A dysrhythmia is any deviation from the normal rhythm of the heart. The term arrhythmia (literally “no rhythm”) implies asystole, or no heartbeat at all. Thus, the more accurate term for an irregular heart rhythm is dysrhythmia. However, arrhythmia is commonly used in clinical practice. Dysrhythmias can develop in association with many conditions, such as after a myocardial infarction (MI), cardiac surgery, or as the result of coronary artery disease. Dysrhythmias are usually serious and may require treatment with an antidysrhythmic drug or nonpharmacologic therapies; however, not all dysrhythmias require medical treatment. A cardiologist is usually consulted to make the judgment.

Disturbances in cardiac rhythm are the result of abnormally functioning cardiac cells. Thus, an understanding of the mechanism responsible for dysrhythmias first requires review of the electrical properties of these cells. Figure 24-1 on p. 384 shows the overall anatomy of the conduction system of the heart. Figure 25-1 illustrates some of the properties of this system from the standpoint of a single cardiac cell. Inside a resting cardiac cell, a net negative charge exists relative to the outside of the cell. This difference in the electronegative charge exists in all types of cardiac cells and is referred to as the resting membrane potential (RMP). The RMP results from an uneven distribution of ions (e.g., sodium, potassium, and calcium) across the cell membrane. This is known as polarization. Each ion moves through its own specific channel, which is a specialized protein molecule that sits across the cell membrane. These proteins work continuously to restore the specific intracellular and extracellular concentrations of each ion. At RMP, the ionic concentration gradient (distribution) is such that potassium ions are more highly concentrated intracellularly, whereas sodium and calcium ions are more highly concentrated extracellularly. For this reason, potassium is generally thought of as an intracellular ion, whereas sodium and calcium are generally thought of as extracellular ions. Negatively charged intracellular and extracellular ions such as chloride (Cl^–) and bicarbonate (HCO₃^–) also contribute to this uneven distribution of ions, which is known as a polarized state. This polarized distribution of ions is maintained by the sodium-potassium adenosine triphosphatase (ATPase) pump, an energy-requiring ionic pump. The energy that drives this pump comes from molecules of adenosine triphosphate (ATP), which are a major source of energy in cellular metabolism.

FIGURE 25-1 Phases of the action potential of a cardiac cell. In resting phase (4), the cell membrane is polarized. The cell’s interior has a net negative charge, and the membrane is more permeable to potassium ions (K) than to sodium ions (Na). When the cell is stimulated and begins to depolarize (0), sodium ions enter the cell, potassium leaves the cell, calcium (Ca) channels open, and sodium channels close. In its depolarized phase (1), the cell’s interior has a net positive charge. In the plateau phase (2), calcium and other positive ions enter the cell and potassium permeability declines, which lengthens the action potential. Then (3), calcium channels close and sodium is pulled from the cell by the sodium-potassium pump. The cell’s interior then returns to its polarized, negatively charged state (4). (From Monahan FD: *Phipps’ medical-surgical nursing: health and illness perspectives,* ed 8, St Louis, 2007, Mosby.)

Cardiac cells become excited when there is a change in the baseline distribution of ions across their membranes (RMP) that leads to the propagation of an electrical impulse. This change is known as an action potential. Action potentials occur in a continuous and regular manner in the cells of the cardiac conduction system, such as the sinoatrial node (SA), atrioventricular node (AV), and His-Purkinje system. All of these tissues have the property of spontaneous electrical excitability known as automaticity. This excited state creates action potentials, which in turn generate electrical impulses that travel through the myocardium ultimately to create the heartbeat via contraction of cardiac muscle fibers.

An action potential has five phases. Phase 0 is also called the upstroke because it appears as an upward line on the graph of an action potential, as shown in Figure 25-2, A and B. Both of these figures graphically illustrate the cycle of electrical changes that create an action potential. Note the variation in the shape of the curve depending on the relative conduction speed of the specific tissue involved (SA node versus Purkinje fiber). A faster rate of conduction corresponds to a steeper slope on the graph.

FIGURE 25-2 Action potentials. *RMP,* Resting membrane potential; *SA,* sinoatrial; *TP,* threshold potential.

During phase 0, the resting cardiac cell membrane suddenly becomes highly permeable to sodium ions, which rush from the outside of the cell membrane to the inside (influx) through what are known as fast channels or sodium channels. This disruption of the earlier polarized state of the membrane is known as depolarization. Depolarization can be thought of as a temporary equalization of positive and negative charges across the cell membrane. This releases electrochemical energy that drives the resulting electrical impulses through adjacent cells. Phase 1 of the action potential begins a rapid process of repolarization that continues through phases 2 and 3 to phase 4, which is the RMP. In phase 1, the sodium channels close and the concentrations of each ion begin to move back toward their ion-specific RMP levels. During phase 2, calcium influx occurs through the slow channels or calcium channels. They are called slow channels because the calcium influx occurs relatively more slowly than the earlier sodium influx. Potassium ions then flow from inside of the cell to outside (efflux) through specific potassium channels. This is done to offset the elevated positive charge caused by the influx of sodium and calcium ions. In the case of the Purkinje fibers, this causes a partial plateau (flattening on the graph) during which the overall membrane potential changes only slightly, as seen in Figure 25-2, B. In phase 3, the ionic flow patterns of phases 0 to 2 are changed by the sodium-potassium ATPase pump (or, more simply, the sodium pump). This reestablishes the baseline polarized state by restoring both intracellular and extracellular concentrations of sodium, potassium, and calcium (see Figure 25-1). As a result, the cell membrane is ultimately repolarized to its baseline level or RMP (phase 4). Note that this entire process occurs over roughly 400 milliseconds—that is, four hundred thousandths (less than one half) of one second.

There is some variation in this time period between different parts of the conduction system. As an example, Figure 25-3 illustrates the pattern of movement of sodium, potassium, and calcium ions into and out of a Purkinje cell during the four phases of the action potential. Note that there are several differences in the action potentials of SA nodal cells and Purkinje cells. The level of the RMP for a given type of cell is an important determinant of the rate of its impulse conduction to other cells. The less negative (i.e., the closer to zero) the RMP at the onset of phase 0 of the action potential, the slower the upstroke velocity of phase 0. The slope of phase 0 is directly related to the impulse velocity. An upstroke with a steeper slope indicates faster conduction velocity. Thus, in Purkinje cells, electrical conduction is relatively fast, and therefore electrical impulses are conducted quickly. These cells are referred to as fast-response cells, or fast-channel cells. Purkinje fibers can therefore be thought of as fast-channel tissue. Many antidysrhythmic drugs affect the RMP and sodium channels, which in turn influences the rate of impulse conduction.

FIGURE 25-3 Purkinje fiber action potential.

In contrast to Purkinje fibers, the cells of the SA node have a slower upstroke velocity, or a slower phase 0. This is illustrated in Figure 25-2, A, as an upstroke curve that is less steep, which indicates a relatively slower rate of electrical conduction in these cells.

AV nodal cells are comparable to SA nodal cells in this regard. This slower upstroke in the SA and AV nodes is primarily dependent on the entry of calcium ions through the slow channels or calcium channels. This means that nodal action potentials are affected by calcium influx as early as phase 0. The nodes are therefore called slow-channel tissue, and conduction is slower than that in other parts of the conduction system. Drugs that affect calcium ion movement into or out of these cells (e.g., calcium channel blockers) tend to have significant effects on the SA and AV nodal conduction rates.

The interval between phase 0 and phase 4 is called the action potential duration (Figure 25-4). The period between phase 0 and midway through phase 3 is called the absolute or effective refractory period. During the effective refractory period, the cardiac cell cannot be restimulated to depolarize and generate another action potential. During the remainder of phase 3 and until the return to the RMP (phase 4), the cardiac cell can be depolarized again if it receives a powerful enough impulse (such as one induced by drug therapy or supplied by an electrical pacemaker). This period is referred to as the relative refractory period. Figure 25-4 illustrates these various aspects of an action potential. Again, the actual shape of the action potential curve varies in different parts of the conduction system.

FIGURE 25-4 Aspects of an action potential. *APD,* Action potential duration; *ERP,* effective refractory period; *RRP,* relative refractory period.

The RMP of certain cardiac cells gradually decreases (becomes less negative) over time in ongoing cycles. This is due to small changes in the flux of sodium and potassium ions. Depolarization eventually occurs when a certain critical voltage is reached (threshold potential). This process of spontaneous depolarization is referred to as automaticity, or pacemaker activity. It is normal when it occurs in the SA node (see Figure 24-1 on p. 384). When spontaneous depolarizations occur elsewhere, however, dysrhythmias often result.

The SA node, the AV node, and His-Purkinje cells all possess the property of automaticity. The SA node is the natural pacemaker of the heart because it spontaneously depolarizes the most frequently. The SA node has an intrinsic rate of 60 to 100 depolarizations or beats per minute; that of the AV node is 40 to 60 beats per minute; and that of the ventricular Purkinje fibers is 40 or fewer beats per minute. The action potentials and other properties in different areas of the heart are compared in Table 25-1.

TABLE 25-1

COMPARISON OF ACTION POTENTIALS IN DIFFERENT CARDIAC TISSUE

TISSUE	ACTION POTENTIAL	SPEED OF RESPONSE	THRESHOLD POTENTIAL (mV)	CONDUCTION VELOCITY (m/sec)
SA node		Slow	260	Less than 0.05
Atrium		Fast	290	1
AV node		Slow	260	Less than 0.05
His-Purkinje system		Fast	295	3
Ventricle		Fast	290	1

AV, Atrioventricular; SA, sinoatrial.

As the pacemaker of the heart, the SA node, which is located near the top of the right atrium, generates the electrical impulse that ultimately produces the heartbeat. First, however, this impulse travels through the atria via specialized pathways called the internodal pathways (Bachmann bundle). This causes the atrial myocardial fibers to contract, which creates the first heart sound. Next, the impulse reaches the AV node, which is located near the bottom of the right atrium. The AV node slows this very fast moving electrical impulse just long enough to allow the ventricles to fill with blood. If the AV node did not slow the impulse in this way, ventricular contraction would overlap that of the atria, which would result in a smaller volume of ejected ventricular blood and reduced cardiac output.

Next, the AV nodal cells generate an electrical impulse that passes into the bundle of His (or His bundle). The bundle of His is a band of cardiac muscle fibers located between the right and left ventricles in what is called the ventricular septum (wall between the ventricles). The bundle of His distributes the impulse into both ventricles via the right and left bundle branches. Each branch terminates in the Purkinje fibers that are located in the myocardium of the ventricles. Stimulation of the Purkinje fibers causes ventricular contraction and ejection of blood from the ventricles. Blood from the right ventricle is pumped into the pulmonary circulation, whereas blood from the left ventricle is pumped into the systemic circulation to supply the rest of the body. The bundle of His and Purkinje fibers are so named for the medical scientists who first identified them. Together, they are often referred to in the literature as the His-Purkinje system. Any abnormality in cardiac automaticity or impulse conduction often results in some type of dysrhythmia.

Electrocardiography

The electrophysiologic cardiac events described thus far in this chapter correspond more simply to the tracings of an electrocardiogram, abbreviated as ECG or EKG (Figure 25-5). The P wave corresponds to spontaneous impulse generation in the SA node followed immediately by depolarization of atrial myocardial fibers and their muscular contraction. This normally determines the heart rate. It is affected by the balance between sympathetic and parasympathetic nervous system tone, the intrinsic automaticity of the SA nodal tissue, the mechanical stretch of atrial fibers due to incoming blood volume, and cardiac drugs. The QRS complex (or QRS interval) corresponds to depolarization and contraction of ventricular fibers. The J point marks the start of the ST segment, which corresponds to the beginning of ventricular repolarization. The T wave corresponds to completion of the repolarization of these ventricular fibers. As an analogy, depolarization can be thought of as discharge or contraction of cardiac muscle fibers, whereas repolarization can be thought of as a relaxation of muscle fibers to prepare for the next contraction (heartbeat). Note that the repolarization of the atrial fibers is obscured on the ECG tracing by the QRS complex and thus has no corresponding deflection in the tracing. The U wave is not always present, and its physiologic basis is uncertain. When the U wave occurs, it is generally correlated with electrophysiologic events such as repolarization of Purkinje fibers. These events may be a source of dysrhythmias caused by a triggered automaticity. Prominent U waves are often associated with sinus bradycardia, hypokalemia, use of quinidine and other class Ia antidysrhythmics, and hyperthyroidism. Abnormal U waves (inverted) are associated with serious conditions such as MI, acute angina, coronary artery spasms, and ischemic heart disease. The PR and QT intervals and the ST segment are parts of the ECG tracing that are often altered by disease or by the adverse effects of certain types of drug therapy or drug interactions, as discussed in later sections of this chapter.

Common Dysrhythmias

A variety of cardiac dysrhythmias are recognized. Some are easier to treat than others using drug therapy and/or interventional cardiology procedures such as pacemaker implantation, catheter ablation, cardioversion, and implantation of cardioverters-defibrillators. Dysrhythmias are subdivided into several broad categories depending on their anatomic site of origin in the heart. Supraventricular dysrhythmias originate above the ventricles in the SA or AV node or atrial myocardium. Ventricular dysrhythmias originate below the AV node in the His-Purkinje system or ventricular myocardium. Dysrhythmias that originate outside the conduction system (i.e., in atrial or ventricular cells) are known as ectopic, and their specific points of origin are called ectopic foci (foci is the plural of the Latin-derived word focus). Conduction blocks are dysrhythmias that involve disruption of impulse conduction between the atria and ventricles through the AV node, directly affecting ventricular function. They may also originate in the His-Purkinje system. Less commonly, impulse conduction between the SA and AV node is affected. Several of the most common dysrhythmias are described in Table 25-2, and corresponding ECG tracings are provided. They are also described further in the following text.

TABLE 25-2

COMMON DYSRHYTHMIAS

DYSRHYTHMIA	DESCRIPTION AND ECG TRACING
Atrial flutter (AF)	Often progresses to atrial fibrillation (F = flutter waves)
Atrial fibrillation (AF)	Rapid, ineffective atrial contractions (f = fibrillation waves)
Paroxysmal supraventricular tachycardia (PSVT)	Heart rate of 180-200 beats/min or higher
Premature ventricular contractions (PVCs)	Contractions generated by impulses arising from ectopic foci within ventricular myocardium
Nonsustained ventricular tachycardia (NSVT)	Relatively brief period (20 sec or less) in which ventricles contract rapidly on their own as well as in response to AV impulses
Sustained ventricular tachycardia (SVT)	Same as above but more prolonged
Torsades de pointes (TdP)	Rapid ventricular tachycardia preceded by QT interval prolongation (often progresses to ventricular fibrillation)
Ventricular fibrillation (VF)	Rapid, ineffective ventricular contractions (fatal if not reversed)

ECG, Electrocardiogram.

Among the supraventricular dysrhythmias, atrial fibrillation is a very common condition. It is characterized by rapid atrial contractions that incompletely pump blood into the ventricles. Atrial fibrillation is notable in that it predisposes the patient to stroke. This is due to the fact that the blood tends to stagnate in the incompletely emptied atria and is therefore more likely to clot. If such blood clots manage to make their way into the left ventricle, they may be embolized to the brain and cause a stroke. Although there is a theoretically similar risk for pulmonary embolism, this seems to be of less clinical concern with atrial fibrillation than the risk for stroke. Patients with ongoing atrial fibrillation are often given anticoagulant therapy with warfarin (see Chapter 26) to reduce the likelihood of stroke.

AV nodal reentrant tachycardia (AVNRT) is a conduction disorder that often gives rise to a dysrhythmia known as paroxysmal supraventricular tachycardia (PSVT). (The word paroxysmal means “sudden.”) AVNRT occurs when electrical impulse transmission from the AV node into the His-Purkinje system of the ventricles is disrupted. As a result, some of the impulses circle backward (retrograde impulses) and reenter the atrial tissues to produce a tachycardic response. In Wolff-Parkinson-White syndrome, ectopic impulses that begin near the AV node actually bypass the AV node and reach the His-Purkinje system before the normal AV-generated impulses. This is one cause of ventricular tachycardia, although it is technically supraventricular in origin.

Varying degrees of AV block (often called heart block) involve different levels of disrupted conduction of impulses from the AV node and His-Purkinje system to the ventricles. Although first-degree AV block is often asymptomatic, third-degree block, or complete heart block, often requires use of a cardiac pacemaker to ensure adequate ventricular function. There can also be blocks within the His-Purkinje system of the ventricles, known as bundle branch blocks.

Premature ventricular contractions (PVCs) occur when impulses originate from ectopic foci within the ventricles (His-Purkinje system). PVCs probably occur periodically in many people; they become problematic when they occur frequently enough to compromise systolic blood volume. Ventricular tachycardia refers to a rapid heartbeat from impulses originating in the ventricles. It can be nonsustained (brief) or sustained, requiring definitive treatment. Worsening ventricular tachycardia can deteriorate into torsades de pointes, an intermediate dysrhythmia that often deteriorates into ventricular fibrillation. Ventricular fibrillation is fatal if not reversed, which most often requires electrical defibrillation. Interestingly, torsades de pointes often responds preferentially to intravenous magnesium sulfate.

Pharmacology Overview

Antidysrhythmic Drugs

Numerous drugs are available to treat dysrhythmias. These drugs are categorized according to where and how they affect cardiac cells. Although other classifications are described in the literature, the most commonly used system for this purpose is still the Vaughan Williams classification. This system is based on the electrophysiologic effect of particular drugs on the action potential. This approach identifies four major classes of drugs: I (including Ia, Ib, and Ic), II, III, and IV. The various drugs in these four classes are listed in Table 25-3.

TABLE 25-3

VAUGHAN WILLIAMS CLASSIFICATION OF ANTIDYSRHYTHMIC DRUGS

FUNCTIONAL CLASS	DRUGS
Class I: membrane-stabilizing drugs; fast sodium channel blockers
Ia: ↑ blockade of sodium channel, delay repolarization, ↑ action potential duration	Quinidine, disopyramide, procainamide
Ib: ↑ blockade of sodium channel, accelerate repolarization, ± action potential duration	Lidocaine, phenytoin
Ic: ↑↑↑ blockade of sodium channel, ± repolarization; also suppress reentry	Flecainide, propafenone
Class II: beta-blocking drugs	All beta blockers
Class III: drugs whose principal effect on cardiac tissue is to ↑ action potential duration	Amiodarone, dronedarone, sotalol,^∗ ibutilide, dofetilide
Class IV: calcium channel blockers	Verapamil, diltiazem
Other: antidysrhythmic drugs that have the properties of several classes and therefore cannot be placed in one particular class	Digoxin, adenosine

↑, Increase; ±, increase or decrease.

^∗Sotalol also has class II properties.

There is currently a gradual trend away from the use of class Ia drugs. The formerly available class Ic drug encainide was removed from the market after research indicated that the risk of fatal cardiac dysrhythmias associated with this drug overshadowed its dysrhythmia suppression effects. Class III drugs have emerged as among the most widely used antidysrhythmics at this time. The class IV drugs (calcium channel blockers) have limited usefulness in treating tachydysrhythmias (dysrhythmias involving tachycardia), unlike most of the other classes. The role of class II drugs (beta blockers) continues to grow in the field of cardiology, including in dysrhythmia management. Digoxin, the cardiac glycoside discussed in Chapter 24, still has a place in dysrhythmia management, especially in the prevention of dangerous ventricular tachydysrhythmias secondary to atrial fibrillation.

Mechanism of Action and Drug Effects

Antidysrhythmic drugs work by correcting abnormal cardiac electrophysiologic function. They do this to varying degrees and by various mechanisms. Class I drugs are membrane-stabilizing drugs and exert their actions on the sodium (fast) channels. There are some slight differences in the actions of the drugs in this class, so they are divided into three subclasses. These subclasses are class Ia, Ib, and Ic drugs. The subclasses are based on the magnitude of the effects each drug has on phase 0, the action potential duration, and the effective refractory period. Class Ia drugs (quinidine, procainamide, and disopyramide) block the sodium channels; more specifically, they delay repolarization and increase the action potential duration. Class Ib drugs (phenytoin, lidocaine) also block the sodium channels, but unlike class Ia drugs, they accelerate repolarization and decrease the action potential duration. Phenytoin is more commonly used as an anticonvulsant (see Chapter 14) than as an antidysrhythmic drug. Class Ic drugs (flecainide, propafenone) have a more pronounced effect on the blockade of sodium channels but have little effect on repolarization or the action potential duration.

Class II drugs are the beta-adrenergic blockers (beta blockers; see Chapter 19), and they are commonly used as antihypertensives (see Chapter 22) and antianginal drugs (see Chapter 23). They work by blocking sympathetic nervous system stimulation to the heart and, as a result, the transmission of impulses in the heart’s conduction system. This results in depression of phase 4 depolarization. These drugs mostly affect slower-conducting cardiac tissues.

Class III drugs (amiodarone, dronedarone, sotalol, ibutilide, and dofetilide) increase the action potential duration by prolonging repolarization in phase 3. They affect fast tissue and are most commonly used to manage dysrhythmias that are difficult to treat. They are usually reserved for patients for whom other therapies have failed. Sotalol actually has properties of both class II and class III drugs, and it may be listed as a member of either one or the other class, depending on the specific reference used.

Class IV drugs are the calcium channel blockers, which, like beta blockers, are also used as both antihypertensives (see Chapter 22) and antianginal drugs (see Chapter 23). As their name implies, they work specifically by inhibiting the calcium channels, which reduces the influx of calcium ions during action potentials. This results in depression of phase 4 depolarization. Diltiazem and verapamil are the calcium channel blockers most commonly used to treat cardiac dysrhythmias.

The mechanisms of action of the major classes of antidysrhythmics are summarized in Table 25-4. The effects of the various classes of antidysrhythmic drugs are presented in Box 25-1.

TABLE 25-4

ANTIDYSRHYTHMIC DRUGS: MECHANISMS OF ACTION

	VAUGHAN WILLIAMS CLASS
	I	II	III	IV
Action	Blocks sodium channels, affects phase 0	Decreases spontaneous depolarization, affects phase 4	Prolongs action potential duration	Blocks slow calcium channels
Tissue	Fast	Slow	Fast	Slow
Effect on action potential