- Email: [email protected]
Rate control during atrial fibrillation achieved by chronic endocardial vagal stimulation: Proof of principle
EDITORIAL COMMENTARY
Rate control during atrial fibrillation achieved by chronic endocardial vagal stimulation: Proof of principle Janet M. McComb, MD From the Freeman Hospital, Newcastle upon Tyne, United Kingdom.
Atrial fibrillation and heart failure Atrial fibrillation and heart failure have together been described as a dual epidemic.1 The prevalence of both increases with increasing age.2,3 Atrial fibrillation affects 1% of the population, and heart failure 2%.3 The 2 conditions may occur in the same patients, perhaps as a result of risk factors in common,1 or because complex relationships exist between the 2: 41% of people with heart failure have atrial fibrillation at some stage, and 42% of patients with atrial fibrillation have heart failure.4 There are a variety of therapeutic options available, involving either rate control with atrioventricular (AV) node blocking drugs, or AV node ablation and permanent pacing, or rhythm control, achieved with antiarrhythmic drugs or pulmonary vein isolation.1 Both strategies have equivalent results in patients selected for study either because of atrial fibrillation alone5 or with both atrial fibrillation and heart failure,6 and neither is ideal.
Vagal stimulation to achieve rate control during atrial fibrillation In this issue of Heart Rhythm, Bianchi et al.7 describe the chronic application of a novel technique that has already been used in animals to control the ventricular rate during atrial fibrillation in humans.
Acute animal studies Slowing of the ventricular response during atrial fibrillation was shown acutely in vitro in rabbit hearts using postganglionic vagal stimulation,8 and in vivo in dogs9 –12 using stimulation of the epicardial AV node fat pad at the junction of the inferior vena cava and the left atrium. Significant increases in blood pressure and stroke volume during atrial fibrillation occur when rate slowing is induced by vagal stimulation.10 The importance of regularization of the heart rate by ventricular pacing during vagally induced slowing has been emphasized,11 although vagal stimulation to achieve the same heart rate as in sinus rhythm was shown to be superior to right ventricular pacing either with a regular rate, or with Address reprint requests and correspondence: Dr. Janet M. McComb, Freeman Hospital, Newcastle upon Tyne, NE7 7DN, United Kingdom. E-mail address: [email protected].
an irregular rate, derived from RR intervals collected during atrial fibrillation.9
Chronic animal studies Schauerte et al.13 showed that vagal stimulation using a basket catheter positioned in either the superior vena cava, the coronary sinus, or the right pulmonary artery in openchest dogs could be maintained for up to 20 hours, and Zhang et al.12 were able to maintain vagal stimulation via the epicardial AV node fat pad in dogs for up to 6 months.
Acute studies during atrial fibrillation in humans Rossi et al.14 have used epicardial vagal stimulation in a small series of patients undergoing coronary artery bypass graft surgery. Functional complete AV block was achieved intraoperatively in 91%; AF was induced in 41%, which persisted until cardioplegia was given. Atrial tachycardia that terminated as soon as stimulation ceased was induced in 31%. No atrial arrhythmias were induced in 28%. Diaphragmatic stimulation occurred in 21%. Post-operatively, atrial fibrillation occurred in 44%. Vagal stimulation was applied, along with amiodarone infusion, achieving satisfactory rate slowing, allowing ventricular pacing. Sinus rhythm resumed within 90 minutes in 36%; 2 of these developed atrial tachycardia during stimulation. The remaining 64% were cardioverted. One patient experienced diaphragmatic stimulation. Endocardial vagal stimulation also has been used in the short term in humans. Quan et al.15 showed rate slowing during atrial fibrillation using vagal stimulation applied to either the posteroseptal space or the proximal coronary sinus using a temporary pacing catheter during electrophysiology study. Bianchi et al.16 have described management of a patient with cardiogenic shock and atrial fibrillation with an uncontrolled ventricular response using a temporary endocardial pacing lead positioned in the posteroseptal area of the right atrium and an external high-frequency stimulator. Achievement of AV block using this technique facilitated left ventricular pacing, and this combination allowed improvement sufficient to discontinue vagal stimulation after 4 days, and recovery to leave hospital.
1547-5271/$ -see front matter © 2009 Heart Rhythm Society. All rights reserved.
doi:10.1016/j.hrthm.2009.05.023
1288 In this issue, Bianchi et al.7 describe the next stage in the pathway from scientific observation in the laboratory to therapeutic option in clinical practice. They have shown that it is possible to implant standard permanent pacing leads in a right posteroseptal site, where high-frequency stimulation achieved AV block. The lead was then attached to a standard implantable cardioverter-defibrillator that could deliver brief bursts of 50-Hz stimulation. AV-node vagal stimulation was achieved using this system both acutely, at implantation, and chronically, 3 months later. Complications included obvious atrial lead displacement in 1, ventricular capture during atrial threshold testing, attributed to microdisplacement in 1, induction of atrial fibrillation (which terminated spontaneously) during high-frequency stimulation in 42%, and pain at high-output high-frequency stimulation in 1.7 Quan et al.15 in their acute study also noted stinging discomfort in 2 of 18 patients. Because chronic use of this type of stimulation will require an implanted generator, and because the energy, charge, and voltages required to achieve rate slowing are within the capacity of conventional pacemakers,17 it is likely that it will be developed initially for patients who already have indications for permanent pacing, cardiac resynchronization therapy, and implantable cardioverter-defibrillator therapy. Rate control during atrial fibrillation has particular advantages in these patients. Atrial fibrillation with a rapid ventricular response is the most common reason for patients with implanted defibrillators receiving inappropriate shocks, and such shocks are associated with excess mortality.18 Avoiding them when possible is obviously desirable, and more effective rate control during atrial fibrillation might achieve that. Atrial arrhythmias are also the most common cause of interruption of cardiac resynchronization therapy.19 The importance of rate control, often by AV node ablation, has been emphasized to maximize the benefits of cardiac resynchronization therapy in patients with atrial fibrillation.20 Clearly, there is much more to be done before this technique can be assessed in routine clinical practice. Technical challenges are probably greater than clinical ones. Technical developments will be required to allow therapy delivery in association with conventional pacing and shock therapy. High-frequency stimulation for possibly prolonged periods may be required, and early battery depletion will be a concern. Interference with routine device sensing may be problematic. There are also obvious concerns about the inadvertent induction of ventricular arrhythmias, either because of high output stimulation or atrial lead displacement. At this early stage, Bianchi et al.7 provide proof of principle.
Heart Rhythm, Vol 6, No 9, September 2009
References 1. Anter E, Jessup M, Callans DJ. Atrial fibrillation and heart failure: treatment considerations for a dual epidemic. Circulation 2009;119:2516 –2525. 2. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors In Atrial Fibrillation (ATRIA) study. JAMA 2001;285:2370 –2375. 3. Redfield MM, Jacobsen SJ, Burnett JC, Jr., Mahoney DW, Bailey KR, Rodeheffer RJ. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA 2003;289: 194 –202. 4. Wang TJ, Larson MG, Levy D, et al. Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study. Circulation 2003;107:2920 –2925. 5. de Denus S, Sanoski CA, Carlsson J, Opolski G, Spinler SA. Rate vs rhythm control in patients with atrial fibrillation: a meta-analysis. Arch Intern Med 2005;165:258 –262. 6. Roy D, Talajic M, Nattel S, et al. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med 2008;358:2667–2677. 7. Bianchi S, Rossi P, Della Scalla A, et al. Atrioventricular node vagal stimulation by transvenous permanent lead implantation to modulate AV node function: safety and feasibility in humans. Heart Rhythm 2009;6:1282–1286. 8. Mazgalev TN, Garrigue S, Mowrey KA, Yamanouchi Y, Tchou PJ. Autonomic modification of the atrioventricular node during atrial fibrillation: role in the slowing of ventricular rate. Circulation 1999;99:2806 –2814. 9. Zhuang S, Zhang Y, Mowrey KA, et al. Ventricular rate control by selective vagal stimulation is superior to rhythm regularization by atrioventricular nodal ablation and pacing during atrial fibrillation. Circulation 2002;106:1853–1858. 10. Wallick DW, Zhang Y, Tabata T, et al. Selective AV nodal vagal stimulation improves hemodynamics during acute atrial fibrillation in dogs. Am J Physiol Heart Circ Physiol 2001;281:H1490 –H1497. 11. Zhang Y, Mazgalev T. Achieving regular slow rhythm during atrial fibrillation without atrioventricular nodal ablation: selective vagal stimulation plus ventricular pacing. Heart Rhythm 2004;1:469 – 475. 12. Zhang Y, Yamada H, Bibevski S, et al. Chronic atrioventricular nodal vagal stimulation: first evidence for long-term ventricular rate control in canine atrial fibrillation model. Circulation 2005;112:2904 –2911. 13. Schauerte P, Scherlag BJ, Scherlag MA, Goli S, Jackman WM, Lazzara R. Ventricular rate control during atrial fibrillation by cardiac parasympathetic nerve stimulation: a transvenous approach. J Am Coll Cardiol 1999;34:2043– 2050. 14. Rossi P, Bianchi S, Barretta A, et al. Post-operative atrial fibrillation management by selective epicardial vagal fat pad stimulation. J Interv Card Electrophysiol 2009;24:37– 45. 15. Quan KJ, Van Hare GF, Biblo LA, Mackall JA, Carlson MD. Endocardial stimulation of efferent parasympathetic nerves to the atrioventricular node in humans: optimal stimulation sites and the effects of digoxin. J Interv Card Electrophysiol 2001;5:145–152. 16. Bianchi S, Rossi P, Della Scala A, Kornet L. Endocardial transcatheter stimulation of the AV nodal fat pad: stabilization of rapid ventricular rate response during atrial fibrillation in left ventricular failure. J Card Electrophysiol 2009; 20:103–105. 17. Soos P, Merkely B, Horvat P, Zima E, Schauerte P. Determinants and effects of electrical stimulation of the inferior interatrial parasympathetic plexus during atrial fibrillation. J Cardiovasc Electrophysiol 2005;16:1362–1367. 18. Daubert JP, Zareba W, Cannom DS, et al. Inappropriate implantable cardioverter-defibrillator shocks in MADIT II: frequency, mechanisms, predictors, and survival impact. J Am Coll Cardiol 2008;51:1357–1365. 19. Knight BP, Desai A, Coman J, Faddis M, Yong P. Long-term retention of cardiac resynchronization therapy. J Am Coll Cardiol 2004;44:72–77. 20. Gasparini M, Auricchio A, Regoli F, et al. Four-year efficacy of cardiac resynchronization therapy on exercise tolerance and disease progression: the importance of performing atrioventricular junction ablation in patients with atrial fibrillation. J Am Coll Cardiol 2006;48:734 –743.
Rate control during atrial fibrillation achieved by chronic endocardial vagal stimulation: Proof of principle Janet M. McComb, MD From the Freeman Hospital, Newcastle upon Tyne, United Kingdom.
Atrial fibrillation and heart failure Atrial fibrillation and heart failure have together been described as a dual epidemic.1 The prevalence of both increases with increasing age.2,3 Atrial fibrillation affects 1% of the population, and heart failure 2%.3 The 2 conditions may occur in the same patients, perhaps as a result of risk factors in common,1 or because complex relationships exist between the 2: 41% of people with heart failure have atrial fibrillation at some stage, and 42% of patients with atrial fibrillation have heart failure.4 There are a variety of therapeutic options available, involving either rate control with atrioventricular (AV) node blocking drugs, or AV node ablation and permanent pacing, or rhythm control, achieved with antiarrhythmic drugs or pulmonary vein isolation.1 Both strategies have equivalent results in patients selected for study either because of atrial fibrillation alone5 or with both atrial fibrillation and heart failure,6 and neither is ideal.
Vagal stimulation to achieve rate control during atrial fibrillation In this issue of Heart Rhythm, Bianchi et al.7 describe the chronic application of a novel technique that has already been used in animals to control the ventricular rate during atrial fibrillation in humans.
Acute animal studies Slowing of the ventricular response during atrial fibrillation was shown acutely in vitro in rabbit hearts using postganglionic vagal stimulation,8 and in vivo in dogs9 –12 using stimulation of the epicardial AV node fat pad at the junction of the inferior vena cava and the left atrium. Significant increases in blood pressure and stroke volume during atrial fibrillation occur when rate slowing is induced by vagal stimulation.10 The importance of regularization of the heart rate by ventricular pacing during vagally induced slowing has been emphasized,11 although vagal stimulation to achieve the same heart rate as in sinus rhythm was shown to be superior to right ventricular pacing either with a regular rate, or with Address reprint requests and correspondence: Dr. Janet M. McComb, Freeman Hospital, Newcastle upon Tyne, NE7 7DN, United Kingdom. E-mail address: [email protected].
an irregular rate, derived from RR intervals collected during atrial fibrillation.9
Chronic animal studies Schauerte et al.13 showed that vagal stimulation using a basket catheter positioned in either the superior vena cava, the coronary sinus, or the right pulmonary artery in openchest dogs could be maintained for up to 20 hours, and Zhang et al.12 were able to maintain vagal stimulation via the epicardial AV node fat pad in dogs for up to 6 months.
Acute studies during atrial fibrillation in humans Rossi et al.14 have used epicardial vagal stimulation in a small series of patients undergoing coronary artery bypass graft surgery. Functional complete AV block was achieved intraoperatively in 91%; AF was induced in 41%, which persisted until cardioplegia was given. Atrial tachycardia that terminated as soon as stimulation ceased was induced in 31%. No atrial arrhythmias were induced in 28%. Diaphragmatic stimulation occurred in 21%. Post-operatively, atrial fibrillation occurred in 44%. Vagal stimulation was applied, along with amiodarone infusion, achieving satisfactory rate slowing, allowing ventricular pacing. Sinus rhythm resumed within 90 minutes in 36%; 2 of these developed atrial tachycardia during stimulation. The remaining 64% were cardioverted. One patient experienced diaphragmatic stimulation. Endocardial vagal stimulation also has been used in the short term in humans. Quan et al.15 showed rate slowing during atrial fibrillation using vagal stimulation applied to either the posteroseptal space or the proximal coronary sinus using a temporary pacing catheter during electrophysiology study. Bianchi et al.16 have described management of a patient with cardiogenic shock and atrial fibrillation with an uncontrolled ventricular response using a temporary endocardial pacing lead positioned in the posteroseptal area of the right atrium and an external high-frequency stimulator. Achievement of AV block using this technique facilitated left ventricular pacing, and this combination allowed improvement sufficient to discontinue vagal stimulation after 4 days, and recovery to leave hospital.
1547-5271/$ -see front matter © 2009 Heart Rhythm Society. All rights reserved.
doi:10.1016/j.hrthm.2009.05.023
1288 In this issue, Bianchi et al.7 describe the next stage in the pathway from scientific observation in the laboratory to therapeutic option in clinical practice. They have shown that it is possible to implant standard permanent pacing leads in a right posteroseptal site, where high-frequency stimulation achieved AV block. The lead was then attached to a standard implantable cardioverter-defibrillator that could deliver brief bursts of 50-Hz stimulation. AV-node vagal stimulation was achieved using this system both acutely, at implantation, and chronically, 3 months later. Complications included obvious atrial lead displacement in 1, ventricular capture during atrial threshold testing, attributed to microdisplacement in 1, induction of atrial fibrillation (which terminated spontaneously) during high-frequency stimulation in 42%, and pain at high-output high-frequency stimulation in 1.7 Quan et al.15 in their acute study also noted stinging discomfort in 2 of 18 patients. Because chronic use of this type of stimulation will require an implanted generator, and because the energy, charge, and voltages required to achieve rate slowing are within the capacity of conventional pacemakers,17 it is likely that it will be developed initially for patients who already have indications for permanent pacing, cardiac resynchronization therapy, and implantable cardioverter-defibrillator therapy. Rate control during atrial fibrillation has particular advantages in these patients. Atrial fibrillation with a rapid ventricular response is the most common reason for patients with implanted defibrillators receiving inappropriate shocks, and such shocks are associated with excess mortality.18 Avoiding them when possible is obviously desirable, and more effective rate control during atrial fibrillation might achieve that. Atrial arrhythmias are also the most common cause of interruption of cardiac resynchronization therapy.19 The importance of rate control, often by AV node ablation, has been emphasized to maximize the benefits of cardiac resynchronization therapy in patients with atrial fibrillation.20 Clearly, there is much more to be done before this technique can be assessed in routine clinical practice. Technical challenges are probably greater than clinical ones. Technical developments will be required to allow therapy delivery in association with conventional pacing and shock therapy. High-frequency stimulation for possibly prolonged periods may be required, and early battery depletion will be a concern. Interference with routine device sensing may be problematic. There are also obvious concerns about the inadvertent induction of ventricular arrhythmias, either because of high output stimulation or atrial lead displacement. At this early stage, Bianchi et al.7 provide proof of principle.
Heart Rhythm, Vol 6, No 9, September 2009
References 1. Anter E, Jessup M, Callans DJ. Atrial fibrillation and heart failure: treatment considerations for a dual epidemic. Circulation 2009;119:2516 –2525. 2. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors In Atrial Fibrillation (ATRIA) study. JAMA 2001;285:2370 –2375. 3. Redfield MM, Jacobsen SJ, Burnett JC, Jr., Mahoney DW, Bailey KR, Rodeheffer RJ. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA 2003;289: 194 –202. 4. Wang TJ, Larson MG, Levy D, et al. Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study. Circulation 2003;107:2920 –2925. 5. de Denus S, Sanoski CA, Carlsson J, Opolski G, Spinler SA. Rate vs rhythm control in patients with atrial fibrillation: a meta-analysis. Arch Intern Med 2005;165:258 –262. 6. Roy D, Talajic M, Nattel S, et al. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med 2008;358:2667–2677. 7. Bianchi S, Rossi P, Della Scalla A, et al. Atrioventricular node vagal stimulation by transvenous permanent lead implantation to modulate AV node function: safety and feasibility in humans. Heart Rhythm 2009;6:1282–1286. 8. Mazgalev TN, Garrigue S, Mowrey KA, Yamanouchi Y, Tchou PJ. Autonomic modification of the atrioventricular node during atrial fibrillation: role in the slowing of ventricular rate. Circulation 1999;99:2806 –2814. 9. Zhuang S, Zhang Y, Mowrey KA, et al. Ventricular rate control by selective vagal stimulation is superior to rhythm regularization by atrioventricular nodal ablation and pacing during atrial fibrillation. Circulation 2002;106:1853–1858. 10. Wallick DW, Zhang Y, Tabata T, et al. Selective AV nodal vagal stimulation improves hemodynamics during acute atrial fibrillation in dogs. Am J Physiol Heart Circ Physiol 2001;281:H1490 –H1497. 11. Zhang Y, Mazgalev T. Achieving regular slow rhythm during atrial fibrillation without atrioventricular nodal ablation: selective vagal stimulation plus ventricular pacing. Heart Rhythm 2004;1:469 – 475. 12. Zhang Y, Yamada H, Bibevski S, et al. Chronic atrioventricular nodal vagal stimulation: first evidence for long-term ventricular rate control in canine atrial fibrillation model. Circulation 2005;112:2904 –2911. 13. Schauerte P, Scherlag BJ, Scherlag MA, Goli S, Jackman WM, Lazzara R. Ventricular rate control during atrial fibrillation by cardiac parasympathetic nerve stimulation: a transvenous approach. J Am Coll Cardiol 1999;34:2043– 2050. 14. Rossi P, Bianchi S, Barretta A, et al. Post-operative atrial fibrillation management by selective epicardial vagal fat pad stimulation. J Interv Card Electrophysiol 2009;24:37– 45. 15. Quan KJ, Van Hare GF, Biblo LA, Mackall JA, Carlson MD. Endocardial stimulation of efferent parasympathetic nerves to the atrioventricular node in humans: optimal stimulation sites and the effects of digoxin. J Interv Card Electrophysiol 2001;5:145–152. 16. Bianchi S, Rossi P, Della Scala A, Kornet L. Endocardial transcatheter stimulation of the AV nodal fat pad: stabilization of rapid ventricular rate response during atrial fibrillation in left ventricular failure. J Card Electrophysiol 2009; 20:103–105. 17. Soos P, Merkely B, Horvat P, Zima E, Schauerte P. Determinants and effects of electrical stimulation of the inferior interatrial parasympathetic plexus during atrial fibrillation. J Cardiovasc Electrophysiol 2005;16:1362–1367. 18. Daubert JP, Zareba W, Cannom DS, et al. Inappropriate implantable cardioverter-defibrillator shocks in MADIT II: frequency, mechanisms, predictors, and survival impact. J Am Coll Cardiol 2008;51:1357–1365. 19. Knight BP, Desai A, Coman J, Faddis M, Yong P. Long-term retention of cardiac resynchronization therapy. J Am Coll Cardiol 2004;44:72–77. 20. Gasparini M, Auricchio A, Regoli F, et al. Four-year efficacy of cardiac resynchronization therapy on exercise tolerance and disease progression: the importance of performing atrioventricular junction ablation in patients with atrial fibrillation. J Am Coll Cardiol 2006;48:734 –743.