MINI-SYMPOSIUM: THE AUTOPSY IN SUDDEN UNEXPECTED ADULT DEATH
The pathological investigation of sudden cardiac death

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Summary

Sudden cardiac death is one of the leading causes of death in many different countries. Epidemiologists have refined criteria progressively for the definition of sudden death, while cardiologists have investigated relevant risk factors, especially in patients with cardiac failure and with inherited diseases of cardiac muscle. In contrast, pathologists are responsible for determining the precise cause of sudden death, but there is considerable variation in the way in which they approach this increasingly complex task. In this article, the methods that should be used in routine practice are described. The ideal autopsy involves careful scrutiny of the clinical records, a full macroscopic and microscopic examination, further laboratory tests and the formulation of a final diagnosis. In addition to a full written report, a synoptic proforma summary is desirable. If a uniform method of investigation is adopted, it will lead to improvements in standards of practice, allow meaningful comparisons between different communities and regions, and, most importantly, permit future trends in the patterns of disease that cause sudden death to be monitored.

Introduction

Although sudden cardiac death is a leading cause of death in all communities of the European Union, Canada and the USA, its exact incidence is unknown. Internationally accepted methods of death certification do not include a specific category of sudden cardiac death. Nevertheless, a task force of the European Society of Cardiology has suggested that the incidence ranges from 36 to 128 deaths/100,000 population/year.1 There is evidence that the incidence of sudden death is declining in the USA2 and Finland.3 However, there has been no significant reduction over a long period in Northern Ireland, where the current incidence is 122/100,000 for men and 41/100,000 for women.4 An apparent increase in rates of sudden cardiac death in women aged between 35 and 44 years in the USA is unexplained.5

Accurate diagnosis of sudden cardiac death can only be made at autopsy, but there is considerable variation in autopsy rates in different countries. While 22% of deaths in England are followed by autopsy, the rates in Scotland and Northern Ireland are lower (12% and 9%, respectively). In a prospective study in 2003 in Southern England, the rate of autopsy confirmed sudden cardiac death was 82/100,000 population.6 When allowance was made for cases that might not have had autopsies, the rates of sudden death were thought to range from 85 to 114/100,000/year. Despite inevitable difficulties in collecting accurate data, it is clear that with sudden cardiac death rates in the order of 80/100,000/year, there will be at least 365,000 sudden cardiac deaths each year in the 457 million population of the European Union. What proportion will be confirmed by autopsy is uncertain, but it is likely that tens if not hundreds of thousands of autopsies will be performed on victims of sudden cardiac death each year.

The definition of sudden cardiac death as death within 1 h of the onset of symptoms was advocated in 1982, and is a good description of many witnessed deaths in the community or in emergency departments.7 It is less satisfactory in pathological practice, where autopsies may be requested on patients whose deaths were not witnessed, occurred during sleep or at an unknown time before their bodies were discovered. Under these circumstances, it is probably satisfactory to assume that the death was sudden if the deceased was known to be in good health 24 h before death occurred.8 In young patients, in particular, symptoms shortly before death may not indicate cardiac disease.9 The majority of sudden cardiac deaths are in elderly patients, and more than 75% occur at home or a care home.6 In majority of cases, ventricular tachycardia is followed by ventricular fibrillation,10 but few cases are resuscitated effectively out of hospital.11

Many reports describe the pathological findings in sudden cardiac death (Table 1, Table 2). These reports differ in many ways, especially in the age and type of patient studied and the extent of histological sampling. In adults, coronary artery disease is by far, the leading cause of death. The proportion of cases with evidence of acute coronary thrombosis or recent myocardial infarction is higher in studies in which detailed histology was performed (Table 1). With detailed histology, acute thrombosis was identified in 72%, 52% and 47% of cases.12, 13, 14 In contrast, two recent studies where histology was limited showed acute thrombosis in 37% and 33% of cases.6, 15 Whether this represents a genuine change in the incidence of acute thrombosis in sudden cardiac death or a failure of pathologists to recognize thrombi without histological confirmation is uncertain. Congenital heart disease, cardiomyopathy and unexplained left ventricular hypertrophy are of particular importance in younger patients (Table 2), especially athletes. Studies with limited histology appear to report a lower incidence of myocarditis. The wide range of uncommon pathology is especially apparent in reports from referral centres.17, 18

Section snippets

Methods of investigation

A variety of book chapters, professional guidelines and articles have described how pathologists should investigate sudden death.18, 19 Despite these guidelines, there is little consistency between centres, even in individual countries. Cardiac pathologists emphasize that the investigation of sudden death involves four steps:20

  • the clinical features, especially the history and circumstances of death;

  • autopsy examination and histology;

  • further laboratory tests; and

  • formulation of a diagnosis.

Deaths due to ischaemic heart disease

In most studies, up to two-thirds of sudden deaths are cardiac in origin and more than 60% of these are the result of ischaemic heart disease.6, 13 Davies was the first to categorize sudden cardiac deaths according to the nature of the findings,12 and with slight modifications, this has been easy to apply to large community surveys6, 13 (Table 3). In a death that is ascribed to ischaemic heart disease (categories 1–3 in Table 3), the following points are of particular importance.

  • The

Deaths due to cardiac muscle disease: cardiac failure

Many clinical trials have demonstrated that the life of patients with heart failure can be prolonged but the overall mortality from this condition has not been reduced.24 A significant proportion of patients with cardiac failure die suddenly and unexpectedly. In published treatment studies, the prevalence of sudden death in patients in placebo arms has ranged from 3.7% to 22.2%.25 Risk factors for sudden death in heart failure include a history of syncope or ventricular arrhythmias, worsening

Deaths due to cardiac muscle disease: cardiomyopathy and unexplained hypertrophy

Many studies in adults and younger patients have demonstrated that cardiomyopathy is a frequent cause of sudden death and that accurate diagnosis is essential (Table 1, Table 2). Although the incidence of disorders varies between reports, hypertrophic cardiomyopathy, arrhythmogenic ventricular cardiomyopathy and dilated cardiomyopathy are the most frequent conditions. A small but significant number of patients have unexplained left ventricular hypertrophy with or without interstitial fibrosis.15

Deaths due to cardiac muscle disease: other disorders

Myocarditis is an important cause of sudden cardiac death, especially in younger patients. It may not be recognized macroscopically.27 This is one of the strongest justifications for routine sampling of the myocardium in every sudden cardiac death autopsy. Up to 50% of patients with liver failure die suddenly. These patients have an increased incidence of ventricular arrhythmias, and this is the presumed mechanism of death. Alcohol abuse with advanced hepatic fatty change is an increasing cause

Unexplained cardiac deaths

It is now widely accepted that there will be no macroscopic or microscopic abnormalities in a proportion of sudden cardiac deaths (Table 2). The author strongly suspects that the number of these unexplained deaths has been underestimated in the past. Correct identification of these cases is important as first-degree relatives should undergo screening by a cardiologist. As with deaths due to cardiomyopathy or myocarditis, detailed macroscopic and microscopic examination is essential. In young

Conclusions

Sudden cardiac death is one of the most important causes of death in the European Union. Pathologists and public heath physicians have not given this problem the attention it deserves. New methods of prevention of potentially fatal arrhythmias have been developed, and the accurate diagnosis of sudden cardiac death is of particular importance. In up to 20% of families in which an unexplained cardiac death has occurred, one or more relatives have been shown to have evidence of inherited cardiac

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