Section 3: Disorders of Rhythm

HISTORY AND INTRODUCTION

The field of cardiac electrophysiology was ushered in with the development of the electrocardiogram (ECG) by Einthoven at the turn of the twentieth century. Subsequent recording of cellular membrane currents demonstrated that the body surface ECG is the timed sum of the cellular action potentials in the atria and ventricles. In the late 1960s, the development of intracavitary recording, in particular, His bundle electrograms, marked the beginning of contemporary clinical electrophysiology. Adoption of radiofrequency (RF) technology to ablate cardiac tissue in the early 1990s heralded the birth of interventional cardiac electrophysiology.

The clinical problem of sudden death caused by ventricular arrhythmias, most commonly in the setting of coronary artery obstruction, was recognized as early as the late nineteenth century. The problem was vexing and led to the development of pharmacologic and nonpharmacologic therapies, including transthoracic defibrillators, cardiac massage, and, most recently, implantable intravascular and subcutaneous defibrillators. Over time the limitations of antiarrhythmic drug therapy have been highlighted repeatedly in clinical trials, and now ablation and devices are first-line therapy for a number of cardiac arrhythmias.

In the last two decades, the genetic basis of a number of heritable arrhythmias has been elucidated, revealing important insights into the mechanisms not only of these rare arrhythmias but also of similar rhythm disturbances observed in more common forms of heart disease.

DESCRIPTIVE PHYSIOLOGY

The normal cardiac impulse is generated by pacemaker cells in the sinoatrial (SA) node situated at the junction of the right atrium and the superior vena cava (see Fig. 235-1). This impulse is transmitted slowly through nodal tissue to the anatomically complex atria, where it is conducted more rapidly to the atrioventricular node (AVN), inscribing the P wave of the ECG (see Fig. 235-2). There is a perceptible delay in conduction through the anatomically and functionally heterogeneous AV. The time needed for activation of the atria and the AVN delay is represented as the PR interval of the ECG. The AVN is the only electrical connection between the atria and the ventricles in the normal heart. The electrical impulse emerges from the AVN and is transmitted to the His-Purkinje system, specifically the common bundle of His, then the left and right bundle branches, and then to the Purkinje network, facilitating activation of ventricular muscle. In normal circumstances, the ventricles are activated rapidly in a well-defined fashion that is determined by the course of the Purkinje network, and this inscribes the QRS complex (see Fig. 235-2). Recovery of electrical excitability occurs more slowly and is governed by the time of activation and duration of regional action potentials. The relative brevity of epicardial action potentials in the ventricle results in repolarization that occurs first on the epicardial surface and then proceeds to the endocardium, which inscribes a T wave normally of the same polarity as the QRS complex. The duration of ventricular activation and recovery is determined by the action potential duration and is represented on the body surface ECG by the QT interval (see Fig. 235-2).

Cardiac myocytes exhibit a characteristically long action potential (200–400 ms) compared with neurons and skeletal muscle cells (1–5 ms). The action potential profile is sculpted by the orchestrated activity of multiple distinctive time- and voltage-dependent ionic currents (Fig. 238-1A). The currents are carried by transmembrane proteins that passively conduct ions down their electrochemical gradients through selective pores (ion channels), actively transport ions against their electrochemical gradient (pumps, transporters), or electrogenically exchange ionic species (exchangers).

Action potentials in the heart are regionally distinct. The regional variability in cardiac action potentials is a result of differences in the number and types of ion channel proteins expressed by different cell types in the heart. Further, unique sets of ionic currents are active in pacemaking and muscle cells, and the relative contributions of these currents may vary in the same cell type in different regions of the heart (Fig. 238-1A).

Ion channels are complex, multisubunit transmembrane glycoproteins that open and close in response to a number of biologic stimuli, including a change in membrane voltage, ligand binding (directly to the channel or to a G protein–coupled receptor), and mechanical deformation (Fig. 238-2). Other ion motive exchangers and transporters contribute importantly to cellular excitability in the heart. Ion pumps establish and maintain the ionic gradients across the cell membrane that serve as the driving force for current flow through ion channels. Transporters or exchangers that do not move ions in an electrically neutral manner (e.g., the sodium-calcium exchanger transports three Na⁺ for one Ca²⁺) are termed electrogenic and contribute directly to the action potential profile.

The most abundant superfamily of ion channels expressed in the heart is voltage gated. Several structural themes are common to all voltage-dependent ion channels. First, the architecture is modular, consisting either of four homologous subunits (e.g., K channels) or of four internally homologous domains (e.g., Na and Ca channels). Second, the proteins fold around a central pore lined by amino acids that exhibit exquisite conservation within a given channel family of like selectivity (e.g., all Na channels have very similar P segments). Third, the general strategy for activation gating (opening and closing in response to changes in membrane voltage) is highly conserved: the fourth transmembrane segment (S4), studded with positively charged residues, lies within the membrane field and moves in response to depolarization, opening the channel. Fourth, most ion channel complexes include not only the pore-forming proteins (α subunits) but also auxiliary subunits (e.g., β subunits) that modify channel function (Fig. 238-2).

Na and Ca channels are the primary carriers of depolarizing current in both the atria and the ventricles; inactivation of these currents and activation of repolarizing K currents hyperpolarize the heart cells, reestablishing the negative resting membrane potential (Fig. 238-1B). The plateau phase is a time when little current is flowing, and relatively minor changes in depolarizing or repolarizing currents can have profound effects on the shape and duration of the action profile. Mutations in subunits of these channel proteins produce arrhythmogenic alterations in the action potentials that cause long and short QT syndrome, Brugada syndrome, idiopathic ventricular fibrillation, familial atrial fibrillation, and some forms of conduction system disease.

MECHANISMS OF CARDIAC ARRHYTHMIAS

Cardiac arrhythmias result from abnormalities of electrical impulse generation, conduction, or both. Bradyarrhythmias typically arise from disturbances in impulse formation at the level of the SA node or from disturbances in impulse propagation at any level, including exit block from the sinus node, conduction block in the AVN, and impaired conduction in the His-Purkinje system. Tachyarrhythmias can be classified according to mechanism, including enhanced automaticity (spontaneous depolarization of atrial, junctional, or ventricular pacemakers), triggered arrhythmias (initiated by afterdepolarizations occurring during or immediately after cardiac repolarization, during phase 3 or 4 of the action potential), or reentry (circus propagation of a depolarizing wavefront). A variety of mapping and pacing maneuvers typically performed during invasive electrophysiologic testing can often determine the underlying mechanism of a tachyarrhythmia (Table 238-1).

Alterations in Impulse Initiation: Automaticity

Spontaneous (phase 4) diastolic depolarization underlies the property of automaticity characteristic of pacemaking cells in the SA and atrioventricular (AV) nodes, His-Purkinje system, coronary sinus, and pulmonary veins. Phase 4 depolarization results from the concerted action of a number of ionic currents, including K⁺ currents, Ca²⁺ currents, electrogenic Na, K-ATPase, the Na-Ca exchanger, and the so-called funny, or pacemaker, current (I_f); however, the relative importance of these currents remains controversial.

The rate of phase 4 depolarization and, therefore, the firing rates of pacemaker cells are dynamically regulated. Prominent among the factors that modulate phase 4 is autonomic nervous system tone. The negative chronotropic effect of activation of the parasympathetic nervous system is a result of the release of acetylcholine that binds to muscarinic receptors, releasing G protein βγ subunits that activate a potassium current (I_KACh) in nodal and atrial cells. The resulting increase in K⁺ conductance opposes membrane depolarization, slowing the rate of rise of phase 4 of the action potential. Conversely, augmentation of sympathetic nervous system tone increases myocardial catecholamine concentrations, which activate both α- and β-adrenergic receptors. The effect of β₁-adrenergic stimulation predominates in pacemaking cells, augmenting both L-type Ca current (I_Ca-L) and I_f, thus increasing the slope of phase 4. Enhanced sympathetic nervous system activity can dramatically increase the rate of firing of SA nodal cells, producing sinus tachycardia with rates >200 beats/min. By contrast, the increased rate of firing of Purkinje cells is more limited, rarely producing ventricular tachyarrhythmias >120 beats/min.

Normal automaticity may be affected by a number of other factors associated with heart disease. Hypokalemia and ischemia may reduce the activity of Na, K-ATPase, thereby reducing the background repolarizing current and enhancing phase 4 diastolic depolarization. The end result would be an increase in the spontaneous firing rate of pacemaking cells. Modest increases in extracellular potassium may render the maximum diastolic potential more positive, thereby also increasing the firing rate of pacemaking cells. A more significant increase in [K⁺]_o, however, renders the heart inexcitable by depolarizing the membrane potential.

Normal or enhanced automaticity of subsidiary latent pacemakers produces escape rhythms in the setting of failure of more dominant pacemakers. Suppression of a pacemaker cell by a faster rhythm leads to an increased intracellular Na⁺ load ([Na⁺]_i), and extrusion of Na⁺ from the cell by Na, K-ATPase produces an increased background repolarizing current that slows phase 4 diastolic depolarization. At slower rates, [Na⁺]_i is decreased, as is the activity of the Na, K-ATPase, resulting in progressively more rapid diastolic depolarization and warm-up of the tachycardia rate. Overdrive suppression and warm-up are characteristic of, but may not be observed in, all automatic tachycardias. Abnormal conduction into tissue with enhanced automaticity (entrance block) may blunt or eliminate the phenomena of overdrive suppression and warm-up of automatic tissue.

Abnormal automaticity may produce atrial tachycardia, accelerated idioventricular rhythms, and ventricular tachycardia, particularly associated with ischemia and reperfusion. It has also been suggested that injury currents at the borders of ischemic myocardium may depolarize adjacent nonischemic tissue, predisposing to automatic ventricular tachycardia.

Afterdepolarizations and Triggered Automaticity

Triggered automaticity or activity refers to impulse initiation that is dependent on afterdepolarizations (Fig. 238-3). Afterdepolarizations are membrane voltage oscillations that occur during (early afterdepolarizations, EADs) or after (delayed afterdepolarizations, DADs) an action potential.

The cellular feature common to the induction of DADs is the presence of an increased Ca²⁺ load in the cytosol and sarcoplasmic reticulum. Digitalis glycoside toxicity, catecholamines, and ischemia all can enhance Ca²⁺ loading sufficiently to produce DADs. Accumulation of lysophospholipids in ischemic myocardium with consequent Na⁺ and Ca²⁺ overload has been suggested as a mechanism for DADs and triggered automaticity. Cells from damaged areas or cells that survive a myocardial infarction may display spontaneous release of calcium from the sarcoplasmic reticulum, and this may generate “waves” of intracellular calcium elevation and arrhythmias.

EADs occur during the action potential and interrupt the orderly repolarization of the myocyte. Traditionally, EADs have been thought to arise from action potential prolongation and reactivation of depolarizing currents, but more recent experimental evidence suggests a previously unappreciated interrelationship between intracellular calcium loading and EADs. Cytosolic calcium may increase when action potentials are prolonged. This, in turn, appears to enhance L-type Ca current, further prolonging action potential duration as well as providing the inward current driving EADs. Intracellular calcium loading by action potential prolongation may also enhance the likelihood of DADs. The interrelationship among intracellular [Ca²⁺], EADs, and DADs may be one explanation for the susceptibility of hearts that are calcium loaded (e.g., in ischemia or congestive heart failure [CHF]) to develop arrhythmias, particularly on exposure to action potential–prolonging drugs.

EAD-triggered arrhythmias exhibit rate dependence. In general, the amplitude of an EAD is augmented at slow rates when action potentials are longer. Indeed, a fundamental condition that underlies the development of EADs is action potential and QT prolongation. Hypokalemia, hypomagnesemia, bradycardia, and, most commonly, drugs can predispose to the generation of EADs, invariably in the context of prolonging the action potential. Antiarrhythmics with class IA and III action (see below) produce action potential and QT prolongation intended to be therapeutic but frequently causing arrhythmias. Noncardiac drugs such as phenothiazines, nonsedating antihistamines, and some antibiotics can also prolong the action potential duration and predispose to EAD-mediated triggered arrhythmias. Decreased [K⁺]_o paradoxically may decrease membrane potassium currents (particularly the delayed rectifier current, I_Kr) in the ventricular myocyte, explaining why hypokalemia causes action potential prolongation and EADs. In fact, potassium infusions in patients with the congenital long QT syndrome (LQTS) and in those with drug-induced acquired QT prolongation shorten the QT interval.

EAD-mediated triggered activity probably underlies initiation of the characteristic polymorphic ventricular tachycardia, torsades des pointes, seen in patients with congenital and acquired forms of LQTS. Structural heart disease, such as cardiac hypertrophy and heart failure, may also delay ventricular repolarization (so-called electrical remodeling) and predispose to arrhythmias related to abnormalities of repolarization. The abnormalities of repolarization in hypertrophy and heart failure are often magnified by concomitant drug therapy or electrolyte disturbances.

Abnormal Impulse Conduction: Reentry

The most common arrhythmia mechanism is reentry resulting from abnormal electrical impulse conduction and is defined as the circulation of an activation wave around an inexcitable obstacle. The requirements for reentry are two electrophysiologically dissimilar pathways for impulse propagation around an inexcitable region (Fig. 238-4). Reentry can occur around a fixed anatomic structure (e.g., myocardial scar), with a stable pattern of cardiac depolarization moving in series over the anterograde and retrograde limbs of the circuit. This form of reentry, referred to as anatomic reentry or excitable gap reentry (see below), is initiated when a depolarizing wavefront encounters an area of unidirectional conduction block in the retrograde limb of the circuit. Conduction across the anterograde limb occurs with a delay that, if of sufficient duration, allows for recovery of conduction in the retrograde limb with reentry of the depolarization wave into the retrograde limb of the circuit. Sustained reentry requires that the functional dimension of depolarized tissue or the tachycardia wavelength (λ = conduction velocity × refractory period) fits within the total anatomic length of the circuit, referred to as the path length. When the path length of the circuit exceeds the λ of the tachycardia, the region between the head of the activation wave and the refractory tail is referred to as the excitable gap. Anatomically determined, excitable gap reentry can explain several clinically important tachycardias, such as AV reentry, atrial flutter, bundle branch reentry ventricular tachycardia, and ventricular tachycardia in scarred myocardium.

Reentrant arrhythmias may exist in the heart in the absence of an excitable gap and with a tachycardia wavelength nearly the same size as the path length. In this case, the wavefront propagates through partially refractory tissue without a fixed anatomic obstacle and no fully excitable gap; this is referred to as leading circle reentry, a form of functional reentry (reentry that depends on functional properties of the tissue). Unlike excitable gap reentry, there is no fixed anatomic circuit in leading circle reentry, and it may, therefore, not be possible to disrupt the tachycardia with pacing or destruction of a part of the circuit. Furthermore, the circuit in leading circle reentry tends to be less stable than that in excitable gap reentrant arrhythmias, with large variations in cycle length and a predilection to termination. There is strong evidence to suggest that less organized arrhythmias, such as atrial and ventricular fibrillation, are associated with more complex activation of the heart and are due to functional reentry.

Catheter-based and pharmacologic therapies for reentrant arrhythmias are designed to disrupt the anatomic circuit or alter the relationship between the wavelength and path length of the arrhythmia circuit, eliminating pathologic conduction. For example, antiarrhythmic drugs that prolong the action potential (Class III) are effective if they sufficiently prolong the λ such that it can no longer fit within the anatomic circuit. Catheter ablation is often undertaken with the goal of identifying and destroying a critical limb of the reentrant circuit (i.e., ablation of the cavotricuspid isthmus in the treatment of typical, right atrial flutter). Due to the less defined pathways of myocardial activation seen in functional reentry, ablation of these rhythms tends to target initiating triggers (e.g., pulmonary vein potentials in catheter ablation of atrial fibrillation) rather than the anatomic circuit.

Structural heart disease is associated with changes in conduction and refractoriness that increase the risk of reentrant arrhythmias. Chronically ischemic myocardium exhibits a downregulation of the gap junction channel protein (connexin 43) that carries intercellular ionic current. The border zones of infarcted and failing ventricular myocardium exhibit not only functional alterations of ionic currents but also remodeling of tissue and altered distribution of gap junctions. The changes in gap junction channel expression and distribution, in combination with macroscopic tissue alterations, support a role for slowed conduction in reentrant arrhythmias that complicate chronic coronary artery disease (CAD). Aged human atrial myocardium exhibits altered conduction, manifest as highly fractionated atrial electrograms, producing an ideal substrate for the reentry that may underlie the very common development of atrial fibrillation in the elderly.

APPROACH TO THE PATIENT

TREATMENT

FURTHER READING

INTRODUCTION

Electrical activation of the heart normally originates in the sinoatrial (SA) node, the predominant pacemaker. Other subsidiary pacemakers in the atrioventricular (AV) node, specialized conducting system, and muscle may initiate electrical activation if the SA node is dysfunctional or suppressed. Typically, subsidiary pacemakers discharge at a slower rate and, in the absence of an appropriate increase in stroke volume, may result in tissue hypoperfusion.

Spontaneous activation and contraction of the heart are a consequence of the specialized pacemaking tissue in these anatomic locales. As described in Chap. 238, action potentials in the heart are regionally heterogeneous. The action potentials in cells isolated from nodal tissue are distinct from those recorded from atrial and ventricular myocytes (Fig. 239-1). The complement of ionic currents present in nodal cells results in a less negative resting membrane potential compared with atrial or ventricular myocytes. Electrical diastole in nodal cells is characterized by slow diastolic depolarization (phase 4), which generates an action potential as the membrane voltage reaches threshold. The action potential upstrokes (phase 0) are slow compared with atrial or ventricular myocytes, being mediated by calcium rather than sodium current. Cells with properties of SA and AV nodal tissue are electrically connected to the remainder of the myocardium by cells with an electrophysiologic phenotype between that of nodal cells and that of atrial or ventricular myocytes. Cells in the SA node exhibit the most rapid phase 4 depolarization and thus are the dominant pacemakers in a normal heart.

Bradycardia results from a failure of either impulse initiation or impulse conduction. Failure of impulse initiation may be caused by depressed automaticity resulting from a slowing or failure of phase 4 diastolic depolarization (Fig. 239-2), which may result from disease or exposure to drugs. Prominently, the autonomic nervous system modulates the rate of phase 4 diastolic depolarization and thus the firing rate of both primary (SA node) and subsidiary pacemakers. Failure of conduction of an impulse from nodal tissue to atrial or ventricular myocardium may produce bradycardia as a result of exit block. Conditions that alter the activation and connectivity of cells (e.g., fibrosis) in the heart may result in failure of impulse conduction.

SA node dysfunction and AV conduction block are the most common causes of pathologic bradycardia. SA node dysfunction may be difficult to distinguish from physiologic sinus bradycardia, particularly in the young. SA node dysfunction increases in frequency between the fifth and sixth decades of life and should be considered in patients with fatigue, exercise intolerance, or syncope and sinus bradycardia.

Permanent pacemaking is the only reliable therapy for symptomatic bradycardia in the absence of extrinsic and reversible etiologies such as increased vagal tone, hypoxia, hypothermia, and drugs (Table 239-1). Approximately 50% of the 160,000 permanent pacemakers implanted in the United States and 20–30% of those in Europe were implanted for SA node disease.

STRUCTURE AND PHYSIOLOGY OF THE SA NODE

The SA node is composed of a cluster of small fusiform cells in the sulcus terminalis on the epicardial surface of the heart at the right atrial–superior vena caval junction, where they envelop the SA nodal artery. The SA node is structurally heterogeneous, but the central prototypic nodal cells have fewer distinct myofibrils than does the surrounding atrial myocardium, no intercalated disks visible on light microscopy, a poorly developed sarcoplasmic reticulum, and no T-tubules. Cells in the peripheral regions of the SA node are transitional in both structure and function. The SA nodal artery arises from the right coronary artery in 55–60% and the left circumflex artery in 40–45% of persons. The SA node is richly innervated by sympathetic and parasympathetic nerves and ganglia.

Irregular and slow propagation of impulses from the SA node can be explained by the electrophysiology of nodal cells and the structure of the SA node itself. The action potentials of SA nodal cells are characterized by a relatively depolarized membrane potential (Fig. 239-1) of −40 to −60 mV, slow phase 0 upstroke, and relatively rapid phase 4 diastolic depolarization compared with the action potentials recorded in cardiac muscle cells. The relative absence of inward rectifier potassium current (I_K1) accounts for the depolarized membrane potential; the slow upstroke of phase 0 results from the absence of available fast sodium current (I_Na) and is mediated by L-type calcium current (I_Ca-L); and phase 4 depolarization is a result of the aggregate activity of a number of ionic currents. Prominently, both L- and T-type (I_Ca-T) calcium currents, the pacemaker current (so-called funny current, or I_f) formed by hyperpolarization-activated cyclic nucleotide-gated channels, and the electrogenic sodium-calcium exchanger provide depolarizing current that is antagonized by delayed rectifier (I_Kr) and acetylcholine-gated (I_KACh) potassium currents. I_Ca-L, I_Ca-T, and I_f are modulated by β-adrenergic stimulation and I_KACh by vagal stimulation, explaining the exquisite sensitivity of diastolic depolarization to autonomic nervous system activity. The slow conduction within the SA node is explained by the absence of I_Na and poor electrical coupling of cells in the node, resulting from sizable amounts of interstitial tissue and a low abundance of gap junctions. The poor coupling allows for graded electrophysiologic properties within the node, with the peripheral transitional cells being silenced by electrotonic coupling to atrial myocardium.

ETIOLOGY OF SA NODAL DISEASE

SA nodal dysfunction has been classified as intrinsic or extrinsic. The distinction is important because extrinsic dysfunction is often reversible and generally should be corrected before pacemaker therapy is considered (Table 239-1). The most common causes of extrinsic SA node dysfunction are drugs and autonomic nervous system influences that suppress automaticity and/or compromise conduction. Other extrinsic causes include hypothyroidism, sleep apnea, and conditions likely to occur in critically ill patients such as hypothermia, hypoxia, increased intracranial pressure (Cushing’s response), and endotracheal suctioning via activation of the vagus nerve.

Intrinsic sinus node dysfunction is degenerative and often is characterized pathologically by fibrous replacement of the SA node or its connections to the atrium. Acute and chronic coronary artery disease (CAD) may be associated with SA node dysfunction, although in the setting of acute myocardial infarction (MI; typically inferior), the abnormalities are transient. Inflammatory processes may alter SA node function, ultimately producing replacement fibrosis. Pericarditis, myocarditis, and rheumatic heart disease have been associated with SA nodal disease with sinus bradycardia, sinus arrest, and exit block. Carditis associated with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and mixed connective tissue disorders (MCTDs) may also affect SA node structure and function. Senile amyloidosis is an infiltrative disorder in patients typically in the ninth decade of life; deposition of amyloid protein in the atrial myocardium can impair SA node function. Some SA node disease is iatrogenic and results from direct injury to the SA node during cardiothoracic surgery.

Rare heritable forms of sinus node disease have been described, and several have been characterized genetically. Autosomal dominant sinus node dysfunction in conjunction with supraventricular tachycardia (i.e., tachycardia-bradycardia variant of sick-sinus syndrome [SSS2]) has been linked to mutations in the pacemaker current (I_f) subunit gene HCN4 on chromosome 15. An autosomal recessive form of SSS1 with the prominent feature of atrial inexcitability and absence of P waves on the electrocardiogram (ECG) is caused by mutations in the cardiac sodium channel gene, SCN5A, on chromosome 3. Variants in myosin heavy chain 6 (MYH6) increase the susceptibility to SSS (SSS3). SA node dysfunction associated with myopia has been described but not genetically characterized. There are several neuromuscular diseases, including Kearns-Sayre syndrome (ophthalmoplegia, pigmentary degeneration of the retina, and cardiomyopathy) and myotonic dystrophy that have a predilection for the conducting system and SA node.

SSS in both the young and the elderly is associated with an increase in fibrous tissue in the SA node. The onset of SSS may be hastened by coexisting disease, such as CAD, diabetes mellitus, hypertension, and valvular diseases and cardiomyopathies.

CLINICAL FEATURES OF SA NODE DISEASE

SA node dysfunction may be completely asymptomatic and manifest as an ECG anomaly such as sinus bradycardia; sinus arrest and exit block; or alternating supraventricular tachycardia, usually atrial fibrillation, and bradycardia. Symptoms associated with SA node dysfunction, in particular tachycardia-bradycardia syndrome, may be related to both slow and fast heart rates. For example, tachycardia may be associated with palpitations, angina pectoris, and heart failure, and bradycardia may be associated with hypotension, syncope, presyncope, fatigue, and weakness. In the setting of SSS, overdrive suppression of the SA node may result in prolonged pauses and syncope upon termination of the tachycardia. In many cases, symptoms associated with SA node dysfunction result from concomitant cardiovascular disease. A significant minority of patients with SSS develop signs and symptoms of heart failure that may be related to slow or fast heart rates.

One-third to one-half of patients with SA node dysfunction develop supraventricular tachycardia, usually atrial fibrillation or atrial flutter. The incidence of persistent atrial fibrillation in patients with SA node dysfunction increases with advanced age, hypertension, diabetes mellitus, left ventricular dilation, valvular heart disease, and ventricular pacing. Remarkably, some symptomatic patients may experience an improvement in symptoms with the development of atrial fibrillation, presumably from an increase in their average heart rate. Patients with the tachycardia-bradycardia variant of SSS, similar to patients with atrial fibrillation, are at risk for thromboembolism, and those at greatest risk, including patients aged ≥65 years and patients with a prior history of stroke, valvular heart disease, left ventricular dysfunction, or atrial enlargement, should be treated with anticoagulants. Up to one-quarter of patients with SA node disease will have concurrent AV conduction disease, although only a minority will require specific therapy for high-grade AV block.

The natural history of SA node dysfunction is one of varying intensity of symptoms even in patients who present with syncope. Symptoms related to SA node dysfunction may be significant, but overall longevity usually is not compromised in the absence of other significant comorbid conditions. These features of the natural history need to be taken into account in considering therapy for these patients.

ELECTROCARDIOGRAPHY OF SA NODE DISEASE

The electrocardiographic manifestations of SA node dysfunction include sinus bradycardia, sinus pauses, sinus arrest, sinus exit block, tachycardia (in SSS), and chronotropic incompetence. It is often difficult to distinguish pathologic from physiologic sinus bradycardia. By definition, sinus bradycardia is a rhythm driven by the SA node with a rate of <60 beats/min; sinus bradycardia is very common and typically benign. Resting heart rates <60 beats/min are very common in young healthy individuals and physically conditioned subjects. A sinus rate of <40 beats/min in the awake state in the absence of physical conditioning generally is considered abnormal. Sinus pauses and sinus arrest result from failure of the SA node to discharge, producing a pause without P waves visible on the ECG (Fig. 239-3). Sinus pauses of up to 3 s are common in awake athletes, and pauses of this duration or longer may be observed in asymptomatic elderly subjects. Intermittent failure of conduction from the SA node produces sinus exit block. The severity of sinus exit block may vary in a manner similar to that of AV block (Chap. 240). Prolongation of conduction from the sinus node will not be apparent on the ECG; second-degree SA block will produce intermittent conduction from the SA node and a regularly irregular atrial rhythm.

Type I second-degree SA block results from progressive prolongation of SA node conduction with intermittent failure of the impulses originating in the sinus node to conduct to the surrounding atrial tissue. Second-degree SA block appears on the ECG as an intermittent absence of P waves (Fig. 239-4). In type II second-degree SA block, there is no change in SA node conduction before the pause. Complete or third-degree SA block results in no P waves on the ECG. Tachycardia-bradycardia syndrome is manifest as alternating sinus bradycardia and atrial tachyarrhythmias. Although atrial tachycardia, atrial flutter, and atrial fibrillation may be observed, the latter is the most common tachycardia. Chronotropic incompetence is the inability to increase the heart rate in response to exercise or other stress appropriately and is defined in greater detail below.

DIAGNOSTIC TESTING

SA node dysfunction is most commonly a clinical or electrocardiographic diagnosis. Sinus bradycardia or pauses on the resting ECG are rarely sufficient to diagnose SA node disease, and longer-term recording and symptom correlation generally are required. Symptoms in the absence of sinus bradyarrhythmias may be sufficient to exclude a diagnosis of SA node dysfunction.

Electrocardiographic recording plays a central role in the diagnosis and management of SA node dysfunction. Despite the limitations of the resting ECG, longer-term recording employing Holter or event monitors may permit correlation of symptoms with the cardiac rhythm. Many contemporary event monitors may be automatically triggered to record the ECG when certain programmed heart rate criteria are met. Implantable ECG monitors permit long-term recording (12–18 months) in particularly challenging patients.

Failure to increase the heart rate with exercise is referred to as chronotropic incompetence. This is alternatively defined as failure to reach 85% of predicted maximal heart rate at peak exercise or failure to achieve a heart rate >100 beats/min with exercise or a maximal heart rate with exercise less than two standard deviations below that of an age-matched control population. Exercise testing may be useful in discriminating chronotropic incompetence from resting bradycardia and may aid in the identification of the mechanism of exercise intolerance.

Autonomic nervous system testing is useful in diagnosing carotid sinus hypersensitivity; pauses >3 s are consistent with the diagnosis but may be present in asymptomatic elderly subjects. Determining the intrinsic heart rate (IHR) may distinguish SA node dysfunction from slow heart rates that result from high vagal tone. The normal IHR after administration of 0.2 mg/kg propranolol and 0.04 mg/kg atropine is 117.2 − (0.53 × age) in beats/min; a low IHR is indicative of SA disease.

Electrophysiologic testing may play a role in the assessment of patients with presumed SA node dysfunction and in the evaluation of syncope, particularly in the setting of structural heart disease. In this circumstance, electrophysiologic testing is used to rule out more malignant etiologies of syncope, such as ventricular tachyarrhythmias and AV conduction block. There are several ways to assess SA node function invasively. They include the sinus node recovery time (SNRT), defined as the longest pause after cessation of overdrive pacing of the right atrium near the SA node (normal: <1500 ms or, corrected for sinus cycle length, <550 ms), and the sinoatrial conduction time (SACT), defined as one-half the difference between the intrinsic sinus cycle length and a noncompensatory pause after a premature atrial stimulus (normal <125 ms). The combination of an abnormal SNRT, an abnormal SACT, and a low IHR is a sensitive and specific indicator of intrinsic SA node disease.

TREATMENT

FURTHER READING

INTRODUCTION

Impulses generated in the sinoatrial (SA) node or in ectopic atrial loci are conducted to the ventricles through the electrically and anatomically complex atrioventricular (AV) node. As described in Chap. 239, the electrophysiologic properties of nodal tissue are distinct from atrial and ventricular myocardium. Cells located in the AV node sit at a relatively higher resting membrane potential than surrounding atrial and ventricular myocytes, exhibit spontaneous depolarization during phase 4 of the action potential, and have slower phase 0 depolarization (mediated by calcium influx in nodal tissue) than that seen in ventricular tissue (mediated by sodium influx).

Bradycardia may occur when conduction across the AV node is compromised, resulting in slow ventricular rates, with the possibility of attendant symptoms, including fatigue, syncope, and (if subsidiary pacemaker activity is insufficient) even death. It is important to recognize that in the setting of disturbed AV conduction, SA activation and atrial systole may occur at normal or even accelerated rates, while ventricular activation is either slowed or nonexistent. Transient AV conduction block is common in the young and is most likely the result of high vagal tone found in up to 10% of young adults. Acquired and persistent failure of AV conduction is decidedly rare in healthy adult populations, with an estimated incidence of 200 per million population per year. In the setting of myocardial ischemia, aging and fibrosis, or cardiac infiltrative diseases, however, persistent AV block is much more common.

As with symptomatic bradycardia arising from SA node dysfunction, permanent pacing is the only reliable therapy for symptoms arising from AV conduction block. Approximately 50% of the 160,000 permanent pacemakers implanted in the United States and 70–80% of those in Europe are implanted for disorders of AV conduction.

STRUCTURE AND PHYSIOLOGY OF THE AV NODE

The AV conduction axis is structurally complex, involving the atria and ventricles as well as the AV node. Unlike the SA node, the AV node is a subendocardial structure originating in the transitional zone, which is composed of aggregates of cells in the posterior-inferior right atrium. Superior, medial, and posterior transitional atrionodal bundles converge on the compact AV node. The compact AV node (~1 × 3 × 5 mm) is situated at the apex of the triangle of Koch, which is defined by the coronary sinus ostium posteriorly, the septal tricuspid valve annulus anteriorly, and the tendon of Todaro superiorly. The compact AV node continues as the penetrating AV bundle where it immediately traverses the central fibrous body and is in close proximity to the aortic, mitral, and tricuspid valve annuli; thus, it is subject to injury in the setting of valvular heart disease or its surgical treatment. The penetrating AV bundle continues through the annulus fibrosis and emerges along the ventricular septum adjacent to the membranous septum as the bundle of His. The right bundle branch (RBB) emerges from the distal AV bundle in a band that traverses the right ventricle (moderator band). In contrast, the left bundle branch (LBB) is a broad subendocardial sheet of tissue on the septal left ventricle. The Purkinje fiber network emerges from the RBB and LBB and extensively ramifies on the endocardial surfaces of the right and left ventricles, respectively.

The blood supply to the penetrating AV bundle is from the AV nodal artery and first septal perforator of the left anterior descending coronary artery. The bundle branches also have a dual blood supply from the septal perforators of the left anterior descending coronary artery and branches of the posterior descending coronary artery. The AV node is highly innervated with postganglionic sympathetic and parasympathetic nerves. The bundle of His and distal conducting system are minimally influenced by autonomic tone.

The cells that constitute the AV node complex are heterogeneous with a range of action potential profiles. In the transitional zones, the cells have an electrical phenotype between those of atrial myocytes and cells of the compact node (see Fig. 239-1). Atrionodal transitional connections may exhibit decremental conduction, defined as slowing of conduction with increasingly rapid rates of stimulation. Fast and slow AV nodal pathways have been described, but it is controversial whether these two types of pathway are anatomically distinct or represent functional heterogeneities in different regions of the AV nodal complex. Myocytes that constitute the compact node are depolarized (resting membrane potential ~–60 mV) and exhibit action potentials with low amplitudes, slow upstrokes of phase 0 (<10 V/s), and phase 4 diastolic depolarization; high-input resistance; and relative insensitivity to external [K⁺]. The action potential phenotype is explained by the complement of ionic currents expressed. AV nodal cells lack a robust inward rectifier potassium current (I_K1) and fast sodium current (I_Na); L-type calcium current (I_Ca-L) is responsible for phase 0; and phase 4 depolarization reflects the composite activity of the depolarizing currents—funny current (I_f), I_Ca-L, T-type calcium current (I_Ca-T), and sodium calcium exchanger current (I_NCX)—and the repolarizing currents—delayed rectifier (I_Kr) and acetylcholine-gated (I_KACh) potassium currents. Electrical coupling between cells in the AV node is tenuous due to the relatively sparse expression of gap junction channels (predominantly connexin-40) and increased extracellular volume.

The His bundle and the bundle branches are insulated from ventricular myocardium. The most rapid conduction in the heart is observed in these tissues. The action potentials exhibit very rapid upstrokes (phase 0), prolonged plateaus (phase 2), and modest automaticity (phase 4 depolarization). Gap junctions, composed largely of connexin-40, are abundant, but bundles are poorly connected transversely to ventricular myocardium.

ETIOLOGY OF AV CONDUCTION DISEASE

Conduction block from the atrium to the ventricle can occur for a variety of reasons in a number of clinical situations, and AV conduction block may be classified in a number of ways. The etiologies may be functional or structural, in part analogous to extrinsic and intrinsic causes of SA nodal dysfunction. The block may be classified by its severity from first to third degree or complete AV block or by the location of block within the AV conduction system. Table 240-1 summarizes the etiologies of AV conduction block. Those that are functional (autonomic, metabolic/endocrine, and drug-related) tend to be reversible. Most other etiologies produce structural changes, typically fibrosis, in segments of the AV conduction axis that are generally permanent. Heightened vagal tone during sleep or in well-conditioned individuals can be associated with all grades of AV block. Carotid sinus hypersensitivity, vasovagal syncope, and cough and micturition syncope may be associated with SA node slowing and AV conduction block. Transient metabolic and endocrinologic disturbances as well as a number of pharmacologic agents also may produce reversible AV conduction block.

Several infectious diseases have a predilection for the conducting system. Lyme disease may involve the heart in up to 50% of cases; 10% of patients with Lyme carditis develop AV conduction block, which is generally reversible but may require temporary pacing support. Chagas’ disease, which is common in Latin America, and syphilis may produce more persistent AV conduction disturbances. Some autoimmune and infiltrative diseases may produce AV conduction block, including systemic lupus erythematosus (SLE), rheumatoid arthritis, mixed connective tissue disease, scleroderma, amyloidosis (primary and secondary), sarcoidosis, and hemochromatosis; rare malignancies also may impair AV conduction.

Idiopathic progressive fibrosis of the conduction system is one of the more common and degenerative causes of AV conduction block. Aging is associated with degenerative changes in the summit of the ventricular septum, central fibrous body, and aortic and mitral annuli and has been described as “sclerosis of the left cardiac skeleton.” The process typically begins in the fourth decade of life and may be accelerated by atherosclerosis, hypertension, and diabetes mellitus. Accelerated forms of progressive familial heart block have been identified in families with mutations in the cardiac sodium channel gene (SCN5A) and other loci that have been mapped to chromosomes 1 and 19.

AV conduction block has been associated with heritable neuromuscular diseases, including the nucleotide repeat disease myotonic dystrophy, the mitochondrial myopathy Kearns-Sayre syndrome (Chap. 441), and several of the monogenic muscular dystrophies. Congenital AV block may be observed in complex congenital cardiac anomalies (Chap. 264), such as transposition of the great arteries, ostium primum atrial septal defects (ASDs), ventricular septal defects (VSDs), endocardial cushion defects, and some single-ventricle defects. Congenital AV block in the setting of a structurally normal heart has been seen in children born to mothers with SLE. Iatrogenic AV block may occur during mitral or aortic valve surgery, rarely in the setting of thoracic radiation, and as a consequence of catheter ablation. AV block is a decidedly rare complication of the surgical repair of VSDs or ASDs but may complicate repairs of transposition of the great arteries.

Coronary artery disease may produce transient or persistent AV block. In the setting of coronary spasm, ischemia, particularly in the right coronary artery distribution, may produce transient AV block. In acute myocardial infarction (MI), AV block transiently develops in 10–25% of patients; most commonly, this is first- or second-degree AV block, but complete heart block (CHB) may also occur. Second-degree and higher-grade AV block tends to occur more often in inferior than in anterior acute MI; however, the level of block in inferior MI tends to be in the AV node with more stable, narrow escape rhythms. In contrast, acute anterior MI is associated with block in the distal AV nodal complex, His bundle, or bundle branches and results in wide complex, unstable escape rhythms and a worse prognosis with high mortality rates.

ELECTROCARDIOGRAPHY AND ELECTROPHYSIOLOGY OF AV CONDUCTION BLOCK

AV conduction block typically is diagnosed electrocardiographically, which characterizes the severity of the conduction disturbance and allows one to draw inferences about the location of the block. AV conduction block manifests as slow conduction in its mildest forms and failure to conduct, either intermittent or persistently, in more severe varieties. First-degree AV block (PR interval >200 ms) is a slowing of conduction through the AV junction (Fig. 240-1). The site of delay is typically in the AV node but may be in the atria, bundle of His, or His-Purkinje system. A wide QRS is suggestive of delay in the distal conduction system, whereas a narrow QRS suggests delay in the AV node proper or, less commonly, in the bundle of His. In second-degree AV block there is an intermittent failure of electrical impulse conduction from atrium to ventricle. Second-degree AV block is subclassified as Mobitz type I (Wenckebach) or Mobitz type II. The periodic failure of conduction in Mobitz type I block is characterized by a progressively lengthening PR interval, shortening of the RR interval, and a pause that is less than two times the immediately preceding RR interval on the electrocardiogram (ECG). The ECG complex after the pause exhibits a shorter PR interval than that immediately preceding the pause (Fig. 240-2). This ECG pattern most often arises because of decremental conduction of electrical impulses in the AV node.

It is important to distinguish type I from type II second-degree AV nodal block because the latter has more serious prognostic implications. Type II second-degree AV block is characterized by intermittent failure of conduction of the P wave without changes in the preceding PR or RR intervals. When AV block is 2:1, it may be difficult to distinguish type I from type II block. Type II second-degree AV block typically occurs in the distal or infra-His conduction system, is often associated with intraventricular conduction delays (e.g., bundle branch block), and is more likely to proceed to higher grades of AV block than is type I second-degree AV block. Second-degree AV block (particularly type II) may be associated with a series of nonconducted P waves, referred to as paroxysmal AV block (Fig. 240-3), and implies significant conduction system disease and is an indication for permanent pacing. Complete failure of conduction from atrium to ventricle is referred to as complete or third-degree AV block. AV block that is intermediate between second degree and third degree is referred to as high-grade AV block and, as with CHB, implies advanced AV conduction system disease. In both cases, the block is most often distal to the AV node, and the duration of the QRS complex can be helpful in determining the level of the block. In the absence of a preexisting bundle branch block, a wide QRS escape rhythm (Fig. 240-4B) implies a block in the distal His or bundle branches; in contrast, a narrow QRS rhythm implies a block in the AV node or proximal His and an escape rhythm originating in the AV junction (Fig. 240-4A). Narrow QRS escape rhythms are typically faster and more stable than wide QRS escape rhythms and originate more proximally in the AV conduction system.

DIAGNOSTIC TESTING

Diagnostic testing in the evaluation of AV block is aimed at determining the level of conduction block, particularly in asymptomatic patients, since the prognosis and therapy depend on whether the block is in or below the AV node. Vagal maneuvers, carotid sinus massage, exercise, and administration of drugs such as atropine and isoproterenol may be diagnostically informative. Owing to the differences in the innervation of the AV node and infranodal conduction system, vagal stimulation and carotid sinus massage slow conduction in the AV node but have less of an effect on infranodal tissue and may even improve conduction due to a reduced rate of activation of distal tissues. Conversely, atropine, isoproterenol, and exercise improve conduction through the AV node and impair infranodal conduction. In patients with congenital CHB and a narrow QRS complex, exercise typically increases heart rate; by contrast, those with acquired CHB, particularly with wide QRS, do not respond to exercise with an increase in heart rate.

Additional diagnostic evaluation, including electrophysiologic testing, may be indicated in patients with syncope and suspected high-grade AV block. This is particularly relevant if noninvasive testing does not reveal the cause of syncope or if the patient has structural heart disease with ventricular tachyarrhythmias as a cause of symptoms. Electrophysiologic testing provides more precise information regarding the location of AV conduction block and permits studies of AV conduction under conditions of pharmacologic stress and exercise. Recording of the His bundle electrogram by a catheter positioned at the superior margin of the tricuspid valve annulus provides information about conduction at all levels of the AV conduction axis. A properly recorded His bundle electrogram reveals local atrial activity, the His electrogram, and local ventricular activation; when it is monitored simultaneously with recorded body surface electrocardiographic traces, intraatrial, AV nodal, and infranodal conduction times can be assessed (Fig. 240-1). The time from the most rapid deflection of the atrial electrogram in the His bundle recording to the His electrogram (AH interval) represents conduction through the AV node and is normally <130 ms. The time from the His electrogram to the earliest onset of the QRS on the surface ECG (HV interval) represents the conduction time through the His-Purkinje system and is normally ≤55 ms.

Rate stress produced by pacing can unveil abnormal AV conduction. Mobitz I second-degree AV block at short atrial paced cycle lengths is a normal response. However, when it occurs at atrial cycle lengths >500 ms (<120 beats/min) in the absence of high vagal tone, it is abnormal. Typically, type I second-degree AV block is associated with prolongation of the AH interval, representing conduction slowing and block in the AV node. AH prolongation occasionally is due to the effect of drugs (beta blockers, calcium channel blockers, digitalis) or increased vagal tone. Atropine can be used to reverse high vagal tone; however, if AH prolongation and AV block at long pacing cycle lengths persist, intrinsic AV node disease is likely. Type II second-degree block is typically infranodal, often in the His-Purkinje system. Block below the node with prolongation of the HV interval or a His bundle electrogram with no ventricular activation (Fig. 240-5) is abnormal unless it is elicited at fast pacing rates or short coupling intervals with extra stimulation. It is often difficult to determine the type of second-degree AV block when 2:1 conduction is present; however, the finding of a His bundle electrogram after every atrial electrogram indicates that block is occurring in the distal conduction system.

Intracardiac recording at electrophysiologic study that reveals prolongation of conduction through the His-Purkinje system (i.e., long HV interval) is associated with an increased risk of progression to higher grades of block and is generally an indication for pacing. In the setting of bundle branch block, the HV interval may reveal the condition of the unblocked bundle and the prognosis for developing more advanced AV conduction block. Prolongation of the HV interval in patients with asymptomatic bundle branch block is associated with an increased risk of developing higher-grade AV block. The risk increases with greater prolongation of the HV interval such that in patients with an HV interval >100 ms, the annual incidence of complete AV block approaches 10%, indicating a need for pacing. In patients with acquired CHB, even if intermittent, there is little role for electrophysiologic testing, and pacemaker implantation is almost always indicated.

TREATMENT

FURTHER READING

INTRODUCTION

Supraventricular tachyarrhythmias originate from or are dependent on conduction through the atrium or atrioventricular (AV) node to the ventricles. Most produce narrow QRS-complex tachycardia (QRS duration <120 ms) characteristic of ventricular activation over the Purkinje system. Conduction block in the left or right bundle branch or activation of the ventricles from an accessory pathway produces a wide QRS complex during supraventricular tachycardia that must be distinguished from ventricular tachycardia (Chap. 249). Mechanisms of supraventricular tachyarrhythmia can be divided into physiologic sinus tachycardia and pathologic tachycardia (Table 241-1). Pathologic tachycardia can be further sub-classified in terms of mechanism as reentrant arrhythmias dependent on AV nodal conduction (e.g., AV reentry), large reentry circuits within the atrial tissue alone (e.g., atrial flutter) or focal atrial tachycardias that can be due to automaticity or small reentry circuits (see Figs. 243-3 and 245-1). The prognosis and treatment vary considerably depending on the mechanism and underlying heart disease.

Supraventricular tachycardia can be of brief duration, termed nonsustained, or can be sustained such that an intervention, such as cardioversion or drug administration, is required for termination. Episodes that occur with sudden onset and termination are referred to as paroxysmal. Paroxysmal supraventricular tachycardia (PSVT) refers to a family of tachycardias including AV node reentry, AV reentry using an accessory pathway, and atrial tachycardia.

CLINICAL PRESENTATION

Symptoms of supraventricular arrhythmia vary depending on the rate, duration, associated heart disease, and comorbidities and include palpitations, chest pain, dyspnea, diminished exertional capacity, and occasionally syncope. Rarely, a supraventricular arrhythmia precipitates cardiac arrest in patients with the Wolff-Parkinson-White syndrome or severe heart disease, such as hypertrophic cardiomyopathy.

Initial Evaluation

Diagnosis requires obtaining an electrocardiogram (ECG) at the time of symptoms. When the arrhythmia is ongoing, the ECG usually establishes or suggests the diagnosis (Figs. 241-1, 241-2, 241-3 and Table 241-2). Treatment is determined by the type of arrhythmia and its hemodynamic effect. For transient arrhythmias, ambulatory ECG recording is warranted. Exercise testing is useful for assessing exercise-related symptoms. Occasionally an invasive electrophysiology study is warranted to provoke the arrhythmia with pacing, confirm the mechanism, and usually, perform catheter ablation.

Paroxysmal supraventricular tachycardia is most commonly encountered in patients who do not have structural heart disease. Other supraventricular arrhythmias, particularly atrial fibrillation, are associated with a variety of heart diseases. At initial evaluation history and examination should assess possible underlying heart disease. Any abnormal findings may warrant further cardiac evaluation.

The most common supraventricular tachycardia is sinus tachycardia in response to physiologic stress, such as exercise, but it can also be a manifestation acute illness. The first step in diagnosis of supraventricular tachycardia is to consider the possibility of sinus tachycardia. (Chap. 242). Therapy is then determined by the clinical findings. If the arrhythmia is ongoing and is not due to sinus tachycardia, initial assessment determines whether immediate therapy is needed to terminate the arrhythmia or slow the rate. Arrhythmias causing hypotension, impaired consciousness, angina, or heart failure warrant immediate therapy, guided by the type of arrhythmia.

FURTHER READING

PHYSIOLOGIC SINUS TACHYCARDIA

The sinus node is comprised of a group of cells dispersed within the superior aspect of the thick ridge of muscle known as the crista terminalis where the posterior smooth atrial wall derived from the sinus venosus meets the trabeculated anterior portion of the right atrium (Fig. 242-1). Sinus p waves are characterized by a frontal plane axis directed inferiorly and leftward, with positive p waves in leads II, III, and aVF; a negative p wave in aVR; and an initially positive biphasic p wave in V1. Normal sinus rhythm has a range of rates between 60–100 beats/min. Sinus tachycardia (>100 beats/min) typically occurs in response to sympathetic stimulation and vagal withdrawal, whereby the rate of spontaneous depolarization of the sinus node increases and the focus of earliest activation within the node typically shifts more leftward and closer to the superior septal aspect of the crista terminalis, thus producing taller p waves in the inferior limb leads when compared to normal sinus rhythm. Sinus bradycardia is defined as rates less than 60 beats/min; however, bradycadia can be normal during sleep and in fit individuals.

Sinus tachycardia is considered physiologic when it is an appropriate response to exercise, stress, or illness. Sinus tachycardia can be difficult to distinguish from focal atrial tachycardia (see below) that originates near the sinus node. A causative factor (such as exertion) and a gradual increase and decrease in rate favor sinus tachycardia, whereas abrupt onset and offset favor atrial tachycardia. The distinction can be difficult and occasionally requires extended ECG monitoring or even invasive electrophysiology study. Treatment for physiologic sinus tachycardia is aimed at the underlying condition (Table 242-1), but frequently no therapy is necessary.

NONPHYSIOLOGIC SINUS TACHYCARDIA

Inappropriate sinus tachycardia is an uncommon condition in which the sinus rate increases spontaneously at rest or out of proportion to physiologic stress or exertion and is within a spectrum of ill-defined conditions associated with autonomic dysregulation. Affected individuals are often women in the third or fourth decade of life. Fatigue, dizziness, and even syncope may accompany palpitations, which can be disabling. Additional symptoms of chest pain, headaches, and gastrointestinal upset are common. It must be distinguished from appropriate sinus tachycardia and from focal atrial tachycardia. The distinction between physiologic sinus tachycardia due to an anxiety disorder and inappropriate sinus tachycardia can be difficult. Therapy is often ineffective or poorly tolerated. Careful titration of beta blockers and/or calcium channel blockers may reduce symptoms. Clonidine and serotonin reuptake inhibitors have also been used. Ivabradine, a drug that blocks the I_f current that causes sinus node depolarization, is now approved in the United States for use in heart failure, but it has also been effective in the treatment of inappropriate sinus tachycardia. Catheter ablation of the sinus node has been performed, but long-term control of symptoms is usually poor, and it often leaves young individuals with a permanent pacemaker.

Postural orthostatic tachycardia syndrome (POTS) is characterized by symptomatic sinus tachycardia that occurs with postural change from a supine position to standing. The sinus rate increases by 30 beats/min or to >120 beats/min within 10 min of standing and in the absence of hypotension. Symptoms are often similar to those in patients with inappropriate sinus tachycardia. POTS is sometimes due to autonomic dysfunction following a viral illness and may resolve spontaneously over 3–12 months. Volume expansion with salt supplementation, oral fludrocortisone, compression stockings, and the α-agonist midodrine, often in combination, can be helpful. Exercise training has also been purported to improve symptoms.

FURTHER READING

INTRODUCTION

Focal atrial tachycardia (AT) can be due to abnormal automaticity, triggered automaticity, or a small reentry circuit confined to the atrium or atrial tissue extending into a pulmonary vein, the coronary sinus, or vena cava. It can be sustained, nonsustained, paroxysmal, or incessant. Focal AT accounts for ~10% of PSVTs in patients referred for catheter ablation. Nonsustained AT is commonly observed on 24-h ambulatory ECG recordings, and the prevalence increases with age. In fact, frequent atrial ectopy and nonsustained AT is often a precursor to more significant arrhythmias such as atrial fibrillation and flutter. Though unsustained, frequent atrial ectopy or short bursts of AT may be symptomatic and require therapy similar to that required for focal AT.

AT can occur in the absence of structural heart disease or may be associated with any condition that causes atrial fibrosis, including prior catheter ablation. Areas of fibrosis can be a nidus for abnormal automaticity from damaged cells or microreentry within zones of slow conduction within and on the border of fibrotic areas. Sympathetic stimulation is a promoting factor and the emergence of AT can be a sign of underlying illness. AT with AV block may occur in digitalis toxicity. Symptoms from AT are highly variable but similar to other supraventricular tachycardias (SVTs). Incessant AT can cause tachycardia-induced cardiomyopathy.

AT typically presents with 1:1 AV conduction or with AV block that can be Wenckebach type conduction or fixed (e.g., 2:1 or 3:1). Because it is not dependent on AV nodal conduction, AT will not terminate with AV block, and the atrial rate will not be affected, which distinguishes AT from most AV nodal–dependent SVTs, such as AV nodal reentry and AV reentry using an accessory pathway (see below). An accelerated warm-up phase after initiation or cool-down phase prior to termination also favors AT rather than AV nodal–dependent SVT, as this is a common observation with triggered automaticity. P waves are often discrete, with an intervening isoelectric segment, in contrast to atrial flutter and macroreentrant AT (see below) because atrial activation from a focal source occurs though a small portion of the tachycardia cycle. When 1:1 conduction to the ventricles is present, the arrhythmia can resemble sinus tachycardia typically with a P-R interval shorter than the R-P interval (Fig. 243-1), particularly when sympathetic tone produces rapid AV nodal conduction. It can be distinguished from sinus tachycardia by the P-wave morphology, which usually differs from sinus p waves depending on the location of the focus. Focal AT tends to originate in areas of complex atrial anatomy, such as the crista terminalis, valve annuli, atrial septum, and atrial muscle extending along cardiac thoracic veins (superior vena cava, coronary sinus, and pulmonary veins) (Fig. 243-2), and the location can often be estimated by the P-wave morphology. AT from the atrial septum will frequently have a narrower P-wave duration than sinus rhythm. AT from the left atrium will usually have a monophasic, positive P wave in lead V₁ and negative P waves in I and aVL indicating movement away from the left atrial free wall. AT that originates from superior atrial locations, such as the superior vena cava or superior pulmonary veins, will be positive in the inferior limb leads II, III, and aVF, whereas AT from a more inferior location, such as the ostium of the coronary sinus, will inscribe negative P waves in these same leads. When the focus is in the superior aspect of the crista terminalis, close to the sinus node, however, the p wave will resemble that of sinus tachycardia. Abrupt onset and offset then favor AT rather than sinus tachycardia. Depending on the atrial rate, the P wave may fall on top of the T wave or, during 2:1 conduction, may fall coincident with the QRS. Maneuvers that increase AV block, such as carotid sinus massage, Valsalva maneuver, or administration of AV nodal–blocking agents, such as adenosine, are useful to create AV block that will expose the p wave (Fig. 243-3).

Acute management of sudden-onset, sustained AT is the same as for other forms of PSVT (Chaps. 241 and 244), but the response to pharmacologic therapy is variable, likely depending on the mechanism. For AT due to reentry, administration of adenosine or vagal maneuvers may transiently increase AV block without terminating tachycardia. Some ATs terminate with a sufficient dose of adenosine, consistent with triggered activity as the mechanism. Cardioversion can be effective in some, but fails in others because of immediate recurrence, suggesting automaticity as the mechanism in these cases. Beta blockers and calcium channel blockers may slow the ventricular rate by increasing AV block, which can improve tolerance of the arrhythmias, but large doses are sometimes required. Potential precipitating factors and intercurrent illness should be sought and corrected. Underlying heart disease should be considered and excluded.

For patients with recurrent episodes, beta blockers, calcium channel blockers such as diltiazem or verapamil, and antiarrhythmic drugs such as flecainide, propafenone, disopyramide, sotalol, and amiodarone can be effective, but potential toxicities and adverse effects often warrant avoidance for long term use (Tables 243-1, 243-2, and 243-3). Catheter ablation targeting the AT focus is effective in more than 80% of patients and is recommended for recurrent symptomatic AT when drugs fail or are not desired or for incessant AT causing tachycardia-induced cardiomyopathy.

FURTHER READING

INTRODUCTION

Atrioventricular Nodal Reentry Tachycardia

AV nodal reentry tachycardia (AVNRT) is the most common form of paroxysmal supraventricular tachycardia (PSVT), representing ~60% of cases referred for catheter ablation. It most commonly manifests in the second to fourth decades of life, often in women. It is often well tolerated, but rapid tachycardia, particularly in the elderly, may cause angina, pulmonary edema, hypotension, or syncope. It is not usually associated with structural heart disease.

The mechanism is reentry involving the AV node and the perinodal atrium, made possible by the existence of multiple pathways for conduction from the atrium into the AV node that are capable of conduction in two directions (Fig. 244-1). Most forms of AVNRT utilize a slowly conducting AV nodal pathway (right inferior extension) that extends from the compact AV node near the His bundle, inferiorly along the tricuspid valve annulus to the floor of the coronary sinus. The reentry wavefront propagates up this slowly conducting pathway to the compact AV node and then exits from the fast pathway at the top of the AV node. The path back to the slow pathway probably involves the left atrial septum which has connections to the coronary sinus musculature. More unusual forms of AVNRT utilize a left inferior extension that connects to the compact AV node through the roof of the coronary sinus, or in extremely rare cases, directly from the mitral valve annulus avoiding the coronary sinus musculature altogether. In typical forms, the conduction time from the compact AV node region to the atrium is similar to that from the compact node to the His bundle and ventricles, such that atrial activation occurs at about the same time as ventricular activation. The p wave is therefore inscribed during, slightly before, or slightly after the QRS and can be difficult to discern. Often the P wave is seen at the end of the QRS complex as a pseudo-r′ in lead V₁ and pseudo-S waves in leads II, III, and aVF (Fig. 244-1A). More unusual forms of AVNRT have P waves falling later, anywhere between QRS complexes, in which case an inverted P wave is seen in the inferior limb leads as seen in Fig. 244-2 where the inverted P wave is seen in the T wave. The rate can vary with sympathetic tone. Simultaneous atrial and ventricular contraction results in atrial contraction against a closed tricuspid valve producing cannon a wave visible in the jugular venous pulse often perceived as a fluttering sensation in the neck. Elevated venous pressures may also lead to release of natriuretic peptides that cause post-tachycardia diuresis. In contrast to ATs, maneuvers or medications that produce AV nodal block terminate the arrhythmia.

Acute treatment is the same as for other forms of PSVT (discussed below). Whether ongoing therapy is warranted depends on the severity of symptoms and frequency of episodes. Reassurance and instruction as to how to perform the Valsalva maneuver to terminate episodes are sufficient for many patients. Administration of an oral beta blocker, verapamil, or diltiazem at the onset of an episode has been used to facilitate termination. Chronic therapy with these medications or flecainide is an option if prophylactic therapy is needed. Catheter ablation of the slow AV nodal pathway is recommended for patients with recurrent or severe episodes or when drug therapy is ineffective, not tolerated, or not desired by the patient. Catheter ablation is curative in >95% of patients. The major risk is atrioventricular (AV) block requiring permanent pacemaker implantation, which occurs in <1% of patients.

Junctional Tachycardia

Junctional ectopic tachycardia (JET) is due to automaticity within the AV node. It is rare in adults and more frequently encountered as an incessant tachycardia in children, often in the perioperative period of surgery for congenital heart disease. It presents as a narrow QRS tachycardia, often with ventriculoatrial (VA) block, such that AV dissociation is present. JET can occur as a manifestation of increased adrenergic tone and may be seen after administration of isoproterenol, particularly after catheter ablation in the perinodal region. It may also occur for a short period of time after ablation for AVNRT.

Accelerated junctional rhythm is a junctional automatic rhythm between 50 and 100 beats/min. Initiation may occur with gradual acceleration in rate, suggesting an automatic focus, or after a premature ventricular contraction, suggesting a focus of triggered automaticity. VA conduction is usually present, with p-wave morphology and timing such that it resembles AVNRT at a slow rate. It can be related to increased sympathetic tone and may produce palpitations. It usually does not require specific therapy.

ACCESSORY PATHWAYS AND THE WOLFF-PARKINSON-WHITE SYNDROME

Accessory pathways (APs) occur in 1 in 1500–2000 people and are associated with a variety of arrhythmias including narrow-complex PSVT, wide-complex tachycardias, and, rarely, sudden death. Most patients have structurally normal hearts, but APs are associated with Ebstein’s anomaly of the tricuspid valve and forms of hypertrophic cardiomyopathy including PRKAG2 mutations, Danon’s disease, and Fabry’s disease.

APs are abnormal connections that allow conduction between the atrium and ventricles across the AV ring (Fig. 244-3). They are present from birth and are due to failure of complete partitioning of atrium and ventricle by the fibrous AV rings. They occur across either an AV valve annulus or the septum, most frequently between the left atrium and free wall of the left ventricle, followed by posteroseptal, right free wall, and anteroseptal locations. If the impulse from the sinus node conducts through the AP to the ventricle (antegrade) before the impulse conducts through the AV node and His bundle, then the ventricles are preexcited during sinus rhythm, and the ECG shows a short P-R interval (<0.12 s), slurred initial portion of the QRS (delta wave), and prolonged QRS duration produced by slow conduction through direct activation of ventricular myocardium over the AP (Fig. 244-3A). The morphology of the QRS and delta wave is determined by the AP location (Fig. 244-4) and the degree of fusion between the excitation wavefronts from conduction over the AV node and conduction over the AP. Right-sided pathways preexcite the right ventricle, producing a left bundle branch block–like configuration in lead V₁, and often create marked preexcitation because of relatively close proximity of the AP to the sinus node (Fig. 244-4). Left-sided pathways preexcite the left ventricle and may produce a right bundle branch–like configuration in lead V₁ and a negative delta wave in aVL, indicating initial depolarization of the lateral portion of the left ventricle that can mimic q waves of lateral wall infarction (Fig. 244-4). Because of the relatively large distance between the sinus node and left free wall APs, preexcitation may be minimal or absent on 12-lead ECG. Preexcitation due to an AP at the diaphragmatic surface of the heart, typically in the paraseptal region, produces delta waves that are negative in leads III and aVF, mimicking the q waves of inferior wall infarction (Fig. 244-4). Preexcitation can be intermittent and disappear during exercise as conduction over the AV node accelerates and may take over ventricular activation completely.

Wolff-Parkinson-White (WPW) syndrome is defined as a preexcited QRS during sinus rhythm and episodes of PSVT. There are a number of variations of APs, which may not cause preexcitation and/or arrhythmias. Concealed APs allow only retrograde conduction, from ventricle to atrium, so no preexcitation is present during sinus rhythm, but SVT can occur. Other unusual forms of APs occur. Fasciculoventricular connections between the His bundle and ventricular septum produce preexcitation but do not cause arrhythmia, probably because the circuit is too short to promote reentry. Atriofascicular pathways, also known as Mahaim fibers, probably represent a duplicate AV node and His-Purkinje system that connect the right atrium to fascicles of the right bundle branch and produce a wide complex tachycardia having a left bundle branch block configuration.

AV Reentry Tachycardia

The most common tachycardia caused by an AP is the PSVT designated orthodromic AV reentry. The circulating reentry wavefront propagates from the atrium anterogradely over the AV node and His-Purkinje system to the ventricles and then reenters the atria via retrograde conduction over the AP (Fig. 244-3B). The QRS is narrow or may have typical right or left bundle branch block, but without preexcitation during tachycardia. Because excitation through the AV node and AP are necessary, AV or VA block results in tachycardia termination. During sinus rhythm, preexcitation is seen if the pathway also allows anterograde conduction (Fig. 244-3A). Most commonly, during tachycardia the R-P interval is shorter than the P-R interval and can resemble AVNRT (see Fig. 242-1). Unlike typical AVNRT, P waves always follow the QRS and are never simultaneous with a narrow QRS complex because the ventricles must be activated before the reentry wavefront reaches the AP and conducts back to the atrium. The morphology of the P wave is determined by the pathway location, but can be difficult to assess because it is usually inscribed during the ST segment. The p wave in posteroseptal APs is negative in leads II, III, and aVF, similar to that of AV nodal reentry, but P-wave morphology differs from AV nodal reentry for pathways in other locations (Fig. 244-4). Figure 241-3 is an example of a pathway that has clear negative P waves in leads I and aVL that was due to an AP inserting in the lateral left atrium.

Occasionally, an AP conducts extremely slowly in the retrograde direction, resulting in tachycardia with a long R-P interval, similar to most ATs. These pathways are usually located in the septal region and have negative p waves in leads II, III, and aVF. Slow AP conduction facilitates reentry, often leading to nearly incessant tachycardia, known as permanent junctional reciprocating tachycardia (PJRT). Tachycardia-induced cardiomyopathy can occur. Without an invasive electrophysiology study, it may be difficult to distinguish this form of orthodromic AV reentry from atypical AV nodal reentry or AT.

Preexcited Tachycardias

Preexcited tachycardia occurs when the ventricles are activated by antegrade conduction over the AP (Fig. 244-3C). The most common mechanism is antidromic AV reentry in which activation propagates from atrium to ventricle via the AP and then conducts retrogradely to the atria via the His-Purkinje system and the AV node (or rarely a second AP). The wide QRS complex is produced entirely via ventricular excitation over the AP because there is no contribution of ventricular activation over more rapidly conducting specialized His-Purkinje fibers. This tachycardia is often indistinguishable from monomorphic ventricular tachycardia. The presence of preexcitation in sinus rhythm suggests the diagnosis.

Preexcited tachycardia also occurs if an AP allows antegrade conduction to the ventricles during AT, atrial flutter, atrial fibrillation (AF) (Fig. 244-5), or AV nodal reentry, otherwise known as bystander AP conduction. AF and atrial flutter are potentially life threatening if the AP allows very rapid repetitive conduction. Approximately 25% of APs causing preexcitation allow minimum R-to-R intervals of <250 ms during AF and are associated with a higher risk of inducing ventricular fibrillation and sudden death. Preexcited AF presents as a wide-complex, very irregular rhythm. During AF, the ventricular rate is determined by the conduction properties of the AP and AV node. The QRS complex can appear quite bizarre and change on a beat-to-beat basis due to the variability in the degree of fusion from activation over the AV node and AP, or all beats may be due to conduction over the AP (Fig. 244-5). Ventricular activation from the Purkinje system may depolarize the ventricular end of the AP and prevent atrial wavefront conduction over the AP. Slowing AV nodal conduction without slowing AP conduction can thereby facilitate AP conduction and dangerously accelerate the ventricular rate. Administration of AV nodal–blocking agents including oral or intravenous verapamil, diltiazem, beta blockers, intravenous adenosine, and intravenous amiodarone are contraindicated during preexcited AF. Rapid preexcited tachycardia should be treated with electrical cardioversion or intravenous procainamide or ibutilide, which may terminate the arrhythmia or slow the ventricular rate.

Management of Patients with APs

Acute management of orthodromic AV reentry is discussed below for PSVT. Patients with WPW syndrome may have wide-complex tachycardia due to antidromic AV reentry, orthodromic AV with bundle branch block, or a preexcited tachycardia, and treatment depends on the underlying rhythm.

Initial patient evaluation should include assessment for aggravating factors, including intercurrent illness and factors that increase sympathetic tone. Examination should focus on excluding underlying heart disease. An echocardiogram is reasonable to exclude Ebstein’s anomaly and forms of hypertrophic cardiomyopathy that can be associated with APs.

Patients with preexcitation who have symptoms of arrhythmia are at risk for developing AF and sudden death if they have an AP that allows rapid antegrade conduction. The risk of cardiac arrest is in the range of 2 per 1000 patients in adults but is likely greater in children. An invasive electrophysiology study is recommended to assess whether the pathway can support dangerously rapid heart rates if AF were to occur, and is usually combined with potentially curative catheter ablation. Catheter ablation is warranted for recurrent arrhythmias when drugs are ineffective, not tolerated, or not desired by the patient (Fig. 244-5). Efficacy is in the range of 95% depending on the location of the AP. Serious complications occur in fewer than 3% of patients, but can include AV block, cardiac tamponade, thromboemboli, coronary artery injury, and vascular access complications. Procedure mortality is <1 in 1000 patients. Alternatively attempts to gain reassurance that the AP is not high risk with ambulatory monitoring or exercise testing; abrupt loss of conduction (preexcitation) at physiologic heart rates is consistent with a low risk pathway, but is not completely reliable. Gradual loss of AP conduction with increased sympathetic tone does not reliably indicate low risk since this can occur as AV nodal conduction time shortens.

For patients with concealed APs or known low-risk APs causing orthodromic AV reentry, chronic therapy is guided by symptoms and frequency of events. Vagal maneuvers may terminate episodes, as may a dose of beta blocker, verapamil, or diltiazem taken at the onset of an episode. Chronic therapy with these agents or flecainide can reduce the frequency of episodes in some patients.

Adults who have preexcitation but no arrhythmia symptoms have a risk of sudden death estimated to be 1 per 1000 patient-years. Electrophysiology study is usually advised for people in occupations for which an arrhythmia occurrence would place them or others at risk, such as police, military, and pilots, or for individuals who desire evaluation for risk. Routine follow-up without therapy is reasonable in others. Children are at greater risk of sudden death, ~2 per 1000 patient-years.

TREATMENT

FURTHER READING

INTRODUCTION

Macroreentrant atrial tachycardia is due to a large reentry circuit, often associated with areas of scar in the atria. Common or typical right atrial flutter is due to a circuit that revolves around the tricuspid valve annulus, bounded anteriorly by the annulus and posteriorly by functional conduction block in the crista terminalis. The wavefront passes between the inferior vena cava and the tricuspid valve annulus, known as the sub-Eustachian or cavotricuspid isthmus, where it is susceptible to interruption by catheter ablation. Thus, common atrial flutter is also known as cavotricuspid isthmus-dependent atrial flutter. This circuit most commonly revolves in a counterclockwise direction (as viewed looking toward the tricuspid annulus from the ventricular apex), which produces the characteristic negative sawtooth flutter waves in leads II, III, and aVF and positive P waves in lead V₁ (Fig. 245-1). When the direction is reversed, clockwise rotation produces the opposite P-wave vector in those leads. The atrial rate is typically 240–300 beats/min but may be slower in the presence of atrial disease or antiarrhythmic drugs. It often conducts to the ventricles with 2:1 AV block, creating a regular tachycardia at 150 beats/min, with p waves that may be difficult to discern. Maneuvers that increase AV nodal block will typically expose flutter waves, allowing diagnosis.

Common right atrial flutter usually occurs in association with atrial fibrillation and often with atrial scar from senescence or prior cardiac surgery. Some patients with atrial fibrillation treated with an antiarrhythmic drug, particularly flecainide, propafenone, or amiodarone, will present with atrial flutter rather than fibrillation, since these agents slow atrial conduction velocity and can promote reentry.

Macroreentrant ATs that are not dependent on conduction through the cavotricuspid isthmus are referred to as atypical atrial flutters. They can occur in either atrium and are almost universally associated with areas of atrial scar. Left atrial flutter and perimitral left atrial flutter are commonly seen after extensive left atrial ablation for atrial fibrillation or atrial surgery. The clinical presentation is similar to common atrial flutter, but with different P-wave morphologies (Fig 245-2). They can be difficult to distinguish from focal AT, and in most cases, the mechanism can only be confirmed by an electrophysiology study.

TREATMENT

MULTIFOCAL ATRIAL TACHYCARDIA

Multifocal AT (MAT) is characterized by a rhythm with at least three distinct P-wave morphologies with rates typically between 100 and 150 beats/min. Unlike atrial fibrillation, there are clear isoelectric intervals between P waves (Fig. 245-3) and the atrial rate is slower. The mechanism is likely triggered automaticity from multiple atrial foci. It is usually encountered in patients with chronic pulmonary disease and acute illness.

Therapy for MAT is directed at treating the underlying disease and correcting any metabolic abnormalities. Electrical cardioversion is ineffective. The calcium channel blockers verapamil or diltiazem may slow the atrial and ventricular rate. Patients with severe pulmonary disease often do not tolerate beta blocker therapy. MAT may respond to amiodarone, but long-term therapy with this agent is usually avoided due to its toxicities, particularly pulmonary fibrosis.

FURTHER READING

INTRODUCTION

Atrial fibrillation (AF) is characterized by disorganized, rapid, and irregular atrial activation with loss of atrial contraction and with an irregular ventricular rate that is determined by AV nodal conduction (Fig. 246-1). In an untreated patient, the ventricular rate also tends to be rapid and variable, between 120 and 160 beats/min, but in some patients, it may exceed 200 beats/min. Patients with high vagal tone or AV nodal conduction disease may have slow ventricular rates.

AF is the most common sustained arrhythmia and is a major public health problem. Prevalence increases with age, and >95% of AF patients are >60 years of age. The prevalence by age 80 is ~10%. The lifetime risk of developing AF for men 40 years old is ~25%. AF is slightly more common in men than women and more common in whites than blacks. Risk factors for developing AF in addition to age and underlying cardiac disease include hypertension, diabetes mellitus, cardiac disease, obesity, and sleep apnea. AF is associated with a 1.5- to 1.9-fold increased risk of mortality after controlling for underlying heart disease. AF is also associated with a risk of developing heart failure and vice-versa—patients with heart failure have an increased risk of developing AF. AF increases the risk of stroke by fivefold and is estimated to be the cause of 25% of strokes. It also increases the risk of dementia and silent strokes detected by MRI. Since AF is a marker for other predictors of mortality and morbidity, such as the severity of heart disease, it is difficult to determine the extent to which AF itself contributes to associated increased mortality and morbidity.

AF is occasionally associated with an acute precipitating factor such as hyperthyroidism, acute alcohol intoxication, or an acute illness such as myocardial infarction or pulmonary embolism. AF occurs in up to 30% of patients recovering from cardiac surgery, associated with inflammatory pericarditis.

The clinical pattern of AF suggests the underlying pathophysiology (Fig. 246-1). Paroxysmal AF is defined by episodes that start spontaneously and stop within 7 days of onset. Paroxysmal AF is often initiated by small reentrant or rapidly firing foci in sleeves of atrial muscle that extend into the pulmonary veins (PV). Catheter ablation that isolates these foci usually abolishes paroxysmal AF, although some patients also have initiating foci in other locations. These non-PV triggers tend to occur in older patients and those with more severe underlying cardiac disease. Persistent AF has a longer duration, exceeding 7 days, and, in many cases, will continue indefinitely unless cardioversion is performed. Cardioversion can be followed by prolonged periods of sinus rhythm. As for paroxysmal AF, episodes are often initiated by rapidly firing foci within PVs, but non-PV sites, including myocardial sleeves around the superior vena cava (SVC) or coronary sinus are encountered more often than when AF is paroxysmal. In addition, persistence of the AF is likely facilitated by structural and electrophysiologic atrial abnormalities, particularly fibrosis that uncouples atrial fibers, promoting reentry and focal automaticity. In patients with long-standing persistent AF (>1 year), significant fibrosis is usually present and it is difficult to restore and maintain sinus rhythm. Some patients progress over years from paroxysmal to persistent AF. Although fibrosis that develops with aging and atrial hypertrophy in response to hypertension and other cardiac disease appears to be an important promoting factor, electrophysiologic remodeling that affects conduction and refractoriness occur as well in response to chronic tachycardia. Thus, AF tends to promote AF.

Clinical consequences of AF are related to rapid ventricular rates, loss of atrial contribution to ventricular filling, and predisposition to thrombus formation in the left atrial appendage with potential embolization. Presentations vary with the ventricular rate and underlying heart disease and comorbidities. Rapid rates may cause hemodynamic collapse or heart failure exacerbation particularly in patients with impaired cardiac function, hypertrophic cardiomyopathy, and heart failure with preserved systolic function. Exercise intolerance and easy fatigability are common despite the absence of palpitations in many patients. Occasionally, dizziness or syncope occurs due to pauses when AF terminates to sinus rhythm (Fig. 246-2). Depressed ventricular function with cardiomyopathy may develop in response to chronic tachycardia (rates persistently faster than 100–110 bpm) and is probably more common in patients who do not sense palpitations, since they may not seek medical care until heart failure symptoms develop. Tachycardia-related cardiomyopathy is usually reversible with control of ventricular rate.

Treatment for AF is primarily guided by patients’ symptoms, the hemodynamic effect of AF, the duration of AF, the risk of stroke and the underlying heart disease. New-onset AF that produces severe hypotension, pulmonary edema, or angina should be electrically cardioverted starting with a QRS synchronous shock of 200 J, ideally after sedation or anesthesia is achieved. Greater shock energy and different electrode placements may be tried if the shock fails to terminate AF. Administration of intravenous ibutilide lowers the energy requirement for atrial defibrillation and may be useful if AF terminates and reinitiates, but should not be used in patients with a prolonged QT interval or severe LV dysfunction because of a significant risk of torsades de Pointes. If the patient is stable, immediate management involves rate control to alleviate or prevent symptoms, and consideration of whether anticoagulation is warranted to reduce stroke risk. Consideration is then given to whether therapy is warranted to restore and maintain sinus rhythm, or whether the patient will be allowed to continue in AF, and managed with rate control and measures for stroke prevention. It is critical to consider the risk of stroke when attempting to restore sinus rhythm. If the duration of AF is unclear or is known to be >48 h, anticoagulation must be commenced before cardioversion. Anticoagulation strategies for new-onset AF are debated. In the absence of contraindications, it is usually appropriate to initiate systemic anticoagulation with heparin immediately or with an oral anticoagulant that has rapid onset of action, while evaluation and other therapies are implemented.

CARDIOVERSION AND ANTICOAGULATION

The major source of thromboembolism and stroke in AF is formation of thrombus in the left atrial appendage where flow is relatively stagnant, although thrombus occasionally forms in other locations as well. Following conversion from prolonged AF to sinus rhythm, atrial mechanical function can be delayed for weeks, such that thrombi can form even during sinus rhythm. When AF has been present for >48 h and in patients at high risk for thromboembolism, such as those with mitral stenosis or hypertrophic cardiomyopathy, conversion to sinus rhythm is associated with an increased risk of thromboembolism. Thromboembolism can occur soon, or several days after restoration of sinus rhythm if appropriate anticoagulation measures are not taken.

Cardioversion within 48 h of the onset of AF is common practice in patients who have not been anticoagulated, provided that they are not at high risk for stroke due to a prior history of embolic events, rheumatic mitral stenosis, or hypertrophic cardiomyopathy with marked left atrial enlargement. These low-risk patients with occasional episodes of AF can be instructed to notify their physician when AF occurs to arrange for cardioversion to be done within 48 h.

If the duration of AF exceeds 48 h or is unknown, there is greater concern for thromboembolism after cardioversion, even in patients considered low risk (CHA₂DS₂-VASc of 0 or 1 [see below]) for stroke. There are two approaches to mitigate the risk related to cardioversion. One option is to anticoagulate continuously for 3 weeks before and a minimum of 4 weeks after cardioversion. A second approach is to start anticoagulation and perform a transesophageal echocardiogram to determine if thrombus is present in the left atrial appendage. If thrombus is absent, cardioversion can be performed and anticoagulation continued for a minimum of 4 weeks to allow time for recovery of atrial mechanical function. In either case, cardioversion of AF is associated with a substantial risk of recurrence, which may not be symptomatic. Longer-term maintenance of anticoagulation is considered based on the patient’s individual risk for stroke, commonly assessed from the CHA₂DS₂-VASc score.

RATE CONTROL

Acute rate control can be achieved with beta blockers and/or the calcium channel blockers verapamil and diltiazem administered either intravenously or orally, as warranted by the urgency of the clinical situation. Digoxin may be added, particularly in heart failure patients, if negative inotropic and other adverse effects of beta blockers and calcium channel blockers limit their use. Digoxin lacks negative inotropic effects, but is less effective in slowing the ventricular rate in AF, particularly when sympathetic tone is high. It is synergistic with the other AV nodal–blocking agents. Its use has been associated with increased mortality in some studies. Typically, the goal of acute rate control is to reduce the ventricular rate to less than 100/min, but the goal must be guided by the clinical situation and the adverse effects of rate control medications.

CHRONIC RATE CONTROL

For patients who remain in AF chronically, the goal of rate control is to alleviate and prevent deterioration of ventricular function from excessive rates. β-Adrenergic blockers and calcium channel blockers are often used in combination. Digoxin is added selectively when these are not sufficient. Exertion-related symptoms are often an indication of inadequate rate control. Rate should be assessed with exertion and medications adjusted accordingly. The initial goal is a resting heart rate of <80 beats/min that increases to <100 beats/min with light exertion, such as walking. If it is difficult to slow the ventricular rate to that degree, allowing a resting rate of up to 110 beats/min is acceptable provided it does not cause symptoms and ventricular function is normal, but periodic assessment of ventricular function is warranted because some patients develop tachycardia-induced cardiomyopathy.

If adequate rate control in AF is difficult to achieve, further consideration should be given to restoring sinus rhythm (see below). Catheter ablation of the AV junction to create heart block and implantation of a permanent pacemaker reliably achieves rate control without the need for AV nodal blocking agents, but mandates lifelong permanent pacing. Right ventricular apical pacing induces dyssynchronous ventricular activation that can depress ventricular function in some patients. Biventricular pacing or direct pacing of the His bundle may be used to minimize the degree of ventricular dyssynchrony.

STROKE PREVENTION IN ATRIAL FIBRILLATION

The majority of patients warrant chronic anticoagulation, but selection of therapy should be individualized based on patient profile and risks and benefits of individual agents. Anticoagulation is warranted for patients with mitral stenosis, hypertrophic cardiomyopathy, and those with a prior history of stroke. Patients without mitral stenosis are often referred to as having nonvalvular AF. The CHA₂DS₂-VASc score (Table 246-1) can be used to estimate stroke risk in these patients. Anticoagulation is recommended for a score of ≥2 and may be considered for a score of 1. The approach to patients with paroxysmal AF is the same as for persistent AF. It is recognized that many patients who appear to have infrequent AF episodes based on office visits often have asymptomatic episodes that put them at risk. Absence of AF during periodic monitoring is not sufficient to indicate low risk. The role of continuous monitoring with implanted recorders or pacemakers is not yet clear as a guide for anticoagulation in patients with a borderline risk profile.

The major options for anticoagulation are the antithrombin inhibitor dabigitran, factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, the vitamin K antagonist warfarin. Antiplatelet agents alone are generally not sufficient. In non-valvular AF, warfarin reduces the annual risk of stroke by 64% compared to placebo and by 37% compared to antiplatelet therapy. Patients with AF with an increased risk of stroke also have an increased risk of venous thromboembolism, which appears to be lower with oral anticoagulation. The direct acting anticoagulants, dabigatran, rivaroxaban, apixaban, and edoxaban were noninferior to warfarin in individual trials, and analysis of pooled data suggests superiority to warfarin by small absolute margins of 0.4–0.7% in reduction of mortality, stroke, major bleeding, and intracranial hemorrhage. Warfarin is the agent required for patients with rheumatic mitral stenosis or mechanical heart valves. The newer, direct acting anticoagulants have not been tested in rheumatic heart disease and a direct thrombin inhibitor did not prevent thromboemboli in patients with mechanical heart valves. Warfarin is an inconvenient agent that requires several days to achieve a therapeutic effect (prothrombin time [PT]/international normalized ratio [INR] >2), requires monitoring of PT/INR to adjust dose, and has many drug and food interactions, that can hinder patient compliance. The direct acting agents are easier to use and achieve reliable anticoagulation promptly without requiring dosage adjustment based on blood tests. Dabigatran, rivaroxaban, and apixaban have renal excretion, cannot be used with severe renal insufficiency (CrCl <15 mL/min), and require dose adjustment for modest renal impairment, which is of particular concern in the elderly, who are at increased bleeding risk. Excretion can also be influenced by P-glycoprotein inducers and inhibitors. Warfarin anticoagulation can be reversed by administration of fresh frozen plasma and vitamin K. A reversal agent (idarucizumab) is available for dabigatran and reversal agents for the Xa inhibitors are being evaluated (andexanet alfa and ciraparantag). For now, bleeding that occurs during Xa inhibitor use must be managed with supportive care, with the expectation that clotting will improve over 12 h as the anticoagulant is excreted, although reversal agents are anticipated.

The antiplatelet agents aspirin and clopidogrel are inferior to warfarin for stroke prevention in AF and do not have less risk of bleeding. Clopidogrel combined with aspirin is better than aspirin alone for stroke prevention, but is inferior to warfarin and has a greater bleeding risk than aspirin alone.

Bleeding is the major risk of anticoagulation. Major bleeding requiring transfusion or intracranial bleeding occurs in ~1% of patients per year with warfarin. Direct acting anticoagulants appear to have a lower risk of intracranial bleeding relative to warfarin without sacrificing protective effects against thromboembolism. Risk factors for bleeding include age >65–75 years, heart failure, renal insufficiency, prior bleeding, and excessive alcohol or nonsteroidal anti-inflammatory drug use. In patients who require dual antiplatelet therapy (e.g., aspirin and clopidogril) after coronary or peripheral arterial stenting, there is a substantially increased bleeding risk when standard oral anticoagulation with warfarin or a direct acting anticoagulant is added. The optimal combination of agents for patients with AF who also require antiplatelet therapy is unclear.

Chronic anticoagulation is contraindicated in some patients due to bleeding risks. Because most atrial thrombi likely originate in the left atrial appendage, surgical removal of the appendage, combined with atrial maze surgery, may be considered for patients undergoing surgery, although removal of the appendage has not been unequivocally shown to reduce the risk of thromboembolism. Percutaneously deployed devices that occlude or ligate the left atrial appendage are also available, appear to be non-inferior to warfarin in reducing stroke risk and are considered in patients who have a high risk of thromboembolism, but serious bleeding risk from chronic oral anticoagulation.

RHYTHM CONTROL

AF is associated with obesity, hypertension, excessive alcohol use and sleep apnea. Aggressive treatment of these risk factors can substantially reduce AF episodes in some patients and is warranted in all patients.

The decision to administer antiarrhythmic drugs or perform catheter ablation to attempt maintenance of sinus rhythm (commonly referred to as the “rhythm control strategy”) is mainly guided by patient symptoms and preferences regarding the benefits and risks of therapies. In general, patients who maintain sinus rhythm have better survival than those who continue to have AF. This may be because continued AF is a marker of disease severity. In randomized trials, administration of antiarrhythmic medications to maintain sinus rhythm did not improve survival or symptoms compared to a rate control strategy, and the drug therapy group had more hospitalizations. Disappointing efficacy and toxicities of available antiarrhythmic drugs and patient selection bias may be factors that influenced the results of these trials. The impact of catheter ablation on mortality is not known but the subject of ongoing randomized, controlled trials. A rhythm control strategy is usually selected for patients with symptomatic paroxysmal AF, recurrent episodes of symptomatic persistent AF, AF with difficult rate control, and AF that has resulted in depressed ventricular function or that aggravates heart failure. A rhythm control strategy is more likely to be favored in younger patients than in sedentary or elderly patients in whom rate control is more easily achieved. Even if sinus rhythm is apparently maintained, anticoagulation is recommended according to the CHA₂DS₂-VASc stroke risk profile because asymptomatic episodes of AF are common. Following a first episode of persistent AF, a strategy using AV nodal–blocking agents, cardioversion, and anticoagulation is reasonable, in addition to addressing possible aggravating factors. If recurrences are infrequent, periodic cardioversion is reasonable.

Pharmacologic Therapy for Maintaining Sinus Rhythm

The goal of pharmacologic therapy is to maintain sinus rhythm or reduce episodes of AF. Risks and side effects of antiarrhythmic drugs are a major consideration in selecting therapy. Drug therapy can be instituted once sinus rhythm has been established or in anticipation of cardioversion. β-Adrenergic blockers and calcium channel blockers help control ventricular rate, improve symptoms, and possess a low-risk profile, but have low efficacy for preventing AF episodes. Class I sodium channel–blocking agents (e.g., flecainide, propafenone, disopyramide) are options for subjects without significant structural heart disease, but negative inotropic and proarrhythmic effects warrant avoidance in patients with coronary artery disease or heart failure. The class III agents sotalol and dofetilide can be administered to patients with coronary artery disease or structural heart disease but have ~3% risk of inducing excessive QT prolongation and torsades des pointes. Dofetilide should be initiated only in a hospital with ECG monitoring, and many physicians take this approach with sotalol as well. Dronedarone increases mortality in patients with heart failure. All of these agents have modest efficacy in patients with paroxysmal AF, of whom ~30–50% will benefit. Amiodarone is more effective, maintaining sinus rhythm in approximately two-thirds of patients. It can be administered to patients with heart failure and coronary artery disease. Over 40% of patients experience amiodarone-related toxicities during long-term therapy.

CATHETER AND SURGICAL ABLATION FOR ATRIAL FIBRILLATION

Successful catheter ablation avoids antiarrhythmic drug toxicities but procedural risks and efficacy depend on operator experience. For patients with previously untreated but recurrent paroxysmal AF, catheter ablation has mildly better efficacy compared to antiarrhythmic drug therapy and is clearly superior to antiarrhythmic drugs for patients who have recurrent AF despite drug treatment. Long-term control of AF is more difficult to achieve in patients with persistent AF, likely because of more extensive atrial abnormality and associated greater co-morbidities in these patients.

Catheter ablation involves cardiac catheterization, trans(atrial) septal puncture, and radiofrequency ablation or cryoablation to electrically isolate the left atrial regions around the PV, abolishing the ability of triggering foci in these regions to initiate AF, and also likely impacting the substrate for reentry in the left atrium. Extensive areas of ablation are required, and gaps in healed ablation areas or emergence of new trigger sites outside the PV necessitate a repeat procedure in 20–50% of patients.

In patients with paroxysmal AF, sinus rhythm is maintained for >1 year after one ablation procedure in ~60% of patients; and is achieved in 70–80% of patients after multiple procedures. Many patients become more responsive to antiarrhythmic drugs after a PV isolation procedure. Ablation is less effective in patients with persistent AF, and particularly long-standing persistent AF, particularly when associated with more extensive cardiac disease and co-morbidities. More extensive ablation is often required, targeting areas that likely support reentry in regions outside but adjacent to the pulmonary venous antra. There is no proven strategy for selecting ablation targets outside the PV antral regions and a variety of approaches have been pursued. Ablation of areas of rapid activity during AF or creation of ablation lines to block conduction across regions of the atria did not improve outcomes in some studies. Other ablation targets include foci that fire in response to isoproterenol, areas of atrial fibrosis, and regions with activation consistent with reentrant rotors during AF. More than one ablation procedure is often required to maintain sinus rhythm in patients with persistent and long-standing persistent AF.

Catheter ablation has a 2–7% risk of major procedure-related complications, including stroke (0.5–1%), cardiac tamponade (1%), phrenic nerve paralysis, bleeding from femoral access sites, and fluid overload with heart failure, that can emerge 1–3 days after the procedure. It is important to recognize the potential for delayed presentation of some complications. Ablation within the PV can lead to PV stenosis, presenting weeks to months after the procedure with dyspnea or hemoptysis. The esophagus abuts the posterior wall of the left atrium where it is subject to injury, and esophageal ulcers can form immediately after the procedure and may rarely lead to a fistula between the left atrium and esophagus (estimated incidence of < 0.1%) that presents as endocarditis and stroke 10 days to 3 weeks after the procedure. Early diagnosis of atrioesophageal fistula is important because delayed diagnosis leads to death. Diagnosis is made by chest CT scan with water soluble oral and IV contrast. Endoscopy should be avoided in patients with a suspected fistula because of the risk of air/esophageal fluid embolus. Definitive repair of the atrioesophageal fistula by emergent cardiothoracic surgery is required.

Surgical ablation of AF is most frequently performed concomitant with cardiac valve or coronary artery surgery and less commonly as a stand-alone procedure. However, for patients with persistent AF, surgical or hybrid procedures appear to have higher single-procedure efficacy than catheter ablation. Risks include sinus node injury requiring pacemaker implantation. Surgical removal of the left atrial appendage may reduce stroke risk, although thrombus can form in the remnant of the appendage or if the appendage is not completely ligated.

FURTHER READING

Ventricular arrhythmias originate from a focus of myocardial or Purkinje cells capable of automaticity, or triggered automaticity, or from reentry through areas of scar or a diseased Purkinje system. They are characterized by their electrocardiographic appearance and duration. Conduction away from the ventricular focus through the ventricular myocardium is slower than activation of the ventricles over the Purkinje system. Hence, the QRS complex during ventricular arrhythmias will be wide, typically >0.12 s.

Premature ventricular beats (also referred to as a premature ventricular contraction or PVC) are single ventricular beats that fall earlier than the next anticipated supraventricular beat (Fig. 247-1). PVCs that originate from the same focus will have the same QRS morphology and are referred to as unifocal (Fig. 247-1A). PVCs that originate from different ventricular sites have different QRS morphologies and are referred to as multifocal (Fig. 247-1B). Two consecutive ventricular beats are ventricular couplets.

Ventricular tachycardia (VT) is three or more consecutive beats at a rate faster than 100 beats/min. Three or more consecutive beats at slower rates are designated an idioventricular rhythm (Fig. 247-1C). VT that terminates spontaneously within 30 s is designated non-sustained (Fig. 247-2) whereas sustained VT persists >30 s or is terminated by an active intervention, such as administration of an intravenous medication, external cardioversion, or pacing or a shock from an implanted cardioverter defibrillator.

Monomorphic VT has the same QRS complex from beat to beat, indicating that the activation sequence is the same from beat to beat, and that each beat likely originates from the same source (Fig. 247-3A). The initial site of ventricular activation largely determines the sequence of ventricular activation. Therefore, the QRS morphology of PVCs and monomorphic VT provides an indication of the site of origin within the ventricles (Fig. 247-4). The likely origin often suggests whether an arrhythmia is idiopathic or associated with structural disease. Arrhythmias that originate from the right ventricle or septum result in late activation of much of the left ventricle, thereby producing a prominent S-wave in V1 referred to as a left bundle branch block–like configuration. Arrhythmias that originate from the free wall of the left ventricle have a prominent positive deflection in V1, thereby producing a right bundle branch block–like morphology in V1. The frontal plane axis of the QRS is also useful. An axis that is directed inferiorly, as indicated by dominant R waves in lead II, III, and AVF, suggests initial activation of the cranial portion of the ventricle, whereas a frontal plane axis that is directed superiorly (dominant S waves in II, III, and AVF) suggests initial activation at the inferior wall.

Very rapid monomorphic VT has a sinusoidal appearance, also called ventricular flutter, because it is not possible to distinguish the QRS complex from the T wave (Fig. 247-3B). Relatively slow sinusoidal VTs have a wide QRS indicative of slowed ventricular conduction (Fig. 247-3C). Hyperkalemia, toxicity from excessive effects of drugs that block sodium channels (e.g., flecainide, propafenone, or tricyclic antidepressants) and severe global myocardial ischemia are causes.

Polymorphic VT has a continually changing QRS morphology indicating a changing ventricular activation sequence. Polymorphic VT that occurs in the context of congenital or acquired prolongation of the QT interval often has a waxing and waning QRS amplitude creating a “twisting about the points” appearance referred to as Torsade de Pointes (Fig. 247-3D).

Ventricular fibrillation (VF) has continuous irregular activation with no discrete QRS complexes (Fig. 247-3E). Monomorphic or polymorphic VT may transition to VF in susceptible patients.

The term idiopathic ventricular arrhythmias generally refers to PVCs or VT that occurs in patients without structural heart disease and which is not associated with a genetic syndrome or risk of sudden death.

CLINICAL MANIFESTATIONS OF VENTRICULAR ARRYTHMIAS

Common symptoms of ventricular arrhythmias include palpitations, dizziness, exercise intolerance, episodes of lightheadedness, syncope or sudden cardiac arrest leading to sudden death. Ventricular arrhythmias can also be asymptomatic and encountered unexpectedly as an irregular pulse or heart sounds on examination, or seen on a routine ECG, exercise test or cardiac ECG monitoring.

Syncope is a concerning symptom, that can be due to an episode of VT that produces severe hypotension, which often indicates that there is a risk for cardiac arrest and sudden death with arrhythmia recurrence. Although benign processes, such as reflex mediated neuro-cardiogenic (vasovagal) syncope and orthostatic hypotension, are the most common causes, it is important to consider the possibility of heart disease or a genetic syndrome causing VT. When these are suspected, hospitalization for further evaluation and monitoring is often appropriate.

Sustained VT may present as a wide QRS complex tachycardia that must be distinguished from supraventricular tachycardia with aberrancy (see Chap. 241) causing symptoms that range from mild to severe impairment with hypotension with syncope and imminent cardiac arrest. Sustained VT may degenerate to VF, particularly if it is rapid and polymorphic. Many patients who are at risk for VT have known heart disease and many have an implantable cardioverter defibrillator (ICD). In patients with an ICD, VT episodes may cause transient lightheadedness, palpitations or syncope that may be followed by a shock from the ICD (see below).

EVALUATION OF PATIENTS WITH DOCUMENTED OR SUSPECTED VENTRICULAR ARRYTHMIAS

There are several important considerations that guide evaluation of patients with documented or suspected cardiac arrhythmias. First, establish whether a ventricular arrhythmia is the cause of the symptoms or clinical presentation. Second, determine whether the arrhythmia is associated with a cardiac disease and establish the prognostic significance of that disease, and in particular whether it is associated with a risk of sudden cardiac death. Finally, define the likelihood of arrhythmia recurrence and the symptoms and risk imposed by the recurrence. The risk of cardiac arrest and sudden cardiac death are largely determined by the cause of the arrhythmia and the associated underlying heart disease.

The diagnosis of ventricular arrhythmias is established by recording of the arrhythmia on an ECG, by an implanted rhythm management device such as a pacemaker or ICD, or in some cases, initiation of the arrhythmia during an electrophysiologic study (Table 247-1). A 12 lead ECG of the arrhythmia should be obtained when possible and often provides clues to the potential site of origin and possible presence of underlying heart disease (see above). For patients with sustained wide complex tachycardia initial management is guided by the patient’s hemodynamic stability. The approach to sustained wide complex tachycardia is discussed in Chap. 249. The management of VT that causes cardiac arrest is discussed in Chap. 299. Once hemodynamic stability is restored further management is guided by the possibility of a recurrence and the risk imposed by a recurrence.

Evaluation of the Patient with Arrhythmia Symptoms

When symptoms are intermittent, initial evaluation aims to establish symptom severity, provocative factors and presence of underlying heart disease. Syncope or near syncope raises concern that an arrhythmia is causing episodes of hypotension and that there may be a risk of cardiac arrest if that persists. Symptoms that occur with exertion suggest arrhythmias that are provoked by sympathetic stimulation, but can also be related to exertional ischemia in patients with coronary artery disease, although non-arrhythmia causes must also be considered. A past history of any cardiac disease is important. A review of all medications is relevant. Medications that prolong the QT interval predispose to polymorphic VT (see Chap. 250). Adrenergic stimulants can provoke premature ventricular contractions.

Family history should determine the presence of premature coronary artery disease, cardiomyopathy, or cardiac arrhythmias, particularly a history of sudden death. Family history may also suggest that a possibility of a genetic cause of an arrhythmia warrants careful consideration. Details of premature deaths are relevant. Sudden death victims are often said to have died of a “massive heart attack” despite absence of definite confirmation of thrombotic myocardial infarction and when other causes such as arrhythmia may have been possible.

The physical examination focuses on evidence of structural heart disease with assessment of pulse, jugular venous pressure lung fields and cardiac auscultation. Stigmata of neuromuscular disease or dysmorphic features may suggest a genetic arrhythmia syndrome.

A 12-lead ECG should be obtained even if the patient is not having symptoms at the time of evaluation. Occasionally premature ventricular beats will be detected. Patients with benign idiopathic arrhythmias usually have a completely normal ECG during sinus rhythm. Any ECG abnormality warrants further evaluation. Particularly relevant findings include Q-waves that indicate prior myocardial infarction, which may have been silent, and ventricular hypertrophy, which may indicate hypertrophic cardiomyopathy or other ventricular disease. An ECG finding is the major diagnostic manifestation of several genetic arrhythmia syndromes in patients without structural heart disease, including the long QT syndrome, Brugada syndrome, and short QT syndrome (see Chap. 250).

If there is suspicion for structural heart disease, cardiac imaging is warranted to assess ventricular function and structure. Transthoracic echocardiography is most frequently employed for initial evaluation. Depressed ventricular function increases concern for a risk of sudden death and warrants further evaluation to establish the cause, which may be cardiomyopathy, coronary artery disease, or valvular heart disease. Ventricular thickening may indicate hypertrophic cardiomyopathy or infiltrative diseases such as amyloidosis. Cardiac MRI with gadolinium contrast imaging provides similar assessment, but also can detect areas of ventricular scar, evident as regions of delayed hyperenhancement, which are usually present in patients who have sustained monomorphic VT (Fig. 247-5). The nature and location of abnormalities is helpful in assessing the type of heart disease. Evaluation to exclude atherosclerotic coronary artery disease should be performed in patients at risk, guided by age and other risk factors.

OVERVIEW OF TREATMENT OF VENTRICULAR ARRYTHMIAS

Treatment of ventricular arrhythmias is guided by the severity and frequency of symptoms. For some, reassurance and removal of aggravating factors (e.g., caffeine) is all that is needed. For arrhythmias associated with a sudden death risk, ICD implantation is usually indicated and will provide a “safety-net” to terminate life-threatening VT or VF, preventing sudden death, but without preventing the arrhythmia. When suppression of the arrhythmia is required, antiarrhythmic drug therapy or catheter ablation are major considerations.

ANTIARRHYTHMIC DRUGS

Use of antiarrhythmic drugs is based on consideration of the risks and potential benefit for the individual patient. Efficacy and side effects for the individual patient is not predictable and is assessed by individual therapeutic trial. Adverse effects are mostly non-cardiac and minor, but can sometimes be severe enough to limit their use. Cardiac side effects, however, include the potential for “pro-arrhythmia” whereby a drug can increase the frequency of arrhythmia or cause a new arrhythmia. Aggravation of bradyarrhythmias is also a common concern. Although anti-arrhythmic drugs are classified based on their actions on receptors or ion channels, most have multiple effects, affecting more than one channel.

Beta-adrenergic Blockers

Many ventricular arrhythmias are sensitive to sympathetic stimulation, and beta-adrenergic stimulation also diminishes the electrophysiologic effects of many membrane active anti-arrhythmic drugs. The safety of beta-blocking agents makes them the first choice of therapy for most ventricular arrhythmias. They are particularly useful for exercise-induced arrhythmias and idiopathic arrhythmias, but have limited efficacy for most arrhythmias associated with heart disease. Bradyarrhythmias and negative inotrophic effects are the major cardiac adverse effects.

Calcium Channel Blockers

The non-dihydropyridine calcium channel blockers diltiazem and verapamil can be effective for some idiopathic VTs. The risk of pro-arrhythmia is low, but they have negative inotropic and vasodilatory effects that can aggravate hypotension.

Sodium Channel Blocking Agents

Drugs whose major effect is mediated through sodium channel blockade include mexiletine, quinidine, disopyramide, flecainide, and propafenone, which are available for chronic oral therapy. Blockade of the fast inward sodium current has been referred to as a Class I antiarrhythmic drug effect. Antiarrhythmic actions are the result of depressing of cardiac conduction and membrane excitability. Conduction slowing can be manifest as a prolongation of QRS duration. Lidocaine, quinidine, and procainamide are available as intravenous formulations. Quinidine, disopyramide, and procainamide also have potassium channel blocking effects that prolong the QT interval (Class III antiarrhythmic drug action) that contributes to its antiarrhythmic effect. These agents have potential pro-arrhythmic effects and, with the possible exception of quinidine, also have negative inotropic effects that may contribute to increased mortality observed when some were administered chronically to patients with prior myocardial infarction. Long-term therapy is generally avoided in patients with structural heart disease, but may be used to reduce symptomatic arrhythmias in patients with ICDs.

Potassium Channel Blocking Agents

Sotalol and dofetilide block the delayed rectifier potassium channel IKr, thereby prolonging action potential duration (QT interval) and the cardiac refractory period, known as the Class III antiarrhythmic drug effect. Sotalol also has non-selective beta-adrenergic blocking activity. It has been shown to have a modest effect on reducing ICD shocks due to ventricular and atrial arrhythmias. Proarrhythmia due to the polymorphic VT torsade de pointes that is associated with QT prolongation occurs in 3–5% of patients. Both sotalol and dofetilide are excreted via the kidneys, necessitating dose adjustment or avoidance in renal insufficiency. These drugs must be avoided in patients with other risk factors for torsade de pointes, including QT prolongation, hypokalemia and significant bradycardia.

Amioderone and Dronederone

Amiodarone blocks multiple cardiac ionic currents and has sympatholytic activity. It is the most effective antiarrhythmic drug for suppressing ventricular arrhythmias. It is administered intravenously for life-threatening arrhythmias. During chronic oral therapy, electrophysiologic effects develop over several days. It is more effective than sotalol in reducing ICD shocks and is the preferred drug for ventricular arrhythmias in patients with heart disease who are not candidates for an ICD. Bradyarrhythmias are the major cardiac adverse effect. Ventricular pro-arrhythmia can occur, but torsade de pointes VT is rare. Non-cardiac toxicities are a major problem and contribute to drug discontinuation in approximately a third of patients during long-term therapy. Hyper or hypothyroidism are related to the iodine content of the drug. Pneumonitis or pulmonary fibrosis occurs in ~1% of patients. Photosensitivity is common, and neuropathy and ocular toxicity can occur. Systematic monitoring is recommended during chronic therapy including assessment for thyroid, liver, and pulmonary toxicity. Intravenous administration of amiodarone via a peripheral vein for >24 h can cause severe peripheral thrombophlebitis. Dronaedarone has structural similarities to amiodarone but without the iodine moiety. Efficacy for ventricular arrhythmias is poor and it increases mortality in patients with heart failure.

IMPLANTABLE CARDIAC DEFIBRILLATORS (ICD)

ICDs detect sustained VT, largely based on heart rate, and then terminate the arrhythmia. VF is terminated by a shock applied between a lead in the RV and the ICD pulse generator. Monomorphic VT can often be terminated by a burst of rapid pacing faster than the VT, known as anti-tachycardia pacing (ATP) (Fig. 247-6A). If ATP fails or is not a programmed treatment, as is often the case for rapid VT or VF, a shock is delivered (Fig. 247-6B). Shocks are painful if the patient is conscious. ICDs are highly effective for termination of VT and VF and also provide bradycardia pacing. The most common ICD complication is the delivery of unnecessary therapy (either ATP or shocks) in response to a rapid supraventricular tachycardia or electrical noise as a result of an ICD lead fracture. ICDs record and store electrograms from arrhythmia episodes which can be retrieved by interrogation of the ICD, which can be performed remotely and communicated via internet. This assessment is critical after an ICD shock to determine the arrhythmia diagnosis and exclude an unnecessary therapy. Device infection occurs in ~1% of patients.

ICDs decrease mortality in patients at risk for sudden death due to structural heart diseases. In all cases ICDs are recommended only if there is also expectation for survival of at least a year with acceptable functional capacity. The exception is in cases of patients with end-stage heart disease who are awaiting cardiac transplantation outside the hospital, or who have left bundle branch block QRS prolongation such that they are likely to have improvement in ventricular function with cardiac resynchronization therapy from a biventricular ICD (Fig. 247-6C).

Despite prompt termination of VT or VF by an ICD, the occurrence of these arrhythmias predicts subsequent increased mortality and risk of heart failure. Occurrence of VT or VF should therefore prompt assessment for potential causes including worsening heart failure, electrolyte abnormalities, and ischemia. Repeated shocks, even if appropriate, often induce posttraumatic stress disorder. Antiarrhythmic drug therapy, most commonly amiodarone, or catheter ablation is often required for suppression of recurrent arrhythmias. Antiarrhythmic drug therapy can alter the VT rate and the energy required for defibrillation, thereby necessitating programming changes in the ICD’s algorithms for detection and therapy.

The commonly used ICD system consists of endocardial leads to the right heart chambers with a pulse generator implanted in the pre-pectoral area (Fig. 247-6C). This transvenous form of ICD has the disadvantage of vascular occlusion, endocarditis in the event of infection, and difficulty with removal. A totally subcutaneous ICD system is now available. While it has the advantage of avoiding endovascular complications, the present iteration lacks the ability to pace the heart for tachycardia termination or for long-term pacing. A wearable ICD system with electrodes incorporated into a vest and an external battery pack is also available for short-term use in patients pending decision regarding a permanent implanted system.

CATHETER ABLATION FOR VENTRICULAR FIBRILATION

Catheter ablation is usually performed by applying radiofrequency (RF) current to cause thermal injury by resistive heating of cardiac tissue responsible for the arrhythmia. An electrode catheter is used to map local electrical activity to identify the ventricular myocardium that is causing the arrhythmia, referred to as the arrhythmia substrate. The size and location of the arrhythmia substrate determines the ease and likely effectiveness of the procedure, as well as the potential complications. When the arrhythmia originates from the endocardium, as is most commonly the case, it can be reached from an endovascular approach via a femoral vein or artery. Less commonly arrhythmias originate from the subepicardium, and percutaneous pericardial puncture, similar to pericardiocentesis, is required to insert a catheter into the pericardial space for mapping and ablation. In patients with scar-related VT due to prior infarction or cardiomyopathy, ablation targets abnormal regions in the scar. Because these scars often contain multiple reentry circuits over relatively large regions, extensive areas of ablation are required and these areas are often identified as regions of low voltage displayed on anatomic reconstructions of the ventricle (Fig. 247-5).

Catheter ablation is often performed in patients with recurrent ventricular arrhythmias associated with poor cardiac function, and the procedure-related mortality in this situation is 0.5–3%. Outcomes are better for patients with prior infarction and VT than for patients with nonischemic cardiomyopathies in which the scar locations are more variable and often intramural or sub-epicardial. Ablation can be lifesaving for patients with very frequent or incessant VT.

Idiopathic VTs and PVCs that occur in the absence of structural heart disease usually originate from a small focus, for which catheter ablation has a higher success rate for preventing recurrent arrhythmia (see Chaps. 248 and 249).

ARRYTHMIA SURGERY

When antiarrhythmic drug therapy and catheter ablation fails, or is not an option, surgical cryoablation, often combined with aneurysmectomy, can be effective therapy for recurrent VT due to prior myocardial infarction and has also been used successfully in a few patients with nonischemic heart disease. Few centers now maintain the expertise for this therapy.

PREMATURE VENTRICULAR CONTRACTIONS AND NON-SUSTAINED VT

Premature ventricular contractions (see Fig. 247-1A) can be due to automaticity or reentry (see Chap. A9). They are often sensitive to sympathetic stimulation and can be a sign of increased sympathetic tone, myocardial ischemia, hypoxia, electrolyte abnormalities, particularly hypokalemia, or underlying heart disease. During myocardial ischemia or in association with other heart disease, PVCs can be a harbinger of sustained VT or VF.

The ECG characteristics of the arrhythmia are often suggestive of whether structural heart disease is present. PVCs with smooth uninterrupted contours and sharp QRS deflections suggest an ectopic focus in relatively normal myocardium whereas broad notching and slurred QRS deflections suggest a diseased myocardial substrate. The QRS morphology also suggests the likely site of origin within the ventricle (see Fig. 247-4). PVCs that have a dominant S-wave in V1, referred to as left bundle branch block–like configuration originate from the right ventricle or interventricular septum. Those with a dominant R-wave in V1 originate from the left ventricle. A superior frontal plane axis (negative in II, III, AVF) indicates initial depolarization of the inferior wall (diaphraghmatic aspect of the heart), while an inferior frontal plane axis (positive in II, III, AVF) indicates an origin in the cranial aspect of the heart. The location of arrhythmia origin often suggests the nature of underlying heart disease. Most ventricular arrhythmias that are not associated with structural heart disease have a left bundle branch block–like configuration. PVCs with RBBB configuration are more likely to be associated with structural heart disease. Multiple morphologies of PVCs (multifocal PVCs) are also more likely to indicate structural heart disease (see Fig. 247-1B). In patients with heart disease, a greater frequency and complexity (couplets and non-sustained VT) of these arrhythmias are associated with more severe disease.

PVCs AND NON-SUSTAINED VT DURING ACUTE ILLNESS

These arrhythmias are often encountered in patients who are being evaluated in the emergency room, or who have been hospitalized and are on a cardiac monitor. When encountered during acute illness or as a new finding, evaluation should focus on detection and correction of potential aggravating factors and causes, specifically myocardial ischemia, ventricular dysfunction and electrolyte abnormalities, most commonly hypokalemia. Underlying heart disease should be defined.

PVCs AND NON-SUSTAINED VT IN PATIENTS WITHOUT HEART DISEASE

The most frequent site of origin for idiopathic ventricular arrhythmias is the right ventricular outflow tract, giving rise to PVCs or VT that have a left bundle branch block–like configuration, with an inferiorly directed frontal plane axis as discussed below (see Fig. 247-2). However, QRS morphology alone is not reliable as an indicator of disease or subsequent risk. Non-sustained VT is usually monomorphic with rates <200 beats/min and typically lasting <8 beats (see Fig. 247-2). Non-sustained VT that is very rapid, polymorphic, or with a first beat that occurs prior to the peak of the T-wave (“short-coupled”) is uncommon and should prompt careful evaluation for underlying disease or genetic syndromes associated with sudden death.

A family history of sudden death should prompt evaluation for genetic syndromes associated with sudden death, including cardiomyopathy, long QT syndrome and arrhythmogenic right ventricular cardiomyopathy (ARVC) (see below). Any abnormality on the 12-lead ECG warrants further evaluation (Fig. 248-1). Repolarization abnormalities are seen in a number of genetically determined syndromes associated with sudden death, including the long QT syndrome, Brugada syndrome, ARVC, and hypertrophic cardiomyopathy (Fig. 248-1). An echocardiogram is often necessary to assess ventricular function, wall motion abnormalities, and valvular heart disease. Contrast enhanced cardiac magnetic resonance imaging is also useful for this purpose and for the detection of ventricular scarring that is the substrate for sustained VT (see Fig. 247-5). Exercise stress testing should be performed in patients with effort-related symptoms and for those at risk for coronary artery disease.

TREATMENT OF IDIOPATHIC ARRHYTHMIAS

For PVC and non-sustained VT in the absence of structural heart disease, or a genetic sudden death syndrome, no specific therapy is needed unless the patient has significant symptoms or evidence that frequent PVCs are depressing ventricular function (see below). Reassurance that the arrhythmia is benign is often sufficient to allow the patient to cope with the symptoms, which will often wax and wane in frequency over years. Avoiding stimulants, such as caffeine and alcohol, is helpful in some patients. If symptoms require treatment, beta-adrenergic blockers and non-dihydropyridine calcium channel blockers (verapamil and diltiazem) are sometimes helpful. If these fail more membrane active antiarrhythmic drugs or catheter ablation are options. Antiarrhythmic agents flecainide, propafenone, mexiletine, and amiodarone can be effective but the potential for side effects, warrants careful consideration. Catheter ablation is effective at suppressing this arrhythmia in about 80% of patients. Failure of ablation is usually due to inability to provoke the arrhythmia for mapping in the electrophysiology laboratory, or an origin that is not accessible, such as deep within the myocardium.

PVCs AND NON-SUSTAINED VT ASSOCIATED WITH ACUTE CORONARY SYNDROMES

During and soon after acute myocardial infarction (MI), PVCs and non-sustained VT are common and can be an early manifestation of ischemia and a harbinger of subsequent VF. Treatment with beta-adrenergic blockers and correction of hypokalemia and hypomagnesemia reduce the risk of VF. Routine administration of antiarrhythmic drugs such as lidocaine does not reduce mortality and is not indicated for suppression of PVCs or asymptomatic non-sustained VT, but may be implemented transiently if an episode of sustained VT or VF occurs, with the goal of reducing the likelihood of a subsequent episode.

Following recovery from acute MI, frequent PVCs (typically >10 PVCs/h), repetitive PVCs with couplets, and non-sustained VT are markers for depressed ventricular function and increased mortality, but routine antiarrhythmic drug therapy to suppress these arrhythmias does not improve mortality and treatment with the sodium channel blocker flecainide increases mortality. Amiodarone therapy reduces sudden death, but does not improve total mortality. Therefore, amiodarone is an option for treatment of symptomatic arrhythmias in this population when the potential benefit outweighs its potential toxicities. Beta-adrenergic blockers reduce sudden death, but have limited effect on spontaneous arrhythmias.

For survivors of an acute MI, an implantable cardioverter defibrillator (ICD) reduces mortality in certain high-risk groups: patients who have survived >40 days after the acute MI and have a left ventricular ejection fraction of ≤0.30, or who have an ejection fraction <0.35 and have symptomatic heart failure (functional Class II or III); and patients >5 days after MI who have a reduced left ventricular ejection fraction, nonsustained VT, and inducible sustained VT or VF on electrophysiological testing. ICDs do not reduce mortality when routinely implanted soon after MI, and have not been demonstrated to improve mortality when implanted soon after coronary artery revascularization.

PVCs AND NON-SUSTAINED VT ASSOCIATED WITH DEPRESSED VENTRICULAR FUNCTION AND HEART FAILURE

Premature ventricular beats and non-sustained VT are common in patients with depressed ventricular function and heart failure, and are markers for disease severity and increased mortality, but antiarrhythmic drug therapy to suppress these arrhythmias has not been shown to improve survival. The use of anti-arrhythmic drugs whose major action is blockade of the cardiac sodium channel (flecainide, propafenone, mexiletine, quinidine, and disopyramide) is avoided in patients with structural heart disease because of a risk of pro-arrhythmia, negative inotropic effects and increased mortality. Therapy with the potassium channel blocker dofetilide, does not reduce mortality. Amiodarone suppresses ventricular ectopy and reduces sudden death but does not improve overall survival. ICDs are the major therapy to protect against sudden death in patients at high risk and are recommended for those with LV ejection fraction <0.35 and NYHA class II and III heart failure, in whom they reduce mortality from 36 to 29%, over 5 years.

PVC AND NON-SUSTAINED VT ASSOCIATED WITH OTHER CARDIAC DISEASES

Ventricular ectopy is associated with increased mortality in patients with hypertrophic cardiomyopathy (Chap. 254) or with congenital heart disease associated with right or left ventricular dysfunction. In these patients, management is similar to that for patients with ventricular dysfunction. Pharmacologic suppression of the arrhythmia has not been shown to improve mortality. ICDs are indicated for patients considered at high risk for sudden cardiac death.

PVC-INDUCED VENTRICULAR DYSFUNCTION

Very frequent ventricular ectopy and repetitive non-sustained VT (see Fig. 247-2) can depress ventricular function, possibly through an effect similar to chronic tachycardia or by inducing ventricular dysynchrony. Depression of ventricular function rarely occurs unless PVCs account for >15 to 20% of total beats over a 24-h period. Often the PVCs are idiopathic and unifocal, most commonly originating from the left ventricular papillary muscles or outflow tract regions where they can be targeted for ablation. The distinction between PVC- induced ventricular dysfunction as compared to a primary cardiomyopathic process causing ventricular dysfunction and arrhythmia is difficult and in some cases can be made only retrospectively by observing an improvement in ventricular function after the arrhythmia is suppressed with an antiarrhythmic drug, such as amiodarone, or by catheter ablation.

IDIOVENTRICULAR RHYTHMS

Three or more ventricular beats at a rate slower than 100 beats/min are termed an idioventricular rhythm (see Fig. 247-1C). Automaticity is the likely mechanism. Idioventricular rhythms are common during acute MI and may emerge during sinus bradycardia. Often, they are not symptomatic, but hemodynamic compromise may occur with the loss of ventricular synchrony in susceptible patients. Atropine may be administered to increase the sinus rates if this is a concern. This rhythm is also common in patients with cardiomyopathies or sleep apnea. It can also be idiopathic, often emerging when the sinus rate slows during sleep. Therapy should target any underlying cause and correction of bradycardia. Specific antiarrhythmic therapy for asymptomatic idioventricular rhythm is not necessary.

FURTHER READING

INTRODUCTION

Sustained monomorphic ventricular tachycardia (VT) presents as a wide QRS tachycardia that has the same QRS configuration from beat to beat indicating an identical sequence of ventricular depolarization for each beat (see Fig. 247-3A). VT originates from a stable focus or reentry circuit. In structural heart disease, the substrate is often an area of patchy replacement fibrosis due to infarction, inflammation or prior cardiac surgery that creates anatomical or functional reentry pathways (see Fig. 247-5). Less commonly, VT is related to reentry or automaticity in a diseased Purkinje system. Idiopathic VT occurs in the absence of structural heart disease and is due to a focal region of automaticity or reentry involving a portion of the Purkinje system.

The clinical presentation varies depending on the rate of the arrhythmia, underlying cardiac function, and autonomic adaptation in response to the arrhythmia. While rapid VT, >200 beats/min, usually causes hypotension that may present as syncope, patients with normal cardiac function might tolerate rapid VT, and those with severe left venricular (LV) dysfunction may experience symptoms of hypotension, even if VT is slower than 150 beats/min. Monomorphic VT that is rapid or associated with structural heart disease may deteriorate to ventricular fibrillation (VF), which may be the initial cardiac rhythm recorded at the time of resuscitation of a cardiac arrest.

DIAGNOSIS

Sustained monomorphic VT has to be distinguished from other causes of uniform wide QRS tachycardia. These include supraventricular tachycardia with left or right bundle branch block aberrant conduction, supraventricular tachycardias conducted to the ventricles over an accessory pathway (Chap. 241), and rapid cardiac pacing in a patient with a pacemaker or defibrillator. In the presence of known heart disease VT is the most likely diagnosis of a wide QRS tachycardia. Hemodynamic stability during the arrhythmia does not exclude VT. A number of ECG criteria have been evaluated to distinguish supraventricular tachycardia with aberrancy from VT. The presence of AV dissociation is usually a reliable marker for VT (Fig. 249-1), but P-waves can be difficult to define. A P-wave following each QRS does not exclude VT because 1:1 conduction from ventricle to atrium can occur. A monophasic R wave or Rs complex in AVR or concordance from V1 to V6 of monophasic R or S waves are also relatively specific for VT (Fig. 249-1). A number of other QRS morphology criteria have also been described, but all have limitations, and are not very reliable in patients with severe heart disease. In patients with known bundle branch block, the same QRS morphology during tachycardia as during sinus rhythm suggests supraventricular tachycardia rather than VT, but is not absolutely reliable. An electrophysiological study is sometimes required for definitive diagnosis. Occasionally, noise and movement artifacts on telemetry recordings can simulate VT; prompt recognition can avoid unnecessary tests and interventions.

When LV function is depressed or there is evidence of structural myocardial disease, scar-related reentry is the most likely cause of sustained monomorphic VT. Scars are suggested by pathologic Q-waves on the ECG, segmental left or right ventricular wall motion abnormalities on echocardiogram or nuclear imaging, and areas of delayed gadolinium enhancement during MR imaging (see Fig. 247-5).

TREATMENT AND PROGNOSIS

Initial management follows Advanced Cardiac Life Support (ACLS) guidelines (Chap. 299). If hypotension, impaired consciousness, or pulmonary edema are present, QRS synchronous electrical cardioversion should be performed, ideally after sedation if the patient is conscious. For stable tachycardia a trial of adenosine is reasonable, as this may clarify a supraventricular tachycardia with aberrancy (Chap. 241). Intravenous amiodarone is the drug of choice if heart disease is present. Following restoration of sinus rhythm, hospitalization and evaluation to define underlying heart disease is required. Assessment of cardiac biomarkers for evidence of myocardial infarction (MI) is appropriate, but acute MI is rarely a cause of sustained monomorphic VT, and elevations in troponin or CK-MB are more likely to indicate myocardial damage that is secondary to hypotension and ischemia from the VT. Subsequent management is determined by the underlying heart disease and frequency of VT. If VT recurs frequently or is incessant, administration of antiarrhythmic medications, or catheter ablation may be required to restore stability. More commonly sustained monomorphic VT occurs as an isolated episode, but with a risk of recurrence. Implantable cardioverter defibrillators (ICDs) are usually warranted for sustained VT associated with structural heart disease.

SUSTAINED MONOMORPHIC VT IN SPECIFIC DISEASES

Coronary Artery Disease

Patients who present with sustained monomorphic VT associated with coronary artery disease typically have a history of prior large MI and present years after the acute infarct with a remodeled ventricle and markedly depressed left ventricular function. Even when there is biomarker evidence of acute MI, a preexisting scar from previous MI should be suspected as the cause of the VT. Infarct scars provide a durable substrate for sustained VT and up to 70% of patients have a recurrence of the arrhythmia within 2 years. Scar-related reentry is not dependent on recurrent acute myocardial ischemia, so coronary revascularization cannot be anticipated to prevent recurrent VT, even when it may be appropriate for treatment of angina or other indications. Depressed ventricular function, which is a risk factor for sudden death, is usually present. Implantation of an ICD is indicated for most patients provided that there is a reasonable expectation of survival with acceptable functional status for the next year after recovery from the VT episode. Compared with antiarrhythmic drug therapy ICDs reduce annual mortality from 12.3 to 8.8% and lower arrhythmic deaths by 50% in patients with hemodynamically significant sustained VT or a history of cardiac arrest. Chronic amiodarone therapy may be considered for patients who are not candidates for, or who decline ICD placement.

Following ICD implantation, patients remain at risk for heart failure, recurrent ischemic events, and recurrent VT, with a 5-year mortality that exceeds 30%. Attention to therapies that benefit patients with depressed ventricular function, including beta-adrenergic blocking agents, angiotensin converting enzyme inhibitors, and statins is important. Patients with frequent symptomatic recurrences of VT require antiarrhythmic drug therapy or catheter ablation.

Nonischemic Dilated Cardiomyopathy

Sustained monomorphic VT associated with nonischemic cardiomyopathy is usually due to scar-related reentry. The etiology of scar is often unclear, but progressive replacement fibrosis is the likely cause. On cardiac MR imaging, scars are detectable as areas of delayed gadolinium enhancement and are more often intramural or sub-epicardial in location as compared with patients with prior MI. Scars that cause VT are often located adjacent to a valve annulus and can occur in either ventricle. Any cardiomyopathic process can cause scars and VT, but cardiac sarcoidosis, Chagas disease, and cardiomyopathy due to Lamin A/C mutations are particularly associated with monomorphic VT (Table 249-1). An ICD is usually indicated with additional drugs or catheter ablation for control of recurrent VT.

MONOMORPHIC VT IN ARRHYTHMOGENIC Right Ventricular (RV) CARDIOMYOPATHY (ARVC)

ARVC (Chap. 254) is a rare genetic disorder most commonly due to mutations in genes encoding for cardiac desmosomal proteins. Approximately 50% have a familial transmission with autosomal dominant inheritance. A less common, autosomal recessive form is associated with cardio-cutaneous syndromes that include Naxos disease and Carvajal syndrome. Patients typically present between the second and fifth decade with palpitations, syncope or cardiac arrest owing to sustained monomorphic VT, although polymorphic VT can also occur. Fibrosis and fibro-fatty replacement most commonly involves the right ventricular myocardium, and provide the substrate for reentrant VT that usually has a left bundle branch block–like configuration, consistent with the right ventricular origin and can resemble idiopathic VT. The sinus rhythm ECG suggests the disease in >85% of patients, most often showing T-wave inversions in V1-V3 (see Fig. 248-1). Delayed activation of the right ventricle may cause a widened QRS (>110 ms) in the right precordial leads and a prolonged S-wave upstroke in those leads, and occasionally a deflection at the end of the QRS known as an “Epsilon” wave (see Fig. 248-1). Cardiac imaging may show right ventricular enlargement or areas of abnormal motion, or reveal areas of scar on contrast enhanced MRI.

Left ventricular involvement can occur and occasionally precede manifest right ventricular disease. Heart failure is rare except in late stages, and survival to advanced age can be anticipated provided that VT can be controlled. An ICD is recommended. When VT is exercise-induced, it may respond to beta-adrenergic blockers and limiting exercise. Sotalol and amiodarone have been used to reduce recurrences. Catheter ablation prevents or reduces VT episodes in 70% of patients, but epicardial mapping and ablation is often required.

Tetralogy of Fallot

Ventricular tachycardia occurs in 3–14% of patients late after repair of tetralogy of Fallot, and contributes to a 2% per decade risk of sudden death. Monomorphic VT is due to reentry around areas of surgically created scar in the RV (Table 249-1). Factors associated with VT risk include age >5 years at the time of repair, high-grade ventricular ectopy, inducible VT on an electrophysiologic study, abnormal RV hemodynamics, and sinus rhythm QRS duration >180 ms. An ICD is usually warranted for patients who have a spontaneous episode of VT, but criteria for a prophylactic ICD in other patients have not been established. Catheter ablation or anti-arrhythmic drug therapy is used to control recurrent episodes.

BUNDLE BRANCH REENTRY VT

Reentry through the Purkinje system occurs in ~5% of patients with monomorphic VT in the presence of structural heart disease. The reentry circuit typically revolves retrograde via the left bundle and anterograde down the right bundle, thereby producing VT that has a left bundle branch block configuration. Catheter ablation of the right bundle branch abolishes this VT. Bundle branch reentry is usually associated with severe underlying heart disease. Other scar-related VTs are often present and often require additional therapy or ICD implantation.

IDIOPATHIC MONOMORPHIC VT

Idiopathic VT in patients without structural heart disease usually presents with palpitations, lightheadedness, and occasionally syncope, often provoked by sympathetic stimulation during exercise or emotional upset. The QRS morphology of the arrhythmia suggests the diagnosis (see below). The sinus rhythm ECG is normal. Cardiac imaging shows normal ventricular function and no evidence of ventricular scar. Occasionally a patient with structural heart disease is found to have concomitant idiopathic VT, unrelated to the structural disease. Sudden death is rare.

Outflow Tract VTs originate from a focus, usually with features consistent with triggered automaticity. The arrhythmia may present with sustained VT, non-sustained VT or PVCs often provoked by exercise or emotional upset. Repeated bursts of non-sustained VT, which may occur incessantly, are known as repetitive monomorphic VT and can cause tachycardia—induced cardiomyopathy with depressed ventricular function that recovers after suppression of the arrhythmia. Most originate in the right ventricular outflow tract, which gives rise to VT that has a left bundle branch block configuration in V1 and an axis that is directed inferiorly, with tall R-waves in II, III, and AVF (see Fig. 247-2). Idiopathic VT can also arise in the left ventricular outflow tract or in sleeves of myocardium that extend along the aortic root. LV origin is suspected when leads V1 or V2 have prominent r-waves (Table 249-1). Although this typical outflow tract QRS morphology favors idiopathic VT, some cardiomyopathies, notably ARVC, can cause PVCs or VT from this region. Excluding these diseases is an initial focus of evaluation.

Left ventricular intrafascicular VT presents with sustained VT that has a right bundle branch block–like configuration. It is often exercise induced and occurs more often in men than women. The mechanism is reentry in or near the septal ramifications of the left ventricular Purkinje system.

MANAGEMENT OF IDIOPATHIC VT

Treatment is required for symptoms or when frequent or incessant arrhythmias depress ventricular function. Beta-adrenergic blockers are first-line therapy. Non-dihydropyridine calcium channel blockers (diltiazem and verapamil) are sometimes effective. Catheter ablation is warranted for severe symptoms or when beta-blockers or calcium channel blockers are not effective or not desired. Efficacy and risks of catheter ablation vary with the specific site of origin of the VT, being most favorable for arrhythmias originating in the right ventricular outflow tract. Failure of ablation is often due to inability to initiate the arrhythmia for mapping in the electrophysiology laboratory.

Left ventricular interfascicular VT can be terminated by intravenous administration of verapamil, although chronic therapy with oral verapamil is not always effective. Catheter ablation is recommended if beta-adrenergic blockers or calcium channel blockers are ineffective or not desired.

FURTHER READING

POLYMORPHIC VENTRICULAR TACHYCARDIA (VT)

Sustained polymorphic VT can be seen with any form of structural heart disease. However, unlike sustained monomorphic VT, polymorphic VT does not always indicate a structural abnormality or focus of automaticity. Reentry with continually changing reentrant paths, spiral wave reentry and multiple automatic foci are potential mechanisms (Chap. A9). Sustained polymorphic VT usually degenerates into ventricular fibrillation (VF). Polymorphic VT is typically seen in association with acute myocardial infarction or ischemia (MI), ventricular hypertrophy, and a number of genetic mutations that affect cardiac ion channels (see Table 249-1).

Polymorphic VT Associated with Acute Myocardial Infarction/Ischemia

Acute MI or ischemia is a common cause of polymorphic VT and should be the initial consideration in management. Approximately 10% of patients with acute MI develop VT that degenerates to VF, likely related to reentry through the infarct border zone. The risk is greatest in the first hour of acute MI. Following defibrillation as per the Advanced Cardiac Life Support (ACLS) guidelines, management is as for acute MI (Chap. 269). Beta-adrenergic blockers, correction of electrolyte abnormalities, and prompt myocardial reperfusion are required. Repeated episodes of polymorphic VT suggest ongoing MI and warrant assessment of adequacy of myocardial reperfusion. Polymorphic VT and VF that occur within the first 48 h of acute MI are associated with greater in-hospital mortality, but those that survive past hospital discharge are not at increased risk for arrhythmic sudden death. Long-term therapy for post-infarct ventricular arrhythmia is determined by residual left ventricular (LV) function with an implantable cardioverter defibrillator (ICD) being indicated for persistent severe left ventricular (LV) dysfunction (LV ejection fraction <0.35).

Repolarization Abnormalities and Genetic Arrhythmia Syndromes

ACQUIRED LONG QT

Abnormal prolongation of the QT interval is associated with the polymorphic VT torsades des pointes (Fig. 250-1). The VT often has a characteristic initiation sequence of a premature ventricular beat that induces a pause, followed by a sinus beat that has a longer QT interval and interruption of the T-wave by the premature ventricular contraction (PVC) that is the first beat of the polymorphic VT. This characteristic initiation is termed “pause-dependent” (Fig. 250-1). Causes of QT prolongation include electrolyte abnormalities, bradycardia, and a number of medications that block repolarizing potassium currents, notably the antiarrhythmic drugs sotalol, dofetilide, and ibutilide, but also a number of other medications used for non-cardiac diseases, including erythromycin, pentamidine, haloperidol, phenothiazines, and methadone (Table 250-1). Individual susceptibility may be related to genetic polymorphisms or mutations that influence repolarization.

Patients typically present with near-syncope, syncope, or cardiac arrest. Sustained episodes degenerate to VF requiring defibrillation. PVCs and non-sustained VT often precede episodes of sustained VT. Intravenous administration of 1–2 g of magnesium sulphate, usually suppresses recurrent episodes. If magnesium alone is ineffective, increasing heart rate with isoproterenol infusion or pacing, to a rate of 100–120 depolarizations/min as required to suppress PVCs, usually suppresses VT recurrences. These maneuvers allow time for correction of associated electrolyte disturbance (hypokalemia and hypocalcemia) and bradycardia and removal of any causative drugs (Table 250-1). Drug interactions that elevate levels of the offending agent are often a precipitating factor. Patients who experience a polymorphic VT induced by QT prolongation should be considered to have a susceptibility to the arrhythmia, and should avoid all future exposure to medications known to prolong the QT interval.

CONGENITAL LONG QT SYNDROME

The congenital long QT syndrome (LQTS) is caused by mutations in genes coding for cardiac ion channels responsible for ventricular repolarization. The corrected QT (QTc) is typically prolonged to >440 ms in men and 460 ms in women. Symptoms are due to torsades des pointes VT (Fig. 250-1). Several forms of congenital LQTS have been identified, but three groups of mutations that lead to LQT-1, LQT-2 or LQT-3 syndromes account for 90% of cases. The most frequently encountered mutations, LQTS 1 and 2, are due to abnormalities of potassium channels, but mutations affecting the sodium channel (LQTS-3) and calcium channels have also been described (Table 250-1).

Typical presentation is with syncope or cardiac arrest, usually during childhood. In LQTS-1, episodes tend to occur during exertion, particularly swimming. In LQTS-2, sudden auditory stimuli or emotional upset predispose to events. In LQTS-3, sudden death tends to occur during sleep. Asymptomatic patients may be discovered in the course of family screening or on a routine ECG. Genotyping can be helpful for family screening and to provide reassurance regarding the diagnosis. Correlations of genotype with risk and response to therapy are beginning to emerge. In most patients with LQT-1 or LQT-2, adequate doses of beta-blocker therapy (the non-selective agents nadolol or propranolol are favored) are sufficient protection from arrhythmia episodes. Markers of increased risk include QTc interval exceeding 0.5 s, female gender, and a history of syncope or cardiac arrest. Recurrent syncope despite beta-blocker therapy or a high-risk profile merits consideration of an ICD. Avoidance of QT prolonging drugs is critical for all patients with the LQTS including those who are genotype positive, but have normal QT intervals.

SHORT QT SYNDROME

Short QT syndrome is very rare compared to the LQTS. The QTc is shorter than 0.36, and usually less than 0.3 s. The genetic abnormality causes a gain of function of the potassium channel (I_Kr) or reduced inward depolarizing currents. The abnormality is associated with atrial fibrillation, polymorphic VT, and sudden death.

BRUGADA SYNDROME

Brugada syndrome is a rare syndrome characterized by >0.2 mV of ST segment elevation with a coved ST segment and negative T-wave in more than one anterior precordial lead (V1–V3) (see Fig. 248-1) and episodes of syncope or cardiac arrest due to polymorphic VT in the absence of structural heart disease. Cardiac arrest may occur during sleep or be provoked by febrile illness. Males are more commonly affected than females. Mutations involving cardiac sodium channels are identified in ~25% of cases. Distinction from patients with similar ST elevation owing to left ventricular hypertrophy, pericarditis, myocardial ischemia or MI hyperkalemia, hypothermia, right bundle branch block and arrhythmogenic right ventricular cardiomyopathy (ARVC) is often difficult. Furthermore, the characteristic ST-segment elevation can wax and wane over time and may become pronounced during acute illness and fever. Administration of the sodium channel blocking drug flecainide, ajmaline, or procainamide can augment or unmask ST elevation in affected individuals. An ICD is indicated for individuals who have had unexplained syncope or been resuscitated from cardiac arrest. Quinidine and catheter ablation of abnormal regions in the epicardial right ventricular (RV) has been used successfully to suppress frequent episodes of VT.

EARLY REPOLARIZATION SYNDROME

Patients resuscitated from VF who have no structural heart disease or other identified abnormality have a higher prevalence of J-point elevation with notching in the terminal QRS. A family history of sudden death is present in some patients, suggesting a potential genetic basis. J-point elevation is also seen in some patients with the Brugada syndrome and is associated with a higher risk of arrhythmias. An ICD is recommended for those who have had prior cardiac arrest. It should be noted that J-point elevation is commonly seen as a normal variant in patients without arrhythmias and in the absence of specific symptoms, the clinical relevance is not known.

CATECHOLAMINERGIC POLYMORPHIC VT

This rare familial syndrome is due to mutations in the cardiac ryanodine receptor and less commonly, the sarcoplasmic calcium binding protein, calsequestin 2. These mutations result in abnormal sarcoplasmic calcium handling and polymorphic ventricular arrhythmias that resemble those seen with digitalis toxicity. The VT is polymorphic or has a characteristic alternating QRS morphology termed bidirectional VT. Patients usually present during childhood with exercise or emotion induced palpitations, syncope, or cardiac arrest. Beta-adrenergic blockers (e.g., nadolol and propranolol) and an implantable defibrillator are usually recommended. Verapamil or flecainide or surgical left cardiac sympathetic denervation reduces or prevents recurrent VT in some patients.

HYPERTROPHIC CARDIOMYOPATHY (HCM)

HCM is the most common genetic cardiovascular disorder occurring in 1 in 500 individuals and is a prominent cause of sudden death before the age of 35 years (Chap. 254). Sudden death can be due to polymorphic VT/VF. Rarely sustained monomorphic VT occurs related to areas of ventricular scar. Risk factors for sudden death in this disease include young age, non-sustained VT, failure of blood pressure to increase during exercise, recent (within 6 months) syncope, ventricular wall thickness >3 cm, and possibly the severity of LV outflow obstruction. An ICD is generally indicated for high-risk subjects, but the specific risk profile warranting an ICD continues to be debated. Surgical myectomy, performed to relieve outflow obstruction has been associated with a sudden death rate of <1% per year. The reported annual rate of sustained VT or sudden death after transcoronary ethanol septal ablation done to relieve outflow obstruction has been reported to range between 1 and 5%.

GENETIC DILATED CARDIOMYOPATHIES

Genetic dilated cardiomyopathies account for 30–40% of cases of nonischemic dilated cardiomyopathies. Some are associated with muscular dystrophy. Autosomal dominant, recessive, X-linked, and mitochondrial inheritance patterns are recognized. Mutations in genes coding for structural proteins of the nuclear lamina (Lamin A/C) and the SCN5A gene are particularly associated with conduction system disease and ventricular arrhythmias. They can experience polymorphic VT and cardiac arrest or develop areas of scar causing sustained monomorphic VT. ICDs are recommended for those who have had a sustained VT or are at high risk due to significantly depressed ventricular function (LV ejection fraction ≤0.35 and associated with heart failure) or a malignant family history of sudden death.

VENTRICULAR FIBRILLATION

VF is characterized by disordered electrical ventricular activation without identifiable QRS complexes (see Fig. 247-3E). Spiral wave reentry and multiple circulating reentry wavefronts are possible mechanisms. Sustained polymorphic or monomorphic VT that degenerates to VF is a common cause of out of hospital cardiac arrest. Treatment follows ACLS guidelines with defibrillation to restore sinus rhythm. If resuscitation is successful, further evaluation is performed to identify and treat underlying heart disease and potential causes of the arrhythmia, including the possibility that monomorphic or polymorphic VT could have initiated VF. If a transient reversible cause such as acute MI is not identified, therapy to reduce the risk of sudden death with an ICD is often warranted. Chronic amiodarone therapy may be considered for individuals who are not ICD candidates.

FURTHER READING

ELECTRICAL STORM