1) The study examined 92 hearts from patients with severe coronary artery disease who died suddenly. The hearts were sectioned and plaque types were classified. 2) The number of "vulnerable" plaques, particularly thin cap atheromas, was highest in hearts of patients who died from acute plaque rupture and lowest in those with incidental disease. 3) Thin cap atheromas and other unstable plaque types were concentrated in the proximal coronary segments, similar to the distribution of plaque ruptures. The study suggests vulnerable plaques contribute to acute coronary syndromes and are non-uniformly distributed within the coronary arteries.

1. The “Vulnerable” Plaque:
Frequencies in Sudden Coronary
Death
Allen P. Burke, M.D.
Frank Kolodgie, Ph.D.
Andrew Farb, M.D.
Renu Virmani, M.D.
Armed Forces Institute of Pathology
Washington, D.C.

2. We serially sectioned the epicardial coronary arteries of 92 hearts from
59 men and 23 women dying with severe coronary disease ( 1≥
epicardial artery with 75% cross sectional luminal area narrowing).≥
The causes of death were assigned as incidental coronary disease, dying
of other causes; coronary thrombosis overlying plaque erosion; acute
thrombus overlying plaque rupture; stable plaque with healed infarct, no
other cause of death found at autopsy; stable plaque with no other cause
of death found at autopsy and no healed infarct. The purpose of the
study was to determine the frequency and distribution of “unstable” or
“vulnerable” plaques by mechanism of death. The number of thin cap
atheromas was greatest in hearts with acute ruptures (2.2 ± 0.4), fewest
in incidental coronary disease (0.4 ± 0.2), and intermediate in stable
plaque (1.2 ± 0.4). The distribution of thin cap atheroma,
fibroatheromas with hemorrhage, acute ruptures, and healed plaque
ruptures was similar to one another, and concentrated in proximal
segments. We conclude that the number of “vulnerable” plaques varies
by acute coronary syndrome, and that they are concentrated in proximal
segments, mirroring the distribution of plaque ruptures.
ABSTRACT

3. Introduction
The identification of “vulnerable plaques,” a term coined by Little
in 1990 and further defined by Muller in 1992, is of paramount
importance in potential imaging screening techniques. It has been
shown that acute narrowing in the coronary arteries often occurs in
areas of only moderate pre-existing atherosclerosis, and that plaque
progression occurs largely as a result of episodic thrombosis and
organization. There is a paradigm for the progression of plaques
that lead to rupture; namely, formation of a large necrotic core,
intraplaque hemorrhage, thinning of the fibrous cap, and ultimate
breaking of the cap leading to thrombus in the lumen. Other forms
of acute thrombus, such as plaque erosion, are less common than
ruptures and do not have candidate precursor lesions at this time
that potential imaging strategies can target. The purpose of this
study is to identify the numbers and distribution of coronary
thrombi and precursor lesions in a series of autopsy hearts,
focusing on thin cap atheromas and their relationship to plaque
rupture.

4. Materials
A series of 92 consecutively hearts were examined, with epicardial
coronary arteries sectioned serially at 3-5 mm intervals. Cases
were selected on the basis of sudden unexpected death and 1≥
epicardial artery showing 75% cross sectional luminal narrowing.≥
Mechanisms of death were classified as noncoronary (incidental
severe coronary disease after another cause of death was found
after complete autopsy, n = 19), sudden death due to plaque erosion
with or without acute myocardial infarction (n=5), sudden death
due to acute plaque rupture, with or without acute myocardial
infarction (n=32), sudden death due to atherosclerosis in the
absence of healed infarct or coronary thrombus (n=17), and sudden
death due to atherosclerosis in the absence of coronary thrombus,
but in the presence of healed infarct (n=19).

5. Methods
Every lesion with >50% cross sectional luminal narrowing was
studied histologically and classified by the Virmani classification.
The mean numbers of each type of plaque were compared by
mechanism of death, and the association between thin cap
atheromas and acute rupture was determined, based on relationship
between the site of thin cap atheroma (same vessel or remote site)
compared to the site of the ruptured plaque. The proximal regions
consisted of the first 3 centimeters for the right coronary, before
the first diagonal branch for the left anterior descending, and the
obtuse marginal for the left circumflex. Middle segments were
between 1st
and 2nd
diagonals for left anterior descending, between
left obtuse marginal 1 and left obtuse marginal 2 for circumflex
and beyond 3 cm of the right to the right marginal branch.

6. Case characteristics
Mechanism
of death
Age,
yrs
(mean
± SD)
Number
of
segments
studied
Mean
heart
weight
(gm)
Male:
female
Non-
coronary (19)
54 ± 11 20 ± 12 534 ±
162
15:4
Plaque
erosion (5)
45 ± 3 17 ± 7 486 ±
133
2:3
Stable plaque
(17)
57 ± 15 28 ± 22 471 ±
92
9:8
Healed
infarct (19)
59 ± 13 31 ± 15 558 ±
142
13:6
Acute plaque
rupture (32)
52 ± 11 29 ± 28 506 ±
107
30:2

7. Classification of plaques
Plaque type n
Fibroatheroma 229
Fibroatheroma with hemorrhage 133
Plaque rupture 32
Plaque erosion 5
Healed rupture 75
Organized thrombus 68
Total 542

8. Frequency of fibroatheroma, by
mechanism of death
00
22
44
66
88
1010
1212
NumbersoffibroatheromasNumbersoffibroatheromas
noncoronarynoncoronary
erosionerosion
stableplaquestableplaque
healedmihealedmi
acuteruptureacuterupture

9. Frequency of intraplaque
hemorrhage, by mechanism of deathNumbersofintraplaquehemorrhageNumbersofintraplaquehemorrhage
noncoronarynoncoronary
erosionerosion
stableplaquestableplaque
healedmihealedmi
acuteruptureacuterupture
00
11
22
33
44
55
66

10. Frequency of healed rupture, by
mechanism of death
00
11
22
33
44
55
66
77
NumbersofhealedrupturesNumbersofhealedruptures
noncoronarynoncoronary
erosionerosion
stableplaquestableplaque
healedmihealedmi
acuteruptureacuterupture

11. Frequency of thin cap atheroma,
by mechanism of death
00
.5.5
11
1.51.5
22
2.52.5
33
NumbersofthincapatheromasNumbersofthincapatheromas
noncoronarynoncoronary
erosionerosion
stableplaquestableplaque
healedmihealedmi
acuteruptureacuterupture

12. Hearts with plaque rupture: distribution
of thin cap atheromas
# TCFA,
same
artery
#TCFA,
same side
(r vs. left)*
#TCFA,
different
side
Mean
number
.48 ± .7 .43 ± .9 .70 ± .9
% with
1 TCFA
37% 32% 41%
* different artery

13. Proportion of types of “unstable” plaques, by
approximate distance from ostium
0
10
20
30
40
50
60
Fibro-
atheroma
hemorrhage
into plaque
thin cap acute
rupture
healed
rupture
left main
proximal
mid
distal
%distribution

14. Conclusions
• The number of “vulnerable” plaques varies in patients dying with
severe coronary disease by mechanism of death
• Plaques with large cores, plaque hemorrhage and thin caps are most
frequent in patients dying with acute plaque rupture, and infrequent in
incidental severe disease and plaque erosion
• Healed ruptures are most frequent in patients dying with acute ruptures
and healed myocardial infarcts
• Thin cap atheromas are are most predominant in the proximal
segments, and are distributed similarly to other “unstable” plaques