REVIEW
Sudden death due to cardiovascular disorders: a review of thestudies on the medico-legal cases in Tokyo
Tatsuya Murai, Mineko Baba, Ayako Ro, Naoko Murai,1 Yoshihiro Matsuo,1 Aya Takada2 and Kazuyuki Saito2
Department of Legal Medicine, School of Medicine, Keio University, Tokyo, 1Tokyo Medical Examiner's Of®ce
Tokyo, 2Department of Forensic Medicine, Saitama Medical School, Saitama, Japan(Received for publication on February 26, 2001)

Abstract. The Tokyo Metropolitan Government has a medical examiner system, in which all cadavers
classi®ed as ``unusual death'' in the city of Tokyo should be examined, and if necessary, autopsied todetermine the cause of death. Of about 10,000 unusual deaths examined per year, two thirds are usually determined to have died of natural causes. The most common cause of sudden natural death isischemic heart disease, especially acute myocardial infarction. Pathological examination, however,proves acute myocardial ischemia in only one third of autopsies. Subarachnoid hemorrhage and intracerebral hemorrhage, acute myocarditis and cardiomyopathies and aortic dissection/aneurysm as well as
pulmonary thromboembolism are frequent causes of death in medical examiner cases. Both pathological and socio-medical problems associated with these diseases are discussed. (Keio J Med 50 (3): 175±
181, September 2001)
Key words: sudden death, unexpected death, medical examiner, medico-legal autopsy, cardiovasculardiseaseIntroduction
The prognosis of several diseases that were once
lethal have been improved through developments inclinical medicine. However, the number of patients who
die suddenly has not decreased in Japan, and this posesa critical problem in social medicine. In this article theauthors present the actual circumstances of sudden
death due to cardiovascular disorders in Tokyo, withreference to studies on medico-legal cases that have
involved medical examiners.
Sudden Death Investigated by Medical Examiners
The Tokyo Medical Examiner's Of®ce (TMEO) is anadministrative body that was established under the direction of the GHQ (General Headquarters) after thesecond World War. All cadavers classi®ed as unusual
according to the Japanese Medical Act in the city ofTokyo, including those whose deaths are due to ectogenic causes and those in which the cause of death isunclear, are examined by medical examiners who werealso trained as forensic pathologists. If the cause ofdeath is not clari®ed by an external examination, an
autopsy is performed, with or without the consent of
the family. The number of the examined bodies has
recently increased, and has reached about 10,000 per
year. Among these, about 2,500 are autopsied.
Natural death accounts for two thirds of the cadavers
investigated by medical examiners and most of these
are considered to be unexpected death (Fig. 1). Morethan half of these unexpected deaths are caused bycardiovascular disorders that mainly consist of diseasesof the heart, the great and intracranial vessels (Fig. 2).
Tokudome et al.1 classi®ed the clinical deaths into thosethat had had a medical history and those who had apparently been healthy. A signi®cant difference was notpresumed in the fraction of deaths due to cardiovascular causes between the two groups.
Ischemic Heart Disease
About 40% of the natural deaths investigated by
Tokyo medical examiners are due to ischemic heartdisease (IHD) or coronary heart disease. Tokudome, etal.1 examined incidents in which the patient had died

Reprint requests to: Dr. Tatsuya Murai, Department of Legal Medicine, School of Medicine, Keio university, Tokyo 160-8582, e-mail: murait@
mc.med.keio.ac.jp
175

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Murai T, et al: Sudden death due to cardiovascular disorders
Table 1 Pathological ®ndings of the heart in the cases of ischemic
heart disease
fresh or recent MI
rupture (ÿ)
()

ACS

5
(6.0%)

20(24.1%)

6(7.2%)j
31 (37.3%)

old MI

focal ®brosis

12(14.5%)

27(32.5%)j
39 (47.0%)

Fig. 1 Annual number of ``unusual death'' in the city of Tokyo.
(Tokyo Medical Examiner's Of®ce)

unclear13(15.7%)j
13 (15.7%)

MI: myocardial infarct, ACS: acute coronary syndrome.
Table 2 Comparison of the site of infarct in cardiac rupture between
hospital (pathological) and medico-legal autopsies
site of myocardial infarct hospital cases* medical examiner cases**
anterior***lateralinferior
postero-lateralmassive LV
LV  RV

21 (75.0%)
2 (7.2%)4 (14.3%)
1 (3.5%)150 (46.0%)
75 (23.0%)
64 (19.6%)
17 (5.2%)
15 (4.6%)
5 (1.5%)* Murai,2 ** Yamaguchi,6 *** including antero-septal and antero-apicalinfarcts.

Fig. 2

Breakdown of natural deaths in the medical examiner cases.

within 24 hours after the onset of attack, and reported
that IHD was the likely cause of death in 1,342 (44.2%)of those among the 3,179 deaths in the apparently
healthy group, and in 6,799 (45.3%) among the 15,010
deaths of individuals with a medical history. Murai2
reported that 8,897 deaths (40.0%) among 22,221 prehospital deaths were due to IHD.
Sudden death due to IHD includes acute myocardial
infarction (AMI), acute coronary syndrome (ACS),
arrhythmogenic myocardial scars and other conditions
that interfere with con®rming the cause of death as
IHD, because early myocardial ischemia cannot be
pathologically proven. A precise histological examination of the coronary arteries is necessary to identify
ruptured atheromatous plaques with thrombosis.
A pathological study of the 83 deaths cases that theauthors had determined to be caused by IHD showedthat acute myocardial ischemia was suspected in 31(37.3%), fresh or recent myocardial infarct in 11 andrupture of the atheromatous plaque of the coronary

artery without pathological infarct in 20 cases (Table 1).
If this result is applied to the total number of deaths
recorded by the TMEO, the estimated incidence of unexpected death due to clinical AMI in Tokyo, including
ACS, is 11±12/100,000 population per year.
Clinical studies of circadian variation in the incidence of sudden death due to IHD in Japan and elsewhere have demonstrated a high frequency of sudden
death in the morning and a low frequency during thenight.3,4 However, Matsuo, et al. reported a high frequency of sudden death due to IHD during the night.5
This discrepancy is explained by the fact that medical
examiner cases include patients who had died at night
are often found dead the next morning.
One fatal complication of myocardial infarction is
cardiac tamponade due to myocardial rupture. Yamaguchi6 stated that the characteristics of cardiac rupture
in deaths investigated by the medical examiner are (1)rupture of the free wall of the left ventricle (LV), (2)relatively high frequency in the lateral wall of the LV,(3) limited area of myocardial infarct, and (4) relatively rare coexistence of old myocardial infarct. Table
2 compares the data reported by Yamaguchi to thoseKeio J Med 2001; 50 (3): 175±181

from pathological autopsies examined by the authors ina hospital setting. Although cardiac rupture usuallyoccurs 3±10 days after the onset of the myocardial
infarction, we occasionally encountered deaths in which
cardiac rupture occurred in a much more recent myocardial infarct (Fig. 3).
Most sudden death caused by IHD happens to individuals over the age of 30 with severe coronary
artery sclerosis. Among children and or young adults
who suddenly die of IHD, such rare coronary lesions
are usually sequelae of Kawasaki disease7 or due to acongenitally anomalous origin of the left coronary
artery.8,9 Rupture of an atheromatous plaque with coronary thrombosis is found in most deaths due to AMI
as well as ACS (Fig. 4), whereas coronary embolism(Fig. 5),10 primary coronary dissection11 and coronary
involvement in aortic dissection (Fig. 6) are rare causesof myocardial infarction.
Cerebrovascular Disorders
Among the cerebrovascular disorders, subarachnoid hemorrhage (SAH) and intracerebral hemorrhage(ICH) are important causes of unexpected death, andfatal cerebral infarction is much rarer in deaths investigated by the medical examiner. SAH and ICH often
occur between the ages of 40±70 years. A gender difference is not apparent in SAH, whereas males predominate in ICH.
Sugai and Kono pathologically examined 117 deaths
due to SAH and found ruptured aneurysms in 110 ofthem (94.0%).12 They reported that the most commonsite of the ruptured aneurysm was the anterior communicating artery followed by the internal carotid arteries,
the middle cerebral arteries and the basilar artery.
Aoki, et al.13 examined autopsy records of SAH andreported that the anterior communicating artery had
the highest incidence of ruptured aneurysm, and the
middle cerebral arteries had the second highest. Although most of the cerebral aneurysms are of the saccular type that usually occurs in the bifurcations of
the cerebral arteries, arteriosclerotic, spindle-shapedand dolichoectatic types were identi®ed by Akimoto.14
Intracranial dissecting aneurysms have recently attracted
attention both clinically and pathologically. Murai, etal.15 reported that about 40% of the vertebral aneurysms with SAH were associated with medial dissectionof the arterial wall (Fig. 7).
Though the frequencies of SAH and ICH are similar among deaths investigated by medical examiners,
patients with SAH often die more rapidly than thosewith ICH, which sometimes results in prehospital death.
Most ICH is regarded as hypertensive, but this is dif®cult to prove pathologically without clinical informa-

177tion. Concentric hypertrophy of the left ventricle andsclerosis of the arterioles and the small arteries in thekidneys, adrenal glands and in other location are usefulfor estimating a history of hypertension. Besides ICH
due to hypertension, Yasuhara16 stated that cerebral
amyoloid angiopathy with cerebral hemorrhage might
be signi®cant in the ®eld of forensic medicine.
Aortic Dissection and Aortic Aneurysm
Among the aortic disorders are aortic dissections andruptured aortic aneurysms important in sudden unexpected death. Aortic dissection has the second highest
frequency as a disease of the heart and great vessels in
sudden deaths investigated by medical examiners, andTokudome, et al.17 reported that the frequency of aortic
dissection is double that of true aortic aneurysm.
Murai18 examined the TMEO autopsy records of
1,320 deaths due to aortic dissection and found thatmost of the sudden death due to this cause occurred
during the acute phase of medial dissection and that
rupture of a chronic dissecting aneurysm of the aorta israre in deaths investigated by the medical examiner.
The features of sudden death due to aortic dissection
are a higher incidence in winter than in summer (Fig.
8), predominance of type II dissection by DeBakey thatwas considered to be rare in clinical deaths, and male
predominance at a gender ratio of 1.53 : 1. Rupture of
the dissected channel was the most frequent causeof death and cardiac tamponade due to a rupture of
the ascending aorta was regarded as the cause of deathin 86.6% of acute dissections. Some patients withacute dissection died although the aortic wall had not
ruptured.19 Acute myocardial ischemia due to the extension of the medial dissection to the left coronary
artery was considered to be a probable cause of suchdeath.20,21
If aortic dissection is found in a child or young adultat autopsy, hereditary connective tissue disorders such
as Marfan's syndrome as well as Ehlers-Danlos' syndrome,22 pregnancy,23 or cardiac anomalies,24,25 especially a bicuspid aortic valve, should be suspected as thepathological base of the aortic dissection. Although the
etiology and pathogenesis of aortic dissection remain
ambiguous, cystic medionecrosis with disruptions ofelastic ®bers is often present. Furthermore, we found 3
cadavers with signi®cant granulomatous aortitis26,27
among 170 deaths due to acute aortic dissection. Hemodynamic factors such as a transient elevation of bloodpressure could have triggered medial dissection of theweakened aortic wall.
True aortic aneurysms are usually arteriosclerotic.
Syphilitic mesaortitis is scarce among recent deaths due
to aortic aneurysm. Takayasu's truncoarteritis, though

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Murai T, et al: Sudden death due to cardiovascular disorders

Fig. 3 Fresh myocardial infarct with a rupture. Myocardial necrosis
with neutrophilic in®ltration is observed, but no granulation tissue isfound. (H±E)

Fig. 4 Rupture of an atheromatous plaque and thrombosis of thecoronary artery. (Elastica van Gieson stain)(a)Fig. 6 Medial dissection of the left coronary artery as a complicationof aortic dissection. (Elastica Masson stain)

Fig. 7 Dissecting aneurysm of the vertebral artery with a rupture
resulting in SAH. (Elastica HE stain)

Fig. 9 Severe myocarditis with multinucleated giant cells (giant cell
myocarditis). Differential diagnosis with myocardial sarcoidosis isnecessary for this ®nding. (H±E)(b)
Fig. 5 Tumor embolism in the coronary artery. (a) Embolization ofa tumor tissue in the right coronary artery resulting in myocardial
infarction. (b) The tumor (papillary ®broelastoma) originated fromthe aortic valve. (Elastica van Gieson stain)

Fig. 10 Marked ®brofatty replacement of the right ventricular myocardium in ARVC/D. The outer layer of the left ventricle also shows airregular and ®brofatty substitution of the myocardium. (Masson'strichrome stain)

Keio J Med 2001; 50 (3): 175±181

Fig. 8 Monthly distribution of sudden death by aortic dissection.
(Tokyo Medical Examiner's Of®ce)rare even in Japan, might have caused sudden death inindividuals with aortic regurgitation.
Acute Myocarditis
Several to tens of deaths due to acute myocarditis(viral or Fiedler's isolated myocarditis) each year are
identi®ed at autopsy by the TMEO. Sudden death iscaused by this disease independently of age and gender.
Murai, et al.28 examined 58 autopsies according to thecriteria for acute myocarditis (Dallas),29 which include
myocardial necrosis and/or degeneration in addition
to interstitial in®ltration of mononuclear cells.30 The
in®ltrated cells consisted mainly of lymphocytes, butmarked in®ltration of eosinophils and/or granulomatousin¯ammation with multinucleated giant cells was sometimes evident (Fig. 9). Under such circumstances, theparticipation of a drug allergy should also be considered. Sudden death due to acute myocarditis occurs
frequently in winter, and incidence of death due to thiscause temporally and spatially accumulates, which arefeatures of death due to infectious diseases.
Murai, et al.28 revealed a socio-medical problem
associated with sudden death caused by acute myocarditis. About half of the patients who presented withfever and/or chest pain had been sent home by a doctor
due to misdiagnosis. Under such circumstances, trouble
arising between the family of the deceased and the
medical institution can develop into a civil action.
Cardiomyopathies
Cardiomyopathies account for 0.4% of the deaths
investigated by the Tokyo Medical Examiners. Mostof these consisted of the hypertrophic (HCM) anddilated types (DCM). The number of deaths due to
HCM and DCM are similar, but the ratios of a clinical179

history of cardiomyopathy differ. A clinical diagnosis ofcardiomyopathy was correct in under 50% of those with
HCM, and in 80% of those with DCM.31 Sudden deathin children and in young adults is often attributed toHCM. Patients with HCM should be carefully monitored at school, because fatal attacks often occur during
or after physical exertion. The heart of a patient with
HCM usually shows asymmetrical septal hypertrophy
as well as bizarre myocardial hypertrophy with ®ber
disarray, but the weight of the heart is not always
increased in younger patients.32
Arrhythmogenic right ventricular cardiomyopathy/
dysplasia (ARVC/D) is not so frequent, but it is important as a cause of death in young adults.33 Myocardial cells of the right ventricular wall are replaced by®brofatty tissue in ARVC/D (Fig. 10) and the left ventricular myocardium, though not to the same extent as
the right, is also affected.34
The secondary, or speci®c, cardiomyopathies that are
signi®cant in medico-legal autopsy consist of fatal myocardial sarcoidosis (FMD)35 and cardiac lesions inmyotonic dystrophy (MyD).36 FMD or MyD are notusually diagnosed until autopsy. Arrhythmia based on
lesions of the atrio-ventricular conducting system leads
to sudden death in FMD and MyD.
Autopsy reports of DCM-like cardiac lesions in ``occult'' progressive muscular dystrophy of the Becker
type37 and eosinophilic heart disease38 are rare.
Pulmonary Thromboembolism
Although pulmonary thromboembolism (PTE) was
rare in Japan, the frequency of sudden death due tomassive PTE has signi®cantly increased in the medical
examiner investigations in Tokyo.39 About 20±30
deaths per year are diagnosed as being caused by PTE
at autopsy by the TMEO, but these numbers remainmuch lower than those of IHD and SAH/ICH.
Obesity is a risk factor for PTE and one third of the
cadavers found to have died due to this cause have abody mass index (BMI) of over 24, whereas cases ofalmost the same number were associated with a BMI ofunder 20. With respect to medical histories, 26 (15.6%)of 167 deaths caused by PTE had psychosis (schizophrenia, circulatory psychosis, and others). The reason
why PTE occurs so frequently in the psychotic patientsremains unknown, but the hypokinetic state of a patientwith psychosis and the acceleration of the thrombogenesis by antipsychotics may be risk factors. Unlike
patients with thromboembolism elsewhere, the factor V
Leiden mutation and the prothrombin G20210A mutation have not been found in Japanese patients with thiscondition.40 Differences in genetic background andlifestyles between Japan and other countries might account for the lower incidence of PTE in Japan.

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