Pathophysiology and Etiology of Sudden Cardiac Arrest: Author: Section Editors: Deputy Editor

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Pathophysiology and etiology of sudden cardiac arrest


Author: Philip J Podrid, MD, FACC
Section Editors: Brian Olshansky, MD, Scott Manaker, MD, PhD
Deputy Editor: Brian C Downey, MD, FACC

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature rev iew current through: Mar 2020. | This topic last updated: Apr 18, 2018.

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".)

ARRHYTHMIC 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 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

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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 or with
a 24-hour ambulatory electrocardiogram (ECG) recording device or 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.

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 [5]. (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 many 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 is uncertain, asystole is often the first rhythm observed [6]. 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 the loss of all electrical activity as a result of hypoxia, acidosis, and death of
myocardial tissue (waveform 1) [7].

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 [8,9]. 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 [9].

● A sustained polymorphic VT can degenerate into VF. This is most often the result of underlying
ischemia (ie, polymorphic VT without QT prolongation of the sinus QRS complex), although it may
also result from acquired or congenital QT prolongation. 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, causes, and
pathophysiology".)

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● 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].

● 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 [10], while
pulseless electrical activity or asystole are the most common rhythms seen with a pulmonary
embolism [11] (see "Treatment, prognosis, and follow-up of acute pulmonary embolism in
adults"). In some cases, the bradyarrhythmia may result in a ventricular tachyarrhythmia as an
escape mechanism.

Mechanism of VF — 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]. (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].

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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 [7,17,18]. 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].
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, 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 arrhythmic, 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

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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 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,

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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, causes, and pathophysiology".)

● 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".)

● 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".)

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● A markedly different distribution was noted in a report from northern Italy where arrhythmogenic
right ventricular cardiomyopathy (ARVC) 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 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 VF resulted in myocardial injury because of the absence
of coronary artery blood flow.

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

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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 [53,54].

Heart failure — The presence of heart failure (HF), regardless of etiology, increases overall mortality

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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. 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]. (See "Clinical implications and treatment of left ventricular hypertrophy in
hypertension".)

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 the
most common underlying disorder, 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]. However, most of these patients have underlying
structural heart disease. The frequency with which this occurs was illustrated in an autopsy study that

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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 [22,58], 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, causes, and pathophysiology")

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


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

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

SUMMARY

● 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.)

● 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.)

● 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

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'Arrhythmic mechanisms' above.)

● 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 would like to thank Dr. Jie Cheng for his past contributions as an author to
prior versions of this topic review.

Use of UpToDate is subject to the Subscription and License Agreement.

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Topic 974 Version 21.0

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GRAPHICS

Continuous electrocardigraphic (ECG) strip during an episode


of ventricular fibrillation (VF) that progresses to fine VF and
then asystole

A t the ons et of v entric ular fibrillation (V F ), the Q R S c omplex es are regular,


widened, and of tall amplitude, s ugges ting a more organized v entric ular
tac hy arrhy thmia. O v er a brief period of time, the rhy thm bec omes more
dis organized with high amplitude fibrillatory wav es ; this is c oars e V F. A fter a
longer period of time, the fibrillatory wav es bec ome fine, c ulminating in as y s tole.

Graphic 67777 Version 3.0

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ECG 12-lead ventricular fibrillation

1 2 - lead E C G s howing c ours e v entric ular fibrillation.

ECG: electrocardiogram.

Graphic 118944 Version 1.0

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Major causes of sudden death

Ischemic heart disease


Coronary artery disease with myocardial infarction or angina

Coronary artery embolism

Nonatherogenic coronary artery disease (arteritis, dissection, congenital coronary artery anomalies)

Coronary artery spasm

Nonischemic heart disease


Hypertrophic cardiomyopathy

Dilated cardiomyopathy

Valvular heart disease

Congenital heart disease

Arrhythmogenic right ventricular dysplasia

Myocarditis

Acute pericardial tamponade

Acute myocardial rupture

Aortic dissection

No structural heart disease


Primary electrical disease (idiopathic ventricular fibrillation)

Brugada syndrome (right bundle branch block and ST segment elevation in leads V1 to V3)

Long QT syndrome

Preexcitation syndrome

Complete heart block

Familial sudden cardiac death

Chest wall trauma (commotio cordis)

Noncardiac disease
Pulmonary embolism

Intracranial hemorrhage

Drowning

Pickwickian syndrome

Drug-induced

Central airway obstruction

Sudden infant death syndrome

Sudden unexplained death in epilepsy (SUDEP)

Graphic 62184 Version 3.0

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Incidence of sudden death in men and women


increases with age

D uring a 3 8 - y ear follow- up of s ubjec ts in the F ramingham H eart S tudy,


the annual inc idenc e of s udden death inc reas ed with age in both men
and women. H owev er, at eac h age, the inc idenc e of s udden death is
higher in men than women.

Data from Kannel WB, Wilson PWF, D'Agostino RB, et al. Am Heart J 1998; 136:205.

Graphic 59028 Version 4.0

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Risk of SCD is related to clinical manifestations of


CHD

D uring a 3 8 - y ear follow- up of s ubjec ts in the F ramingham H eart S tudy,


the annual inc idenc e of s udden c ardiac death (S C D ) in both men and
women was related to the c linic al manifes tations of c oronary heart
dis eas e (C H D ). I t was highes t in thos e with a my oc ardial infarc tion,
intermediate in thos e with angina and no prior infarc tion, and lowes t in
thos e without ov ert C H D .

Data from: Kannel WB, Wilson PWF, D'Agostino RB, et al. Am Heart J 1998; 136:205.

Graphic 52309 Version 2.0

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Heart failure predicts increased sudden cardiac


death and overall mortality

D uring a 3 8 - y ear old follow- up of s ubjec ts in the F ramingham H eart


S tudy, the pres enc e of heart failure (H F ) s ignific antly inc reas ed
s udden death and ov erall mortality in both men and women.

* p <0.01.
• p <0.001.

Data from: Kannel WB, Wilson PWF, D'Agostino RB, et al. Am Heart J 1998; 136:205.

Graphic 58658 Version 4.0

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Contributor Disclosures
Philip J Podrid, MD, FACC Nothing to disclose Brian Olshansky, MD Speaker’s Bureau: Lundbeck [Orthostatic
hypotension (Droxidopa)]. Consultant/Advisory Boards: Lundbeck [Orthostatic hypotension (Droxidopa)]; Sanofi
Aventis; Respircardia. Other Financial Interest: Amarin [Hypertriglyceridemia (EPA; Chair, Data and Safety Monitoring
Board)]; Boehringer Ingelheim [Atrial fibrillation (GLORIA AF trial)]. Scott Manaker, MD, PhD Consultant/Advisory
Boards: Expert w itness in w orkers' compensation and in medical negligence matters [General pulmonary and critical
care medicine]. Equity Ow nership/Stock Options (Spouse): Johnson & Johnson; Pfizer. Other Financial Interest:
National Board for Respiratory Care [Director]. Brian C Dow ney, MD, FACC Nothing to disclose

Contributor disclosures are review ed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be provided
to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate
standards of evidence.

Conflict of interest policy

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