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REVIEW ARTICLES

MEDICAL PROGRESS

CARDIAC PACING FRED M. KUSUMOTO, M.D., NORA GOLDSCHLAGER, M.D.

AND

A

PPROXIMATELY 1 million people in the United States have permanent pacemakers, and 426 new pacemakers were implanted per million members of the population in 19931,2 (and Bernstein AD, Parsonnet V: personal communication). Since the late 1950s, when the first asynchronous single-chamber permanent pacemakers were placed in patients,3-5 cardiac pacing has become a complex and self-contained subspecialty within cardiology that requires special training.6 However, primary care providers commonly encounter patients in whom permanent pacemakers have been implanted and evaluate patients to determine the need for permanent pacing. For this reason, it is essential that all physicians understand how pacemakers function, particularly the complex, multiprogrammable dual-chamber, rate-adaptive pacemakers that are now commonly implanted; a recent survey of medical practice in the United States found that, currently, 60 percent of pacemakers are dual-chamber, 70 percent are rate-adaptive, and 30 percent have both capabilities1 (and Bernstein AD, Parsonnet V: personal communication). Which pacemaker is most appropriate for a patient depends on many interrelated factors; the primary care provider must understand the options available and participate in the selection of the pulse generator. During the 1980s, research in this field focused on creating pacemakers that simulate normal sinus-node automaticity and atrioventricular conduction. The indications for the implantation of permanent pacemakers have also evolved. In this article, we review the currently accepted indications for permanent pacing and provide an overview of recent technological advances. For additional information, readers are referred to several recently published monographs.7-9 INDICATIONS The decision to implant a permanent pacemaker is an important one that involves the pacemaker specialist, the primary physician, and the patient. It is critical From the Electrophysiology and Pacing Service, Division of Cardiology, Department of Medicine, Lovelace Medical Center, Albuquerque, N.M. (F.M.K.); and the Division of Cardiology, Department of Medicine, University of California, San Francisco, and San Francisco General Hospital (N.G.), both in San Francisco. Address reprint requests to Dr. Kusumoto at the Electrophysiology and Pacing Service, Cardiology Division, Lovelace Medical Center, 5400 Gibson Blvd. SE, Albuquerque, NM 87108. 1996, Massachusetts Medical Society.

that the need for pacing be clearly documented. To evaluate patients more uniformly, the Joint American College of Cardiology–American Heart Association Task Force established a classification system for the indications for pacemaker implantation.10 Class I includes all conditions for which it is generally agreed that a permanent pacemaker should be implanted; class II, all conditions for which such pacemakers are frequently used but for which there is disagreement about the need for their use; and class III, all conditions for which it is generally agreed that permanent pacing is not required. Additional factors that must be taken into account include the patient’s overall health and condition; the patient’s desires with respect to operating a motor vehicle, pursuing a particular occupation, or following a particular lifestyle; and the various types of concern expressed by family members. The indications for pacing and the types of permanent pacemaker recommended in several commonly encountered clinical situations are shown in Table 1. Sinus-Node Dysfunction

Sinus-node dysfunction (also known as the “sick-sinus syndrome”) encompasses a broad spectrum of disorders of sinus rhythm, including sinus bradycardia, sinus arrest, sinoatrial block, and paroxysmal tachycardias (the bradycardia–tachycardia syndrome). Among patients in the United States in whom permanent pacemakers are implanted, sinus-node dysfunction is probably the primary indication for implantation in over 50 percent.1 Before a pacemaker is implanted, attempts should be made to correlate the patient’s symptoms with the findings of ambulatory monitoring or patient-activated event recorders. It must be emphasized, however, that a precise correlation between symptoms of cerebral hypoperfusion and bradycardia may not be found. Such lack of correlation may be due to the cerebral hypoperfusion itself, which may cause the event to go unrecognized at the time of its occurrence; misinterpretation of symptoms; lack of activity on the patient’s part; or the fact that the patient was supine at the time of bradycardia, so that symptoms were minimal or not even present.11 Documented symptomatic bradycardia due to sinusnode dysfunction is considered a class I indication for pacing, whereas documented bradycardia in a symptomatic patient in whom no precise correlation is found between symptoms and sinus rhythm is considered a class II indication. Atrioventricular Block

Atrioventricular block can be classified as first-degree, second-degree, or third-degree (i.e., complete) heart block. Generally, first-degree atrioventricular block is not considered an indication for pacing, but some patients with severe first-degree block can become symptomatic because of the nonphysiologic timing of the atrial

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Table 1. Indications for Permanent Pacemakers and Recommended Pacing Modes.* DISORDER

Sinus-node dysfunction

CLASS

OF I NDICATION †

RECOMMENDED PACING MODE‡

I: Sinus-node dysfunction with documented symptomatic bradycardia; possibly a consequence of necessary longterm drug therapy II: Sinus-node dysfunction with heart rates 40 bpm; no clear association between symptoms and bradycardia III: No symptoms

AV block

I: Symptomatic complete or second-degree AV block, asymptomatic complete heart block with heart rates 40 bpm, or consequence of His-bundle ablation

AAI if no evidence of AV-node or other conduction-tissue disease; DDD if concomitant AV-node disease present; DDDR if chronotropic response absent; DDIR if episodes of supraventricular tachycardia present

DDD if chronotropic competence of the sinus node preserved; VVI if no organized atrial activity; DDDR or VVIR if chronotropic response absent

II: Asymptomatic second-degree type II or complete heart block with heart rates 40 bpm III: First-degree AV block or asymptomatic second-degree type I AV block Bifascicular or trifascicular block

I: Fascicular block with intermittent complete heart block associated with symptoms or second-degree type II block with or without symptoms II: HV intervals 100 msec or fascicular block associated with syncope that cannot be ascribed to other causes III: Asymptomatic fascicular block or fascicular block with associated first-degree AV-node block

Neurogenic syncope

Cardiomyopathy

I: Recurrent syncope provoked by carotid-sinus stimulation; pauses of 3 seconds induced by minimal carotid-sinus pressure II: Syncope associated with bradycardia reproduced by head-up tilting III: Recurrent syncope in the absence of a cardioinhibitory response I: None

DDD if chronotropic competence of the sinus node preserved; VVI if no organized atrial activity; DDDR or VVIR if chronotropic response absent

DDD or DDI

DDD if condition refractory to medicines and chronotropic competence of the sinus node preserved; DDDR if chronotropic response absent

II: Severely symptomatic patients with hypertrophic obstructive cardiomyopathy refractory to drug therapy (may become class I in the future) III: Severely symptomatic patients with dilated cardiomyopathy (may become class II in the future) *AV denotes atrioventricular, and HV interval the conduction interval between the His bundle and the ventricular myocardium. †According to the classification system established by the Joint American College of Cardiology–American Heart Association Task Force.10 ‡Pacing modes are described in Table 3.

and the ventricular responses; and the condition of such patients may be improved if a paced ventricular response is allowed to follow the atrial rhythm at normal, rather than long, intervals. Second-degree atrioventricular block is subclassified as type I (in which there is progressive prolongation of the PR interval before a blocked beat), type II (in which there is no such progressive prolongation), or advanced (in which two or more consecutive P waves are blocked). Second-degree type I atrioventricular block usually occurs in the atrioventricular node, whereas type II and the advanced type usually occur in tissues below the node. When every other beat is conducted (in what is known as 2:1 block), the distinction between types I and II often cannot be made with certainty, and the site of the block may be either at or below the atrioventricular node. Any form of second-degree atrioventricular block that is correlated with symptoms is a class I indication for pacing. Asymptomatic second-degree type II and advanced atrioventricular blocks are class II indications for pacing. An asymptomatic patient with a second-degree type I atrioventricular block should not

receive a permanent pacemaker. Asymptomatic patients who have second-degree atrioventricular block with 2:1 conduction and evidence of infranodal block (based on the results of electrophysiologic study or the presence of a bundle-branch block) are considered to have a class II indication for pacing. Third-degree atrioventricular block is a class I indication for pacing if symptoms are present, if pauses in the QRS rhythm exceed three seconds in length, or if there are escape rates (those of the atrioventricular node, the His–Purkinje system, or ventricular tissue) of 40 beats per minute or less. Thirddegree atrioventricular block in asymptomatic patients with escape rates of more than 40 beats per minute constitutes a class II indication for pacing. Two specific situations with respect to atrioventricular block require special mention. First, vagotonic atrioventricular block results from vagal input to the atrioventricular node and is often accompanied by a slowing of the sinus rate and by changing PR intervals. It commonly occurs at night, when sympathetic tone is low and vagal tone is high; it is an incidental finding in the majority of patients, who are asymptomatic. Thus, va-

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Table 2. Common Programmable Features Available in Pacemakers with Pulse Generators. FEATURE

MEASURES

AND

OPTIONS

DESCRIPTION

Pacing mode

AOO, AAI, VOO, VVI, AAIR, and VVIR (single-chamber pacemakers); DOO, DDI, DDD, VDD, DDIR, and DDDR (dual-chamber pacemakers)

Output

Voltage, current, and duration of pulse

Sensitivity

Atrial, ventricular, or both

Rate

Lower rate limit, upper rate limit (some dual-chamber pacemakers only), and sensor-based lower and upper rate limits (rate-adaptive pacemakers)

Refractory period

Single-chamber pacemakers: atrial refractory period (atrial pacemakers) and ventricular refractory period (ventricular pacemakers); dual-chamber pacemakers: atrial refractory periods (atrioventricular interval and the post-ventricular atrial refractory period [PVARP]) and ventricular refractory periods (blanking period and ventricular refractory period)

Rate adaptation

On–off modes, threshold, and slope

gotonic block is not an indication for pacing. Second, radiofrequency-catheter ablation of the His bundle has become an increasingly popular strategy for treating patients with atrial fibrillation and rapid ventricular rates that are not controlled with medication. Because of the resulting atrioventricular block, a permanent pacemaker is usually implanted when His ablation is performed. Fascicular Block

After traveling through the bundle of His, the cardiac electrical impulse travels down the right bundle branch and the posterior and anterior fascicles of the left bundle branch. Blocks in one or two of these fascicles are identified by electrocardiographic criteria. A block in all three fascicles may be suggested by a prolonged PR interval in association with fascicular block patterns. Electrophysiologic studies can identify patients with advanced fascicular disease by documenting a prolonged conduction interval between the His bundle and the ventricular myocardium (the HV interval). Syncope is common in patients with bifascicular or trifascicular block and may be due to transient episodes of complete heart block.12 Symptomatic or asymptomatic bifascicular or trifascicular block with intermittent type II or advanced second-degree atrioventricular block is a class I indication for pacing, as is symptomatic bifascicular block with intermittent complete heart block. Asymptomatic bifascicular block with intermittent complete heart block is considered a class II indi-

Provides a shorthand description of what chamber or chambers a pacemaker paces (first letter) and senses (second letter), what the response to a sensed beat is (third letter), and whether the pacemaker has a rateadaptive sensor that is activated (fourth letter). Indicates the amount of energy generated by the pacemaker when it delivers a stimulus. Total energy delivered is defined by the equation E  I  V  (PW), where V is the voltage, I the current, and PW the pulse width or duration of the stimulus. V and I are related by Ohm’s law (IR  V), where R is resistance. Indicates the amplitude of the intracardiac signal that will be sensed as intrinsic atrial or ventricular activity. Specifies programmable measures of the minimal intrinsic heart rate tolerated before pacing begins (lower rate limit); for dual-chamber pacemakers that are programmed to sense intrinsic atrial activity, the maximal rate at which the pacemaker tracks atrial activity in a 1: 1 relation (upper rate limit). Refers to periods during which the pulse generator will not respond to electrical signals. In dual-chamber pacemakers, the atrial refractory period comprises the programmable atrioventricular interval and the PVARP, and the ventricular channel does not respond during the blanking period, a short period just after the delivery of the atrial stimulus, and during a longer ventricular refractory period that begins after a sensed or paced ventricular beat. Rate-adaptation features can be turned on or off. Threshold is the level of activity required to engage the sensor, and slope is the rate of change in the pacing rate caused by activity.

cation, since patients with such a block are asymptomatic at what is probably their slowest heart rate. Some data suggest that 25 percent of patients with bifascicular block and HV intervals greater than 100 msec will have complete heart block within three years and should be considered for pacing.13 Neurocardiogenic Syncope

Disorders of autonomic nervous control of blood pressure and heart rate can cause syncope. These disorders have been classified as either the carotid sinus syndrome or vasovagal syncope. Exaggerated responses to pressure in the carotid sinus can cause periods of asystole (cardioinhibition) and pronounced hypotension (vasodepression). Although cardiac pacing treats only the cardioinhibitory aspect of this syndrome, dualchamber pacing with either a DDI or DDD pacing mode has been found to reduce the incidence of frank syncope.14,15 (Pacing modes are described below.) The pathophysiologic features of vasovagal syncope are not entirely understood; this type of syncope is thought to result in part from the activation of myocardial mechanoreceptors, leading to inhibited efferent sympathetic tone and increased efferent parasympathetic tone, which in turn result in peripheral vasodilatation and inappropriate bradycardia. Cardiac pacing may be beneficial in patients with marked bradycardia or ventricular asystole. More commonly, however, a vasodepressor response precedes bradycardia, or bradycardia and hypotension occur simultaneously.16 In this circumstance, the benefits of pacing are controversial: some investiga-

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Table 3. Explanation of the Three- and Four-Letter Designations for Commonly Used Pacing Modes.*

(INDICATES THE CHAMBER SENSED)

3RD LETTER (INDICATES THE MODE OF RESPONSE TO S ENSED B EAT )

4TH LETTER (INDICATES PROGRAMMABLE FEATURES PRESENT)

A A

A A

I I

— R

V

V

I

—

V

V

I

R

V

D

D

—

D

D

I

—

D

D

I

R

D

D

D

—

D

D

D

R

1ST LETTER

2ND LETTER

(INDICATES THE CHAMBER PACED)

DESCRIPTION

Atrial pacing on demand; output inhibited by sensed atrial signals. Atrial pacing on demand; output inhibited by sensed atrial signals. Atrial pacing rates can decrease and increase in response to sensor input, up to the programmed sensor-based upper limit of the rate. Ventricular pacing on demand; output inhibited by sensed ventricular signals. Ventricular pacing on demand; output inhibited by sensed ventricular signals. Ventricular pacing rates can decrease and increase in response to sensor input, up to the programmed sensorbased upper limit of the rate. Paces the ventricle; senses in both the atrium and the ventricle; synchronizes with atrial activity and paces the ventricle after a preset atrioventricular interval up to the programmed upper limit of the rate. Paces and senses in both the atrium and the ventricle; the only response to a sensed P or R wave is inhibition. No tracking of intrinsic atrial activity. Paces and senses in both the atrium and the ventricle; the only response to a sensed P or R wave is inhibition. Atrial and ventricular pacing rates increase and decrease independently in response to sensor input. Atrioventricular synchrony may not be achieved. Paces and senses in both the atrium and the ventricle; paces the ventricle in response to sensed atrial activity up to the programmed upper limit of the rate. Atrial and ventricular pacing rates can increase and decrease in response to sensor input up to the programmed sensor-based upper limit of the rate.

*In the designations, A denotes atrial, I inhibited, R rate-adaptive, V ventricular, and D dual.

tors report a symptomatic benefit, whereas others report no response.17,18 Carotid-sinus hypersensitivity associated with pauses of more than three seconds in sinus rhythm in symptomatic patients is a class I indication for pacing. For syncope due to a vasovagal syndrome refractory to drug therapy, a positive tilt-table test with the patient tilted at 60 degrees for 30 to 45 minutes, manifested by symptomatic bradycardia, is considered a class II indication for pacing.10,17,18 Cardiomyopathy

Pacemakers may be useful in the care of patients with hypertrophic or dilated cardiomyopathy. In those with hypertrophic cardiomyopathy refractory to medical therapy, early results suggest that both symptoms and hemodynamic function can be improved if dualchamber pacing with a short atrioventricular interval is used.19,20 A reduced gradient across the left ventricular outflow tract, caused by creating a functional left bundle-branch block and paradoxical motion of the interventricular septum (as a result of pacing from the right ventricular apex), appears to be primarily responsible for the salutary effects.19 In patients with dilated cardiomyopathy that does not respond to medical therapy, preliminary studies suggest that dual-chamber pacing with a short atrioventricular interval may improve the hemodynamic state and reduce symptoms.21 Increased left ventricular filling, reduced mitral regurgitation, and decreased ventricular-wall stress are thought to account for the

clinical improvement.22 Recent data confirm that hemodynamic benefit occurs primarily in patients with prolonged PR intervals, indicating the importance of an optimal PR relation.23 Cardiac pacing should be considered in patients with hypertrophic cardiomyopathy and symptoms refractory to drug therapy, but it should be viewed as investigational in patients with dilated cardiomyopathy. PROGRAMMABLE PACEMAKERS The modern pacemaker system consists of a lithium– iodine battery that generates an electrical impulse, the pacemaker output. The impulse passes through specialized wires (leads), excites endocardial cells, and produces a propagating wave of depolarization in the myocardium. Electronic circuitry can modulate the frequency and the amount of current flow and in addition sense spontaneous electrical activity in the heart through the leads. The circuitry and battery are enclosed in a hermetically sealed metal container that weighs 20 to 30 g and is 5 to 7 mm thick. During the 1980s, microcomputer-based programmers were developed that, through emitted radiofrequency waves or magnetic fields, could modulate the special circuits of pacemakers and in turn instantaneously adjust almost any functional measure of pacemaker operation. In addition, many programmers can acquire stored information and real-time electrograms from the pacemaker, which can help in assessing function and troubleshooting. The commonly programmable features can be classified into six major groups

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(Table 2). The most important feature with which the primary care physician should be familiar is the pacing mode (Table 3). PACING MODES Pacemakers are classified according to codes containing three to five letters, a system first proposed in 1974 by the Inter-Society Commission for Heart Disease Resources and revised subsequently (Table 3).10,24 The first letter denotes the chamber that is paced: A for atrium, V for ventricle, and D for dual (both chambers). The second letter denotes the chamber or chambers where sensing occurs: A, V, D, or O, for atrium, ventricle, dual, or none, respectively. The third letter indicates the type of response the pacemaker makes to a sensed signal — either inhibited (I), activated (or triggered, T), or dual (D). In most dual-chamber pacing modes, the atrial pacemaker output is inhibited when an atrial signal is sensed, and if no intrinsic ventricular activity is sensed by the end of a programmable atrioventricular interval, a ventricular output is activated; if intrinsic ventricular activity is sensed, however, the ventricular output is inhibited. The fourth letter, originally developed to describe programmable functions, is now used to designate the presence of rate-adaptive abilities, in which the paced rates vary with metabolic need. An R indicates that the pacing system contains a sensor (other than sinus rhythm) that can modulate the interval between the lower and the upper rates. A fifth letter may also be used to indicate the presence of antitachycardia pacing capabilities, although most such capabilities are currently incorporated into automatic implantable defibrillators. Single-chamber pacing modes (AOO, VOO, AAI, AAT, VVI, and VVT) and the older, largely obsolete dual-chamber systems (DVI and VAT) have been reviewed elsewhere and are not discussed here.11 However, we describe newer pacing modes that have come into wide use in the past decade, such as DDD, DDI, and rate-adaptive single- and dual-chamber devices. DDD Pacing

The DDD mode of function is the most versatile pacing mode used today. Atrial events, both sensed and paced, initiate (or trigger) the atrioventricular interval so that atrioventricular synchrony is maintained over a wide range of sinus-rhythm rates (Fig. 1). The DDD mode allows the pacing system to respond to increases in the sinus rate during exercise, but it can also permit unwanted sensing and tracking of atrial arrhythmias. Special algorithms, discussed below, have been developed to minimize the problem of unwanted rapid ventricular rates. Numerous studies have demonstrated better shortterm and long-term hemodynamic improvement with atrioventricular synchronous pacing than with ventricular pacing, especially in patients at rest, but also to a variable extent during exercise.25-29 Atrioventricular synchrony allows efficient filling of the left ventricle, with up to 20 percent augmentation of end-diastolic volume and stroke volume.26 In addition, retrospective-

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ly acquired data suggest that the maintenance of atrioventricular synchrony in patients with the sick-sinus syndrome is associated with improved rates of longterm survival and a reduced incidence of atrial fibrillation and thromboembolic events.30,31 DDD pacing has also reduced the incidence of the pacemaker syndrome, which is the constellation of symptoms associated with ventricular pacing, including syncope or presyncope, weakness, light-headedness, orthopnea, paroxysmal nocturnal dyspnea, dizziness, and frank pulmonary edema.27,30,32,33 The pathophysiologic features of this syndrome are complex, but it arises in part from a reduction in cardiac output and hypotension that in turn result from the loss of atrial contribution to left ventricular filling; a contributing variable is the elevation in atrial pressures that results from the contraction of the atrium against closed mitral and tricuspid valves; this occurs when the ventricle is paced and there is atrioventricular dissociation or the atria are activated retrogradely. In addition, the activation of baroreceptors from inappropriate atrial stretch can lead to reflex peripheral vasodilatation.34 The pacemaker syndrome has been estimated to occur in approximately 7 to 10 percent of patients with sinus rhythm who receive pacing from the ventricle (in the VVI mode), but it may be much higher and has approached 70 percent in some studies.32,35 The symptoms are usually eliminated by any pacing mode that allows the restoration of consistent atrioventricular synchrony.32 Since dual-chamber pacemakers require a greater output of energy than single-chamber units, they have shorter life spans. Although VVI pacemakers can be expected to function for 10 to 15 years, depending on programmed variables and intrinsic rhythm, most dualchamber devices have projected life spans of 7 to 10 years. With new forms of technology, such as steroideluting leads, more efficiently shaped and smaller electrodes, and new electrode-surface treatments, a greater density of current can be achieved at the electrode–tissue interface, producing a propagating wave of myocardial depolarization at much lower levels of output and increasing the longevity of the pacemaker. Despite their somewhat shortened life span, dual-chamber DDD pacemakers provide the important benefits of maintaining atrioventricular synchrony and minimizing the incidence of the pacemaker syndrome. Inhibited Pacing of the Atrium and Ventricle (DDI)

In the DDI pacing mode, there is sensing in both the atrium and the ventricle, but the only response to a sensed event is inhibition (Fig. 1). If the pacemaker senses atrial activity, it does not deliver an atrial stimulus, and the timer of the atrioventricular interval does not start, so that the pacemaker neither delivers ventricular output in response to spontaneous atrial activity nor “tracks” such activity. The atrioventricular-interval timer starts only after a paced atrial event; atrioventricular synchrony is present only while the atrium is being paced or during sinus rhythm, provided that the patient has intact atrioventricular-node conduction. In DDI pacing, the paced rate is never higher than the pro-

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DDD Mode Electrocardiogram

P AVI

PVARP

AVI

PVARP

AVI

PVARP

Atrial sensing channel Blanking period

VRP

VRP

VRP

Ventricular sensing channel Safety-pacing period

R

Alert period

Escape-rate timer E

DDI Mode Electrocardiogram

P AVI

PVARP

PVARP

VRP

VRP

AVI

PVARP

Atrial sensing channel VRP

Ventricular sensing channel R

Escape-rate timer E

E

Figure 1. Comparison of the DDD Mode with the DDI Mode in a Dual-Chamber Pacemaker. The upper panel shows timing cycles and refractory periods for a dual-chamber pacemaker in DDD mode. After an atrial stimulus (the first beat), the AV-interval (AVI) timer starts. The atrial sensing channel is refractory throughout the AVI (hatched areas). In the ventricular sensing channel, the AVI is usually divided into the blanking period, the safety-pacing period, and the alert period. During the blanking period (designed to prevent the ventricular channel from sensing the atrial pacing output), the ventricular channel is refractory. During the safety-pacing period (designed to prevent inappropriate inhibition of ventricular output and resulting ventricular asystole), any activity sensed in the ventricular channel is interpreted as noise and triggers a ventricular output at the end of the period. In this figure, no activity is sensed during the safety-pacing period, so the alert period begins. Any activity sensed during this period inhibits the ventricular output. If the AVI ends and the ventricular channel has sensed no activity, a ventricular output is delivered (the first paced QRS complex). After an event (sensed or paced) in the ventricular channel, the post-ventricular atrial refractory period (PVARP), the ventricular refractory period (VRP), and the escape-rate timer begin. In the second beat, a spontaneous P wave is sensed (arrow P) and the AVI begins again. This AVI ends without any activity sensed in the ventricular channel, so a ventricular output is delivered, starting the PVARP, the VRP, and the escape-rate timer. In the third beat, the escape-rate timer expires (E) without sensing any atrial activity, so an atrial pacing stimulus is delivered. The AVI timer is interrupted by a spontaneous QRS complex (arrow R) caused by the conducted paced P wave. When the R wave is sensed, the PVARP, the VRP, and the escape-rate timer begin again. The lower panel shows timing cycles and refractory periods for a dual-chamber pacemaker in DDI mode. Only after an atrial output does the AVI timer start. After the first paced QRS complex, atrial activity is sensed (arrow P); since in this mode the only response to a sensed event is inhibition, the AVI timer does not start, and a ventricular output is delivered only when the escape interval expires (E). After the second paced QRS complex, no atrial activity is sensed, so that when the difference between the escape interval and the AV interval is reached (E), an atrial output is delivered. In this case, however, intrinsic ventricular activation is sensed before the expiration of the AVI (arrow R), and the ventricular channel is inhibited from delivering a ventricular output. However, the PVARP and VRP do start. Although the DDI mode prevents unwanted tracking of atrial activity, it may be associated with less-than-optimal timing of atrial and ventricular contractions.

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grammable low rate interval; no adaptation of the rate occurs unless the sinus node responds appropriately to increased metabolic demand (a response defined as “chronotropic competence”) and the patient has intact atrioventricular-node conduction. DDI pacing (particularly the DDIR mode) may be suitable when there are frequent atrial tachyarrhythmias that might be inappropriately tracked by a DDD pacemaker, resulting in rapid paced ventricular rates.36 Rate-Adaptive Pacemakers (AAIR, VVIR, DDIR, and DDDR)

Since the mid-1970s, a series of studies has demonstrated the importance of appropriate increases in the heart rate (chronotropic responses) during exercise.26,27,37,38 The definition of an “appropriate” increase is not uniform, although an increase to heart rates above 120 beats per minute (or 70 percent of the agepredicted maximum) is a reasonable expectation. Since up to half of patients who undergo the insertion of a pacemaker have some degree of sinus-node dysfunction that blunts the response of the heart rate to exercise,37 manufacturers began developing pacemakers with separate sensors that could respond to changes in metabolic need. These sensors can be incorporated into both single-chamber (i.e., AAIR and VVIR) and dual-chamber (i.e., DDIR and DDDR) pacemakers. A rate-adaptive pacemaker should be considered for any patient whose heart rate does not increase appropriately in response to exercise (anyone with chronotropic incompetence). Recently, there has been considerable debate over the relative importance of rate adaptation and atrioventricular synchrony.38 This debate has been fueled mainly by earlier technological limitations, which prevented pacemakers from including capabilities for both rate adaptation and atrioventricular synchrony. However, the two techniques are not exclusive, but complementary. Atrioventricular synchrony contributes more to cardiac output at rest and at low levels of exertion.26 At higher levels of exercise, rate adaptation becomes more critical. Now that pacemakers using both forms of technology are widely available, a pacemaker should be chosen to suit the specific needs of the patient; recent data have demonstrated that patients prefer dual-chamber, rate-adaptive systems to single-chamber systems.39 Sensors

Sensors are designed so that the pulse generator can mimic the response of the normal heart rate to increased metabolic need. Sensors have been developed that respond to a variety of electrical, physical, or chemical stimuli; currently, the sensor-based systems used most widely in the United States incorporate sensors of motion or minute ventilation. The rationale for using motion sensors is that body movement correlates with activity, at least to some degree. Motion can be sensed either with a piezoelectric crystal that flexes and deforms in response to mechanical movement or pressure and generates an electrical current, or with an integrated-circuit silicon accelerometer. Since motion sensors are simple, responsive, and compatible with any standard system of leads, they are

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the most widely used sensors in rate-adaptive pacemakers. There are important limitations to motion sensors, however. First, body vibration or motion is only loosely correlated with metabolic demand.40 Effort that generates substantial motion, such as running in place, can be associated with a greater rate response than activities such as bicycling or isometric exercise. Second, environmentally induced vibrations, such as those associated with driving an automobile or riding in an elevator, may be related to inappropriate increases in the pacing rate.40,41 Thus, motion sensors are not specific for increased metabolic need. Minute ventilation correlates closely with oxygen consumption.42 Some manufacturers’ pulse generators use measurements of cyclic changes in thoracic impedance during inspiration and expiration to estimate changes in the respiratory rate (the frequency of changes in impedance), tidal volume (the amplitude of changes in impedance), or minute ventilation (the product of frequency and amplitude).43,44 Thoracic impedance is measured by delivering frequent pulses of constant current at low amplitude (well below the threshold required for myocardial stimulation) through the proximal electrode of the ventricular or atrial lead; the voltage between the tip electrode and the generator is measured, and the impedance calculated with Ohm’s law. Minute ventilation is an excellent physiologic sensor, but it can be affected by arm movement, coughing, or speaking.44,45 Although the question has not been well studied, minute-ventilation sensors should probably not be used in patients with lung disease; with such a sensor, inappropriate tachycardia has been reported in a patient with heart failure and Cheyne–Stokes breathing.42 Rate-adaptive pacemakers that use impedance sensors appear to have a decreased battery life, probably because of the energy consumed by the frequent (albeit intermittent) pulses of current.43,44 Programmability

In a rate-adaptive pacing system, the sensor generates electrical signals that are delivered to an algorithmic device that translates them into changes in the pacing rate. In programming most currently available devices of this type, the clinician must consider the desired level of activity at which the change in the rate should begin (the “sensitivity” or “threshold”), how rapidly the rate should increase with exercise (the “responsiveness” or “slope”), and how rapidly it should decrease after exercise. In addition, rate-adaptive pacing requires the use of new timing intervals: the upper and lower limits of the sensorbased pacing rate, which will affect the behavior of the pacemaker at high and low rates, respectively, when increased metabolic need is indicated by signals to the sensor. The upper limit of the rate can be set at a level higher than the upper limit of the atrial-based rate, so that higher heart rates can be achieved when the pacemaker senses strenuous activity (Fig. 2). Therefore, in patients with AAIR or DDDR pacemakers, heart rates will be determined by either the rate of sinus rhythm or sensor signals, and in patients with VVIR pacemakers heart rates will be determined by the intrinsic QRS rate or sensor signals. In some commercially available rate-adaptive,

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Heart Rate (beats/min)

dual-chamber pacemakers, certain timing intervals, such as the atrioventricular interval, decrease rapidly, permitting 1:1 atrioventricular synchrony to continue to exist at high heart rates. Many of the new rate-adaptive pacemakers have specialized algorithms that may be particularly important to individual patients. For example, for many years patients with episodic supraventricular arrhythmias could not benefit from dual-chamber pacing because of the possibility that the tracking of rapid atrial rates might lead to nonphysiologic rapid ventricular paced responses. Algorithms have been developed to modulate the pacemaker when it detects an atrial rate that appears abnormal. One design allows the atrial channel to sense during the period just after ventricular depolarization, known as the post-ventricular atrial refractory period. If atrial activity is identified in this interval, the pacemaker diagnoses the existence of a nonphysiologic atrial arrhythmia and switches from the DDDR mode to the VVIR mode.46 Another design has a programmable option that compares the sensor-based rate with the sensed spontaneous atrial rate; if the sensed atrial rate is rapid but the sensor indicates that the patient is at rest, the pacemaker assumes that the patient is having a nonphysiologic atrial arrhythmia and begins ventricular pacing at a preset lower rate.47 Although these methods both allow dual-chamber pacing to be used in patients with atrial tachyarrhythmias, they remain imperfect solutions, and we expect further refinements in these and other algorithms in the future. Rate-adaptive pacemakers have several shortcomings that must be acknowledged. First, the additional circuitry required for rate adaptation reduces the life of the battery. Although the rate-adaptive functions can be turned off, any benefit gained from implanting this more costly type of pacemaker is then lost. Second, pro-

200

Sensor-based upper rate limit Atrial-based upper rate limit

100 Increasing workload

Sinus rate DDD mode DDDR mode

0

Minutes Figure 2. Comparison of the Dual-Chamber Mode (DDD) with the Rate-Adaptive Dual-Chamber Mode (DDDR) with Respect to Upper-Rate Behavior in a Patient with an Inappropriate Sinus Response to Activity. With increasing workload, the intrinsic atrial rate increases slightly but plateaus below 100 beats per minute, well below the atrial-based upper limit of the rate. In the DDD pacing mode, the response of the heart rate to exercise parallels the inappropriate sinus rate. In the DDDR mode, the atrial rate is also tracked in 1:1 fashion, but at a certain level of exertion (arrow) the pacemaker is driven by the sensor rather than the sinus node, and pacing continues at increasing rates until the sensor-based upper limit is reached. In the DDDR mode, the pacemaker can be driven by either the sinus node or the sensor, and higher heart rates can be achieved in response to exercise.

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gramming a rate-adaptive pacemaker is complex and time-consuming. In the early months after implantation, patients must be seen relatively often for adjustments in the responsiveness of the adaptation. Third, commercially available sensors can be associated with problems or limitations regarding specificity of response, reliability, and the proportionality of the response to the workload. To address the limitations associated with the use of individual sensors, the possibility of combining two or more sensors in a single pacemaker is being explored.48-50 Finally, angina may develop in patients with coronary artery disease because of sensordriven tachycardia. Despite these shortcomings, rateadaptive devices can be very useful in many patients and should be considered for any patient who does not have an appropriate chronotropic response to increased metabolic demand. CHOICE

OF

PACING MODE

Once the decision to implant a pacemaker is made, the type of pacing system chosen depends on the primary indication, the accompanying clinical problems, the responsiveness of the sinus node, the presence of any paroxysmal tachyarrhythmias, and the patient’s general health and level of activity. If the patient has sinus-node disease and no evidence of disease of the atrioventricular node or His bundle when evaluated by atrial pacing in the laboratory, an atrial (AAI) pacemaker can be used, because the rate of progression to second- or third-degree atrioventricular block has been documented to be less than 1 percent per year.51 However, if the patient has accompanying disease of the atrioventricular node or His bundle, bundle-branch block, or a requirement for therapy with drugs that slow atrioventricular-node conduction, such as beta-blockers or calcium-channel blockers, a dual-chamber (DDD) system is appropriate, regardless of the patient’s age.49 If a patient with sinus-node dysfunction has intermittent atrial tachyarrhythmias, a pacemaker that can be programmed to the DDI or DDIR mode or that has specialized algorithms to detect tachycardia should be considered. Patients with disease of the atrioventricular node, His bundle, or fascicles who are in sinus rhythm should receive either a pacing system that preserves atrioventricular synchrony through separate atrial and ventricular leads (DDD) or one of the newer single-lead systems that have a pair of sensing electrodes floating freely in the right atrium (VDD).52 If the patient has chronic atrial fibrillation, a single-chamber ventricular (VVI or VVIR) pacemaker should be implanted. Patients with sinus-node disease, atrioventricularnode disease, or fascicular disease whose heart rates do not respond appropriately to activity should be considered for rate-adaptive pacing systems, especially if they have effort-related symptoms, including exertional fatigue. Finally, in patients who have intermittent, rare episodes of symptomatic bradycardia due to atrioventricular-node or sinus-node disease, single-chamber ventricular (VVI) pacemakers may be the most appropriate. When a pacing system is implanted because of neu-

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MEDICAL PROGRESS

rocardiogenic syncope, a dual-chamber pacemaker is usually required, for either carotid-sinus hypersensitivity or vasovagal syncope.14,17 If a pacemaker is considered in a patient with hypertrophic cardiomyopathy, a dual-chamber system is required so that the clinician can control the atrioventricular interval.19,20 CONCLUSIONS AND FUTURE DIRECTIONS Techniques of cardiac pacing have advanced remarkably since this therapy was introduced almost four decades ago. Although the current generation of pacemakers seems more than adequate to meet the needs of most patients, we expect that advances making it possible to mimic normal physiology more closely will continue into the next decade and beyond. Rate-adaptive pacemakers allow patients with chronotropic incompetence to enjoy the hemodynamic benefits of rate modulation. Although a perfect sensor has not been developed, devices that use new sensors or incorporate combinations of sensors are being evaluated in clinical trials, as has been recently summarized.49 Truly physiologic sensors that can estimate right ventricular stroke volume, right ventricular pressure, the rate of change in right ventricular pressure over time, or the level of oxygen saturation are being studied and have potential for guiding the medical therapy of various clinical conditions. Pacemakers with extended memory and built-in capabilities for ambulatory electrocardiographic monitoring are being developed and may help in the care of patients with infrequent arrhythmias or symptoms. The design of new leads will help prolong the life of generators and reduce the incidence of lead fracture and problems with insulation. New techniques for removing dysfunctional or infected leads have been developed that make extracting a lead safer.53 Finally, the idea of a universal programmer capable of interrogating and programming pacemakers made by any manufacturer may become a reality. Although there have been many major achievements in cardiac pacing in the past decade and there is great promise of further technological breakthroughs, this growth will not be without cost. The care of patients with pacemakers has become far more difficult because of the often bewildering array of features and options available in pulse generators. Nevertheless, it is important that primary care physicians remain well informed about the function and features of currently available devices, that they continue to have an active role in deciding whether a pacemaker should be implanted, and that, once the decision to implant a pacemaker has been made, they help choose the type of pacemaker most appropriate for each patient’s needs. REFERENCES 1. Buckingham TA, Volgman AS, Wimer E. Trends in pacemaker use: results of a multicenter registry. PACE Pacing Clin Electrophysiol 1991;14:1437-9. 2. Bernstein AD, Parsonnet V. Survey of cardiac pacing in the United States in 1989. Am J Cardiol 1992;69:331-8. 3. Zoll PM, Linenthal AJ. Long-term electrical pacemakers for Stokes-Adams disease. Circulation 1960;22:341-5. 4. Chardack WM, Gage AA, Greatbatch W. A transistorized, self-contained, implantable pacemaker for the long-term correction of complete heart block. Surgery 1960;48:643-54. 5. Elmquist R, Senning A. Proceedings, 2nd International Conference on Medical Electrical Engineering. London: Illife, 1960.

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44. Vanerio G, Patel S, Ching E, et al. Early clinical experience with a minute ventilation sensor DDDR pacemaker. PACE Pacing Clin Electrophysiol 1991;14:1815-20. 45. Lau CP, Antoniou A, Ward DE, Camm A. Reliability of minute ventilation as a parameter for rate responsive pacing. PACE Pacing Clin Electrophysiol 1989;12:321-30. 46. Lau CP, Tai YT, Fong PC, Li JPS, Chung FLW. Atrial arrhythmia management with sensor controlled atrial refractory period and automatic mode switching in patients with minute ventilation sensing dual chamber rate adaptive devices. PACE Pacing Clin Electrophysiol 1992;15:1504-14. 47. Lee MT, Adkins A, Woodson D, Vandegriff J. A new feature for control of inappropriate high rate tracking in DDDR pacemakers. PACE Pacing Clin Electrophysiol 1990;13:1852-5. 48. Landman MAJ, Senden PJ, van Rooijen H, van Hemel NM. Initial clinical experience with rate adaptive cardiac pacing using two sensors simultaneously. PACE Pacing Clin Electrophysiol 1990;13:1615-22. 49. Benditt DG, Mianulli M, Lurie K, Sakaguchi S, Adler S. Multiple-sensor systems for physiologic cardiac pacing. Ann Intern Med 1994;121:960-8. 50. Alt E, Theres H, Heinz M, Matula M, Thilo R, Blomer H. A new rate-modulated pacemaker system optimized by combination of two sensors. PACE Pacing Clin Electrophysiol 1988;11:1119-29. 51. Sutton R, Kenny RA. The natural history of sick sinus syndrome. PACE Pacing Clin Electrophysiol 1986;9:1110-4. 52. Longo E, Catrini V. Experience and implantation of a single-pass lead VDD pacing system. PACE Pacing Clin Electrophysiol 1990;13:927-36. 53. Byrd CL, Schwartz SJ, Hedin N. Lead extraction: indications and techniques. Cardiol Clin 1992;10:735-48.