Cardiac Sudden Death

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Cardiac Sudden Death



Sudden Cardiac Death
Ali A Sovari, MD, FACP Fellow in Clinical Cardiac Electrophysiology, Cedars Sinai Medical Center/Heart

Practice Essentials
Sudden cardiac death (SCD) is an unexpected death due to cardiac causes
that occurs in a short time period (generally within 1 hour of symptom onset)
in a person with known or unknown cardiac disease. It is estimated that more
than 7 million lives per year are lost to SCD worldwide, including over 300,000
in the United States. See the image below.

Interplay of various risk factors
that can lead to sudden cardiac death.

Signs and symptoms
Patients at risk for SCD may have prodromes of chest pain, fatigue,
palpitations, and other nonspecific complaints. Factors relating to the
development of coronary artery disease (CAD) and, subsequently, myocardial
infarction (MI) and ischemic cardiomyopathy include the following:

Family history of premature coronary artery disease

Sedentary lifestyle
Specific factors relating to cardiovascular disease are listed below.
Coronary artery disease

Previous cardiac arrest
Prior myocardial infarction, especially within 6 months
Ejection fraction of less than 30-35%
History of frequent ventricular ectopy: More than 10 premature
ventricular contractions (PVCs) per hour or nonsustained ventricular
tachycardia (VT)
Dilated cardiomyopathy

Previous cardiac arrest
Ejection fraction of less than 30-35%
Use of inotropic medications
Hypertrophic cardiomyopathy

Previous cardiac arrest
Family history of SCD
Symptoms of heart failure
Drop in systolic blood pressure (SBP) or ventricular ectopy upon stress


Most persons are asymptomatic
Valvular disease

Valve replacement within past 6 months
History of frequent ventricular ectopy

Symptoms associated with severe, uncorrected aortic stenosis or mitral
Long QT syndrome

Family history of long QT and SCD
Medications that prolong the QT interval
Bilateral deafness
See Clinical Presentation for more detail.

Laboratory studies

Cardiac enzymes (creatine kinase, myoglobin, troponin)
Electrolytes, calcium, and magnesium
Quantitative drug levels (quinidine, procainamide, tricyclic
antidepressants, digoxin): High or low drug levels may have a proarrhythmic

Toxicology screen: For drugs, such as cocaine, that cause vasospasminduced ischemia

Thyroid-stimulating hormone

Brain natriuretic peptide (BNP)
Other tests to evaluate or predict risk of SCD

Imaging studies: Chest radiography, echocardiography, nuclear

Electrocardiography (ECG): Including, possibly, signal-averaged ECG

Coronary angiography

See Workup for more detail.

In general, advanced cardiac life support (ACLS) guidelines should be
followed in all cases of sudden cardiac arrest (SCA).
Bystander cardiopulmonary resuscitation (CPR)
Immediate chest compression and defibrillation are reportedly the most
important interventions to improve the outcome in SCA. Research indicates
that bystander use of automated external defibrillators increases

neurologically intact survival to discharge (14.3% without bystander
defibrillation; 49.6% with defibrillation).[1]
Pharmacologic therapy
Medications used in SCD include the following:

Ventricular arrhythmia: Epinephrine or vasopressin; amiodarone and
lidocaine can be used as antiarrhythmic drugs if defibrillation does not
control the arrhythmia

Pulseless electrical activity (PEA): Epinephrine; atropine used in case of

Asystole: One study suggested that vasopressin is more effective in
acute therapy for asystole than epinephrine [2]

Medical stabilization: Empiric beta blockers are reasonable in many
Therapeutic hypothermia
This intervention limits neurologic injury associated with brain ischemia during
a cardiac arrest and reperfusion injury associated with resuscitation.[3]

Temporary cardiac pacing
Radiofrequency ablation
Cardioverter defibrillator therapy
Coronary artery bypass grafting (CABG)
Excision of ventricular tachycardia foci
Excision of left ventricular aneurysms
Aortic valve replacement
Orthotopic heart transplantation
See Treatment for more detail.

Sudden cardiac death (SCD) is an unexpected death due to cardiac causes
occurring in a short time period (generally within 1 h of symptom onset) in a
person with known or unknown cardiac disease. Most cases of SCD are
related to cardiac arrhythmias. Approximately half of all cardiac deaths can be
classified as SCDs. SCD represents the first expression of cardiac disease in
many individuals who experience out-of-hospital cardiac arrest.

This article explores the epidemiology and pathophysiology of SCD. It also
discusses the diagnostic approach to patients at risk for SCD, as well as the
prevention of SCD and the treatment of sudden cardiac arrest.

The most common electrophysiologic mechanisms leading to SCD are
tachyarrhythmias such as ventricular fibrillation (VF) or ventricular tachycardia
(VT). Interruption of tachyarrhythmias, using either an automatic external
defibrillator (AED) or an implantable cardioverter defibrillator (ICD), has been
shown to be an effective treatment for VF and VT.[4] The implantable
defibrillator has become the central therapeutic factor in the prevention and
treatment of sudden cardiac death. Patients with tachyarrhythmias, especially
VT, carry the best overall prognosis among patients with sudden cardiac
arrest (SCA).
There are multiple factors at the organ (eg imbalance of autonomic tone),
tissue (eg reentry, wave break, and action potential duration alternans),
cellular (eg triggered activity, and automaticity) and subcellular (abnormal
activation or deactivation of ion channels) level involved in generation of VT or
VF in different conditions. An anatomical or a functional block in the course of
impulse propagation may create a circuit with the wave front circling around it
and resulting in VT. Other mechanisms such as wave break and collisions are
involved in generating VF from VT. While at the tissue level the abovementioned reentry and wave break mechanisms are the most important
known mechanisms of VT and VF, at the cellular level increased excitation or
decreased repolarization reserve of cardiomyocytes may result in ectopic
activity (eg automaticity, triggered activity), contributing to VT and VF initiation.
At the subcellular level, altered intracellular Ca2+ currents, altered intracellular
K+ currents (especially in ischemia), or mutations resulting in dysfunction of a
sodium channel (Na+ channelopathy) can increase the likelihood of VT and
Approximately 20-30% of patients with documented sudden death events
have bradyarrhythmia or asystole at the time of initial contact. Oftentimes, it is
difficult to determine with certainty the initiating event in a patient presenting
with a bradyarrhythmia because asystole and pulseless electrical activity
(PEA) may result from a sustained VT. Less commonly, an initial
bradyarrhythmia producing myocardial ischemia may then provoke VT or VF.

Most cases of SCD occur in patients with structural abnormalities of the heart.
Myocardial infarction (MI) and post-MI remodeling of the heart is the most
common structural abnormality in patients with SCD. In patients who survive a
myocardial infarction, the presence of premature ventricular contractions
(PVCs), particularly complex forms such as multiform PVCs, short coupling
intervals (R-on-T phenomenon), or VT (salvos of 3 or more ectopic beats),
reflect an increased risk of sudden death. However suppression of the PVCs
with antiarrhythmic drugs increases mortality, owing to the proarrhythmic risk
of currently available medications.
Hypertrophic cardiomyopathy and dilated cardiomyopathy are associated with
an increased risk of SCD. Various valvular diseases such as aortic stenosis
are associated with increased risk of SCD. Acute illnesses, such as
myocarditis, may provide both an initial and sustained risk of SCD due to
inflammation and fibrosis of the myocardium.
Less commonly, SCD happens in patients who may not have apparent
structural heart disease. These conditions are usually inherited arrhythmia
Even though many patients have anatomic and functional cardiac substrates
that predispose them to develop ventricular arrhythmias, only a small
percentage develop SCD. Identifying the patients at risk for SCD remains a
challenge. The strongest known predictor of SCD is significant left
ventricular dysfunction of any cause. The interplay between the regional
ischemia, LV dysfunction, and transient inciting events (eg, worsened
ischemia, acidosis, hypoxemia, wall tension, drugs, metabolic disturbances)
has been proposed as being the precipitator of sudden death (see the image

Interplay of various risk factors
that can lead to sudden cardiac death.

United States
SCD accounts for approximately 325,000 deaths per year in the United
States; more deaths are attributable to SCD than to lung cancer, breast
cancer, or AIDS. This represents an incidence of 0.1-0.2% per year in the
adult population. SCD is often the first expression of CAD and is responsible
for approximately 50% of deaths from CAD.
In several population-based studies, the incidence of out-of-hospital cardiac
arrest has been noted as declining in the past 2 decades, but the proportion of
sudden CAD deaths in the United States has not changed. A high incidence of
SCD occurs among certain subgroups of high-risk patients (congestive heart
failure with ejection fraction < 30%, convalescent phase after myocardial
infarction, patients who survived cardiac arrest). However, these populations
are much smaller than patients with minimal or even inapparent coronary
artery disease. Consequently, in the overall population, most SCD occurs in
lower risk patients. The time dependence of risk for SCD has been noted in
several studies, with an increased number of events in the first 6-24 months
after surviving a major cardiovascular event.

The frequency of SCD in Western industrialized nations is similar to that in the
United States. The incidence of SCD in other countries varies as a reflection
of the prevalence of coronary artery disease or other high-frequency
cardiomyopathies in those populations. The trend toward increasing SCD
events in developing nations of the world is thought to reflect a change in
dietary and lifestyle habits in these nations. It has been estimated that SCD
claims more than 7,000,000 lives per year worldwide.[5]

Of more than 300,000 deaths attributed to SCD in the United States each
year, a large portion (as many as 40%) are unwitnessed. For most people who
experience SCD, their survival depends on the presence of individuals who
are competent in performing basic life support, the rapid arrival of personnel
and apparatus for defibrillation and advanced life support, and transfer to a
hospital. Even under ideal circumstances, only an estimated 20% of patients
who have out-of-hospital cardiac arrest survive to hospital discharge. In a
study of out-of-hospital cardiac arrest survival in New York City, only 1.4% of
patients survived to hospital discharge. Other studies in suburban and rural
areas have indicated higher rates of survival (as high as 35%). Placement of
automatic external defibrillators throughout communities and training people
to use them has the potential to markedly improve outcomes from SCD.

Upon emergency department (ED) presentation, the most important
determinants of survival include (1) an unsupported systolic blood pressure
(SBP) greater than 90 mm Hg, (2) a time from loss of consciousness to
return of spontaneous circulation (ROSC) of less than 25 minutes, and (3)
some degree of neurological responsiveness.

A major adverse outcome from a SCD event is anoxic encephalopathy,
which occurs in 30-80% of cases.
Most studies demonstrate inconclusive data with regard to racial differences
as they relate to the incidence of sudden death. Some studies suggest that a
greater proportion of coronary deaths were "sudden" in blacks compared to
whites. In a report by Gillum et al on SCD from 1980-1985, the percentage of
coronary artery disease deaths occurring out of the hospital and in EDs was
found to be higher in blacks than in whites (see the image below).[6]

Cardiac death, sudden. Plots of
mortality rates (deaths per 1000 persons) for ischemic heart disease occurring out of
the hospital or in the emergency department (top) and occurring in the hospital (bottom)
by age, sex, and race in 40 states during 1985.

Men have a higher incidence of SCD than women, with a ratio of 3:1. This
ratio generally reflects the higher incidence of obstructive coronary artery
disease in men. Recent evidence suggests that a major sex difference may
exist in the mechanism of myocardial infarction. Basic and observational data
point to the fact that men tend to have coronary plaque rupture, while women
tend to have plaque erosion. Whether this biologic difference accounts for the
male predominance of SCD is unclear.

The incidence of SCD parallels the incidence of coronary artery disease, with
the peak of SCD occurring in people aged 45-75 years. The incidence of SCD
increases with age in men, women, whites, and nonwhites as the prevalence
of coronary artery disease increases with age. However, the proportion of
deaths that are sudden from coronary artery disease decreases with age. In
the Framingham study, the proportion of coronary artery disease deaths that
were sudden was 62% in men aged 45-54 years, but this percentage fell to
58% in men aged 55-64 years and to 42% in men aged 65-74 years.
According to Kuller et al, 31% of deaths are sudden in people aged 20-29


Obtaining a thorough history from the patient, family members, or other
witnesses is necessary to obtain insight into the events surrounding the
sudden death. Patients at risk for SCD may have prodromes of chest pain,
fatigue, palpitations, and other nonspecific complaints. History and associated
symptoms, to some degree depend on the underlying etiology of SCD. For
example, SCD in an elderly patient with significant coronary artery disease
may be associated with preceding chest pain due to a myocardial infarction,
while SCD in a young patient may be associated with history of prior syncopal
episodes and/or a family history of syncope and SCD and due to inherited
arrhythmia syndromes. As many as 45% of persons who have SCD were
seen by a physician within 4 weeks before death, although as many as 75% of
these complaints were not related to the cardiovascular system. A prior history
of LV impairment (ejection fraction < 30-35%) is the most potent common risk
factor for sudden death.
Risk factors that relate to coronary artery disease and subsequent myocardial
infarction and ischemic cardiomyopathy also are important and include a
family history of premature coronary artery disease, smoking, dyslipidemia,
hypertension, diabetes, obesity, and a sedentary lifestyle. Specific
considerations include the following:

Coronary artery disease
See the list below:

Previous cardiac arrest
Prior myocardial infarction, especially within 6 months
Ejection fraction less than 30-35%
History of frequent ventricular ectopy (more than 10 PVCs per h or
nonsustained VT)
Dilated cardiomyopathy
See the list below:

Previous cardiac arrest
Ejection fraction less than 30-35%
Use of inotropic medications
Hypertrophic cardiomyopathy
See the list below:

Previous cardiac arrest
Family history of SCD
Symptoms of heart failure
Drop in SBP or ventricular ectopy upon stress testing
Most are asymptomatic
Valvular disease
See the list below:

Valve replacement within 6 months
History of frequent ventricular ectopy
Symptoms associated with severe uncorrected aortic stenosis or mitral
Long QT syndrome
See the list below:

Family history of long QT and SCD
Medications that prolong the QT interval
Bilateral deafness
Wolff-Parkinson-White (WPW) syndrome (with atrial fibrillation or
atrial flutter with extremely rapid ventricular rates)
With extremely rapid conduction over an accessory pathway, degeneration to
VF can occur.

See the list below:

Brugada syndrome , arrhythmogenic right ventricular (RV)
cardiomyopathy/dysplasia, and others

The physical examination may reveal evidence of underlying myocardial
disease or may be entirely normal, depending on the underlying cause. Initial
evaluation studies show that patients who survive to ED presentation can be
stratified by a cardiac arrest score, which has excellent diagnostic value. The
cardiac arrest score, developed by Thompson and McCullough, can be used

for patients with witnessed out-of-hospital cardiac arrest and is defined by the
following criteria:[9, 10]

Clinical characteristic points
See the list below:

ED SBP greater than 90 mm Hg = 1 point
ED SBP less than 90 mm Hg = 0 points
Time to ROSC less than 25 minutes = 1 point
Time to ROSC more than 25 minutes = 0 points
Neurologically responsive = 1 point
Comatose = 0 point
Maximum score = 3 points
Patients with a score of 3 points can be expected to have an 89% chance of
neurologic recovery and an 82% chance of survival to discharge (see the
image below).

Cardiac death, sudden. Figure a
shows neurologic outcome stratified by initial cardiac arrest score. Neurologic recovery
is defined as discharged home and able to care for self. Figure b shows overall survival
stratified by initial cardiac arrest score.

McCullough indicates that even in the setting of ST elevation and early
invasive management with primary angioplasty and intraaortic balloon pump
insertion, patients with low cardiac scores are unlikely to survive.[11]
Severe anoxic encephalopathy in patients with scores of 0, 1, or 2 mitigates
conservative management with empiric supportive and medical therapy. Given
the very poor actuarial survival rates for these patients, invasive management
with catheterization and electrophysiology studies (EPS) is rarely justified.

Ischemic heart disease

Cardiac arrest due to ventricular arrhythmias may be due to post-MI
remodeling of the heart with scar formation and interstitial fibrosis
(intramyocardial collagen deposition) or to acute MI/ischemia. A chronic infarct
scar can serve as the focus for reentrant ventricular tachyarrhythmias. This
can occur shortly after the infarct or years later. Interestingly, post-MI
remodeling and ischemic cardiomyopathy may be associated with increased
interstitial fibrosis even in noninfarcted areas of the heart.[12] Interstitial fibrosis
can provide anatomical block similar to a scar. Fibroblasts and myocytes
shown to be coupled through gap junctions and fibroblasts can reduce
repolarization reserve of myocytes. In addition to post-MI remodeling, many
other structural heart diseases associated with SCD (eg, dilated
cardiomyopathy, hypertrophic cardiomyopathy, and aortic stenosis) are also
associated with increased myocardial fibrosis.[13, 14, 15]
Many studies support the relationship of symptomatic and asymptomatic
ischemia as a factor for risk of SCD. Patients resuscitated from out-of-hospital
cardiac arrest represent a group of patients with increased recurrence of
cardiac arrest and have been shown to express an increased incidence of
silent ST-segment depression. Experiments inducing myocardial ischemia in
animal models have a strong relationship with the development of VF.
However, in patients with prior myocardial infarction and scarring, ventricular
arrhythmias, especially VT, do not require an acute ischemic trigger.
In postmortem studies of people who have died from SCD, extensive
atherosclerosis is a common pathologic finding. In survivors of cardiac arrest,
coronary heart disease with vessels showing greater than 75% stenosis is
observed in 40-86% of patients, depending on the age and sex of the
population studied. Autopsy studies show similar results; in one study of 169
hearts, approximately 61% of patients died of SCD, and more than 75%
stenosis in 3 or 4 vessels and similar severe lesions were present in at least 2
vessels in another 15% of cases. No single coronary artery lesion is
associated with an increased risk for SCD. Despite these findings, only
approximately 20% of SCD-related autopsies have shown evidence of a
recent MI. A greater proportion of autopsies (40-70%) show evidence of a
healed MI. Many of these hearts also reveal evidence of plaque fissuring,
hemorrhage, and thrombosis.
The Cardiac Surgery Study (CASS) showed that improving or restoring blood
flow to an ischemic myocardium decreased the risk of SCD, especially in
patients with 3-vessel disease and heart failure, when compared with medical
treatment over a 5-year period.

The efficacy of beta-blocking agents, such as propranolol, in decreasing
sudden death mortality, especially when administered to patients who had MI
with VF, VT, and high-frequency PVCs, may be due in part to the ability of
beta-blockers to decrease ischemia, but they are also effective in patients with
nonischemic cardiomyopathy for reduction of SCD. Beta-blockers also
increase the VF threshold in ischemic animals and decrease the rate of
ventricular ectopy in patients who had MI.
Reperfusion of ischemic myocardium with thrombolysis or direct percutaneous
coronary intervention can induce transient electrical instability by several
different mechanisms.
Coronary artery spasm is a condition that exposes the myocardium to both
ischemia and reperfusion insults. It is occasionally associated with VT, VF, and
SCD. Since some of the episodes of coronary vasospasm may be silent, this
disease should be considered in a patient with unexplained SCA.[16] The exact
mechanism of ventricular arrhythmia in coronary vasospasm is not known, but
factors associated with both ischemia and reperfusion may contribute in
induction of arrhythmia.
Nonatherosclerotic coronary artery abnormalities, including congenital lesions,
coronary artery embolism, coronary arteritis, and mechanical abnormalities of
the coronary artery, have been associated with an increased incidence of
sudden death.

Nonischemic cardiomyopathies
Patients with nonischemic cardiomyopathies represent the second largest
group of patients who experience SCD in the United States. Nonischemic
myopathies, for the purpose of this article, can be divided into the categories
dilated and hypertrophic.
Dilated cardiomyopathy
Dilated cardiomyopathy can result from prior ischemia and myocardial
infarction or from nonischemic causes. Nonischemic dilated cardiomyopathy
(DCM) is becoming increasingly more common, with an incidence of
approximately 7.5 cases per 100,000 persons each year. Of cases of SCD,
10% are estimated to be attributable to DCM. The prognosis is very poor for
these patients, with a 1-year mortality rate of 10-50%, depending on the New
York Heart Association functional class; approximately 30-50% of these
deaths are SCD.

The causes of DCM are uncertain; viral, autoimmune, genetic, and
environmental (alcohol) origins are implicated. The predominant mechanism
of death appears to be ventricular tachyarrhythmia, although bradyarrhythmia
and electromechanical dissociation also have been observed, especially in
patients with advanced LV dysfunction. Extensive fibrosis of the
subendocardium, leading to dilated ventricles and subsequent generation of
reentrant tachyarrhythmias, is a proposed factor in mechanism of sudden
death. Multiple factors have been shown to contribute to increased risk for
SCD in this population. The most important hemodynamic predictor is an
increase in end-diastolic pressure and subsequent wall tension. Other
important factors are increased sympathetic tone, neurohumoral activation,
and electrolyte abnormalities.
Many drugs used in the treatment of heart failure, such as antiarrhythmics,
inotropic agents, and diuretics, have direct or indirect (eg, through electrolyte
abnormalities) proarrhythmic properties, which may provoke arrhythmias in
some cases. Potassium-sparing diuretics may be helpful in decreasing SCD.
Nonsustained ventricular tachycardia (NSVT) is common in patients with
dilated cardiomyopathy and approximately 80% of persons with DCM have
abnormalities on Holter monitoring. Although NSVT may be a marker, it has
not been shown to be a reliable predictor of SCD in these patients. Recent
studies have shown possibility of increased mortality following suppression of
NSVT by antiarrhythmic medications due to proarrhythmic properties of these
medications and involvement of several other factors in generation of VT and
VF. Given the possibility of sustained VT being the underlying cause, a history
of syncope should be aggressively pursued. Unexplained syncope, especially
in patients with class 3 or 4 heart failure, has been shown to be a predictor of
SCD in most patients with cardiomyopathy
Hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is an autosomal-dominant, incompletely
penetrant genetic disorder resulting from a mutation in one of the many (>45)
genes encoding proteins of the cardiac muscle sarcomere. Among the genetic
abnormalities described, mutations in the genes coding for the beta-myosin
heavy chains, and cardiac troponin T make up most cases. Other mutations
may include alpha-myosin heavy chain MYH6), cardiac troponin C (TNNC1),
alpha-tropomyosin (TPM1), myosin binding protein-C (MYBPC3), cardiac
troponin (TNNI3), essential and regulatory light-chain genes
(MYL3 and MYL2, respectively), cardiac alpha-actin gene (ACTC), and titin
(TTN). The incidence of SCD in this population is 2-4% per year in adults and

4-6% per year in children and adolescents. HCM is the most common cause
of SCD in people younger than 30 years.
The vast majority of young people who die of HCM are previously
asymptomatic. The patients may experience SCD while at rest or with mild
exertional activity; however, in a significant portion of these patients, the SCD
event occurs after vigorous exertion. HCM is the single greatest cause of SCD
in young athletes and, hence, is the major entity for which to screen during the
physical examination of an athlete.
The mechanism of SCD in HCM is not entirely understood. Initially, it was
thought to be due to obstruction of the outflow tract because of catecholamine
stimulation. However, later studies suggested that individuals with
nonobstructive HCM are at high risk for SCD as well, primarily related to VT or
VF. The mechanism of arrhythmia in this setting is not clear, and hypertrophy
may be a part of cardiac remodeling in these patients that provides the
substrate for lethal arrhythmia.
Rapid or polymorphic symptomatic NSVT may have better predictive value
compared with asymptomatic and monomorphic NSVT. Other clinical markers
that may have predictive value for SCD in patients with HCM are young age at
onset, thickness of the septum, and family history of SCD.
Arrhythmogenic right ventricular cardiomyopathy
Arrhythmogenic RV cardiomyopathy is characterized by replacement of the
RV wall with fibrofatty tissue. Involvement of the interventricular septum and
left ventricle is associated with poorer outcomes.
About 30-50% of cases occur as a phenotypically apparent familial disorder.
Several genetic defects, including mutations in the desmoplakin domain locus
on chromosome 6 and the ryanodine receptor locus on chromosome 1
(although this has been debated), have been correlated with SCD. Again,
interstitial fibrosis plays an important role in ventricular arrhythmia in this
condition. Autosomal dominant inheritance is common, but autosomal
recessive transmission has been reported for select mutations. The autosomal
recessive form, Naxos disease (named after the Greek Island), has been
reported in a geographically isolated area mainly in Mediterranean countries
and is usually associated with wooly hair and palmoplantar keratoderma or
similar skin disorder. This disorder is associated with mutation in the gene for
plakoglobin, a protein involved in cellular adhesion, found on chromosome

Arrhythmogenic RV dysplasia affects men more often than women. The
annual incidence rate of SCD in this population is approximately 2%. Patients
may present with signs and symptoms of RV hypertrophy and dilation, often
with sustained monomorphic or polymorphic VT of a left bundle-branch block
morphology with an axis usually between negative 90-100°
Atrial arrhythmias may be present in as many as 25% of patients. Syncope
and sudden death often are associated with exercise. In many patients,
sudden death is the first manifestation of the disease. Clinicians should be
alerted to the epsilon wave finding on ECG studies (see the image below).
The epsilon wave can be present in as many as 23% of patients after the first
VT event. The percentage of patients with the epsilon wave finding on ECG
increases to 27% and 34% at 5 and 10 years, respectively, after the first VT

Cardiac death, sudden. Epsilon wave in a
patient with arrhythmogenic right ventricular dysplasia.

Uhl anomaly is a condition in which the RV wall is extremely thin secondary to
apposition of endocardial and epicardial layers.

Valvular disease
Prior to the advent of surgical therapy for valvular heart disease, SCD was
fairly common in patients with progressive aortic stenosis.

Most aortic stenosis deaths were sudden. In a study by Chizner et al of 42
patients who had isolated aortic stenosis and did not undergo valve
replacement, as many as 56% of deaths were sudden at 5 years of follow-up.
Of these 42 patients, 32 were symptomatic and 10 were asymptomatic. [17]
The mechanism of sudden death is unclear, and both malignant ventricular
arrhythmia and bradyarrhythmia have been documented.
The incidence of SCD has decreased significantly with advent of aortic valve
replacement. However, it still accounts for the second most common cause of
death postoperatively in this population and especially in those with prosthetic
and heterograft aortic valve replacement. The incidence of SCD after aortic
valve surgery is highest in the first 3 weeks after the procedure and then
plateaus at 6 months of follow-up.

Other valvular lesions
The risk of SCD is much lower in other valvular diseases compared with aortic
Aortic insufficiency usually presents with signs of heart failure and progressive
LV dilatation. As part of this process, reentrant or automatic ventricular foci
may develop and ultimately lead to a symptomatic ventricular arrhythmia. After
valve replacement, LV wall tension can be expected to reduce and the risk of
arrhythmia can be expected to decrease.
Mitral stenosis is becoming increasingly uncommon in the United States
because of widespread use of antibiotics in primary streptococcal infections.
SCD due to mitral stenosis is very rare.
The incidence of SCD is low in patients with mitral valve prolapse (MVP).
MVP has a 5-7% incidence in the general population. In clinically significant
MVP, the risk of SCD seems to rise along with total mortality. Kligfield et al
estimated that the incidence of sudden death varies with the presence of
symptoms and the severity of mitral regurgitation. Ventricular
tachyarrhythmias are the most frequent arrhythmia in patients with SCD. Risk
factors for SCD to consider in these patients include a family history of SCD,
echocardiographic evidence of a redundant mitral valve, repolarization
abnormalities, and lengthening of the corrected QT interval (>420 ms in
women and >450 ms in men).

Congenital heart disease

In the pediatric and adolescent age groups, SCD occurs with an incidence of
1.3-8.5 cases per 100,000 patients annually, accounting for approximately 5%
of all deaths in this group. The causes of SCD are much more diverse in
children than adults. In reviewing 13 studies involving 61 children and
adolescents with SCD, Driscoll found 50% of cases were due to HCM; 25%
were due to anomalous origin of the left coronary artery; and the remaining
patients had aortic stenosis, cystic medial necrosis, and sinus node artery
obstruction. The following is a classification of SCD in the pediatric population.
In patients with known, previously recognized (including repaired) congenital
heart disease, abnormalities associated with SCD include the following:

Tetralogy of Fallot
Transposition of the great arteries
Fontan operation
Aortic stenosis
Marfan syndrome
Mitral valve prolapse
Hypoplastic left heart syndrome
Eisenmenger syndrome
Congenital heart block
Ebstein anomaly
In patients with known, previously recognized (including repaired) heart
disease, acquired causes of SCD include the following:

Kawasaki syndrome
DCM or myocarditis
In patients with previously unrecognized heart disease who have structural
heart disease, causes of SCD include the following:

Congenital coronary artery abnormalities
Arrhythmogenic RV cardiomyopathy
In patients with previously unrecognized heart disease who do not have
structural heart disease, causes of SCD include the following:

Long QT syndrome
WPW syndrome
Primary ventricular tachycardia and ventricular fibrillation
Primary pulmonary hypertension

Commotio cordis - Traumatic blow to the chest wall (eg, from a hockey
puck or baseball) causing VT/VF and SCD in the absence of significant
identifiable trauma
The predominant mechanism is ventricular arrhythmias. In tetralogy of Fallot
after postoperative correction of the anomaly, as many as 10% of these
patients have VT and the incidence of sudden death is 2-3%. In the Fontan
procedure, ie, to correct a physiologic single ventricle, even atrial arrhythmias
can cause severe hemodynamic compromise and arrhythmic death. Patients
who develop secondary pulmonary hypertension (Eisenmenger syndrome),
despite attempted correction of the anatomic defects, have a very poor
prognosis. The terminal event may be bradycardia or VT progressing to VF.

Primary electrophysiologic abnormalities
This generally represents a group of abnormalities in which patients have no
apparent structural heart disease but have a primary electrophysiologic
abnormality that predisposes them to VT or VF. Some imaging techniques
have detected abnormal sympathetic neural function in these patients. An
ECG study can provide clues to the diagnosis; consider a familial component
to these conditions. Normal early repolarization may be associated with
increased SCD, though this often represents a benign finding.[18]
Results from the Cardiac Arrest Survivors With Preserved Ejection Fraction
Registry (CASPER) suggest early repolarization is present in a significant
proportion of causally diagnosed and idiopathic VF.[19]
Long QT syndrome
Idiopathic long QT syndrome, in which patients have a prolonged QT with a
propensity to develop malignant ventricular arrhythmias, is a rare familial
Two inheritance patterns of congenital long QT syndrome have been
described. The Jervell-Lange-Nielsen syndrome, associated with congenital
deafness, has an autosomal-recessive pattern of inheritance. The RomanoWard syndrome is not associated with deafness and has an autosomal
dominant pattern of inheritance with variable penetration. This syndrome
accounts for 90% of long QT syndrome cases. More than 200 mutations in the
10 or more genes related to long QT syndrome have been found. Among the
most common are mutations of SCN5A on chromosome 3, the HERG gene on
chromosome 7, and the KVLTQT1 gene on chromosome 11.

Alteration in the function of a myocellular channel protein that regulates the
potassium flux during electrical repolarization is thought to be causative,
though in some subsets of long QT syndrome, such as those with mutations
in SCN5A (long QT3), Na channels are primarily impaired. A relationship with
sympathetic nervous system imbalance also appears to exist. The
prolongation that occurs makes these patients susceptible to develop a
specific form of VT called torsade de pointes.
The clinical course of patients with long QT syndrome is quite variable, with
some patients remaining asymptomatic while others develop torsade de
pointes with syncope and sudden death. Symptoms and SCD are more
common among homozygous individuals (those with two copies of the mutant
allele), compared with heterozygous individuals (who have a single mutant
allele). The risk of SCD is impacted by environmental factors such as
hypokalemia, medications and the presence of sinus pauses. SCD in these
patients also has been associated with emotional extremes, auditory auras or
stimulation, and vigorous physical activity. Symptoms usually begin in
childhood or adolescence.
The probability that a specific patient has congenital long QT syndrome is
divided to low, intermediate, and high probability based on the following
criteria: (1) ECG criteria including long QT, torsade de pointes, notched T
wave, T wave alternans, bradycardia for age; (2) clinical criteria including
syncope with or without stress, deafness; and (3) family history of long QT
syndrome or SCD.
When measuring QTc, selecting rhythm strips that have minimal variability of
RR intervals and a stable heart rate is important.
Treatment for long QT syndrome includes beta-blockers and often pacemaker
or ICD implantation. Beta-blockers decrease the overall mortality in patients
with long QT syndrome. However, they do not eliminate the risk of syncope,
cardiac arrest, and SCD completely. They are not effective in patients with
mutation in Na channel genes (long QT3). Torsade de pointes in patients with
long QT syndrome is associated with bradycardia and pauses. Therefore, a
pacemaker can prevent torsade de pointes in these patients by preventing
bradycardia. ICD therapy may be indicated in patients with recurrent
symptoms despite treatment with beta-blockers.
Acquired long QT syndrome

A number of antiarrhythmics (especially class Ia and class III) and other
medications, electrolyte abnormalities, cerebrovascular diseases, and altered
nutritional states are known to cause QT prolongation and put patients at risk
for torsade de pointes. This usually occurs when QT prolongation is
associated with a slow heart rate and hypokalemia.
The QT interval is prolonged in as many as 32% of patients with intracranial
hemorrhage (especially in subarachnoid hemorrhages). Lesions in the
hypothalamus are thought to lead to this phenomenon.
Reports of sudden death due to ventricular arrhythmia in patients with
hypocalcemia, hypothyroidism, nutritional deficiencies associated with
modified starvation diets, and in patients who are obese and on severe
weight-loss programs have been reported.
Class Ia antiarrhythmic drugs that cause acquired long QT syndrome include
quinidine, disopyramide, and procainamide. Class III antiarrhythmic drugs that
cause acquired long QT syndrome include sotalol, N -acetyl procainamide,
bretylium, amiodarone, and ibutilide.
Other drugs that cause acquired long QT syndrome include bepridil, probucol,
tricyclic and tetracyclic antidepressants, phenothiazines, Haldol,
antihistamines (eg, terfenadine, astemizole), antibiotics (eg, erythromycin,
sulfamethoxazole/trimethoprim), chemotherapeutics (eg, pentamidine,
anthracycline), serotonin antagonists (eg, ketanserin, zimeldine), and
organophosphorus insecticides.
Electrolyte abnormalities that cause acquired long QT syndrome include
hypokalemia, hypomagnesemia, and hypocalcemia.
Altered nutritional states and cerebrovascular disease that cause acquired
long QT syndrome include intracranial and subarachnoid hemorrhages,
stroke, and intracranial trauma.
Hypothyroidism and altered autonomic status (eg, diabetic neuropathy) can
cause acquired long QT syndrome.
Hypothermia can cause acquired QT prolongation. The ECG will typically also
demonstrate an Osborn wave, a distinct bulging of the J point at the beginning
of the ST segment. This ECG finding resolves upon warming.
Short QT syndrome

The short QT syndrome is a newly recognized syndrome, first time described
in 2000, which can lead to lethal arrhythmias and SCD. Three mutations in
potassium channels have been described that lead to gain of function in
potassium channels and shortening of action potential and decreased QT
To diagnose short QT syndrome, the QTc should be less than 330 msec and
tall and peaked T waves should be present. Clinical manifestations are
variable from no symptoms, to palpitations due to atrial fibrillation, syncope
due to VT, and SCD. VF is easily inducible at electrophysiology study in these
patients, and SCD can happen at any age.
A study by Gollob et al proposes diagnostic criteria that include QTc interval, J
point–to–T peak interval, clinical history (eg, SCA, atrial fibrillation [AF],
syncope), family history and genotyping.[20]
Although antiarrhythmic medications, such as sotalol, ibutilide, and
procainamide, have been proposed as a therapy (to prolong the QT), data to
support this approach are insufficient at present. ICD placement may be
considered to prevent VT and SCD, although T-wave oversensing, resulting in
inappropriate ICD discharges, has been problematic.
Because no long-term outcome data are available, Giustetto et al investigated
the clinical characteristics and the long-term course of a large cohort of
patients with short QT syndrome (defined as QT of ≤360 ms). Their findings
suggest short QT syndrome carries a high risk of sudden death in all age
groups, with the highest risk in symptomatic patients. Hydroquinidine therapy
appeared to reduce the antiarrhythmic event rate from 4.9% 0%. However,
this was a small registry studying a rare disease; thus, the true benefit is
Wolff-Parkinson-White syndrome
WPW syndrome is a recognized but rare cause of sudden death. The
existence of an atrioventricular accessory pathway in this syndrome results in
ventricular preexcitation, which appears with short PR interval, wide QRS
complex, and delta wave on ECG. The refractory period in the anterograde
direction of accessory pathway determines the ventricular rate in the setting of
atrial fibrillation and WPW. Most patients with WPW syndrome and SCD
develop atrial fibrillation with a rapid ventricular response over the accessory
pathway, which induces VF (see the image below). In a study by Klein et al of
31 patients with VF and WPW syndrome, a history of atrial fibrillation or

reciprocating tachycardia was an important predisposing factor. The presence
of multiple accessory pathways, posteroseptal accessory pathways, and a
preexcited R-R interval of less than 220 ms during atrial fibrillation are
associated with higher risk for SCD.

Cardiac death, sudden.
Ventricular fibrillation appeared during rapid atrial fibrillation in a patient with WolffParkinson-White syndrome.

Symptomatic patients should be treated by antiarrhythmic medications (eg,
procainamide), catheter ablation of the accessory pathway, or electrical
cardioversion depending on the severity and frequency of symptoms.
Asymptomatic patients may be observed without treatment.
Medications such as digoxin, adenosine, and verapamil that block the AV
node are contraindicated in patients with WPW and atrial fibrillation because
they may accelerate conduction through the accessory pathway, potentially
causing VF and SCD.
Brugada syndrome
In 1992, Brugada and Brugada described a syndrome of a specific ECG
pattern of right bundle-branch block and ST-segment elevation in leads
V1 through V3 without any structural abnormality of the heart, that was
associated with sudden death.
In 25-30% of these patients, a mutation in SCN5A on chromosome 3 is
detected. This mutation results in a sodium channelopathy. The most common
clinical presentation is syncope, and this mutation is most common in young
males and in Asians. It is associated with VT, VF, and SCD.
Three ECG types of Brugada pattern are described. Only type 1,- which
consists of a coving ST elevation in V1 to V3 with downsloping ST segment
and inverted T waves, pseudo RBBB pattern with no reciprocal ST changes
and normal QTc, is specific enough to be diagnostic for Brugada syndrome
when it is associated with symptoms. The other two ECG patterns of Brugada
are not diagnostic, but they merit further evaluation.

The Brugada ECG pattern can be dynamic and not found on an index ECG.
When clinical suspicion is high, a challenge test with procainamide or some
other Na channel blocker may be diagnostic by reproducing the type 1 ECG
Although antiarrhythmic medications, catheter ablation and pacemaker
therapies all have potential, in young and symptomatic patients, an ICD
should be implanted to prevent VF and SCD. ICD therapy is the only proven
treatment to date. Whether ICD placement is indicated in older or
asymptomatic patients is controversial at present.
A prospective study by Delise et al suggests using a combination of clinical
risk factors (syncope and family history of SCD) with VT inducibility in EP
study to risk stratify patients with the type 1 ECG pattern of Brugada
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a syndrome
that presents with polymorphic VT, syncope, or SCD, and in about half of
these patients, a mutation in one of two different genes have been detected.
The polymorphic VT is characteristically induced by emotional or physical
stress (eg, exercise stress test). The medical therapy of choice is
administration of beta-blockers, and ICD may be indicated. New data may
support the use of flecainide in the treatment of this disease.[23]
Primary ventricular fibrillation occurs in a structurally normal heart due to
idiopathic etiology.
An estimated 3-9% of cases of VT and VF occur in the absence of myocardial
ischemia. As many as 1% of patients with out-of-hospital cardiac arrest have
idiopathic VF with no structural heart disease. As many as 15% of patients
younger than 40 years who experience VF have no underlying structural heart
disease. Viskin and Behassan noted that of 54 patients with idiopathic VF, 11
patients had histologic abnormalities on endomyocardial biopsy.
SCD is often the first presentation of VF in patients at risk but who have had
no preceding symptoms. In those patients who survive, VF may recur in as
many as one third of patients.
The options for medical therapy include beta-blockers and class 1A
antiarrhythmic drugs, but limited data are available regarding their efficacy.
The mainstay of treatment is preventing VF by ICD placement. Mapping and

radiofrequency ablation of the triggering foci is an option for those patients
who experience frequent episodes of VF following ICD placement.
Right ventricular outflow tract (RVOT) tachycardia is the most common form of
idiopathic VT, comprising 70-80% of all idiopathic VTs. RVOT tachycardia is a
very rare cause of SCD. It also has been referred to as exercise-induced VT,
adenosine-sensitive VT, and repetitive monomorphic VT.
RVOT tachycardia occurs in patients without structural heart disease and
arises from the RV outflow region. Current data suggest that triggered activity
is the underlying mechanism of RVOT tachycardia. RVOT tachycardia is
believed to be receptor-mediated because exogenous and endogenous
adenosine can terminate this process. Maneuvers that increase endogenous
acetylcholine also have been demonstrated to antagonize this process.
Symptoms typical of RVOT tachycardia include palpitations and presyncope
or syncope, often occurring during or after exercise or emotional stress. VT
also can occur at rest. The ECG during VT displays a left bundle-branch
block/inferior axis morphology.
Treatment is based on frequency and severity of symptoms. The first line of
therapy is a beta-blocker or calcium channel blocker. Patients with symptoms
not relieved by medical therapy are best treated with radiofrequency catheter
ablation. Successful ablation is reported in 83-100% of cases.

Other causes of sudden death
Two major causes of sudden cardiopulmonary death deserve mention.
Pulmonary embolism is a frequent cause of sudden death in people at risk.
Risk factors include previous personal or family history of deep venous
thromboembolism, malignancy, hypercoagulable states, and recent
mechanical trauma such as hip or knee surgery.
Aortic dissection or aneurysmal rupture is the other major cause of out-ofhospital nonarrhythmic cardiovascular death. Predisposing factors for aortic
dissection include genetic deficiencies of collagen such as Marfan syndrome,
Ehlers-Danlos syndrome, and aortic cystic medial necrosis.

Diagnostic Considerations

Other conditions to be considered in patients with suspected sudden cardiac
death include arrhythmogenic RV dysplasia and Brugada syndrome.
Important considerations include the following:

Recognize and initiate early management of patients with ischemic
heart disease. The importance of this cannot be overestimated, because
approximately 80% of SCD cases can be attributed to ischemic heart

Use appropriate medical therapy for ischemic heart disease (eg, betablockers).

It is very important to involve a specialist in cardiovascular disease in
the care of patients who have had a cardiac arrest or have symptoms of
ischemic heart disease, valvular disorders, or presentations with complex

It is very important to educate patients about the consequences of
noncompliance with medical therapy.
For patient education information, see the Heart Health Center and Healthy
Living Center, as well as Chest Pain, Heart Rhythm Disorders, Coronary
Heart Disease,Heart Attack, and Cardiopulmonary Resuscitation (CPR).

Differential Diagnoses

Angina Pectoris

Aortic Stenosis

Coronary Artery Atherosclerosis

Dilated Cardiomyopathy

Ebstein Anomaly

Hypertrophic Cardiomyopathy

Lown-Ganong-Levine Syndrome

Myocardial Infarction

Tetralogy of Fallot

Torsade de Pointes

Ventricular Fibrillation

Ventricular Premature Complexes

Ventricular Tachycardia

Wolff-Parkinson-White Syndrome

Laboratory Studies
Laboratory studies in the workup of sudden cardiac death include the

Cardiac enzymes (creatine kinase, myoglobin, troponin): Elevations in
these enzyme levels may indicate ischemia and MI. The extent of
myocardial damage usually can be correlated to the extent of elevation in
the enzyme levels. Patients are at increased risk for arrhythmia in the periinfarct period.

Electrolytes, calcium, and magnesium: Severe metabolic acidosis,
hypokalemia, hyperkalemia, hypocalcemia, and hypomagnesemia are some
of the conditions that can increase the risk for arrhythmia and sudden death.

Quantitative drug levels (quinidine, procainamide, tricyclic
antidepressants, digoxin): Drug levels higher than the levels indicated in the
therapeutic index may have a proarrhythmic effect. Subtherapeutic levels of
these drugs in patients being treated for specific cardiac conditions also can
lead to an increased risk for arrhythmia. Most of the antiarrhythmic
medications also have a proarrhythmic effect.

Toxicology screen: Looking for drugs, such as cocaine, that can lead to
vasospasm-induced ischemia is warranted if suspicion exists. Obtaining
levels of drugs (antiarrhythmics) also may be warranted.

Thyroid-stimulating hormone: Hyperthyroidism can lead to tachycardia
and tachyarrhythmias. Over a period of time, it also can lead to heart failure.
Hypothyroidism can lead to QT prolongation.

Brain natriuretic peptide (BNP): BNP has predictive value especially in
post MI patients and in patients with heart failure. Although preliminary and
not conclusive, emerging data support the notion that an elevated BNP level
may provide prognostic information on the risk of SCD, independent of
clinical information and LVEF.

Imaging Studies
Chest Rradiography
This may reveal whether someone is in congestive heart failure. It also can
show signs suggesting LV enlargement or RV enlargement. Signs of
pulmonary hypertension also may be evident on the chest radiograph.

Two-dimensional echocardiography with Doppler is essential in the evaluation
of SCD. A number of studies have demonstrated that the use of 2-dimensional
echocardiogram to evaluate left wall motion abnormalities after an acute MI
(using the LV wall-motion score index) is useful in predicting the risk for major
cardiac events, including sudden death. A decrease in the ejection fraction
and worsening wall motion abnormalities upon exercise echocardiography in
patients who have had an MI has been suggested to confer increased risk of
cardiac death.

Nuclear Imaging
Resting thallium or technetium-99m scintigraphy is helpful in assessing
myocardial damage after MI. A larger defect has been associated with greater
risk for future cardiac events. Exercise nuclear scintigraphy is very sensitive
for detecting the presence, extent, and location of myocardial ischemia.
Gibson et al found that pharmacologic-stress nuclear (dipyridamole or
adenosine) scintigraphy was better than submaximal exercise ECG and
coronary angiography in predicting cardiac death and other cardiac events.
These tests can be very helpful in patients with low functional capacity such
as chronic obstructive pulmonary disease, peripheral vascular disease, or

orthopedic problems. The Multi-Center Post-Infarction Research Group
provided evidence that resting ejection fraction was the most important
noninvasive predictor of SCD and other cardiac events in patients with MI.

Other Tests
Other diagnostic studies include the following:

Electrocardiogram: This study is indicated in all patients. Evidence of
MI, prolonged QT interval, short QT interval, epsilon wave, Brugada sign,
short PR, a WPW pattern, or other conditions should be sought.

Signal-averaged ECG (SAECG) has been variably reported to be useful
in analysis of patients with SCD. What may be more useful is analysis of Twave alternans in patients with VT, VF, and/or SCD. Small changes in Tamplitude are not detected in 12-lead ECG. Microvolt T wave alternans
(MTWA) amplifies the alternans and may be used in the workup to predict
the risk of SCD. MTWA appears to have high negative predictive value for
the risk of SCD in patient with low LVEF (< 35%).[24] In addition, a pooledanalysis from 5 prospective studies showed that SCA happens in
approximately 3% of patients with an abnormal MWTA test and LVEF >35%,
suggesting that MTWA may be considered as a tool to identify patients at
risk for SCA.[24]However, further studies are required to determine how
MTWA alone or perhaps in combination with other electrophysiologic tools
can be used to risk stratify the patients at risk for SCA.

Genetic testing: The value of genetic testing in conditions such as
congenital long QT and HCM is still being evaluated. Some studies have
recommended the testing of siblings and close relatives of people with SCD
due to these conditions.

Coronary angiography
Perform cardiac catheterization in patients who survive SCD to assess the
state of ventricular function and the severity and extent of CAD. The number
of vessels with severe obstruction and the degree of LV dysfunction are
important variables in predicting cardiac events. Ejection fraction is the best
predictor of significant cardiac events and survival. Coronary angiography also
can help identify coronary anomalies and other forms of congenital heart
disease. Angiography is performed with the aim of identifying patients who
may benefit from revascularization. Revascularization is indicated when
ischemic myocardium is present as the underlying substrate of VT/VF.

Electrophysiology studies
In targeted patients, EPS play diagnostic, prognostic, and therapeutic roles.
EPS usually are performed after ischemic and structural heart disease has
been diagnosed and addressed. These studies have been used to identify
patients who have inducible versus noninducible sustained monomorphic VT.
The presence of inducible sustained VT, at baseline or when the patient is on
antiarrhythmic medications, confers a higher risk for sudden death.
Significantly lower ventricular function also has been observed in patients with
inducible sustained VT. Inducible bundle-branch reentrant VT can be seen in
patients with DCM and in the postoperative period after valvular replacement.
As many as 20% of patients with HCM have inducible sustained monomorphic
The identification of accessory pathways also is possible with these studies.
EPS are performed with an eye toward the following:

Ablation of VT foci, eg, bundle branch VT, RVOT VT, and some cases of
idiopathic LV tachycardia

ICD implantation, which is generally the case in survivors of SCD


Medical Care
Advanced cardiac life support (ACLS): In the event of cardiac arrest, the
immediate implementation of ACLS guidelines is indicated. Widespread
interest in improving rates of public ACLS training with a special emphasis on
use of early defibrillation by public service personnel (eg, police, fire, airline
attendants) exists. Through these measures, the greatest public health
benefits can be achieved in the fight against sudden death. In 2010, the
American Heart Association (AHA) published new Guidelines for
Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
The 2009 American Heart Association Cardiac Arrest Survival Summit
released consensus recommendations for implementation strategies to

optimize the care of patients with out-of-hospital sudden cardiac arrest
(OHCA).[26] These recommendations included collection of national data on
OHCA and local culture changes because incomplete implementation of
existing standards was seen as the limiting problem.
In general, ACLS guidelines should be followed in all cases of SCA; however,
depending on the presented rhythm, the following should be considered in
acute therapy of SCA:

Bystander CPR
The best techniques for bystander CPR continue to evolve based on rigorous
scientific evaluation and considerations of practical applicability. Recent data
suggest, for example, that compression-only CPR may be of equal or greater
effectiveness than traditional compression plus ventilation techniques.[27]
Adielsson et al suggest that the long-term perspective data among patients in
VF or pulseless VT who were given bystander CPR revealed that survival to 1
month after VF almost doubled.[28]
Berdowski and colleagues in a recent cohort study demonstrated that the
bystander use of automated external defibrillators can reduce the time to
defibrillation from 11 minutes to 4.1 minutes and improves neurologically intact
survival to discharge from 14.3% to 49.6%.[1] That observation is consistent
with already known facts that the main initiating mechanisms of sudden
cardiac death are ventricular tachycardia and ventricular fibrillation, and that
time to defibrillation is a critical factor in restoring the rhythm.
The conclusion that may be drawn from the above studies is that immediate
chest compression and defibrillation are the most important interventions to
improve the outcome in sudden cardiac arrest, whereas ventilation does not
play as important a role.

Ventricular arrhythmia (VF and VT)
Defibrillation is the mainstay of the acute therapy of SCA due to VF or VT.
Epinephrine (1 mg q3-5min) or vasopressin (40 U single dose) are given.

Amiodarone (300 mg IV push and 150 mg repeat IV push if needed) and
lidocaine (1 mg/kg IV push q3-5min up to 3 doses) can be used as
antiarrhythmic drugs if defibrillation does not control the VF/VT. In case of
polymorphic VT or suspected hypomagnesemia, 1-2 g IV push of magnesium
is recommended.

Pulseless electrical activity (PEA)
Epinephrine (1 mg q3-5min) can be used as there is no evidence supporting
the use of vasopressin in PEA. Atropine (1 mg q3-5min) should be used in
case of bradycardia. Sodium bicarbonate (1 meq/kg) should be given if there
is associated hyperkalemia and its use may be considered in long arrest
intervals and suspected metabolic acidosis.

One study suggested that vasopressin is more effective in acute therapy of
asystole than epinephrine.[2] Atropine and sodium bicarbonate are used with
similar indications in PEA.

Medical stabilization
Careful postresuscitative care is essential to survival because studies have
shown a 50% repeat inhospital arrest rate for people admitted after an SCD
event. Treatment of myocardial ischemia, heart failure, and electrolyte
disturbances are all justified by the results of multiple acute MI and congestive
heart failure randomized trials. Empiric beta-blockers are reasonable in many
circumstances because of favorable properties discussed in Causes. Empiric
antiarrhythmics, including amiodarone, should not supersede ICD implantation
unless control of recurrent VT is needed while the patient is in the hospital.

Therapeutic hypothermia
This intervention limits neurologic injury associated with brain ischemia during
a cardiac arrest and reperfusion injury associated with resuscitation.[3]

There are several plausible ways that therapeutic hypothermia may prevent
neurologic injury, including reduction in metabolism and oxygen consumption
of the brain, inhibition of glutamate and dopamine release, and prevention of
oxidative stress and apoptosis. Therefore, therapeutic hypothermia should be
considered for patients who have been successfully resuscitated from SCA
and who are comatose.
In a prospective study of 1145 consecutive patients with out-of-hospital
cardiac arrest who had successful resuscitation, therapeutic hypothermia was
associated with increased odds of good neurological outcome (odds ratio, 1.9;
95% confidence interval, 1.18-3.06) in patients with VT or VF.[29]
Therapeutic hypothermia is more effective in patients with initial rhythm of
VF/VT but is also recommended for patients presenting with asystole and
Patients who should not receive this therapy include (1) those with tympanic
membrane temperature of below 30ºC at the time of presentation, (2) those
who were comatose before SCA, (3) those who are pregnant, (4) those who
have inherited coagulation disorders, and (5) those who are terminally ill. Two
main techniques for induction of therapeutic hypothermia are surface cooling
methods with the use of precooled surface cooling pads and core cooling
methods with the use of cold intravenous fluids.

Primary prevention of SCD
Several studies have evaluated the use of prophylactic ICDs in patients who
have not yet experienced SCD but are at high risk for future SCD. The first of
these trials, Multicenter Automatic Defibrillator Implantation Trail (MADIT)
demonstrated that patients with ischemic cardiomyopathy (LVEF ≤35%) and
inducible but nonsuppressible VT on EPS had a survival advantage by
implanting an ICD.[30]
This study was followed by MADIT-2, demonstrating that post-MI patients with
an LVEF ≤30% have a survival benefit with ICD implantation.[31] The
Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation
(DEFINITE) study showed that implantation of an ICD reduced the risk of

sudden cardiac death in a patient population of nonischemic cardiomyopathy
(LVEF < 36%) who also had PVCs or nonsustained VT.[32]
Finally, the Sudden Cardiac Death in Heart Failure Trial (SCD-Heft)
demonstrated that patients with either ischemic or nonischemic
cardiomyopathy on optimal medical therapy, LVEF ≤35%, and NYHA II or III
treated with an ICD demonstrate greater survival as compared with either
amiodarone or placebo.[33]
The recent Home Automated Defibrillator Trial (HAT) demonstrated no survival
benefit for the use of a home AED in patients surviving a recent anterior MI
who were not candidates for an ICD.[34] However, the overall mortality and
incidence of SCD was much lower than predicted from previous data and the
noncardiac mortality was as high as cardiac mortality in the population of this
study. These factors led to much less power than initially projected in this trial
to detect a significant difference in the mortality rate between the arms.
The use of microvolt T wave alternans (MTWA) to determine which patients
with depressed LV systolic function would best benefit from prophylactic ICD
placement has been the subject of several recent clinical trials. To date, the
results of these clinical trials has not been conclusive.

Surgical Care
Temporary cardiac pacing
Transcutaneous of transvenous cardiac pacing may be considered in the
patients with bradycardia and asystole.

Radiofrequency ablation
Radiofrequency ablation, now routinely available, may be indicated for
patients with accessory pathways, bundle-branch block VT, RVOT VT,
idiopathic LV tachycardia, and more rare forms of automatic focus VT.
Unfortunately, most cases of SCD are not amenable to radiofrequency
ablation and require ICD implantation. Radiofrequency ablation may be useful
in the treatment of patients with SCD who experience frequent recurrent

VT/VF after ICD placement, especially those who require frequent

Cardioverter defibrillator therapy
Several multicenter trials examining the prophylactic use of cardioverter
defibrillator therapy in patients at high risk for SCD have been performed.
The annual SCD rate in patients with these devices has been reduced from
25% to 1-2%. Studies have shown that in patients at high risk in whom
electrophysiologic-guided therapy with antiarrhythmics has failed, ICD
placement is beneficial. In several studies comparing ICD placement to
antiarrhythmic therapy in patients with VT and/or prior cardiac arrest, ICD
placement has been shown to be associated with decreased mortality.
The use of ICDs for primary prevention of SCD is now standard care for most
patients with LVEF ≤35%. Newer ICDs with pacing capabilities have
addressed bradyarrhythmias either causing or complicating VT or VF.

Cardiac surgery
Cardiac surgery can be a primary treatment for SCD via a variety of
Surgical treatment in patients with ventricular arrhythmias and ischemic heart
disease includes coronary artery bypass grafting (CABG). The CASS study
illustrated that patients with significant CAD and operable vessels who
underwent CABG had a decrease in the incidence of sudden death when
compared to patients on conventional medical treatment. The reduction was
most evident in patients who had 3-vessel disease and CHF.
Surgical treatment of ventricular arrhythmias in patients with nonischemic
heart disease includes excision of VT foci after endocardial mapping and
excision of LV aneurysms. This is performed with decreasing frequency,
because of perioperative mortality and the alternative, transvenous ICD

Aortic valve replacement is associated with improved outcome in patients with
hemodynamically significant valvular stenosis and well-preserved ventricular
function. In patients with MVP associated with significant valvular regurgitation
and LV dysfunction, malignant tachyarrhythmias and SCD have been
reported. These patients are candidates for mitral valve repair or replacement.
Orthotopic heart transplantation is indicated in cases of SCD and refractory
heart failure in which significant improvement in actuarial survival is expected.
Given a limited donor service, this form of treatment is expected to be
beneficial for very few people who survive SCD.
Patients with long QT syndrome who do not respond to beta-blockers are
candidates for ICD implantation or high thoracic left sympathectomy.

A cardiologist always should be participating in the care of these patients.
Cardiac electrophysiologists should be involved in the care of these patients,
which generally involves ICD implantation.
Other consultations for expertise include an interventional cardiologist and
cardiac surgeon and are made on an individual basis.

Patients with coronary artery disease are advised to follow a diet low in fat
and cholesterol. Patients with severe heart failure should monitor their fluid
and sodium intake.

Patients should be at centers where intensive cardiac monitoring and
appropriate invasive and noninvasive studies can be performed. In general, a
cardiovascular service, including interventional cardiology, electrophysiology,
and cardiac surgery, is needed.

Prognosis of morbidity and mortality for people who have had SCA can be
made using the cardiac arrest score developed by McCullough and Thompson
(see Physical). The detection of the underlying cause of SCD and available
treatment options play an important role in the natural history and prognosis of
SCD/SCA is a frequently encountered problem for emergency physicians,
internists, and cardiologists. Ischemic cardiomyopathy in all adult cases and
HCM in pediatric and adolescent cases are at the top of the list of causes of
The clinical course, once the patient is resuscitated, largely is predicted by the
ED presentation of hemodynamic stability, early neurologic recovery, and the
duration of the resuscitation.
Patients who survive the initial phases require a systematic evaluation of LV
performance, myocardial perfusion, and electrophysiologic instability.
Survivors of SCA have a recurrence rate on the order of 20-25% per year,
making ICD implantation important in the majority of these patients.
ICD implantation saves lives. Risk stratification will continue to be an area of
active research.
Preventive measures, at their roots, are measures of coronary artery disease
prevention. Efforts to inform and train the public about external defibrillator use
likely will have a great public health impact on improving survival rates of
SCA. However, more basic and clinical research is required to understand the
mechanism of VF/VT and to be able to identify the patients at risk who benefit
from ICD therapy.

Patient Education
For patient education information, see the Heart Center and Public Health
Center, as well as Chest Pain, Heart Rhythm Disorders, Coronary Heart
Disease, Heart Attack, and Cardiopulmonary Resuscitation (CPR).

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