Device Therapy for Cardiac Arrhythmias

Since the introduction of the implantable pacemaker in 1958 and the implantable cardioverter defibrillator (ICD) in 1980, implantable devices for rhythm control are now commonly used for treating bradycardia and certain types of ventricular arrhythmias. The first pacemakers and ICDs were large devices (40-200 cm³) that required a prolonged hospitalization for implantation and postoperative recovery, and had few programmable features. In contrast, the current devices are significantly smaller (9-45 cm³), can be implanted on an outpatient basis, and provide a myriad of programming options to optimize therapy. During the last several years, the actual and potential indications for pacemaker and ICD implantation have expanded significantly as results from several large clinical trials have become available. These advances have led to increased patient and physician acceptance and a steady increase in implantation rates. In 1997, 153 000 new pacemakers and 29 000 ICDs were implanted in the United States.¹ We summarize the function of and current indications for pacemakers and ICDs. More comprehensive discussions can be found elsewhere.^{2 - 5}

The modern pacing system is traditionally composed of 1 or 2 leads positioned in the right atrium and right ventricle via the subclavian or cephalic vein with a pulse generator placed subcutaneously in the shoulder area. The pacing system delivers a small amount of current (2-4 mA) to myocardial tissue that can initiate a propagating wave of depolarization. In addition, the pacemaker can sense intrinsic cardiac activity (or its absence). These functions provide optimal timing of atrial and ventricular activation as well as prevent bradycardia (Figure 1). For example, in a dual-chamber pacing system implanted in a patient with complete heart block, the patient's intrinsic P wave will be sensed by the pacemaker and initiate the atrioventricular (AV) interval, which is designed to mimic the PR interval, and deliver an appropriately timed ventricular stimulus to cause ventricular depolarization.

Pacing systems have traditionally been implanted for patients with bradycardia due to sinus node or AV node/His-Purkinje disease. Recent data suggest that pacemakers may be useful in a variety of other conditions.^{2 ,6 - 15}

Several types of pacemakers can be used in patients with sinus node dysfunction (sinus pauses, sick sinus syndrome, bradycardia-tachycardia syndrome). A single-chamber atrial pacemaker will prevent bradycardia due to sinus node dysfunction and maintain AV synchrony but will not prevent bradycardia if AV block develops. A single-chamber ventricular pacemaker will prevent bradycardia caused by either AV block or sinus node dysfunction but AV synchrony is not maintained. In addition, ventricular pacing can lead to retrograde conduction through the AV node to the atria. Elevated atrial pressures, due to atrial contraction when the mitral and tricuspid valves are closed, and loss of properly timed AV depolarization and contraction can lead to symptoms including syncope and presyncope, weakness, and dizziness, called pacemaker syndrome. A dual-chamber pacing system reduces the incidence of pacemaker syndrome by maintaining AV synchrony. Fifty percent of patients with sinus node dysfunction may have a blunted heart rate response to exercise. Rate-adaptive pacing systems use a separate sensor (body motion, minute ventilation) to estimate metabolic need and will vary the pacing rate depending on input from the sensor. Although more complex in design and follow-up, the majority (70%) of implanted pacemakers today are dual chamber with rate-adaptive capabilities.¹

Several recent studies have evaluated the short- and long-term effects of the type of pacemaker selection in patients with sinus node dysfunction. Andersen et al¹⁶ randomized 225 patients to single-chamber atrial pacing or single-chamber ventricular pacing; after 3.3 years of follow-up, atrial pacing was associated with a nonsignificant decrease in atrial fibrillation (AF) (atrial 14%, ventricular 23%) but significant decreases in thromboembolic events (atrial 6%, ventricular 17%) and heart failure progression (atrial 4%, ventricular 16%).¹⁶ Data from this and other small studies provided the impetus for several large trials. In the Canadian Trial of Physiologic Pacing (CTOPP), 2268 patients were randomized to single-chamber ventricular pacing or a physiologic pacing mode that preserved AV synchrony (single-chamber atrial pacing or dual-chamber pacing).¹⁷ Although no differences in overall mortality or the incidence of stroke were detected between the ventricular pacing and physiologic pacing groups, physiologic pacing was associated with a significant (27%) decrease in the development of chronic AF. In the Mode Selection Trial (MOST), 2010 patients with sinus node dysfunction were randomized to dual-chamber pacing or single-chamber ventricular pacing.¹⁸ After a 5-year follow-up, no differences in mortality or stroke were detected; however, the crossover rate to dual-chamber pacing was 31% due to symptoms of pacemaker syndrome and dual-chamber pacing was associated with improved quality of life.

Pacemakers should be implanted in symptomatic patients with AV block and in asymptomatic patients with complete heart block or type II 2° AV block.² A pacing system should not be implanted for AV block occurring in the setting of enhanced vagal tone (vagotonic block). Vagotonic block usually occurs at night, is asymptomatic, and is often an incidental finding on Holter monitoring or telemetric monitoring during hospitalization.²

Patients with AV block can be treated with either a single-chamber (rate-adaptive) ventricular pacemaker or a dual-chamber pacemaker. Although single-chamber ventricular pacemakers do not maintain AV synchrony, the pacemaker syndrome may be less common in patients with AV block than those with sinus node dysfunction because retrograde conduction is usually (70%-75%) not present. A large multicenter trial (United Kingdom Pacing and Cardiovascular Events, UK-PACE) is currently under way to evaluate whether pacemaker selection is associated with differences in clinical outcome in patients with AV block.¹⁹ At present, patients with AV block should receive a dual-chamber pacing system. Exceptions to this recommendation include patients with chronic AF, patients who are severely incapacitated, or who have a short life expectancy due to other medical problems.

Pacing therapy can be a useful adjunctive therapy for selected patients with advanced heart failure due to dilated cardiomyopathy not only by optimizing the timing between atrial and ventricular contraction but also by improving the pattern of ventricular activation. Approximately 5% to 15% of patients with dilated cardiomyopathy have a wide QRS complex (>0.12 seconds) due to abnormal ventricular activation.⁶ Delayed electrical activation of the left ventricle can lead to a relative decrease in diastolic filling time and worsen mitral regurgitation, due in part to loss of normal papillary muscle function. Separate leads can be placed in the right ventricle and over the left ventricle via the coronary sinus (biventricular pacing) to allow earlier and more coordinated activation of the left ventricle.

Two multicenter studies have demonstrated that biventricular pacing can improve symptoms associated with heart failure. In the Multisite Stimulation in Cardiomyopathy (MUSTIC) trial, 58 patients with dilated left ventricles, reduced function (ejection fraction <35%), and wide QRS complexes (>0.15 seconds) were randomized in a blinded crossover design to biventricular pacing or no pacing.⁷ Biventricular pacing was associated with improved quality of life and a 20% increase in 6-minute walk distance. Using similar patients, in the Multisite In-Synch Randomized Clinical Evaluation (MIRACLE) trial, biventricular pacing was associated with improved New York Heart Association functional class, quality of life, and left ventricular dimensions.⁸ At present, patients with enlarged hearts, ejection fractions less than 35%, and QRS duration of more than 0.13 seconds who have symptoms despite optimal medical therapy should be considered for biventricular pacing.

Initial uncontrolled studies suggested that pacemakers can improve functional capacity in patients with hypertrophic cardiomyopathy associated with left ventricular outflow tract (LVOT) pressure gradients.⁹ Pacing from the right ventricular apex causes paradoxical motion of the interventricular septum that can reduce the LVOT pressure gradient. However, results from 2 prospective randomized controlled trials have yielded mixed results. In both the Pacing in Cardiomyopathy (PIC) trial and the Multicenter Study of Pacing Therapy for Hypertrophic Cardiomyopathy (M-PATHY) trials, pacing reduced LVOT pressure gradients but had minimal effects on functional status.^{10 - 11} Interestingly, post hoc analysis from both trials suggested that pacing might benefit certain patients (older age groups, severe effort intolerance).

Vasovagal syncope is a relatively common condition that is associated with transient vasodilation and bradycardia. Vasovagal syncope is usually an isolated event that does not require treatment; however, in a small subset of patients, symptoms can be frequent and debilitating. In addition to management of the vasodepressor component by fluids, mineralocorticoids, and α-agonists, pacemakers may be useful for attenuating symptoms by preventing bradycardia. Two randomized multicenter studies, North American Vasovagal Pacemaker Study and Vasovagal Syncope International Study, in patients with drug-refractory vasovagal syncope found that pacing was associated with an 80% to 90% decrease in syncopal episodes.^{12 - 13} Although the data are preliminary, dual-chamber pacemakers may be considered in patients with severe drug-refractory vasovagal syncope.

Pacing therapy is a useful treatment for patients with symptomatic carotid sinus hypersensitivity (CSH), in which carotid sinus massage leads to profound bradycardia (>3-second pauses), hypotension (>50-mm Hg decrease in blood pressure), or both. Carotid sinus hypersensitivity is uncommon in patients younger than 50 years but may be present in 25% to 40% of older patients with syncope or unexplained falls.¹⁴ In a recent study, a group of 175 patients older than 50 years with a history of falls and CSH were randomized to pacing or no pacing.¹⁴ Patients in the no pacing group had a 4-fold greater chance of having recurrent falls when compared with the pacing group.

Pacing therapy may be a useful adjunct for the treatment of AF. As discussed earlier, atrial pacing may reduce the incidence of AF in patients with sinus node dysfunction. Recent data suggest that pacing from 2 sites in the right atrium, the right atrial appendage and the coronary sinus os, may reduce the frequency of paroxysmal AF. In the Dual Site Atrial Pacing for Prevention of Atrial Fibrillation (DAPPAF) trial, 120 patients with recurrent symptomatic AF were randomized to dual-site right atrial pacing, single-site atrial pacing, or no pacing in a randomized crossover design.¹⁵ Dual-site atrial pacing reduced the frequency of AF episodes, though antiarrhythmic drug therapy was required in most patients. Additional studies will be required to determine the appropriate use of pacing therapy for treatment of patients with AF.

Through a lead placed in the right ventricle, ICDs continuously monitor the heart rate. When the rate is more than a programmable value, the ICD will assume the patient has a malignant ventricular arrhythmia and provide therapy, usually a 10-J to 30-J shock delivered between a large electrode on the right ventricular lead and the surface of the ICD pulse generator (Figure 2). In addition, the newest generation of ICDs can be programmed to initially provide a short burst of rapid ventricular pacing (5-10 stimuli at 150-220 beats/min) that may terminate some types of ventricular tachycardia. Currently, ICDs are used in 2 situations: patients at high risk for ventricular arrhythmias (primary prevention) and patients who have already had an episode of aborted sudden cardiac death (secondary prevention).

Patients with nonsustained ventricular tachycardia and reduced left ventricular function due to coronary artery disease have a 20% to 30% chance of having a cardiac arrest during the 5-year period after initial identification.²⁰ The Multicenter Automatic Defibrillator Trial (MADIT) and the Multicenter Unsustained Tachycardia Trial (MUSTT) found that ICD implantation is beneficial in patients with reduced ejection fraction due to coronary artery disease (<35%-40%), nonsustained ventricular tachycardia, and ventricular arrhythmias inducible at electrophysiologic testing.^{21 - 22} Implantation of an ICD was associated with a 54% decrease in mortality at 2 years in MADIT and a 60% decrease at 5 years in MUSTT. A recent retrospective analysis from a 40 000 patient registry has suggested that ICD implantation may be particularly cost-effective in patients with severely reduced ejection fraction (<30%) due to myocardial infarction.²³ Recently, the results from the MADIT II trial have been released.²⁴ In the MADIT II trial, 1232 patients with prior myocardial infarction and severly reduced ejection fraction (<30%) were randomized to receive an ICD or conventional therapy. After a 20-month follow-up, there was a 31% decrease in mortality for patients that received an ICD. At the present time, patients with decreased ejection fraction due to myocardial infarction who have nonsustained ventricular tachycardia should be referred to a cardiologist for evaluation, particularly if the ejection fraction is less than 30%.

Two large studies have evaluated the use of ICDs in patients after an episode of sudden cardiac death or who have had syncope and have ventricular tachycardia induced at electrophysiologic testing. In the Antiarrhythmics Versus Implantable Defibrillator (AVID) study, 1016 patients were randomized to ICD implantation or antiarrhythmic drug therapy. The ICD was associated with a 31% decrease in mortality at 3 years.²⁵ In the Canadian Implantable Defibrillator Study (CIDS), 659 patients were randomized to ICD therapy or amiodarone.²⁶ At 3 years, the ICD was associated with a 20% risk decrease in mortality that approached statistical significance. Although subsequent subgroup analysis of the AVID data has suggested that ICDs provided benefit only in patients with ejection fractions less than 40%, it is currently recommended that an ICD should be implanted in patients who have had a cardiac arrest not due to reversible causes or who have unexplained syncope and have ventricular tachycardia induced at electrophysiologic testing.^{2 ,5}

The indications for the use of implantable cardiac devices have expanded significantly over the past several years. While pacemakers have traditionally been used for the treatment of bradycardia due to sinus node dysfunction or AV block, referral to a cardiologist for pacing therapy should also be considered in selected patients with dilated and hypertrophic cardiomyopathy, autonomic nervous system disorders, or AF. The patient with resuscitated cardiac arrest (secondary prevention) should be referred for ICD implantation. The use of ICDs for primary prevention of sudden cardiac death is more controversial; MADIT was a relatively small study and MUSTT was not designed specifically to evaluate the effectiveness of ICD therapy. However, the recent results from the MADIT II trial suggest that ICDs do have a role for primary prevention of sudden death in patients with reduced ejection fraction (<30%) due to prior myocardial infarction. Results from a large trial sponsored by the National Institutes of Health, the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), will be available next year and will provide further information on the appropiate use of ICDs for primary prevention. We believe that use of implantable devices for the treatment of cardiac arrhythmias and for improving hemodynamic function will continue to expand over the next decade. As ICDs and pacemakers become more common in clinical practice, it is essential for all physicians to appreciate the basic function of implantable devices and their therapeutic uses.