SA node.

Under normal circumstances, the SA node serves as the pacemaker for the heart. Pacemaker activity results from spontaneous phase 4 depolarization (see below). Because cells of the sinus node usually discharge faster than other cells that display automaticity, the SA node normally dominates all other potential pacemakers.

After the SA node discharges, impulses spread rapidly through the atria along the internodal pathways. This rapid conduction allows the atria to contract in unison.

AV node.

Impulses originating in the atria must travel through the AV node to reach the ventricles. In the healthy heart, impulses arriving at the AV node are delayed before going on to excite the ventricles. This delay provides time for blood to fill the ventricles prior to ventricular contraction.

His-Purkinje system.

The fibers of the His-Purkinje system consist of specialized conducting tissue. The function of these fibers is to conduct electrical excitation very rapidly to all parts of the ventricles. Stimulation of the His-Purkinje system is caused by impulses leaving the AV node. These impulses are conducted rapidly down the bundle of His, enter the right and left bundle branches, and then distribute to the many fine branches of the Purkinje fibers (see Fig. 49–1). Because impulses travel quickly through this system, all regions of the ventricles are stimulated almost simultaneously, producing synchronized ventricular contraction with resultant forceful ejection of blood.

Phase 0.

In phase 0, the cell undergoes rapid depolarization in response to influx of sodium ions. Phase 0 is important in that the speed of phase 0 depolarization determines the velocity of impulse conduction. Drugs that decrease the rate of phase 0 depolarization (by blocking sodium channels) slow impulse conduction through the His-Purkinje system and myocardium.

Phase 1.

During phase 1, rapid (but partial) repolarization takes place. Phase 1 has no relevance to antidysrhythmic drugs.

Phase 2.

Phase 2 consists of a prolonged plateau in which the membrane potential remains relatively stable. During this phase, calcium enters the cell and promotes contraction of atrial and ventricular muscle. Drugs that reduce calcium entry during phase 2 do not influence cardiac rhythm. However, since calcium influx is required for contraction, these drugs can reduce myocardial contractility.

Phase 3.

In phase 3, rapid repolarization takes place. This repolarization is caused by extrusion of potassium from the cell. Phase 3 is relevant in that delay of repolarization prolongs the action potential duration, and thereby prolongs the effective refractory period (ERP). (The ERP is the time during which a cell is unable to respond to excitation and initiate a new action potential. Hence, extending the ERP prolongs the minimum interval between two propagating responses.) Phase 3 repolarization can be delayed by drugs that block potassium channels.

Phase 4.

During phase 4, two types of electrical activity are possible: (1) the membrane potential may remain stable (solid line in Fig. 49–2A), or (2) the membrane may undergo spontaneous depolarization (dashed line). In cells undergoing spontaneous depolarization, the membrane potential gradually rises until a threshold potential is reached. At this point, rapid phase 0 depolarization takes place, setting off a new action potential. Hence, it is phase 4 depolarization that gives cardiac cells automaticity (ie, the ability to initiate an action potential through self-excitation). The capacity for self-excitation makes potential pacemakers of all cells that have it.

Under normal conditions, His-Purkinje cells undergo very slow spontaneous depolarization, and myocardial cells do not undergo any. However, under pathologic conditions, significant phase 4 depolarization may occur in all of these cells, and especially in Purkinje fibers. When this happens, a dysrhythmia can result.

Phase 0.

Phase 0 (depolarization phase) of slow potentials differs significantly from phase 0 of fast potentials. As we can see from Figure 49–2, whereas phase 0 of fast potentials is caused by a rapid influx of sodium, phase 0 of slow potentials is caused by slow influx of calcium. Because calcium influx is slow, the rate of depolarization is slow; and because depolarization is slow, these potentials conduct slowly. This explains why impulse conduction through the AV node is delayed. Phase 0 of the slow potential is of therapeutic significance in that drugs that suppress calcium influx during phase 0 can slow (or stop) AV conduction.

Phases 1, 2, and 3.

Slow potentials lack a phase 1 (see Fig. 49–2B). Phases 2 and 3 of the slow potential are not significant with respect to the actions of antidysrhythmic drugs.

Phase 4.

Cells of the SA node and AV node undergo spontaneous phase 4 depolarization. The ionic basis of this phenomenon is complex and incompletely understood.

Under normal conditions, the rate of phase 4 depolarization in cells of the SA node is faster than in all other cells of the heart. As a result, the SA node discharges first and determines heart rate. Hence, the SA node is referred to as the cardiac pacemaker.

As indicated in Figure 49–2B, two classes of drugs (beta blockers and calcium channel blockers) can suppress phase 4 depolarization. By doing so, these agents can decrease automaticity in the SA node.

Atrioventricular block.

Impaired conduction through the AV node produces varying degrees of AV block. If impulse conduction is delayed (but not prevented entirely), the block is termed first degree. If some impulses pass through the node but others do not, the block is termed second degree. If all traffic through the AV node stops, the block is termed third degree.

Reentry (recirculating activation).

Reentry, also referred to as recirculating activation, is a generalized mechanism by which dysrhythmias can be produced. Reentry causes dysrhythmias by establishing a localized, self-sustaining circuit capable of repetitive cardiac stimulation. Reentry results from a unique form of conduction disturbance. The mechanism of reentrant activation and the effects of drugs on this process are described below.

The mechanism for establishing a reentrant circuit is depicted in Figure 49–4, panels A and B. In the figure, the inverted Y-shaped structure represents a branched Purkinje fiber terminating on a strip of ventricular muscle, which appears as a horizontal bar. Normal impulse conduction is shown in Figure 49–4A. As indicated by the arrows, impulses travel down both branches of the Purkinje fiber to cause excitation of the muscle at two locations. Impulses created within the muscle travel in both directions (to the right and left) away from their sites of origin. Those impulses that are moving toward each other meet midway between the two branches of the Purkinje fiber. Since in the wake of both impulses the muscle is in a refractory state, neither impulse can proceed further, and hence both impulses stop.

Figure 49–4B depicts a reentrant circuit. The shaded area in branch 1 of the Purkinje fiber represents a region of one-way conduction block. This region prevents conduction of impulses downward (toward the muscle) but does not prevent impulses from traveling upward. (Impulses can travel back up the block because impulses in muscle are very strong, and hence are able to pass the block, whereas impulses in the Purkinje fiber are weaker, and hence are unable to pass.) A region of one-way block is essential for reentrant activation.

How does one-way block lead to reentrant activation? As an impulse travels down the Purkinje fiber, it is stopped in branch 1 but continues unimpeded in branch 2. Upon reaching the tip of branch 2, the impulse stimulates the muscle. As described above, the impulse in the muscle travels to the right and to the left away from its site of origin. However, in this new situation, as the impulse travels toward the impaired branch of the Purkinje fiber, it meets no impulse coming from the other direction, and hence continues on, resulting in stimulation of the terminal end of branch 1. This stimulation causes an impulse to travel backward up the Purkinje fiber. Since blockade of conduction is unidirectional, the impulse passes through the region of block and then back down into branch 2, causing reentrant activation of this branch. Under proper conditions, the impulse will continue to cycle indefinitely, resulting in repetitive ectopic beats.

There are two mechanisms by which drugs can abolish a reentrant dysrhythmia. First, drugs can improve conduction in the sick branch of the Purkinje fiber, and can thereby eliminate the one-way block (Fig. 49–4C). Alternatively, drugs can suppress conduction in the sick branch, thereby converting one-way block into two-way block (Fig. 49–4D).

Atrial fibrillation.

Atrial fibrillation is the most common sustained dysrhythmia, affecting about 2.2 million people in the United States. The disorder is caused by multiple atrial ectopic foci firing randomly; each focus stimulates a small area of atrial muscle. This chaotic excitation produces a highly irregular atrial rhythm. Depending upon the extent of impulse transmission through the AV node, ventricular rate may be very rapid or nearly normal.

In addition to compromising cardiac performance, atrial fibrillation carries a high risk of stroke. Why? Because in patients with atrial fibrillation, some blood can become trapped in the atria (rather than flowing straight through to the ventricles), thereby permitting formation of a clot. When normal sinus rhythm is restored, the clot may become dislodged, and then may travel to the brain to cause stroke.

Treatment of atrial fibrillation has two goals: improvement of ventricular pumping and prevention of stroke. Pumping can be improved by either (1) restoring normal sinus rhythm or (2) slowing ventricular rate. The preferred method is to slow ventricular rate. How? By long-term therapy with a beta blocker (atenolol or metoprolol) or a cardioselective calcium channel blocker (diltiazem or verapamil), both of which impede conduction through the AV node. If episodes of atrial fibrillation are infrequent (eg, less than 12 a year), they can be managed with PRN flecainide or propafenone. This so-called pill-in-the-pocket approach is analogous to treating infrequent attacks of angina with sublingual nitroglycerin. For patients who elect to restore normal rhythm, options are DC cardioversion, short-term treatment with drugs (eg, amiodarone, sotalol), or RF ablation of the dysrhythmia source.

To prevent stroke, most patients are treated with warfarin. For those undergoing treatment to restore normal sinus rhythm, warfarin should be taken for 3 to 4 weeks prior to the procedure and for several weeks after. For those taking an antidysrhythmic drug long term to control ventricular rate, warfarin must be taken long term too. Alternatives to warfarin include two new oral anticoagulants—dabigatran [Pradaxa] and rivaroxaban [Xarelto]—and antiplatelet drugs (either aspirin alone or aspirin plus clopidogrel).

Atrial flutter.

Atrial flutter is caused by an ectopic atrial focus discharging at a rate of 250 to 350 times a minute. Ventricular rate is considerably slower, however, because the AV node is unable to transmit impulses at this high rate. Typically, one atrial impulse out of two reaches the ventricles. The treatment of choice is DC cardioversion, which almost always converts atrial flutter to normal sinus rhythm. Cardioversion may also be achieved with IV ibutilide. To prevent the dysrhythmia from recurring, patients may need long-term therapy with drugs—either a class IC agent (flecainide or propafenone) or a class III agent (amiodarone, dronedarone, sotalol, dofetilide).

There are two alternatives to cardioversion: (1) RF ablation of the dysrhythmia focus and (2) control of ventricular rate with drugs. As with atrial fibrillation, ventricular rate is controlled with drugs that suppress AV conduction: verapamil, diltiazem, or a beta blocker.

Like atrial fibrillation, atrial flutter poses a risk of stroke, which can be reduced by treatment with warfarin.

Sustained supraventricular tachycardia (SVT).

Sustained SVT is usually caused by an AV nodal reentrant circuit. Heart rate is increased to 150 to 250 beats/min. SVT often responds to interventions that increase vagal tone, such as carotid sinus massage or the Valsalva maneuver. If these are ineffective, an IV beta blocker or calcium channel blocker can be tried. With these drugs, ventricular rate will be slowed even if the dysrhythmia persists. Once the dysrhythmia has been controlled, beta blockers and/or calcium channel blockers can be taken orally to prevent recurrence. As a last resort, amiodarone can be used for prevention.

Sustained ventricular tachycardia.

Ventricular tachycardia arises from a single, rapidly firing ventricular ectopic focus, typically located at the border of an old infarction. The focus drives the ventricles at a rate of 150 to 250 beats/min. Since the ventricles cannot pump effectively at these rates, immediate intervention is required. Cardioversion is the treatment of choice. If cardioversion fails to normalize rhythm, IV amiodarone should be administered; lidocaine and procainamide are alternatives. For long-term management, drugs (eg, sotalol, amiodarone) or an implantable cardioverter-defibrillator (ICD) may be employed.

Ventricular fibrillation.

Ventricular fibrillation is a life-threatening emergency that requires immediate treatment. This dysrhythmia results from the asynchronous discharge of multiple ventricular ectopic foci. Because many different foci are firing, and because each focus initiates contraction in its immediate vicinity, localized twitching takes place all over the ventricles, making coordinated ventricular contraction impossible. As a result, the pumping action of the heart stops. In the absence of blood flow, the patient becomes unconscious and cyanotic. If heartbeat is not restored rapidly, death soon follows. Electrical countershock (defibrillation) is applied to eliminate fibrillation and restore cardiac function. If necessary, IV lidocaine can be used to enhance the effects of defibrillation. Procainamide may also be helpful. Amiodarone can be used for long-term suppression. As an alternative, an ICD may be employed.

Ventricular premature beats (vpbs).

VPBs are beats that occur before they should in the cardiac cycle. These beats are caused by ectopic ventricular foci. VPBs may arise from a single ectopic focus or from several foci. In the absence of additional signs of heart disease, VPBs are benign and not usually treated. However, in the presence of acute myocardial infarction, VPBs may predispose the patient to ventricular fibrillation. In this case, therapy is required. A beta blocker is the agent of choice. Because VPBs are associated with a premature QRS complex on the ECG, this dysrhythmia is also known as premature ventricular complexes.

Digoxin-induced ventricular dysrhythmias.

Digoxin toxicity can mimic practically all types of dysrhythmias. Varying degrees of AV block are among the most common. Ventricular flutter and ventricular fibrillation are the most dangerous. Digoxin causes dysrhythmias by increasing automaticity in the atria, ventricles, and His-Purkinje system, and by decreasing conduction through the AV node.

With proper treatment, digoxin-induced dysrhythmias can almost always be controlled. Treatment is discussed at length in Chapter 48. If antidysrhythmic drugs are required, lidocaine and phenytoin are the agents of choice. In patients with digoxin toxicity, DC cardioversion may bring on ventricular fibrillation. Accordingly, this procedure should be used only when absolutely required.

Torsades de pointes.

Torsades de pointes is an atypical, rapid, undulating ventricular tachydysrhythmia that can evolve into potentially fatal ventricular fibrillation. The main factor associated with development of torsades de pointes is prolongation of the QT interval, which can be caused by a variety of drugs (see Table 7–2 in Chapter 7), including class IA and class III antidysrhythmic agents. Acute management consists of IV magnesium plus cardioversion for sustained ventricular tachycardia.

Sustained versus nonsustained dysrhythmias.

As a rule, nonsustained dysrhythmias require intervention only when they are symptomatic; in the absence of symptoms, treatment is usually unnecessary. In contrast, sustained dysrhythmias can be dangerous; hence, the benefits of treatment generally outweigh the risks.

Asymptomatic versus symptomatic dysrhythmias.

No study has demonstrated a benefit to treating dysrhythmias that are asymptomatic or minimally symptomatic. In contrast, therapy may be beneficial for dysrhythmias that produce symptoms (palpitations, angina, dyspnea, faintness).

Supraventricular versus ventricular dysrhythmias.

Supraventricular dysrhythmias are generally benign. The primary harm comes from driving the ventricles too rapidly to allow adequate filling. The goal of treatment is to either (1) terminate the dysrhythmia or (2) prevent excessive atrial beats from reaching the ventricles (using a beta blocker, calcium channel blocker, or digoxin). In contrast to supraventricular dysrhythmias, ventricular dysrhythmias frequently interfere with pumping. Accordingly, the goal of treatment is to terminate the dysrhythmia and prevent its recurrence.