Etiology And Pathogenesis

Syncope occurs when cerebral blood flow decreases below 30% to 50% of baseline. This decrease may be the result of systemic vasodilation, decreased cardiac output, or both. This results in transient ischemia, causing temporary loss of consciousness and motor tone. Syncope may also be accompanied by brief autonomic movements. Syncope should be distinguished from presyncope (dizziness or lightheadedness without loss of consciousness), vertigo (the sensation of spinning), and syncopal-like events (e.g., seizures, migraines, or conversion disorder). The causes of syncope can be divided into three major categories: neurally mediated, cardiac, and metabolic (Box 48-1). Syncopal-like events are discussed briefly in the following section.

Cardiac Syncope

Although a cardiac cause is found in fewer than 2% of previously healthy children with syncope, it is important to recognize because it can be associated with an increased risk of sudden death. Cardiac syncope results from abrupt decline in cardiac output as the result of obstructive lesions (aortic stenosis, hypertrophic cardiomyopathy [HCM]), myocardial dysfunction (ischemia, cardiomyopathy), or primary arrhythmias (Figure 48-1). Many of these conditions can be asymptomatic until syncope or sudden death occurs. Arrhythmias can also occur secondary to structural heart disease, to myocardial dysfunction, or to postoperative changes in association with congenital heart disease. Any concern for a cardiac syncope warrants a referral to a pediatric cardiologist. Sudden cardiac death (SCD) in the young is estimated to affect between one in 50,000 and one in 200,000 children.

Figure 48-1 Sudden cardiac death.

Arrhythmias

Some of the arrhythmias associated with cardiac syncope are reviewed here. For further discussion of arrhythmias, please refer to Chapter 45.

Long QT Syndrome

Long QT syndrome (LQTs) results from mutations in genes that regulate myocardial repolarization and manifests in prolongation of the corrected QT (QTc) interval on electrocardiography (ECG). It results in a predisposition to life-threatening ventricular arrhythmias, such as torsades de pointes. It is commonly defined as a QTc longer than 460 msec in children younger than 15 years old, longer than 450 msec in men and longer than 470 msec in women, but in some forms, the QTc can be normal on resting ECG.

LQT can be congenital or acquired (as the result of medications or electrolyte disturbances). To date, mutations in 12 genes have been identified, involving potassium, sodium, and calcium channels (LQT1–LQT12). For patients testing positive on genetic studies, LQT1, LQT2, and LQT3 are the most common (45%, 45%, and 7%, respectively). Whereas patients with LQT1 appear to be at a particularly high risk of sudden death with exercise, patients with LQT2 appear to be at most increased risk in the presence of loud noises and emotional stimuli. Treatment with β-blockers has been shown to markedly reduce the incidence of sudden death, especially in patients with LQT1 and to a lesser extent in LQT2. Although there is some benefit of β-blockers in LQT3, these patients may be more likely to require an implantable cardioverter defibrillator.

Preexcitation Syndromes

Preexcitation syndromes are characterized by premature ventricular stimulation. The classic, and most common, preexcitation syndrome is Wolff-Parkinson-White (WPW) syndrome, which is estimated to occur in 0.1% to 0.4% of the population. Preexcitation in WPW syndrome is the result of rapid impulse conduction through an accessory pathway connecting the atria and ventricles and is described in detail in Chapter 45. This predisposes patients to atrioventricular (AV) reentrant tachycardia, atrial flutter, and atrial fibrillation. SCD can occur as a result of 1 : 1 conduction of an atrial tachycardia (namely atrial flutter or fibrillation) through the accessory pathway, resulting in a rapid ventricular rate.

Short QT Syndrome

Short QT syndrome (QTc <300-340 msec) is a rare condition associated with syncope and sudden death as the result of ventricular fibrillation. This entity is significantly rarer than LQTs. There are increasing numbers of case reports, however, and at least three associated genes have been identified.

Brugada Syndrome

Brugada syndrome is associated with syncope or sudden death at rest or during sleep, often in the setting of elevated body temperature (e.g., with fever or after vigorous exercise), or in the early morning. Presentation, therefore, can sometimes be confused with febrile seizures. Patients with this condition have normal QT intervals, ST-segment elevation with a “coved” appearance, and right ventricular conduction delay, although this pattern can be transient or absent (see Figure 48-1). As many as 50% of cases may be sporadic mutations. The other 50%, however, are associated with a positive family history, so special attention should be paid where there is a positive family history of syncope, abnormal ECG, or sudden death.

Catecholaminergic Polymorphic Ventricular Tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is caused by abnormalities in calsequestrin and ryanodine receptor (RYR2) genes. It predisposes patients to exercise-induced polymorphic ventricular tachycardia, syncope, and a high risk of sudden death in the setting of normal resting ECGs. CPVT can be diagnosed by stress testing.

Bradycardia

Bradycardia can result from sinus node or AV nodal abnormalities and is reviewed in further detail in Chapter 45. Syncope can sometimes occur from bradycardia because of a decrease in cardiac output and cerebral perfusion pressure.

Structural Heart Disease

Hypertrophic Cardiomyopathy

HCM is the most common cause of SCD in children and young adults in the United States. Its incidence has been reported to be as high as one in 500 individuals, with an estimated 2% to 8% chance of death per patient per year. In patients with HCM, the left ventricle is hypertrophied but not dilated in the absence of other structural heart disease. It is inherited in an autosomal dominant pattern and results in disordered myocardial architecture with hypertrophied myocytes. Syncope and SCD may result from ventricular tachyarrhythmias because of an abnormal myocardium and increasing left ventricular outflow tract obstruction leading to decreased cardiac output and coronary ischemia. The presence of small vessel disease in intramural coronary arteries may result in ischemia, myocardial death, and intramural scarring, all of which contribute to the electrical instability of the ventricle. Children with a family history of HCM-related deaths, prior cardiac arrest, sustained ventricular tachycardia, syncope, and left ventricular wall thickness 30 mm or larger are at the greatest risk for sudden death. The physical examination in patients with obstruction will reveal a systolic ejection murmur that increases in intensity with Valsalva or moving from sitting to standing. ECGs are abnormal in 90% of patients with HCM.

Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia

Arrhythmogenic right ventricular cardiomyopathy (ARVC also known as ARVD) is a primary myocardial disease associated with the replacement of normal myocardium with fibrofatty tissue and is most commonly associated with an autosomal dominant transmission in familial cases. ARVC results in an increased frequency of ventricular arrhythmias, which lead to syncope and sudden death.

Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) represents another potential cause of syncope and SCD in the young. The disease is characterized by left ventricular dilatation; impaired systolic function; and segmental wall motion abnormalities, which result in cardiac ischemia, leading to myocardial arrhythmias.

Aortic Stenosis

Valvar stenosis, either congenital or acquired, may lead to syncope as the result of insufficient cardiac output to meet demands because of fixed narrowing of the valve orifice or secondary arrhythmias as the result of decreased coronary perfusion in the setting of myocardial thickening or a combination of the two.

Abnormal Origin of the Coronary Arteries

Anomalous origin of the left coronary artery has been associated with syncope and SCD, particularly when the left coronary artery has an intramural course, because this is associated with left coronary ostial stenosis or a “slitlike” orifice of the left coronary. Myocardial ischemia can result predisposing to ventricular arrhythmias. Up to 40% of these patients have symptoms before SCD, and up to 20% to 30% may have ischemic changes on ECG during exercise.

Pulmonary Hypertension

Children with pulmonary hypertension can experience exercise-induced syncope. For these children, however, syncope is a late sign that is associated with decreased cardiac output and hypoxia related to right heart failure.

Acute Myocarditis

Acute myocarditis is the result of inflammation of the myocardium, typically secondary to infection (e.g., enterovirus, adenovirus, or parvovirus) or toxin (e.g., cocaine). As inflammatory cells infiltrate the myocardium, interstitial edema, myocyte death, and fibrotic replacement of myocytes occur. Myocarditis can lead to myocardial electrical instability and left ventricular dysfunction. Children typically present with chest or abdominal pain, exertional dyspnea, palpitations, acute heart failure, or ST changes on ECG. Syncope is associated with the presence of serious ventricular arrhythmias. These children can remain at risk of ventricular arrhythmias, particularly exercise induced, even after resolution of the acute myocarditis.

Congestive Heart Failure

As cardiac output declines, patients with congestive heart failure may experience syncope. This is rarely a presenting sign and is typically accompanied by other signs or symptoms of heart failure, such as exercise intolerance, edema, hepatomegaly, shortness of breath, and respiratory distress.

Evaluation And Diagnostic Approach

A thorough history and physical examination alone can suggest the diagnosis in the majority of cases of syncope (Figure 48-2). History of the present illness should include a detailed account of the event (including the duration, associated motor activity, and the circumstances surrounding recovery), triggers (including emotional, auditory, and exertional), and prodrome (including palpitations, chest pain, nausea or abdominal pain, diaphoresis, and lightheadedness). Past medical and family histories should focus on previous syncope and cardiac, neurologic, and psychiatric conditions. Family history should also include sudden or unexplained deaths, including sudden infant death syndrome, unexplained motor vehicle accidents, or a history of drowning or near drowning. Physical examination should include orthostatic vital signs and thorough cardiac and neurological examinations. Any patient with suspected cardiac cause should have an ECG as part of the evaluation. Patients with prolonged loss of consciousness, history of seizurelike movements, postepisode lethargy, or neurologic deficit should instead be evaluated with electroencephalography, head computed tomography, or magnetic resonance imaging; patients with suspected metabolic causes should be evaluated with a D-stick, basic metabolic panel, and toxicology screen; and patients with concerns for blood loss or signs of anemia should be evaluated with a complete blood cell count. Any female patient of childbearing age should also undergo a urine pregnancy test because the hemodynamic shifts associated with pregnancy predispose patients to syncope. If these tests do not reveal a diagnosis, most argue for ECG screening.

Figure 48-2 Diagnosis and management of syncope.

Management: Indications For Referral And Admission

Most patients who present with syncope can be discharged to home from the primary care clinic or ED after evaluation. It is generally recommended that those with focal neurologic signs be admitted to the hospital for further workup and neurologic consult. Similarly, patients with an abnormal ECG; chest pain with exercise; cyanosis; congenital heart disease; syncope triggered by exertion, fright, or noise; or abnormal cardiac examination results should undergo cardiology consult or hospital admission as deemed necessary. Admission should also be considered for children who are ill appearing or have positive toxicology screens, significant electrolyte abnormalities, hypoglycemia not responsive to glucose administration, apnea or bradycardia that resolves only with vigorous stimulation, severe anemia, or orthostatic hypotension that does not resolve with fluid administration.

Children with presumed NMS should be instructed to increase their water (0.25-0.5 oz/kg/d) and salt intake to offset the decreases in blood pressure that occur with stimulation of the autonomic nervous system. Electrolyte-containing fluids can often be helpful. Patients should also avoid caffeine, alcohol, and other diuretics. If presyncopal symptoms (e.g., dizziness, lightheadedness, flushing, or tunnel vision) recur, patients should lie supine with their legs elevated because this will often abort syncope. If syncope is refractory to these interventions, alternate diagnoses should be reconsidered.

Future Directions

Continued work is underway to streamline the diagnostic approach and to perfect an evidence-based algorithm. With rising health care costs, much attention has been paid to the large number and low yield of the ancillary studies historically ordered in the evaluation of syncope. Current recommendations remain controversial. It has been found that adding an ECG to a targeted history and physical examination is 96% sensitive for the detection of cardiac abnormalities. Some argue against this because of the low incidence of cardiac abnormalities as the primary cause of syncope in previously healthy children, which leads to a low diagnostic yield and high cost of ECGs per positive result (<0.4% and $28,665/positive result). Prospective cost-effectiveness analyses are necessary to better determine effective patient screening for cardiac causes of syncope.