European Journal of Heart Failure (2014) 16, 1157–1159 doi:10.1002/ejhf.189
EDITORIAL
How do patients with previous RV pacing respond to upgrading to CRT? Important messages for pacemaker and ICD follow-up Cecilia Linde1,2,* Institutet, Department of Medicine, Stockholm, Sweden; and 2 Karolinska University Hospital, Department of Cardiology, Stockholm, Sweden
The opinions expressed in this article are not necessarily those of the Editors of the European Journal of Heart Failure or of the European Society of Cardiology. This article refers to ‘Echocardiographic and clinical response to cardiac resynchronization therapy in heart failure patients with and without previous right ventricular pacing’, by R.M.. Page et al. on page XXX Before the pacemaker era, patients with life-threatening bradycardia died. The invention of the implantable ventricular pacemaker almost 50 years ago improved survival. In the 1980s it was believed that physiological pacing by adding an atrial lead to the right ventricular (RV) lead to maintain atrioventricular (AV) synchrony would further promote survival in paced patients. Although such AV synchronous (DDD) pacing was indeed superior regarding exercise tolerance and quality of life, it did not improve survival when compared with VVI in randomized controlled trials (RCTs) either in patients with complete degree AV block1 or in those with mixed bradycardias.2 There was thus no evidence to suggest that the presence or absence of AV synchrony (VVI) would influence survival in patients paced for bradycardia. Instead, prognosis and morbidity were shown to be related to the extent of RV pacing.3 Unlike in UKPACE1 and CTOPP,2 the MOST3 trial only included patients with sinus node disease. Such patients often have normal AV conduction and hence are not expected to be dependent on RV pacing like those with complete AV block. In MOST, a high extent of RV pacing of >40% was related to greater need for heart failure (HF) hospitalizations.3 Cumulative percentage RV pacing was greater in those randomized to DDD than to VVI pacing. This relationship was later corroborated in implantable cardioverter defibrillator (ICD) trials. In the DAVID trial,4 patients with an indication for an ICD were randomized to single- or dual-chamber ICD. Unlike in MOST, patients in DAVID were not free from HF or LV dysfunction at the study start. Their mean LVEF was 28%, and 50% had NYHA class II–IV HF. The extent of delivered ventricular pacing was >60% in the dual-chamber ICD arm and only 1% in the single-chamber ICD arm. Dual-chamber ICD was linked to increased risk of death and hospitalizations for new or worsened
..............................................................................................................
1 Karolinska
HF. Like in MOST,3 this negative effect was present in those RV paced ≥41%. Hence modern device programming of ICDs and pacemakers aims to avoid unnecessary RV pacing. Taken together, the results of the MOST and DAVID4 studies suggest that RV pacing when delivered (and not needed) may induce ventricular dyssynchrony and result in HF over time. Neither the MOST nor the DAVID trials, however, evaluated ventricular function over time. In the PACE trial,5 Yu et al. studied LV function over 1 year in patients with normal LVEF randomly assigned to CRT or VVI pacing due to bradycardia. While LV function remained preserved in those assigned to CRT, there was a significant deterioration in the VVI group, with a further deterioration over the second year. The extent of ventricular pacing was close to 100% in both randomization arms. These findings suggest that CRT can prevent deterioration of LV function in patients with 100% ventricular pacing, at least in those with initially healthy left ventricles and no HF symptoms. It is well known that LV activation in LBBB is delayed and dyssynchronous.6 Chronic RV pacing results in a similar LBBB contraction pattern; but not, however, identical to intrinsic LBBB.6 In the study now published in this issue by Gage et al.,7 echocardiographic and clinical response to CRT was compared in HF patients with our without previous significant RV pacing defined as a history of at least 40% RV pacing. The criteria for CRT implantation were otherwise conventional. Patients with previous RV pacing were older and more often had AF than those not paced at all or with a previous limited extent of RV pacing 40% and, even so, many may not develop HF. Secondly, RV pacing-induced LV dysfunction appears to create a separate and less severe disease state that responds particularly well to CRT. Thirdly, the complication rate of device implantation is related to the number of leads,12 so it may be wise to wait to implant an LV lead until needed. Fourthly, and most importantly, the results emphasize the need for a strict follow-up of paced patients including always recording the extent of ventricular pacing (often done), to perform regular echocardiograms in those with >40% RV pacing (less often done), and to consider upgrading in the case of deterioration of LV function. Since pacemaker and ICD follow-up are performed by different professional groups and sometimes by remote follow-up, we may need to improve our routines to spare patients from unnecessary development of HF.
Funding C.L. was supported by the Swedish Heart Lung Foundation [grants 20080498 and 20110406] and the Stockholm County Council [grants 20090376 and 20110610]. No funding organization had any role in the collection, analysis, or interpretation of data or approval/disapproval for publication. Conflict of interest: C.L. was principal investigator of REVERSE, a CRT study sponsored by Medtronic; and reports research grants, speaker honoraria, and consulting fees from Medtronic, and speaker honoraria and consulting fees from St. Jude Medical. © 2014 The Authors European Journal of Heart Failure © 2014 European Society of Cardiology
1159
References 1. Toff WD, Camm AJ, Skehan D. for the United Kingdom Pacing and Cardiovascular Events (UKPACE) Trial Investigators. Single-chamber versus dual-chamber pacing for high-grade atrioventricular block. N Engl J Med 2005;353:145–155. 2. Kerr CR, Connolly SJ, Abdollah HA, Toberts RS, Gent M, Yusuf S, Gillis AM, Tang AS, Talajic M, Klein GJ, Newman DM. Canadian Trial of Physiological Pacing: effects of physiological pacing during long-term follow-up. Circulation 2004;109:357–362. 3. Sweeney MO, Hellkamp AS, Ellenbogen KA, Greenspon AJ, Freedman RA, Lee KL, Lamas GA, MOde Selection Trial Investigators. Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in clinical trial of pacemaker therapy for sinus node dysfunction. Circulation 2003;107:2932–2937. 4. The Dual Chamber and VVI implantable Defibrillator (DAVID) trial. Dual chamber pacing or ventricular backup pacing in patients with an implantable defibrillator. JAMA 2002;288:3115–3123. 5. Yu CM, Chan JYS, Zhang Q, Omar R, Yip GWK, Hussin A, Fang F, Lam KH, Chan HC, Fung JW. Biventricular pacing in patients with bradycardia and normal ejection fraction. N Engl J Med 2009;361:2123–2134. 6. Bank AJ, Schwarzman DS, Burns KV, Kaufman CL, Adler SW, Kelly AS, Johnson L, Kaiser DR. Intramural dyssynchrony from acute right ventricular apical pacing in human subjects with normal left ventricular function. J Cardiovasc Trans Res 2010;3:321–329. 7. Gage RM, Burns KV, Bank AJ. Echocardiographic and clinical response to cardiac resynchronization therapy in heart failure patients with and without previous right ventricular pacing. Eur J Heart Fail 2014;16:XXX–XXX.
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Editorial
© 2014 The Authors European Journal of Heart Failure © 2014 European Society of Cardiology
8. European Society of Cardiology (ESC); European Heart Rhythm Association (EHRA), Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G, Breithardt OA, Cleland J, Deharo JC, Delgado V, Elliott PM, Gorenek B, Israel CW, Leclercq C, Linde C, Mont L, Padeletti L, Sutton R, Vardas PE. 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Europace 2013;15:1070–1118. 9. Bogale N, Witte K, Priori S, Auricchio A, Cleland J, Gitt A, Limbourg T, Linde C, Dickstein K, Scientific Committee, National coordinators and the investigators. The European Cardiac Resynchronization Therapy Survey: comparison of outcomes between de novo cardiac resynchronization therapy implantations and upgrades. Eur J Heart Fail 2011;13:974–984. 10. Curtis AB, Worley SJ, Adamson PB, Chung ES, Niazi I, Sherfesee L, Shinn T, Sutton MS, Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) Trial Investigators. Biventricular pacing for atrioventricular block an systolic dysfunction. N Engl J Med 2013;368:1585–1593. 11. Funck RC, Mueller HH, Lunati M, Piorkowski C, De Roy L, Paul V, Wittenberg M, Wuensch D, Blanc JJ, BioPace study group. Characteristics of a large sample size of candidates for permanent ventricular pacing included in the biventricular pacing for atrioventricular block to prevent cardiac desynchronization study (BioPace). Europace 2014;16:354–362. 12. Kirkfeldt RE, Johansen JB, Nohr EA, Jörgensen OD, Nielsen JC. Complications after cardiac implantable electronic device implantations: an analysis of a complete nationwide cohort in Denmark. Eur Heart J 2014;35:1186–1194.
Copyright of European Journal of Heart Failure is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
EDITORIAL
How do patients with previous RV pacing respond to upgrading to CRT? Important messages for pacemaker and ICD follow-up Cecilia Linde1,2,* Institutet, Department of Medicine, Stockholm, Sweden; and 2 Karolinska University Hospital, Department of Cardiology, Stockholm, Sweden
The opinions expressed in this article are not necessarily those of the Editors of the European Journal of Heart Failure or of the European Society of Cardiology. This article refers to ‘Echocardiographic and clinical response to cardiac resynchronization therapy in heart failure patients with and without previous right ventricular pacing’, by R.M.. Page et al. on page XXX Before the pacemaker era, patients with life-threatening bradycardia died. The invention of the implantable ventricular pacemaker almost 50 years ago improved survival. In the 1980s it was believed that physiological pacing by adding an atrial lead to the right ventricular (RV) lead to maintain atrioventricular (AV) synchrony would further promote survival in paced patients. Although such AV synchronous (DDD) pacing was indeed superior regarding exercise tolerance and quality of life, it did not improve survival when compared with VVI in randomized controlled trials (RCTs) either in patients with complete degree AV block1 or in those with mixed bradycardias.2 There was thus no evidence to suggest that the presence or absence of AV synchrony (VVI) would influence survival in patients paced for bradycardia. Instead, prognosis and morbidity were shown to be related to the extent of RV pacing.3 Unlike in UKPACE1 and CTOPP,2 the MOST3 trial only included patients with sinus node disease. Such patients often have normal AV conduction and hence are not expected to be dependent on RV pacing like those with complete AV block. In MOST, a high extent of RV pacing of >40% was related to greater need for heart failure (HF) hospitalizations.3 Cumulative percentage RV pacing was greater in those randomized to DDD than to VVI pacing. This relationship was later corroborated in implantable cardioverter defibrillator (ICD) trials. In the DAVID trial,4 patients with an indication for an ICD were randomized to single- or dual-chamber ICD. Unlike in MOST, patients in DAVID were not free from HF or LV dysfunction at the study start. Their mean LVEF was 28%, and 50% had NYHA class II–IV HF. The extent of delivered ventricular pacing was >60% in the dual-chamber ICD arm and only 1% in the single-chamber ICD arm. Dual-chamber ICD was linked to increased risk of death and hospitalizations for new or worsened
..............................................................................................................
1 Karolinska
HF. Like in MOST,3 this negative effect was present in those RV paced ≥41%. Hence modern device programming of ICDs and pacemakers aims to avoid unnecessary RV pacing. Taken together, the results of the MOST and DAVID4 studies suggest that RV pacing when delivered (and not needed) may induce ventricular dyssynchrony and result in HF over time. Neither the MOST nor the DAVID trials, however, evaluated ventricular function over time. In the PACE trial,5 Yu et al. studied LV function over 1 year in patients with normal LVEF randomly assigned to CRT or VVI pacing due to bradycardia. While LV function remained preserved in those assigned to CRT, there was a significant deterioration in the VVI group, with a further deterioration over the second year. The extent of ventricular pacing was close to 100% in both randomization arms. These findings suggest that CRT can prevent deterioration of LV function in patients with 100% ventricular pacing, at least in those with initially healthy left ventricles and no HF symptoms. It is well known that LV activation in LBBB is delayed and dyssynchronous.6 Chronic RV pacing results in a similar LBBB contraction pattern; but not, however, identical to intrinsic LBBB.6 In the study now published in this issue by Gage et al.,7 echocardiographic and clinical response to CRT was compared in HF patients with our without previous significant RV pacing defined as a history of at least 40% RV pacing. The criteria for CRT implantation were otherwise conventional. Patients with previous RV pacing were older and more often had AF than those not paced at all or with a previous limited extent of RV pacing 40% and, even so, many may not develop HF. Secondly, RV pacing-induced LV dysfunction appears to create a separate and less severe disease state that responds particularly well to CRT. Thirdly, the complication rate of device implantation is related to the number of leads,12 so it may be wise to wait to implant an LV lead until needed. Fourthly, and most importantly, the results emphasize the need for a strict follow-up of paced patients including always recording the extent of ventricular pacing (often done), to perform regular echocardiograms in those with >40% RV pacing (less often done), and to consider upgrading in the case of deterioration of LV function. Since pacemaker and ICD follow-up are performed by different professional groups and sometimes by remote follow-up, we may need to improve our routines to spare patients from unnecessary development of HF.
Funding C.L. was supported by the Swedish Heart Lung Foundation [grants 20080498 and 20110406] and the Stockholm County Council [grants 20090376 and 20110610]. No funding organization had any role in the collection, analysis, or interpretation of data or approval/disapproval for publication. Conflict of interest: C.L. was principal investigator of REVERSE, a CRT study sponsored by Medtronic; and reports research grants, speaker honoraria, and consulting fees from Medtronic, and speaker honoraria and consulting fees from St. Jude Medical. © 2014 The Authors European Journal of Heart Failure © 2014 European Society of Cardiology
1159
References 1. Toff WD, Camm AJ, Skehan D. for the United Kingdom Pacing and Cardiovascular Events (UKPACE) Trial Investigators. Single-chamber versus dual-chamber pacing for high-grade atrioventricular block. N Engl J Med 2005;353:145–155. 2. Kerr CR, Connolly SJ, Abdollah HA, Toberts RS, Gent M, Yusuf S, Gillis AM, Tang AS, Talajic M, Klein GJ, Newman DM. Canadian Trial of Physiological Pacing: effects of physiological pacing during long-term follow-up. Circulation 2004;109:357–362. 3. Sweeney MO, Hellkamp AS, Ellenbogen KA, Greenspon AJ, Freedman RA, Lee KL, Lamas GA, MOde Selection Trial Investigators. Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in clinical trial of pacemaker therapy for sinus node dysfunction. Circulation 2003;107:2932–2937. 4. The Dual Chamber and VVI implantable Defibrillator (DAVID) trial. Dual chamber pacing or ventricular backup pacing in patients with an implantable defibrillator. JAMA 2002;288:3115–3123. 5. Yu CM, Chan JYS, Zhang Q, Omar R, Yip GWK, Hussin A, Fang F, Lam KH, Chan HC, Fung JW. Biventricular pacing in patients with bradycardia and normal ejection fraction. N Engl J Med 2009;361:2123–2134. 6. Bank AJ, Schwarzman DS, Burns KV, Kaufman CL, Adler SW, Kelly AS, Johnson L, Kaiser DR. Intramural dyssynchrony from acute right ventricular apical pacing in human subjects with normal left ventricular function. J Cardiovasc Trans Res 2010;3:321–329. 7. Gage RM, Burns KV, Bank AJ. Echocardiographic and clinical response to cardiac resynchronization therapy in heart failure patients with and without previous right ventricular pacing. Eur J Heart Fail 2014;16:XXX–XXX.
............................................................
Editorial
© 2014 The Authors European Journal of Heart Failure © 2014 European Society of Cardiology
8. European Society of Cardiology (ESC); European Heart Rhythm Association (EHRA), Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G, Breithardt OA, Cleland J, Deharo JC, Delgado V, Elliott PM, Gorenek B, Israel CW, Leclercq C, Linde C, Mont L, Padeletti L, Sutton R, Vardas PE. 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Europace 2013;15:1070–1118. 9. Bogale N, Witte K, Priori S, Auricchio A, Cleland J, Gitt A, Limbourg T, Linde C, Dickstein K, Scientific Committee, National coordinators and the investigators. The European Cardiac Resynchronization Therapy Survey: comparison of outcomes between de novo cardiac resynchronization therapy implantations and upgrades. Eur J Heart Fail 2011;13:974–984. 10. Curtis AB, Worley SJ, Adamson PB, Chung ES, Niazi I, Sherfesee L, Shinn T, Sutton MS, Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK HF) Trial Investigators. Biventricular pacing for atrioventricular block an systolic dysfunction. N Engl J Med 2013;368:1585–1593. 11. Funck RC, Mueller HH, Lunati M, Piorkowski C, De Roy L, Paul V, Wittenberg M, Wuensch D, Blanc JJ, BioPace study group. Characteristics of a large sample size of candidates for permanent ventricular pacing included in the biventricular pacing for atrioventricular block to prevent cardiac desynchronization study (BioPace). Europace 2014;16:354–362. 12. Kirkfeldt RE, Johansen JB, Nohr EA, Jörgensen OD, Nielsen JC. Complications after cardiac implantable electronic device implantations: an analysis of a complete nationwide cohort in Denmark. Eur Heart J 2014;35:1186–1194.
Copyright of European Journal of Heart Failure is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
