Chapter 11: Sudden Cardiac Death

This chapter focuses on the epidemiology and pathophysiology of sudden cardiac death in adults and strategies for prevention and treatment. Discussions of sudden infant death syndrome and cardiac arrest in children are found in chapter 126, Congenital and Acquired Heart Disease, and chapter 127, Syncope, Dysrhythmias, and ECG Interpretation in Children. Chapters 22 and 23 discuss basic and advanced life support, respectively. Chapters 23 and 33 discuss defibrillation and cardioversion, and cardiac pacing, respectively.

Sudden, unexpected out-of-hospital cardiac arrest occurs in approximately 382,800 adult Americans each year.¹ Estimated national survival of EMS-treated cardiac arrest cases is 11.4%, yielding an estimated overall out-of-hospital cardiac arrest survival rate of 6.8% (EMS-treated plus deceased-on-EMS-arrival cases).¹ There is substantial variability in the odds for survival across various geographic locations.²

Most episodes of sudden cardiac death occur in the home, although victims who experience cardiac arrest in a public place have a much better chance of survival.³ The initial recorded cardiac arrest rhythm is more likely to be ventricular fibrillation when cardiac arrest occurs in a public location rather than in the home, likely because patients who experience cardiac arrest in the home are typically older and more likely to have one or more chronic diseases that limit or exclude participation in activities outside the home.³ Sudden cardiac death is 30% to 80% higher among residents in the lowest compared with the highest socioeconomic quartile.⁴ This association is likely due to lifestyle and healthcare disparity issues.

There is a circadian pattern of sudden cardiac death and acute myocardial infarction,^5,6 and both are most likely to occur within the first few hours after awakening from sleep, when there is increased sympathetic stimulation. β-Blockade provides some protection from sudden cardiac death, particularly in patients with known coronary artery disease who have had myocardial infarction and have a low ejection fraction.⁷

There are two peaks in the age-related prevalence of sudden cardiac death: infancy (representing sudden infant death syndrome) and age greater than 45 to 50 years, with 60% in males.⁴ There are multiple known factors contributing to the likelihood of sudden cardiac death (Table 11-1).

Coronary artery disease (which is often undiagnosed before the event) is the major cause of sudden cardiac death in adults and is present in 80% of cases, followed by cardiomyopathy (10% to 15%) and other miscellaneous conditions (e.g., hereditary channelopathies, valvular disease, congenital anomalies), which account for most of the remaining 5% to 10% of cases.⁴

CORONARY ARTERY DISEASE

Coronary atherosclerosis is present on autopsy in 80% of sudden cardiac death victims.⁸ Coronary artery disease is also found in 70% to 80% of cardiac arrest victims who survive and undergo coronary angiography.^9,10,11,12 Approximately one third have evidence of acute plaque rupture in areas of long-segment coronary stenosis.^10,11 A documented initial cardiac arrest rhythm of ventricular fibrillation (or shockable rhythm if an automated external defibrillator was applied) suggests that an acute coronary syndrome is the cause, since ventricular fibrillation is noted in the majority of cases in which a coronary occlusion is found on angiography.^9,10,11,12 However, ventricular fibrillation is present in only 23% of all cardiac arrests.¹³

SEVERE LEFT VENTRICULAR DYSFUNCTION

Severe left ventricular dysfunction with a reduced ejection fraction is currently the best available predictor of sudden death risk.⁴ Patients with an ejection fraction ≤35% are the primary candidates for an implantable cardioverter-defibrillator. However, almost half of sudden deaths occur in individuals with normal left ventricular function.

CARDIOMYOPATHY

Cardiomyopathy with reduced left ventricular function, regardless of cause or presence of decompensated heart failure, is another predictor of sudden cardiac death. Dilated ventricles promote dispersion of ventricular depolarization and/or repolarization, allowing "islands" of ventricular tissue to depolarize and repolarize at different rates. The lack of homogeneity in electrical activation and recovery fosters the development of circus movement reentry, which can initiate and sustain ventricular tachyarrhythmias. Myocardial ischemia and/or infarction can also transiently diminish the homogeneity of left ventricular depolarization and repolarization. Left ventricular hypertrophy (often a result of hypertension and/or valvular heart disease) or conduction disturbances (left or right bundle-branch block or a nonspecific intraventricular conduction disturbance) can create similar functional disturbances.

In-hospital cardiac arrest patients with heart failure are more likely to have ventricular fibrillation as the initial documented cardiac arrest rhythm compared with non–heart failure patients.¹⁴ New York Heart Association functional class II (symptoms with moderate exertion) and III (symptoms with mild exertion) patients are at higher risk of sudden cardiac death than death from pump failure, whereas class IV patients (symptoms at rest) are more likely to die of pump failure than sudden cardiac death.^5,15

Hypertrophic cardiomyopathy is characterized by unexplained left ventricular hypertrophy associated with nondilated ventricular chambers.¹⁶ The disorder can cluster in families, and the risk of sudden cardiac death increases at a rate of approximately 1% per year.¹⁶ Hypertrophic cardiomyopathy is the most common cardiovascular cause of sudden cardiac death in young athletes, accounting for one third of such events, and its presence disqualifies affected individuals from competitive sports.¹⁶ Implantable cardioverter-defibrillator placement is recommended for individuals with prior documented cardiac arrest; ventricular fibrillation; hemodynamically significant or nonsustained ventricular tachycardia; patients with a first-degree relative who has had sudden cardiac death; one or more recent, unexplained episodes of syncope; a maximum left ventricular wall thickness ≥30 mm; an abnormal blood pressure response to exercise in the presence of other sudden death risk factors or modifiers; or high-risk children with unexplained syncope, massive left ventricular hypertrophy, or family history of sudden cardiac death.¹⁶

Arrhythmogenic right ventricular cardiomyopathy is a hereditary form of cardiac muscle disease that is characterized by right-sided heart failure, ventricular arrhythmias of right ventricular origin (i.e., ventricular tachycardia with a left bundle-branch block morphology), syncope, and sudden cardiac death.^17,18 The electrocardiogram typically shows T-wave inversion in the right precordial leads (V_1-3). Severe right heart failure develops in the majority of cases. Patients suspected of having this disorder should be referred for cardiology evaluation. Implantable cardioverter-defibrillator placement is often the treatment of choice since β-blockers and other antiarrhythmics do not usually prevent symptomatic ventricular arrhythmias in these patients.¹⁷

CONGENITAL HEART DISEASE

Congenital heart disease occurs in approximately 0.8% of all live births.¹⁹ Because many children with congenital heart disease survive to adulthood as a result of improvements in cardiac surgery, sudden cardiac death is a frequent cause of later morbidity and mortality. Congenital heart defects commonly associated with sudden cardiac death in children and adults are listed in Table 11-2.¹⁹

The most frequent coronary artery anomaly associated with sudden cardiac death is anomalous origin of the left coronary artery from the pulmonary artery syndrome, which results in the left coronary artery traversing between the aorta and main pulmonary artery. This disorder is being diagnosed more frequently in adults by cardiac CT and MRI.²⁰ Ischemic symptoms, ventricular arrhythmias, and sudden death can be triggered during exercise as a result of increasing venous return, which dilates the main pulmonary artery and compresses the anomalous coronary artery in the space between the aorta and main pulmonary artery. Treatment is surgical correction.

The greatest risk of sudden cardiac death in children and adults with congenital heart disease exists in those with left heart obstructive lesions (e.g., aortic stenosis, aortic coarctation) and cyanotic defects (e.g., Ebstein's anomaly, corrected transposition of the great vessels, tetralogy of Fallot).¹⁹ Most sudden death events in this population occur during exercise, with half of cases resulting from ventricular fibrillation.¹⁹ Nonventricular arrhythmias (e.g., sinus node dysfunction, atrioventricular block, supraventricular tachyarrhythmias) are also common, even after surgical correction.¹⁹

VALVULAR HEART DISEASE

Hemodynamically severe aortic stenosis can cause effort-induced dyspnea, myocardial ischemia, and ventricular arrhythmias, which can trigger syncope and sudden cardiac death. The most common causes of aortic stenosis are a congenitally bicuspid aortic valve that typically calcifies and narrows its orifice in mid-adulthood or sclerosis/calcification of a tricuspid aortic valve, which can occur in individuals who are older than 70 or 80 years of age. A harsh, late-peaking systolic murmur at the upper-right sternal border with radiation to the neck is a typical finding in hemodynamically significant aortic stenosis.

CARDIAC PACEMAKER AND CONDUCTING SYSTEM DISEASE

Sick sinus syndrome affects the heart's primary pacemaker and can cause intermittent lightheadedness, syncope, or sudden cardiac death. Although it is more common with advancing age, primary electrical failure of the heart can occur in infants and children. The cause is unknown, but pathologic studies reveal histologic degeneration of the sinoatrial node. In addition, the disorder often involves the atrioventricular node and the conduction tissue between the sinoatrial and atrioventricular nodes. Therefore, sick sinus syndrome should be thought of as a diffuse degenerative disease of the heart's electrical generation and conduction system. Idiopathic sclerodegeneration of the AV node and the bundle branches (Lenègre's disease) or invasion of the conduction system by fibrosis or calcification spreading from adjacent cardiac structures (Lev's disease) can lead to bradyasystolic heart block with or without cardiac arrest. In rare cases, a clinical presentation resembling the sick sinus syndrome can occur when the heart's electrical system is affected by systemic disease, vascular compromise, or tumor. Symptomatic bradycardia is treated with pacemaker placement.

HEREDITARY CHANNELOPATHIES

Sudden Arrhythmic Death Syndrome

The sudden arrhythmic death syndrome is characterized by sudden cardiac death occurring out of hospital in relatively young adults (mostly men), often during sleep or at rest, usually without any premonitory symptoms (including syncope) and with no anatomic abnormality identified at autopsy.^18,19 Genetic disorders are associated with sudden arrhythmic death syndrome, and many cases can be identified clinically based on their characteristic electrocardiogram patterns.

Ion Channel Disease

Cardiovascular and genetic examination of first-degree relatives can identify an inherited form of heart disease known as a "channelopathy" or "ion channel disease" in almost half of cases. Ion channel flux is responsible for the initiation, propagation, and repolarization of the cardiac action potential. Ion channel disease is caused by mutations in the genes that encode the proteins responsible for forming and interacting with the specialized sodium, potassium, and calcium ion channels within the heart.²¹ There are many known ion channelopathies, modulated by a variety of causative gene defects that can have variable phenotype penetration in a given family. Genetic testing is used to screen family members for a known mutation. Common subtypes are listed in Table 11-1.

Brugada's Syndrome

Brugada's syndrome most commonly affects men and consists of a prominent J-wave with a characteristic downsloping ST-segment elevation in electrocardiogram leads V_1–3 (Figure 11-1). This electrocardiogram pattern resembles a right bundle-branch block and is associated with a 40% to 60% incidence of life-threatening ventricular arrhythmias (particularly polymorphic ventricular tachycardia that degenerates into ventricular fibrillation) and sudden cardiac death. The syndrome exhibits an autosomal dominant inheritance that results in total loss of function of the sodium channel or in acceleration of recovery from sodium channel activation.²² Brugada's syndrome is common in Southeast Asia (where it is called sudden unexplained nocturnal death syndrome), in the Philippines (bangungut, "to rise and moan in sleep"), in Japan (pokkuri, "sudden and unexpectedly ceased phenomena"), and in Thailand (lai tai, "death during sleep"). It is crucial for emergency physicians to identify this condition from its characteristic electrocardiogram pattern, because the risk of sudden cardiac death is high and can be prevented by internal cardioverter-defibrillator placement.²³

Early Repolarization Syndrome

Early repolarization syndrome is present in 1% to 2% of adults (mostly males) and has long been considered to be a benign variant of normal ventricular repolarization.²⁴ Its prevalence is higher (10%) in general athletes and reaches as high as 100% in top-performing, endurance-trained individuals.²⁵ Classic electrocardiogram diagnostic criteria are a prominent, notch-like J wave on the QRS down-slope, followed by upsloping ST-segment elevation (Figure 11-2). These changes are seen most prominently in the mid to lateral precordium but can also occur just laterally or inferiorly. There is commonly reciprocal ST-segment depression in aVR. Rapid ventricular pacing or exercise usually normalizes these changes.

There may be similarity or overlap between Brugada's and early repolarization syndromes, but as of this writing, the clinical significance of early repolarization syndrome has not been established.²⁴ Both syndromes are often familial and more prominent in males, and drugs alter their characteristic electrocardiogram patterns (sodium channel blockers and β-blockers increase, and isoproterenol decreases the ST-segment elevation).^26,27 At this time, cardiology referral might only be warranted in the case of a teenager or young adult with syncope of unknown origin or with a family history of sudden cardiac death at an early age and with an electrocardiogram pattern of early repolarization.

Long QT Syndrome

The long QT syndrome is characterized by prolongation of the corrected QT interval (QT_c), syncope, and sudden death caused by torsade de pointes and ventricular fibrillation.²¹ The QT_c can be calculated by Bazett's equation:

where QT_c is the corrected QT interval in seconds, QT_m is the measured QT interval in seconds, and R-R is the interval between any two consecutive R waves on the electrocardiogram in seconds. Because the QT interval is heart-rate dependent, the formula "corrects" the measured QT interval to a heart rate of 60 beats/min (at which the R-R interval is 1 second). Because the square root of 1 = 1, the QT_c equals the QT_m at a heart rate of 60 beats/min (at which the normal QT interval limits are 0.35 to 0.44 second).

Prolongation of the QT_c represents dispersion in ventricular repolarization and can be hereditary or acquired (caused by hypokalemia, hypomagnesemia, hypocalcemia, anorexia, ischemia, central nervous system pathology, terfenadine-ketoconazole combinations, or certain antipsychotic or antiarrhythmic drugs).^21,28 Hereditary long QT syndrome can have an autosomal recessive (Jervell and Lange-Neilsen syndrome with nerve deafness) or dominant (Romano-Ward syndrome without nerve deafness) mode of inheritance.²¹ Management of patients with long QT syndrome involves avoidance of QT-prolonging drugs (an up-to-date list can be found at http://www.azcert.org) and high-intensity sports, as well as cardiology/electrophysiology referral.²¹ A β-blocker is typically prescribed as prophylaxis against sudden cardiac death. Long QT syndrome patients who have syncope, torsade de pointes, or ventricular fibrillation despite β-blocker therapy are candidates for implantable cardioverter-defibrillator placement.²⁹

Short QT Syndrome

An abnormally short QT_c (i.e., <0.34 second) can be secondary to hypercalcemia, hyperkalemia, acidosis, systemic inflammatory syndrome, myocardial ischemia, or increased vagal tone or can be inherited in an autosomal dominant genetic pattern.³⁰ The genetic variety, dubbed the "short QT syndrome" (SQTS), is associated with atrial arrhythmia, including atrial fibrillation, syncope, polymorphic ventricular tachycardia, ventricular fibrillation, and sudden cardiac death.³⁰ Early repolarization, especially in the inferolateral leads, is noted in 65% of patients.³¹ These individuals should also be referred for cardiology/electrophysiology evaluation and are candidates for cardioverter-defibrillator placement if syncope or life-threatening ventricular arrhythmias are documented.³⁰

Catecholaminergic Polymorphic Ventricular Tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is another genetically determined disorder involving defective myocardial cellular calcium handling. Affected individuals have exercise- and stress-related ventricular tachycardia, syncope, and sudden cardiac death, usually in childhood or early adulthood. Although there are no characteristic abnormalities in the electrocardiogram pattern, a significant number of affected individuals have sinus bradycardia that is not otherwise explainable. Almost half of these individuals carry a diagnosis of epilepsy as the cause of their recurrent syncope before the true cause (i.e., catecholaminergic polymorphic ventricular tachycardia) is identified.³² β-blockers are the mainstay of prophylaxis, with implantable cardioverter-defibrillator placement as the next step if syncope recurs.³²

Unfortunately, the majority of sudden cardiac death victims cannot be identified in advance. Prodromal symptoms in the days to weeks preceding cardiac arrest are common but are usually too nonspecific to be of important predictive value.³³ The most common premonitory symptoms reported by sudden cardiac death survivors or family members of victims are chest discomfort, dyspnea, and "not feeling well."

Various tests have been used to try to "risk stratify" potential sudden cardiac death patients, but none are sensitive or specific enough to be useful. Tests include invasive and noninvasive assessment of left ventricular ejection fraction, coronary angiography, ambulatory electrocardiogram monitoring, exercise testing, detection of ventricular late potentials by using signal averaging, programmed ventricular stimulation of the heart to test the inducibility of ventricular tachyarrhythmias, assessment of heart rate variability, and T-wave alternans (alternating T-wave amplitude from beat to beat on the electrocardiogram, which is only visible with special recording equipment).³⁴ The only opportunity for prevention is to recognize signs and symptoms of the syndromes that place a patient at higher risk of sudden cardiac death and to admit or refer such patients for proper evaluation and prophylaxis.

ANTIARRHYTHMIC DRUG AND DEVICE THERAPY

The Cardiac Arrhythmia Suppression Trial showed that potent class I sodium channel–blocking antiarrhythmic drugs (encainide, flecainide, and moricizine) are proarrhythmic and paradoxically increase the odds of developing sudden cardiac death, as compared with placebo, in patients at relatively low risk for death.³⁵ The benefits of β-blockade, sotalol, and amiodarone in decreasing mortality from sudden cardiac death pale in comparison with the protective effects of the implantable cardioverter-defibrillator in high-risk patients,³⁶ including those who have been resuscitated from ventricular fibrillation or cardioverted out of sustained ventricular tachycardia.³⁷ Although these devices are expensive to insert, their effectiveness over conventional therapy results in a cost of less than $30,000 per year of life saved, which makes them relatively cost-effective for implantation in high-risk individuals.

The outcome of resuscitation is influenced strongly by the patient's initial cardiac rhythm. In most cases in which the event has been captured during monitoring, the initiating event is either pulseless ventricular tachycardia that degenerates rapidly to ventricular fibrillation or "primary" ventricular fibrillation.³⁸

EMS and in-hospital resuscitation systems are the most effective means currently known to rescue patients from sudden cardiac death. Survival from pulseless ventricular tachycardia or ventricular fibrillation is inversely related to the time interval between its onset and termination. Survival is optimal when both CPR and advanced cardiac life support, including defibrillation and drug therapy, are provided early. Community resuscitation strategies should include provision of early CPR, early activation of the EMS system, early defibrillation (including public access defibrillation), early advanced cardiac life support, and regionalized systems of post-resuscitation care.^39,40

See Chapters 22, 23, and 24 Basic Cardiopulmonary Resuscitation and Defibrillation and Cardioversion, and Advanced Cardiac Life Support, respectively, and Chapter 18, Cardiac Rhythm Disturbances, for detailed discussion of resuscitation pharmacotherapy.

Bystanders who witness the event can improve a victim's chances for survival significantly by alerting the emergency response system promptly. The best survival is attained in EMS systems that can provide early defibrillation to a large percentage of patients. In most cases, this is most cost-effectively accomplished by a tiered response system, in which large numbers of rapid first responders are trained and equipped to provide first aid, CPR, and early defibrillation using an automated external defibrillator. The Public Access Defibrillation randomized clinical trial showed that laypersons trained and equipped to use automated external defibrillators in public places can double survival to hospital discharge compared with that which can be achieved by layperson rescuers who can only perform CPR while awaiting EMS arrival.⁴¹ These results have been confirmed in an analysis of 13,769 out-of-hospital cardiac arrest registry cases.⁴²

PULSELESS VENTRICULAR TACHYCARDIA/VENTRICULAR FIBRILLATION

The likelihood of survival is relatively high if the initial rhythm is ventricular tachycardia or ventricular fibrillation (particularly if the ventricular fibrillation is "coarse," the arrest is witnessed, and prompt CPR and defibrillation are provided). If the initial rhythm is not ventricular tachycardia or ventricular fibrillation, survival is typically <5% in most reported series. Asystolic patients whose cardiac arrest is unwitnessed rarely survive to hospital discharge neurologically intact. The only common exceptions are witnessed cardiac arrest patients whose initial asystole is a result of increased vagal tone or other relatively easily correctible factors, such as hypoxia of brief duration.

PULSELESS ELECTRICAL ACTIVITY

Some sudden cardiac death events begin with a bradyarrhythmia or an organized rhythm without a pulse (e.g., pulseless electrical activity). Bradyasystole in adults is defined as a ventricular rate <60 beats/min or periods of absent heart rhythm (asystole). Bradyasystolic rhythms other than asystole can be accompanied by a pulse, or there can be no discernible pulse with each QRS (i.e., pulseless electrical activity). Bradyasystole with a pulse is often accompanied by a significant decrease in cardiac output, leading to hypotension and/or syncope. Bradycardia with or without a pulse occurs frequently during cardiac arrest, either as the initial rhythm, during the course of resuscitation, or after electrical defibrillation. Obviously, asystole occurs eventually in all dying patients. To ensure that ventricular fibrillation is not masquerading as asystole, rescuers can switch to another lead whenever a "flat line" is recorded on the electrocardiogram during resuscitation or use US if available.

Primary bradyasystole occurs when the heart's electrical system fails to generate and/or propagate an adequate number of ventricular depolarizations per minute to sustain consciousness and other vital functions. Secondary bradyasystole is present when factors external to the heart's electrical system cause it to fail (e.g., hypoxia). Common causes of bradyasystolic arrest are listed in Table 11-3.

One of the most baffling mysteries of bradyasystolic cardiac arrest relates to myocardial mechanics. Bradyasystole, unlike ventricular fibrillation, is accompanied by very little myocardial oxygen consumption in animal models. Because of this, myocardial high-energy phosphate stores should decay relatively slowly during bradyasystole. This should theoretically result in a high incidence of return of spontaneous circulation after restoration of a more normal rhythm (e.g., with the early use of electrical pacing). It is unclear why conventional treatment of bradyasystolic cardiac arrest with atropine, epinephrine, or electrical pacemakers rarely results in survival to hospital discharge. Return of spontaneous circulation is infrequent, and long-term neurologically intact survival is rare in bradyasystolic cardiac arrest.

Other factors must play a determining role in the pathophysiology and subsequent outcome of bradyasystolic cardiac arrest. Bradyasystolic arrest is not just a disorder of rhythm generation or propagation; it is a perplexing syndrome characterized by such rhythm disturbances accompanied, in many cases, by profound depression of myocardial and vascular function. Suspected causes include endogenous myocardial depressants (including down-regulation of catecholamine receptors and/or toxic influences of intense sympathetic stimulation), neurogenic influences, postischemic myocardial stunning, and/or free radical injury.

It is important to differentiate pulseless electrical activity from conditions in which the rescuer is unable to detect a pulse, but there is unmistakable evidence that there is adequate blood pressure and cardiac output to maintain vital organ perfusion (e.g., a conscious patient with profound vasoconstriction caused by hypothermia, or "pseudo pulseless electrical activity").⁴³

The underlying physiologic cause of pulseless electrical activity is a marked reduction in cardiac output due to either profound myocardial depression or mechanical factors that reduce venous return or impede the flow of blood through the cardiovascular system. Common conditions that can cause pulseless electrical activity are shown in Table 11-4. The management of patients with pulseless electrical activity is directed at identifying and treating the underlying cause or causes.