20 Sudden Cardiac Death in the Young

(1)

Sudden Cardiac Death in the Young

Christopher B. Stefanelli

Sudden unexpected cardiac death (SCD) in the young is rare. Nonetheless, it has a dev- astating impact on families and communities.

It is important to note that most pediatric car- diopulmonary arrests are of respiratory and trauma etiology. However, the death of several prominent young athletes, most from cardiac abnormalities, during the last two decades has led to an increase in public and media aware- ness of SCD as a medical, legal, and public health issue.

Sudden cardiac death can be deﬁned as biologic death resulting from abrupt, unex- pected cardiovascular collapse from which an individual does not recover or regain con- sciousness. Sudden usually implies an interval of less than one hour from the onset of symp- toms to the time of death. Sudden arrhythmic (often presumed) and non-arrhythmic cardiac death in infants, children, and adolescents can occur in the absence or presence of known heart disease or other underlying medical con- dition. Sudden infant death syndrome (SIDS) represents a mechanistic spectrum of death in infants without suspected heart disease and in whom no cause can be found at stan- dard necropsy. Recently, the use of “molecular autopsy” indicates that a minority of SIDS in- fants may exhibit one of the genetic cardiac ion channel mutations that can cause lethal

arrhythmias. Resuscitated or aborted sudden cardiac death implies successful interruption of SCD by resuscitative efforts, and connotes a high recurrence risk.

The incidence of SCD in young persons is unknown. An estimated 4,000 to 8,000 chil- dren (≤18 years) in the United States die from sudden cardiac death annually, compared to more than 300,000 older individuals, most of whom die from ventricular ﬁbrillation due to ischemic heart disease. In a review of nine re- ports, the rate of sudden death in children var- ied from 1.3 to 8.5 per 100,000 patient-years.

Although much less common than in adults, SCD in children and young persons is more varied in both mechanism and cause. In con- trast to adults, terminal bradycardia and ven- tricular ﬁbrillation following profound brady- cardia or asystole are not uncommon as a mechanism of SCD in newborns, infants, and young children (Figure 1).

SCD in athletic, competitive young per- sons is also rare. There are approximately ten million children and adolescents that partic- ipate in competitive athletics in the U.S. In the high school male athlete, the risk of SCD is less than 1 in 100,000 patient-years; the risk for female athletes is only a fraction of that. In most cases of SCD in children and young competitive athletes, a speciﬁc, often

257

(2)

FIGURE 1. Several strips of ECG tracing over several minutes in 1-month-old boy during failing resuscitative efforts.

congenital, cardiovascular cause can be deter- mined.

The causes of SCD in the young (Table 1) vary with age. In the infant (≤1 year), approx- imately one half may have coronary artery anomalies and in the other half, no structural cause can be identiﬁed, even after a thorough review of the history, death scene and a com- plete autopsy. This later group, by deﬁnition, is SIDS, and, as noted above, a “molecular autopsy” may identify a minority with a ge- netic cardiac ion channel mutations such as the long QT syndrome. In patients less than 21 years of age, the most frequent causes are hy- pertrophic cardiomyopathy, myocarditis, pri- mary electrical disturbances, coronary artery abnormalities, and known, preexisting, struc- tural congenital heart disease.

HYPERTROPHIC CARDIOMYOPATHY

Hypertrophic cardiomyopathy is a di-

verse disease in its genetic, biochemical, cel-

lular, phenotypic, and clinical features. It is a

result of different mutations in one of at least

ten genes that encode protein elements of the

cardiac sarcomere, and is inherited, as most

defects in structural proteins, as an autoso-

mal dominant trait (Chapter 18). Although it is

relatively common, with an estimated preva-

lence of 1 in 500, it does not uniformly portend

an unfavorable prognosis; overall, the annual

mortality is about 1%, with a near normal life

expectancy and little morbidity in most pa-

tients. There exists, however, a subset of pa-

tients, 10%–20% of those with hypertrophic

(3)

TABLE 1. Causes of SCD in the Young

Condition Types

Myocardial Abnormalities Hypertrophic Cardiomyopathy Dilated Cardiomyopathy Myocarditis

Ventricular Noncompaction

Primary Electrical Disorders Long QT Syndrome: Congenital and Acquired Ventricular Pre-excitation (WPW)

Brugada Syndrome

Catecholaminergic Ventricular Tachycardia Primary Ventricular Tachycardia/Fibrillation Complete Heart Block, Congenital and Surgical Arrhythmogenic Right Ventricular Dysplasia Commotio Cordis

Coronary Abnormalities Congenital Anomalies

Anomalous origins from the aorta

Anomalous origins from the pulmonary artery Ostial abnormality

Myocardial bridge (tunneled) Kawasaki Disease

Transplant Vasculopathy Cocaine Vasospasm Coronary Atherosclerosis Congenital Heart Disease Aortic Stenosis

Coarctation of the Aorta

Tetralogy of Fallot (including variants) Transposition of the Great Arteries Atrioventricular Discordance Hypoplastic Left Heart Syndrome Single Ventricle/Fontan Ebstein’s Anomaly Truncus Arteriosus

Miscellaneous Primary Pulmonary Hypertension Marfan’s Syndrome

Eisenmenger Syndrome Mitral Valve Prolapse

cardiomyopathy, in whom the annual mortal- ity from SCD exceeds 5%.

A sudden arrhythmia is the most frequent means of sudden death, too often as the first clinical manifestation of the disease, and can occur at rest or during mild or strenuous ex- ertion. It occurs most commonly in young adults, adolescents, and children, a popula- tion with an estimated annual risk of mortality secondary to SCD of 2%–5%. Primary ven- tricular tachycardia and its degeneration to ventricular fibrillation is the predominant mechanism of SCD. Patchy and confluent

myocardial scars, as a result of abnormal coro- nary architecture, diminished coronary ﬂow reserve, coronary-myocardial mismatch and consequent myocardial ischemia, in addition to cellular disarray and collagen inﬁltration, serve as electrophysiologic substrates for the ventricular arrhythmias. Acute ischemia and vascular instability with hypotension are pro- posed triggers for ventricular arrhythmias.

Substantial effort has lead to the recogni-

tion of risk factors for SCD in individuals with

hypertrophic cardiomyopathy (Table 2). Elec-

trophysiology testing for inducible ventricular

(4)

TABLE 2. Risk Factors for SCD in Individuals with Hypertrophic Cardiomyopathy

Risk Factors

History of resuscitated cardiac arrest

Family history of SCD (particularly ﬁrst-degree or multiple relatives)

History of sustained ventricular tachycardia Nonsustained ventricular tachycardia

Syncope or presyncope (particularly if exertional, recurrent, or with documented arrhythmia) Hypotensive exercise blood pressure response Left ventricular wall thickness 30 mm or greater

arrhythmias is controversial; monomorphic ventricular tachycardia is infrequently in- duced and polymorphic tachycardia with ag- gressive extrastimulus protocols is a nonspe- ciﬁc ﬁnding.

Most patients are free of risk factors and SCD in such patients is rare, but those with two or more risk factors are at substantially increased risk. Patients with no risk factors have been shown to have a six-year SCD-free survival rate of 95%, while the corresponding rate for those with two or more risk factors was 72%. Implantable cardioverter deﬁbrillator therapy is recommended for secondary pre- vention following events of resuscitated SCD and should be considered for primary preven- tion in those with two or more risk factors.

MYOCARDITIS

Acute and chronic myocarditis are as- sociated with SCD. Acutely, myocyte necro- sis and diffuse inflammatory infiltrates and, in the chronic form, patchy fibrosis and persis- tence of a low-grade inflammatory state, serve as an arrhythmogenic substrate for ventricular tachycardia (Figure 2). Ventricular ectopy or SCD may be the initial clinical manifestation of acute myocarditis and can occur in the pres- ence of preserved ventricular function, con- founding the diagnosis. Optimal treatment is unclear and the benefits of steroids and intra- venous gamma globulin are unproven. Recov-

V6 V5 V4

V3 V2 V1

aVL

aVP I

II

FIGURE 2. 12 lead electrocardiogram in a 7 month old boy with autopsy proven myocarditis. Note wide QRS tachycardia and the global ST elevations in the anterior lateral leads with reciprocal changes in the other leads.

ery can be complete, but is dependent upon the severity and persistence of the inﬂammatory process.

CONGENITAL LONG QT SYNDROME

The congenital Long QT syndrome rep- resents a spectrum of genetic disorders (Chap- ter 18) that share in common the prolongation of ventricular repolarization due to abnormal- ities in potassium or sodium (LQT3) ion chan- nels. The prolongation of repolarization can lead to delayed after-depolarization-mediated polymorphic ventricular tachycardia (tor- sades de pointes), which can degenerate into ventricular ﬁbrillation and SCD.

Overall risk and environmental condi- tions and activities associated with ventric- ular arrhythmias and SCD have been shown, to an extent, to be gene speciﬁc. The risk of SCD is greatest in those with LQT3. SCD oc- curs most commonly during exercise among patients with LQT1, the most common sub- type; there is also a tendency with LQT1 to- ward ventricular arrhythmias and SCD dur- ing recreational swimming. SCD occurs most commonly during emotional arousal or with auditory stimulus among those with LQT2 (Figure 1, Chapter 18), and during sleep or rest among patients with LQT3.

The genetic and phenotypic heterogene-

ity contributes to the difﬁculty in diagnosing

and managing patients with the congenital

long QT syndrome. The wide range of cor-

rected QT interval values in both unaffected

(5)

and affected individuals, as well as age-related variation in heart rate and sinus arrhythmia, also confound the diagnosis, particularly in the absence of symptoms or family history.

Although a corrected QT interval of greater than 450–460 msec is a reasonable thresh- old to be concerned for an abnormality, the majority of individuals in this range are not affected.

Symptoms include syncope, seizures, and SCD. Patients with very prolonged event- free intervals or positive family history should be treated pharmacologically. In most cases, therapy involves β-blockade; the exception being individuals with LQT3 (Figure 3, Chap- ter 18), in whom ventricular arrhythmias are pause- or bradycardia-dependent and in whom permanent pacing may be beneﬁcial.

Mexilitine may be useful as well. In addition, secondary prevention of aborted SCD with an implantable deﬁbrillator is indicated; the role of ICDs for primary prevention has not been established, but is a valid consideration, par- ticularly for individuals with LQT3 and those in whom there is a strong family history of SCD. In the future, genetic testing will likely be instrumental in the diagnosis and guidance of therapy.

BRUGADA SYNDROME

The Brugada syndrome is characterized by the electrocardiographic ﬁndings of right bundle branch block and unusual ST eleva- tion in leads V1–V3 (Figure 4, Chapter 18), polymorphic ventricular tachycardia, a struc- turally normal heart, and autosomal domi- nant inheritance with variable penetrance. It has emerged as an important cause of SCD worldwide and is the leading cause of SCD in South Asian males. Defects in the SCN5A human cardiac sodium channel gene result in loss of function producing epicardial action potential prolongation, dispersion of ventric- ular myocardial refractoriness, and suscepti- bility to early after-depolarization-mediated ventricular tachycardia (phase 2 reentry). This is in contradistinction to the gain of func-

tion defect in the same gene associated with LQT3, which results in phase 2 prolonga- tion, rendering susceptibility to delayed after- depolarization. Like the congenital long QT syndrome, the Brugada syndrome is represen- tative of several described and undetermined genetic defects. Unfortunately, the disorder is also difficult to diagnose, as the elec- trocardiographic features may manifest only occasionally. Provocative testing with ajma- line, flecainide or procainamide may uncover repolarization abnormalities in affected indi- viduals. The use of implantable cardiover- tor defibrillators is indicated for secondary prevention following resuscitated SCD and should be strongly considered for primary pre- vention as well since there is no preventive pharmacologic agent.

WOLFF-PARKINSON-WHITE SYNDROME

Patients with Wolff-Parkinson-White

(WPW) syndrome have a very low risk of

SCD, probably less than 1 per 1000 patient-

years. The mechanism is rapid anterograde

conduction across a fast-conducting acces-

sory pathway(s) during atrial ﬁbrillation,

either spontaneous or initiated by atrioventric-

ular reentrant tachycardia. The lack of sensi-

tivity and speciﬁcity of noninvasive markers

of SCD risk, such as intermittent loss of ven-

tricular preexcitation or response to exercise

testing or antiarrhythmic medications, limits

their clinical usefulness. Patients at risk can

be identiﬁed using electrophysiology study to

determine the presence of multiple accessory

connections, the inducibility of atrial ﬁbrilla-

tion, the anterograde effective refractory pe-

riod, and the shortest pre-excited RR interval

during atrial ﬁbrillation or rapid atrial pacing

(Figure 3). Patients with slow anterograde ac-

cessory pathway conduction (accessory path-

way effective refractory period

>280 msec)

are not at risk. On the other hand, the speci-

ﬁcity for development of ventricular ﬁbrilla-

tion with short pre-excited RR intervals dur-

ing electrophysiology study is low.

(6)

1)

2)

3)

4)

5)

6)

FIGURE 3. Panels 1-2: Atrial fibrillation in a 9-year-old boy with a very rapid ventricular response deteriorating into ventricular fibrillation (Panels 3 and 4) and cardiac arrest. He was successfully defibrillated (Panels 4 and 5) into sinus tachycardia with no preexcitation (Panel 6). At electrophysiologic study had an intermittent anterograde left lateral accessory pathway with an effective refractory period of 190 msec. It was successfully interrupted by radiofrequency ablation. Reprinted with permission from O’Connor, BK et al. What every pediatrician should know about supraventricular tachycardia. Pediatric Annals 1991;20(7):368–376.

It has been shown that arrhythmia inducibility and young age (adolescents and young adults) are associated with a signiﬁcantly increased risk of arrhythmic events, including SCD, in previously asymp- tomatic patients. However, because of a small atrial mass, atrial ﬁbrillation is very un- common in infants and young children. The indications for radiofrequency ablation in pa- tients with WPW and SVT are individualized, depending upon the frequency, duration, and associated symptoms of arrhythmias, as well as patient and family preference. The indi- cations for electrophysiology testing to de- termine risk of SCD are also individualized.

Family history, occupation, and involvement in athletic and other risk-laden activities are important considerations in making an in- formed decision with patients and families.

Guidelines for ablation in the young have re- cently been published by the Heart Rhythm Society (Chapter 22).

CONGENITAL CORONARY ARTERY ANOMALIES

Congenital coronary artery anomalies are diverse and occur with and without asso- ciated structural congenital heart disease. The congenital coronary anomaly most strongly associated with SCD is anomalous origin of the left coronary artery from the right sinus of Valsalva. If the anomalous artery courses between the great arteries particularly a long intramural segment, the risk of SCD is in- creased (Figure 4). Alternative courses in- clude anterior to the pulmonary artery, poste- rior to the aorta and in the septal myocardium.

Some hypothesize that in the hyperdynamic state, during or following exercise, the vessel may become compressed, resulting in acute ischemia and ventricular arrhythmias. Origin of the right coronary artery from the left coro- nary artery or sinus that courses between the great arteries is also associated with SCD.

A N

A L R

RCA

LAD RCA

LAD CX

CX R.V

Inf R.V

Inf

A B

FIGURE 4. Panel A: Left coronary artery arising from the right coronary artery and coursing between the aorta and right ventricular outﬂow tract. Panel B: The right artery arises from the left coronary cusp and courses between the aorta and right ventricular outﬂow tract.

Reprinted with permission from “Congenital Coronary Artery Anomalies” by Herlong JR in The Science and Practice of Pediatric Cardiology, Lippincott, Williams and Wilkins. 2nd Ed, 1998, p. 1657.

(7)

Other congenital coronary anomalies im- plicated in SCD include an acute angle of origin, ostial stenosis, transmural course and

“myocardial bridge”. These subtle abnormal- ities are more frequently diagnosed by experi- enced pathologists and have been implicated in a signiﬁcant number of infantile cases of SCD. However, the majority of experts con- sider the “myocardial bridge” to be a nor- mal variant and not predictably causative of SCD.

When abnormalities are discovered ei- ther fortuitously or following resuscitated SCD, surgery can be curative. Unfortunately, SCD is often the initial manifestation.

ACQUIRED CORONARY ARTERY ANOMALIES

Prior to the therapeutic implementation of intravenous immunoglobulin for Kawasaki disease, reports of SCD early in the disease process and with the development of aneurys- mal and thrombotic complications were more common. SCD in association with Kawasaki disease is now a rarity. Transplant coronary vasculopathy, particularly in an accelerated form, is associated with both acute ischemia and chronic myocardial scarring and is, as such, associated with SCD.

STRUCTURAL CONGENITAL HEART DISEASE

Tetralogy of Fallot

Tetralogy of Fallot has long been asso- ciated with ventricular arrhythmias and SCD.

The risk is small, however, probably 1–2 per 1000 patient-years. Risk factors include sig- niﬁcant chronic pulmonary or conduit insuf- ﬁciency and right ventricular dilation, and prolonged and prolonging (associated with worsening volume overload) QRS duration (

>170 msec). Other potential risk factors,

including residual right ventricular pressure

load and non-sustained ventricular ectopy are in question. The risk of SCD among patients more recently repaired appears to be substan- tially less, as there has been a trend toward transatrial repairs, smaller or no ventriculo- tomy incisions and preservation of right ven- tricular outﬂow valve function.

Transposition of the Great Arteries

Late postoperative arrhythmias, most commonly intra-atrial reentrant tachycardia (IART, Chapter 8) and sick sinus syndrome (SSS), are common following atrial switch (Mustard or Senning) procedures, as is sys- temic right ventricular dysfunction; both are risk factors for SCD, which occurs in 5–10 per 1000 patient-years. Mechanisms include IART with rapid atrioventricular conduction and subsequent hemodynamic and metabolic instability, and pause dependent dispersion of ventricular refractoriness associated with sick sinus syndrome. The incidence and risk fac- tors of late SCD associated with the arterial switch (Jatene) operation are unknown but are thought to be considerably less. The risk of SCD with L-TGA (ventricular inversion, atrioventricular discordance) is variable and dependent on the anatomy, surgical repair(s), and conduction system disease, but it is nei- ther well established nor negligible.

Fontan Operation

Single ventricle palliation with varia- tions of the Fontan operation (cavopulmonary or atriopulmonary anastamosis) is associated with a high incidence of IART (Chapter 8), and sinus node and ventricular dysfunction.

Patients are thus at risk for SCD secondary to

mechanisms similar to those following atrial

switch procedures. Lateral tunnel and exter-

nal cardiac conduit Fontan connections, as

well as strategically-placed surgical incisions

or cryoablation lesions, may lessen the inci-

dence of atrial arrhythmias and SCD.

(8)

Left Heart Obstructive Lesions

SCD occurs in association with unre- paired aortic stenosis, almost exclusively with moderately severe or severe left ventricular outﬂow obstruction. Resultant left ventricu- lar hypertrophy results in acute and chronic subendocardial ischemia, a substrate for ven- tricular arrhythmias. Embolism in association with endocarditis is a known cause of SCD with aortic stenosis. Symptoms, including chest pain, presyncope, syncope and palpita- tions, should not be taken lightly. Associated coronary artery abnormalities, most com- monly ostial stenosis, contribute to risk. Tran- scatheter or surgical relief of the obstruction alleviates, but does not nullify the risk of SCD, particularly among those with aortic regurgi- tation, residual left ventricular dysfunction, or a mechanical aortic valve.

SCD occurs infrequently following re- pair for coarctation of the aorta. Mechanisms include aneurysm rupture associated with aor- toplasty and those associated with progressive left ventricular hypertrophy, despite relief of repair.

Hypoplastic left heart syndrome in the newborn left untreated is lethal. SCD can oc- cur following the three stages of repair. It oc- curs most often following the Norwood pro- cedure, when coronary perfusion is tenuous and reliant on balance between the pulmonary and systemic vascular resistances. Diastolic

“runoff” to the low-resistance pulmonary bed compromises coronary (particularly subendo- cardial) perfusion. The Sano operation (right ventricular to pulmonary artery conduit, i.e.,

“shunt”) is designed and advanced as an an- tidote to the diastolic “run off.” Similarly, the mechanism of diastolic “run off” can lead to congestive heart failure, ventricular arrhyth- mias, and SCD in infants with unrepaired trun- cus arteriosus.

COMMOTIO CORDIS

A blunt, non-penetrating chest wall blow to an otherwise normal child or adolescent that

results in SCD, commotio cordis, is a rare and unfortunate event. The mechanism involves a precisely timed precordial impact, typically of a low-energy, low-velocity, solid core pro- jectile object during a narrow window of ven- tricular repolarization, just prior to the T-wave peak. Ventricular tachycardia and ﬁbrillation, unusually recalcitrant to resuscitative efforts, follows the impact. Prompt deﬁbrillation is the major survival determinant. Commotio cordis occurs most often in school age, ado- lescent, and young adult males participating in competitive athletics, particularly baseball, and less often in ice hockey and lacrosse (pre- sumably because of fewer participants). A recent comprehensive report, however, high- lights several cases that occurred under un- usual circumstances that were not regarded as threatening, such as a snowball or the head of a pet dog impacting the chest of a small child.