++
In the normal human heart, each beat originates in the SA node (normal sinus rhythm, NSR). The heart beats about 70 times a minute at rest. The rate is slowed (bradycardia) during sleep and accelerated (tachycardia) by emotion, exercise, fever, and many other stimuli. In healthy young individuals breathing at a normal rate, the heart rate varies with the phases of respiration: It accelerates during inspiration and decelerates during expiration, especially if the depth of breathing is increased. This sinus arrhythmia (Figure 29–10) is a normal phenomenon and is primarily due to fluctuations in parasympathetic output to the heart. During inspiration, impulses in the vagi from the stretch receptors in the lungs inhibit the cardio-inhibitory area in the medulla oblongata. The tonic vagal discharge that keeps the heart rate slow decreases, and the heart rate rises. Disease processes affecting the sinus node lead to marked bradycardia accompanied by dizziness and syncope (Clinical Box 29–2).
++
++
The AV node and other portions of the conduction system can, in abnormal situations, become the cardiac pacemaker. In addition, diseased atrial and ventricular muscle fibers can have their membrane potentials reduced and discharge repetitively.
++
As noted above, the discharge rate of the SA node is more rapid than that of the other parts of the conduction system, and this is why the SA node normally controls the heart rate. When conduction from the atria to the ventricles is completely interrupted, complete (third-degree) heart block results, and the ventricles beat at a low rate (idioventricular rhythm) independently of the atria (Figure 29–11). The block may be due to disease in the AV node (AV nodal block) or in the conducting system below the node (infranodal block). In patients with AV nodal block, the remaining nodal tissue becomes the pacemaker and the rate of the idioventricular rhythm is approximately 45 beats/min. In patients with infranodal block due to disease in the bundle of His, the ventricular pacemaker is located more peripherally in the conduction system and the ventricular rate is lower; it averages 35 beats/min, but in individual cases it can be as low as 15 beats/min. In such individuals, there may also be periods of asystole lasting a minute or more. The resultant cerebral ischemia causes dizziness and fainting (Stokes–Adams syndrome). Causes of third-degree heart block include septal myocardial infarction and damage to the bundle of His during surgical correction of congenital interventricular septal defects.
++
++
CLINICAL BOX 29–2 Sick Sinus Syndrome
Sick sinus syndrome (bradycardia-tachycardia syndrome; sinus node dysfunction) is a collection of heart rhythm disorders that include sinus bradycardia (slow heart rates from the natural pacemaker of the heart), tachycardias (fast heart rates), and bradycardia-tachycardia (alternating slow and fast heart rhythms). Sick sinus syndrome is relatively uncommon and is usually found in people older than 50, in whom the cause is often a nonspecific, scar-like degeneration of the heart’s conduction system. When found in younger people, especially in children, a common cause of sick sinus syndrome is heart surgery, especially on the upper chambers. Holter monitoring is an effective tool for diagnosing sick sinus syndrome because of the episodic nature of the disorder. Extremely slow heart rate and prolonged pauses may be seen during Holter monitoring, along with episodes of atrial tachycardias.
THERAPEUTIC HIGHLIGHTS Treatment depends on the severity and type of disease. Tachycardias are frequently treated with medication. When there is marked bradycardia in patients with sick sinus syndrome or third-degree heart block, an electronic pacemaker is frequently implanted. These devices, which have become sophisticated and reliable, are useful in patients with sinus node dysfunction, AV block, and bifascicular or trifascicular block. They are useful also in patients with severe neurogenic syncope, in whom carotid sinus stimulation produces pauses of more than 3 s between heartbeats.
++
When conduction between the atria and ventricles is slowed but not completely interrupted, incomplete heart block is present. In the form called first-degree heart block, all the atrial impulses reach the ventricles but the PR interval is abnormally long. In the form called second-degree heart block, not all atrial impulses are conducted to the ventricles. For example, a ventricular beat may follow every second or every third atrial beat (2:1 block, 3:1 block, etc). In another form of incomplete heart block, there are repeated sequences of beats in which the PR interval lengthens progressively until a ventricular beat is dropped (Wenckebach phenomenon). The PR interval of the cardiac cycle that follows each dropped beat is usually normal or only slightly prolonged (Figure 29–11).
++
Sometimes one branch of the bundle of His is interrupted, causing right or left bundle branch block. In bundle branch block, excitation passes normally down the bundle on the intact side and then sweeps back through the muscle to activate the ventricle on the blocked side. The ventricular rate is therefore normal, but the QRS complexes are prolonged and deformed (Figure 29–11). Block can also occur in the anterior or posterior fascicle of the left bundle branch, producing the condition called hemiblock or fascicular block. Left anterior hemiblock produces abnormal left axis deviation in the ECG, whereas left posterior hemiblock produces abnormal right axis deviation. It is not uncommon to find combinations of fascicular and branch blocks (bifascicular or trifascicular block). The HBE permits detailed analysis of the site of block when there is a defect in the conduction system.
+++
ECTOPIC FOCI OF EXCITATION
++
Normally, myocardial cells do not discharge spontaneously, and the possibility of spontaneous discharge of the His bundle and Purkinje system is low because the normal pacemaker discharge of the SA node is more rapid than their rate of spontaneous discharge. However, in abnormal conditions, the His–Purkinje fibers or the myocardial fibers may discharge spontaneously. In these conditions, increased automaticity of the heart is said to be present. If an irritable ectopic focus discharges once, the result is a beat that occurs before the expected next normal beat and transiently interrupts the cardiac rhythm (atrial, nodal, or ventricular extrasystole or premature beat). If the focus discharges repetitively at a rate higher than that of the SA node, it produces rapid, regular tachycardia (atrial, ventricular, or nodal paroxysmal tachycardia or atrial flutter).
++
A more common cause of paroxysmal arrhythmias is a defect in conduction that permits a wave of excitation to propagate continuously within a closed circuit (circus movement). For example, if a transient block is present on one side of a portion of the conducting system, the impulse can go down the other side. If the block then wears off, the impulse may conduct in a retrograde direction in the previously blocked side back to the origin and then descend again, establishing a circus movement. An example of this in a ring of tissue is shown in Figure 29–12. If the reentry is in the AV node, the reentrant activity depolarizes the atrium, and the resulting atrial beat is called an echo beat. In addition, the reentrant activity in the node propagates back down to the ventricle, producing paroxysmal nodal tachycardia. Circus movements can also become established in the atrial or ventricular muscle fibers. In individuals with an abnormal extra bundle of conducting tissue connecting the atria to the ventricles (bundle of Kent), the circus activity can pass in one direction through the AV node and in the other direction through the bundle, thus involving both the atria and the ventricles.
++
++
Excitation spreading from an independently discharging focus in the atria stimulates the AV node prematurely and is conducted to the ventricles. The P waves of atrial extrasystoles are abnormal, but the QRST configurations are usually normal (Figure 29–13). The excitation may depolarize the SA node, which must repolarize and then depolarize to the firing level before it can initiate the next normal beat. Consequently, a pause occurs between the extrasystole and the next normal beat that is usually equal in length to the interval between the normal beats preceding the extrasystole, and the rhythm is “reset” (see below).
++
++
Atrial tachycardia occurs when an atrial focus discharges regularly or there is reentrant activity producing atrial rates up to 220/min. Sometimes, especially in digitalized patients, some degree of atrioventricular block is associated with the tachycardia (paroxysmal atrial tachycardia with block).
++
In atrial flutter, the atrial rate is 200–350/min (Figure 29–13). In the most common form of this arrhythmia, there is large counterclockwise circus movement in the right atrium. This produces a characteristic sawtooth pattern of flutter waves due to atrial contractions. It is almost always associated with 2:1 or greater AV block, because in adults the AV node cannot conduct more than about 230 impulses per minute.
++
In atrial fibrillation, the atria beat very rapidly (300–500/min) in a completely irregular and disorganized fashion. Because the AV node discharges at irregular intervals, the ventricles also beat at a completely irregular rate, usually 80–160/min (Figure 29–13). The condition can be paroxysmal or chronic, and in some cases there appears to be a genetic predisposition. The cause of atrial fibrillation is still a matter of debate, but in most cases it appears to be due to multiple concurrently circulating reentrant excitation waves in both atria. However, some cases of paroxysmal atrial fibrillation seem to be produced by discharge of one or more ectopic foci. Many of these foci appear to be located in the pulmonary veins as much as 4 cm from the heart. Atrial muscle fibers extend along the pulmonary veins and are the origin of these discharges.
+++
CONSEQUENCES OF ATRIAL ARRHYTHMIAS
++
Occasional atrial extrasystoles occur from time to time in most normal humans and have no pathologic significance. In paroxysmal atrial tachycardia and flutter, the ventricular rate may be so high that diastole is too short for adequate filling of the ventricles with blood between contractions. Consequently, cardiac output is reduced and symptoms of heart failure appear. Heart failure may also complicate atrial fibrillation when the ventricular rate is high. Acetylcholine liberated at vagal endings depresses conduction in the atrial musculature and AV node. This is why stimulating reflex vagal discharge by pressing on the eyeball (oculocardiac reflex) or massaging the carotid sinus often converts tachycardia and sometimes converts atrial flutter to normal sinus rhythm. Alternatively, vagal stimulation increases the degree of AV block, abruptly lowering the ventricular rate. Digitalis also depresses AV conduction and is used to lower a rapid ventricular rate in atrial fibrillation.
+++
VENTRICULAR ARRHYTHMIAS
++
Premature beats that originate in an ectopic ventricular focus usually have bizarrely shaped prolonged QRS complexes (Figure 29–14) because of the slow spread of the impulse from the focus through the ventricular muscle to the rest of the ventricle. They are usually incapable of exciting the bundle of His, and retrograde conduction to the atria therefore does not occur. In the meantime, the next succeeding normal SA nodal impulse depolarizes the atria. The P wave is usually buried in the QRS of the extrasystole. If the normal impulse reaches the ventricles, they are still in the refractory period following depolarization from the ectopic focus.
++
++
However, the second succeeding impulse from the SA node produces a normal beat. Thus, ventricular premature beats are followed by a compensatory pause that is often longer than the pause after an atrial extrasystole. Furthermore, ventricular premature beats do not interrupt the regular discharge of the SA node, whereas atrial premature beats often interrupt and “reset” the normal rhythm.
++
Atrial and ventricular premature beats are not strong enough to produce a pulse at the wrist if they occur early in diastole, when the ventricles have not had time to fill with blood and the ventricular musculature is still in its relatively refractory period. They may not even open the aortic and pulmonary valves, in which case there is, in addition, no second heart sound.
++
Paroxysmal ventricular tachycardia (Figure 29–14) is in effect a series of rapid, regular ventricular depolarizations usually due to a circus movement involving the ventricles. Torsades de pointes is a form of ventricular tachycardia in which the QRS morphology varies (Figure 29–15). Tachycardias originating above the ventricles (supraventricular tachycardias such as paroxysmal nodal tachycardia) can be distinguished from paroxysmal ventricular tachycardia by use of the HBE; in supraventricular tachycardias, a His bundle H deflection is present, whereas in ventricular tachycardias, there is none. Ventricular premature beats are not uncommon and, in the absence of ischemic heart disease, usually benign. Ventricular tachycardia is more serious because cardiac output is decreased, and ventricular fibrillation is an occasional complication of ventricular tachycardia.
++
++
In ventricular fibrillation (Figure 29–15), the ventricular muscle fibers contract in a totally irregular and ineffective way because of the very rapid discharge of multiple ventricular ectopic foci or a circus movement. The fibrillating ventricles, like the fibrillating atria, look like a quivering “bag of worms.” Ventricular fibrillation can be produced by an electric shock or an extrasystole during a critical interval, the vulnerable period. The vulnerable period coincides in time with the midportion of the T wave; that is, it occurs at a time when some of the ventricular myocardium is depolarized, some is incompletely repolarized, and some is completely repolarized. These are excellent conditions in which to establish reentry and a circus movement. The fibrillating ventricles cannot pump blood effectively, and circulation of the blood stops. Therefore, in the absence of emergency treatment, ventricular fibrillation that lasts more than a few minutes is fatal. The most frequent cause of sudden death in patients with myocardial infarcts is ventricular fibrillation.
++
An indication of vulnerability of the heart during repolarization is the fact that in patients in whom the QT interval is prolonged, cardiac repolarization is irregular and the incidence of ventricular arrhythmias and sudden death increases. The syndrome can be caused by a number of different drugs, by electrolyte abnormalities, and by myocardial ischemia. It can also be congenital. Mutations of eight different genes have been reported to cause the syndrome. Six cause reduced function of various K+ channels by alterations in their structure; one inhibits a K+ channel by reducing the amount of the ankyrin isoform that links it to the cytoskeleton; and one increases the function of the cardiac Na+ channel. Long QT syndrome is discussed in Clinical Box 5–5.
+++
ACCELERATED AV CONDUCTION
++
An interesting condition seen in some otherwise normal individuals who are prone to attacks of paroxysmal atrial arrhythmias is accelerated AV conduction (Wolff-Parkinson-White syndrome). Normally, the only conducting pathway between the atria and the ventricles is the AV node. Individuals with Wolff-Parkinson-White syndrome have an additional aberrant muscular or nodal tissue connection (bundle of Kent) between the atria and ventricles. This conducts more rapidly than the slowly conducting AV node, and one ventricle is excited early. The manifestations of its activation merge with the normal QRS pattern, producing a short PR interval and a prolonged QRS deflection slurred on the upstroke (Figure 29–16), with a normal interval between the start of the P wave and the end of the QRS complex (“PJ interval”). The paroxysmal atrial tachycardias seen in this syndrome often follow an atrial premature beat. This beat conducts normally down the AV node but spreads to the ventricular end of the aberrant bundle, and the impulse is transmitted retrograde to the atrium. A circus movement is thus established. Less commonly, an atrial premature beat finds the AV node refractory but reaches the ventricles via the bundle of Kent, setting up a circus movement in which the impulse passes from the ventricles to the atria via the AV node.
++
++
In some instances, the Wolff-Parkinson-White syndrome is familial. In two such families, there is a mutation in a gene that codes for an AMP-activated protein kinase. Presumably, this kinase is normally involved in suppressing abnormal atrioventricular pathways during fetal development.
++
Attacks of paroxysmal supraventricular tachycardia, usually nodal tachycardia, are seen in individuals with short PR intervals and normal QRS complexes (Lown-Ganong-Levine syndrome). In this condition, depolarization presumably passes from the atria to the ventricles via an aberrant bundle that bypasses the AV node but enters the intraventricular conducting system distal to the node.
+++
TREATMENTS FOR ARRHYTHMIAS
++
Many different drugs used in the treatment of arrhythmias slow conduction in the conduction system and the myocardium. This depresses ectopic activity and reduces the discrepancy between normal and reentrant paths so that reentry does not occur. Drugs that target Na+ channels (eg, quinidine) can slow INa and prolong refractoriness (eg, quinidine, disopyramide), inhibit INa with minimal prolongation of refractoriness (eg, flecainide, propafenone) or shorten refractoriness in depolarized cells (eg, lidocaine, mexiletine). Drugs that target K+ channels can prolong refractoriness (eg, amiodarone, sotalol, dofetilide). Drugs that block L-type Ca2+ channels can slow SA pacemaker and AV conduction (eg, nifedipine, verapamil, diltiazem). Finally, drugs that block β-adrenergic receptors thus reduce the activation of ICaL (eg, propanolol, metoprolol). Interestingly, it has become clear that in some patients any of these drugs can be proarrhythmic rather than antiarrhythmic—that is, they can also cause various arrhythmias. Therefore, careful monitoring and alternative procedures are extremely important when using antiarrhythmic drugs.
++
An alternative treatment is radiofrequency catheter ablation of reentrant pathways. Catheters with electrodes at the tip can be inserted into the chambers of the heart and its environs and used to map the exact location of an ectopic focus or accessory bundle responsible for the production of reentry and supraventricular tachycardia. The pathway can then be ablated by passing radiofrequency current with the catheter tip placed close to the bundle or focus. In skilled hands, this form of treatment can be very effective and is associated with few complications. It is particularly useful in conditions that cause supraventricular tachycardias, including Wolff-Parkinson-White syndrome and atrial flutter. It has also been used with success to ablate foci in the pulmonary veins causing paroxysmal atrial fibrillation.