lesion, or a
atheroma, the softer plaques are prone to lipid-laden soft lesion. Therefore, adjunc-
Coronary artery disease stress.6 Early in atherosclerosis, the exter- tive technologies have developed and are
Coronary artery disease is a disease of nal elastic membrane of the arterial wall currently used to delineate further coro-
the vessel wall caused by inflammation undergoes positive remodeling, allowing nary arterial lesions and to measure, quan-
and leukocyte recruitment by dysfunc- the vessel size to enlarge and preserving tify, and qualify the underlying patho-
tional vascular endothelium. Inflamma- the size of the lumen. As the atheroscle- logical atheroma.
34 APPLICATIONS IN IMAGING • CARDIAC INTERVENTIONS Supported by an educational grant from GE Healthcare DECEMBER 2004
SCAI 2004 CARDIAC INTERVENTIONS
FIGURE 1. Intravascular ultrasound of a coronary vessel with disease showing ruptured plaque with positive remodeling. An angiogram (left) was
obtained after thrombolysis for acute myocardial infarction. The black arrow indicates the occlusion site, and the gray arrow shows the proximal refer-
ence site. At the reference site, the external elastic membrane area is smaller (14.3 mm2) than the area at the ruptured site (18.9 mm2), indicating pres-
ence of positive remodeling. (Figure reprinted with permission from Nissen SE, Yock P. Intravascular ultrasound. Novel pathophysiological insights and
current clinical applications. Circulation. 2001;103:604-616.15)
Intravascular ultrasound: wall can be examined, the detection of the to see these layers of the artery at a level of
The present extent and severity of atherosclerotic dis- 100 to 200 µm. The intima, media, and
Intravascular ultrasound has character- ease is much more sensitive by IVUS than adventitial layer can easily be discerned to
ized atheroma pathology since the mid- by angiography. give an estimation of the plaque burden
1980s, when cardiologists found a growing Intravascular ultrasound provides single present in the intimal layer. Ultrasound
need to define the lesion morphology and cross-sectional areas of the arterial wall to can detect the presence or absence of
length during angioplasty. It is a supple- enable the viewer to look at the length and structural abnormalities of the vessel wall
mental technique when performing angiog- thickness of the preintervention lesions. after mechanical interventions, including
raphy. The resolution of the ultrasound Intravascular ultrasound does not measure dissections, tissue flaps, intramural he-
system is directly related to its frequency. functional ability. Currently, it is the most matomas, perforations, and irregular sur-
Using a 20- to 40-MHz transducer at commonly used imaging modality that face features12-14 (Figure 115). Limitations
the end of a catheter, clinicians can per- provides images in which variations in of IVUS include nonuniform rotational
form early atheroma monitoring. This arterial geometry and atherosclerotic distortion (NURD). This distortion is
technology provides 2D cross-sectional plaque can be studied and monitored.10,11 caused by tortuous, calcified, or stenotic
tomographic images of the arterial wall Particularly with complex lesions and vessels and must be recognized. The oper-
with an axial resolution of 150 µm and a left main coronary atherosclerosis, IVUS ator must ensure that the catheter is not
lateral resolution of 250 µm,9 resulting in has become an important adjunctive tool flexed and may need to change the direc-
an excellent histologic representation of in the catheterization laboratory. After tion of the guiding catheter to eliminate
the inner vessel wall. Intimal thickness intervention, IVUS can also provide accu- the distortion. Another limitation of IVUS
increases with age, and this is a sign of rate images to ensure that stents are includes decreased visualization of the
early atheroma. Intravascular ultrasound deployed correctly. layers of wall due to the backscatter of
can characterize plaque components, Intravascular ultrasound has allowed blood and components within the lumen.
including the stiffness of the wall and the cardiologists to monitor plaques in the A complication of IVUS is coronary
composition of the plaque. Because the coronary arteries by allowing the observer spasm; the guidewire and catheter sys-
DECEMBER 2004 Supported by an educational grant from GE Healthcare APPLICATIONS IN IMAGING • CARDIAC INTERVENTIONS 35
CARDIAC INTERVENTIONS SCAI 2004
OPTICUS22 trial was a neutral study that
did not show any long-term angiographic
or clinical benefit for IVUS.
Elastography is a new use for IVUS in
monitoring atheromas. This technique is
based on the principle that tissue compo-
nents differ in hardness as a result of their
histopathologic composition. The various
tissues compress differently if a defined
pressure is applied.23 Elastography is able
to discriminate between soft or hard mate-
rial located in the vessel wall24 and has the
potential to identify plaque vulnerability
in regions of high stress. Limitations of
elastography are the artifacts caused by
cardiac motion during the cardiac cycles
(Figure 28).
Optical coherence tomography
In the Fall of 2004, a new forerunner of
imaging called optical coherence tomog-
raphy (OCT) will emerge for coronary
imaging. This is a technique used in oph-
thalmology25 to assess the anterior cham-
FIGURE 2. Intravascular ultrasound (upper panel, left) and elastogram (upper panel right) and his-
tologic sections with alfa-actin stain, picro Sirius red stain without and with polarized light of a
ber and retina of the eye with unprece-
femoral artery. The ultrasound reveals an eccentric plaque between the 2 o’clock and 11 o’clock dented resolution. It will become an
positions. The elastogram shows that the plaque can be divided into 2 sections: A low-strain part important adjunct to angiography and
(4 o’clock to 11 o’clock) and a high-strain part (2 o’clock to 4 o’clock). The histologic study reveals IVUS and has the approval of the U.S.
that the material between the 4 o’clock and 11 o’clock positions is fibrous as opposed to the region Food and Drug Administration for use in
between the 2 o’clock and 4 o'clock positions,which is more vulnerable with no smooth muscle or
collagen. (Figure reprinted with permission from Pasterkamp G, Falk E, Woutman H, Borst C. Tech-
coronary artery disease.
niques characterizing the coronary atherosclerotic plaque: Influence on clinical decision making? Optical coherence tomography is based
J Am Coll Cardiol. 2000;36:13-21.8) on fiberoptics that produce a cross-
sectional image using the optical reflec-
tem may cause irritation or spasm to the guided placement of stents, the 2-year tar- tance properties of the underlying tissue.26
coronary vessel. This can become a seri- get lesion restenosis rate was 17% com- Using infrared light and mirrors through
ous problem if the guidewire is advanced pared with 29%. The AVID trial18 showed a catheter, the histologic features of
into a tight stenosis or a smaller distal that 33% of angiographically expanded the plaque can be accurately depicted.
vessel. Nitroglycerin prior to insertion of stents were actually underexpanded, Infrared wavelength (850 to 1300 Hz) is
the instrument is advised to prevent which is a major cause of stent stenosis delivered into the artery, where the reflec-
spasm. Prompt withdrawal is recom- and/or thrombosis. tive backscatter on a mirror measures
mended if there is resistance to the cath- Other trials have also supported the use depth and position of the lesion. The
eter to avoid dissection. of stent placement using IVUS, including intensity of the reflective light provides
Since IVUS has been used in conjunc- the MUSIC trial19 (1998) that showed that the signal intensity. Studies have shown
tion with stent deployment, there has been IVUS guidance could improve restenosis that the properties of various cells and tis-
a decrease in restenosis rates. Trials have after stenting. The BEST trial20 was a mul- sue have different reflective indexes and
suggested a benefit of IVUS guidance. ticenter randomized trial that proved that that when the cells take up collagen,
Colombo et al16 looked at 359 patients IVUS-guided percutaneous transhepatic fibrous material, or lipid, a different re-
with IVUS after angiographically ade- cholangiography (PTCA) was not inferior flective index is obtained.27
quate stent implantation. The results to routine angiographically guided stent Optical coherence tomography will
showed that 30% of stents placed had implantation. The results of the CRUISE21 allow more exact definition of the plaque
optimal expansion after angiographic trial showed that IVUS guidance signifi- composition. The resolution with OCT at 4
guidance; with IVUS guidance, there was cantly reduced lesion revascularization to 10 µm is much better than the resolution
an increase to 96%. The results of the rates from 15.3% (angiographically with IVUS (100 µm). This high resolution
SIPS trial17 indicated that with IVUS- guided) to 8.5% (IVUS-guided). The allows for the inspection of the fibrous cap
36 APPLICATIONS IN IMAGING • CARDIAC INTERVENTIONS Supported by an educational grant from GE Healthcare DECEMBER 2004
SCAI 2004 CARDIAC INTERVENTIONS
of the atherosclerotic plaque to determine if
there is infiltration of macrophages or
inflammatory cell migration. Because acti-
vated macrophages are often found in
patients having an acute coronary syndrome
or sudden cardiac death, high-resolution
technology with OCT would be extremely
valuable in assessing which plaques are the
most vulnerable and need treatment imme-
diately. Limitations of OCT include the
inability to see through blood. Also, because
it is an optical reflective technique, its depth
is only 2 mm. Therefore, one cannot see
through to the adventitia when looking from
FIGURE 3. Fibrous coronary plaque imaged in vivo by (A) optical coherence tomography (OCT) and the luminal surface (Figure 328).
(B) intravascular ultrasound (IVUS). (A) An echolucent atherosclerotic plaque extends from 5 o’clock
to 12 o’clock with regions of fibrous [f] (echo-dense) areas present. The arrowhead measures the Acoustic emissions: The future
plaque cap by OCT (122 µm ± 7 µm). (B) In the corresponding IVUS image, the fibrous echolucent
plaque (arrow) is also visualized. (Reprinted with permission from Jang IK, Bouma BE, Kang DH, et
During percutaneous coronary interven-
al. Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: tions, balloon angioplasty causes damage to
Comparison with intravascular ultrasound. J Am Coll Cardiol. 2002;39:604-609.28) the atherosclerotic lesion and to the arterial
wall. Some of the arterial wall injuries
A C
B D
FIGURE 4. The sound waves generated from the dissection of coronary vessels. Composite figure depicts the postintervention tissue segments in
which dissection was absent along with corresponding and pressure data not suggesting sound emission. (A) Two segments exhibit progressively
more traumatic dissections (B and C) along with simultaneous vascular acoustic emissions and pressure signals recorded during dilation of these spec-
imens. (D) Vascular acoustic emissions and pressure signals collected from inflation of balloon without tissue specimen. This image shows significant
dissections occurring following in vitro angioplasty, which can be postulated as a cause of the neointimal hyperplastic response following angioplasty.
This has been postulated as a cause of restenosis.39 (Reprinted with permission from Vonesh MJ, Mockros LF, Davidson CJ. In Vitro identification of
angioplasty induced injury by use of vascular acoustic emissions. Circulation. 1997;95:1022-1029.37)
DECEMBER 2004 Supported by an educational grant from GE Healthcare APPLICATIONS IN IMAGING • CARDIAC INTERVENTIONS 37
CARDIAC INTERVENTIONS SCAI 2004
include disruption of the intima, fracture unstable angina and acute myocardial 4. Sambola A, Osende J, Hathcock J, et al. Role of risk
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DECEMBER 2004 Supported by an educational grant from GE Healthcare APPLICATIONS IN IMAGING • CARDIAC INTERVENTIONS 39
