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CORONARY ARTERY DISEASE
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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
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SEVERE LEFT VENTRICULAR DYSFUNCTION
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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.
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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.
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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
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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
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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 (V1-3). 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
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CONGENITAL HEART DISEASE
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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
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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.
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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
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VALVULAR HEART DISEASE
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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.
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CARDIAC PACEMAKER AND CONDUCTING SYSTEM DISEASE
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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.
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HEREDITARY CHANNELOPATHIES
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Sudden Arrhythmic Death Syndrome
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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.
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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.
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Brugada's syndrome most commonly affects men and consists of a prominent J-wave with a characteristic downsloping ST-segment elevation in electrocardiogram leads V1–3 (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
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Early Repolarization Syndrome
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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.
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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.
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The long QT syndrome is characterized by prolongation of the corrected QT interval (QTc), syncope, and sudden death caused by torsade de pointes and ventricular fibrillation.21 The QTc can be calculated by Bazett's equation:
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where QTc is the corrected QT interval in seconds, QTm 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 QTc equals the QTm at a heart rate of 60 beats/min (at which the normal QT interval limits are 0.35 to 0.44 second).
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Prolongation of the QTc 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
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An abnormally short QTc (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
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Catecholaminergic Polymorphic Ventricular Tachycardia
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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