Sheldon H. Gottlieb
Joseph E. Marine
Hugh Calkins
Contraction of the heart normally is the result of a well-orchestrated electromechanical system. The orderly function of the system is maintained by domination of the heart rate by a single biologic pacemaker (the sinoatrial [SA] node), by the relatively fast and uniform conduction of the electrical signal via specialized conduction pathways (His-Purkinje system), and by the relatively long and uniform duration of the electrical signal relative to its velocity of conduction through these pathways, which ensures uniform electrical excitation and contraction of the heart. A cardiac arrhythmia is any disturbance in the normal sequence of impulse generation and conduction in the heart.
Arrhythmias may occur in the absence of heart disease, may be symptoms of severe disease, or may themselves cause disease. Their significance and the need for treatment must be evaluated in the context of the clinical situation in which they occur. A precise etiologic diagnosis and an understanding of the pharmacology of the medications used are necessary to treat arrhythmias effectively. In recent years, there have been major advances in nonpharmacologic therapy of arrhythmias with a corresponding de-emphasis on treatment with antiarrhythmic drugs.
Physiology of Impulse Generation and Conduction
Action Potential
Muscle contraction is stimulated by an electrical impulse, the action potential. In skeletal muscle, the action potential lasts several milliseconds, and the electrical activity is dissipated before the beginning of contraction. In cardiac muscle, however, the action potential lasts several hundred milliseconds, almost as long as the mechanical contraction of the myocyte itself (Fig. 64.1). In this way, the action potential not only stimulates contraction of the heart but also determines the duration and intensity of contraction. Furthermore, as long as the action potential is maintained, the heart cannot be stimulated to contract again.
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FIGURE 64.1. Comparison between relative time scales of electrical (solid curve) and mechanical (dashed curve) activity in skeletal (A) and cardiac (B) muscle. (From Noble D. The initiation of the heart beat. Oxford, England: Clarendon Press, 1975 , with permission.) |
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The action potential is generated by depolarization and repolarization of the cardiomyocyte (Fig. 64.2). In the resting state, the intracellular concentration of potassium is high and that of sodium is low compared with the concentrations in extracellular fluid. The resting gradients of these ions are maintained by metabolic activity within the cell membrane, resulting in the resting membrane potential. This potential is strongly negative (i.e., there is an electrochemical gradient across the membrane so that the inside of the membrane is negatively charged compared with the outside of the membrane). If an electrical stimulus is applied, the membrane becomes highly permeable to sodium ions, which rapidly enter the cell (phase 0). The membrane is thus depolarized (loses its negative charge) and is transiently positively charged (overshoot). Repolarization occurs relatively slowly as chloride (phase 1), calcium (phase 2), and then potassium ions (phase 3) move back into the cell and thereby restore the resting potential (phase 4) (Fig. 64.2) (1).
Relationship to the Electrocardiogram
In the heart, the phases of rapid depolarization and overshoot correspond to the QRS complex of the electrocardiogram (ECG); phase 2 corresponds to the ST segment and phase 3 to the T wave (Fig. 64.2). During phase 2 the membrane is absolutely, and in phase 3 it is relatively, refractory to propagation of another electrical impulse.
Fast and Slow Currents
In most cardiac tissue, excitation is propagated by the rapidly depolarizing sodium current so that the impulses are conducted rapidly. However, in the SA node and the proximal part of the atrioventricular (AV) node, excitation is propagated by a slowly depolarizing current generated by the influx of calcium ions into the cell. Furthermore, in diseased cardiac muscle, the sodium current may be inhibited and depolarization may occur entirely via the slow calcium current; therefore, the action potential may be conducted very slowly. This difference in conduction velocity between cells depolarized by the sodium versus the calcium current has important implications in the generation and treatment of arrhythmias.
Pacemaker Generation
In most cardiac cells, an action potential is not generated until an electrical stimulus is applied. In pacemaker cells, slow spontaneous depolarization occurs during phase 4 until a threshold is reached, whereupon phase 0 rapidly ensues (Fig. 64.2); this process is calledautomaticity. In the absence of heart block, the heart rate is controlled by the pacemaker cells that depolarize most rapidly, because then the action potential is conducted rapidly throughout the heart and initiates rapid depolarization of other cells, even if they already have begun spontaneous slow depolarization. Automaticity is affected by the rate of slow spontaneous depolarization and the threshold potential. Automaticity is enhanced by increased sympathetic tone, decreased vagal tone, increased catecholamine concentration in the blood, thyroxine, and digoxin. It is suppressed by decreased sympathetic tone, increased vagal tone, decreased thyroxine concentration, and numerous drugs, including those used in the treatment of arrhythmias. Antiarrhythmic drugs may increase automaticity under some conditions.
Impulse Generation and Conduction
Sinoatrial Node
The SA node is composed of pacemaker cells and is located at the junction of the right atrium and the superior vena cava (Fig. 64.3). The cells of the SA node spontaneously depolarize more rapidly than any other cells within the heart and thereby control the heart rate under normal conditions.
Atrioventricular Node
The AV node is part of the specialized conduction system that carries the electrical impulse from the atrium to the ventricle. The AV node lies at the junction of the right
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atrium and the interventricular septum, just above the tricuspid valve. Conduction through the AV node, which is mediated by calcium channels, is unique in that it is relatively slow; as a result, there is a 100- to 200-millisecond delay between activation of the atria and ventricles. This delay is important because it ensures that ventricular contraction occurs after atrial contraction is complete, thus maximizing the filling of the ventricles with blood. Another unique property of the AV node is that conduction is decremental; as more impulses arrive at the AV node, fewer get through, and those that do conduct through the AV node travel at a slower rate. The property of decremental conduction allows the AV node to serve as a protective gate, shielding the ventricles from excessively rapid stimulation from the atria, as can occur during atrial fibrillation and atrial flutter. The AV node also has intrinsic pacemaker activity, similar to that of the sinus node but slower (usually at a rate of 40–60 bpm). Because of the slower rate, the AV node may function as a subsidiary pacemaker if the SA node fails or if AV conduction is blocked.
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FIGURE 64.2. Transmembrane potentials from the sinus node and a Purkinje fiber. Note the spontaneous diastolic depolarization in theupper panel, characteristic of pacemaker fibers. The numbers in the middle panel are explained in the text. The lower panel shows the correlation of the time sequence of changes in the action potential with the surface electrocardiogram. Alterations in depolarization are reflected in changes in the QRS duration of the surface record; those in repolarization are associated with alterations in the QT interval. (From Singh BN, Collett JT, Chew CYC. New perspectives in the pharmacologic therapy of cardiac arrhythmias. Prog Cardiovasc Dis 1980;22:243 , with permission.) |
Bundle of His
When the action potential leaves the AV node, it enters the specialized conducting fibers known as the bundle of His. The main bundle of His divides into three branches: the right bundle branch, which runs along the right ventricular surface of the septum; the left anterior superior branch, which runs along the left ventricular (LV) surface of the septum; and the left posterior inferior branch, which runs along the posterior wall of the left ventricle. The action
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potential is conducted through the bundle branches and into the myocardium by a widespread network of smaller fibers known as Purkinje fibers.
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FIGURE 64.3. Anatomy of impulse generation. (From Willerson JT, ed. Treatment of heart diseases. London: Gower Medical Publishers, 1992 . By permission of Mosby International.) |
Mechanism of Cardiac Arrhythmias
Bradyarrhythmias result from one of two mechanisms: suppression of impulse formation and conduction block. Tachyarrhythmias result from one of three mechanisms: enhanced impulse formation, triggered activity, and reentry of the action potential into a pathway through which it has already passed (1). Multiple mechanisms may coexist in the same patient (e.g., atrial fibrillation with high-degree AV block in a patient with sinus node dysfunction). Furthermore, an arrhythmia may be initiated by one mechanism (enhanced automaticity of pulmonary vein tachycardia) and become sustained by another (reentry), as in the case of paroxysmal atrial fibrillation.
Suppression of Impulse Formation and Conduction Block
A disease process that interferes with pacemaker activity within the SA node or with the movement of the electrical impulse through the normal conduction pathways of the heart results in abnormal slowing of the heart rate (bradyarrhythmia) and/or in one of the various forms of heart block.
Enhanced Impulse Formation
Enhanced automaticity of a part of the cardiac conduction system may result in the initiation of an impulse more rapidly than is normally generated by the SA node. If that happens episodically, occasional premature contractions occur, the nature of which depends on the location of the ectopic pacemaker. On the other hand, if there is rapid sustained firing of the ectopic focus, an ectopic tachycardia ensues.
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Triggered Activity
Triggered arrhythmias are the least common; they result from after depolarizations that follow an action potential and that reach threshold for triggering additional impulses (2). Examples of triggered arrhythmias include torsade de pointes, multifocal atrial tachycardia, and atrial tachycardia resulting from digitalis toxicity.
Reentry
Most clinically significant arrhythmias result from reentry (Fig. 64.4). Reentrant arrhythmias occur in the setting of two anatomically or functionally distinct conduction pathways, unidirectional conduction block in one of the pathways, and slowed conduction. When these three conditions are fulfilled, the electrical impulse may travel down one limb of the reentrant circuit and return via the second limb of the circuit, resulting in a “short circuit” or “circus” arrhythmia. These arrhythmias may result from anatomic abnormalities such as an accessory AV connection, as in the case of the Wolff-Parkinson-White (WPW) syndrome.
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FIGURE 64.4. Sequence of activation of a loop of Purkinje fiber bundles and ventricular muscle during reentry. A region of unidirectional conduction block is indicated by the dark shaded area in branch B. Conduction cannot occur through this area in the antegrade direction (from B to ventricular muscle) but only in the retrograde direction (from ventricular muscle to B). Slow conduction is present in the loop. The bottom of the figure shows an electrocardiographic pattern that may result from this type of reentry. (From Wit AL, Rosen MR, Hoffman BF. Electrophysiology and pharmacology of cardiac arrhythmias. II: Relationship of normal and abnormal electrical activity of cardiac fibers to the genesis of arrhythmias. B: re-entry, section I. Am Heart J 1974;88:664 , with permission.) |
Diagnosis of Arrhythmias: General Considerations
History
Arrhythmias may cause a variety of symptoms, or they may be asymptomatic. Symptoms are principally caused by an appreciation of an irregular or rapid rhythm (palpitations) (3,4) or by a reduction in cardiac output (light-headedness, dizziness, presyncope, syncope). Other symptoms may include dyspnea, diaphoresis, chest pain, and anxiety. When taking a history from a patient with a suspected arrhythmia, it is important to define the onset, regularity, and duration of symptoms and whether any factors seem to trigger symptoms (e.g., drinking coffee, smoking, exercise, emotional stress, taking or forgetting to take medications).
It is important to determine whether there is a history or symptoms of an underlying disease that may be associated with arrhythmia (e.g., hypertension, heart failure, ischemic or valvular heart disease, thyrotoxicosis), because the prognosis and recommended treatment depend to a large extent on the nature and severity of underlying heart disease. Patients should be asked about a family history of arrhythmias or sudden death; the taking of stimulant drugs either illicitly (see Chapter 29) or as an attempt to lose weight (see Chapter 83) or to stay awake; and the taking of prescription drugs that can cause arrhythmias (digoxin, theophylline, diuretics, β-blockers, α-agonists, tricyclic antidepressants, and antihypertensives) or even of over-the-counter medicines that might be associated with torsade de pointes (see below for additional discussion).
Palpitations are heartbeats that are sensed, usually because the beats are fast or irregular. However, they do not necessarily imply a significant arrhythmia, and they may represent only sinus tachycardia in an otherwise healthy person (3). In contrast, patients with paroxysmal supraventricular arrhythmias may be misdiagnosed as having a panic disorder (see Chapter 22) (5). Clinical descriptors of palpitations that are predictive of an arrhythmia include “heart fluttering,” “heart stopping,” and “irregular heartbeat” (1,3). Palpitations often are localized to the area of the apex beat, but paroxysmal supraventricular tachycardias (PSVTs) are commonly sensed in the side of the neck or under the upper sternum. Some people primarily sense the compensatory pause after an extra heartbeat, whereas others sense the extra beat itself. Usually the contraction after an extra beat is more powerful than a normal beat (i.e., postextrasystolic potentiation), and this
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stronger beat may be the one that is sensed. Supraventricular beats are more commonly sensed as palpitations than are ventricular beats; in fact, prognostically significant runs of ventricular tachycardia (VT) may be asymptomatic.
Light-headedness, dizziness, presyncope, and syncope are potential symptoms of a variety of arrhythmias, both life-threatening and benign. A variety of nonarrhythmic conditions may cause these symptoms as well. Chapter 89 discusses in detail these symptoms and the conditions associated with them.
Physical Examination
Paroxysmal arrhythmias are rarely present when the patient is being examined in the outpatient setting; therefore, attention should be focused on obtaining orthostatic vital signs and examining the patient for conditions associated with arrhythmia, such as hypertensive heart disease (see Chapter 67), heart failure (see Chapter 66), chronic obstructive lung disease (see Chapter 60), ischemic heart disease (seeChapter 62), or valvular heart disease (see Chapter 65). These conditions sometimes can be recognized by characteristic clinical findings.
When an arrhythmia is present while the patient is being seen, the characteristics of the arrhythmia may be revealed on physical examination by inspection of the jugular venous pulse, palpation of the arterial pulse, and auscultation of the heart. Inspection of the jugular venous pulse may reveal atrial activity. If the patient has AV dissociation, so-called “cannon waves” may be seen intermittently in the jugular veins. They are caused by sudden elevation of central venous pressure when the right atrium contracts against a closed tricuspid valve. Atrial tachycardia may be revealed by rapid, prominent jugular waves at a rate that is faster than the arterial pulse or heart sounds.
Auscultation of the heart establishes the ventricular rate and rhythm. One should note the intensity of the first heart sound (S1), which is the most useful heart sound in the evaluation of arrhythmia. For example, variation in the intensity of S1 during a regular tachycardia suggests AV dissociation; variation during a regular bradycardia suggests second- or third-degree AV block. The intensity of S1 also is a function of the PR interval. A loud S1 suggests a short PR interval; a soft S1 suggests a long PR interval. The latter may be caused by digitalis toxicity, drugs that block the AV node (e.g., β-blockers, calcium channel blockers, or amiodarone), disease of the AV node, or electrolyte abnormalities (for other cardiac conditions affecting the intensity of S1, see Chapter 65).
Use of the Electrocardiogram
Obtaining a 12-lead ECG when evaluating a patient who is suspected of having an arrhythmia is essential (6). An ECG obtained while the patient is experiencing the arrhythmia often will provide a definitive diagnosis. An ECG obtained while the patient is asymptomatic may provide important clues to the presence of electrical or structural substrate for arrhythmias, such as the presence of delta waves, bundle-branch block, prolonged QT interval, Q waves, atrial enlargement, or LV hypertrophy. Ambulatory (Holter) monitoring, event monitoring (loop recorder) (7), or exercise electrocardiography often is required to detect a sporadic arrhythmia or an arrhythmia that is induced by exertion (8). Upright tilt-table testing may be necessary to differentiate presyncope or syncope caused by an arrhythmia from neurocardiogenic syncope (also called vasodepressor or vasovagal syncope). Chapter 89 discusses the use of this test.
In situations where an arrhythmia cannot be diagnosed accurately by standard ECG or surface monitoring, an invasive electrophysiologic study can be obtained by catheterization in order to make a precise diagnosis. Increasingly, curative therapy of the arrhythmia by catheter ablation can be provided during the same procedure.
The Electrocardiogram
A full discussion of ECG interpretation is beyond the scope of this chapter, and the reader is referred to several excellent textbooks on the subject (see Constant J., http://www.hopkinsbayview.org/PAMreferences). When evaluating a patient with an arrhythmia, a number of features of the standard 12-lead ECG should be assessed.
Atrial Activity
Atrial activity is best assessed in leads II, III, aVF, and V1. The presence of P waves should be identified. If P waves are present, their configuration and their relationship to the QRS complexes should be established. Normally the PR interval is between 120 and 200 milliseconds (each 1-mm segment on the ECG = 40 milliseconds), and each QRS complex is preceded by a P wave whose vector is such that the P wave is upright in leads II, III, and aVF. If P waves are not present, other evidence of atrial activity (fibrillation or flutter waves) should be sought.
Ventricular Activity
The duration of the QRS complexes (normally <100 milliseconds) should be measured and the regularity of ventricular activity assessed. A regular rhythm may be interrupted by so-called premature beats—QRS complexes that appear before the next regular beat is expected. If premature beats are present, then whether the premature beats have a fixed relationship to the preceding normal beat and whether their configuration is the same as that of the regularly occurring complexes should be noted.
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Ambulatory Electrocardiogram
The ambulatory (Holter) ECG records the electrical activity of the heart from two or three surface leads, usually for a 24- to 48-hour period (9). The recording device is small and does not interfere with any of the patient's activities (except bathing and swimming). The technique is useful in the following circumstances:
Episodic arrhythmias are not commonly detected during 24 hours of Holter monitoring (10). If symptoms are infrequent, it may be necessary to record the ambulatory ECG for 48 to 72 hours or to use an event monitor (see later discussion). The patient should be asked to keep a record of symptoms while being monitored to determine whether these symptoms are attributable to arrhythmia. Repeated documentation of normal rhythm occurring during symptoms can be as valuable as detection of an arrhythmia. Patients should be instructed to record symptoms associated with their palpitations, including dizziness, nausea, shortness of breath, chest discomfort, or arm pain (10).
If symptoms are infrequent, an event monitor, also known as a cardiac event recorder or external loop recorder, may be useful in making a diagnosis of an arrhythmia (7). These pager-sized devices are worn clipped to the patient's belt or dress during all daily activities. The patient wears two chest electrodes that are attached to the monitor by snap-on leads. The patient may easily remove the monitor and leads to shower or bathe, and fresh electrodes are easily applied by the patient. Event monitors record a 30- to 60-second “loop” of the patient's cardiac electrical activity on a computer chip. If the patient experiences symptoms, he or she can activate the device by pushing a button; this saves the loop of beats in the device memory. The recorded ECG is transmitted via an audiotelephonic interface to a central monitor, where the rhythm strip is printed out and sent to the referring clinician by telefax or e-mail. The recording technician will contact the referring clinician directly if potentially dangerous arrhythmias are detected. The devices usually are worn for 30 days or until an event is recorded.
If events are extremely infrequent or are associated with syncope, which may preclude patient activation of the recorder, an insertable loop recorder may be advised. These devices, which are smaller than permanent pacemakers, are implanted under the skin in the left upper chest. The device can be implanted in a 20-minute outpatient procedure and can remain in place for >1 year, after which they are easily explanted. They can be activated with the use of an external magnetic activator, which is a pager-sized device given to the patient. Recorded events are downloaded through a standard pacemaker programmer during an office visit. Second-generation external and insertable loop recorders also can be programmed to automatically detect and store bradyarrhythmias or tachyarrhythmias without external activation.
Studies show that event monitors, when used for diagnosis of intermittent palpitations, are more likely than Holter monitors to record diagnostic arrhythmias and do so at a lower cost (10). The cost of Holter monitoring and external event monitoring is approximately five to ten times that of a standard ECG. Insertable loop recorders, although more expensive, may be cost-effective in the evaluation of patients with recurrent undiagnosed syncope by obviating the need for other tests and repeated hospitalizations.
Exercise Electrocardiogram
Chapter 62 describes exercise ECG in detail. It is a useful test in the evaluation of patients who have symptoms suggestive of an arrhythmia during or after exercise and in those with premature ventricular contractions to determine whether they become more or less frequent during or after exercise (see Ventricular Premature Beats and Ventricular Tachycardia) (11). It also may be helpful in assessing the adequacy of ventricular rate control in patients with atrial fibrillation.
General Principles in Management of Arrhythmias
Once a patient has been established as having a particular arrhythmia, the practitioner must decide whether treatment is necessary. A general principle is that treatment should be limited to symptomatic patients or to patients with prognostically significant arrhythmias (12). Alternatives to antiarrhythmic medications should generally be considered whenever possible (13). Another essential determination to be made is whether the arrhythmia is caused by a metabolic abnormality (e.g., hypoxia, electrolyte imbalance, fever, drug toxicity) or by heart disease (e.g., heart failure, ischemia, pericarditis), the correction of which will restore a normal cardiac rhythm. If specific therapy is indicated, an appropriate regimen should be selected: one or more of the antiarrhythmic drugs, electrical conversion of the arrhythmia, a cardiac pacemaker or antitachycardia device, catheter or surgical ablation
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of the arrhythmia focus, or a combination of these approaches. Whether the potential benefits of the proposed antiarrhythmic therapy outweigh the risks and whether the cost, side effects, and inconvenience of the therapy are justified must be determined.
Antiarrhythmic Drug Therapy
An important and often difficult issue to determine is whether hospitalization is required for the initiation of therapy. A consensus exists that antiarrhythmic therapy should be initiated in the hospital for patients with hemodynamically unstable arrhythmias, such as sustained VT, or for initiation of antiarrhythmic agents (other than amiodarone) in patients with significantly compromised cardiac function as evidenced by LV ejection fraction (LVEF) <40%. Antiarrhythmic therapy often can be initiated on an ambulatory basis in patients with functionally normal hearts in the absence of a hemodynamically compromising arrhythmia. Although there is some debate, many cardiologists believe that, in the absence of a hemodynamically compromising arrhythmia, even patients with ejection fraction (EF) <40% can undergo amiodarone initiation on an outpatient basis (14).
Some antiarrhythmic drugs prolong the QT interval and may induce torsade de pointes (polymorphic VT; see later discussion), particularly when therapy is first started (for a list of these drugs, see http://www.torsades.org). Two such drugs are sotalol and dofetilide. Patients must be monitored as inpatients when therapy with these agents is started. Given this risk, a cardiologist should be consulted whenever these two drugs are begun. Consultation with a cardiologist may be helpful in deciding which patients who are beginning therapy with other antiarrhythmic drugs, such as procainamide, quinidine, disopyramide, and flecainide, require hospitalization for continuous ECG monitoring.
Pharmacology of Antiarrhythmic Drugs
Antiarrhythmic drugs are traditionally grouped into four classes (1,15). Class I drugs (sodium channel blockers), such as quinidine (16), lidocaine, and flecainide, interfere with the fast inward sodium current. Class II drugs (beta blockers), such as propranolol, metoprolol, and atenolol, affect sympathetically mediated excitability through competitive blockade of the β-adrenergic receptor. Class III drugs (potassium channel blockers), such as sotalol and dofetilide, prolong the action potential duration by decreasing the late inward (phase 3) potassium current. Class IV drugs (calcium channel blockers), such as verapamil and diltiazem, block calcium-mediated slow channel currents in the myocardium (17). Amiodarone, although generally categorized as a class III agent, is a unique antiarrhythmic drug with properties of all four classes (18).
Digitalis and adenosine do not fit into this classification scheme. Strictly speaking, digitalis is not an antiarrhythmic drug in that it does not have a direct effect on membrane function. It acts indirectly as an antiarrhythmic agent by increasing vagal activity, thereby increasing the refractory period of specialized conduction tissue and slowing the velocity of the action potential through the AV node. Digitalis also increases the frequency of fibrillatory waves in atrial fibrillation, thereby presenting more impulses to the AV node, making the node refractory to conduction (this process is called concealed conduction). Chapter 66 discusses general considerations in the use of digitalis, including dosages, choice of preparation, and recognition and treatment of toxicity. The pharmacology and use of adenosine are discussed below.
Table 64.1 lists some of the characteristics of the orally administered antiarrhythmic drugs that can be used to treat ambulatory patients.
Most antiarrhythmic drugs have a low toxic/therapeutic ratio, and all have potentially life-threatening side effects (Table 64.2). In addition to direct toxic effects, antiarrhythmic drugs often have complex interactions with commonly used drugs such as digoxin, warfarin, and certain antihistamines and antibiotics (see Torsade de Pointes and the Long QT Interval Syndrome). They may paradoxically induce arrhythmias and increase the incidence of sudden cardiac death, a clinical scenario called proarrhythmia. Proarrhythmic effects can include virtually any arrhythmia but often are seen as an increased frequency of premature ventricular contractions (PVCs) or sudden onset of VT, torsade de pointes, or ventricular fibrillation. Although in the past it was believed that proarrhythmic effects of drugs usually are seen within several days after an antiarrhythmic drug is started or the dosage is changed, the results of the Cardiac Arrhythmia Suppression Trial (CAST) showed that the appearance of proarrhythmia may be delayed by weeks or months (19). In general, the proarrhythmic effects of antiarrhythmic drugs usually are seen in patients with severe heart disease, prior myocardial infarction (MI), and depressed LV systolic function (EF <40%) (20,21).
The risk of antiarrhythmic drug treatment has been highlighted by several clinical trials and reviews based on meta-analyses. An almost fourfold increase in mortality was demonstrated in patients with myocardial dysfunction and nonsustained VT after an MI when they were treated with either flecainide or encainide (19). Also, a significant increase in post-MI mortality has been shown in patients treated with class I antiarrhythmic agents (22). A meta-analysis of patients with atrial fibrillation treated with quinidine showed an increase in mortality (23), and an analysis of antiarrhythmic drug use in the Stroke Prevention in Atrial Fibrillation Trial reported an almost fivefold increased risk of cardiac death among patients with heart failure who were receiving an antiarrhythmic drug
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(24). These studies have resulted in more cautious use of these medications, especially in patients with structural heart disease.
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TABLE 64.1 Characteristics of Antiarrhythmic Drugs |
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TABLE 64.2 Adverse Effects of Antiarrhythmic Drugs |
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Class I Drugs
All class I drugs block the sodium channel, but the effects on the action potential duration and on repolarization vary depending on the kinetics of channel blockade. This fact has practical application in the choice of drugs for treatment of specific arrhythmias and in the use of a combination of drugs (1), although consultation with a cardiologist is advisable before combining these drugs.
Class I drugs have been subdivided into three classes based on the kinetics of sodium channel blockade: IA, IB, and IC (Table 64.1).
Class IA Drugs
Class IA drugs prolong the action potential duration (Fig. 64.1) and so prolong the QRS duration, QT interval, and effective refractory period. These drugs include quinidine, procainamide, and disopyramide.
Quinidine
In addition to its direct effects on the heart, quinidine blocks parasympathetic stimulation by the vagus nerve and may enhance AV conduction (and the ventricular rate) in some patients. For this reason, patients with supraventricular tachyarrhythmias should generally be treated with a drug to slow AV nodal conduction (e.g., digitalis, a β-blocker) before they are given quinidine. Quinidine also is a moderately potent inhibitor of α-adrenergic activity and may cause orthostatic hypotension (16).
Several preparations of quinidine are available. Quinidine sulfate is the least expensive, but quinidine gluconate has a lower incidence of gastrointestinal side effects. A sustained-release preparation containing gluconate (Quinaglute Dura Tabs) can be given every 8 to 12 hours.
Quinidine has a number of possible toxic effects. The most common are gastrointestinal (especially diarrhea) and often occur within hours after the drug is administered. Cinchonism (tinnitus, headache, visual disturbances) is uncommon if blood levels are checked periodically and if the dosage is appropriately adjusted. Hypersensitivity reactions (e.g., rash, arthralgias, immune thrombocytopenia, hemolytic anemia) occur occasionally.
Cardiac toxicity usually is dose related and often is preceded by prolongation of the QT interval; QT prolongation ≥25% beyond baseline is an indication for reduction of the quinidine dosage. Serious toxicity is manifested by high-degree AV block, VT, torsade de pointes (see later discussion), or ventricular fibrillation—all emergency situations that may require cardiorespiratory support and warrant immediate hospitalization. Patients receiving quinidine (or other drugs that prolong the QT interval, such as procainamide or sotalol) should be checked periodically by ECG (e.g., after initiation, after dose increase, and every 6 months) to monitor the QT interval. Patients whose QT interval is >450 milliseconds or whose QT increases consistently over time should be referred to a cardiologist for re-evaluation of the need for a particular drug or for determination of either a dose reduction or drug discontinuation.
Quinidine may have interactions with other drugs. It is especially important to recognize that digoxin levels may increase significantly in patients given quinidine because it decreases renal clearance of digoxin. Therefore it is important to monitor serum digoxin concentrations when quinidine is first prescribed and to alter the dosage of digoxin to prevent intoxication. Quinidine is an α-adrenergic blocker and, if prescribed with vasodilators (e.g., nitrates, nifedipine, hydralazine, prazosin, angiotensin-converting enzyme inhibitors) or with potent diuretics (e.g., furosemide), can cause symptomatic (especially postural) hypotension. Drugs that are metabolized by hepatic microsomal enzymes may alter the pharmacokinetics of quinidine, and, conversely, quinidine may alter the kinetics of one of these drugs. For example, phenytoin may accelerate the metabolism of quinidine, shortening its effect, and quinidine may inhibit the metabolism of warfarin, prolonging its effect.
Most importantly, the patient and clinician both must be aware of the need to avoid other drugs that prolong the QT interval. Drugs that prolong the QT interval and/or induce torsade de pointes are listed on a convenient website at http://www.torsades.org. Although quinidine has been used to treat a variety of supraventricular and ventricular arrhythmias, it is not commonly used today because of concerns about proarrhythmia, the availability of other effective and safer antiarrhythmic drugs, and the development of gastrointestinal side effects in a large proportion of patients taking the drug. The indications for quinidine (and all other antiarrhythmic drugs) should be regularly and critically reviewed by clinicians who prescribe it (16).
Procainamide
The suppressive effects of procainamide on the electrical activity of the heart are the same as those of quinidine, but, unlike quinidine, procainamide has little effect on vagal or α-adrenergic activity. In addition, unlike quinidine, procainamide has the active metabolite N-acetyl procainamide (NAPA), which has potassium channel blocking properties.
Like quinidine, procainamide can be used to treat many supraventricular arrhythmias. Its use today is limited because of concerns about proarrhythmia, the availability of other effective and safer antiarrhythmic drugs, and the high proportion of patients who develop a lupus-like syndrome after long-term treatment with procainamide.
The noncardiac toxicity of procainamide is different from that of quinidine. Gastrointestinal symptoms occur
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less often, and, when they do, nausea and vomiting are more common than diarrhea. Fever and chills or granulocytopenia occurs occasionally.
Within 3 months, 50% of people taking procainamide develop antinuclear antibodies (ANAs), and 90% do so within 12 months (25). From 20% to 30% of patients with ANAs develop a lupus-like syndrome characterized by serositis (pleuritis, pericarditis, synovitis), fever, and hepatomegaly. Unlike classic systemic lupus erythematosus, vasculitis is not a manifestation of drug-induced lupus, so renal disease, for example, does not occur. Most important, the syndrome often abates, usually within days, when the drug is discontinued (ANAs may persist for months). The major threat of the syndrome is hemorrhagic pericarditis, and one must watch for signs and symptoms of pericardial tamponade. For these reasons, procainamide is not recommended for long-term use.
Disopyramide
Disopyramide has direct membrane effects very much like those of quinidine. Like quinidine, disopyramide blocks parasympathetic activity. It is approved by the United States Food and Drug Administration (FDA) for the treatment of specific ventricular arrhythmias: unifocal or multifocal PVCs and VT. Like quinidine and procainamide, disopyramide is not often used in ambulatory practice for treatment of patients with supraventricular or ventricular arrhythmias. One useful niche for this drug is in the treatment of the small subset of patients with vagally mediated atrial fibrillation. Perhaps the most common use of disopyramide today is in the treatment of patients with vasodepressor syncope (see Chapter 89). The effectiveness of disopyramide in the treatment of this condition is related to its vagolytic and negative inotropic effects. Disopyramide has also proved useful in the treatment of hypertrophic cardiomyopathy because of its negative inotropic effects.
The noncardiac toxicity of disopyramide results mainly from its anticholinergic effects, which include dry mouth, blurred vision, urinary hesitancy, and constipation. For these reasons, disopyramide generally is not advised for elderly patients. Nausea, vomiting, and diarrhea are less common than after administration of quinidine or procainamide. The cardiac toxicity of the drug is somewhat similar to that of quinidine in that it can prolong the QT interval and produce torsade de pointes (see later discussion). Disopyramide may cause or intensify heart failure or cause hypotension in patients who have compromised LV function, so it should not be administered to patients with these conditions.
Class IB Drugs
Class IB drugs shorten repolarization and the QT interval and have little effect on the duration of the QRS complex. They are generally not effective for supraventricular arrhythmias. Mexiletine is the principal drug of this class in the United States. This drug has electrophysiologic effects similar to those of lidocaine. Adverse effects include nausea, tremulousness, dizziness, and anxiety. It may be useful in combination with a class IA or III drug (see later discussion), but consultation with a cardiologist is advisable before the drug is prescribed.
Class IC Drugs
Class IC drugs slow conduction and widen the QRS complex but cause only small changes in refractoriness or the QT interval. Flecainide and propafenone, the class IC drugs currently available, both are effective against serious ventricular arrhythmias and may be particularly useful in the treatment of supraventricular arrhythmias, especially atrial fibrillation. Because flecainide has been shown to be associated with an elevated risk of sudden death when used in patients with ventricular dysfunction after MI (19), it should generally not be used in patients with ischemic heart disease, particularly if EF <40%. Common noncardiac side effects are nausea and epigastric pain. These side effects are controlled largely by dosing with meals to reduce peak drug levels. Class IC drugs should be used with caution in patients with a history of atrial flutter, because the anticholinergic effects of these drugs may increase AV conduction and result in 1:1 conduction of atrial flutter at a heart rate of 250 to 300 bpm. These drugs should be used only in consultation with a cardiologist.
Class II Drugs (β-Adrenergic Blocking Agents)
These drugs block the effects of catecholamines (which may potentiate the development of arrhythmias) and slow conduction in the atria, AV node, and ventricular myocardium.
β-Blockers are used to slow the ventricular response in patients with atrial tachyarrhythmia; occasionally, in the process, they convert paroxysmal atrial tachycardia, atrial flutter, or atrial fibrillation to normal sinus rhythm. In addition, ventricular arrhythmias initiated by exercise or ischemia or associated with the congenital long QT syndrome may be prevented by the use of these drugs. Low dosages of a β-blocker (e.g., sustained-release metoprolol) may be effective in controlling heart rate in patients with atrial fibrillation or in maintaining normal sinus rhythm in patients who have been cardioverted. β-Blockers are the only antiarrhythmic medications that have been convincingly shown to reduce the incidence of sudden death after MI (22). Chapter 63 discusses in detail the use of beta blockers in this regard.
A range of side effects is associated with β-blocker use. Although they have proved useful in the management of chronic heart failure (seeChapter 66), β-blockers can precipitate heart failure if their dose is not appropriately titrated in patients with poor ventricular function. They are contraindicated in patients with asthma. Most β-blockers occasionally cause hair thinning; this effect appears
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to be reversible when the dosage is reduced or the drug is discontinued. Many young patients taking β-blockers for supraventricular arrhythmias develop fatigue, malaise, and other symptoms requiring drug discontinuation.
Table 64.3 lists the properties of the currently available β-blocking agents. Propranolol crosses the blood–brain barrier and may cause side effects such as depression and sleep disturbance, although the evidence supporting an association between β-blocker use and depression is not strong (26). Atenolol and metoprolol are long acting, do not cross the blood–brain barrier, and are cardioselective. Because it is largely cleared by renal excretion, atenolol should be dosed carefully in patients with renal insufficiency. The main advantage of the longer-acting agents or sustained-release preparations is the likelihood of better compliance.
Class III (Potassium Channel Blockers)
Sotalol
Sotalol is a racemic mixture of both a class II agent (i.e., a β-blocker, L-sotalol) and a class III agent (i.e., D-sotalol) (27). Although it has few extracardiac side effects, serious ventricular arrhythmias are seen in 3% to 5% of patients. Sotalol should be used with particular caution in patients with heart failure and should not be initiated on an ambulatory basis.
Sotalol, which previously carried an indication only for ventricular arrhythmias, has been repackaged as Betapace-AF and marketed specifically for control of atrial fibrillation in patients with or without structural heart disease. Because of the risk of torsade de pointes, however, a patient beginning sotalol should be monitored as an inpatient for at least several days.
Dofetilide
Dofetilide is approved by the FDA for treatment of atrial arrhythmias. It is used in ambulatory practice for the maintenance of sinus rhythm in patients who have been converted from atrial fibrillation. Initiation of dofetilide requires 72 hours of in-hospital monitoring and careful adjustment based on creatinine clearance and effect on the QT interval.
Amiodarone
Amiodarone is a potent drug that effectively suppresses both supraventricular and ventricular arrhythmias (18). It is unique among the antiarrhythmic drugs in that it has properties of all four classes. Especially at high dosages (>300 mg/day), amiodarone is associated with a number of troublesome side effects, including photosensitivity, hypothyroidism or hyperthyroidism, pulmonary interstitial fibrosis, hepatotoxicity, and a variety of neurologic abnormalities. However, use of the drug is not associated with a high risk of proarrhythmia, and a number of trials of amiodarone in patients with structural heart disease have shown no increased risk of cardiac death. Each 200-mg tablet of amiodarone contains 75 mg of iodine; the likelihood of thyroid dysfunction is high when the drug is taken chronically (28).
Amiodarone interacts with many other drugs. For example, it may potentiate the toxic effects of digoxin and β-blocking agents. It also interferes with the metabolism of warfarin and may markedly prolong the prothrombin time and international normalized ratio (INR) (18). Because of these problems, the risks and benefits of amiodarone must be considered on a patient-by-patient basis. Today amiodarone is one of the most commonly used drugs for treatment of atrial fibrillation (see later discussion). Amiodarone is frequently used in the treatment of patients with sustained ventricular arrhythmias. A cardiologist familiar with the drug should be closely involved in the patient's care. Because of the drug's long mean half-life (almost 2 months), the effects may persist for many weeks after amiodarone is discontinued.
Class IV Drugs (Calcium Channel Blockers)
Calcium channel blockers are effective and useful drugs for controlling supraventricular arrhythmias. Conduction through the AV node is dependent on calcium-mediated currents. By blocking these currents, calcium channel blockers may control the ventricular response in atrial fibrillation and may convert to sinus rhythm those supraventricular arrhythmias that depend on conduction through the AV node. Verapamil may be useful in an ambulatory setting for the conversion of paroxysmal atrioventricular nodal reentrant tachycardia (AVNRT) to sinus rhythm. Doses of 80 to 120 mg orally can be used safely in patients known to have AVNRT; conversion to sinus rhythm usually occurs in 30 to 60 minutes. Alternatively, a dose of 5 to 10 mg intravenously may convert AVNRT in minutes. If the drug is not effective, referral to a hospital emergency room should be considered. Oral verapamil at dosages of 240 to 360 mg/day can be used for prophylaxis against supraventricular arrhythmias. Verapamil also can be used at dosages of 240 to 360 mg/day for ventricular rate control in patients with atrial fibrillation. Diltiazem at dosages of 120 to 300 mg/day also may be effective. The dihydropyridine calcium channel blockers, such as nifedipine and amlodipine, are not useful for control of atrial arrhythmias, nor are calcium channel blockers in general effective for control of ventricular arrhythmias (an unusual exception is idiopathic VT arising from the left ventricle).
Calcium channel blockers such as verapamil and diltiazem, which may be useful in AVNRT, can cause a dangerous acceleration of heart rate in patients with WPW syndrome and atrial fibrillation. If supraventricular tachycardia degenerates to atrial fibrillation in patients with WPW syndrome who are treated with a calcium channel
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blocker, the ventricular rate may suddenly accelerate to >300 bpm. For this reason, calcium channel blockers should generally not be used in patients with WPW syndrome, unless the accessory pathway has been proven to conduct poorly in the anterograde (atrium-to-ventricle) direction.
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TABLE 64.3 Characteristics of Currently Available β-Blockers |
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Verapamil is metabolized by the liver and should be used with caution in patients with impaired hepatic function. Both verapamil and diltiazem are available in extended-release formulations that can be taken once daily. Except perhaps for initial dosage titration, the once-daily formulations are preferred over the short-acting forms. Some elderly patients are very sensitive to diltiazem and require only low dosages of the drug.
The most common side effects of calcium channel blockers are headache, light-headedness, dizziness, hypotension, peripheral edema, and constipation. Both verapamil and diltiazem interfere with renal clearance of digoxin and may precipitate digitalis intoxication. All calcium channel blockers are myocardial depressants, and both verapamil and diltiazem may suppress the sinus node, decrease heart rate, and prolong the PR interval. Verapamil should be used with caution in patients with LV dilation and EF ≤40%, although diltiazem can be used with caution in such patients. There is concern that the use of short-acting calcium channel blockers (i.e., nifedipine, verapamil, diltiazem) may be associated with an increased risk of cardiovascular morbidity and mortality, but an increased risk does not appear to be present in patients using long-acting calcium channel blockers (29).
Pacemaker Therapy
Implantable electrical pulse generators (pacemakers) are the treatment of choice for patients with symptomatic bradyarrhythmias and heart block (30,31). The decision to implant a pacemaker and the type of unit to use must be determined in consultation with a cardiologist. In general, patients in atrial fibrillation who require a pacemaker (see later discussion) require ventricular demand pacemakers. Most patients in sinus rhythm are best served by a multiprogrammable AV sequential unit. The modest increases in cost and complexity of the AV sequential units appear to be more than offset by the improved long-term physiologic response of patients. Patients with heart failure, depressed LV systolic function, and interventricular conduction delay have recently been shown to benefit from biventricular pacing, even in the absence of a bradycardia indication (32,33). Pacemaker generators are <0.5 cm thick and may function for up to 10 years. Pacemaker leads are implanted via a percutaneous transvenous technique and rarely become dislodged, even during vigorous activity. Symptoms are relieved in most patients with bradyarrhythmias and conduction block (see later discussion).
Patient Experience
Pacemakers usually are implanted in cardiac catheterization laboratories with fixed fluoroscopy; some operators use surgical operating rooms with portable fluoroscopy. Pacemakers are implanted subcutaneously in the pectoral area with the patient under local anesthesia. The pacemaker lead is inserted via the cephalic vein or directly with the use of a special introducer into the axillary or subclavian vein and lodged in the apex of the right ventricle or in the right atrial appendage. Patients requiring biventricular pacing have a third, specially designed pacemaker lead inserted into a branch of the coronary sinus. The procedure takes approximately 60 to 120 minutes, depending on the number of leads inserted. The patient experiences some discomfort when the anesthetic is injected and, often, an unpleasant sensation when the tissues are manipulated to create a pocket for the pacemaker unit.
After the procedure, patients are discharged from the hospital the next day. Patients with sedentary jobs can return to work within 1 week after pacemaker insertion, but patients with more active jobs should not return to work for up to 4 to 6 weeks to allow the wound to heal completely. After that time, the patient experiences little or no discomfort. The unit feels like part of the chest wall, and no restrictions are placed on the patient's activity. Microwave ovens do not interfere with pacemaker functions, but cellular phones may do so if they are held directly over the pacemaker (34). Magnetic resonance imaging (MRI) currently is contraindicated in patients with permanent pacemakers, but investigation into the compatibility of newer pacemaker models with MRI is ongoing.
Patients with implanted pacemakers require regular long-term followup. The frequency of followup depends on the original indication for the pacemaker. Patients who require constant pacing should be seen more often (approximately every 3–6 months) than patients who require episodic pacing (approximately every 6–12 months). At these followup visits, pacemaker function must be assessed by 12-lead ECG and a computerized pacemaker analyzer, which measures pacemaker data including battery voltage and lead resistance. The pacemaker and its registration number should be entered into the patient's record, and the patient should keep the registration card for the pacemaker on his or her person in the event of device malfunction or an emergency intercurrent problem.
Implantable Cardioverter-Defibrillator Therapy
The implantable cardioverter-defibrillator (ICD) has had a major impact on the clinical approach to prevention of sudden cardiac death from ventricular arrhythmias (35). ICDs are implanted in the same way as are pacemakers, and specific devices can perform all pacemaker functions, including biventricular pacing. They are capable of detecting different forms of ventricular arrhythmias in different rate zones and of treating each with a different sequence of antitachycardia pacing (ATP) and shock therapies. They
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are capable of storing large amounts of information from each arrhythmia episode that can be retrieved by specialized computers for later analysis.
ICDs detect ventricular arrhythmias from the tip electrode of the lead, which usually is implanted at the right ventricular apex. When a ventricular rate exceeding the programmed detection rate for ventricular fibrillation (usually 150–200 bpm) for the programmed number of beats (usually 10–20) is detected, the ICD begins charging the capacitors. The charging period generally is between 1 and 5 seconds, after which the device confirms continuation of tachycardia before delivering the programmed energy (usually 10–35 J) between the metal shell of the generator and one or more coils on the ICD lead. The ventricular rate then is reanalyzed to determine whether therapy was successful. Further therapies are delivered if needed, up to a maximum of six to eight.
When first released for clinical use in the early 1980s, ICDs were targeted toward patients who had survived multiple cardiac arrests with recurrent ventricular arrhythmias that were refractory to conventional antiarrhythmic drug treatment. As the design of ICDs improved over the next decade and the limitations of antiarrhythmic drugs were exposed through randomized clinical trials, the ICD gained increasing favor for treatment of cardiac arrest survivors and other patients with unstable ventricular arrhythmias. In this setting, several clinical trials were organized to test the efficacy of the ICD in secondary prevention (for patients who had survived a sustained life-threatening ventricular arrhythmia) and primary prevention (for high-risk patients without a history of sustained arrhythmia) of sudden cardiac death.
The Antiarrhythmics Versus Implantable Defibrillators (AVID) trial, published in 1997, established the efficacy of the ICD for patients with prior cardiac arrest or symptomatic sustained VT (36). The Multicenter Automatic Defibrillator Implantation Trial (MADIT) (37) published in 1996 and the Multicenter Unsustained Tachycardia Trial (MUSTT) (38) published in 2000 showed that the ICD improved survival in MI survivors with depressed LV systolic function, nonsustained VT, and inducible sustained VT at electrophysiologic study. MADIT-II, published in 2002, extended the indication for primary prevention ICD therapy to all patients with prior MI and LVEF ≤30%, regardless of symptoms or arrhythmia history (39). Most recently, the Sudden Cardiac Death in Heart Failure (SCD-HeFT) investigators demonstrated a significant mortality reduction with primary prevention ICD therapy in patients with depressed LVEF (≤35%) and New York Heart Association (NYHA) class II or III congestive heart failure regardless of etiology (40).
Patient Experience
ICDs are implanted similarly to pacemakers, usually with the patient under local anesthesia. The main differences are that a larger generator is implanted under the skin, and ICD function is tested with the patient under deep sedation. During the latter procedure, known as defibrillation threshold (DFT) testing or noninvasive programmed stimulation (NIPS), VT and/or ventricular fibrillation is induced and then terminated by the device using programmed therapies. External defibrillation is immediately available if the ICD therapy is not successful.
Cardioversion
Electrical conversion of atrial tachyarrhythmias is performed by the application of a short burst of direct current to the chest wall. The shock is synchronized with the QRS complex of the ECG to avoid shock application during the vulnerable period of the cardiac cycle, when VT or ventricular fibrillation might be induced.
Cardioversion is a more reliable technique for conversion of tachyarrhythmias than is administration of antiarrhythmic drugs. It may be required on an emergency basis if a patient has developed severe heart failure, hypotension, or ischemia as a result of an arrhythmia. Otherwise, the procedure should be planned in consultation with a cardiologist. A number of factors must be considered when deciding whether elective cardioversion is appropriate for a patient with atrial fibrillation (41) (see later discussion).
The most cost-effective strategy, in terms of quality-adjusted life years, is to attempt cardioversion before initiation of antiarrhythmic therapy. Typically, patients are anticoagulated for at least 3 weeks before elective cardioversion and for 4 weeks afterward. However, clinical trials have shown that if transesophageal echocardiography (TEE) does not reveal an atrial thrombus, cardioversion may be done without prior anticoagulation (42). (The need for anticoagulation for at least 4 weeks after cardioversion, however, is not obviated.) If atrial fibrillation recurs soon after cardioversion, an antiarrhythmic agent can be started and cardioversion can be repeated (43).
Patient Experience
Cardioversion is performed by a cardiologist in a hospital, either with an anesthesiologist or a nurse experienced in administering conscious sedation, and with resuscitation equipment available. The patient is sedated, usually with intravenous midazolam given to effect. Normally the patient cannot recall afterward any experience of the procedure. For atrial fibrillation, cardioversion is attempted at 200 J; if that attempt is unsuccessful, the energy level is increased and other shocks are administered until conversion occurs or until a level of 360 J is reached. If an initial attempt using anteroposterior patch placement fails, another attempt at cardioversion can be undertaken using an apex–base paddle position. If available, a biphasic defibrillator should be used because of the higher conversion rates with this device. If external cardioversion is unsuccessful, shock delivery through an intracardiac electrode (referred to as internal cardioversion) may be successful. Administration of ibutilide, an intravenous class III antiarrhythmic agent, immediately before cardioversion also can lower the amount of energy
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required for cardioversion (44,45). With the recent availability of biphasic waveforms, this approach is rarely required. Complications, such as embolism or a new arrhythmia, are unusual; however, even with optimal anticoagulation, patients should be aware of a small (0.5%) risk of periprocedural stroke. After cardioversion, the patient is observed for several hours while rhythm is monitored. If the rhythm is stable, then the patient is discharged.
Invasive Electrophysiologic Study
Several categories of patients should be referred for electrophysiologic study; most of these patients already are under the care of a cardiologist. They include patients with a sustained wide-complex tachycardia and those who have survived an episode of sudden cardiac death; patients with nonsustained VT (particularly in the setting of a prior MI) who are thought to be at increased risk for sudden cardiac death; patients with syncope of unknown origin in the setting of structural heart disease; and patients who are considered candidates for a curative catheter ablation procedure for treatment of any of a large variety of supraventricular arrhythmias (including WPW syndrome and PSVT, see below), atrial flutter, atrial tachycardia, atrial fibrillation), and some types of ventricular arrhythmias (frequent PVCs or sustained VT). Although empiric antiarrhythmic drug treatment is appropriate for many patients with PSVT, catheter ablation is also considered appropriate first-line therapy (46,47). Catheter ablation has been shown to be a more cost-effective approach compared with lifelong drug therapy, and it has a much higher success rate in keeping patients free of arrhythmia (48,49).
Patient Experience
The patient's experience during electrophysiologic study is similar in some respects to that during cardiac catheterization (see Chapter 62) in that the patient must lie flat on a table in the cardiac catheterization laboratory. Patients typically receive moderate sedation with midazolam. Catheters usually are advanced, under fluoroscopy, through the femoral vein rather than through the artery, as is done during coronary angiography. The procedure takes longer than does coronary angiography; the average diagnostic procedure takes approximately 1 hour, whereas a radiofrequency catheter ablation procedure can take up to 3 to 5 hours. In a typical diagnostic procedure, intracardiac electrical activity is recorded and the heart is stimulated (either pharmacologically or electrically through a catheter) in an attempt to induce the clinical arrhythmia. If a significant arrhythmia is induced and does not resolve spontaneously, antiarrhythmic drugs or electrical cardioversion is used to restore the patient's intrinsic rhythm. The risks of a diagnostic electrophysiologic study in experienced hands are low and comparable to the risk of diagnostic coronary angiography. The risks associated with catheter ablation vary based on the target arrhythmia. There is a small risk that a permanent pacemaker will be required because of induction of complete heart block during an ablation procedure in no more than 1% of patients (46). The risk of major morbidity (e.g., stroke, MI, significant valve damage) or mortality is generally approximately 0.1%.
Specific Arrhythmias
Sinus Tachycardia
Definition and Causes
In adults, the normal resting sinus rate is 50 to 100 bpm. Sinus tachycardia, a sinus rhythm at a rate >100 bpm, usually is a physiologic rhythm in that the rate is ordinarily appropriate to the physiologic state of the patient, a state that requires increased cardiac output to meet increased metabolic demands. The maximal sinus heart rate that can be attained varies with age but usually does not exceed 140 bpm unless demands are excessive (e.g., vigorous exercise). The common factors that stimulate an increase in the rate of sinus rhythm, other than exercise, are fever, emotional stress, intravascular volume depletion, heart failure, hypoxia, and a variety of drugs that affect the autonomic nervous system, including caffeine, aminophylline, amphetamine, alcohol, antidepressants, phenothiazines, and calcium channel blockers of the dihydropyridine class (e.g., nifedipine).
Physical Findings
A regular rapid pulse and heart rate are detected, although there may be a slight variation in rate, called sinus arrhythmia. S1 is normal, and the jugular venous pulsations are normal.
Electrocardiogram
A P wave precedes each QRS complex; the PR interval is normal for the rate (0.16–0.17 second at rates >130 per minute), and the P-wave vector is normal (upright P waves in II, III, and aVF).
Treatment
In most cases, persistent sinus tachycardia need not be treated; it is the underlying condition that requires therapy. In particular, digitalis should not be used to treat a patient with sinus tachycardia unless there is associated heart failure.
In the occasional patient with an unexplained sinus tachycardia for whom a thorough evaluation fails to reveal an underlying cause and in whom tachycardia is symptomatic, use of small dosages of a β-blocker may be
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justified. Low-dose β-blockers also may be helpful in treating the anxiety and tachycardia associated with anticipated stressful situations.
Sinus Bradycardia
Definition and Causes
Sinus bradycardia is a heart rate <50 bpm (50). Impulse generation in the sinus node often is slow in aerobically well conditioned people (e.g., long-distance runners, heavy laborers) because of high vagal tone. In fact, trained athletes may have asymptomatic sinus bradycardia with resting heart rates as low as 40 bpm. Inappropriately low sinus rates are also commonly caused by increased vagal tone, as is seen in association with pain, vomiting, or vasovagal syncope. A hypersensitive carotid sinus, more common in elderly people, may result in marked bradycardia when the sinus is compressed by a tight collar or by the patient's tensing his or her neck. Parasympathomimetic drugs such as neostigmine, tranquilizers, phenothiazines, digitalis, and sympatholytic drugs such as methyldopa, clonidine, and all β-blockers also may produce sinus bradycardia. Vagally induced bradycardia may be severe and result in asystole (and loss of consciousness) when the stimulus is marked or prolonged or occurs in a hypoxic patient.
Physical Findings
A regular slow pulse and heart rate are detected. S1 is normal, and the jugular venous pulsations are normal.
Electrocardiogram
A P wave precedes each QRS complex; the PR interval is normal for the rate (up to 0.20–0.21 second), and the P-wave vector is normal (upright P waves in II, III, and aVF).
Treatment
Asymptomatic sinus bradycardia discovered as an incidental finding does not require treatment. If there are no ECG signs of conduction block and structural heart disease is not present, resting heart rates as low as 40 bpm may be well tolerated. However, patients who present with symptoms of light-headedness or syncope and are found to have sinus bradycardia may have underlying sinus node disease or may be subject to paroxysms of tachycardia and bradycardia, the so-called sick sinus syndrome (see Sick Sinus Syndrome). Patients with sinus bradycardia and symptoms should be evaluated with an ambulatory ECG to determine whether they have this condition. In any case, patients with symptomatic sinus bradycardia not caused by a drug are best treated with permanent pacemaker implantation.
Sick Sinus Syndrome
Definition and Causes
The term sick sinus syndrome refers to a heterogeneous group of arrhythmias involving defective impulse generation by the sinus node or abnormal impulse conduction in the atria and AV node (51). The syndrome is characterized by periods of inappropriate sinus bradycardia (often severe, with rates between 25 and 40 bpm), which may precede or follow supraventricular tachyarrhythmias, and by varying degrees of SA block, sometimes including sinus arrest. The rubrics bradycardia–tachycardia syndrome and tachycardia–bradycardia syndrome are sometimes used, depending on whether bradycardia precedes or follows a tachyarrhythmia (usually atrial fibrillation), respectively.
The sick sinus syndrome is caused by degenerative fibrotic changes within the sinus node. It often is associated with similar abnormalities in other parts of the cardiac conduction system that result in varying degrees of AV and intraventricular block. These pathologic changes are much more common in patients older than 60 years. Although their precise cause is unknown, they are often associated with hypertensive or ischemic heart disease.
Symptoms and Signs
Many patients are asymptomatic. When symptoms do occur, they are produced either by spontaneous sinus arrest or by the tachyarrhythmia itself (palpitations). If LV dysfunction or coronary artery disease is coexistent, symptoms of heart failure or ischemia may occur as a result of reduced cardiac output or increased cardiac demand.
The results of physical examination often are normal unless the patient is examined during an episode of bradyarrhythmia or tachyarrhythmia, in which case the findings depend on the type of arrhythmia present (see later discussion). Sometimes light carotid sinus massage produces symptomatic bradyarrhythmia in a patient with sick sinus syndrome who is in normal sinus rhythm.
Electrocardiogram
The ECG may be normal or may simply reveal sinus bradycardia. Often, there are varying degrees of SA block, characterized by varying P–P intervals on the ECG. Sometimes sinus arrest occurs, manifested by absent P waves and usually associated with a junctional escape rhythm. Some patients have atrial fibrillation with a slow ventricular response, reflecting a concomitant AV conduction abnormality (see earlier discussion). The ECG changes of the various atrial tachyarrhythmias are described in the discussions of these entities.
If the patient has a history of unexplained syncope or palpitations and the resting ECG is normal, ambulatory
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ECG monitoring is indicated (see Diagnosis of Arrhythmias).
Treatment and Course
The treatment of choice for patients with the sick sinus syndrome who are symptomatic from bradyarrhythmias is permanent pacemaker implantation (see Pacemaker Therapy). Otherwise, symptoms are often progressive. Patients with minor symptoms (e.g., light-headedness, dizziness) often feel significantly better after pacemaker therapy.
Tachyarrhythmias associated with the syndrome generally are not prevented by cardiac pacing. However, pacing does allow the use of drugs such as digitalis, calcium channel blockers, amiodarone, and β-blockers that depress the sinus node and increase the likelihood of sinus arrest or asystole. After a pacemaker is implanted, it is reasonable to administer metoprolol 25 mg twice per day and to increase the dosage to 50 mg or 100 mg twice per day in an attempt to prevent tachyarrhythmias. If the β-blocker is not effective, diltiazem or verapamil may be administered in low doses as well, unless the patient has a depressed EF. If tachyarrhythmias continue, then consideration in conjunction with the consulting cardiologist should be given to the use of another antiarrhythmic drug, catheter ablation of the tachyarrhythmia, or ablation of the AV node.
Patients with sick sinus syndrome and atrial fibrillation have an incidence, unaffected by pacemaker therapy, of arterial embolization of approximately 5% to 10% per year. These patients should be anticoagulated with warfarin. The sick sinus syndrome is not itself associated with increased mortality. Life expectancy in these patients is a function of the patient's age and comorbid conditions (51). Patients with chronic atrial fibrillation as a manifestation of sick sinus syndrome should be treated with warfarin (discussed later) or with aspirin if the patient cannot, or will not, take warfarin. Warfarin may generally be restarted within 1 to 2 days after implantation of a permanent pacemaker.
Premature Atrial and Junctional Contractions
Definition and Causes
Premature atrial contractions (PACs) and premature junctional contractions (PJCs) are commonly seen in patients who are otherwise well. They often are induced by the same stimuli that produce sinus tachycardia, especially caffeine or nicotine. However, in patients with congestive heart failure or chronic pulmonary disease, PACs or PJCs may progress to atrial fibrillation or flutter.
Symptoms and Signs
Usually patients are unaware of PACs or PJCs; occasionally they note the PAC or PJC as a palpitation. The clinician, on listening to the heart or palpating the arterial pulse, is aware of a slight irregularity in the cardiac rhythm.
Electrocardiogram
PACs are reflected on the ECG by a premature, morphologically abnormal P wave followed by a premature, morphologically normal QRS complex. Sometimes these impulses are not conducted (Fig. 64.5), in which case, if the P wave is buried in the preceding T wave, a false diagnosis of sinus arrest may be made. At other times the premature impulse is aberrantly conducted, the result of refractoriness of one of the bundle branches (usually a right bundle-branch pattern is seen after the premature atrial beat).
PJCs are reflected on the ECG by a retrograde P wave (negatively deflected in leads II, III, and aVF) that may follow, be hidden in, or precede a morphologically normal but premature QRS complex.
Treatment
Patients with PACs or PJCs who are otherwise well do not require treatment. Rarely, a β-blocker or another antiarrhythmic agent, such as sotalol, flecainide, or amiodarone, is prescribed to reduce the frequency of PACs in patients
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who have annoyingly frequent palpitations. Quinidine or procainamide is effective for controlling PACs, but the risk associated with the use of these drugs usually is not warranted (see earlier discussion).
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FIGURE 64.5. Premature atrial contraction (arrowhead). Note the normal configuration of the premature QRS complex. |
Paroxysmal Supraventricular Tachycardia
Definition and Causes
The term paroxysmal supraventricular tachycardia (PSVT) refers to a group of supraventricular arrhythmias that start and terminate abruptly and generally result from reentry (47,52). The most common cause of PSVT is AVNRT, which accounts for two thirds of all cases of PSVT (53). AVNRT occurs in the setting of two functionally distinct conduction pathways in the region of the AV node (called the fast andslow pathways). The second most common cause of PSVT is an accessory pathway-mediated tachycardia called orthodromic AV reciprocating tachycardia. This type of tachycardia, which accounts for approximately one third of all cases of PSVT, results when the electrical impulse travels from the atria to the ventricles via the AV node and returns to the atria via an accessory pathway that connects the atrium and ventricle. The third, and least common, cause of PSVT is an ectopic atrial tachycardia that is confined to the atrium. This type accounts for <5% of all cases.
The heart rate during episodes of PSVT may vary from 130 to 250 bpm. In general, PSVT involving an accessory pathway tends to be more rapid, and PSVT caused by an atrial tachycardia tends to be slower. However, because of a large degree of overlap, the rate of the tachycardia usually is not helpful in establishing a diagnosis.
Nonparoxysmal atrial tachycardia with block (caused by gradually accelerated automaticity of an ectopic atrial focus) as a manifestation of digitalis toxicity is now rarely seen. If nonparoxysmal atrial tachycardia occurs in association with an AV conduction abnormality (commonly 2:1 block) and the patient is taking digitalis, the drug should be withheld and the serum potassium concentration measured. If the patient is hypokalemic, potassium repletion is in order; usually this can be accomplished by administration of oral potassium salts (i.e., 20 mEq three times per day; see Chapter 50). Patients with refractory arrhythmias with block caused by digitalis toxicity should be hospitalized for more aggressive treatment.
Symptoms and Signs
PSVT usually is suspected or diagnosed based on a careful history. The most important features of PSVT are its abrupt onset and termination and its sustained rapid and regular rate. Patients may complain of dyspnea, diaphoresis, light-headedness, presyncope, or chest pain. Often the patient is able to terminate the arrhythmia abruptly by performing actions that increase vagal stimulation of the heart, such as a Valsalva maneuver, coughing, or placing a cold wet towel over the face (diving reflex). Occasionally, polyuria is experienced for as long as the arrhythmia lasts; this may be due to atrial dilation and release of atrial natriuretic peptide (54).
Attacks often occur spontaneously but may be precipitated by physical or emotional stress, caffeine, or nicotine. The attacks may be as short as a few seconds or as long as several weeks. The frequency of the attacks is variable: Some people have attacks every day, whereas others have only a few attacks during their lifetime.
On examination, a rapid, regular arterial pulse and heart rate are noted, often faster than those measured in patients with sinus tachycardia and usually not associated with the same stimuli. When the atria and ventricles contract simultaneously, cannon waves are seen in the jugular veins.
Electrocardiogram
PSVT is characterized by a rapid, regular heart rate. There is a fixed relationship of the P wave to the QRS complex. If the impulse is generated in the AV node (as in AVNRT), the P wave may be buried in the QRS complex, but the process can be identified by the normal appearance of the QRS complex and the regularity of the rate. When the P wave is visible, it may follow the QRS complex (in some nodal reentry rhythms and most accessory pathway reentry rhythms). It may also precede the QRS complex and may appear morphologically normal (atrial reentry or ectopic rhythm), in which case the diagnosis can be made (by ECG) only if the rate is sufficiently high to make sinus tachycardia unlikely. The P wave also may be hidden in the T wave, but again the regularity of the rate and the usually normal duration of the QRS complex establish the diagnosis (6,53).
If the ECG recorded from a patient with PSVT demonstrates various degrees of AV block (Fig. 64.6), the most likely cause of the arrhythmia is an atrial tachycardia. The presence of an accessory pathway-mediated tachycardia can be completely eliminated, and the possibility of AVNRT is very unlikely.
Treatment and Course
Therapy for PSVT always starts with attempts to increase vagal tone. As mentioned earlier, the patient often has learned to do this. If the arrhythmia persists despite the patient's efforts, carotid sinus massage should be applied. This must be done after auscultation of the carotid arteries to ensure that there are no bruits; if there are, carotid
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sinus massage is contraindicated. The carotid sinus is located at the point of maximal impulse of the carotid artery in the neck. The right sinus should be massaged first for up to 20 seconds; if that has no effect, the left sinus should be massaged. The two sinuses should never be massaged simultaneously. During massage, the patient's ECG should be monitored continuously, and resuscitation equipment should be available.
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FIGURE 64.6. Supraventricular tachycardia with 2:1 AV block. Arrowheads point to consecutive P waves. |
If carotid sinus massage fails, pharmacologic therapy is indicated. This is best done in an emergency room or a similar facility and always with continuous ECG monitoring. The drug of choice is adenosine (which slows conduction through the AV node), 6 to 18 mg, because the effect of the drug dissipates only 10 to 15 seconds after intravenous administration. Adenosine usually converts the arrhythmia to normal sinus rhythm within 5 to 10 seconds. It is critical that adenosine be administered as a bolus into a rapidly flowing intravenous line. This is best accomplished by using a stopcock and immediately flushing the line with 10 mL of saline after adenosine injection. If PSVT persists after adenosine administration, electrical cardioversion should be considered. Administration of intravenous adenosine should be performed only in a setting where emergency defibrillation can be performed. Alternatives to adenosine include verapamil (80–120 mg orally or 5–10 mg intravenously), diltiazem (60–120 mg orally) (discussed earlier), or metoprolol (25–50 mg orally or 5–10 mg intravenously). As noted previously, calcium channel blockers may increase conduction in the accessory pathway in patients with WPW syndrome. Therefore, calcium channel blockers should not be used to treat PSVT in patients who are known to have an accessory pathway, in order to avoid dangerous acceleration of the ventricular rate if PSVT degenerates to atrial fibrillation.
PSVT can be prevented or the number of episodes reduced by a variety of antiarrhythmic agents. If an initial episode of PSVT terminates spontaneously and is associated with mild symptoms, it would be reasonable to instruct the patient about techniques to terminate the arrhythmia and to delay initiation of antiarrhythmic therapy. On the other hand, if the patient has had multiple episodes of tachycardia, has required emergency room evaluation for termination of tachycardia, or has symptoms of hemodynamic compromise, chronic antiarrhythmic therapy or radiofrequency catheter ablation is indicated.
Digoxin may be used to treat PSVT and perhaps is the most convenient, best tolerated, and least expensive, but it also is the least effective medication for this purpose. β-Blockers and calcium channel blockers are somewhat more effective, are more expensive, and, when given at once-a-day dosing, are equally convenient. On the other end of the spectrum are class IC antiarrhythmic agents such as propafenone and flecainide, which are effective but even more expensive and less convenient. Although amiodarone can be used to treat patients with PSVT, this drug is rarely prescribed because of the benign nature of this arrhythmia, the potential for serious side effects of the drug (see earlier discussion), and the alternative of radiofrequency catheter ablation.
Radiofrequency catheter ablation (described earlier) has evolved from an experimental technique to the preferred therapy for treatment of patients with symptomatic
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or frequently recurrent PSVT (47,55). Success rates are >95%, complications are rare (<1%), and the procedure is well tolerated. For this reason, patients with PSVT should be informed about the existence of a curative catheter-based procedure that can be considered as an alternative to lifelong antiarrhythmic therapy or that can be used if antiarrhythmic therapy fails. Electrophysiologic testing and radiofrequency catheter ablation should be recommended as first-line therapy if PSVT occurs in the setting of WPW syndrome (see later discussion). Because of the potentially life-threatening nature of WPW syndrome, these patients should be referred for electrophysiologic testing and radiofrequency catheter ablation (46). Similarly, if a patient with PSVT has symptoms of severe hemodynamic compromise (i.e., syncope), electrophysiologic testing and radiofrequency catheter ablation should be considered early in management.
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FIGURE 64.7. Multifocal atrial tachycardia. Note the variation in the morphology of the P waves and the duration of the PR intervals. |
Although PSVT is generally a benign arrhythmia, it rarely disappears without treatment. Once a patient has had one episode of PSVT, other episodes probably will occur. The frequency of episodes of PSVT increases over time in most patients. In contrast to this generally benign course, the prognosis of patients with PSVT who have WPW syndrome, severe structural heart disease, or symptoms of hemodynamic compromise is not as favorable. For this reason, more aggressive approaches to treatment are used early in these settings.
Multifocal Atrial Tachycardia
Multifocal atrial tachycardia is a chaotic supraventricular arrhythmia characterized on ECG by varying morphology of the P waves, varying PR intervals, and a rapid heart rate, usually 100 to 200 bpm; QRS morphology is normal, and every QRS complex is preceded by a P wave (Fig. 64.7) (56). The arrhythmia usually is seen in patients with serious underlying disease, especially decompensated chronic obstructive pulmonary disease, and is better treated by, for example, improving ventilatory function than by attempting directly to suppress the rhythm. Digitalis does not alter this arrhythmia (which usually is well tolerated) and therefore should not be administered. Either verapamil or diltiazem can be used to control the heart rate in patients with multifocal atrial tachycardia. Oral dosages of verapamil 40 to 80 mg three to four times per day or diltiazem 30 to 60 mg three to four times per day should be tried. If they are effective, a sustained-release preparation of verapamil or diltiazem at the same total daily dosage can be used. Magnesium was effective treatment in one small study (57).
Atrial Fibrillation
Definition and Causes
Atrial fibrillation is defined electrophysiologically as the generation of multiple reentrant wavefronts by the atria. It usually is initiated by one or more PACs (see earlier discussion) that trigger the development of these wavefronts and result in an atrial rate >300 bpm. These impulses enter the AV node randomly. Because of the unique conduction properties of the AV node, including slow conduction and decremental conduction, only a small proportion of the impulses are conducted to the ventricle. This results in a slower (typically 100–180 bpm) and an irregularly irregular ventricular rate.
Atrial fibrillation is classified as paroxysmal (starts and stops on its own within 48 hours), persistent (continues until/unless converted by drugs, cardioversion, or ablation), or permanent (persistent and attempts at conversion either unsuccessful or believed to be futile or medically unnecessary) (58). Studies have shown that paroxysmal atrial fibrillation usually is initiated by triggering PACs or bursts of atrial tachycardia arising in the pulmonary veins (59). The causes of persistent and permanent atrial fibrillation are less clear, but the posterior left atrium and pulmonary veins appear to be important for initiation and/or maintenance of the arrhythmia in a significant percentage of patients.
The prevalence of atrial fibrillation increases with age and with the development of structural heart disease (60). When atrial fibrillation occurs in the absence of any evidence of structural heart disease in patients younger than 50 years, it is called lone atrial fibrillation. In some patients, factors that trigger episodes of atrial fibrillation can be identified (e.g., physical or emotional stress, alcohol, nicotine, caffeine). The major noncardiac illness associated with atrial fibrillation is hyperthyroidism. The presence of a fast ventricular response refractory to drugs given to slow the ventricular rate may be a clue to the diagnosis (61).
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FIGURE 64.8. Atrial fibrillation. The ventricular rate is 90 to 100 bpm, indicative (because digitalis had not been administered) of an associated disorder of atrioventricular conduction. |
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Hypertensive and rheumatic heart disease (especially if it involves the mitral valve) predisposes to the development of atrial fibrillation, but almost every kind of myocardial disorder has been associated with it. In addition, the tachyarrhythmic component of the sick sinus syndrome (see earlier discussion) usually is atrial fibrillation.
Symptoms and Signs
Atrial fibrillation can be asymptomatic. The most common symptoms of atrial fibrillation are palpitations and fatigue. If the ventricular response is fast, patients often complain of feeling disoriented, light-headed, weak, or faint, especially if they are elderly. Because atrial contraction normally provides approximately 20% of the total cardiac output, patients with incipient heart failure, ischemic heart disease, or valvular heart disease may develop symptoms and signs of those disorders (especially on exertion) when cardiac output is reduced as the result of atrial fibrillation.
Atrial fibrillation is characterized by an irregularly irregular heartbeat and pulse, with variation in intensity of the sounds (including murmurs) on both auscultation and palpation. It is prudent to look for signs of diseases known to be associated with atrial fibrillation (coronary heart disease, heart failure, hypertension, mitral stenosis or regurgitation, and hyperthyroidism), especially because those signs may be subtle or may be altered by the arrhythmia.
Electrocardiogram
The ECG shows rapid irregular fibrillatory atrial activity at rates of 300 to 500 per minute; no P waves are present. The ventricular rhythm is irregularly irregular, at rates that at onset usually are 120 to 180 per minute, unless AV node disease is coexistent or the patient is taking a medication that slows AV conduction, in which case slower rates are likely (Fig. 64.8).
The QRS complex usually is morphologically normal. Occasionally there is aberrant conduction of an impulse in the ventricles, after a beat that has been preceded by a long pause. The aberrant beat usually has a right bundle-branch block (RBBB) configuration. This so-calledAshman phenomenon is caused by prolonged refractoriness of (usually) the right bundle branch after the long pause. These aberrant beats must be distinguished from ventricular premature beats (VPBs). Apart from their typical relationship to a preceding long R–R interval, aberrant beats often are triphasic (RSR′) in lead V1, and their initial vector is the same as that of the normally conducted beats. Neither of these features is characteristic of VPBs.
Other Studies
In addition to ECG and chest x-ray film, all patients presenting for the first time with atrial fibrillation should undergo thyroid function studies and a two-dimensional echocardiogram. Unusual causes of atrial fibrillation, such as atrial myxoma or chronic pericardial effusion, may require echocardiography for diagnosis.
Treatment and Course
The approach to treatment of atrial fibrillation should always include a search for underlying or precipitating factors. Treatment of the arrhythmia has two objectives: to slow the ventricular rate if it is fast and to convert the rhythm to sinus rhythm if symptoms are present.
Paroxysmal atrial fibrillation in a patient who does not have underlying heart disease often reverts to normal sinus rhythm once precipitating factors (e.g., fever, stress, alcohol, nicotine) are controlled or removed. Specific treatment is indicated in the following circumstances: rapid ventricular response associated with symptoms (e.g., extreme fatigue, syncope, angina, shortness of breath); presence of known severe underlying structural heart disease (e.g., aortic stenosis, severe mitral stenosis, ischemic heart disease, chronic congestive heart failure), because such patients are unlikely to revert to normal sinus rhythm spontaneously; and persistent atrial fibrillation, especially if the resting ventricular rate is >110 bpm or the rate after moderate exercise (e.g., climbing a flight of stairs) is >150 bpm.
Symptomatic patients and patients with underlying structural heart disease usually require hospital admission immediately after onset of the arrhythmia for cardioversion (see previous discussion) or for pharmacotherapy.
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Cardioversion of atrial fibrillation should be considered in these patients if the arrhythmia has been present for <6 months and significant atrial enlargement (i.e., greater than approximately 5 cm) is not present. Successful cardioversion and maintenance of sinus rhythm are less likely if atrial fibrillation has been present for >6 months or if marked atrial enlargement is noted on echocardiography. Although comparisons of rate control and cardioversion strategies have not shown that patients randomly assigned to cardioversion achieve greater symptomatic improvement or improved quality of life (41) or that cardioversion offers any survival advantage over rate control (62), cardioversion still is typically recommended to highly symptomatic AF patients in whom maintenance of sinus rhythm is believed to be likely and to patients in whom rate control in atrial fibrillation is difficult to achieve. If electrical cardioversion is recommended, the patient should be anticoagulated for at least 3 weeks and then considered for elective cardioversion unless a TEE-guided approach is used (see earlier discussion). In general, cardioversion restores normal sinus rhythm in most patients, but the relapse rate is high (50% in 1 year and 90% in 3 years) unless an underlying disorder can be identified and corrected, the atrial fibrillation has been of short duration, or antiarrhythmic therapy or radiofrequency ablation therapy is used.
Following a second episode of sustained atrial fibrillation, antiarrhythmic therapy is often used, after a repeat successful cardioversion, in an attempt to maintain sinus rhythm. Because no study has demonstrated that antiarrhythmic therapy in patients with atrial fibrillation prolongs survival or reduces the incidence of strokes, the main indication for antiarrhythmic therapy should be symptom reduction.
The selection of an appropriate antiarrhythmic agent for maintaining normal sinus rhythm depends to a large degree on whether structural heart disease is present. For patients with no structural heart disease, almost any antiarrhythmic agent is safe. Class IC antiarrhythmic agents, such as flecainide or propafenone, or the class III antiarrhythmic agent sotalol are often used as first-line antiarrhythmic therapy in this setting. If these drugs are ineffective, low-dose amiodarone can be considered. In contrast, the risk of proarrhythmia is high among patients with impaired ventricular function. Perhaps the most effective and safest antiarrhythmic agent in the setting of structural heart disease is low-dose amiodarone (100– 200 mg/day) (63,64). It should be recognized that atrial fibrillation is a difficult arrhythmia to treat and that, even with the most effective antiarrhythmic agents, sinus rhythm can be maintained during long-term followup in <50% to 60% of patients.
If antiarrhythmic therapy fails or is poorly tolerated, the goal of treatment should be to achieve adequate rate control and effective long-term anticoagulation (65). When rate control is attempted, the goal should be to achieve a resting ventricular rate between 70 and 100 bpm and a rate <150 bpm after modest exercise. Digoxin slows the ventricular response in acute atrial fibrillation, but it does not enhance conversion to sinus rhythm (66) and is of limited use in controlling heart rate in paroxysmal atrial fibrillation. The chronic maintenance dose of digoxin is generally 0.125 to 0.25 mg/day.
In contrast to digoxin, calcium channel blockers such as verapamil (120–240 mg/day, sustained-release), diltiazem (120–240 mg/day, sustained-release), or small dosages of a β-blocker (e.g., atenolol 25–50 mg/day, metoprolol 25 mg twice per day, propranolol 10–20 mg four times per day) effectively control heart rate during exercise and are preferred to digoxin (see General Principles in Management of Arrhythmias). Once effectiveness is demonstrated, the drugs can be taken once daily in a sustained-release form at the same total daily dosage.
In patients with permanent atrial fibrillation and a rapid ventricular rate in whom pharmacologic approaches to heart rate control are ineffective or result in intolerable side effects, electrophysiologic modification or ablation of the AV node and permanent pacemaker implantation should be performed (67).
Radiofrequency catheter ablation is emerging as an alternative treatment strategy for selected patients with paroxysmal and persistentatrial fibrillation that is refractory to pharmacologic therapy (67). Evidence suggests that paroxysmal atrial fibrillation is commonly triggered by rapid bursts of tachycardia arising from muscle sleeves that extend from the left atrium into the pulmonary veins. Radiofrequency catheter ablation targeting these pulmonary vein sleeves may cure atrial fibrillation in up to 70% to 80% of patients (59,68,69). The role of radiofrequency catheter ablation in the management of patients with persistent or chronic atrial fibrillation (other than ablation of the AV node for rate control) is not as well established, but several centers have reported encouraging results using newer ablation techniques (70,71).
A slow ventricular response to atrial fibrillation by untreated patients suggests an associated disorder of AV conduction. Such patients do not require specific therapy for the arrhythmia (other than anticoagulation) unless they are hemodynamically compromised (i.e., in refractory heart failure) and their heart rate is <60 to 70 bpm, in which case implantation of a ventricular pacemaker may be indicated.
Anticoagulation
Patients with chronic atrial fibrillation are at increased risk for arterial embolization. For example, the Framingham study reported that, over a 24-year period, patients with chronic atrial fibrillation with and without rheumatic heart disease had a 17-fold and fivefold increase in the incidence of stroke, respectively (72). Overall, the incidence
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of arterial embolization in untreated patients with chronic atrial fibrillation is approximately 5% to 10% per year (65). In general, patients should be anticoagulated with warfarin for at least 3 weeks before, and at least 4 weeks after, elective cardioversion (see earlier discussion). An alternative approach is to refer the patient for TEE and, if no intracardiac clots are demonstrated, to perform cardioversion without preliminary anticoagulation but followed by at least 4 weeks of warfarin therapy (42). Prospective randomized trials support the use of anticoagulants in patients with chronic atrial fibrillation if there are no contraindications (73). Anticoagulation with warfarin to obtain an INR of 2.0 to 3.0 is recommended for all patients with atrial fibrillation who are older than 65 years or who have other risk factors for stroke, such as hypertension, diabetes, or a prior transient ischemic episode or stroke. Warfarin should generally be continued indefinitely. The optimal duration of anticoagulation for a patient who is converted to sinus rhythm is unclear, but some clinicians recommend continuing warfarin regardless of whether sinus rhythm is maintained. In patients who cannot, or will not, take warfarin, some studies support the use of aspirin 325 mg/day, particularly in young patients with no risks for embolism (74,75).
Apart from the morbidity and mortality associated with arterial embolization, the prognosis of patients with atrial fibrillation depends on the nature and extent of underlying heart disease.
Atrial Flutter
Definition and Causes
Atrial flutter is a reentrant arrhythmia that usually is confined to the right atrium and results in an atrial rate of approximately 240 to 300 bpm. Usually there is a 2:1 AV conduction block so that the ventricular response is approximately 120 to 150 bpm. In contrast to atrial fibrillation, both atrial and ventricular responses often are regular. Atrial flutter usually is seen in patients who have underlying cardiopulmonary disease—ischemic heart disease, rheumatic heart disease, congestive cardiomyopathy, atrial septal defect, mitral valve disease, chronic obstructive pulmonary disease, or thyrotoxicosis—the same diseases often associated with atrial fibrillation. In contrast to atrial fibrillation, however, atrial flutter is rarely seen in patients who are otherwise healthy.
Symptoms and Signs
Patients usually are aware of a rapid heart rate. Whether other symptoms develop depends on the severity and nature of the underlying heart disease.
A regular, rapid heart rate and arterial pulse are detected. Sometimes the flutter waves are visible in the jugular venous pulse. An S4 is occasionally audible (in contrast to atrial fibrillation).
Electrocardiogram
In atrial flutter, the ECG commonly shows rapid, regular sawtooth flutter waves at approximately 240 to 300 bpm (Fig. 64.9). The ventricular response may be regular, usually at approximately 120 to 150 bpm, and the QRS complex ordinarily is morphologically normal. If the AV node is diseased or the patient is taking a medication that slows AV conduction, higher degrees of AV block may be seen, usually a multiple of two (e.g., 4:1, 8:1). Aberrant conduction is unusual.
If the diagnosis is unclear, carotid sinus massage may help distinguish atrial flutter from other paroxysmal supraventricular tachyarrhythmias. It usually causes an abrupt temporary slowing of the rate. Flutter waves, which may have been difficult to detect at a higher rate, are visible on the ECG, most commonly in leads II, III, aVF, and V1 (Fig. 64.9). Diagnostic workup is the same as for atrial fibrillation.
Treatment and Course
Atrial flutter often is a chronic and highly refractory arrhythmia that is difficult to treat with medical therapy. The initial goal of therapy should be to slow the ventricular response, but, in contrast to the situation with atrial fibrillation, it often is difficult to lower the ventricular rate with drugs.
If there is no contraindication, electrical cardioversion (see previous discussion) is the treatment of choice if atrial flutter persists. Most patients can be converted to normal
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sinus rhythm, usually after application of a lower-energy shock than is necessary to convert atrial fibrillation. If atrial flutter recurs after cardioversion, radiofrequency catheter ablation should be considered.
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FIGURE 64.9. Atrial flutter. The flutter waves are clearly revealed after carotid sinus massage (arrowhead). |
Considerations regarding pharmacologic therapy for atrial flutter are the same as for atrial fibrillation (see previous discussion). Perhaps the only difference is that atrial flutter is even less likely to respond to antiarrhythmic therapy. Patients who have recurrent symptomatic atrial flutter should be considered for electrophysiologic study with possible radiofrequency catheter ablation of the reentrant circuit. Radiofrequency catheter ablation of atrial flutter can be accomplished successfully in >95% of patients, with a very low incidence of complications (76,77). Radiofrequency catheter ablation has been demonstrated to be more effective than antiarrhythmic therapy for treatment of atrial flutter (77).
Ventricular Premature Beats and Ventricular Tachycardia
Definition and Causes
Ventricular premature beats (VPBs) or premature ventricular contractions (PVCs) are impulses generated in the ventricles, usually as the result of reentry of an impulse conducted down from the atria through the AV node, but sometimes as the result of the firing of an ectopic (parasystolic) focus. Ventricular tachycardia (VT) consists of at least three consecutive PVCs occurring at a rate of at least 100 bpm.
Occasional VPBs occur in many healthy people sporadically during their lives, more often in older people. However, often VPBs are associated with underlying organic heart disease (e.g., hypertensive heart disease, ischemic heart disease, cardiomyopathy). The frequency of VPBs may be increased by caffeine, alcohol, sympathomimetic drugs, tricyclic antidepressants, phenothiazines, hypokalemia, hypomagnesemia, hypoxia, or emotional stress in people both with and without heart disease. VPBs are a common manifestation of digitalis intoxication. Exercise usually abolishes VPBs in people without structural heart disease; conversely, an increase in the number of VPBs after exertion is highly suggestive of structural heart disease.
Symptoms and Signs
Patients may be unaware that they have had a VPB, but often they experience a palpitation. They sense either the premature beat itself or the more forceful normal beat that follows it after a compensatory pause.
Electrocardiogram
The ECG shows a premature ventricular response with a morphologically abnormal, often bizarre, wide QRS complex. No P wave precedes a VPB, but by retrograde conduction a P wave sometimes follows it. The ST segment and T wave have an opposite vector from the QRS complex. Typically, a VPB is followed by a compensatory pause, that is, the R–R interval between two normal beats separated by a VPB is the same as that between two normal beats separated by another normal beat if the patient is in normal sinus rhythm (Fig. 64.10). This occurs because retrograde conduction of the premature beat to the AV node blocks the succeeding sinus beat.
When VPBs are caused by reentry, they have a fixed temporal (coupled) relationship to the preceding normal beats. When they are caused by the firing of an ectopic (parasystolic) focus, they have no fixed relationship to the preceding normal beats but do have a regular pattern (i.e., the ectopic intervals are constant or are multiples of a constant). Ectopic beats occasionally fuse with normal beats, producing a complex that is intermediate between the two (Fig. 64.11).
Treatment and Course
VPBs in patients with otherwise normal hearts are not harmful. However, there is an increased incidence of sudden death and MI in patients with VPBs who have underlying ischemic heart disease (11). Suppression of VPBs has
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not been demonstrated to alter their course in these latter patients (13). Because all antiarrhythmic agents have potentially serious side effects (Table 64.2), the practitioner must consider for each patient the relative risks of treating versus not treating VPBs. The following generalizations may be useful:
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FIGURE 64.10. Premature ventricular beat. Note that the R–R interval between the two normal beats separated by the premature ventricular beat is the same as that between two normal beats separated by another normal beat. |
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FIGURE 64.11. Premature ventricular beats caused by firing of an ectopic focus. Arrowhead points to a fusion beat. |
The management of patients with, or at risk for, VT is evolving rapidly with the more widespread use of catheter ablation and ICD therapy. Patients with significant structural heart disease (evidenced by EF <40%) and symptomatic ventricular arrhythmias, especially symptomatic multifocal premature ventricular beats with a frequency >10 per hour or runs of VT, have an increased risk of sudden death. These patients should be referred to a cardiologist for consideration of electrophysiologic testing and/or ICD therapy. MADIT demonstrated that placement of an implantable defibrillator improves survival among patients with a prior MI and EF <35% who have inducible sustained VT during electrophysiologic testing that is not suppressed with intravenous procainamide (37,79). Sustained VT usually is defined as VT that lasts >30 seconds or requires termination because of hemodynamic compromise, whereas nonsustained VT terminates spontaneously within 30 seconds. MUSTT confirmed these findings and demonstrated that placement of an implantable defibrillator improves survival among patients with a prior MI and EF <40% who have inducible sustained VT during electrophysiologic testing (38). Based on the results of this study, the current recommendation is that patients with nonsustained VT, in the setting of an ischemic cardiomyopathy, undergo electrophysiologic testing and that an implantable defibrillator be placed in patients with inducible VT.
The optimal approach to the management of nonsustained VT in the setting of a nonischemic cardiomyopathy often also involves ICD therapy, as a result of the findings of the SCD-HeFT trial (40). This trial (see discussion earlier in this chapter) showed that prophylactic placement of an ICD decreased mortality in patients with LVEF ≤35% and NYHA class II or III heart failure, regardless of cause.
When ventricular arrhythmias occur in the setting of congestive heart failure, an attempt should be made to achieve a maximal state of cardiac compensation before antiarrhythmic therapy is instituted. Hemodynamic compensation may decrease or eliminate VPBs so that specific antiarrhythmic therapy is not required. Disopyramide and flecainide are myocardial depressants and are specifically contraindicated in patients whose hearts are enlarged and hypocontractile. Furthermore, patients in severe chronic heart failure, many of whom are taking diuretics, are more likely to experience problems such as hypokalemia, hypomagnesemia, alkalosis, hypoxemia, and digitalis toxicity, thus increasing the risk of serious side effects from antiarrhythmic agents (80). Such patients are best treated in consultation with a cardiologist.
Patients with structural heart disease who have a sustained ventricular arrhythmia (sustained monomorphic VT or ventricular fibrillation) are best managed based on the results of electrophysiologic evaluation. Implantable defibrillators are generally the treatment of choice in this patient population. This approach requires hospitalization and consultation with a cardiologist. Radiofrequency catheter ablation in this patient population is generally used as adjunctive therapy for patients who have undergone placement of an implantable defibrillator and are experiencing frequent shocks because of recurrent slow sustained monomorphic VT (81).
Sustained VT that occurs in the absence of structural heart disease (referred to as idiopathic VT) is generally associated with a benign prognosis. Treatment is indicated for relief of symptoms. This type of VT usually responds to treatment with most types of antiarrhythmic agents, including β-blockers, calcium channel blockers, and class IC antiarrhythmic agents. Radiofrequency catheter ablation, which has success rates >90% and a low incidence of
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complications, is another commonly used treatment option in this patient population (82).
Primary care providers occasionally assume the care of patients who are taking antiarrhythmic agents because of a history of symptomatic ventricular arrhythmias caused by structural heart disease. Consultation with a cardiologist is advisable before therapy is stopped. The possibility that a patient will experience a proarrhythmic effect from an antiarrhythmic agent must always be considered (see earlier discussion).
Preexcitation Syndrome
Definition and Causes
In normal hearts, the atria and ventricles are electrically isolated from each other by the AV groove, and the electrical signal from the atrium is conducted to the ventricle via the AV node and conducting system. If the AV groove is short-circuited by muscle fibers, if muscle fibers from the atria enter the His bundle below the AV node, or if muscle fibers from the His bundle bypass the bundle branches, a variable portion of the right or left ventricle is depolarized early. These short-circuiting fibers are known as accessory AV, nodoventricular, and fasciculoventricular pathways—the atriofascicular bypass tract and the intranodal bypass tract, depending on their location (Fig. 64.12).
The classic example of preexcitation is WPW syndrome. This syndrome is characterized electrocardiographically by a short PR interval followed by a wide QRS complex, which is a fusion beat between the ventricular myocardium that is preexcited and that which is excited via normal conduction pathways (Fig. 64.13). The portion of the complex caused by preexcitation is called the delta wave because of its resemblance to the Greek capital letter. If the accessory bundle connects the atria with the left ventricle, the ECG pattern resembles RBBB (type A WPW). On the other hand, if the connection is with the right ventricle, the pattern resembles left bundle-branch block (LBBB; type B WPW). The negative delta wave in lead II in this situation may be taken for a Q wave, and the mistaken diagnosis of remote MI may be made.
If the atrial fibers insert into the bundle of His and short-circuit the AV node, the PR interval is short but no delta wave is seen because conduction below the AV node occurs along the usual pathways. This syndrome is known as Lown-Ganong-Levine syndrome. A number of other variants of preexcitation syndrome have been described but are much rarer than these two more common disorders (83).
The ECG manifestations of preexcitation may vary from time to time within a given patient because, if conduction occurs through the normal anatomic pathways rather than through accessory fibers, no preexcitation is seen on the ECG. If preexcitation is facilitated because of disease in the AV node or because of drugs that suppress conduction through the AV node (e.g., digitalis, calcium channel blockers, β-blockers), ECG abnormalities are seen.
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FIGURE 64.12. Schematic diagram of possible accessory conduction pathways (old eponymic nomenclature given in parentheses). A, atriofascicular (atrio-Hisian) bundles; J, intranodal bypass (James) tracts; K, accessory atrioventricular (Kent) bundles; M (Mahaim) fibers—M1, accessory nodoventricular; M2, accessory fasciculoventricular; M3, nodofascicular fibers. Dual atrioventricular node pathways are represented by the fast and slow labels. (Adapted from Wellens HJJ, Brugada P, Penn OC. The management of preexcitation syndromes. JAMA 1987;257:2325 , with permission.) |
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FIGURE 64.13. Wolff-Parkinson-White syndrome. Note the delta wave (arrowhead). |
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Supraventricular arrhythmias are found in 13% to 60% of patients with preexcitation. PSVT is most commonly observed, but atrial fibrillation and flutter also occur (84). Accessory pathways can conduct anterograde (from the atrium to the ventricle), retrograde (from the ventricle to the atrium), or both. The morphology of the QRS complex during the tachyarrhythmia depends on the direction in which the reentrant tachycardia occurs. If reentry occurs with anterograde conduction through the AV conducting system and retrograde conduction through an accessory pathway, then the ventricles are depolarized through the normal AV conduction system, and the QRS duration during the tachyarrhythmia may be normal (i.e., no delta wave is seen during tachycardia). This type of tachycardia, known as orthodromic atrioventricular reentrant tachycardia (AVRT), is by far the most common supraventricular tachycardia in patients with WPW syndrome. In a small percentage of patients with WPW syndrome and AVRT, the circuit is established in the opposite direction, with depolarization of the ventricle over the accessory pathway during the tachycardia. In this circumstance, known as antidromic AVRT, the QRS complex is wide and the arrhythmia can easily be confused with VT.
It should be noted that the term preexcitation refers to evidence of an anterograde-conducting accessory pathway on the ECG. WPW syndrome refers to a specific syndrome of supraventricular tachycardia in the setting of preexcitation on the ECG. A patient who has evidence of preexcitation on the ECG but no supraventricular tachycardia is properly described as having asymptomatic preexcitation. Accessory pathways that conduct only in the retrograde direction and therefore are not associated with a delta wave on the ECG are referred to as concealed accessory pathways; these pathways cannot be identified by a routine 12-lead ECG.
Symptoms and Signs
Preexcitation may be an incidental finding on an ECG, or it may come to the attention of the health care provider because of symptoms of palpitations. Other symptoms of tachyarrhythmia depend on the nature of the arrhythmia and the presence or absence of other structural heart disease.
No physical findings are caused by preexcitation other than an occasional loud S1, except during periods of tachyarrhythmia, when the findings depend on the type of arrhythmia present.
Prevalence
Preexcitation syndromes are not rare. The prevalence of preexcitation is between one and three per 1,000 people, or approximately 0.15% to 0.3% of the normal population (84). Accurate prevalence rates are difficult to obtain because short PR intervals with normal QRS durations are commonly seen in people without arrhythmias, so no studies are performed to determine whether a bypass tract exists.
Preexcitation syndromes occasionally are associated with certain forms of congenital heart disease. Preexcitation of the WPW type is associated with Ebstein anomaly of the tricuspid valve, corrected transposition of the great vessels, and hypertrophic cardiomyopathy (83).
Treatment and Course
The presence of preexcitation in an asymptomatic patient is associated with an approximately 0.1% annual risk of sudden cardiac death. Because this is not markedly greater than the risk of sudden cardiac death in the general population and because treatment itself is associated with some
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risk (i.e., the risk of death during catheter ablation is approximately 0.1%) (85), asymptomatic patients with preexcitation on the ECG may not require electrophysiologic testing or specific treatment. On the other hand, it is difficult to identify low-risk patients with preexcitation or to reassure the patient based on clinical assessment alone (i.e., without an electrophysiologic test). For this reason, the approach to the patient with asymptomatic preexcitation must be individualized, and referral of patients with asymptomatic preexcitation to a cardiologist for discussion of possible approaches to this condition is reasonable. Competitive athletes and people in high-risk occupations (e.g., bus drivers, pilots) who have preexcitation on the ECG should generally undergo an electrophysiologic study to determine whether the accessory pathway has the capacity to conduct rapidly (which increases the risk of sudden cardiac death fivefold) and whether a sustained arrhythmia can be induced. In these settings, radiofrequency catheter ablation often is performed. All patients with evidence of preexcitation on the ECG should be instructed to contact their health care provider if symptoms develop. Because of the increased risk of sudden cardiac death among symptomatic patients with preexcitation (WPW syndrome), electrophysiologic testing with radiofrequency catheter ablation now is recommended as first-line therapy for symptomatic patients.
Patients with occasional symptoms often can be taught to break the arrhythmia with the use of vagal maneuvers. These maneuvers should be tried as soon as possible after the onset of tachycardia because sympathetic tone quickly increases and interferes with the effectiveness of the maneuvers. Effective vagal maneuvers include straining against a closed glottis (Valsalva maneuver), self-applied carotid sinus massage, and placing a cold wet towel over the face (diving reflex).
Torsade De Pointes and the Long QT Interval Syndrome
Torsade de pointes—literally, “twisting of the points” (QRS complexes)—is a potentially life-threatening arrhythmia characterized by a form of polymorphic VT in which the QRS axis seemingly twists about the isoelectric line. Torsade de pointes is seen most often in the setting of acquired QT prolongation caused by drug interactions, but it may be seen with the syndrome of idiopathic or congenital QT prolongation, or without QT prolongation in the setting of ischemia (2).
Antiarrhythmic drugs that prolong the QT interval, such as quinidine and sotalol, are the most common cause of torsade de pointes. In most patients, predisposing factors such as diuretic use with associated hypokalemia or hypomagnesemia are present. Severe bradycardia is another important predisposing factor, as is female gender, which is associated with 70% of cases of torsade de pointes in the setting of acquired QT prolongation (86). Besides antiarrhythmic drugs, a variety of other drugs may cause QT prolongation and have been associated with torsade de pointes. These include antipsychotics (e.g., chlorpromazine and haloperidol); some antibiotics, particularly erythromycin (87) and clarithromycin; and many other drugs (a more complete list is available at http://www.torsades. org). Although the incidence of torsade de pointes in patients taking these drugs is rare, they should be used with caution in women; in patients who are taking several of these drugs in combination, especially in the setting of hypokalemia or hypomagnesemia; and in patients with the long QT syndrome.
In contrast to acquired QT prolongation, idiopathic or congenital long QT syndrome is a relatively uncommon congenital disorder in which delayed repolarization is expressed as a long QT interval (>0.45 second when corrected for heart rate) (88). In some families, the inheritance is autosomal recessive and is associated with neurologic deafness; in most others, the inheritance is autosomal dominant and hearing is normal. The congenital syndrome has been shown to be caused by mutations in genes encoding components of cardiac sodium or potassium channels. Diagnostic criteria, using a point scale, have been published (89). The long QT interval predisposes to torsade de pointes, which often causes syncope and may cause sudden death, especially in the setting of acute stress (88). The QT interval should be measured routinely on the ECG of patients who complain of syncope for which there is no explanation.
The most effective treatment of symptomatic patients with the congenital long QT syndrome is β-blocker therapy, in contrast to acquired QT prolongation, in which bradycardia may provoke torsade de pointes. If β-blocker therapy does not suppress arrhythmic attacks, ICD therapy should be considered. Appropriate treatment reduces the long-term mortality rate from 50% to <5%. Whether patients with long QT intervals who are asymptomatic benefit from antiadrenergic therapy is not known, but treatment is reasonable if the patient has a family history of sudden death. An exercise ECG is indicated for patients with long QT intervals who have negative personal and family histories of arrhythmias to determine whether arrhythmias can be induced by exertion.
Arrhythmias in Pregnancy
Clinically significant arrhythmias occur rarely during pregnancy, but the awareness of ventricular ectopy and VT is increased (90). The most common arrhythmia, other than isolated premature atrial beats and premature ventricular beats, is PSVT (see above) caused by AV nodal reentry, a common arrhythmia (see previous discussion). Occasionally, nonsustained VT is detected as an incidental finding in an otherwise asymptomatic patient. Antiarrhythmic
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treatment options are limited in pregnancy. Fluoroscopy, which is necessary for radiofrequency catheter ablation, is relatively contraindicated, and antiarrhythmic drug options are limited. β-Blockers, especially atenolol, have been reported to be safe for use during pregnancy, and quinidine and procainamide have been used as well (90). Submaximal exercise stress testing has been shown to be safe up to 25 weeks’ gestation (91). Ventricular arrhythmias that suppress with exercise are thought to have a benign prognosis (92). Patients with symptomatic arrhythmias should be referred to a cardiologist for evaluation.
Heart Block
Heart block, a delay or failure of conduction of the cardiac impulse, is categorized electrocardiographically.
Right Bundle-Branch Block
RBBB, a delay or block of conduction through the right bundle branch (Fig. 64.14), causes a modest prolongation of the QRS complex (>0.12 second). The initial QRS vector is unaffected because it is accounted for normally by initial LV (septal) depolarization. The right ventricle is activated by spread of the action potential from the left ventricle, which is seen best in leads I and V6, where the S waves are wide and slurred, and in lead V1, where there is a double peak (RR′) of the R wave. RBBB is sometimes seen on the ECG of patients who have otherwise normal hearts. More often it is associated with an underlying congenital or acquired disorder, such as atrial septal defect and hypertensive or ischemic heart disease. Patients with newly acquired RBBB have an increased risk of cardiovascular morbidity and death from cardiovascular disease (93).
Left Bundle-Branch Block
LBBB, a delay or block of conduction through the left bundle branch (Fig. 64.15), causes marked prolongation of the QRS complex (0.14–0.16 second). The entire sequence of ventricular depolarization is affected so that the QRS complex is widened and the QRS axis is directed to the left and posteriorly. Abnormal repolarization is reflected in the T wave, which is always in the direction opposite that of the QRS complex.
LBBB almost always signifies heart disease, usually ischemic heart disease or cardiomyopathy (94).
Hemiblock
Left Anterior Hemiblock
If the cardiac impulse in the anterosuperior portion of the left bundle branch delayed or blocked (Fig. 64.3), the corresponding wall of the left ventricle is activated late, resulting in marked left-axis deviation on the ECG (Fig. 64.14). The duration of the QRS complex usually is normal or slightly prolonged (>0.10 second). The causes of left anterior hemiblock (LAH) are the same as those of LBBB. LAH is occasionally seen in patients with no discernible heart disease. Whatever the cause, LAH in itself is not a poor prognostic sign and, at least in an ambulatory setting, requires no specific therapy.
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FIGURE 64.14. Right bundle-branch block and left anterior hemiblock (bifascicular block). |
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FIGURE 64.15. Left bundle-branch block. |
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Left Posterior Hemiblock
If the cardiac impulse in the posterior portion of the left bundle branch is delayed or blocked (Fig. 64.3), activation of the posterior wall of the left ventricle is delayed. The ECG pattern of left posterior hemiblock (LPH) is characterized by marked right-axis deviation (more than +110 degrees). The causes of LPH are the same as those of LAH and LBBB. Because the posterior portion of the left bundle branch is larger and better perfused than the anterosuperior portion, LPH is less common than LAH and usually indicates more extensive LV disease (95).
Bifascicular Block
RBBB with LAH (manifested by an RBBB pattern and left-axis deviation; Fig. 64.14) or RBBB with LPH (manifested by an RBBB pattern and right-axis deviation) indicates that only one pathway is available to maintain passage of the cardiac impulse from the atria to the ventricles. If bifascicular block is detected in an ambulatory setting, especially if the patient has a history of syncope or light-headedness, a cardiologist should be consulted to determine whether electrophysiologic studies (see Diagnosis of Arrhythmias) or pacemaker implantation is indicated. The risk that unselected patients with bifascicular block will develop complete heart block is 2% to 4% per year (96). Evidence on the course of patients with bifascicular block conflicting: Some report no increased morbidity, whereas others report a considerably shortened survival time. Although there is no consensus about how to deal with the problem, the prognosis seems to be related to the extent of underlying disease rather than the conduction abnormality per se.
First-Degree Atrioventricular Block
Definition and Causes
The PR interval normally varies with heart rate but should not exceed 0.20 second in persons in normal sinus rhythm. First-degree AV block is defined as a prolonged PR interval. The block may be caused by prolongation of conduction in any of the structures between the SA node and the bundle of His (Fig. 64.3). Most commonly, when the QRS duration is normal, a long PR interval is caused by a delay in conduction in the AV node. When first-degree block coincides with LBBB, there is a delay in conduction in the His bundle. A prolonged PR interval with RBBB may be caused by a block in the AV node or in the His bundle.
Prolongation of the PR interval usually is caused by degenerative, ischemic, or inflammatory changes in the AV conduction systems. It is commonly seen in older people without other evidence of heart disease, in patients who have had an inferior wall MI, or in patients in association with myocarditis (including acute rheumatic fever). Drugs such as digitalis, which affect vagal activity, and sympatholytic drugs also may produce first-degree AV block.
Symptoms and Signs
First-degree AV block in itself does not produce symptoms or abnormal physical findings except for reduced intensity of S1.
Treatment and Course
Patients with first-degree AV block who are asymptomatic and have no other evidence of heart disease do not require treatment. If patients with first-degree block complain of
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light-headedness or dizziness, an ambulatory ECG or event monitor should be obtained (see Use of the Electrocardiogram) because some of these patients can have episodic higher degrees of block.
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FIGURE 64.16. Mobitz-I or Wenckebach second-degree atrioventricular block. |
Second-Degree Atrioventricular Block
Definition and Causes
Second-degree AV block is present when some, but not all, P waves are followed by QRS complexes. Second-degree AV block is caused by conduction delay or block in either the AV node or the conduction system below the AV node, most commonly resulting from ischemic heart disease, cardiomyopathy, or drug toxicity (e.g., calcium channel blockers). The site of block has important therapeutic implications.
Mobitz-I or Wenckebach Second-Degree Atrioventricular Block
Second-degree AV block within the AV node results in the Wenckebach phenomenon. It is characterized by progressive lengthening of the PR interval with shortening of the R–R interval for several cycles until the P wave is blocked completely (Fig. 64.16) (97). The sequence then begins again, often with a normal PR interval in the beat that follows the blocked P wave. In the absence of disease elsewhere in the conducting system, the QRS complex is normal. The degree of Wenckebach block is characterized by the ratio of the number of P waves to the number of QRS complexes in each cycle of block. In other words, if block occurs after every third P wave, it is called 3:2 Wenckebach.
Because conduction through the AV node is influenced by vagal tone, type I second-degree AV block may be precipitated by anything that increases vagal tone. Therefore, it is sometimes seen as a transient phenomenon in people with no other evidence of heart disease. Otherwise, it is produced by the same processes that are associated with first-degree AV block.
Mobitz-II Second-Degree Atrioventricular Block
Mobitz-II block is defined as intermittent failure to conduct a P wave caused by block below the level of the AV node (Fig. 64.17). The PR interval of the conducted beat before a blocked P wave usually is normal. The block may be intermittent, or it may occur in a fixed 2:1 or 3:1 ratio. Coexistent bundle-branch block is commonly seen. Progression to higher degrees of block or to asystole may occur rapidly.
Vagal influences have little effect on conduction below the AV node, so changes in vagal tone do not influence
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Mobitz-II block. The common causes of Mobitz-II block are degenerative or ischemic changes in the His-Purkinje system.
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FIGURE 64.17. Mobitz-II second-degree atrioventricular block. |
Symptoms and Signs
Mobitz-I Second-Degree Atrioventricular Block
Patients often are asymptomatic, but if vagal tone is increased (e.g., by digitalis or a β-blocker or central sympatholytics such as clonidine), profound bradycardia may ensue, sometimes with rates <30 bpm. Such patients may complain of light-headedness, syncope, or extreme fatigue.
Physical findings are subtle; irregularity of the heart rhythm and arterial pulse may be noted when a beat is dropped. The S1 of the last beat before the dropped beat is softer than that of the first beat after the pause (because of the variation in PR interval; see Chapter 65).
Mobitz-II Second-Degree Atrioventricular Block
Symptoms and physical findings are similar to those of patients with Mobitz-I block except that they are not influenced by changes in vagal activity and the intensity of S1 is constant.
Treatment and Course
Mobitz-I First-Degree Atrioventricular Block
Asymptomatic patients do not require treatment because the risk of rapid progression of the block and of asystole is slight. Symptomatic patients usually have pronounced bradycardia. If so, medications that may be increasing the block should be discontinued if they are not required. If such medications are essential to the patient's management, a cardiac pacemaker should be implanted (see Pacemaker Therapy).
Mobitz-II Second-Degree Atrioventricular Block
Because of the high risk of rapid progression of the block and of asystole, all patients, even if asymptomatic, should be treated with a permanent cardiac pacemaker unless a reversible cause is identified and treated.
Patients with a history of light-headedness or dizziness who have new bundle-branch block should be suspected of having had Mobitz-II block. This suspicion often can be confirmed by ambulatory ECG or event monitor (see Use of the Electrocardiogram). A diagnostic electrophysiologic study (discussed earlier) may be helpful to look for prolonged conduction through the His-Purkinje system.
Third-Degree (Complete) Heart Block
Definition and Causes
Complete heart block occurs when there is total failure of conduction of impulses from the atria through the AV junction to the bundle of His (or, more rarely, if all three fascicles below the His bundle are diseased). The life of the patient then depends on the escape of a ventricular pacemaker. A rhythm generated in the upper portion of the His bundle may have a QRS configuration nearly identical to that of normally conducted impulses and has a rate between 40 and 60 bpm (Fig. 64.18). It is more likely to be a stable rhythm than is a rhythm generated by a lower pacemaker. If the pacemaker is located more distally in the conducting system, the ventricular rate decreases, the QRS morphology becomes wider and more bizarre, and the risk of asystole increases. In children or young adults, complete heart block may occur because of congenital defects in development of the AV cushion or of the conduction system itself. In such cases, escape rhythms usually are generated high in the bundle of His. In older people, complete heart block is most commonly caused by degenerative and fibrotic changes in the conduction system. It is also seen sometimes in association with infiltrative disease of the myocardium (e.g., sarcoid, amyloid), inflammatory processes (e.g., rheumatoid arthritis), and myocardial infections (e.g., bacterial endocarditis with valve ring abscess) or ischemic heart disease. Occasionally digitalis toxicity produces complete heart block, as may excessive dosages of β-blockers, amiodarone, or calcium channel blockers.
Complete heart block is a subcategory of AV dissociation, a situation in which the atria and ventricles are depolarized independently. In instances of AV dissociation other than complete heart block, the ventricles may be paced independently because of enhancement of the rate of discharge of a latent ventricular pacemaker (e.g., VT) or because of marked slowing of the rate of discharge of the ordinarily dominant atrial pacemaker. In these instances, the ventricular rate usually is greater than the atrial rate
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and is also usually greater than in patients with complete heart block.
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FIGURE 64.18. Third-degree heart block. |
Symptoms and Signs
A major symptom of complete heart block is sudden loss of consciousness (Stokes-Adams attack), the result of asystole or tachyarrhythmia (VT or ventricular fibrillation). The asystole is caused by failure of the ventricular pacemaker; the tachyarrhythmia is caused by escape of another focus when the idioventricular rate falls too low (a variant of the bradycardia-tachycardia syndrome; see Sick Sinus Syndrome). If the heart begins to pump effectively again within seconds, as it usually does, the patient promptly regains consciousness and is alert and oriented. If perfusion of vital organs is delayed, seizure-like activity (ordinarily not generalized) and even death may ensue. Patients who are unconscious for more than a few minutes may not become fully alert for hours.
Complete heart block in patients with underlying myocardial disease can cause symptoms of heart failure (see Chapter 66), primarily because of further reduction in cardiac output as the result of bradycardia.
Physical findings of heart block—variation in the intensity of S1, variation in systolic blood pressure, variation in the intensity of heart murmurs and of S3 and S4, and the appearance of cannon waves in the jugular venous pulse—all are attributable to the dissociation between atrial and ventricular contraction. The heart rate, of course, is slow.
Treatment and Course
The treatment of complete heart block is permanent pacemaker implantation unless a reversible cause is identified and treated. Even patients with a potentially reversible cause of complete heart block usually require hospitalization for temporary transvenous pacemaker therapy until normal rhythm is restored. The life expectancy of treated patients with complete heart block who have no other evidence of cardiac or systemic disease is excellent and approaches that of their age-matched cohort. Patients with complete heart block caused by coronary disease have a prognosis that is determined by the extent of their underlying coronary artery disease and their myocardial function.
Specific References*
For annotated General References and resources related to this chapter, visit http://www.hopkinsbayview.org/PAMreferences.
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