Sudden cardiac death

Abstract

The rate of cardiac deaths that are sudden is approximately 50%, and decreases with age. The causes of sudden cardiac death are diverse, and are a function of age. In children and adolescents, coronary anomalies, hypertrophic cardiomyopathy and myocarditis are frequent substrates for lethal arrhythmias; in adults, coronary atherosclerosis and acquired forms of cardiomyopathy are the most common findings at autopsies of sudden cardiac death. This review focuses on coronary causes of sudden cardiac death, especially congenital coronary artery anomalies, which result in sudden death almost exclusively in adults younger than age 35, and coronary thrombosis. The most lethal coronary artery anomaly is the left coronary artery arising from the right sinus of Valsalva; this anomaly often results in fatal arrhythmias, often with exercise. The right coronary artery arising from the left sinus of Valsalva may also be lethal in adolescents and young adults, but, unlike the anomalous left, is more often an incidental finding at autopsy. Approximately 60% of sudden coronary death is caused by coronary thrombosis, the rest die with severe coronary disease in the absence of thrombosis. The two major substrates of coronary thrombosis are plaque rupture and plaque erosion, and are not only different pathologically, but are seen in patients with divergent risk factor profiles. Plaque rupture is the most common cause of fatal coronary thrombus, and is characterized by necrotic core with a thin fibrous cap, infiltrated by macrophages. The factors that result in plaque instability and rupture are largely unknown, and are under intense scrutiny; morphologic studies have identified serum lipid abnormalities as a key risk factor in the development of plaque rupture. Plaque erosion, in contrast to plaque rupture, is seen in younger men and women, is not associated with lipid abnormalities, and does not result from exposure of the lipid core to the lumen. The heterogeneity of the atherosclerotic plaque and the diverse mechanics of plaque progression and thrombosis have only been relatively recently explored, and are largely elucidated by autopsy studies of victims of sudden coronary death.

Introduction

Sudden death is reported to occur in 300,000 to 400,000 individuals a year in the USA and is most prevalent from birth to 6 months (sudden infant death syndrome) and between 45 and 75 years. Only 19% of sudden natural deaths in children between 1 and 13 years are cardiac in origin, whereas in the 14–21-year age range, 30% are cardiac [1]. In the adult population, the commonest cause of sudden death is coronary heart disease. The highest prevalence is seen in those with prior history of cardiac arrest and myocardial infarction, with the risk of sudden death being highest between 6 to 18 months after the event. The incidence of sudden death declines with advancing age. In the Framingham study, 62% of all coronary heart disease deaths were sudden in men aged 45–54 years, whereas in the 55–64- and 65–74-year age groups, the percentage of sudden death fell to 58% and 42%, respectively [2]. The incidence of sudden death is higher in men than women, largely because women are protected from coronary heart disease during the premenopausal years. In the Framinghan study there was a 3.8-fold higher incidence of sudden cardiac death in men than women [2]. The excess relative risk in men peaked at 55 to 64 years reflected in a male to female ratio of 6.75:1; this ratio fell to 2.17:1 in the 65–74-year age group. Racial differences in the incidence of sudden cardiac death have also been noted, Blacks having an increased risk as compared to Whites [3] (Table 1).

The prevalence of sudden death varies with the age of the patient but also by the definition of sudden death. Most of the deaths reported as sudden have occurred outside the hospital or in emergency rooms, reflecting their unexpected nature. Clinicians define sudden cardiac death as natural, nonviolent, unexpected, and occurring within 1 h of the onset of acute symptoms. The World Health Organization defines sudden death as death within 24 h following onset of symptoms [4]. However, this definition includes many cases of well-established acute myocardial infarction, and therefore should not be considered as sudden cardiac deaths. Kuller et al. [5], [6] have shown the influence of the definition of sudden death on the incidence of cardiac causes: When the definition of sudden death was less than 2 h after onset of symptoms, 12% of deaths were sudden and 88% were due to cardiac causes; when applying a symptom duration of less than 24 h, 32% of deaths were sudden but cardiac causes of death fell to 75%. In most of our studies, we have defined sudden cardiac death as natural, nonviolent, unexpected, and witnessed within 6 h of the onset of symptoms from a stable medical condition. For unwitnessed deaths, the definition of sudden death requires that the deceased had been seen in stable condition less than 24 h before being found dead, and any potentially lethal noncardiac cause must be ruled out.

The cause of death is defined as the disease or injury initiating the train of events producing death. Cardiac causes of death are generally related to coronary, valvular, or myocardial diseases. Aortic rupture may result in cardiac tamponade and sudden death, and is occasionally considered part of the spectrum of cardiac death, although the underlying cause is vascular, not cardiac. The manner of death refers to the circumstances of death, and is classified as natural or violent (unnatural or traumatic). The distinction between natural and accidental iatrogenic deaths may be difficult and somewhat arbitrary. Generally, the death is considered natural if the procedure carries a significant risk of a fatal complication, and the condition is life threatening.

The mechanism of death is the terminal physiologic or biochemical disturbance that leads to sudden death. In most cases of cardiac death, the physiologic abnormality is a cardiac arrhythmia, although other mechanisms include acute heart failure and obstruction of blood flow (see Table 2).

The causes of death vary with the age of the patient. In neonates and infants, a common cause of sudden unexpected death is the sudden infant death syndrome, which has been defined as the sudden death of an infant under 1 year of age, which remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of the clinical history. A cardiac cause of sudden infant death syndrome has yet to be established.

Steinberger et al. [7] reported their experience in 20 patients less than 1 year of age dying suddenly (Table 3). In 65% of cases, a cause of death was identified, 80% of which were ectopic aortic origin of one or more coronary arteries. In older infants and young children, up to 75% of sudden unexpected deaths are not attributed to heart disease [8], [9]. Up to 50% of cardiac causes in children dying during exercise are idiopathic arrhythmias with apparently normal heart at autopsy [10]. In the 50 cases of sudden cardiac death reported by Steinberger et al. in patients aged 1–20 years, cardiac abnormalities were present in 80% [7]. The most common identifiable cause of sudden death in young children is myocarditis and congenital heart disease, including coronary artery anomalies and hypertrophic cardiomyopathy. In young patients with known heart disease who are followed in cardiology clinic, causes of sudden death are generally structural.

In adolescents and young adults, myocarditis, cardiomyopathies (right ventricular dysplasia, hypertrophic and idiopathic left ventricular hypertrophy), and coronary artery anomalies are the most common causes of sudden cardiac death in individuals with structural heart disease [3], [11]. In developed countries, coronary atherosclerosis is by far the most common finding in cases of sudden cardiac death in patients over 30–35 years of age Table 4, Table 5, Table 6.