Pacemaker Selection — The Changing Definition of Physiologic Pacing
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《新英格兰医药杂志》
Almost 50 years after the first report of the use of cardiac pacing, in the Journal,1 pacing is playing an increasingly important role in the management of cardiac disease. Cardiologists have evaluated single-chamber, dual-chamber, and triple-chamber pacemakers in patients with different types of conduction-system disease and underlying cardiac function. The goal of these increasingly complex pacing systems is to reproduce the normal electrical activation of the heart.
Dual-chamber pacing confers potentially important hemodynamic advantages over ventricular pacing by linking the timing of atrial and ventricular contraction, a phenomenon called atrioventricular synchrony.2 In short-term and long-term studies, atrioventricular synchrony improves stroke volume, raises systolic blood pressure, reduces right atrial pressure and pulmonary-capillary wedge pressure, and is less likely to elicit cardioinhibitory reflexes than is ventricular pacing. The importance of the atrial contribution to cardiac output has been demonstrated in a variety of patient groups as well as at different heart rates. The restoration of atrioventricular synchrony by pacing was branded early on as "physiologic pacing" because it mimics the normal sequence of atrioventricular activation. The expectation was that the hemodynamic benefits of atrioventricular synchrony would translate into reductions in cardiac mortality, a reduced risk of heart failure, and a better quality of life.
These expectations have been examined in two previous large, randomized clinical trials comparing dual-chamber pacing with single-chamber pacing. These trials, predominantly involving patients with the sick sinus syndrome and having a combined enrollment of more than 4500 patients, showed a relative reduction in the risk of atrial fibrillation that ranged from 18 to 23 percent.3,4 No difference in total mortality, mortality from cardiovascular causes, or stroke was observed.
It was only natural that a similar evaluation would be conducted in patients with high-grade atrioventricular block, who make up a substantial portion of patients now receiving pacemakers. In this issue of the Journal, Toff and colleagues report the results of the United Kingdom Pacing and Cardiovascular Events (UKPACE) trial, a comparison of single-chamber pacing with dual-chamber pacing in elderly patients with high-grade atrioventricular block.5 The patient population studied differs in important ways from that in other clinical trials in that there was a higher mean age (80 years) and higher annual mortality (7.2 to 7.4 percent). Dual-chamber pacing did not reduce the rate of death from all causes or from cardiovascular causes, nor did it decrease the incidence of atrial fibrillation, myocardial infarction, congestive heart failure or stroke, transient ischemic attack, or other thromboembolism. The authors conclude that, in this patient population, there is no additional benefit to dual-chamber pacing as compared with the simpler and easier-to-implant single-chamber ventricular pacemaker.
The UKPACE trial did not examine quality of life, but this is an important issue. The quality of life in patients with pacemakers is often poor and in one trial was found to be similar to that of patients who require long-term hemodialysis.4 It has been difficult to demonstrate improved quality of life with dual-chamber pacing in the elderly. In the Pacemaker Selection in the Elderly (PASE) trial, in which the primary end point was quality of life, no overall benefit from dual-chamber pacing as compared with single-chamber ventricular pacing was found in an elderly cohort.6 In a subgroup analysis, patients with sinus-node dysfunction did appear to benefit from dual-chamber pacing, but those with pacemakers implanted because of heart block did not. For the general pacing population, no large trial has yet been reported that used quality of life as the primary end point, although several such trials are in progress.
Dual-chamber pacing does appear to improve the quality of life when comparisons within individual patients, rather than between patients, are made. For example, in a randomized crossover study, Sulke and colleagues compared the effects of different pacing modes on symptoms, functional class, and perceived health status.7 Single-chamber pacing was the least acceptable pacing mode for 73 percent of patients, and dual-chamber pacing was the preferred mode for 86 percent. Only 9 percent of patients showed no preference for pacing mode, and 5 percent chose single-chamber ventricular pacing. In trials involving the selection of pacing mode in which a dual-chamber pacemaker was implanted, 18 to 26 percent of patients randomly assigned to single-chamber ventricular pacing were unable to tolerate this pacing mode and were switched to a dual-chamber pacing mode. After crossover, patients had significant improvements in quality of life in almost all areas measured.8 Finally, even patients who have felt generally well for many years with single-chamber pacemakers have noted improvements in their quality of life after being upgraded to dual-chamber pacemakers at the time of a pulse-generator change.9 Although dual-chamber pacing has not been fully studied, most cardiologists expect that this pacing mode will be shown to improve the quality of life.
The failure to easily demonstrate clinical benefits of dual-chamber pacing has forced a rethinking of what is meant by "physiologic pacing." It is now well accepted that long-term right ventricular pacing causes a deterioration of left ventricular function through complex effects on regional ventricular wall strain and loading conditions. This deterioration is thought to be a result of dyssynchrony between the walls of the left ventricle that is induced by pacing in the right ventricular apex. Sweeney et al. demonstrated, by careful review of data from a large pacing trial, that an increase in the frequency of ventricular pacing in patients with the sick sinus syndrome who had a narrow native QRS complex was associated with an increased incidence of atrial fibrillation and congestive heart failure.10 These observations were confirmed by Wilkoff et al. in the Dual Chamber and VVI Implantable Defibrillator (DAVID) study, in which backup ventricular pacing and dual-chamber pacing were prospectively compared in patients with dual-chamber defibrillators.11 The primary end point was a composite of congestive heart failure, hospitalization, and death and was increased by a factor of 1.6 in patients with an increased frequency of ventricular pacing. Thus, right ventricular pacing is a two-edged sword, conferring atrioventricular synchrony but at the same time possibly negating its benefit by inducing ventricular dysfunction.
Cardiac-resynchronization therapy, with pacing of both ventricles as well as of the right atrium (i.e., triple-chamber pacing), has been introduced to compensate for ventricular dyssynchrony. In patients without bradycardia as an indication for pacing but with conduction-system disease and heart failure, cardiac-resynchronization therapy reduces the symptoms of heart failure and improves exercise tolerance, the quality of life, and survival.12,13 The yet-untested concept is that cardiac-resynchronization therapy, if applied to the general population of people who may benefit from the use of a pacemaker, may overcome the deficiencies of dual-chamber pacing in terms of clinical outcomes.
What can now be said about the selection of patients for dual-chamber, right ventricular pacing? In elderly patients with heart block, dual-chamber pacing will not result in a benefit with respect to hard end points, such as death from cardiovascular disease, heart failure, stroke, or the prevention of atrial fibrillation. Although the expectation of improved survival has been dashed by the results of clinical trials, the question of improvement in the quality of life has not been thoroughly examined. The available evidence suggests that dual-chamber pacing improves the quality of life in at least some patient groups. Furthermore, to the extent that frequent or persistent right ventricular pacing worsens outcomes by inducing left ventricular dysfunction, new pacing algorithms are now available that lead to a dramatic reduction in the amount of unnecessary ventricular pacing while still preventing ventricular asystole. There are not yet sufficient data to recommend cardiac-resynchronization therapy (i.e., triple-chamber pacing) in patients with bradyarrhythmias who have normal left ventricular function.
It is fair to say that 50 years after the introduction of pacing, this field is undergoing a tremendous revolution. We are learning from both physiology and clinical trials. The best mode of pacing, the best type of pacemaker, and the best position for the pacemaker lead or leads are still not known. What was once heralded as "physiologic" pacing now is regarded in terms of many end points as ineffective at best and deleterious at worst. Much work remains to be done with regard to the development of true physiologic pacing that broadly improves both survival and the quality of life. Cardiologists will have to await the results of ongoing trials involving the quality of life and the further evaluation of triple-chamber pacing systems in a broad range of patients with pacemakers.
Dr. Ellenbogen reports having received lecture fees and grant support from Medtronic, Guidant, and St. Jude Medical. Dr. Wood reports having received consulting fees from Medtronic and lecture fees from Guidant and Stereotaxis.
Source Information
From Virginia Commonwealth University School of Medicine, Richmond.
References
Furman S, Schwedel JB. An intercardiac pacemaker for Stokes-Adams seizures. N Engl J Med 1959;261:943-948.
Janosik DL, Ellenbogen KA. Basic physiology of cardiac pacing and pacemaker syndrome. In: Ellenbogen KA, Kay GN, Wilkoff BL, eds. Clinical cardiac pacing and defibrillation. Philadelphia: W.B. Saunders, 2000:333-82.
Connolly SJ, Kerr CR, Gent M, et al. Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. N Engl J Med 2000;342:1385-1391.
Lamas GA, Lee KL, Sweeney MO, et al. Ventricular pacing or dual-chamber pacing for sinus-node dysfunction. N Engl J Med 2002;346:1854-1862.
Toff WD, Camm AJ, Skehan JD. Single-chamber versus dual-chamber pacing for high-grade atrioventricular block. N Engl J Med 2005;353:145-155.
Lamas GA, Orav EJ, Stambler BS, et al. Quality of life and clinical outcomes in elderly patients treated with ventricular pacing as compared with dual-chamber pacing. N Engl J Med 1998;338:1097-1104.(Kenneth A. Ellenbogen, M.)
Dual-chamber pacing confers potentially important hemodynamic advantages over ventricular pacing by linking the timing of atrial and ventricular contraction, a phenomenon called atrioventricular synchrony.2 In short-term and long-term studies, atrioventricular synchrony improves stroke volume, raises systolic blood pressure, reduces right atrial pressure and pulmonary-capillary wedge pressure, and is less likely to elicit cardioinhibitory reflexes than is ventricular pacing. The importance of the atrial contribution to cardiac output has been demonstrated in a variety of patient groups as well as at different heart rates. The restoration of atrioventricular synchrony by pacing was branded early on as "physiologic pacing" because it mimics the normal sequence of atrioventricular activation. The expectation was that the hemodynamic benefits of atrioventricular synchrony would translate into reductions in cardiac mortality, a reduced risk of heart failure, and a better quality of life.
These expectations have been examined in two previous large, randomized clinical trials comparing dual-chamber pacing with single-chamber pacing. These trials, predominantly involving patients with the sick sinus syndrome and having a combined enrollment of more than 4500 patients, showed a relative reduction in the risk of atrial fibrillation that ranged from 18 to 23 percent.3,4 No difference in total mortality, mortality from cardiovascular causes, or stroke was observed.
It was only natural that a similar evaluation would be conducted in patients with high-grade atrioventricular block, who make up a substantial portion of patients now receiving pacemakers. In this issue of the Journal, Toff and colleagues report the results of the United Kingdom Pacing and Cardiovascular Events (UKPACE) trial, a comparison of single-chamber pacing with dual-chamber pacing in elderly patients with high-grade atrioventricular block.5 The patient population studied differs in important ways from that in other clinical trials in that there was a higher mean age (80 years) and higher annual mortality (7.2 to 7.4 percent). Dual-chamber pacing did not reduce the rate of death from all causes or from cardiovascular causes, nor did it decrease the incidence of atrial fibrillation, myocardial infarction, congestive heart failure or stroke, transient ischemic attack, or other thromboembolism. The authors conclude that, in this patient population, there is no additional benefit to dual-chamber pacing as compared with the simpler and easier-to-implant single-chamber ventricular pacemaker.
The UKPACE trial did not examine quality of life, but this is an important issue. The quality of life in patients with pacemakers is often poor and in one trial was found to be similar to that of patients who require long-term hemodialysis.4 It has been difficult to demonstrate improved quality of life with dual-chamber pacing in the elderly. In the Pacemaker Selection in the Elderly (PASE) trial, in which the primary end point was quality of life, no overall benefit from dual-chamber pacing as compared with single-chamber ventricular pacing was found in an elderly cohort.6 In a subgroup analysis, patients with sinus-node dysfunction did appear to benefit from dual-chamber pacing, but those with pacemakers implanted because of heart block did not. For the general pacing population, no large trial has yet been reported that used quality of life as the primary end point, although several such trials are in progress.
Dual-chamber pacing does appear to improve the quality of life when comparisons within individual patients, rather than between patients, are made. For example, in a randomized crossover study, Sulke and colleagues compared the effects of different pacing modes on symptoms, functional class, and perceived health status.7 Single-chamber pacing was the least acceptable pacing mode for 73 percent of patients, and dual-chamber pacing was the preferred mode for 86 percent. Only 9 percent of patients showed no preference for pacing mode, and 5 percent chose single-chamber ventricular pacing. In trials involving the selection of pacing mode in which a dual-chamber pacemaker was implanted, 18 to 26 percent of patients randomly assigned to single-chamber ventricular pacing were unable to tolerate this pacing mode and were switched to a dual-chamber pacing mode. After crossover, patients had significant improvements in quality of life in almost all areas measured.8 Finally, even patients who have felt generally well for many years with single-chamber pacemakers have noted improvements in their quality of life after being upgraded to dual-chamber pacemakers at the time of a pulse-generator change.9 Although dual-chamber pacing has not been fully studied, most cardiologists expect that this pacing mode will be shown to improve the quality of life.
The failure to easily demonstrate clinical benefits of dual-chamber pacing has forced a rethinking of what is meant by "physiologic pacing." It is now well accepted that long-term right ventricular pacing causes a deterioration of left ventricular function through complex effects on regional ventricular wall strain and loading conditions. This deterioration is thought to be a result of dyssynchrony between the walls of the left ventricle that is induced by pacing in the right ventricular apex. Sweeney et al. demonstrated, by careful review of data from a large pacing trial, that an increase in the frequency of ventricular pacing in patients with the sick sinus syndrome who had a narrow native QRS complex was associated with an increased incidence of atrial fibrillation and congestive heart failure.10 These observations were confirmed by Wilkoff et al. in the Dual Chamber and VVI Implantable Defibrillator (DAVID) study, in which backup ventricular pacing and dual-chamber pacing were prospectively compared in patients with dual-chamber defibrillators.11 The primary end point was a composite of congestive heart failure, hospitalization, and death and was increased by a factor of 1.6 in patients with an increased frequency of ventricular pacing. Thus, right ventricular pacing is a two-edged sword, conferring atrioventricular synchrony but at the same time possibly negating its benefit by inducing ventricular dysfunction.
Cardiac-resynchronization therapy, with pacing of both ventricles as well as of the right atrium (i.e., triple-chamber pacing), has been introduced to compensate for ventricular dyssynchrony. In patients without bradycardia as an indication for pacing but with conduction-system disease and heart failure, cardiac-resynchronization therapy reduces the symptoms of heart failure and improves exercise tolerance, the quality of life, and survival.12,13 The yet-untested concept is that cardiac-resynchronization therapy, if applied to the general population of people who may benefit from the use of a pacemaker, may overcome the deficiencies of dual-chamber pacing in terms of clinical outcomes.
What can now be said about the selection of patients for dual-chamber, right ventricular pacing? In elderly patients with heart block, dual-chamber pacing will not result in a benefit with respect to hard end points, such as death from cardiovascular disease, heart failure, stroke, or the prevention of atrial fibrillation. Although the expectation of improved survival has been dashed by the results of clinical trials, the question of improvement in the quality of life has not been thoroughly examined. The available evidence suggests that dual-chamber pacing improves the quality of life in at least some patient groups. Furthermore, to the extent that frequent or persistent right ventricular pacing worsens outcomes by inducing left ventricular dysfunction, new pacing algorithms are now available that lead to a dramatic reduction in the amount of unnecessary ventricular pacing while still preventing ventricular asystole. There are not yet sufficient data to recommend cardiac-resynchronization therapy (i.e., triple-chamber pacing) in patients with bradyarrhythmias who have normal left ventricular function.
It is fair to say that 50 years after the introduction of pacing, this field is undergoing a tremendous revolution. We are learning from both physiology and clinical trials. The best mode of pacing, the best type of pacemaker, and the best position for the pacemaker lead or leads are still not known. What was once heralded as "physiologic" pacing now is regarded in terms of many end points as ineffective at best and deleterious at worst. Much work remains to be done with regard to the development of true physiologic pacing that broadly improves both survival and the quality of life. Cardiologists will have to await the results of ongoing trials involving the quality of life and the further evaluation of triple-chamber pacing systems in a broad range of patients with pacemakers.
Dr. Ellenbogen reports having received lecture fees and grant support from Medtronic, Guidant, and St. Jude Medical. Dr. Wood reports having received consulting fees from Medtronic and lecture fees from Guidant and Stereotaxis.
Source Information
From Virginia Commonwealth University School of Medicine, Richmond.
References
Furman S, Schwedel JB. An intercardiac pacemaker for Stokes-Adams seizures. N Engl J Med 1959;261:943-948.
Janosik DL, Ellenbogen KA. Basic physiology of cardiac pacing and pacemaker syndrome. In: Ellenbogen KA, Kay GN, Wilkoff BL, eds. Clinical cardiac pacing and defibrillation. Philadelphia: W.B. Saunders, 2000:333-82.
Connolly SJ, Kerr CR, Gent M, et al. Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. N Engl J Med 2000;342:1385-1391.
Lamas GA, Lee KL, Sweeney MO, et al. Ventricular pacing or dual-chamber pacing for sinus-node dysfunction. N Engl J Med 2002;346:1854-1862.
Toff WD, Camm AJ, Skehan JD. Single-chamber versus dual-chamber pacing for high-grade atrioventricular block. N Engl J Med 2005;353:145-155.
Lamas GA, Orav EJ, Stambler BS, et al. Quality of life and clinical outcomes in elderly patients treated with ventricular pacing as compared with dual-chamber pacing. N Engl J Med 1998;338:1097-1104.(Kenneth A. Ellenbogen, M.)