Kei Takahashi, MD0.18 Histopathological analysis of sudden death adults with coronary artery aneurysms

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O-18

Histopathological analysis of sudden death adults with coronary artery aneurysms

Kei Takahashi1, Toshiaki Oharaseki1, Yuki Yokouchi1, Yasunori Enomoto1, , Kino Hayashi2, Kumiko Asakura2, Kazuyuki Saito2,3, Aya Takada2,4

1 Department of Pathology, Toho University Ohashi Medical Center2 Tokyo Medical Examiner's Office3 Department of Forensic Medicine, Juntendo University School of Medicine4 Department of Forensic Medicine, Saitama Medical University Faculty of Medicine

IKDS2015

0-4歳人口

10万対

第22回全国調査成績 日本川崎病グループ

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male

female

incidence rate

Up to 1993年 122,237ptsSequela 3% 3,667pts

5% 6,112pts10% 12,224pts

Up to 1973年 5,450ptssequel 10% 545pts

Total Number of KD Patients 299,440ptsCardiovascular abnormalities in acute phase 9.3%Cardiovascular sequela 2.8%

【Aims】

To clarify the long-term changes in coronary artery lesions in Kawasaki disease (KD) by investigating autopsy cases of adults who had post-inflammatory coronary artery lesions.

【Materials】

Sixteen autopsy cases over 18 years of age, with1) a history of KD in infancy or childhood, or2) coronary artery aneurysms at autopsy despite no confirmed history of KD.

Age at death : 18 to 57 years old.

Males : Females = 11 : 5

1 18 F 165cm58Kg

Student 8yo: viral infection suspected, positive for anti-nuclear ab, collagen disease suspected 2013.4Rested in a sickbay owing to bad health and suddenly stopped and collapsed

2 19 M Student 10yo：fever of unknown origin 2000.1Collapsed suddenly while playing basketball in PE class

3 19 M 174cm73Kg

Student 3yo: KD under follow-up 1994.11 Complained about epigastralgia and collapsed suddenly in class a few days later

4 20 F 164cm53Kg

Office worker 5yo, 7yo: acute febrile exanthematous disease, 17yo: arrhythmia, under f/u 1984Was found lying in an office.

5 20 M Student 4yo: KD under f/u 1989.4Was quarreling on the road, then ran away with a bicycle. Suddenly stopped and collapsed.

6 24 F 160cm53Kg

Office worker Elementary student：Juvenile rheumatoid arthritis

2004.5Got a day off work for feeling unwell. Father took her to a hospital in the evening.

Suffered sudden cardiopulmonary arrest after vomiting and suffering convulsion.

7 25 M 171cm88Kg

Office worker 4yo: KD, f/u until 15yo 2013.11Was found lying on a road while jogging in a evening.8 27 M 173cm

59KgOffice worker childhood: slapped cheek disease 2013.4Was found lying on a road after drinking at mid-night.

9 33 M 184cm76Kg

none 25yo: integration disorder, under f/u 1998.2Was found lying in a bathroom at home at night10 34 M 175cm

90KgCarrier 1y6mo: KD, no CAL, f/u until15 yo 2011.1Complained about bad health in a morning and suddenly collapsed in a evening

11 40 M 174cm65Kg

Pipe fitter 20yo: hypertension, cardiac hypertrophy, 38yo: heart failure 1985.11Collapsed suddenly while working

12 40 F 160cm46Kg

Housekeeper 37yo: first attack of AMI, stent implantation in #6&7, repeated stent thrombosis (BMSx1, DESx2). 2006.2

Suffered sudden cardiopulmonary arrest after 5months of the last DES implantation

13 44 F good nutrition

Office worker KD (age unknown), Hashimoto disease (detail unknown)2009.12

Got on a bus after riding bicycle in a morning. deteriorated suddenly in a bus. Vf to stand still on EMS arrival.

14 45 M 188cm107Kg

Sheet-metal worker 2013.5Was found lying on a road in a morning after riding bicycle15 50 M 165cm

50KgElectrician 3yo: cyanosis, pertussis? , 44yo: alcohol abuse 2008.2

Worked as usual. Had difficulty in breathing while a passenger in a car and lost consciousness suddenly.

16 57 M 171cm 67Kg

Office worker infant: Rheumatic fever because of high fever 2004.1Sudden death (detail unknown)

Sudden death 16 ptsHistory of KD 5 ptsHistory of acute febrile disorder 6 ptsin childhoodPositive antinuclear antibody test 1 ptUnspecified 4 pts

Summary of the 16 autopsied casesAge at death 10s – 3 pts,

20s – 5 pts, 30s – 2 pts, 40s – 4 pts, 50s – 2 pts

【Observation items】Clinical CourseCoronary Arterial Lesions

Aneurysm 【＋ / －】Size 【Diameter】Site 【LMT-LAD / LCX / RCA (segment)】Form 【Dilated AN / Recanalized AN】

Calcification 【Lamellar / Granular】Mural thrombosis 【＋ / －】Atherosclerosis【AHA classification】Thrombotic occlusion 【＋ / －】Plaque injury 【Erosion / Rupture】

Myocardium LesionsIschemic lesion 【＋ / －, Site, AMI/ OMI】Interstitial fibrosis 【＋ / －】Endocaridial thickening【＋ / －】Intramural Artery

Two Forms of Coronary Artery AneurysmDilated AN Recanalized AN

Nomenclature and main histology

Initial LesionType I (initial) lesionisolated macrophage foam cells

Type II (fatty streak) lesionmainly intracellular lipid accumulationType III (intermediate) lesionType II changes & small extracellular lipid pools

Advanced LesionType IV (atheroma) lesionType II changes & core of extracellular lipidType V (fibroatheroma) lesionLipid core & fibrotic layer, or multiple lipid cores & fibrotic layers, or mainly calcific, or mainly fibroticType VI (complicated) lesionSurface defect, hematoma-hemorrhage, thrombusStary H C et al. Circulation 1995;92:1355-1374

A Definition of Advanced Types of Atherosclerotic Lesions and a Histological Classification of Atherosclerosis

Age Sex weight LMT-LAD LCX RCA

1 18 F 374g AN, Dil, Type III AN, Dil, Type II, AN, Dil,, Type IThromb occlusion

2 19 M AN, Dil, Type II non-AN, Type I AN, Dil, Type II, Thromb occlusion

3 19 M 370g AN, Dil, Type I non-AN, Type I AN, Recanal, Type I

4 20 F 320g AN､Recanal, Type I non-AN, Type I AN, Recanal, Type I

5 20 M AN, Recanal, Type II, non-AN, Type II AN, Dil, Type I

6 24 F 278g AN, Dil, Type VIThromb occlusion

AN, Dil, Type II, Thromb occlusion, AN, Recanal, Type I

7 25 M 446g non-AN, Type II non-AN, Type II non-AN, Type II

8 27 M 342g AN, Thromb occlusion, Type I, Thromb occlusion non-AN, Type I AN, Recanal, Type I

9 33 M 580g non-AN, Type I non-AN, Type II AN, Dil, Type II, Thromb occlusion

10 34 M 450g non-AN, Type V, Thromb occlusion non-AN, Type II non-AN, Type V

11 40 M 670g AN, Dil, Type V non-AN, Type II AN, Recanal, Type II

12 40 F 330g AN, Dil, Type I, Thromb occlusion AN, Dil, Type I AN, Dil, Type I

13 44 F 290g AN, Dil, Type I, Thromb occlusion non-AN , Type I AN, Dil, Recanal, Type II

14 45 M 527g AN, Dil, Type III, Thromb occlusion non-AN, Type II non-AN, Type II

15 50 M 333g AN, Dil, Type VI, Thromb occlusion non-AN, Type I AN, Recanal, Type II

16 57 M 345g AN, Dil,Type VI, Thromb occlusion

AN, Dil, Type VI, Thromb occlusion

AN, Dil, Type VI, Thromb occlusion

LMT－LADAN(＋) (13pts)

Dilated(11)

Recanalized(2)An(－) (3pts)

LCXAN(＋) (4pts) Dilated

(4)

An(－) (12pts)

RCAAN(＋) (13pts)

Dilated(7)

Recanalized(6)An(－) (3pts)

Presence and Form of Aneurysm in each Coronary Artery Branch

Athero-sclerosis

Initial (Type I-III) Advanced (Type IV-VI)40 branches 8 branches

Coronary Artery Lesion

AN (+) AN(-) AN (+) AN(-)Dilated Recanalized Dilated Recanalized

16 8 16 6 0 2

Atherosclerosis and Coronary Artery Lesions

24yo: LAD, 40yo: LAD, 50yo: LAD, 57yo: LAD , LCX, RCA

Aneurysm AN(+) AN(-)13 1

Type of AN Dilated Recanalized13 0

Atheroscleroticlesion

Initial Advanced Initial Advanced Initial Advanced

8 5 0 0 0 1

Fourteen Coronary Artery Lesions with Thrombotic occlusion

18yo RCA, 19yo RCA, 24yo LCX, 27yo LAD, 33yo RCA, 40yo LAD, 44yo LAD, 45yo LAD

24yo LAD, 50yo LAD,57yo LAD, LCX, RCA

34yo LAD

24yo, female, LCX 57yo, male, LAD

2mm 2mm

Initial Lesion Advanced Lesion

Dilated Coronary Artery Aneurysm with Thrombotic Occlusion

40yo. Male, RCA44yo, female, RCA

Recanalized Coronary Artery Aneurysm -Initial Lesion -

25yo, male

LMT RCA

Non-aneurysmal Coronary Artery - Initial Lesion -

Histopathological studies were conducted on adult autopsy cases of patients who had either a history of KD or coronary artery aneurysms.

In regard to atherosclerosis, most coronary artery lesions were initial lesions (40/48 branches, 83%), while few were advanced lesions (8/48 branches, 17%).

Most advanced atherosclerotic lesions (75%) were observed to be in dilated aneurysms.

Thrombotic occlusion was found in 14/48 coronary artery branches. Almost all sites of thrombotic occlusion (13/14, 93%) were in a dilated aneurysm.

Advanced atherosclerotic lesion was confirmed in 5 of 13 branches of the dilated aneurysms with thrombotic occlusion. However, the remaining 8 branches of the thrombotic occlusions were seen in the initial lesion.

A pathological study of cases of adult sudden death due to coronary artery thrombosis (not be associated with KD) found that the 80% of cases of thrombotic occlusion were due to plaque rupture associated with advanced lesion, while only the 20% of cases were due to intimal erosion corresponding to initial lesion (Sato Y. Heart 91: 2005).

Our present findings indicate the possibility that, in adults as well as in children, a different mechanism of thrombus formation may be involved when there are remaining aneurysms compared with the cases of atherosclerosis.

Most cases of atherosclerosis with recanalized aneurysms and/or aneurysm-non-forming arteries were initial lesions, while thrombus formation was rare.

Does post-inflammatory arterial lesion become a risk factorof atherosclerosis?

- Investigation of sixteen autopsy cases over 18 years of age -

The dilated aneurysm is likely to become a risk factor for atherosclerosis and thrombotic occlusion. However, it must be kept in mind that thrombotic occlusion occur even in the initial atherosclerotic lesion in the dilated aneurysm.

Dilated AN (22)AdvancedAtherosclerosis (8)

Thrombotic Occlusion (14)

In case of recanalized aneurysm and aneurysm-non-forming artery, there are no evidence that both lesions have risk factors for atherosclerosis and for thrombotic occlusion.

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