Author's Accepted Manuscript
Finding the optimal ablation site in ventricular tachycardia through a single electrogram: Is it too good to be true? Umjeet S. Jolly MD, Kevin K. Ng MBChB, Allan C. Skanes MD, FHRS
www.elsevier.com/locate/buildenv
PII: DOI: Reference:
S1547-5271(15)00680-3 http://dx.doi.org/10.1016/j.hrthm.2015.05.033 HRTHM6296
To appear in:
Heart Rhythm
Cite this article as: Umjeet S. Jolly MD, Kevin K. Ng MBChB, Allan C. Skanes MD, FHRS, Finding the optimal ablation site in ventricular tachycardia through a single electrogram: Is it too good to be true?, Heart Rhythm, http://dx.doi.org/10.1016/j. hrthm.2015.05.033 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 galley proof before it is published in its final citable 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.
Finding the optimal ablation site in ventricular tachycardia through a single electrogram: Is it too good to be true? Umjeet S. Jolly, MD, Kevin K. Ng, MBChB and Allan C. Skanes, MD, FHRS
Arrhythmia Service Department of Cardiology Schulich School of Medicine Western University London, ON N6A 5A5 Primary contact: [email protected]
Disclosure and Financial Sources: No conflict of interest for all authors and no sources of funding were sought.
Catheter ablation for ventricular tachyarrhyhthmias (VT) has steadily improved in patients with ischaemic cardiomyopathy and in fact, international guidelines recommend its use as an adjunct to antiarrhythmic therapy in patients experiencing appropriate ICD shocks.1,2 The procedure, however, is not without its challenges. Ablation of a VT circuit is dependent on multiple factors, the most important being the identification of a critical isthmus of slow conduction that facilitates re-entry. Slow conduction through surviving fibers of any infarct zone may produce late or isolated diastolic potentials as well as fractionated electrograms that may or may not play a role in a given VT. Studies characterising the spatial relationship between late diastolic potentials and the components of re-entrant VT circuits (entrance, mid-isthmus, exit and outer loops) based on timing alone3,4 have found it difficult to distinguish a critical ablation site from bystander sites.5 Strict entrainment criteria have been invoked to
1
select appropriate ablation target sites,6 but repeated entrainment as a method to identify critical diastolic potentials has a number of practical challenges. First, up to two thirds of patients do not tolerate VT for a sufficient period of time for detailed activation and entrainment mapping.7 Additionally, the clinical VT may not be inducible at the time of the procedure, or mechanical block may be induced during activation mapping rendering the clinical tachycardia non-inducible. Finally, entrainment mapping may convert one VT circuit to another, accelerate the tachycardia or cause its degeneration into ventricular fibrillation. Methods to circumvent these issues have been proposed including mapping scar substrate during sinus rhythm or limited tachycardia but additional manoeuvres are still needed to increase the specificity of the potentials related to the tachycardia isthmus. In the current issue of HeartRhythm, Das et al.8 describe a novel method to determine the importance of a diastolic potential without the need for pacing or entertainment. Specifically, based on timing alone, diastolic potential were identified as bystander or exit sites during VT. They retrospectively analyzed sixteen VTs that were induced in twelve patients with ischemic cardiomyopathy who were undergoing cardiac surgical mapping and cryoablation of VT circuits. High-density activation maps of the entire VT circuit were created, made possible by a combination of surgical access to the ventricle and a specially designed mapping system as pioneered by Dr. Eugene Downar and his group in the mid to late 1990’s.9 Mapping was performed with a custom-made 112, 2mm bipolar electrode endocardial contact array with 1-3 cm spacing recorded on a custom-made 720 channel mapping system. The authors defined the exit site in 2 ways: (1) the location where a transition from diastolic conduction to systolic activation of healthy myocardium was observed and (2) where cryoablation terminated VT. Bystander sites were defined as locations next to identified isthmus locations without continuous activation on surrounding bipoles, essentially identifying ‘dead-ends’ within conduction. These definitions were critically dependent on having mapped and identified the entire VT circuit using the high-resolution methods as noted above. Bipolar electrograms, recorded during VT, were analyzed both manually, and
2
using a spectral analysis technique that limited noise and separated the high frequency near-field components from the low frequency far-field components. On bipolar electrogram analysis, the interval between local activation and surface QRS did not differ significantly between bystander sites and exit sites (60 + 31.5 ms vs 72 + 55 ms, p = 0.63), and the exit site was never found to be less than 20 ms before the surface QRS. However the interval from local near-field activity to far field activity by manual measurement, and spectral analysis, was significantly shorter at exit sites (10.0 + 13.1 ms vs 89.0 + 64.5 ms respectively, p = 0.0003.) Unipolar electrograms did not have a consistent and reliable time point for local activation, and therefore were not used. The authors concluded that component analysis of diastolic electrograms that have a near-field to far-field measurement of approximately 25 ms coupled with a transition from diastolic conduction to systolic activation of healthy myocardium on average 60 ms ahead of the surface QRS suggest an exit site, without the need for pacing manoeuvres. In addition, these values differentiate an exit site not only from a post-exit site, where ablation may have no effect, but also from a bystander site – thereby potentially allowing determination of an optimal ablation site. Does such a simplified measurement make electrophysiological sense? The observation may be conceptually explained by considering a simplified VT circuit with (1) an entry site, (2) a slowly conducting critical isthmus, (3) one or more bystander sites, and (4) an exit site where the wave front leaves the scar and activates the healthy myocardium. Using this model, one can conceptualize why the local signal to surface QRS may not differentiate exit sites from bystander sites. A hypothetical bystander site, activated in parallel with the isthmus, may have the same timing as the exit site, and would therefore have the same near-field timing relative to the QRS. However, because the far-field signal adjacent to the bystander would be activated later, the near-field to far-field timing would be longer. As such, the exit site should have a very short near-field to far-field measurement, whereas bystander sites should have a much longer near-field to far-field measurement. Essentially, relative to
3
the scar, the isthmus generating near field signal, is activated from entry to exit, while the remaining myocardium generating far-field signal is activated from exit back to entry as illustrated in figure 1. Like all novel work, a number of questions are raised about both the validity and generalizability of the methods. The findings were generated from a very unique data set that allowed the entire VT circuit to be known to the authors, including bystander sites and exit sites partly defined by the application of a large cryoablation probe. Translation to contemporary catheter ablation techniques will require prospective validation. Bipolar signals are highly sensitive to both the size and the spacing of the electrodes. As such, it is not obvious that these data can be reproduced using a relatively large tip ablation catheter with wider electrode spacing. Using a multi-electrode catheter with closer bipolar spacing may more closely mimic the methods used in the analysis. Despite the use of closely spaced bipoles, the choice of timing of near-field and far-field electrograms remains somewhat open to interpretation. Spectral analysis, as performed by the authors, served to make the process more objective, but inter and intra-observer variability was not measured. In real-time, reproducible measures of near-field to far-field timing may be a challenge. It also remains to be tested whether exit sites can be so accurately identified using this method as to allow successful ablation with a much smaller radiofrequency tip catheter as compared to the large surgical cryoablation tip. Finally, the ability of this method to differentiate bystander sites from exit sites that are anatomically very close together with similar near-field to far-field measurements, is not clear. No doubt these questions will be addressed in future work. Overall however the authors provide a novel method of diastolic electrogram analysis that allows localization of VT exit sites from a single recording, without the need for perturbing or mapping the entire circuit. If true, this method could greatly facilitate VT mapping and ablation in both hemodynamically stable and potentially unstable VT. In either situation, identifying an optimal ablation
4
site quickly, accurately, and reproducibly (without the use of pacing manoeuvres) would be a very welcome addition to our toolkit.
References: 1. Stevenson WG, Wilber DJ, Natale A, et al. Multicenter Thermocool VT Ablation Trial Investigators. Irrigated radiofrequency catheter ablation guided by electroanatomic mapping for recurrent ventricular tachycardia after myocardial infarction: the multicenter thermocool ventricular tachycardia ablation trial. Circulation. 2008 Dec 16;118(25):2773-82j. 2. Aliot EM, Stevenson WG, Almendral-Garrote JM, et al. EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias: developed in a partnership with the European Heart Rhythm Association (EHRA), a Registered Branch of the European Society of Cardiology (ESC), and the Heart Rhythm Society (HRS); in collaboration with the American College of Cardiology (ACC) and the American Heart Association (AHA). Heart Rhythm 2009 Jun;6(6):886-933. 3. Hsia HH, Lin D, Sauer WH, Callans DJ, Marchlinski FE. Relationship of late potentials to the ventricular tachycardia circuit defined by entrainment. J Interv Card Electrophysiol 2009; 26:21-9. 4. Stevenson WG, Khan H, Sager P, Saxon LA, Middlekauff HR, Natterson PD, Wiener I. Identification of reentry circuit sites during catheter mapping and radiofrequency ablation of ventricular tachycardia late after myocardial infarction. Circulation 1993;88(Pt 1):1647–70. 5. Cassidy DM, Vassallo JA, Buxton AE, Doherty JU, Marchlinski FE, Josephson ME. The value of catheter mapping during sinus rhythm to localize site of origin of ventricular tachycardia. Circulation 1984;69:1103-1110. 6. El-Shalakany A, Hadjis T, Papageorgiou P, Monahan K, Epstein L, Josephson ME.. Entrainment/mapping criteria for the prediction of termination of ventricular tachycardia by single radiofrequency lesion in patients with coronary artery disease. Circulation 1999;99:2283-2289.
5
7. Sacher F, Tedrow UB, Field ME, Raymond JM, Koplan BA, Epstein LM, Stevenson WG. Ventricular tachycardia ablation: evolution of patients and procedures over 8 years. Circ Arrhythmia Electrophysiol. 2008; 1: 153–161. 8. Das M, Downar E, Massé S, Harris L, Cameron D, Nair K, Chauhan VS, Spears DA, Ha AC, Jackson N, Nanthakumar K. Temporal-component analysis of diastolic electrograms in ventricular tachycardia differentiates non-vulnerable regions of the circuit. Heart Rhythm 2015; in press 9. Downar E, Harris L, Mickleborough LL, Shaikh N, Parson ID. Endocardial mapping of ventricular tachycardia in the intact human ventricle: Evidence for reentrant mechanisms. Journal of the American College of Cardiology 1988 Apr;11(4):783-791.
6
Finding the optimal ablation site in ventricular tachycardia through a single electrogram: Is it too good to be true? Umjeet S. Jolly MD, Kevin K. Ng MBChB, Allan C. Skanes MD, FHRS
www.elsevier.com/locate/buildenv
PII: DOI: Reference:
S1547-5271(15)00680-3 http://dx.doi.org/10.1016/j.hrthm.2015.05.033 HRTHM6296
To appear in:
Heart Rhythm
Cite this article as: Umjeet S. Jolly MD, Kevin K. Ng MBChB, Allan C. Skanes MD, FHRS, Finding the optimal ablation site in ventricular tachycardia through a single electrogram: Is it too good to be true?, Heart Rhythm, http://dx.doi.org/10.1016/j. hrthm.2015.05.033 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 galley proof before it is published in its final citable 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.
Finding the optimal ablation site in ventricular tachycardia through a single electrogram: Is it too good to be true? Umjeet S. Jolly, MD, Kevin K. Ng, MBChB and Allan C. Skanes, MD, FHRS
Arrhythmia Service Department of Cardiology Schulich School of Medicine Western University London, ON N6A 5A5 Primary contact: [email protected]
Disclosure and Financial Sources: No conflict of interest for all authors and no sources of funding were sought.
Catheter ablation for ventricular tachyarrhyhthmias (VT) has steadily improved in patients with ischaemic cardiomyopathy and in fact, international guidelines recommend its use as an adjunct to antiarrhythmic therapy in patients experiencing appropriate ICD shocks.1,2 The procedure, however, is not without its challenges. Ablation of a VT circuit is dependent on multiple factors, the most important being the identification of a critical isthmus of slow conduction that facilitates re-entry. Slow conduction through surviving fibers of any infarct zone may produce late or isolated diastolic potentials as well as fractionated electrograms that may or may not play a role in a given VT. Studies characterising the spatial relationship between late diastolic potentials and the components of re-entrant VT circuits (entrance, mid-isthmus, exit and outer loops) based on timing alone3,4 have found it difficult to distinguish a critical ablation site from bystander sites.5 Strict entrainment criteria have been invoked to
1
select appropriate ablation target sites,6 but repeated entrainment as a method to identify critical diastolic potentials has a number of practical challenges. First, up to two thirds of patients do not tolerate VT for a sufficient period of time for detailed activation and entrainment mapping.7 Additionally, the clinical VT may not be inducible at the time of the procedure, or mechanical block may be induced during activation mapping rendering the clinical tachycardia non-inducible. Finally, entrainment mapping may convert one VT circuit to another, accelerate the tachycardia or cause its degeneration into ventricular fibrillation. Methods to circumvent these issues have been proposed including mapping scar substrate during sinus rhythm or limited tachycardia but additional manoeuvres are still needed to increase the specificity of the potentials related to the tachycardia isthmus. In the current issue of HeartRhythm, Das et al.8 describe a novel method to determine the importance of a diastolic potential without the need for pacing or entertainment. Specifically, based on timing alone, diastolic potential were identified as bystander or exit sites during VT. They retrospectively analyzed sixteen VTs that were induced in twelve patients with ischemic cardiomyopathy who were undergoing cardiac surgical mapping and cryoablation of VT circuits. High-density activation maps of the entire VT circuit were created, made possible by a combination of surgical access to the ventricle and a specially designed mapping system as pioneered by Dr. Eugene Downar and his group in the mid to late 1990’s.9 Mapping was performed with a custom-made 112, 2mm bipolar electrode endocardial contact array with 1-3 cm spacing recorded on a custom-made 720 channel mapping system. The authors defined the exit site in 2 ways: (1) the location where a transition from diastolic conduction to systolic activation of healthy myocardium was observed and (2) where cryoablation terminated VT. Bystander sites were defined as locations next to identified isthmus locations without continuous activation on surrounding bipoles, essentially identifying ‘dead-ends’ within conduction. These definitions were critically dependent on having mapped and identified the entire VT circuit using the high-resolution methods as noted above. Bipolar electrograms, recorded during VT, were analyzed both manually, and
2
using a spectral analysis technique that limited noise and separated the high frequency near-field components from the low frequency far-field components. On bipolar electrogram analysis, the interval between local activation and surface QRS did not differ significantly between bystander sites and exit sites (60 + 31.5 ms vs 72 + 55 ms, p = 0.63), and the exit site was never found to be less than 20 ms before the surface QRS. However the interval from local near-field activity to far field activity by manual measurement, and spectral analysis, was significantly shorter at exit sites (10.0 + 13.1 ms vs 89.0 + 64.5 ms respectively, p = 0.0003.) Unipolar electrograms did not have a consistent and reliable time point for local activation, and therefore were not used. The authors concluded that component analysis of diastolic electrograms that have a near-field to far-field measurement of approximately 25 ms coupled with a transition from diastolic conduction to systolic activation of healthy myocardium on average 60 ms ahead of the surface QRS suggest an exit site, without the need for pacing manoeuvres. In addition, these values differentiate an exit site not only from a post-exit site, where ablation may have no effect, but also from a bystander site – thereby potentially allowing determination of an optimal ablation site. Does such a simplified measurement make electrophysiological sense? The observation may be conceptually explained by considering a simplified VT circuit with (1) an entry site, (2) a slowly conducting critical isthmus, (3) one or more bystander sites, and (4) an exit site where the wave front leaves the scar and activates the healthy myocardium. Using this model, one can conceptualize why the local signal to surface QRS may not differentiate exit sites from bystander sites. A hypothetical bystander site, activated in parallel with the isthmus, may have the same timing as the exit site, and would therefore have the same near-field timing relative to the QRS. However, because the far-field signal adjacent to the bystander would be activated later, the near-field to far-field timing would be longer. As such, the exit site should have a very short near-field to far-field measurement, whereas bystander sites should have a much longer near-field to far-field measurement. Essentially, relative to
3
the scar, the isthmus generating near field signal, is activated from entry to exit, while the remaining myocardium generating far-field signal is activated from exit back to entry as illustrated in figure 1. Like all novel work, a number of questions are raised about both the validity and generalizability of the methods. The findings were generated from a very unique data set that allowed the entire VT circuit to be known to the authors, including bystander sites and exit sites partly defined by the application of a large cryoablation probe. Translation to contemporary catheter ablation techniques will require prospective validation. Bipolar signals are highly sensitive to both the size and the spacing of the electrodes. As such, it is not obvious that these data can be reproduced using a relatively large tip ablation catheter with wider electrode spacing. Using a multi-electrode catheter with closer bipolar spacing may more closely mimic the methods used in the analysis. Despite the use of closely spaced bipoles, the choice of timing of near-field and far-field electrograms remains somewhat open to interpretation. Spectral analysis, as performed by the authors, served to make the process more objective, but inter and intra-observer variability was not measured. In real-time, reproducible measures of near-field to far-field timing may be a challenge. It also remains to be tested whether exit sites can be so accurately identified using this method as to allow successful ablation with a much smaller radiofrequency tip catheter as compared to the large surgical cryoablation tip. Finally, the ability of this method to differentiate bystander sites from exit sites that are anatomically very close together with similar near-field to far-field measurements, is not clear. No doubt these questions will be addressed in future work. Overall however the authors provide a novel method of diastolic electrogram analysis that allows localization of VT exit sites from a single recording, without the need for perturbing or mapping the entire circuit. If true, this method could greatly facilitate VT mapping and ablation in both hemodynamically stable and potentially unstable VT. In either situation, identifying an optimal ablation
4
site quickly, accurately, and reproducibly (without the use of pacing manoeuvres) would be a very welcome addition to our toolkit.
References: 1. Stevenson WG, Wilber DJ, Natale A, et al. Multicenter Thermocool VT Ablation Trial Investigators. Irrigated radiofrequency catheter ablation guided by electroanatomic mapping for recurrent ventricular tachycardia after myocardial infarction: the multicenter thermocool ventricular tachycardia ablation trial. Circulation. 2008 Dec 16;118(25):2773-82j. 2. Aliot EM, Stevenson WG, Almendral-Garrote JM, et al. EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias: developed in a partnership with the European Heart Rhythm Association (EHRA), a Registered Branch of the European Society of Cardiology (ESC), and the Heart Rhythm Society (HRS); in collaboration with the American College of Cardiology (ACC) and the American Heart Association (AHA). Heart Rhythm 2009 Jun;6(6):886-933. 3. Hsia HH, Lin D, Sauer WH, Callans DJ, Marchlinski FE. Relationship of late potentials to the ventricular tachycardia circuit defined by entrainment. J Interv Card Electrophysiol 2009; 26:21-9. 4. Stevenson WG, Khan H, Sager P, Saxon LA, Middlekauff HR, Natterson PD, Wiener I. Identification of reentry circuit sites during catheter mapping and radiofrequency ablation of ventricular tachycardia late after myocardial infarction. Circulation 1993;88(Pt 1):1647–70. 5. Cassidy DM, Vassallo JA, Buxton AE, Doherty JU, Marchlinski FE, Josephson ME. The value of catheter mapping during sinus rhythm to localize site of origin of ventricular tachycardia. Circulation 1984;69:1103-1110. 6. El-Shalakany A, Hadjis T, Papageorgiou P, Monahan K, Epstein L, Josephson ME.. Entrainment/mapping criteria for the prediction of termination of ventricular tachycardia by single radiofrequency lesion in patients with coronary artery disease. Circulation 1999;99:2283-2289.
5
7. Sacher F, Tedrow UB, Field ME, Raymond JM, Koplan BA, Epstein LM, Stevenson WG. Ventricular tachycardia ablation: evolution of patients and procedures over 8 years. Circ Arrhythmia Electrophysiol. 2008; 1: 153–161. 8. Das M, Downar E, Massé S, Harris L, Cameron D, Nair K, Chauhan VS, Spears DA, Ha AC, Jackson N, Nanthakumar K. Temporal-component analysis of diastolic electrograms in ventricular tachycardia differentiates non-vulnerable regions of the circuit. Heart Rhythm 2015; in press 9. Downar E, Harris L, Mickleborough LL, Shaikh N, Parson ID. Endocardial mapping of ventricular tachycardia in the intact human ventricle: Evidence for reentrant mechanisms. Journal of the American College of Cardiology 1988 Apr;11(4):783-791.
6
