Pacing for Atrioventricular Block
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《新英格兰医药杂志》
To the Editor: The report by Toff and colleagues on the United Kingdom Pacing and Cardiovascular Events (UKPACE) trial (July 14 issue),1 evaluating cardiovascular end points in elderly patients with atrioventricular block, showed that the use of dual-chamber pacing to maintain atrioventricular synchrony conferred no survival advantage over the use of single-chamber pacing. These results may be considered along with those of recent trials involving patients with atrial fibrillation that showed a lack of mortality benefit associated with a strategy that maintains atrioventricular synchrony by restoring sinus rhythm.2 Perhaps the consequences of atrioventricular synchrony deserve closer inspection.
As Ellenbogen and Wood mention in the accompanying editorial,3 atrioventricular pacing increases stroke volume and systolic blood pressure, as compared with ventricular pacing. These effects are probably more pronounced in elderly persons because of reduced aortic compliance and an increased incidence of diastolic dysfunction. Did the different pacing strategies lead to a meaningful difference in blood-pressure control or medication requirements? The harmful effects of higher blood pressure in the dual-chamber group may have offset any benefit from this pacing mode. In addition, how was baseline hypertension ascertained? A prevalence of 33 percent is about half what one would expect for an elderly population.
James L. Amato, Jr., M.D.
Saint Michael's Medical Center
Newark, NJ 07102
jimamato@opton.net
References
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.
Steinberg JS, Sadaniantz A, Kron J, et al. Analysis of cause-specific mortality in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. Circulation 2004;109:1973-1980.
Ellenbogen KA, Wood MA. Pacemaker selection -- the changing definition of physiologic pacing. N Engl J Med 2005;353:202-204.
To the Editor: A well-designed study, the UKPACE trial showed that, among elderly patients with high-grade atrioventricular block, the pacing mode (single-chamber or dual-chamber) does not influence the rate of death during the first five years after implantation of a pacemaker or the incidence of cardiovascular events during the first three years after implantation. There was a higher incidence of atrial fibrillation in the dual-chamber group during the first 18 months after implantation. The authors suggest that the atrial lead may be arrhythmogenic during this period. By contrast, other authors have found a reduction in atrial fibrillation with physiologic pacing among some patients with atrioventricular block.1 An interesting approach in the care of elderly patients would be to use or evaluate prospectively an atrial synchronous ventricular inhibited (VDD) pacing mode with a single VDD lead that has the capacity for atrial sensing, resulting in a physiologic pacing mode with atrioventricular synchrony and with a theoretic lack of atrial arrhythmogenicity.2,3
Laurent Fauchier, M.D.
Dominique Babuty, M.D.
Centre Hospitalier Universitaire Trousseau
37044 Tours, France
lfau@med.univ-tours.fr
References
Skanes AC, Krahn AD, Yee R, et al. Progression to chronic atrial fibrillation after pacing: the Canadian Trial of Physiologic Pacing. J Am Coll Cardiol 2001;38:167-172.
Huang M, Krahn AD, Yee R, Klein GJ, Skanes AC. Optimal pacing for symptomatic AV block: a comparison of VDD and DDD pacing. Pacing Clin Electrophysiol 2004;27:19-23.
Wiegand UK, Bode F, Bonnemeier H, Eberhard F, Schlei M, Peters W. Long-term complication rates in ventricular, single lead VDD, and dual chamber pacing. Pacing Clin Electrophysiol 2003;26:1961-1969.
To the Editor: The UKPACE study showed that among elderly patients with atrioventricular block, the pacing mode did not influence either the rate of death from all causes or secondary outcomes. In our opinion, this may underestimate the benefits of dual-chamber pacing. The UKPACE trial did not examine the effect of the pacing mode on the quality of life. Evidence indicates that VVIR pacing (ventricular pacing, ventricular sensing, inhibition response, rate-adaptive), as compared with DDDR pacing (atrial and ventricular pacing, atrial and ventricular sensing, dual response, rate-adaptive) can significantly influence the quality of life and the development of pacemaker syndrome.1
Furthermore, as has been found with right ventricular pacing, evidence is emerging that right atrial pacing can be detrimental, resulting in interatrial dyssynchrony, delayed left atrial contraction, and reduced left ventricular filling. Studies support avoiding right atrial pacing, with the use of either the VDD mode2 or biatrial pacing.3 Programming in the UKPACE trial encouraged right atrial pacing (DDDR, 60 to 125 beats per minute; rate-responsive atrioventricular delay, 75 to 150 msec), and the resulting effects on interatrial conduction and left ventricular filling may have reduced the benefit of atrioventricular dual-chamber (DDD) pacing.
Therefore, we believe that it would be premature to withhold dual-chamber pacing completely from the elderly population. Future studies to address the effects of pacing mode on the quality of life and to minimize right ventricular pacing could answer these important questions.
E. Kevin Heist, M.D., Ph.D.
J. Warren Harthorne, M.D.
Jagmeet P. Singh, M.D., Ph.D.
Massachusetts General Hospital
Boston, MA 02114
kheist@partners.org
Dr. Heist reports having received lecture fees from Guidant, and Dr. Singh consulting fees from Guidant and lecture fees from Medtronic and St. Jude Medical.
References
Link MS, Hellkamp AS, Estes NA III, et al. High incidence of pacemaker syndrome in patients with sinus node dysfunction treated with ventricular-based pacing in the Mode Selection Trial (MOST). J Am Coll Cardiol 2004;43:2066-2071.
Bernheim A, Ammann P, Sticherling C, et al. Right atrial pacing impairs cardiac function during resynchronization therapy: acute effects of DDD pacing compared to VDD pacing. J Am Coll Cardiol 2005;45:1482-1487.
Doi A, Takagi M, Toda I, Yoshiyama M, Takeuchi K, Yoshikawa J. Acute hemodynamic benefits of bi-atrial atrioventricular sequential pacing with the optimal atrioventricular delay. J Am Coll Cardiol 2005;46:320-326.
The authors reply: We agree with Drs. Fauchier and Babuty that a prospective evaluation of single-lead VDD pacing would be of interest. Single-lead VDD pacing is regarded as an acceptable alternative to dual-chamber pacing in atrioventricular block,1 but there are few comparative data.2
Dr. Amato raises the possibility that deleterious effects of higher systolic blood pressure due to improved hemodynamic function might offset any benefit of dual-chamber pacing. Blood pressure was not recorded during follow-up, so we cannot test this hypothesis on the basis of our data. The rate of use of beta-blockers during follow-up was higher in the dual-chamber group than in the single-chamber group (6.5 percent vs. 3.2 percent at 10 months), but there was little difference in the use of diuretics (50.1 percent vs. 49.9 percent), angiotensin-converting–enzyme inhibitors (21.3 percent vs. 21.6 percent), or calcium-channel blockers (16.9 percent vs. 12.5 percent). The reported prevalence of hypertension at baseline was determined on the basis of direct questioning of the patients and review of case notes, and it relates to a previously established diagnosis of hypertension. The actual prevalence is probably higher, since population screening data suggest that only 50 to 75 percent of elderly patients with hypertension are aware of having it.3
We agree with Dr. Heist and colleagues, and with the editorialists, Drs. Ellenbogen and Wood, that the quality of life is an important consideration. This was, in fact, assessed as a secondary outcome in UKPACE with the use of patients' responses to the Medical Outcomes Study 36-item Short-Form General Health Survey and the EuroQoL EQ-5D questionnaire.4 Spatial constraints precluded the inclusion of these data. We previously reported the low incidence of suspected pacemaker syndrome (2.7 percent) in our study and the lack of evidence to suggest the presence of a subclinical form.5
Heist and colleagues suggest that our recommended pacemaker settings, which investigators were free to change on clinical grounds, might have reduced the benefits of dual-chamber pacing by encouraging right atrial pacing. The median proportion of atrial beats that were paced in the dual-chamber group, obtained from pacemaker interrogation at 1, 10, and 36 months, was 15.0 percent, 20.0 percent, and 24.0 percent, respectively. Although we support the principle that unnecessary pacing (of the atrium or ventricle) should be minimized, the trial design was pragmatic, and the implementation of the pacing modes under investigation was intended to reflect standard clinical practice.
We believe that the data support our conclusion that for elderly patients with atrioventricular block, the choice between single-chamber or dual-chamber pacing is unlikely to influence the risk of death from all causes or of cardiovascular events in the early years after pacemaker implantation.
William D. Toff, M.D.
University of Leicester Glenfield Hospital
Leicester LE3 9QP, United Kingdom
w.toff@le.ac.uk
A. John Camm, M.D.
St. George's University of London
London SW17 0RE, United Kingdom
J. Douglas Skehan, M.B., B.S.
University Hospitals of Leicester NHS Trust
Leicester LE3 9QP, United Kingdom
for the UKPACE Trial Investigators
References
Gregoratos G, Cheitlin MD, Conill A, et al. ACC/AHA guidelines for implantation of cardiac pacemakers and antiarrhythmia devices: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Pacemaker Implantation). J Am Coll Cardiol 1998;31:1175-1209.
Ovsyshcher IE, Crystal E. VDD pacing: underevaluated, undervalued and underused. Pacing Clin Electrophysiol 2004;27:1335-1338.
Primatesta P, Brookes M, Poulter NR. Improved hypertension management and control: results from the Health Survey for England 1998. Hypertension 2001;38:827-832.
Toff WD, Skehan JD, De Bono DP, Camm AJ. The United Kingdom Pacing and Cardiovascular Events (UKPACE) trial. Heart 1997;78:221-223.
Toff WD, Camm AJ, Skehan JD. Low incidence of pacemaker syndrome in elderly patients paced for high-grade atrioventricular block. Heart Rhythm 2004;1:383-383.
As Ellenbogen and Wood mention in the accompanying editorial,3 atrioventricular pacing increases stroke volume and systolic blood pressure, as compared with ventricular pacing. These effects are probably more pronounced in elderly persons because of reduced aortic compliance and an increased incidence of diastolic dysfunction. Did the different pacing strategies lead to a meaningful difference in blood-pressure control or medication requirements? The harmful effects of higher blood pressure in the dual-chamber group may have offset any benefit from this pacing mode. In addition, how was baseline hypertension ascertained? A prevalence of 33 percent is about half what one would expect for an elderly population.
James L. Amato, Jr., M.D.
Saint Michael's Medical Center
Newark, NJ 07102
jimamato@opton.net
References
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.
Steinberg JS, Sadaniantz A, Kron J, et al. Analysis of cause-specific mortality in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. Circulation 2004;109:1973-1980.
Ellenbogen KA, Wood MA. Pacemaker selection -- the changing definition of physiologic pacing. N Engl J Med 2005;353:202-204.
To the Editor: A well-designed study, the UKPACE trial showed that, among elderly patients with high-grade atrioventricular block, the pacing mode (single-chamber or dual-chamber) does not influence the rate of death during the first five years after implantation of a pacemaker or the incidence of cardiovascular events during the first three years after implantation. There was a higher incidence of atrial fibrillation in the dual-chamber group during the first 18 months after implantation. The authors suggest that the atrial lead may be arrhythmogenic during this period. By contrast, other authors have found a reduction in atrial fibrillation with physiologic pacing among some patients with atrioventricular block.1 An interesting approach in the care of elderly patients would be to use or evaluate prospectively an atrial synchronous ventricular inhibited (VDD) pacing mode with a single VDD lead that has the capacity for atrial sensing, resulting in a physiologic pacing mode with atrioventricular synchrony and with a theoretic lack of atrial arrhythmogenicity.2,3
Laurent Fauchier, M.D.
Dominique Babuty, M.D.
Centre Hospitalier Universitaire Trousseau
37044 Tours, France
lfau@med.univ-tours.fr
References
Skanes AC, Krahn AD, Yee R, et al. Progression to chronic atrial fibrillation after pacing: the Canadian Trial of Physiologic Pacing. J Am Coll Cardiol 2001;38:167-172.
Huang M, Krahn AD, Yee R, Klein GJ, Skanes AC. Optimal pacing for symptomatic AV block: a comparison of VDD and DDD pacing. Pacing Clin Electrophysiol 2004;27:19-23.
Wiegand UK, Bode F, Bonnemeier H, Eberhard F, Schlei M, Peters W. Long-term complication rates in ventricular, single lead VDD, and dual chamber pacing. Pacing Clin Electrophysiol 2003;26:1961-1969.
To the Editor: The UKPACE study showed that among elderly patients with atrioventricular block, the pacing mode did not influence either the rate of death from all causes or secondary outcomes. In our opinion, this may underestimate the benefits of dual-chamber pacing. The UKPACE trial did not examine the effect of the pacing mode on the quality of life. Evidence indicates that VVIR pacing (ventricular pacing, ventricular sensing, inhibition response, rate-adaptive), as compared with DDDR pacing (atrial and ventricular pacing, atrial and ventricular sensing, dual response, rate-adaptive) can significantly influence the quality of life and the development of pacemaker syndrome.1
Furthermore, as has been found with right ventricular pacing, evidence is emerging that right atrial pacing can be detrimental, resulting in interatrial dyssynchrony, delayed left atrial contraction, and reduced left ventricular filling. Studies support avoiding right atrial pacing, with the use of either the VDD mode2 or biatrial pacing.3 Programming in the UKPACE trial encouraged right atrial pacing (DDDR, 60 to 125 beats per minute; rate-responsive atrioventricular delay, 75 to 150 msec), and the resulting effects on interatrial conduction and left ventricular filling may have reduced the benefit of atrioventricular dual-chamber (DDD) pacing.
Therefore, we believe that it would be premature to withhold dual-chamber pacing completely from the elderly population. Future studies to address the effects of pacing mode on the quality of life and to minimize right ventricular pacing could answer these important questions.
E. Kevin Heist, M.D., Ph.D.
J. Warren Harthorne, M.D.
Jagmeet P. Singh, M.D., Ph.D.
Massachusetts General Hospital
Boston, MA 02114
kheist@partners.org
Dr. Heist reports having received lecture fees from Guidant, and Dr. Singh consulting fees from Guidant and lecture fees from Medtronic and St. Jude Medical.
References
Link MS, Hellkamp AS, Estes NA III, et al. High incidence of pacemaker syndrome in patients with sinus node dysfunction treated with ventricular-based pacing in the Mode Selection Trial (MOST). J Am Coll Cardiol 2004;43:2066-2071.
Bernheim A, Ammann P, Sticherling C, et al. Right atrial pacing impairs cardiac function during resynchronization therapy: acute effects of DDD pacing compared to VDD pacing. J Am Coll Cardiol 2005;45:1482-1487.
Doi A, Takagi M, Toda I, Yoshiyama M, Takeuchi K, Yoshikawa J. Acute hemodynamic benefits of bi-atrial atrioventricular sequential pacing with the optimal atrioventricular delay. J Am Coll Cardiol 2005;46:320-326.
The authors reply: We agree with Drs. Fauchier and Babuty that a prospective evaluation of single-lead VDD pacing would be of interest. Single-lead VDD pacing is regarded as an acceptable alternative to dual-chamber pacing in atrioventricular block,1 but there are few comparative data.2
Dr. Amato raises the possibility that deleterious effects of higher systolic blood pressure due to improved hemodynamic function might offset any benefit of dual-chamber pacing. Blood pressure was not recorded during follow-up, so we cannot test this hypothesis on the basis of our data. The rate of use of beta-blockers during follow-up was higher in the dual-chamber group than in the single-chamber group (6.5 percent vs. 3.2 percent at 10 months), but there was little difference in the use of diuretics (50.1 percent vs. 49.9 percent), angiotensin-converting–enzyme inhibitors (21.3 percent vs. 21.6 percent), or calcium-channel blockers (16.9 percent vs. 12.5 percent). The reported prevalence of hypertension at baseline was determined on the basis of direct questioning of the patients and review of case notes, and it relates to a previously established diagnosis of hypertension. The actual prevalence is probably higher, since population screening data suggest that only 50 to 75 percent of elderly patients with hypertension are aware of having it.3
We agree with Dr. Heist and colleagues, and with the editorialists, Drs. Ellenbogen and Wood, that the quality of life is an important consideration. This was, in fact, assessed as a secondary outcome in UKPACE with the use of patients' responses to the Medical Outcomes Study 36-item Short-Form General Health Survey and the EuroQoL EQ-5D questionnaire.4 Spatial constraints precluded the inclusion of these data. We previously reported the low incidence of suspected pacemaker syndrome (2.7 percent) in our study and the lack of evidence to suggest the presence of a subclinical form.5
Heist and colleagues suggest that our recommended pacemaker settings, which investigators were free to change on clinical grounds, might have reduced the benefits of dual-chamber pacing by encouraging right atrial pacing. The median proportion of atrial beats that were paced in the dual-chamber group, obtained from pacemaker interrogation at 1, 10, and 36 months, was 15.0 percent, 20.0 percent, and 24.0 percent, respectively. Although we support the principle that unnecessary pacing (of the atrium or ventricle) should be minimized, the trial design was pragmatic, and the implementation of the pacing modes under investigation was intended to reflect standard clinical practice.
We believe that the data support our conclusion that for elderly patients with atrioventricular block, the choice between single-chamber or dual-chamber pacing is unlikely to influence the risk of death from all causes or of cardiovascular events in the early years after pacemaker implantation.
William D. Toff, M.D.
University of Leicester Glenfield Hospital
Leicester LE3 9QP, United Kingdom
w.toff@le.ac.uk
A. John Camm, M.D.
St. George's University of London
London SW17 0RE, United Kingdom
J. Douglas Skehan, M.B., B.S.
University Hospitals of Leicester NHS Trust
Leicester LE3 9QP, United Kingdom
for the UKPACE Trial Investigators
References
Gregoratos G, Cheitlin MD, Conill A, et al. ACC/AHA guidelines for implantation of cardiac pacemakers and antiarrhythmia devices: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Pacemaker Implantation). J Am Coll Cardiol 1998;31:1175-1209.
Ovsyshcher IE, Crystal E. VDD pacing: underevaluated, undervalued and underused. Pacing Clin Electrophysiol 2004;27:1335-1338.
Primatesta P, Brookes M, Poulter NR. Improved hypertension management and control: results from the Health Survey for England 1998. Hypertension 2001;38:827-832.
Toff WD, Skehan JD, De Bono DP, Camm AJ. The United Kingdom Pacing and Cardiovascular Events (UKPACE) trial. Heart 1997;78:221-223.
Toff WD, Camm AJ, Skehan JD. Low incidence of pacemaker syndrome in elderly patients paced for high-grade atrioventricular block. Heart Rhythm 2004;1:383-383.