- Email: [email protected]
Electrophysiology testing and pacing in octogenarians with unexplained syncope—time to reconsider?
Accepted Manuscript Electrophysiology testing and pacing in octogenarians with unexplained syncopetime to reconsider? Peter Santucci, MD, FHRS PII:
S1547-5271(17)30148-0
DOI:
10.1016/j.hrthm.2017.01.037
Reference:
HRTHM 7017
To appear in:
Heart Rhythm
Received Date: 20 January 2017
Please cite this article as: Santucci P, Electrophysiology testing and pacing in octogenarians with unexplained syncope- time to reconsider?, Heart Rhythm (2017), doi: 10.1016/j.hrthm.2017.01.037. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1 Editorial/ Commentary of JHRM-D-16-01295R1
RI PT
Electrophysiology testing and pacing in octogenarians with unexplained syncope- time to reconsider?
Peter Santucci MD, FHRS. Loyola University Medical Center,
SC
2160 S First Ave, Bldg 110-6220 Maywood, IL 60439
M AN U
[email protected]
Conflict of Interest: None
AC C
EP
TE D
Word Count : 1505
ACCEPTED MANUSCRIPT 2
RI PT
The history of pacemakers represents a triumph in medical engineering and pioneered the use of implantable electronic devices to manage life-threatening conditions. Initial applications of pacemakers were based upon obvious needs. As technology, reliability, and safety grew, so did the uses of these devices to treat conditions that were less clear-cut. Current uses for pacing remain significantly based on historical developments and clinical judgements. Guidelines have been developed from consensus opinion utilizing available data, but data limitations exist. Often, randomized trials of such practices have not been and are unlikely ever to be performed.
SC
In particular, the management of patients with syncope of undetermined etiology remains problematic. Despite significant progress, we still lack clear answers to seemingly simple questions including the appropriate use of EP studies and the exact criteria for pacing based on the results.
TE D
M AN U
With the emergence of ILRs and ICD indications for patients with low ejection fractions, the role for electrophysiological testing in unexplained syncope has diminished over the years. Historically, testing has been insensitive in syncope from bradycardia. In one study of unexplained syncope, the yield of testing was especially low in patients with a normal ECG without organic heart disease (2.6%). 1 Also, testing may reveal unrelated arrhythmias that may mistakenly be designated causal. 2,3 As a high proportion may have nondiagnostic studies, unclear is whether testing should be performed at all. In patients without underlying heart disease, this test is no longer routinely recommended. 4 However, considering the high risk of recurrent syncope with potential harm, the risk- benefit ratio may favor testing in some, particularly those with a malignant episode of syncope. 5,6
AC C
EP
The ACC/AHA/HRS 2008 Device Guidelines give a Class IIa pacing indication for syncope of unexplained origin “when clinically significant abnormalities of sinus node function are discovered or provoked in electrophysiological studies”, but with a Level of Evidence C. In chronic bifascicular block, pacing is a Class IIa indication for syncope “when other likely causes have been excluded”. They state that “although syncope may be recurrent, it is not associated with an increased incidence of sudden death.” and pacing does not reduce sudden death. For potential AV block based on testing (without bifascicular block), pacing indications are unclear. 7 ESC 2013 guidelines state that in patients with unexplained syncope at the end of a complete work-up and absence of any conduction disturbance, pacemaker therapy is not recommended until a diagnosis is made. The value of EP testing in this is not fully defined. 8 With these uncertainties, the current study in this issue of Heart Rhythm by Giannopoulos et al, examining the outcomes of pacemaker implantation in octogenarians with syncope and abnormal EP studies, adds to our knowledge in this area. 9 Patients receiving pacemakers had a significantly lower rate of recurrent syncope and overall mortality compared to a similar population in which pacemakers were not implanted.
ACCEPTED MANUSCRIPT 3
RI PT
This is an observational, retrospective study. The main limitation is the non-randomized nature of the treatment, based on physician judgement, introducing a potential for bias. Baseline characteristics were largely similar between the groups, but those receiving pacers had a higher incidence of LBBB, and averaged two syncopal events vs one for those not implanted (which may have been the main difference for the treatment between arms). This would not clearly suggest the pacemaker group was a lower risk group prior to treatment, though it could conceivably select a group more likely to benefit from pacing. Mulitivariate analysis did not appear to alter the results.
SC
Interestingly, when looking at mortality alone, a lower incidence was seen in those receiving a pacemaker. Particularly, the incidence of sudden death, over about 4 years, was 0.7 % in those receiving a pacemaker vs 6.0% (p=0.015) in those not, suggesting continued observation may not be as benign as previously thought.
M AN U
Beyond the prevention of bradycardic morbidity or mortality, other salutary effects of pacing may have contributed to the observed results. In particular, the diagnosis of AF lead to a higher use of anticoagulation, and we cannot exclude effects on followup intensity, falls, or pause- dependent tachyarrhythmias.
EP
TE D
Despite limitations, this data should be of interest. Questions remain as to the optimal definition of an abnormal study, and the value of pacing when found. Criteria for a positive study vary amongst studies. While not fully answering this question, this study provides much needed additional information to guide decision-making. The definitions of an abnormal study were set to maximize sensitivity, with a “positive” study defined by any of the following: a CSNRT>525 ms, basic HV >55 ms, detection of infraHisian block on atrial pacing or 2nd degree atrioventricular block during atrial pacing at a cycle length >400 ms (after atropine for Wenckebach). Notably, the inclusion of minor HV prolongation >55 ms (rather than >70-100 ms) and 2nd deg AVB at >400 ms are not “standard” criteria, and contributed to a high rate of positive testing, including the screening population that was not limited to octogenarians. This could be related to the criteria or to patient selection. Most patients examined had conduction abnormalities at EPS. This resulting “high yield” of abnormal studies did not, however, lead to a nonspecific population without benefit from pacing.
AC C
An obvious question is whether these results would be similar in those without an abnormal study, and whether the study is needed at all. Elderly patients with unexplained syncope often receive pacemakers despite the absence of a class I indication. Patients with syncope and a baseline bundle branch block, have high rates of asystole even with a negative study. 10 However, the International Study on Syncope of Unexplained Etiology (ISSUE) investigators showed that patients with unexplained syncope, structural heart disease, and negative study had a favorable medium-term outcome with no death and a low recurrence of syncope, without injury. The mechanism of syncope was heterogeneous, and VT was unlikely. Thus, in patients with negative studies, routine device implantation may not be appropriate generally. However, further monitoring (with an ILR) might be. In the specific subgroup of octogenarians, the answer remains unclear. The mean age in the ISSUE study was 66 years. The incidence of bradycardic cause is expected to be higher in octogenarians than in
ACCEPTED MANUSCRIPT 4 younger populations, and perhaps in this group even those with negative testing would benefit from pacing.
RI PT
Overall, at least in this population, this data suggests there may be value to proceeding with an EP study, using criteria that maximize sensitivity, and proceeding to pacing when abnormal. Certainly, further prospective data would be welcome before making more definitive recommendations. However, the mortality difference, as well as the reduction in recurrent syncope seen here should give us pause in using continued observation alone without either an EP study or the placement of a pacemaker.
M AN U
SC
Though medicine has moved increasingly to an evidence based science, it is obvious that many common practices developed historically with limited data. Artful judgement of experienced clinicians and experts has undoubtedly served mankind well many times. However, we still need the additional guidance of data for optimal decisions, particularly when the correct course of action is debatable. This study helps us to make those decisions.
References:
AC C
EP
TE D
1. Sagrista-Sauleda J, Romero-Ferrer B, Moya A, Permanyer-Miralda G, Soler-Soler J. Variations in diagnostic yield of head-up tilt test and electrophysiology in groups of patients with syncope of unknown origin. Eur Heart J 2001;22:857– 65. 2. Fujimura O, Yee R, Klein GJ, Sharma AD, Boahene KA. The diagnostic sensitivity of electrophysiologic testing in patients with syncope caused by transient bradycardia. N Engl J Med. 1989;321:1703–1707. 3. Englund A, Bergfeldt L, Rehnquist N, et al. Diagnostic value of programmed ventricular stimulation in patients with bifascicular block: a prospective study in patients with and without syncope. J Am Coll Cardiol. 1995;26:1508–1515. 4. Moya A, Sutton R, Ammirati F, et al. Guidelines for the diagnosis and management of syncope (version 2009). European Heart J. 2009;30(21):2631–2671. 5. Garcia-Civera R, Ruiz-Granell R, Morell-Cabedo S, et al. Selective use of diagnostic tests in patients with syncope of unknown cause. J Am Coll Cardiol 2003;41:787–90. 6. Strickberger SA, Benson DW, Biaggioni I, et al. AHA/ ACCF scientific statement on the evaluation of syncope. J Am Coll Cardiol 2006;47:473–84. 7. Sweeney M, Page L, Schoenfeld M, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities. Journal of the American College of Cardiology Vol. 51, No. 21, 2008 e1-e62. 8. Brignole M, Auricchio A, Baron-Esquivias G, et al. 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). Eur Heart J. 2013 Aug;34(29):2281-329. 9. Giannopoulos G, Kossyvakis C, Panagopoulou V, Tsiachris D, Doudoumis K, Mavri M, Vrachatis D, Letsas K, Efremidis M, Katsivas A, Lekakis J, Deftereos S. Permanent pacemaker implantation in octogenarians with unexplained syncope and positive electrophysiologic study. Heart Rhythm. 2017.
ACCEPTED MANUSCRIPT 5
AC C
EP
TE D
M AN U
SC
RI PT
10. Brignole M, Menozzi C, Moya A, et al.; International Study on Syncope of Uncertain Etiology (ISSUE) Investigators. Mechanism of Syncope in Patients With Bundle Branch Block and Negative Electrophysiological Test Circulation. 2001;104:2045-2050.
S1547-5271(17)30148-0
DOI:
10.1016/j.hrthm.2017.01.037
Reference:
HRTHM 7017
To appear in:
Heart Rhythm
Received Date: 20 January 2017
Please cite this article as: Santucci P, Electrophysiology testing and pacing in octogenarians with unexplained syncope- time to reconsider?, Heart Rhythm (2017), doi: 10.1016/j.hrthm.2017.01.037. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1 Editorial/ Commentary of JHRM-D-16-01295R1
RI PT
Electrophysiology testing and pacing in octogenarians with unexplained syncope- time to reconsider?
Peter Santucci MD, FHRS. Loyola University Medical Center,
SC
2160 S First Ave, Bldg 110-6220 Maywood, IL 60439
M AN U
[email protected]
Conflict of Interest: None
AC C
EP
TE D
Word Count : 1505
ACCEPTED MANUSCRIPT 2
RI PT
The history of pacemakers represents a triumph in medical engineering and pioneered the use of implantable electronic devices to manage life-threatening conditions. Initial applications of pacemakers were based upon obvious needs. As technology, reliability, and safety grew, so did the uses of these devices to treat conditions that were less clear-cut. Current uses for pacing remain significantly based on historical developments and clinical judgements. Guidelines have been developed from consensus opinion utilizing available data, but data limitations exist. Often, randomized trials of such practices have not been and are unlikely ever to be performed.
SC
In particular, the management of patients with syncope of undetermined etiology remains problematic. Despite significant progress, we still lack clear answers to seemingly simple questions including the appropriate use of EP studies and the exact criteria for pacing based on the results.
TE D
M AN U
With the emergence of ILRs and ICD indications for patients with low ejection fractions, the role for electrophysiological testing in unexplained syncope has diminished over the years. Historically, testing has been insensitive in syncope from bradycardia. In one study of unexplained syncope, the yield of testing was especially low in patients with a normal ECG without organic heart disease (2.6%). 1 Also, testing may reveal unrelated arrhythmias that may mistakenly be designated causal. 2,3 As a high proportion may have nondiagnostic studies, unclear is whether testing should be performed at all. In patients without underlying heart disease, this test is no longer routinely recommended. 4 However, considering the high risk of recurrent syncope with potential harm, the risk- benefit ratio may favor testing in some, particularly those with a malignant episode of syncope. 5,6
AC C
EP
The ACC/AHA/HRS 2008 Device Guidelines give a Class IIa pacing indication for syncope of unexplained origin “when clinically significant abnormalities of sinus node function are discovered or provoked in electrophysiological studies”, but with a Level of Evidence C. In chronic bifascicular block, pacing is a Class IIa indication for syncope “when other likely causes have been excluded”. They state that “although syncope may be recurrent, it is not associated with an increased incidence of sudden death.” and pacing does not reduce sudden death. For potential AV block based on testing (without bifascicular block), pacing indications are unclear. 7 ESC 2013 guidelines state that in patients with unexplained syncope at the end of a complete work-up and absence of any conduction disturbance, pacemaker therapy is not recommended until a diagnosis is made. The value of EP testing in this is not fully defined. 8 With these uncertainties, the current study in this issue of Heart Rhythm by Giannopoulos et al, examining the outcomes of pacemaker implantation in octogenarians with syncope and abnormal EP studies, adds to our knowledge in this area. 9 Patients receiving pacemakers had a significantly lower rate of recurrent syncope and overall mortality compared to a similar population in which pacemakers were not implanted.
ACCEPTED MANUSCRIPT 3
RI PT
This is an observational, retrospective study. The main limitation is the non-randomized nature of the treatment, based on physician judgement, introducing a potential for bias. Baseline characteristics were largely similar between the groups, but those receiving pacers had a higher incidence of LBBB, and averaged two syncopal events vs one for those not implanted (which may have been the main difference for the treatment between arms). This would not clearly suggest the pacemaker group was a lower risk group prior to treatment, though it could conceivably select a group more likely to benefit from pacing. Mulitivariate analysis did not appear to alter the results.
SC
Interestingly, when looking at mortality alone, a lower incidence was seen in those receiving a pacemaker. Particularly, the incidence of sudden death, over about 4 years, was 0.7 % in those receiving a pacemaker vs 6.0% (p=0.015) in those not, suggesting continued observation may not be as benign as previously thought.
M AN U
Beyond the prevention of bradycardic morbidity or mortality, other salutary effects of pacing may have contributed to the observed results. In particular, the diagnosis of AF lead to a higher use of anticoagulation, and we cannot exclude effects on followup intensity, falls, or pause- dependent tachyarrhythmias.
EP
TE D
Despite limitations, this data should be of interest. Questions remain as to the optimal definition of an abnormal study, and the value of pacing when found. Criteria for a positive study vary amongst studies. While not fully answering this question, this study provides much needed additional information to guide decision-making. The definitions of an abnormal study were set to maximize sensitivity, with a “positive” study defined by any of the following: a CSNRT>525 ms, basic HV >55 ms, detection of infraHisian block on atrial pacing or 2nd degree atrioventricular block during atrial pacing at a cycle length >400 ms (after atropine for Wenckebach). Notably, the inclusion of minor HV prolongation >55 ms (rather than >70-100 ms) and 2nd deg AVB at >400 ms are not “standard” criteria, and contributed to a high rate of positive testing, including the screening population that was not limited to octogenarians. This could be related to the criteria or to patient selection. Most patients examined had conduction abnormalities at EPS. This resulting “high yield” of abnormal studies did not, however, lead to a nonspecific population without benefit from pacing.
AC C
An obvious question is whether these results would be similar in those without an abnormal study, and whether the study is needed at all. Elderly patients with unexplained syncope often receive pacemakers despite the absence of a class I indication. Patients with syncope and a baseline bundle branch block, have high rates of asystole even with a negative study. 10 However, the International Study on Syncope of Unexplained Etiology (ISSUE) investigators showed that patients with unexplained syncope, structural heart disease, and negative study had a favorable medium-term outcome with no death and a low recurrence of syncope, without injury. The mechanism of syncope was heterogeneous, and VT was unlikely. Thus, in patients with negative studies, routine device implantation may not be appropriate generally. However, further monitoring (with an ILR) might be. In the specific subgroup of octogenarians, the answer remains unclear. The mean age in the ISSUE study was 66 years. The incidence of bradycardic cause is expected to be higher in octogenarians than in
ACCEPTED MANUSCRIPT 4 younger populations, and perhaps in this group even those with negative testing would benefit from pacing.
RI PT
Overall, at least in this population, this data suggests there may be value to proceeding with an EP study, using criteria that maximize sensitivity, and proceeding to pacing when abnormal. Certainly, further prospective data would be welcome before making more definitive recommendations. However, the mortality difference, as well as the reduction in recurrent syncope seen here should give us pause in using continued observation alone without either an EP study or the placement of a pacemaker.
M AN U
SC
Though medicine has moved increasingly to an evidence based science, it is obvious that many common practices developed historically with limited data. Artful judgement of experienced clinicians and experts has undoubtedly served mankind well many times. However, we still need the additional guidance of data for optimal decisions, particularly when the correct course of action is debatable. This study helps us to make those decisions.
References:
AC C
EP
TE D
1. Sagrista-Sauleda J, Romero-Ferrer B, Moya A, Permanyer-Miralda G, Soler-Soler J. Variations in diagnostic yield of head-up tilt test and electrophysiology in groups of patients with syncope of unknown origin. Eur Heart J 2001;22:857– 65. 2. Fujimura O, Yee R, Klein GJ, Sharma AD, Boahene KA. The diagnostic sensitivity of electrophysiologic testing in patients with syncope caused by transient bradycardia. N Engl J Med. 1989;321:1703–1707. 3. Englund A, Bergfeldt L, Rehnquist N, et al. Diagnostic value of programmed ventricular stimulation in patients with bifascicular block: a prospective study in patients with and without syncope. J Am Coll Cardiol. 1995;26:1508–1515. 4. Moya A, Sutton R, Ammirati F, et al. Guidelines for the diagnosis and management of syncope (version 2009). European Heart J. 2009;30(21):2631–2671. 5. Garcia-Civera R, Ruiz-Granell R, Morell-Cabedo S, et al. Selective use of diagnostic tests in patients with syncope of unknown cause. J Am Coll Cardiol 2003;41:787–90. 6. Strickberger SA, Benson DW, Biaggioni I, et al. AHA/ ACCF scientific statement on the evaluation of syncope. J Am Coll Cardiol 2006;47:473–84. 7. Sweeney M, Page L, Schoenfeld M, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities. Journal of the American College of Cardiology Vol. 51, No. 21, 2008 e1-e62. 8. Brignole M, Auricchio A, Baron-Esquivias G, et al. 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). Eur Heart J. 2013 Aug;34(29):2281-329. 9. Giannopoulos G, Kossyvakis C, Panagopoulou V, Tsiachris D, Doudoumis K, Mavri M, Vrachatis D, Letsas K, Efremidis M, Katsivas A, Lekakis J, Deftereos S. Permanent pacemaker implantation in octogenarians with unexplained syncope and positive electrophysiologic study. Heart Rhythm. 2017.
ACCEPTED MANUSCRIPT 5
AC C
EP
TE D
M AN U
SC
RI PT
10. Brignole M, Menozzi C, Moya A, et al.; International Study on Syncope of Uncertain Etiology (ISSUE) Investigators. Mechanism of Syncope in Patients With Bundle Branch Block and Negative Electrophysiological Test Circulation. 2001;104:2045-2050.