Pathophysiology and etiology of sudden cardiac arrest

INTRODUCTION — Sudden cardiac arrest (SCA) and sudden cardiac death (SCD) refer to the sudden cessation of cardiac activity with hemodynamic collapse, typically due to sustained ventricular tachycardia/ventricular fibrillation. These events mostly occur in patients with structural heart disease (that may not have been previously diagnosed), particularly coronary heart disease.

The event is referred to as SCA (or aborted SCD) if an intervention (eg, defibrillation) or spontaneous reversion restores circulation. The event is called SCD if the patient dies. However, the use of SCD to describe both fatal and nonfatal cardiac arrest persists by convention. (See "Overview of sudden cardiac arrest and sudden cardiac death", section on 'Definitions'.)

The cardiac diseases that lead to the genesis of the arrhythmia resulting in cardiac collapse and sudden death are varied, and the association with sudden death in some cases is poorly understood [1]. Identification of the patient at risk for sudden death and identification of the factors that precipitate the fatal arrhythmia continue to represent a major challenge. This topic will review the mechanisms and etiology of SCA. Treatment for SCA, the evaluation of survivors, and the outcomes of SCA are discussed separately. (See "Advanced cardiac life support (ACLS) in adults" and "Cardiac evaluation of the survivor of sudden cardiac arrest" and "Prognosis and outcomes following sudden cardiac arrest in adults".)

TYPES OF ARRHYTHMIAS LEADING TO SUDDEN CARDIAC DEATH — The exact mechanism of collapse in an individual patient is often impossible to establish since, for the vast majority of patients who die suddenly, cardiac activity is not being monitored at the time of their collapse. As a result, the mechanism can only be inferred based upon information obtained after the process has been initiated.

However, there have been many cases in which the initiating event has been witnessed or recorded [2-4]. This has usually occurred in patients being continually monitored in the coronary care unit, those with a 24-hour ambulatory electrocardiogram (ECG) recording device, or those with an implantable cardioverter-defibrillator (ICD). Ventricular tachycardia (VT) or ventricular fibrillation (VF) account for the majority of episodes [2,4]. However, a bradyarrhythmia is responsible for some cases of SCD.

A bradyarrhythmia and asystole were, in initial studies, less common causes of SCD, being observed in only about 10 percent of cases documented on an ambulatory monitor [2]. A bradyarrhythmia is more often associated with a nonischemic cardiomyopathy [5], while pulseless electrical activity, electromechanical dissociation, or asystole are the most common rhythms seen with a pulmonary embolism [6]. Other causes for pulseless electrical activity include myocardial rupture, tamponade, pneumothorax, hypoxemia, or drug overdose. In some cases, the bradyarrhythmia may result in a ventricular tachyarrhythmia as an escape mechanism.

The distribution is different among patients with an ICD. Arrhythmic death accounts for 20 to 35 percent of deaths; post-shock or primary pulseless electrical activity (PEA, also called electromechanical dissociation) is a frequent cause of SCD in this setting [7]. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on 'Epidemiology'.)

The distribution of causes is also different with unmonitored out-of-hospital SCD. VF and pulseless VT appear to be responsible for 25 to 35 percent of episodes, although estimates vary widely. PEA accounts for as much as 25 percent of all cases of SCD.

Among patients who collapse in an unmonitored setting in whom the exact time of onset and the etiologic arrhythmia are uncertain, asystole is often the first rhythm observed [8]. Asystole correlates with the duration of the arrest and may be the result of VF that has been present for several minutes or longer and then leads to loss of all electrical activity as a result of hypoxia, acidosis, and death of myocardial tissue (waveform 1) [9].

ARRHYTHMIC MECHANISMS

Mechanism of ventricular tachycardia — In approximately 80 percent of patients with VT/VF, the sustained ventricular arrhythmia is preceded by an increase in ventricular ectopy and the development of repetitive ventricular arrhythmia, particularly runs of nonsustained VT [2]. These spontaneous arrhythmias are present for a variable period of time prior to the development of VT/VF.

●Sustained monomorphic VT can accelerate to a rapid rate and then degenerate into VF. However, the relationship between monomorphic VT and SCD has been debated, with some studies suggesting that this arrhythmia is present in only a minority of patients with SCD [10,11]. Thus, sustained monomorphic VT may simply be the company kept by VF or, in the appropriate setting such as recurrent coronary ischemia, it may provide a rapid wavefront that becomes fractionated, leading to VF [11].

●A sustained polymorphic VT can degenerate into VF. This is most often the result of underlying ischemia (ie, polymorphic VT without QT prolongation or a short QT interval of the sinus QRS complex), although it may also result from acquired or congenital QT prolongation or congenital short QT interval. A very rare cause of polymorphic VT without QT prolongation is a genetic abnormality associated with catecholaminergic polymorphic VT (a result of an abnormality of a ryanodine or calsequestrin gene). (See "Catecholaminergic polymorphic ventricular tachycardia" and "Acquired long QT syndrome: Definitions, pathophysiology, and causes".)

●VF can develop as a primary event.

In approximately one-third of cases, the tachyarrhythmia is initiated by an early R on T premature ventricular complex/contraction (PVC; also referred to a premature ventricular beats or premature ventricular depolarizations); in the remaining two-thirds, the arrhythmia is initiated by a late cycle PVC [2].

Mechanism of ventricular fibrillation — VF results from multiple localized areas of microreentry without any organized electrical activity [12]. The most likely mechanism is rotating spiral waves [13]. This almost always occurs in the setting of underlying myocardial disease (or abnormalities in repolarization as in the long QT syndrome) that is often diffuse, resulting in heterogeneity of depolarization and the dispersion of repolarization. This disparity of electrophysiologic properties is a precondition for reentry. A triggering event is usually necessary to precipitate the arrhythmia in a vulnerable heart [14]. The identification of a precipitating factor is more likely if there is less heart disease, and when there is more heart disease, a precipitating factor may be more difficult to define. (See "Reentry and the development of cardiac arrhythmias".)

The diversity in conduction and recovery parameters (myocardial heterogeneity) results in fragmentation of the impulse as it travels through the myocardium, producing multiple areas of localized reentry or multiple spiral wavelets of myocardial activation [12]. Since there is no organized electrical activity or myocardial depolarization, there is no uniform ventricular contraction resulting in failure of the heart to generate a cardiac output. With the development of global ischemia, the rate of VF decreases because of a reduction in the rotation period of the spiral waves which results from the increase in their core area [13].

The ECG in established VF shows high-frequency undulations or fibrillatory waves that are irregular in amplitude, morphology, and periodicity, occurring at a rate above 320/minute; organized QRS complexes are not seen (waveform 1) [15]. However, at the very onset of VF, the irregular fibrillatory waves may be coarse with a tall amplitude (and may resemble polymorphic VT) or may occasionally appear to be regular (waveform 2). The QRS complexes in this latter setting are indistinguishable from the T waves, and they appear to be sinusoidal in configuration. This finding may represent a brief period of an organized ventricular flutter, with a rate exceeding 260 beats per minute. In cases where the coarse fibrillatory waves resemble polymorphic VT, these initial ECG changes are collectively referred to as type I VF and may be associated with spontaneous defibrillation [16,17]. Importantly, polymorphic VT may spontaneously terminate, while VF never self-terminates but only responds to defibrillation. (See "Cardioversion for specific arrhythmias".)

As the duration of VF increases, progressive cellular ischemia and acidosis develop, resulting in an electrophysiologic deterioration, manifested by an increase in fibrillation cycle length and prolonged diastole duration between fibrillation action potentials [9,17,18]. During this later (type II) VF, the fibrillatory waves rapidly become finer and more irregular in amplitude, duration, and cycle length; spontaneous resolution or reversion with an antiarrhythmic drug has not been observed [16,17]. Over a period of several minutes, the fibrillatory waves become so fine that there does not appear to be any electrical activity (waveform 1) [15].

ETIOLOGY OF SCD — There are many cardiac and noncardiac causes for a sustained ventricular tachyarrhythmia that can result in sudden cardiac death (SCD) (table 1).

Common causes of SCD — The following approximate frequency of causes of out-of-hospital SCDs have been described [19-25]:

●Sixty-five to 70 percent of all SCDs are attributable to coronary heart disease (CHD) [19,20]. Most often, there is no evidence for an acute myocardial infarction, although acute ischemia may be the precipitating cause. Cardiac biomarkers are often elevated as a result of ischemia due to the arrhythmia or the result of defibrillation, making the diagnosis of an acute myocardial infarction preceding the event difficult to establish. However, the frequency of CHD is much lower in SCDs occurring under the age of 30 to 40 (eg, 24 percent under the age of 30 in a review of SCDs in the United States in 1999, and 8 percent in a series of autopsies in military recruits) [19,26].

These observations were largely made from analyses of all reported SCDs in the United States using the diagnosis on the death certificate, which is of uncertain accuracy. A similar frequency of CHD was noted in a study of 84 consecutive survivors of out-of-hospital cardiac arrest [21]. Immediate coronary angiography revealed clinically significant coronary disease in 60 (71 percent) of the patients, 40 of whom (48 percent of all patients) had an occluded coronary artery. The absence of an occluded coronary artery in the other 20 patients does not preclude an acute coronary syndrome (or ischemia) since absence of occlusion on early angiography is seen in 60 to 85 percent of patients with a non-ST elevation acute coronary syndrome and in up to 28 percent of patients with an ST elevation MI.

●Ten percent of SCDs are due to other types of structural heart disease (eg, any type of cardiomyopathy, congenital coronary artery anomalies, myocarditis, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy) [19,20,26]. The frequency is much higher in subjects under the age of 30 (over 35 percent in a review of SCDs in the United States in 1999, and over 40 percent in a series of autopsies in military recruits) [19,26].

●Five to 10 percent of SCDs are primary arrhythmogenic, occurring in the absence of structural heart disease (eg, long QT syndrome, Brugada syndrome, Wolff-Parkinson-White syndrome, catecholaminergic polymorphic ventricular tachycardia [VT]). In the absence of any structural abnormality or electrophysiologic abnormality on the ECG, these entities are often termed primary electrical disease [22-24].

●Fifteen to 25 percent of cardiac arrests are noncardiac in origin [22,25]. The causes include trauma, bleeding, drug intoxication, intracranial hemorrhage, pulmonary embolism, near-drowning, and central airway obstruction.

Although not specifically mentioned in most of these studies, heart failure (HF) is a relatively common cause of SCD. SCD accounts for 30 to 50 percent of deaths in patients with heart failure (HF) [27], and the incidence of SCD appears to be increased during periods of worsening HF symptoms [28]. Although the risk of both arrhythmic and nonarrhythmic death can be reduced with appropriate chronic HF therapy, the SCD risk remains elevated. Thus, virtually all SCD survivors with HF receive an ICD. A detailed discussion of arrhythmic events and the effect of medical therapy in HF patients is presented separately. (See "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy".)

The incidence of SCD increases with age in both men and women; however, at any level of multivariate risk, women are less vulnerable to sudden death than men and a higher fraction of sudden deaths in women occur in the absence of prior overt CHD (figure 1) [18,29].

Transient or reversible causes — A number of transient or reversible conditions may precipitate arrhythmic events and SCD. Identification of such conditions is critical both for the management of the underlying disorder and for determining the likelihood of recurrent SCD. (See "Cardiac evaluation of the survivor of sudden cardiac arrest", section on 'Initial evaluation'.)

In some of these cases, management of the underlying disorder is all that is necessary to reduce the risk of recurrent events. However, despite an apparently reversible trigger for SCD, many patients have a persistent risk of recurrent events (due to the presence of irreversible structural heart disease) and may benefit from implantable cardioverter-defibrillator (ICD) therapy or, in some cases, pharmacologic therapy with an antiarrhythmic drug. (See "Prognosis and outcomes following sudden cardiac arrest in adults".)

Potentially reversible triggers for SCD include the following:

●Acute cardiac ischemia and myocardial infarction – Because CHD is the most common cause of SCD, acute coronary ischemia, even in the absence of evidence for an acute myocardial infarction, should be considered in all survivors of SCD. (See "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features" and "Cardiac evaluation of the survivor of sudden cardiac arrest", section on 'Coronary angiography'.)

●Antiarrhythmic drugs – All antiarrhythmic drugs have proarrhythmic properties, particularly in patients with underlying cardiac disease, especially when heart failure is present [30-32]. Among SCD survivors who have been taking antiarrhythmic medications, it is difficult to be certain if the arrest was provoked by the drug or occurred despite its use [33]. Thus, it is often difficult to know if antiarrhythmic medications should be discontinued, increased, or adjusted. In such patients, involvement of an arrhythmia specialist is recommended.

●Medication (eg, QT prolonging drugs), toxin, or illicit drug ingestion [34,35]. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes".)

●Electrolyte abnormalities, most notably hypokalemia, hyperkalemia, and hypomagnesemia.

●pH changes, especially acidemia (respiratory or metabolic).

●Heart failure – The incidence of SCD appears to be increased during periods of worsening HF symptoms [28]. However, HF is a chronic disease, and although acute episodes may be managed, the condition is not truly transient or reversible. Even with appropriate chronic HF therapy, the SCD risk remains elevated. (See "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy".)

●Severe hypoxemia.

●Autonomic nervous system activation, especially sympathetic neural inputs.

Autopsy studies — The distribution of cardiac causes of SCD varies with age, the population studied, and geography. While coronary heart disease (CHD) is listed as the underlying cause of SCD on 62 percent of death certificates among the general population in the United States [20], younger patients, athletes, and those without known prior disease have a different distribution of causes [22,36,37]:

●In an autopsy study of 902 persons with suspected SCD (mean age 38 years), 715 cases (79 percent) occurred in persons with underlying cardiac pathology [38]. CHD was felt to be the primary cause of SCD in 511 patients (57 percent); however, CHD was far more common in persons 35 years of age or older (73 percent versus 23 percent in those <35 years), whereas those under 35 years of age were significantly more likely to die from non-CHD causes such as sudden unexplained death (primary arrhythmic death, 41 versus 11 percent), hypertrophic cardiomyopathy (13 versus 3 percent), or myocarditis (6 versus 2 percent).

●An autopsy study from Israel evaluated 162 subjects aged 9 to 39 years with SCD; none had previously diagnosed underlying cardiac disease, and death occurred in the absence of trauma within 24 hours of onset of symptoms [22]. Approximately 15 percent of deaths were noncardiac (most often intracranial hemorrhage), and 73 percent were cardiac. Among those 20 to 29 years of age, CHD was found in 24 percent, myocarditis in 22 percent, and hypertrophic cardiomyopathy (HCM) in 13 percent. Among those 30 to 39 years of age, CHD was found in 58 percent, myocarditis in 11 percent, and HCM in 2 percent.

●An autopsy series from the United States evaluated 286 competitive athletes under age 35 in whom cardiovascular disease was shown to be the cause of SCD [36]. The most common underlying disorders were HCM (36 percent, with possible HCM in another 10 percent), an anomalous origin of a coronary artery (13 percent), and myocarditis (7 percent). (See "Athletes: Overview of sudden cardiac death risk and sport participation".)

●A markedly different distribution was noted in a report from northern Italy where arrhythmogenic right ventricular cardiomyopathy or dysplasia (ARVC or ARVD) is relatively common [37]. Among 49 sudden deaths in young athletes, ARVC was most common (22 percent), followed by coronary atherosclerosis (18 percent), an anomalous origin of a coronary artery (12 percent), and HCM in only 2 percent.

Myocardial ischemia and infarction — Approximately 65 to 70 percent of SCDs are attributable to CHD [19,20], and it is estimated that SCD accounts for 30 to 50 percent of coronary deaths [18,39]. The incidence of SCD is related to the clinical manifestations of preexisting CHD, being highest in those with a prior myocardial infarction (MI) and intermediate in those who have angina without a prior infarction (figure 2) [18]. However, SCD can occur in patients with silent (or discomfortless) ischemia and can be the initial manifestation of CHD. (See "Silent myocardial ischemia: Epidemiology, diagnosis, treatment, and prognosis".)

Among SCD episodes that occur without warning, angiography demonstrates an occluded coronary artery in almost one-half of patients [21]. Clinical and ECG changes appear to correlate poorly with coronary occlusion. Furthermore, among patients with typical ECG changes or cardiac enzyme elevations after resuscitation, it may be difficult on clinical grounds alone to determine whether an acute MI caused ventricular fibrillation (VF), or if VF resulted in myocardial injury because of the absence of coronary artery blood flow and/or the result of defibrillation.

Among patients who present with an acute MI rather than SCD, the incidence of VF varies with the type of infarct and time. This topic is discussed in detail separately but will be briefly reviewed here. (See "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features", section on 'Incidence'.)

●The largest experience with acute ST elevation MI comes from the GUSTO-1 trial of 40,895 patients who were treated with thrombolytic therapy [40]. The overall incidence of VT or VF was 10.2 percent: 3.5 percent developed VT, 4.1 percent VF, and 2.7 percent both VT and VF. Approximately 80 to 85 percent of these arrhythmias occurred in the first 48 hours.

●The best data in non-ST elevation acute coronary syndrome come from a pooled analysis of four major trials of over 25,000 patients [41]. The overall incidence of VT or VF was 2.1 percent: VT occurred in 0.8 percent, VF in 1 percent, and VT and VF in 0.3 percent. The median time to arrhythmia was 78 hours, with the 25th and 75th percentiles being 16 hours and seven days.

A peak incidence of VF within the first 48 hours after acute MI has also been noted in other reports [42,43]. These episodes are presumably due to ischemia, while later onset VF may be related to healing of the infarct with the development of scar (and an increased risk of monomorphic VT) and associated with an increased risk of late SCD. Late SCD most often occurs in the first year, with the majority of events seen within the first few months and being due to a ventricular tachyarrhythmia [44,45]. The risk of late VT/VF appears to be equivalent in patients with ST elevation and non-ST elevation infarctions [44]. (See "Ventricular arrhythmias during acute myocardial infarction: Incidence, mechanisms, and clinical features".)

These data do not include patients with SCD who do not survive until hospitalization. It has been estimated that more than 50 percent of deaths due to acute MI occur out of the hospital, and most episodes occur within one hour of symptom onset [46]. Among patients with out-of-hospital cardiac arrest, the risk is greater in those with acute occlusion of the left anterior descending or left circumflex arteries (odds ratio 4.82 and 4.92, respectively, compared with those with a right coronary artery occlusion).

In addition, there are patients who have unstable coronary lesions that may be responsible for acute ischemic events, short of infarction, and that can cause electrical instability [21,47,48]. The potential frequency of this effect was illustrated in a report of 84 resuscitated patients who underwent coronary angiography immediately upon admission: 76 percent had significant coronary disease, spasm, or an unstable lesion, and almost one-half had coronary occlusion [21]. (See "Cardiac evaluation of the survivor of sudden cardiac arrest".)

The importance of unstable plaques has been confirmed in a number of autopsy studies of men and women with coronary disease who died suddenly [48-52]. (See "Mechanisms of acute coronary syndromes related to atherosclerosis".)

●In a report of 113 such men: 59 had an acute coronary thrombus and 54 had severe narrowing of the coronary artery by an atherosclerotic plaque without acute thrombosis (stable plaque) [48]. Among those with acute thrombosis, 41 resulted from rupture of a vulnerable plaque (a thin fibrous cap overlying a lipid-rich core) and 18 from erosion of a fibrous plaque rich in smooth-muscle cells and proteoglycans.

●The likelihood of plaque rupture may vary in different subgroups. In a review of 141 men with SCD associated with coronary artery disease, the 25 patients who died during exertion were significantly more likely to have plaque rupture (72 versus 23 percent in those who died at rest) and hemorrhage into the plaque (72 versus 41 percent) [50].

●Among patients with SCD associated with unstable angina, the thrombi typically have a layered appearance indicative of episodic growth [51]. Episodic growth may alternate with intermittent fragmentation of the thrombus, leading to distal embolization of both thrombus and platelet aggregates and microinfarction [51,52].

The presence of severe coronary disease alone in a survivor of SCD does not prove a cause-and-effect relationship. Among patients who are not in the acute phase of a myocardial infarction, an appreciable risk of recurrent VT/VF may persist despite successful revascularization as a result of underlying myocardial disease and fibrosis [53,54].

Heart failure — The presence of heart failure (HF), regardless of etiology, increases overall mortality and the incidence of SCD in both men and women. This was illustrated in a 38-year follow-up of patients in the Framingham Heart Study: the incidence of SCD in those with HF, compared with those without HF, was increased fivefold in both sexes, although the absolute risk in women was only one-third that of men (figure 3) [18]. The SCD death potential in men and women with HF was as great as that noted in patients with overt coronary heart disease (13.7 and 3.8 versus 12.9 and 2.4 per 1000 patients, respectively). (See "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy".)

Published series suggest a relatively consistent pattern with 30 to 50 percent of all cardiac deaths in patients with HF being categorized as sudden deaths, with or without preceding symptoms. However, it is often difficult to distinguish those dying suddenly and unexpectedly from those experiencing terminal arrhythmias in the setting of progressive hemodynamic deterioration. It has been suggested that progressive pump failure, sudden arrhythmic death, and sudden death during episodes of clinical worsening each account for approximately one-third of deaths [27]. In the AIRE trial, for example, only 39 percent of sudden deaths were thought to be due to arrhythmia [28]. VT degenerating into VF is the most common cause of SCD; a bradyarrhythmia or PEA is responsible in 5 to 33 percent of cases [27].

An acute coronary event appears to be the precipitating factor in some patients with HF. The prevalence of coronary thrombus, ruptured plaque, or myocardial infarction and its relationship to SCD was examined in an autopsy study of 171 patients with HF in the ATLAS trial [55]. In patients with significant coronary artery disease, an acute coronary finding was found in 54 percent who died suddenly and in 32 percent who died of myocardial failure, although an acute coronary event had not been clinically diagnosed before death. In contrast, an acute coronary finding was uncommon in those without coronary disease, occurring in only 5 percent of those who died suddenly and in 10 percent of those who died of myocardial failure.

Left ventricular hypertrophy — Hypertension with left ventricular hypertrophy (LVH) appears to increase the risk of SCD. Myocardial hypertrophy due to hypertension is often associated with myocardial fibrosis and may be a precondition for ventricular arrhythmia. In addition, chronic subendocardial ischemia (accounting for the ST-T wave changes that are often seen) is often present with the hypertrophy and the increased oxygen demands; the subendocardium, which is the last part of the myocardium to receive blood supply, may have a reduced oxygen supply resulting in ischemia. In addition, many patients with hypertension and LVH have underlying coronary artery disease. Such patients appear to be less likely to have coronary thrombi than normotensives who had SCD [56]. However, most such patients have severe coronary disease suggesting that the hypertrophied myocardium is more susceptible than normal myocardium to the effects of ischemia [56].

SCD also occurs more commonly in patients with hypertrophic cardiomyopathy. Among competitive athletes who die from SCD due to proven cardiac cause, hypertrophic cardiomyopathy may be one of the most common underlying disorders, accounting for 36 percent of 286 cases in an autopsy series [36]. (See "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death".)

Absence of known structural heart disease — Sudden cardiac death can occur in patients who have no previous history of heart disease [22,29,57]. Other causes of death that could be misinterpreted as SCD (eg, acute drug overdose or intoxication) should also be excluded [58]. However, most of these patients with SCD have underlying structural heart disease. (See "General approach to drug poisoning in adults" and "Acute opioid intoxication in adults".)

The frequency with which this occurs was illustrated in an autopsy study that evaluated 162 subjects aged 9 to 39 years with SCD; none had previously diagnosed underlying disease and death occurred in the absence of trauma and within 24 hours of onset of symptoms [22]. The following findings were noted:

●Approximately 15 percent of deaths were noncardiac (most often intracranial hemorrhage) and 73 percent were cardiac.

●The most common causes of heart disease were coronary disease (58 percent in those over age 30 compared with 22 percent in younger subjects), myocarditis (11 and 22 percent in the two age groups), hypertrophic cardiomyopathy (13 percent in younger subjects), sarcoidosis, and arrhythmogenic right ventricular cardiomyopathy.

●Approximately one-half had some prodromal symptoms, such as chest pain or dizziness.

●SCD occurred during routine activity in 49 percent, during sleep in 23 percent, and in relation to exercise in 23 percent.

The association with exercise has also been described in competitive athletes. In a United States registry of SCD in 286 competitive athletes under age 35 in whom cardiovascular disease was shown to be the cause at autopsy, the most common underlying disorders were hypertrophic cardiomyopathy (36 percent, with possible HCM in another 10 percent), an anomalous coronary artery of wrong sinus origin (13 percent), and myocarditis (7 percent) [36]. (See "Athletes: Overview of sudden cardiac death risk and sport participation".)

A different distribution of causes was noted in a series of 49 athletes under age 35 with SCD from northern Italy [37]. The most common causes were arrhythmogenic right ventricular cardiomyopathy (22 percent, which occurs more frequently in this region), coronary atherosclerosis (18 percent), anomalous origin of a coronary artery (12 percent), mitral valve prolapse (10 percent), myocarditis (6 percent), and hypertrophic cardiomyopathy (2 percent).

Absence of structural heart disease — In different reports, 10 to 12 percent of younger patients have VF in the true absence of structural heart disease [22,59], while a lower value of approximately 5 percent has been described when older patients are included [23,24]. This can occur in a variety of settings:

●Brugada syndrome (see "Brugada syndrome: Clinical presentation, diagnosis, and evaluation")

●Commotio cordis (see "Commotio cordis")

●Idiopathic VF, also called primary electrical disease (see "Approach to sudden cardiac arrest in the absence of apparent structural heart disease", section on 'Idiopathic VF')

●Catecholaminergic polymorphic VT (see "Catecholaminergic polymorphic ventricular tachycardia")

●Congenital or acquired long QT syndrome (see "Congenital long QT syndrome: Diagnosis" and "Acquired long QT syndrome: Definitions, pathophysiology, and causes")

●Short QT syndrome (see "Short QT syndrome")

●Wolff-Parkinson-White syndrome (see "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis")

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Ventricular fibrillation (The Basics)")

SUMMARY

●Background – Sudden cardiac arrest (SCA) and sudden cardiac death (SCD) refer to the sudden cessation of organized cardiac electrical activity with hemodynamic collapse. The event is referred to as SCA (or aborted SCD) if an intervention (eg, defibrillation, cardioversion, antiarrhythmic drug) or spontaneous reversion restores circulation. The event is called SCD if the patient dies. However, the use of SCD to describe both fatal and nonfatal cardiac arrest persists by convention. (See 'Introduction' above.)

●Mechanisms – The exact mechanism of collapse in an individual patient is often impossible to establish since, for the vast majority of patients who die suddenly, cardiac electrical activity is not being monitored at the time of their collapse. However, in studies of patients who were having cardiac electrical activity monitored at the time of their event, ventricular tachycardia (VT) or ventricular fibrillation (VF) accounted for the majority of episodes, with bradycardia or asystole accounting for nearly all of the remainder. (See 'Arrhythmic mechanisms' above.)

●Arrhythmic mechanisms – In the majority of patients with VT/VF, sustained ventricular arrhythmia is preceded by an increase in ventricular ectopy and the development of repetitive ventricular arrhythmia, particularly runs of nonsustained VT. In approximately one-third of cases, the tachyarrhythmia is initiated by an early R on T PVC; in the remaining two-thirds, the arrhythmia is initiated by a late cycle PVC. (See 'Arrhythmic mechanisms' above.)

●Common causes – There are many cardiac and noncardiac causes for a sustained ventricular tachyarrhythmia that can result in SCD (table 1). Among all SCD in all age groups, the majority (65 to 70 percent) are related to coronary heart disease, with other structural cardiac disease (approximately 10 percent), arrhythmias in the absence of structural heart disease (5 to 10 percent), and noncardiac causes (15 to 25 percent) responsible for the remaining deaths. (See 'Etiology of SCD' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff thank Dr. Jie Cheng for his past contributions as an author to prior versions of this topic review.