Bradycardia: General Comments

Bradycardia is defined as a heart rate below the normal range for age that may result from intrinsic injury to the sinus node, atrioventricular (AV) node, or His-Purkinje conduction system or secondary to extrinsic factors acting on native conduction. The decision to intervene for bradycardia often relates to its impact on systemic perfusion, exacerbation of heart failure, or the possibility of pause-dependent tachyarrhythmias. Symptoms of bradycardia—such as syncope, dizziness, chest pain, shortness of breath, and fatigue—especially in younger children, are not always readily apparent. The differential diagnosis of symptomatic bradycardia is broad ( Box 22.1 ), and aside from structural congenital heart defects and cardiomyopathies, consideration should be given to endocrinopathies, infections, drug ingestion, breath-holding spells, apnea, anorexia, and central nervous system disorders. In addition, various genetic abnormalities (i.e., NKX2.5, SCN5A, SCN1B and TRPM4 ) have been implicated in the pathogenesis of sinus node dysfunction or progressive cardiac conduction defects. A simplistic yet clinically relevant approach to the patient with bradycardia from a conduction vantage point begins with abnormalities in the sinus node and progresses through block within the AV node/His-Purkinje system.

Sinus Node Dysfunction

The sinus node is located at the cavoatrial junction between the crista terminalis and the sulcus terminalis on the epicardial surface. The sinus node comprises a complex and heterogeneous arrangement of ion channels including the I _f (“funny hyperpolarization-activated inward current” and the L- and T-type calcium currents) responsible for a self-propagating action potential (Video 22.1 ). Sinus node abnormalities may be secondary to a slower than normal sinus rate (sinus bradycardia), sinus arrest, sinus pause, sinuatrial block, loss of a normal P-wave axis with default to an ectopic atrial rhythm (most often low right atrial), or complete loss of atrial activity and default to a junctional rhythm (typically narrow QRS complex). Sinus pauses or sinus arrest are almost always related to previous surgeries in the region of the sinus node or its blood supply, drugs, enhanced vagatonia, metabolic derangements, or hypoxemia.

Sinus node dysfunction is increasingly recognized as a late complication following congenital heart surgery either from scarring of the sinus node or injury to the sinus nodal artery or its autonomic inputs. In addition, certain anatomic substrates, such as left atrial isomerism (heterotaxy), may have an absent sinus node as part of their anatomic constellations.

Patients with sinus node dysfunction are frequently asymptomatic; however, that does not reliably translate into the fact that those individuals would not benefit from atrial pacing. Patients with sinus node dysfunction may exhibit chronotropic incompetence and have symptoms of exertional fatigue. Each of these bradycardias may also occur as part of the bradycardia-tachycardia syndrome with concomitant atrial reentrant arrhythmias.

The primary criterion for antibradycardia pacing is the presence of symptoms at rest or with exercise. The relative heart rate labeling someone as bradycardic is age dependent. For example, a resting heart rate of 45 beats/min may be a normal heart rate in a fit adolescent, but in a neonate would invoke significant concerns. Symptomatic bradycardia is defined as a documented bradyarrhythmia that is directly responsible for the clinical manifestations of syncope or near syncope, transient dizziness, light-headedness, or periods of confusion resulting from cerebral hypoperfusion. Fatigue, exercise intolerance, and heart failure may also result from bradycardia.

Although a resting electrocardiogram (ECG) will give a snapshot assessment of the sinus node, 24-hour ambulatory monitors are better measures of the sinus node and provide low, average, and high heart rates. Guidelines for the Holter diagnosis of sinus bradycardia have been proposed; for neonates and infants, they are less than 60 beats/min sleeping and less than 80 beats/min while awake. However, there is little distinction between the low heart rate at rest and the low heart rate while awake. The relevant rate for children aged 1 to 6 years is less than 60 beats/min; for those aged 7 to 11 years, less than 45 beats/min; for adolescents and young adults, less than 40 beats/min; and in highly trained athletes, less than 30 beats/min. None of these numbers are based on children and adolescents with congenital heart disease. Correlation of symptoms with periods of bradycardia should be sought before a patient receives a permanent pacemaker. Likewise, elite athletes may have low resting heart rates, and this level of physiologic sinus bradycardia should not be confused with a pathologic mechanism.

Certain channelopathies (i.e., long-QT syndrome [LQTS] may manifest as bradycardia; see later). Patients with congenital heart disease may have significant hemodynamic perturbations due to the loss of AV synchrony even with acceptable normal junctional rates and may benefit from atrial pacing. This has been well demonstrated in single-ventricle patients after the Fontan procedure and in adults who underwent an atrial baffle procedure for transposition of the great arteries. Rychik showed that in patients with a univentricular circulation following a superior cavopulmonary connection, junctional rhythm results in early systolic flow reversal in the pulmonary veins and reduces effective single-ventricular cardiac output.

Bradycardia in the Neonate

In the healthy newborn the heart rate ranges from 120 to 160 beats/min, but the range exists from 90 to 230 beats/min. Transient bradycardia is relatively common in newborns in the form of sinus bradycardia, sinus arrest, and junctional escape rhythm; it may relate to stressful labor or delivery and typically resolves within 48 to 72 hours. Potential causes of transient bradycardia in the neonate relate to sedation given to the mother that crosses the placenta to the baby as well as jaundice, hypothyroidism, increased intracranial pressure, apnea, and increased vagal tone. Pauses of greater than 1 second are not infrequently observed in neonates and generally do not require anything beyond observation. Pauses greater than 2 seconds are less common and should be considered abnormal.

Bradycardia in the preterm and term neonate can also be a result of blocked premature atrial contractions (PACs). PACs are relatively common (0.7% to 14%) in healthy newborns. As in older children, PACs may be conducted, blocked, or conducted with aberrancy. In an otherwise well-appearing acyanotic neonate with PACs, there is near-zero morbidity, and they will persist in fewer than 5% of those beyond 12 weeks of age. Premature atrial beats may appear in patterns of bigeminy, trigeminy, or quadrigeminy but still have a relatively benign prognosis. It is important that nonconducted PACs are not confused with complete AV block. Careful observation of P-wave morphology and the P-wave axis may be helpful in confirming atrial and AV nodal escape beats in neonates.

Episodes of apnea in term and preterm infants may precede transient bradycardia. Longitudinal polysomnographic studies have reported these transient episodes of bradycardia to be a normal neonatal reflex. Premature ventricular beats have been reported in 0.2% of healthy newborns; however, an echocardiogram should likely be performed to rule out structural heart defects or an associated cardiomyopathy. Rare, isolated premature ventricular contractions in an otherwise healthy newborn with a structurally normal heart are generally considered to have a similarly benign natural history to their premature atrial counterparts. Increasing the sinus rate typically abolishes both the atrial and ventricular ectopy.

Atrioventricular Block

First-degree AV block is PR prolongation beyond the upper limit of normal for age. Normative pediatric ECG data have been published. First-degree AV block may be observed in patients with dilated atria, where the impulse takes longer to propagate through the atrial tissue. This is frequently seen in patients with a functionally univentricular heart following an atriopulmonary Fontan procedure. First-degree AV block is one of the minor criteria used in the affirmation of rheumatic heart disease. Second-degree AV block can be subdivided into Mobitz type I (Wenckebach) and Mobitz II second-degree block. Mobitz I AV block is typically associated with a narrow QRS complex and is typically considered benign. In contradistinction, Mobitz II AV block is a rare pattern with less reliable escape rhythms and is always infranodal.

Mobitz type I AV block ( Fig. 22.1 ) is characterized by progressive PR prolongation before a single nonconducted P wave and is typically associated with a narrow QRS complex unless the patient has an underlying bundle-branch block. Clues to the diagnosis include the observation that the postblock PR interval is shorter than the preblock PR interval as well as the recognition of what has been described as grouped beating. Mobitz I AV block is frequently observed in very healthy adolescents with high vagal tone in the early morning hours of sleep. In contrast, type II second-degree AV block is characterized by fixed PR intervals before and after blocked beats and is usually associated with a wide QRS. Caution should be exercised before labeling someone as having type II second-degree AV ( Fig. 22.2 ) block, as the natural history and management of Mobitz type I ( Fig. 22.3 ) and Mobitz type II AV block are different. It is often helpful to obtain a long rhythm strip to accurately measure the PR intervals over a period of time. Generally it would be uncommon to see both Mobitz I and Mobitz II in the same patient, as one relates to block above the node and one below the node. It is important to pay close attention to a 2 : 1 pattern of AV block whereby neither Mobitz I nor Mobitz II may be affirmed, although a wide QRS in the setting of 2 : 1 AV block suggests Mobitz II AV block.

Rhythm strip demonstrating Mobitz I atrioventricular block (Wenckebach pattern); PR prolongation with a dropped ventricular beat. The PP interval is constant.

Rhythm strip demonstrating Mobitz type II atrioventricular block. There is baseline first-degree atrioventricular block and a wide QRS complex. The PR interval after failure of atrioventricular conduction is identical to the preblock PR interval. This patient had syncope in the postoperative period after implantation of a prosthetic mitral valve. A pacemaker was subsequently placed.

A 12-lead electrocardiogram showing progressive PR prolongation with a narrow QRS complex. Mobitz type II atrioventricular block. The rhythm strip at the bottom portion shows a normal PR interval and eventually a dropped beat. The pattern of “grouped beating” is a frequent observation in patients with Mobitz I atrioventricular block.

Advanced second-degree AV block refers to lack of conduction of two or more consecutive P waves but with some conducted beats indicating some preservation of AV conduction. Third-degree AV block (complete heart block) refers to complete dissociation of the atrial and ventricular conduction ( Fig. 22.4 ). Although patients with congenital complete AV block typically have a regular slow escape rhythm, the same may not hold true for third-degree AV block following cardiac surgery, where the escape rhythm may not be as reliable. In patients with AV dissociation secondary to third-degree block the atrial rate (PP) tends to be faster than the junctional rate (RR) (PP > RR). This is generally in contradistinction to junctional ectopic tachycardia (JET), where AV dissociation exists but the ventricular rate is faster than the atrial rate (RR > PP). In patients with AV dissociation suspected to be secondary to JET, atrial pacing (AAI) faster than the junctional rate reestablishes AV synchrony, whereas the same would not hold true for complete AV block.

Complete atrioventricular block. The atrial rate is 135 beats/min. The ventricular rate is 50 beats/min. The P waves bear no relationship to the QRS complexes, which are regular. The QRS complex is wide, which in this patient with congenital complete heart block is an indication for antibradycardia pacing.

2 : 1 Atrioventricular Block

The occurrence of 2 : 1 AV block is a form of second-degree AV nodal block whereby every other P wave is not conducted through the AV node and into the ventricles. Thus a QRS complex does not follow every other P wave. This type of AV block can result from either second-degree type I or type II AV block. As a general rule, if the PR interval of the conducted beat is prolonged and the QRS complex is narrow, then it is most likely second-degree Mobitz type I block. Alternatively, if the PR interval is normal and the QRS duration is prolonged, then it is most likely second-degree AV block type II.

This distinction is critical, as the former tends to have a very benign course and the latter requires ongoing follow-up, as AV block may progress and the nature and rate of the escape rhythm are unpredictable. The pathophysiology of the two variants of AV block is quite disparate, with Mobitz type I block being a disease of the AV node and subject to sympathetic and parasympathetic inputs. Type II second-degree AV block is infranodal and relates to perturbations in the His-Purkinje conduction axis; it is not subject to the same level of parasympathetic and sympathetic inputs. Various maneuvers (atropine, adenosine, exercise) can distinguish between the two forms of 2 : 1 AV block based on these principles.

Congenital Complete Atrioventricular Block ( Box 22.2 )

In 1982, Michaëlsson and Engle published the well-known natural history study of congenital complete AV block, with a reported incidence between 1 in 15,000 and 1 in 23,000 and a familial incidence of 2.3%. However, more recent evidence out of Finland, likely a result of improved perinatal monitoring and increased successful deliveries of mothers with connective tissues disorders, revealed an incidence closer to 1 in 11,000. Of the patients diagnosed with congenital complete AV block, approximately 25% to 35% have associated structural heart defects. The pathophysiology of congenital complete AV block in structural heart disease may relate to a lack of communication between the AV node and the penetrating bundle. There may also be a lack of communication between the atria and AV node such that the AV node may be totally absent, or there may be an aberrant conduction system such that the AV node and distal conduction tissue may be formed from anterior endocardial tissue. In the original natural history study of congenital complete AV block, mortality was 15% in infants without congenital heart disease compared with 43% if congenital heart disease was present. This early observation partly explains the difference in antibradycardia pacing recommendations between the two cohorts.

The pathogenesis of congenital complete AV block related to maternal autoimmune conditions is incompletely understood but is believed to be a result of SSA (Ro) and SSB (La) immunoglobulins crossing the placenta between 12 and 23 weeks of gestation and interacting with antigens on AV node, fibrous body, and annulus. Despite what seems to be a simple pathophysiologic explanation, only 5% of fetuses exposed to maternal immunoglobulins develop congenital complete AV block. Part of this observation may relate to varying amounts of anti-Ro and anti-La that cross the placenta as well as potential differences related to ethnicity. Significant predictors of death appear to be low ventricular rate (<55 beats/min), hydrops, endocardial fibroelastosis, and right ventricular (RV) endocardial wall thickness. The most sensitive predictors of increased risk of congenital complete AV block are having a child with previous AV block, high anti-Ro/La titer, or the presence of HLA-DR3 titers. The indications for pacemaker implantation are discussed further on.

The primary goal of antibradycardia pacing for congenital complete AV block is to prevent syncope, Stokes-Adams attacks, and sudden cardiac death. Patients with symptoms of heart failure have a class I indication for pacemaker implantation. However, not all children display classic heart failure symptoms, and the clinician caring for the younger child should be aware of atypical symptoms such as long naps and nightmares as well as exertional fatigue compared with siblings around the same age. Predictors of symptoms include atrial enlargement, QT prolongation, and cardiomegaly. Additional class I indications include a wide QRS escape rhythm, complex ventricular ectopy, or ventricular dysfunction. Congenital third-degree AV block in an infant with a ventricular rate less than 50 to 55 beats/min or in association with congenital heart disease and a ventricular rate less than 70 beats/min is considered a class I recommendation for permanent pacing. If such rate criteria are met, it is standard practice to place a pacing system using epicardial leads (preferably bipolar) along with an abdominally placed generator. Newborns can be paced VVI at rates generally between 70 and 90 beats/min; however, if easily achievable, an atrial and ventricular lead dual-chamber system should be placed to maintain AV synchrony. Whereas pacemaker syndrome is unusual in small children, it remains preferable to have an atrial and ventricular lead unless technical challenges limit such an application. A recent study by Janousek and colleagues has shown that left ventricular (LV) pacing in patients with AV block and a structurally normal heart has had a major impact on LV mechanical synchrony and efficiency; it has the potential to reduce pacing-induced ventricular dysfunction. A novel fetal micropacemaker has recently been invented by Vest and colleagues and is in early clinical trials for fetuses with serologically positive congenital complete heart block and associated hydrops. It is unclear whether early pacing can alter the natural history in this exceedingly high-risk cohort.

Pacing recommendations for those with congenital complete AV block beyond the first year of life are a mean heart rate below 50 beats/min (class IIA) or pauses of at least 3 seconds while awake or 5 seconds while asleep ( Fig. 22.5 ). One concern for children with isolated congenital complete AV block is the development of a dilated cardiomyopathy. This is reported in 6% to 11% of patients, even when pacing suggestive of a pacing-induced ventricular dyssynchrony is a contributor to the development of ventricular dysfunction. Unfortunately, pacing-induced dyssynchrony cannot explain all causes of a dilated cardiomyopathy, as reports of a myopathic process occurred in relation to some children who were not paced. There are early data that pacing the left ventricle (apical) at a young age may prevent the development of pacing-induced dyssynchrony and dilated cardiomyopathy. Longer-term follow-up of such patients will be required to see whether, in this rare condition of congenital complete heart block, LV pacing will abolish the even rarer development of a dilated cardiomyopathy. However, such a simplistic explanation cannot address the presence of a dilated cardiomyopathy in all such patients.

A significant pause of 5.8 seconds was recorded overnight in a 10-year-old patient with congenital complete heart block. The pause length is not a multiple of the previous RR interval, so it is not of the type referred to by class IIa, recommendation 2. The presence of multiple pauses like this, however, led to insertion of an antibradycardia pacemaker.

High-grade functional AV block (≥2 : 1 AV block) with concomitant QT prolongation ( Fig. 22.6 ) is a class IIA indication for a permanent pacemaker and relates to extreme prolongation of ventricular refractoriness. Whereas prolonged QT intervals can be seen with AV block, concomitant torsades de pointes (TdP) is rare. However, the presence of TdP in the setting of AV block may be a marker of underlying repolarization reserve, and genetic variants of LQTS have been identified in 36% of this high-risk cohort. Michaëlsson has recommended that all patients with congenital complete AV block be paced by the time they reach adolescence because of a significant risk of syncope or sudden death at any time thereafter, even in the absence of poor prognostic signs. Although this recommendation is class IIB, it is increasingly accepted.

Rhythm strip demonstrating functional 2 : 1 atrioventricular block in the presence of QT prolongation (prolonged ventricular refractoriness).

Patients with significant and persistent bradycardia and sinus node or AV block who do not undergo antibradycardia pacing require ongoing follow-up with serial ECGs, Holter monitors, and echocardiograms. The frequency of such testing should be based on the clinical status of the patient after discussions with the medical team caring for him or her. There are few data on the use of serial echocardiograms in establishing definitive recommendations for a pacemaker, but it is generally helpful to assess ventricular size and function, the degree of AV valve regurgitation, and atrial size.

Postoperative Atrioventricular Block

Postoperative AV block occurs in 1% to 3% of cardiac operations, with the greatest risk occurring following repair of AV canal defects, tetralogy of Fallot, and ventricular septal defects as well as in hearts with AV discordance (L-looped) and heterotaxy syndrome. Although transient AV block has been reported in nearly 7% of surgical cases, resolution may occur; if so, it will do so in 97% by 10 days following surgery. As such, the risk of sudden cardiac death following surgical advanced second- or third-degree AV block that is not expected to resolve or persists for at least 7 days after cardiac surgery is a class I indication for pacemaker implantation. In addition, junctional JET may be a concomitant observation in patients with complete AV block. Patients in whom postoperative advanced second- or third-degree AV block has resolved and in whom conduction returns to normal have a good prognosis, and pacing is not indicated. If there is incomplete recovery with new residual bifascicular block (complete right-bundle-branch block [RBBB] and left axis deviation), uncertainty remains (class IIB in the American College of Cardiology/American Heart Association recommendations and class IIa in the European Society of Cardiology). Postoperative AV interval determination may help to assess the risk of late-onset AV block in patients with residual conduction disorders (bifascicular block and PR prolongation); however, this is not always practical. If epicardial wires are available and there is concern about the stability of the residual conduction abnormality, it may be worth evaluating the AV node’s Wenkebach cycle length. Discussions with the cardiac intensive care unit and surgical teams regarding leaving epicardial wires in place to assess AV nodal conduction should occur. Long-term instability of the conduction system has been postulated in patients with transient postoperative heart block and is thought to contribute to late sudden death in some patients. Thus patients should be monitored for any recurrence of heart block or evidence of arrhythmia with regular ambulatory monitors.

Reentrant Tachycardias

Reentry SVT ( Fig. 22.8 ) requires an anatomic substrate for abnormal conduction and the appropriate electrophysiologic environment. Reentrant tachycardias, such as AVRT and AVNRT, require a difference in the electrophysiologic properties of two AV pathways to initiate tachycardia; this allows the occurrence of unidirectional block in one pathway while maintaining conduction in the other. Patients presenting with a reentrant arrhythmia often report symptoms consistent with an abrupt onset and termination. They may go so far as to recognize that coughing or holding their breath (vagal maneuvers) will terminate the tachycardia. Both AVRT and AVNRT are typically narrow QRS tachycardias with a 1 : 1 relationship between the atrium and ventricles. One exception to this rule is patients who have an underlying bundle-branch block (i.e., tetralogy of Fallot), as the tachycardia will have the same underlying wide QRS morphology as seen in sinus rhythm. In this regard it is always helpful to review old ECGs, if available, in patients presenting with palpitations ( Figs. 22.9A and B ). Both tachycardias use the AV node as the anterograde limb of the tachycardia circuit and thus will terminate with vagal maneuvers and AV nodal blocking agents such as adenosine.

A 12-lead electrocardiogram demonstrating short RP′ narrow complex supraventricular tachycardia with a normal QRS axis.

(A) A 22-year-old patient with tetralogy of Fallot underwent repair and subsequent transcatheter pulmonary valve baseline electrocardiography that showed sinus rhythm and right-bundle-branch block with a QRS duration of 200 ms. The same patient (B) presenting with a wide complex tachycardia with an identical QRS morphology in all leads and no evidence of atrioventricular dissociation. This electrocardiogram represents atrial tachycardia with an underlying right-bundle-branch block.

Atrioventricular Reentry Tachycardia

AVRT is usually due to a reentrant circuit that involves anterograde conduction over the AV node and retrograde conduction over an accessory AV pathway (orthodromic reentrant SVT). The accessory pathway or bypass tract is a microscopic muscular connection that traverses the mitral or tricuspid annulus, allowing electrical continuity between the atrium and the ventricles. Some accessory pathways allow conduction from the atrium to the ventricle anterograde; thus there is a pattern of manifest preexcitation, a delta wave, on the surface ECG. Some pathways can conduct only in the retrograde (ventricle-to-atrium) direction and are thus concealed, without evidence of a delta wave on the surface ECG. Finally, some pathways can conduct in both directions. There is an association between AVRT and structural heart disease, especially the Ebstein malformation of the tricuspid valve and congenitally corrected transposition of the great arteries (AV and ventriculoatrial [VA] discordance), cardiac tumors, tuberous sclerosis, and hypertrophic cardiomyopathy. These conditions may have concealed or manifest accessory pathways; if surgery is being contemplated, a discussion with the medical team regarding a presurgical assessment and catheter ablation is often warranted.

Wolff-Parkinson-White Syndrome

Wolff-Parkinson-White Syndrome (WPW) syndrome is a condition in which anterograde conduction occurs over the accessory pathway during sinus rhythm and results in a manifest change on the surface ECG ( Fig. 22.10 ). Because accessory pathways may be capable of a more rapid rate of conduction from the atria to the ventricles than the normal AV node, ventricular depolarization occurs before activation from the AV node and bundle of His (preexcitation), causing a short PR interval and wide QRS complex with a “slurred” upstroke or a delta wave. Patients with WPW syndrome may have no symptoms (asymptomatic WPW syndrome), reentrant SVT (typical WPW SVT), or rarely but incredibly concerning degeneration of SVT into atrial fibrillation (AF) over the accessory pathway followed by ventricular fibrillation (VF) and potentially sudden cardiac death. Although AF occurs more commonly in children with WPW syndrome than in those without, AVRT is the most common arrhythmia seen in WPW syndrome. Antidromic reciprocating tachycardia is far less common and is a tachycardia circuit that uses the accessory pathway in the anterograde direction and the AV node retrograde. This is a maximally preexcited tachycardia and therefore is a wide QRS tachycardia that can be mistaken for VT.

A 12-lead electrocardiogram demonstrating ventricular preexcitation consistent with a Wolff-Parkinson-White pattern.

Sudden death occurs in WPW syndrome as consequence of rapid anterograde conduction of AF over the accessory pathway resulting in VF ( Fig. 22.11 ). The incidence of sudden death in WPW syndrome is low (estimated at 1 in 1000 patients per year); but without a premortem ECG or comprehensive autopsy evaluation of the conduction system and AV junction, it is impossible to be certain. It is disconcerting that studies have identified previously asymptomatic children with ventricular preexcitation whose only symptom was VF. Although it would seem reasonable that symptomatic patients would constitute a higher-risk cohort than asymptomatic patients, the risk profiles may be relatively similar. Catheter ablation seems to be effective at eliminating the WPW substrate and the risk of sudden cardiac death; however, ablation itself carries a risk of adverse events, including AV block, coronary artery injury, and vascular injury. As an initial starting point, the Pediatric and Congenital Electrophysiology Society in conjunction with the Heart Rhythm Society published recommendations regarding the management of the asymptomatic child/adolescent with ventricular preexcitation and a structurally normal heart. The recommendations centered on understanding the refractoriness of the accessory pathway. Clear and abrupt loss of the delta wave on the exercise test has been shown to correlate with a low-risk accessory pathway, with confirmatory invasive testing showing accessory pathway block at a heart rate below 222 beats/min (100% sensitivity and positive predictive value). Unfortunately, less than 20% of children demonstrate this finding. Therefore invasive electrophysiology testing has been recommended with the goal of assessing the shortest RR interval during inducible AF or rapid atrial pacing. This test has had relatively good sensitivity in identifying a low-risk accessory pathway in asymptomatic children (sensitivity 88% to 100%), and the use of isoproterenol may increase the sensitivity to counter the effects of general anesthesia. However, no noninvasive or invasive electrophysiologic testing is 100% predictive of a completely benign accessory pathway. In fact, reports of patients with intermittent ventricular preexcitation, previously thought to be completely benign, may warrant additional testing ( Fig. 22.12 ). Identification of a low-risk accessory pathway by electrophysiologic testing (an accessory pathway that cannot conduct 250 beats/min or more at baseline or on isoproterenol) may point to a low-risk accessory pathway but does not confer zero risk of a life-threatening event. In a recent multicenter study of children with WPW syndrome, patients with a life-threatening event were compared with those without. In this study, there were 96 children who had experienced a life-threatening event: rapidly conducted preexcited AF (49%), aborted sudden death (45%), and sudden death (6%); there were 816 controls without an event. In the cohort with a life-threatening event, this was the sentinel symptom in 65%. Risk factors for a life-threatening event included male sex, the Ebstein malformation, rapid pathway conduction, and multiple pathways. Among the cohort who had experienced a life-threatening event, 60 had had an electrophysiologic study (EPS) that was of adequate detail to characterize risk; of these, 37% had no data to suggest a high-risk accessory pathway, and 25% had neither concerning pathway characteristics nor inducible SVT. Thus, even data obtained at the time of an EPS may not allow complete identification of children with WPW syndrome who are at risk for sudden death. Careful and thoughtful discussions must take place with the patient and family regarding the short-term potential complications associated with catheter ablation versus the rare but lifetime risk of a life-threatening arrhythmia. Patients and families who choose not to proceed with invasive electrophysiologic testing and catheter ablation must be seen for follow-up and report any symptoms such as syncope or palpitations. One must balance the risks of the procedure—which should take into account the age and size of the patient and the location of the accessory pathway—with the long-term risk of developing SVT or AF.

A 12-lead electrocardiogram (ECG) demonstrating a wide complex irregular rhythm in a patient with known ventricular preexcitation who presented with a syncopal event that was triggered by complaints about a rapid heartbeat. The patient was cardioverted to normal sinus (preexcited) rhythm and subsequently underwent catheter ablation fo the manifest accessory pathway. This ECG is consistent with preexcited atrial fibrillation.

Rhythm strip demonstrating an intermittent Wolff-Parkinson-White pattern. Every other beat appears to be preexcited, with a delta wave and alternating beats showing a normal sinus (normal PR interval) rhythm. This patient still had supraventricular tachycardia, as the retrograde limb of the circuit allowed for ventriculoatrial conduction and the propagation of reentrant supraventricular tachycardia.

Atrioventricular Reentrant Tachycardia

The ability to generate AVNRT implies dual AV node physiology, likely a consequence of two or more distinct AV nodal pathways with distinct electrophysiologic properties. Anterograde conduction occurs over one AV nodal pathway; usually the slower and retrograde conduction occurs over the other in typical AVNRT, and the converse is atypical AVNRT. Atypical AVNRT is very uncommon in children. AVNRT is less common than AVRT in the neonate and infant, occurring in 10% to 15% of patients under age 1; it increases in frequency with age. The development of AVNRT in children as they age may be due to maturational changes in the electrophysiologic properties of the AV node. In an attempt to assess this, AV node function was evaluated by electrophysiologic testing in two different pediatric age groups (approximately 4 months to 13 years and from 13 to 20 years). The AV node in the younger patients was able to tolerate much faster pacing rates before developing anterograde AV block. In contrast, retrograde VA conduction was not age dependent and was common, with no differences related to age. Dual AV node pathways occurred significantly more often in the older children. These observations indicate that the substrate for AVNRT (dual AV node pathways, with inducible anterograde block in one limb at moderately rapid rates) is more likely to be present in adolescents and is rare in children and infants. AVNRT is also seen in simple as well as complex congenital heart disease either before or after surgical or interventional cardiac catheterization procedures. AVNRT appears to be more common in substrates that have either a pressure- or volume-loaded RV. An unsuccessful AVNRT ablation was more common in those with complex congenital heart disease, likely related to the malposition of the AV node.

Management of Reentrant Supraventricular Tachycardia

Acute events of tachycardia can terminate with vagal maneuvers, adenosine, and overdrive pacing ( Figs. 22.13 and 22.14 ). Cardioversion is usually restricted to hemodynamically unstable patients or those where other termination methods have been unsuccessful. Decisions concerning chronic medical therapy or a cure by catheter ablation must take into account the natural history, SVT burden and symptoms, patient age and size, structural and functional heart disease, and whether the patient has WPW syndrome.

Combined limb and chest leads showing a narrow complex tachycardia in this 15-year-old patient who presented to the emergency department complaining of palpitations. The tracings show a narrow complex supraventricular tachycardia at 182 beats/min, which terminated with intravenous adenosine to a normal sinus (nonpreexcited) rhythm.

Rhythm strip from a 4-month-old with a narrow complex supraventricular tachycardia (SVT) breaking through on flecainide and propranolol. The rate of the SVT is 190 beats/min. The tachycardia broke as an intravenous line was being placed. The arrow shows the first sinus beat. The abrupt termination of the SVT is consistent with a reentrant type of arrhythmia.

Natural History of Neonatal/Infant Supraventricular Tachycardia

Although episodes of SVT are common during infancy, most patients are free of tachycardia during early childhood, although some infants do not have a recurrence of SVT after the initial presentation. Natural history studies have suggested that approximately 30% of infants lose SVT inducibility by 1 year of age. Factors at presentation, characteristics of the tachycardia, or data from an initial esophageal EPS failed to predict which infants would have continued SVT recurrences and thus require antiarrhythmic medication and which infants would not need medication. However, all infants with the diagnosis of AVNRT continued to have inducible SVT at 1 year of age. Most infants are free of medications at 1 year of age.

Medical Management of Supraventricular Tachycardia

The use of chronic antiarrhythmic medications in the infant may prevent recurrent SVT events and allow the time needed for SVT resolution. There have been few clinical trials to direct chronic SVT management in children, and the choice of antiarrhythmic medications is often based on personal preference and institutional practice as opposed to data from controlled clinical trials. In the first randomized controlled trial of medical prophylaxis for SVT in a pediatric population, the researchers detected no differences in SVT recurrence between digoxin and propranolol, the two most common clinical choices for SVT prophylaxis in infants. A low SVT recurrence rate was seen in both groups. In this study, all recurrences were seen in the first few weeks of life, and the majority of patients were arrhythmia free at 4 months of age. Currently it is standard practice to use prophylactic medication for 6 to 12 months, but this duration of therapy may not be necessary. Both digoxin and propranolol represent a reasonable first-line choice for the neonate with SVT. However, if WPW syndrome is present, digoxin is not recommended owing to reports that this can shorten the effective refractory period of the accessory connection. In an older child a β-blocker with twice daily dosing may be preferable and atenolol is a reasonable first-line agent.

Decisions concerning the need for other antiarrhythmic agents depend on the tachycardia burden and symptoms, coexisting structural and functional heart disease, personal experience, and institutional practice. Numerous agents exist, although few have had rigorous testing in a pediatric population.

Catheter Ablation of Supraventricular Tachycardia

Decisions are often based on input from the patient and family. Pediatric catheter ablation indications were assessed in two large pediatric studies, and the most common indication for catheter ablation was patient and parent wishes.

Children with WPW syndrome are different. Because this condition is associated with a small risk of sudden death, there should be a low threshold for ablation in this population, with patient age and size factored into the decision. Animal studies suggest lesion growth when ablations are undertaken in immature animals, and risks have been shown to be increased in children weighing less than 15 kg. Postponing an ablation allows time for substrate resolution as well as the patient’s somatic growth, which can decrease the risk of the procedure. Ablation is not without risk, but the risk is small. Thus the small and immediate risk of the ablation must be weighed against the lifetime symptom burden, ease of SVT management, and—in children with WPW syndrome—the lifetime risk of sudden death.

Permanent Form of Junctional Reciprocating Tachycardia

PJRT is an accessory pathway–mediated tachycardia with a long RP interval; it occurs predominantly in infants and children ( Fig. 22.15 ). The pathway can be located anywhere in the AV junction but is usually located in the posteroseptal region. This is a tachycardia with a long VA interval, called a long RP′ tachycardia. The typical ECG of PJRT is that of negative P waves in leads II, III, aVF, given the typical inferior location of this unique accessory pathway. Because the AV node constitutes the anterograde limb of this tachycardia, it will likely terminate with adenosine; most often, however, it quickly recurs. Pathways are tortuous and slow conducting; thus the tachycardia is often incessant, and PJRT is the second most common cause of arrhythmia-induced cardiomyopathy in children. In a large review of children with PJRT, 27% presented in fetal life, 7% of these with hydrops, which is a fetal manifestation of arrhythmia-induced cardiomyopathy. Isolation of the AV junction is a continuing process that may not be complete at birth, and the presence of accessory connections crossing the annulus fibrosus could result in persistent perinatal SVT. Although most children with PJRT present with palpitations or are noted to have rapid heart rates, in this series of 194 children, 18% presented with cardiomyopathy. Cardiomyopathy was more likely to occur in children with longer RP interval/cycle length ratios, consistent with an accessory pathway with slow retrograde conduction and a wide, excitable gap. PJRT is often incessant, and those with incessant PJRT had longer RP intervals, were younger at diagnosis, and more often had cardiomyopathy. The clinical course of PJRT is not benign and spontaneous resolution is unlikely.

Run of permanent junctional reciprocating tachycardia with a typical long RP interval and retrograde atrial activation, which breaks to sinus on the second-to-last beat of the tracing.

A number of antiarrhythmic medications have been used to treat PJRT, and a single most effective agent has not emerged. β-blockers are the common first choice, likely reflecting physician comfort rather than proven efficacy. Caution should be exercised when β-blockers are being given to neonates as they may cause hypoglycemia and sleep disturbances; moreover, occasionally infants do not eat as well while on antiarrhythmic medications. Complete tachycardia suppression with medications varies from 25% in the recent series to more than 80% in a study using regimens that included amiodarone. Medical therapy is commonly employed in neonates and infants, whereas older children typically undergo ablation. Catheter ablation is the primary treatment for PJRT in older children or small children who fail medical management or have frequent bouts tachycardia with echocardiographic evidence of ventricular dysfunction or clinical signs of heart failure. Success rate for catheter ablation of PJRT is 90% (Kang).

Atrial Flutter in the Newborn

Although atrial flutter is uncommon in children with structurally normal hearts, neonatal atrial flutter does occur ( Fig. 22.16 ). This can be seen in utero; in the neonate, it usually occurs in the first 48 hours of life. Unrecognized, this can result in an arrhythmia-induced cardiomyopathy. Cardioversion is effective and the arrhythmia usually does not recur. Most neonates do not require antiarrhythmic medications. There is an association between atrial flutter in the fetus and the newborn and the subsequent development of AVRT.

A 12-lead rhythm strip showing a narrow complex tachycardia in a 12-hour-old baby. The sawtooth pattern of atrial flutter becomes even more manifest with transient atrioventricular nodal block.

Automatic Tachycardias

Unlike reentrant tachycardias, automatic tachycardias are rapid discharges from an automatic focus distinct from the sinus node. Typically these tachycardias have a “warm up and a cool-down” phase and respond to the autonomic tone of the individual. Distinct from reentrant tachycardia, automatic tachycardias often cannot be initiated or terminated with programmed electrical stimulation and are less likely to terminate with cardioversion. They do not use the AV node as part of the tachycardia circuit so do not routinely terminate with adenosine, although the use of this medication may allow for AV block and unmask an atrial tachycardia.

Atrial Ectopic Tachycardia

AET is the most common arrhythmia associated with arrhythmia-induced cardiomyopathy in children. Although a P-wave morphology and axis usually differ from sinus rhythm, an AET focus near the sinus node or right upper pulmonary vein is hard to differentiate from sinus tachycardia, especially in patients with heart failure, where sinus tachycardia is expected. Increased automaticity is the most likely mechanism; others include triggered activity and microreentry. AET usually occurs without structural heart disease but has been described after congenital heart disease surgery and in the setting of channelopathies. Arrhythmia-induced cardiomyopathy may occur in 1 in 4 children with AET; however, the presentation may vary from mild LV dysfunction to the need for heart failure medications; in rare cases it may require advanced mechanical heart failure therapies. Although β-blockers are often the first line of therapy in AET, drug failures are common and multiple antiarrhythmics may be utilized. Catheter ablation is effective in AET. In this procedure conscious sedation may be preferred to negate the potential that general anesthesia will suppress the tachyarrhythmia and reduce the likelihood of a successful ablation. The use of electroanatomic mapping for ablation has improved success and decreased recurrence. Spontaneous resolution of AET can occur, especially in those presenting within the first year of life, where 74% had resolution. Although ablation has proven safe and effective, a trial of medical therapy in the youngest patients, in whom ablation may have more risk and where spontaneous resolution, is prudent.

Junctional Ectopic Tachycardia

JET has two forms: occurring immediately after surgery (postoperative) or as a primary idiopathic arrhythmia (congenital). JET is due to abnormal automaticity in the region of the AV junction and is defined as a narrow QRS complex often with AV dissociation or retrograde atrial conduction in a 1 : 1 pattern. JET is most commonly seen in young children following complex congenital heart surgery ( Fig. 22.17 ) around the AV node with long cardiopulmonary bypass times and need for significant inotropic support. Postoperative JET is unique in that it is potentially life-threatening yet is self-limited. Because of the clinical context involving a small child after open-heart surgery, it is often a serious arrhythmia, associated with hemodynamic compromise and a high morbidity and mortality. Treatment is often needed and historically has included maximization of the patient’s hemodynamics, correcting electrolyte abnormalities, minimizing inotropic agents when possible, and atrial pacing at rates exceeding the JET rate to provide AV synchrony when the JET rate will allow. A number of agents have been shown to be effective, including, magnesium, procainamide, esmolol, amiodarone, and dexemedetomidine. Although many treatment approaches exist, we advocate normalization of the electrolytes and acid base status, cooling to a temperature of 36°C to 37°C, and atrial pacing if JET rates are below 160 beats/min to reestablish AV synchrony. If this regimen is not adequate for control and hemodynamic improvement is not achieved, the addition of dexmedetomidine followed by intravenous amiodarone can be considered. If a bolus of amiodarone can be avoided and a drip instituted, this can prove effective over time and can avoid the risk of serious hemodynamic collapse, which has been described with the use of intravenous amiodarone in infants with acidosis, ventricular dysfunction, and prolonged tachycardia. If a bolus of amiodarone is required (2.5 to 5.0 mg/kg), it is prudent to give the bolus over a period of 45 to 60 minutes to reduce the possibility of cardiovascular collapse. The infusion rate for pediatric patients is 5 to 15 μg/kg per minute, using the lowest effective dose.

Rhythm strips showing a narrow complex tachycardia in a 4-month-old following repair of tetralogy of Fallot with pulmonary atresia who had a prior BT shunt. The atrial wave pressure tracing had cannon A waves. The rhythm strips demonstrate atrioventricular dissociation with the RR interval faster (shorter cycle length) than the PP interval. A combination of intravenous amiodarone along with atrial pacing faster than the junctional rhythm restored atrioventricular synchrony and the cannon A waves resolved.

JET unassociated with cardiac surgery (congenital JET) can present at any age. In the past, when congenital JET presented in infancy, it was associated with high morbidity and mortality. In a more recent multicenter study of nonoperative JET, overall mortality was lower, with all deaths occurring in children 6 months of age or less. Although only 16% presented with heart failure, the tachycardia was incessant in more than 40%. JET can be incessant or paroxysmal, although infants below 6 months of age are more likely to have incessant tachycardia. Medical management is commonly undertaken (89%) as the first step, but it was variably effective, with a variety of drugs used. β-blockers were the most common first-line agent, but the majority of patients required two or more drugs for control, with complete suppression seen in only 11%. Amiodarone alone or in combination was cited as the most effective for rate or rhythm control. A newer agent, ivabradine, may prove useful in nonoperative JET. Catheter ablation for JET can be accomplished with the preservation of AV nodal conduction, and cryoablation has been associated with success rates similar to those of radiofrequency (RF) ablation but without AV block.

Multifocal Atrial Tachycardia

MAT, also known as chaotic atrial rhythm, is rare, accounting for only 1% of SVT in children. The condition is characterized by the ECG finding of (1) multiple (at least three) distinct P-wave morphologies, (2) irregular P-P intervals, (3) an isoelectric baseline between P waves (to distinguish this from AF), and (4) a ventricular rate greater than 100 beats/min ( Fig. 22.18 ). Similar to the more common forms of SVT in childhood, MAT is very rapid, with atrial rates approaching 400 beats/min and ventricular rates at 150 to 250 beats/min. But, unlike most SVT in children, it is markedly irregular. Pauses may be observed following blocked premature atrial impulses and aberrant ventricular conduction might resemble nonsustained VT. In most children the irregular rapid rate alternates with periods of normal sinus rhythm. In adult patients, MAT is associated with underlying lung disease, heart disease, diabetes, and other noncardiac diagnoses. In children, MAT is most common in infancy. MAT can be seen in patients with respiratory infections and with structural heart disease; however, it can also be seen in previously healthy infants. There is no standard, proven therapeutic approach to patients with MAT. Cardioversion is largely ineffective, and its lack of efficacy has been considered a hallmark of this arrhythmia. Although arrhythmia-induced cardiomyopathy has been described in MAT patients, a large series studying MAT in children identified that most are neither very ill at the onset of the arrhythmia nor adversely affected by it over the several months it typically persists. Our current practice is to treat the underlying illness and to treat those with documented ventricular dysfunction with digoxin or an AV nodal blocking agent for rate control, such as a β-blocker or calcium channel blocker. Asymptomatic patients are followed without pharmacologic treatment, and medications such as amiodarone are reserved for symptomatic patients with persistent MAT and those who do not respond to the rate-slowing agents. Ablation has been described in MAT, but small patient size, the multifocal nature of the condition, and its tendency to resolve spontaneously or with treatment of the underlying problem make this a less attractive option for most.

A 12-lead electrocardiogram from a 5-month-old female who presented with a viral pneumonia (coronavirus and rhinovirus). The electrocardiogram demonstrates a narrow complex tachycardia with a variable ventricular rate with multiple different P wave morphologies, as shown by different arrows.

Accelerated Idioventricular Rhythm

In adults, numerical criteria differentiate VT from accelerated idioventricular rhythm. In children, however, the age-based variability of sinus rates precludes this. Nevertheless, the relationship to the sinus rate is used. Ventricular escape rhythms are defined as slower than sinus rhythm; idioventricular rhythms are similar to sinus rhythm, and accelerated idioventricular rhythms are slightly faster, defined as within 10% of the underlying sinus rate. Accelerated idioventricular rhythm appears to be due to enhanced automaticity of myocardium or His-Purkinje fibers. Although typically benign, in the setting of metabolic disarray, ischemia or myocardial disease may be a harbinger of more malignant ventricular arrhythmias. Accelerated idioventricular rhythm of the newborn may present in the first hours of life, may be discovered because of a slightly irregular rhythm, or may be noted in a child who is being monitored for another reason. In the asymptomatic infant, once structural heart disease has been ruled out—as have temperature, metabolic, and electrolyte abnormalities—this is considered a benign phenomenon and does not require treatment. The child should be monitored longitudinally to ensure that he or she remains asymptomatic and the rhythm resolves as anticipated, usually within the first year of life. Idioventricular rhythm can be seen in older children and is similarly benign. The asymptomatic patient should be monitored for a potential decline in cardiac function, although this is a rare occurrence, related to arrhythmia burden and possibly dyssynchrony. Ablation of the ventricular focus may be indicated in these cases to restore cardiac synchrony and has been demonstrated to restore normal cardiac function.

Monomorphic Ventricular Tachycardia

Right ventricular outflow tract (RVOT) VT is the most common form of idiopathic VT in children and is usually seen in those with structurally and functionally normal hearts. The VT originates most commonly from the posteroseptal region or the RV free wall just below the pulmonary valve. The tachycardia is monomorphic, with left-bundle-branch block, QRS morphology, and an inferior axis. There is often a late transition (>V ₃ ) in the precordial leads. The most common mechanism of RVOT tachycardia is triggered automaticity due to cyclic adenosine monophosphate–mediated activity. Thus this VT is responsive to adenosine, calcium-channel blockers, and β-blockers and often responds to maneuvers that decrease cyclic adenosine monophosphate levels, including vagal maneuvers. Rarely, RVOT tachycardia may be due to automaticity or reentry, which may be sensitive to verapamil. Symptoms of palpitations or near-syncope occur commonly, but frank syncope is rare and should raise the suspicion of an alternative diagnosis or associated ventricular dysfunction. RVOT tachycardia can be reproduced during exercise stress testing. Within the differential diagnosis of RVOT VT, one must consider and assess for tumors, myocarditis and arrhythmogenic right ventricular cardiomyopathy (ARVC). Unlike RVOT tachycardia, the VT associated with ARVC is usually due to reentry and is not typically responsive to adenosine or vagal maneuvers. Distinct from ARVC, the natural history and prognosis of RVOT tachycardia is benign and the long-term prognosis good. The tachycardia burden seems to decrease over time and spontaneous remission can occur, especially in infants. Recent studies have shown no mortality with up to 80-month follow-up in children with structurally normal hearts. The LV outflow tract can be the origin for a mechanistically similar VT.

Treatment of outflow tract VT in infants and children should be reserved for those with symptoms or frequent, prolonged, or rapid episodes or echocardiographic evidence of ventricular dysfunction. When indicated, the choice of medical therapy versus catheter ablation should be driven by institutional experience, patient age and size considerations, and family input. Initial therapy with lower-risk medication is recommended, with class I and III agents reserved for failure to control VT with a β-blocker or calcium-channel blocker in the older child. Catheter ablation is effective and can be performed at a relatively low risk.

Infrafascicular verapamil-sensitive reentrant tachycardia or idiopathic left VT is a ventricular arrhythmia arising from the mid- to the apical portion of the LV septum and is less common that RVOT tachycardia ( Fig. 22.19 ). This is a monomorphic tachycardia with a right-bundle-branch-block QRS morphology and a superior axis. It is thought to be due to a reentry near the left posterior fascicle and has commonly been referred to as fascicular VT or Belhassen VT. This tachycardia is more common in boys and is usually sensitive to verapamil; it sometimes responds to adenosine but not to vagal maneuvers. Clinically this VT is triggered by stress or exercise, with rates usually from 150 to 200 beats/min. This form of VT has a relatively narrow QRS owing to its origin adjacent to the normal conduction system, and it is often misdiagnosed as SVT in children. However, despite the relatively narrow QRS complex, the superior axis (negative QRS in aVF) is often a clue. The tachycardia is generally well tolerated, especially at the slower rates, and symptoms overlap with SVT, palpitations, and dizziness. Spontaneous remission can occur and the outcome is favorable; sudden death is rare.

A 12-lead electrocardiogram demonstrating a wide complex right-bundle-branch block tachycardia with left axis deviation (curved arrow) consistent with a fascicular ventricular tachycardia. The asterisk shows VA association due to retrograde conduction.

Infants with this VT, as with many other forms of arrhythmia, frequently experience resolution over time. Resolution is much less common in older children and adolescents. Episodes are often paroxysmal, frequently brought on by stress or exercise; they may last for hours before terminating spontaneously. VT is generally well tolerated, although patients are usually symptomatic during the events. Prolonged episodes can lead to tachycardia-induced ventricular dysfunction. Observation alone is usually not adequate owing to the symptomatic nature of the arrhythmia, but it may be useful in children with infrequent self-terminating episodes. Although this form of VT is highly responsive to intravenous verapamil during acute events, oral verapamil to prevent episodes has been shown to be ineffective in more than 20% of these patients. In such instances, another pharmacologic agent, such as a β-blocker, a class III antiarrhythmic agent, or catheter ablation is warranted.

Ablation in infants is generally a last resort and should be reserved for arrhythmias that are incessant, sufficiently frequent to contribute to ventricular dysfunction, and cannot be controlled medically. In general, catheter ablation for children with VT should be deferred, if possible, until the child is larger, especially since many resolve spontaneously. For older children, the decision to proceed to ablation is determined by assessment of the VT burden and diagnosis, procedural risks and benefits, and patient and family considerations. Although ablation of VT has been performed effectively in infants, risks are likely greater for children weighing less than 15 kg. The risks of growth of the ablation lesion and injury to adjacent coronary arteries remain concerns. The recent adoption of advanced three-dimensional mapping techniques has all but eliminated the use of fluoroscopy and its associated risks.

Polymorphic Ventricular Tachycardia

Polymorphic VT is characterized by beat-to-beat variations in QRS morphology and/or axis. It is uncommon in the pediatric population and carries a less favorable prognosis than does monomorphic VT. This is rare in children with structurally normal hearts or a channelopathy. Events are often hemodynamically unstable, and although they may terminate spontaneously, the potential for degeneration into VF exists. Polymorphic VT can be divided into bidirectional VT and true polymorphic VT, a classic example of which is TdP. Polymorphic VT in a young person without structural heart disease can occur in the setting of QT prolongation, either at baseline or precipitated by drugs, hypokalemia, or hypomagnesemia. Although provocation of polymorphic VT by a noncardiac medication is less common than by antiarrhythmic medications, a number of noncardiovascular drugs have been withdrawn from the market because of unexpected sudden cardiac death associated with prolongation of the QT interval and TdP. The hallmark mechanism of drug-induced QT prolongation and TdP is blockade of the cardiac delayed rectifier potassium channel. Incidence is difficult to estimate, and the occurrence of acquired QT prolongation and TdP is unpredictable. Often multiple risk factors are present in a given individual, for example drug exposure coupled with electrolyte imbalance. A female preponderance has been borne out in multiple studies. Cocaine, amphetamines, the weight-reducing substances phentermine and chlorpheniramine, and methadone have been associated with the occurrence of polymorphic VT; multiple agents are often present and interacting. Methadone is mainly metabolized by the CYP3A4 isoenzyme of the hepatic cytochrome P450 system, which is used by numerous other QT-prolonging agents.

TdP ( Fig. 22.20 ) can also be seen in LQTS following a long pause and triggered by early afterdepolarizations, with repetitive ventricular beats leading to TdP.

Rhythm strip demonstrating torsades de pointes (twisting around the points) in a patient with LQT type I. The tachycardia is wide complex, irregular, and of different QRS morphologies and axes.

Complex ventricular arrhythmias have been documented in myocarditis, even without demonstrable ventricular dysfunction. A series of 17 patients with otherwise clinically silent lymphocytic myocarditis presented with potentially life-threatening ventricular arrhythmias.

Polymorphic and bidirectional VT are sufficiently rare in pediatric patients that this arrhythmia should alert one to the potential for underlying pathology, such as a channelopathy, drug toxicity including digoxin toxicity, and myocarditis ( Fig. 22.21 ). Therapy for hemodynamically significant events includes magnesium, β-blocking agents, and possibly lidocaine. The use of other antiarrhythmic agents, with their tendency to prolong the QT interval owing to I _Kr (delayed rectifier potassium current) blockade, should be approached cautiously. Correction of the underlying cause, including normalizing electrolyte abnormalities, is imperative. Pacing at a relatively rapid rate may suppress the arrhythmia if it does not respond to magnesium.

A 12-lead electrocardiogram from a 5-year-old child with active viral myocarditis. The electrocardiogram demonstrates salvos of nonsustained ventricular tachycardia. Note the very low voltages in the lateral leads.

Long QT Syndrome

Significant clinical, research as well as genetic and therapeutic advances in the diagnosis of LQTS have made this channelopathy one of the most exciting and enlightening bench-to-bed success stories in the field of cardiology. LQTS ( Fig. 22.22 ) is a disease of cardiac repolarization characterized by a prolonged QT interval on the ECG, a risk for syncope, seizures, and sudden death due to TdP that can terminate spontaneously or degenerate into VF. Patients are increasingly diagnosed in the presymptomatic phase due to cascade family screening. Cascade screening identifies affected family members and presymptomatic therapy can save lives. LQTS, like many cardiac diseases of genetic origin, is characterized by incomplete penetrance and variable expressivity.

Three-channel Holter monitor in a 2-month-old with known LQT1. The Holter monitor demonstrates profound QT prolongation along with a pattern that suggests T-wave alternans. The baseline QTc on the electrocardiogram was 590 ms.

QT prolongation, a consequence of disordered cardiac repolarization, is due to mutations that encode cardiac ion channels or their accessory subunits. To date there are 17 LQTS-susceptibility genes that account for approximately 75% to 80% of clinical disease. The majority of patients are affected by the earliest of these identified; mutations in KCNQ1 (LQT1), KCNH2 (LQT2) and SCN5A (LQT3). Loss-of-function mutations in KCNQ1 -encoded Kv7.1 channels and KCNH2 -encoded Kv11.1 channels lead to a decrease in I _Ks and I _Kr , respectively. Normally, due to its fast inactivation (voltage-dependent closing), Nav1.5 does not conduct current (or only minimally) during the repolarization phases of the action potential. However, LQT3-linked mutations in SCN5A are gain-of-function mutations that impair the inactivation of Nav1.5, resulting in a late (sustained or persistent) depolarizing Na ⁺ current ( I Na , L).

Genetic testing in LQTS has allowed better understanding the phenotype-genotype correlations. There are clinical features that are mutation-specific but also features that are common to the entire group. Understanding the unique features of the specific mutations has led to gene-specific counseling and therapy. However, it is clear that the phenotype of patients with LQTS is affected by more than the single gene mutations. Genotype–phenotype studies have shown differences in the effects of the autonomic nervous system on the phenotype in different types of LQTS. Assessing large populations with the same genetic mutation has uncovered differences between individuals with the identical mutations, some of which are based on autonomic nervous system responses. For example, in a large LQT1 kindred with an A341V mutation in KCNQ1 , those with slower heart rates were at lower risk of developing symptoms. In addition to the phenotypic differences noted in LQTS patients, even those carrying the same mutation, there are variations in disease expression in single individuals over time. Fever, medications, and electrolyte levels factor into disease expression. Medications have long been associated with arrhythmic events in LQTS patients, unmasking the disease in some and contributing to sudden death in others. Most drugs affect KCNH2 -encoded Kv11.1 channels, possibly as a consequence of the channel structure. This effect has been utilized for benefit when one considers that this is the mechanism of effect for most antiarrhythmic agents but has been a clear detriment in other medications, some of which have been removed from the market as a consequence of this effect.

Patient age and sex modify the QT interval and disease expression. Our youngest patients, those identified in utero, often have the most concerning disease expression. Symptomatic infants with LQTS represent a high-risk group. Using data from the International LQTS Registry, Spazzolini et al. focused on a group with cardiac events occurring in the first year of life and on the prognostic significance of these events to age 10 years. They found that LQTS infants with QTc prolongation, slow heart rate, and female sex are at increased risk for cardiac events during the first year of life. Infants who experienced a cardiac arrest in the first year of life were at very high risk for near fatal or fatal cardiac events during the next 10 years. Male LQTS patients experience 90% of the first cardiac events before adolescence, whereas female patients experience their first events in the postadolescence period. This has been attributed in part by a complex interplay between sex hormones and cardiac ion channel current. The net effect of sex hormones on the expression and function of cardiac ion channels is thought to be a lower repolarization reserve in women than in men, rendering women more prone to QTc prolongation and TdP occurrence in the presence of a LQTS-causing mutation.

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  Long QT1 ( KCNQI ): The most common type of LQTS and the first described is LQT1. LQT1 patients are particularly vulnerable to life-threatening events during exertion and are most responsive to β-blockers. Swimming is a known trigger.

  
  
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  Long QT2 ( KCNH2 ): LQT2 patients may be at risk for life-threatening arrhythmias during sudden noises and startle. LQT2 is particularly known to be life-threatening in females of childbearing age as compared with male counterparts of the same generational age. Postpartum LQT2 women are also a high-risk cohort.

  
  
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  Long QT3 ( SCN5A ): LQT3 events occur during times of relative bradycardia and thus may manifest during sleep. Patients with SCN5A mutations have a Na ⁺ channel gain-of-function mutation. In some LQT3 patients with phenotypic prolonged QT intervals, shortening of the QT intervals with lidocaine or mexiletine has established a paradigm shift from β-blockers alone to consideration of a Na ⁺ blocker in conjunction with a β-blocker.

  
  
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  Neonatal LQTS: Symptomatic LQTS in the first year of life is of significant concern, and this is a high-risk patient population. Reports of extreme bradycardia as well as 2 : 1 functional AV block have raised QT awareness. Although early mortality rates for neonates with LQTS and 2 : 1 AV block was as high as 50% to 60%, recent publications have shown a more optimistic outcome with use of β-blockers, occasional mexiletine, and pacing. Important in this retrospective review was the observation that 75% of patients have improvement in their conduction (2 : 1 to 1 : 1) over the first year of life.

Treatmentof Long QT Syndrome

Traditionally, the management options with LQTS were primarily determined by a combination of factors, including the baseline QT interval and clinical symptoms. Untreated patients with symptomatic LQTS or significant QT prolongation are at a risk of developing syncope and sudden cardiac death. Given that effective treatments are available, there is little excuse not to recommend treatment for symptomatic LQTS patients and asymptomatic patients who are genotype/phenotype positive. The treatment of asymptomatic patients and those with borderline QT prolongation (460 to 470 ms) is more controversial. Treatment can be divided antiadrenergic therapies (β-blockers and left cardiac sympathetic denervation [LCSD]), ICDs, and gene-specific therapies such as mexiletine. In addition, avoidance of excessive stimulant intake, heat exhaustion, electrolyte perturbations, and medications known to prolong the QT interval should be avoided.

Catecholaminergic Polymorphic Ventricular Tachycardia

CPVT, a rare genetic arrhythmia syndrome, is characterized by polymorphic VT with physical or emotional stress in patients with a structurally normal heart ( Fig. 22.23 ). CPVT can be a particularly lethal channelopathy, resulting in symptoms during childhood and cardiac arrest as a frequent presentation. Mutations in the genes encoding the cardiac ryanodine receptor 2 calcium release channel or cardiac calsequestrin are implicated in approximately 60% of cases. These proteins regulate intracellular calcium homeostasis in myocytes, and disruptions result in excessive release of calcium from the sarcoplasmic reticulum; they are also arrhythmogenic. Although SVT can occur in CPVT, the typical arrhythmias are bidirectional or polymorphic VT. The resting ECG is usually normal, but exercise testing results in a gradually increasing burden of ventricular arrhythmia as exercise progresses. β-blockers are the mainstay of therapy, but many argue that a second line of therapy is required in symptomatic CPVT patients and those with arrhythmias despite β-blockade. There is compelling evidence that the addition of flecainide to β-blocker therapy is superior. A randomized placebo-controlled crossover study demonstrated that flecainide added to β-blocker therapy was superior to maximal β-blocker therapy alone in reducing exercise-induced ventricular arrhythmias in patients with CPVT. LCSD can be an effective addition if flecainide is not tolerated or medication noncompliance is an issue. In a large multicenter retrospective cohort study of CPVT in children, 226 patients were studied. Symptoms were common at presentation, present in 78% with symptom onset at about age 10 years, but often with a delay to diagnosis of 0.5 (0 to 2.6) years. Syncope, cardiac arrest, and treatment failure occurred more often in probands. Although β-blockers were prescribed in 97%, 25% experienced at least one treatment failure event. ICDs were used in 54% and associated with electrical storm in 18%. Flecainide was used in 24% and LCSD in 8%. The 6 deaths (3%) during a cumulative follow-up of 788 patient-years confirm a malignant phenotype, with probands being more severely affected. Treatment failure, noncompliance, and subtherapeutic dosing were often reported, and ICDs were common despite numerous device-related complications. Treatment failure was rare in the 25% of patients on flecainide.

A 12-lead electrocardiogram demonstrating an irregular wide rhythm with alternating QRS complex patterns (arrows) and axes in a patient with catecholaminergic polymorphic ventricular tachycardia.

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