14th Vietnam National Congress of Cardiology
Da Nang City Vietnam 2014

New Insights In AMI:
From Vulnerable to Ruptured Plaque

Dr Tan Huay Cheem
MBBS, M Med(Int Med) MRCP(UK), FRCP(Edinburgh), FAMS, FACC, FSCAI
Director, National University Heart Centre, Singapore
Associate Professor of Medicine, Yong Loo Lin School of Medicine
National University of Singapore
President, Asia Pacific Society of Interventional Cardiologhy


100 Years Ago!

“……that thrombosis in the coronary artery
leads to the symptoms and abnormalities of
heart attacks……..
and that this was not inevitably fatal ”

JB Herrick JAMA 59:2015-2020, 1912


Non Progressive and Progressive Coronary Plaques

Virmani R et al Arterioscler Thromb Vasc Biol 2000; 20: 1262


Early Stages of Atherosclerosis Development

Pathologic Intimal Thickening (PIT) vs Atheroma

• PIT poorly defined entity sometimes referred to
as an "intermediate lesion"
• PIT fibrous cap overlying the areas of lipid is
rich in smooth muscle cells and proteoglycans.
Sparsely scattered macrophages and
lymphocytes may be present
• In contrast, fibrous cap atheroma, classically
shows a "true" necrotic core (NC) containing
cholesterol esters, free cholesterol,
phospholipids, and triglycerides. The
fibrous cap consists of smooth muscle cells in
a proteoglycan-collagen matrix, with a variable
number of macrophages and lymphocytes.

Virmani R et al Arterioscler Thromb Vasc Biol 2000; 20: 1262

2


Mechanisms of Early Necrotic Core Formation in Human Atherosclerosis

Pathologic intimal thickening and lipid pool is
converted to necrotic core from macrophages
infiltration and apoptosis leading to early necrotic core
formation



Mechanisms of Late Necrotic Core Formation in Human Atherosclerosis

Late necrotic core is likely the result of defective
efferocytosis as well as plaque hemorrhage which
contribute to free cholesterol within necrotic core


Coronary Thrombosis


Types of Lesions That Cause Coronary Thrombosis

• Plaque Rupture
• Plaque Erosion
• Calcified Nodule

Virmani R et al Arterioscler Thromb Vasc Biol 2000; 20: 1262


Gross and Light Microscopic Features of Plaque Rupture
60 to 65% of thrombi in sudden coronary death occurs from plaque rupture

Virmani R et al Arterioscler Thromb Vasc Biol 2000; 20: 1262


Gross and Light Microscopic Features of Plaque Erosion
30 to 35% of thrombi in sudden coronary death occurs from plaque rupture

Virmani R et al Arterioscler Thromb Vasc Biol 2000; 20: 1262



Histological Characteristics of Plaque Erosion,
Plaque Rupture and a Stable Plaque

(A) Eroded plaque: Subcritical stenosis, unremarkable necrotic core, and overlying thrombus on an
intact fibrous cap. The cap is rich in smooth muscle cells and proteoglycans, and there is minimal
inflammation at the base of the thrombus. The plaque does not show any positive modeling.
(B) Ruptured plaque: Positively remodeled, critically occlusive atherosclerotic plaque with a cholesterol
crystal-rich large necrotic core ((NC) covered by a very thin and inflammed fibrous cap,
which is disrupted

Prati et al JACC CV Imaging 2013: 6: 283-287


Light Microscopic Features of Calcified Nodule
2 to 7% of thrombi in sudden coronary death occurs from plaque rupture

• Calcified nodules are plaques with luminal thrombi showing calcific
nodules protruding into the lumen through a disrupted thin fibrous
cap. There is absence of an endothelium at the site of the thrombus, and
inflammatory cells (macrophages, T lymphocytes) are absent.
• Occurs in older individuals, usually men, type 2 diabetes mellitus,
metabolic syndrome, hypertension, smoking
Virmani R et al Arterioscler Thromb Vasc Biol 2000; 20: 1262


Distribution of Culprit Plaques by Sex and Age
in 241 Cases of Sudden Coronary Death
Acute Thrombi


Organized
Thrombi

No Thrombi:
Fibrocalcific Plaque

Totals

Rupture

Erosion

Calcified
Nodule

<50 years

45 (46)

17 (17)

2 (2)

15 (15)

20 (20)

99

>50 years


19 (23)

8 (10)

3 (4)

27 (33)

26 (31)

83

<50 years

1 (3)

14 (42)

0

5 (15)

13 (40)

33

>50 years

9 (35)


6 (23)

1 (4)

5 (19)

5 (19)

26

Total

74 (31)

45 (19)

6 (2)

52 (22)*

64 (26)†

241

Men

Women

Values correspond to the number of cases; those in parentheses are percentages.

*Organised thrombi with healed myocardial infarct (HMI) = 46/52, 89%.
†No thombi (stable plaque) with HMI=32/64 (50%); thus, 32/241, or 13%, of sudden death cases have stable
plaque with HMI.

Virmani R et al Arterioscler Thromb Vasc Biol 2000; 20: 1262


Optical Coherence Tomography Compared with IVUS
and Coronary Angioscopy In Assessing MI Culprit Lesion

Typical fibrous cap disruption

Typical fibrous cap erosion

• OCT identified plaque rupture and plaque
erosion better than IVUS and coronary
angioscopy
• Can measure fibrous cap thickness
• TCFA in 83% of 30 patients

Typical intraluminal thrombi

Kubo T et al J Am Coll Cardiol 2007; 50:933-9


OCT Study of STEMI and NSTEMI Lesions

• 89 ACS pts (STEMI=40, NSTEMI=49)
• STEMI: Higher Incidence of
- plaque rupture,

- thin-cap fibroatheroma
- red thrombus
- and larger area of ruptured cavity
• Ruptured plaque of which aperture
open-wide against direction of coronary
flow (46% vs 17%, p=0.036)

Ino Y et al J Am Coll Cardiol Intv 2011; 4: 76-82



Vulnerable Plaque


Vulnerable Plaque Consensus: Clinical Definition
Vulnerable plaque after 2003 (broad clinical-pathologic
definition derived from currently available knowledge and
recognizing retrospective and prospective aspects):
Any thrombosis-prone plaque or plaque at a risk of rapid
progression, with potential of becoming a culprit lesion and
triggering an ACS independent of its specific morphology
(although TCFA is still believed to be the most prevalent lesion
type in 60-70% of cases)

Circulation 2003; 108: 1664-1672


Accepted Histological Definition of TCFA or Vulnerable Plaque

Modified from Juan Granada TCT 2012



TCFA Presence is the Focal Manifestation of a Systemic Disease

• TCFA and ruptured plaques accounted
for only 1.6% and 1.2% of the total length
of the coronary tree examined in patients
dying of cardiovascular cause
• Majority occurred in proximal third of arteries
• 92% clustered within 2 or fewer
nonoverlapping 20-mm segment

Suspected precursor of rupture-mediated thrombosis occur in a
limited focal distribution in the coronary arteries

Cheruvu PK et al J Am Coll Cardiol 2007; 50: 940-9


Differing Plaque Morphologies (On OCT) In
Exercise-Triggered and Rest-Onset Acute Coronary Syndrome
Rest (n=28)

Exertion
(n=15)

p

Thrombus

27 (96)


11 (73)

0.04

Thin-Cap Fibroatheroma at culprit site

16 (57)

6 (40)

0.35

Broken at plaque shoulder

16 (57)

14 (93)

0.017

Thickness of broken fibrous cap, µm

50 (15)

90 (65)

0.0017

Data presented are median (interquartile median) or n (%)


• Thickness of broken fibrous cap correlated positively with activity
at the onset of ACS

• TCFA is predisposed to rupture at rest and during day-to-day activities
• Plaque rupture may occur in thick fibrous cap (up to 140 µm)
depending on exertion level
Tanaka A et al Circulation 2008; 118: 2368-73


Coronary CTA Images with Napkin-Ring Signs
and Invasive Angiographic Images

Conclusion: Napkin-ring sign characterised by plaque core with low CT attenuation
surrounded by a rimlike area of higher attenuation
Strongly associated with future ACS event, independent of other high-risk coronary CTA features

Otsuka K et al J am Coll Cardiol Img 2013; 6: 448-57


Are Mildly Obstructive Lesions More Likely
To Cause Acute Coronary Events?


Stenosis Severity of Culprit Atherosclerotic Plaque Causing AMI

5-Year Frequency (%)

Frequency


Luminal Stenosis

14%

>70

18%

50-70%

68%

<50%

Severity of Luminal Stenosis (%)

MI

Culprit Coronary Lesion in AMI

Coronary occlusion

86% of lesions causing AMI
were <70% diameter stenosis

DE Newby et al Heart 2010; 96: 1247-1251