- Email: [email protected]
Catheter ablation guided by termination of postinfarction ventricular tachycardia by pacing with nonglobal capture
Catheter ablation guided by termination of postinfarction ventricular tachycardia by pacing with nonglobal capture Frank Bogun, MD,a Subramaniam C. Krishnan, MD,b Joseph E. Marine, MD,b Stefan H. Hohnloser, MD,c Claudio Schuger, MD,b Hakan Oral, MD,a Frank Pelosi, MD,a Aman Chugh, MD,a Fred Morady, MDa a
From the University of Michigan, Ann Arbor, Michigan, Henry Ford Hospital, Detroit, Michigan; and c Division of Cardiology, J.W. Goethe University, Frankfurt, Germany. b
OBJECTIVES We prospectively investigated the prevalence and value of this criterion for identifying a target site for ablation in patients with postinfarction ventricular tachycardia (VT). BACKGROUND Termination of postinfarction VT by pacing with nonglobal capture identifies a critical component of the reentrant circuit. METHODS In a consecutive series of 34 patients with prior infarction (age 67 ⫾ 10 years, ejection fraction 0.26 ⫾ 0.1) referred for radiofrequency catheter ablation, mapping was performed in the left ventricle. At sites with abnormal electrograms, pacing was performed during VT. If VT terminated with nonglobal capture during the pacing train, radiofrequency energy was delivered. RESULTS Sixty-two VTs (cycle length 450 ⫾ 84 ms) were mapped and targeted for radiofrequency ablation. Concealed entrainment was present at 101 endocardial sites. Among the 101 sites, VT terminated by pacing with nonglobal capture at 5 sites (5%). At 10 additional sites in 10 patients, VT terminated by pacing with nonglobal capture, and concealed entrainment could not be documented at these sites because of reproducible termination of the VT. An application of radiofrequency energy resulted in VT termination at all 15 sites where nonglobal capture was documented and the targeted VTs were no longer inducible after ablation. CONCLUSIONS Termination of VT by pacing with nonglobal capture can be demonstrated in approximately one third of patients with postinfarction VT and is a specific criterion for identifying a critical component of the reentrant circuit, whether or not concealed entrainment can be documented at that site. KEYWORDS Catheter ablation; Mapping; Ventricular tachycardia; Myocardial infarction © 2004 Heart Rhythm Society. All rights reserved.
Nonglobal capture has been defined as termination of ventricular tachycardia (VT) by a pacing stimulus that does not result in global ventricular capture. Nonglobal capture during entrainment mapping has been described1– 6 and has been helpful in guiding radiofrequency ablation of postinfarction VT in conjunction with concealed entrainment.7 In theory, nonglobal capture identifies sites that are critical for the reentrant circuit. The purpose of this study was to prospectively assess the prevalence and value of VT termination by pacing with nonglobal capture as the only map-
Address reprint requests and correspondence: Dr. Frank Bogun, Division of Cardiology, University of Michigan Health System, 3119 TC, 1500 E. Medical Center Drive, Ann Arbor, Michigan 48109-0366. E-mail address: [email protected]. (Received March 22, 2004; accepted June 10, 2004.)
ping criterion in patients undergoing radiofrequency ablation of postinfarction VT.
Methods Patient characteristics Thirty-four consecutive patients (30 men and 4 women; mean age 67 ⫾ 10 years [⫾ SD]) with coronary artery disease underwent radiofrequency ablation of drug-refractory VT. Mean left ventricular ejection fraction was 0.26 ⫾ 0.1. All patients had a history of at least one myocardial infarction (anterior in 8, inferior in 13, and both anterior and inferior in 13).
1547-5271/$ -see front matter © 2004 Heart Rhythm Society. All rights reserved. doi:10.1016/j.hrthm.2004.06.009
Heart Rhythm (2004) 4, 422– 426
Bogun et al
Ventricular Tachycardia
423
A total of 62 VTs with a mean cycle length of 450 ⫾ 84 ms were mapped, all of which were sustained and reproducibly inducible. None of these VTs was ever observed to terminate spontaneously. Six of the 62 VTs were not hemodynamically tolerated. Thirteen of the VTs had a left bundle branch block morphology, and 48 had a right bundle branch block morphology. All but one patient had an implantable cardioverter-defibrillator (ICD). The indication for ablation was incessant VT in 5 patients, frequent ICD discharges in 18 patients, and recurrent episodes of monomorphic VT resulting in palpitations in 11 patients. All patients had failed treatment with at least one antiarrhythmic drug. Eighteen patients were taking amiodarone at the time of the mapping procedure. Twelve of the 34 patients were part of a prior report.7
Definitions Nonglobal capture was defined as termination of VT by pacing stimuli that did not result in global ventricular capture (Figure 1). At sites with nonglobal capture, we assessed whether or not there was evidence of capture of the local electrogram that was recorded by electrodes 2 and 4 (Figure 1).
Electrophysiologic study and mapping After informed consent was obtained, two or three quadripolar electrode catheters were inserted into a femoral vein and positioned in the right atrium, His-bundle position, and right ventricular apex. A 7-Fr, quadripolar, temperaturesensing electrode catheter with interelectrode spacing of 2-5-2 mm and a deflectable 4-mm tip (Webster, Mansfield, or EP Technologies) was inserted into a femoral artery and used for mapping and ablation in the left ventricle via a retrograde aortic approach during systemic heparinization. Pacing was performed with a programmable stimulator (Bloom Associates Ltd., Redding, PA, USA; Biotronik, Erlangen, Germany; or EP Med Systems, New Jersey). If the VT was not incessant, right ventricular programmed stimulation was performed using up to four extrastimuli. The same protocol was repeated at the end of the procedure. Left ventricular mapping was performed, and at sites with abnormal ventricular electrograms (amplitude ⱕ0.5mV, duration ⱖ133 ms, presence of isolated potentials),8,9 pacing trains of 8 to 15 stimuli were delivered at a cycle length 20 to 100 ms shorter than the VT cycle length. The pacing current was 1 to 2 mA greater than the capture threshold measured during sinus rhythm at sites with abnormal electrograms in the left ventricle. The pacing current subsequently was increased to a maximum of 10 mA at a pulse width of 2 ms, as needed to achieve capture when entrainment mapping was performed. The mean capture threshold at left ventricular sites with abnormal electrograms was 5.9 ⫾ 2.8 mA at a pulse duration of 2 ms. The first stimulus of the pacing train was synchronized to be simultaneous with either the QRS complex or the right
Figure 1 A: Episode of nonglobal capture with local capture resulting in ventricular tachycardia (VT) termination. Surface ECG leads V1, I, II, and III, and intracardiac recordings from poles 2 and 4 of the mapping catheter (Map 2/4) and the right ventricular apex (RVA) are shown. Two different gain settings (80 and 20 mm/mV) of the recordings from the mapping catheter are shown. The first pacing stimulus (S) terminates the VT without global capture. Local capture (arrow) after the first stimulus results in VT termination without global capture. The second stimulus results in a paced QRS complex during sinus rhythm. Radiofrequency ablation at this site resulted in successful ablation of this VT. B: Episode of nonglobal capture without local capture resulting in VT termination during left ventricular mapping. Surface ECG leads V1, I, II, and III, and intracardiac tracings from the right ventricular apex (RVA) and the recordings from poles 2/4 of the mapping catheter (Map) are displayed (gain settings of 20 and 80 mm/mV). The first pacing stimulus (S) from the mapping catheter terminates the VT without global capture. There is no local capture after the first pacing stimulus, as the local electrogram of the mapping catheter is unchanged. The second stimulus results in global capture during sinus rhythm. Radiofrequency ablation at this site resulted in successful ablation of this VT.
424 ventricular electrogram. In an attempt to cover most of the diastolic interval as well as electrical systole with pacing stimuli, the coupling interval of subsequent drive trains was progressively shortened by 10 to 20 ms until there was entrainment or capture without entrainment. If VT terminated during pacing with nonglobal capture, we determined whether or not the local electrogram was captured by the terminating stimulus (Figure 1). Repeated pacing trains were delivered after VT was reinduced, in an attempt to demonstrate concealed entrainment. If VT was terminated repeatedly by pacing with nonglobal capture, radiofrequency energy was delivered during VT at that site. If there was classic entrainment, the catheter was moved to another location. Electrodes 1/2 or 1/3 of the mapping catheter were used for bipolar pacing, and electrodes 1/2 and 2/4 were used for bipolar recording. The intracardiac electrograms and leads V1, I, II, and III were displayed on an oscilloscope and recorded at a paper speed of 100 mm/s. Left ventricular electrograms were recorded simultaneously at gain settings of 20 and 80 mm/mV, with filter settings of 30 to 500 Hz. The recordings were stored on optical diskette (Prucka, Bard, or EP Technologies).
Radiofrequency ablation Radiofrequency energy was applied at sites where concealed entrainment was present or where VT was terminated by pacing with nonglobal capture. The power was titrated automatically to maintain an electrode-tissue interface temperature of 60°C. Applications of energy were delivered during VT and continued for only 20 seconds if VT did not terminate. If the VT terminated during delivery of radiofrequency energy, the application was continued for 60 seconds. Programmed ventricular stimulation then was repeated to determine whether the ablated VT was still inducible. A successful outcome was defined as termination of the VT during an application of radiofrequency energy and the inability to reinduce the VT using a complete programmed stimulation protocol.
Data analysis We determined the prevalence of VT termination by pacing with nonglobal capture during mapping. Only sites where concealed entrainment could be identified as well as sites where VT was terminated by pacing with nonglobal capture (with or without demonstration of concealed entrainment) were analyzed. Other mapping criteria, including the stimulus-QRS interval, electrogram-QRS interval, prevalence of isolated potentials during VT, and prevalence of matching electrogram-QRS intervals and stimulus-QRS intervals, were documented. These mapping criteria have been described in detail in prior reports.10
Heart Rhythm, Vol 1, No 4, October 2004
Statistical analysis Continuous variables are expressed as mean ⫾ 1 SD. Comparisons were performed using Student’s t-test, Chisquare analysis, or Fisher’s exact test, as appropriate. P ⬍ .05 was considered statistically significant.
Results Termination of VT with nonglobal capture Overall, reproducible termination of VT by pacing with nonglobal capture occurred at 15 sites in 15 (24%) of 62 VTs, in 11 (32%) of 34 patients. At all of the sites where VT was terminated by pacing with nonglobal capture, there was global capture when pacing was performed during sinus rhythm at the same stimulus output. Concealed entrainment was present at 101 endocardial sites. Among these 101 sites, VT was terminated by pacing with nonglobal capture at 5 sites (10%) in 52 VTs. At 10 sites identified in 10 patients, VT was terminated by pacing with nonglobal capture, and concealed entrainment could not be tested for because of reproducible termination of VT by pacing. There was evidence of local capture by the stimulus that terminated VT at 2 of 15 sites. At the other 13 sites where there was termination of VT by pacing with nonglobal capture, there was no alteration of the local electrogram by the terminating stimulus (Figure 1). VT termination by pacing with nonglobal capture occurred in 11 patients during 15 different VTs, and 8 (73%) of these 11 patients were being treated with amiodarone. In comparison, among the 22 patients in whom termination of VT by pacing with nonglobal capture could not be demonstrated, 10 (45%) were being treated with amiodarone (P ⫽ .2).
Successful ablation sites Fifty-three (85%) of 62 VTs were successfully ablated. The specificity and positive predictive value of termination of VT by pacing with nonglobal capture for a successful ablation site were 100% each. The sensitivity and negative predictive values were 16% and 58%, respectively. Table 1 compares the sensitivity, specificity, and positive and negative predictive values of other mapping criteria.
Follow-up Mean follow-up was 12 ⫾ 8.4 months (range 1–26). In 3 of 29 patients, VTs that had a cycle length similar to that of the targeted VT recurred. This resulted in a repeat procedure in two of three patients and a change in the antiarrhythmic medications in one patient. In the remaining patients, neither change in the antiarrhythmic regimen nor revascularization procedures were done during the follow-up period.
Bogun et al Table 1
Ventricular Tachycardia
425
Comparison of mapping criteria
Variables
PPV
NPV
Sensitivity
Specificity
P value
N-G capture without CE (n ⫽ 10) N-G capture ⫾ CE (n ⫽ 15) S-QRS ⫽ EGM QRS (n ⫽ 37) IP-dissoc. (n ⫽ 23) SQRS/VTCL ⬍ 0.7 (n ⫽ 33)
100% 100% 84% 79% 56%
53% 56% 83% 67% 74%
24% 29% 84% 64% 83%
100% 100% 83% 81% 43%
0.001 ⬍0.001 ⬍0.001 ⬍0.001 0.01
P value indicates the ability of the mapping criterion to differentiate effective from ineffective sites. N-G capture ⫽ nonglobal capture; CE ⫽ concealed entrainment; S-QRS ⫽ stimulus-QRS interval; EGM-QRS ⫽ electrogram-QRS interval; IP-dissoc. ⫽ isolated potential that cannot be dissociated from VT; S-QRS/VTCL ⫽ stimulus-QRS interval/VT cycle length ratio; PPV ⫽ positive predictive value; NPV ⫽ negative predictive value.
Discussion Main findings This study demonstrates that termination of VT by pacing with nonglobal capture is demonstrable in approximately one third of patients with postinfarction VT, and that this criterion is very specific for identifying a critical component of the reentrant circuit, whether or not concealed entrainment can be demonstrated at the pacing site. In most instances, there was no evidence of local capture when VT was terminated by nonglobal capture.
Mapping criteria During entrainment mapping, the presence of concealed entrainment identifies a protected area that is within or connected to the reentrant circuit. However, not all sites with concealed entrainment are critical to the reentrant circuit, and the positive predictive value of concealed entrainment for an effective target site is only 50%. Prior studies have described the incremental value of mapping criteria other than concealed entrainment.10 The present study demonstrates that VT termination by pacing with nonglobal capture improves the positive predictive value of concealed entrainment for effective ablation sites from approximately 50% to 100%. Based on our results, termination of VT by pacing with nonglobal capture may be sufficient by itself to justify delivery of radiofrequency energy. We found VT termination with nonglobal capture to be the most specific mapping criterion for identification of critical areas of postinfarction VT reentrant circuits.
Possible mechanisms of arrhythmia termination Different electrophysiologic mechanisms may be responsible for the phenomenon of VT termination despite nonglobal capture.1,3,4 Local capture of the isthmus without global ventricular capture may terminate VT by resulting in block in both directions within the isthmus. This mechanism appears to be uncommon, as local capture was observed at only 2 of 15 sites where VT termination occurred.
Prior studies have demonstrated that an impulse delivered during the refractory period may prolong repolarization and refractoriness of tissue.3,4 In poorly coupled tissues with diminished excitability and complex anisotropy (such as scar), a nonexcitatory impulse also may induce postrepolarization refractoriness locally.11 This may explain how pacing stimuli may terminate VT in the absence of local capture. For VT to terminate due to prolongation of repolarization, a prerequisite would be for the tachycardia to have a long wavelength and a short excitable gap. Conversely, if the arrhythmia had a long excitable gap with slow conduction through the isthmus, a nonexcitatory impulse could induce postrepolarization refractoriness and conduction block by electrotonic inhibition.12 In this scenario, the head of the wavefront encounters refractory tissue within the isthmus, and the VT terminates. Poorly coupled tissues with diminished excitability would be a prerequisite for this mechanism to occur.
Prior studies Different terms have been used to describe VT termination during pacing with nonglobal capture. Subthreshold stimulation is one of these terms. It has been recognized that subthreshold stimulation delivered within the effective refractory period of the atrium or the ventricle prolongs the refractory period locally.3,4,13 Ruffy et al14 described this phenomenon for the first time in a postinfarction patient. Subthreshold stimulation subsequently was described in case reports as a criterion to identify critical sites of the reentrant circuit of postinfarction VT.1 Several reports stress that the stimuli must be delivered close to the site of origin of the VT in order to terminate the VT with subthreshold stimulation.1,15,16 However, no prior studies have systematically determined the prevalence of termination of VT by pacing with nonglobal capture and the value of nonglobal capture as a mapping criterion to guide radiofrequency ablation.
Study limitations The majority of the targeted VTs were hemodynamically stable; therefore, the results of this study cannot be extrap-
426 olated to unstable VTs. The sample size was small, and the results need to be confirmed in a larger series. VT termination with nonglobal capture might have been observed more frequently if the entire cycle length of the VT had been scanned with a pacing stimulus rather than using a fixed coupling interval. Finally, given the inherent limitations of extracellullar recordings, it is difficult to identify the exact mechanisms of VT termination by pacing with nonglobal capture.
Clinical implications The presence of nonglobal capture during pacing is of great clinical value because it predicts an effective ablation site with some certainty. The low sensitivity limits the applicability of nonglobal capture as the only mapping criteria. Further studies in which the entire cardiac cycle length is scanned with a subthreshold stimulus will be helpful in determining whether the sensitivity of this criterion can be improved.
References 1. Podczeck A, Borggrefe M, Martinez-Rubio A, Breithardt G. Termination of re-entrant ventricular tachycardia by subthreshold stimulus applied to the zone of slow conduction. Eur Heart J 1988;9:1146 – 1150. 2. Ruffy R. Termination of ventricular tachycardia by nonpropagated local depolarization: further observations on entrainment of ventricular tachycardia from an area of slow conduction. Pacing Clin Electrophysiol 1990;13:852– 858. 3. Windle JR, Miles WM, Zipes DP, Prystowsky EN. Subthreshold conditioning stimuli prolong human ventricular refractoriness. Am J Cardiol 1986;57:381–386. 4. Skale BT, Kallok MJ, Prystowsky EN, Gill RM, Zipes DP. Inhibition of premature ventricular extrastimuli by subthreshold conditioning stimuli. J Am Coll Cardiol 1985;6:133–140.
Heart Rhythm, Vol 1, No 4, October 2004 5. Shenasa M, Cardinal R, Kus T, Savard P, Fromer M, Page P. Termination of sustained ventricular tachycardia by ultrarapid subthreshold stimulation in humans. Circulation 1988;78(5 Pt 1):1135– 1143. 6. Garan H, Ruskin JN. Reproducible termination of ventricular tachycardia by a single extrastimulus within the reentry circuit during the ventricular effective refractory period. Am Heart J 1988;116(2 Pt 1): 546 –550. 7. Bogun F, Hohnloser SH, Bender B, Li YG, Groenefeld G, Pelosi F, Oral H, Knight B, Strickberger SA, Morady F. Mechanism of ventricular tachycardia termination by pacing at left ventricular sites in patients with coronary artery disease. J Interv Card Electrophysiol 2002;6:35– 41. 8. Josephson ME. Clinical cardiac electrophysiology: techniques and interpretations, 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 2002. 9. Josephson M. Clinical cardiac electrophysiology techniques and interpretations, 2nd edition. Philadelphia; Lea & Febiger, 1993: 427. 10. Bogun F, Bahu M, Knight B, Weiss R, Paladino W, Harvey M, Goyal R, Daoud E, Man K, Strickberger S, Morady F. Comparison of effective and ineffective target sites that demonstrate concealed entrainment in patients with coronary artery disease undergoing radiofrequency ablation of ventricular tachycardia. Circulation 1997;95:183–190. 11. Antzelevitch C. Electrotonus and reflection. In: Rosen MR, Wit AL, Janse MJ, eds. Cardiac electrophysiology: a textbook. Mount Kisco, NY: Futura Publishing Co., 1990:491–516. 12. Antzelevitch C, Moe GK. Electrotonic inhibition and summation of impulse conduction in mammalian Purkinje fibers. Am J Physiol 1983;245:H42–H53. 13. Prystowsky EN, Zipes DP. Inhibition in the human heart. Circulation 1983;68:707–713. 14. Ruffy R, Friday KJ, Southworth WF. Termination of ventricular tachycardia by single extrastimulation during the ventricular effective refractory period. Circulation 1983;67:457– 459. 15. Shenasa M, Fromer M, Borggrefe M, Breithardt G. Subthreshold electrical stimulation for termination and prevention of reentrant tachycardias. J Electrocardiol 1992;24(Suppl):25–31. 16. Shenasa M, Fromer M. Termination of sustained ventricular tachycardia by subthreshold electrical stimulation via epicardial patch electrodes (abstr). Circulation 1991;85:II-427.
From the University of Michigan, Ann Arbor, Michigan, Henry Ford Hospital, Detroit, Michigan; and c Division of Cardiology, J.W. Goethe University, Frankfurt, Germany. b
OBJECTIVES We prospectively investigated the prevalence and value of this criterion for identifying a target site for ablation in patients with postinfarction ventricular tachycardia (VT). BACKGROUND Termination of postinfarction VT by pacing with nonglobal capture identifies a critical component of the reentrant circuit. METHODS In a consecutive series of 34 patients with prior infarction (age 67 ⫾ 10 years, ejection fraction 0.26 ⫾ 0.1) referred for radiofrequency catheter ablation, mapping was performed in the left ventricle. At sites with abnormal electrograms, pacing was performed during VT. If VT terminated with nonglobal capture during the pacing train, radiofrequency energy was delivered. RESULTS Sixty-two VTs (cycle length 450 ⫾ 84 ms) were mapped and targeted for radiofrequency ablation. Concealed entrainment was present at 101 endocardial sites. Among the 101 sites, VT terminated by pacing with nonglobal capture at 5 sites (5%). At 10 additional sites in 10 patients, VT terminated by pacing with nonglobal capture, and concealed entrainment could not be documented at these sites because of reproducible termination of the VT. An application of radiofrequency energy resulted in VT termination at all 15 sites where nonglobal capture was documented and the targeted VTs were no longer inducible after ablation. CONCLUSIONS Termination of VT by pacing with nonglobal capture can be demonstrated in approximately one third of patients with postinfarction VT and is a specific criterion for identifying a critical component of the reentrant circuit, whether or not concealed entrainment can be documented at that site. KEYWORDS Catheter ablation; Mapping; Ventricular tachycardia; Myocardial infarction © 2004 Heart Rhythm Society. All rights reserved.
Nonglobal capture has been defined as termination of ventricular tachycardia (VT) by a pacing stimulus that does not result in global ventricular capture. Nonglobal capture during entrainment mapping has been described1– 6 and has been helpful in guiding radiofrequency ablation of postinfarction VT in conjunction with concealed entrainment.7 In theory, nonglobal capture identifies sites that are critical for the reentrant circuit. The purpose of this study was to prospectively assess the prevalence and value of VT termination by pacing with nonglobal capture as the only map-
Address reprint requests and correspondence: Dr. Frank Bogun, Division of Cardiology, University of Michigan Health System, 3119 TC, 1500 E. Medical Center Drive, Ann Arbor, Michigan 48109-0366. E-mail address: [email protected]. (Received March 22, 2004; accepted June 10, 2004.)
ping criterion in patients undergoing radiofrequency ablation of postinfarction VT.
Methods Patient characteristics Thirty-four consecutive patients (30 men and 4 women; mean age 67 ⫾ 10 years [⫾ SD]) with coronary artery disease underwent radiofrequency ablation of drug-refractory VT. Mean left ventricular ejection fraction was 0.26 ⫾ 0.1. All patients had a history of at least one myocardial infarction (anterior in 8, inferior in 13, and both anterior and inferior in 13).
1547-5271/$ -see front matter © 2004 Heart Rhythm Society. All rights reserved. doi:10.1016/j.hrthm.2004.06.009
Heart Rhythm (2004) 4, 422– 426
Bogun et al
Ventricular Tachycardia
423
A total of 62 VTs with a mean cycle length of 450 ⫾ 84 ms were mapped, all of which were sustained and reproducibly inducible. None of these VTs was ever observed to terminate spontaneously. Six of the 62 VTs were not hemodynamically tolerated. Thirteen of the VTs had a left bundle branch block morphology, and 48 had a right bundle branch block morphology. All but one patient had an implantable cardioverter-defibrillator (ICD). The indication for ablation was incessant VT in 5 patients, frequent ICD discharges in 18 patients, and recurrent episodes of monomorphic VT resulting in palpitations in 11 patients. All patients had failed treatment with at least one antiarrhythmic drug. Eighteen patients were taking amiodarone at the time of the mapping procedure. Twelve of the 34 patients were part of a prior report.7
Definitions Nonglobal capture was defined as termination of VT by pacing stimuli that did not result in global ventricular capture (Figure 1). At sites with nonglobal capture, we assessed whether or not there was evidence of capture of the local electrogram that was recorded by electrodes 2 and 4 (Figure 1).
Electrophysiologic study and mapping After informed consent was obtained, two or three quadripolar electrode catheters were inserted into a femoral vein and positioned in the right atrium, His-bundle position, and right ventricular apex. A 7-Fr, quadripolar, temperaturesensing electrode catheter with interelectrode spacing of 2-5-2 mm and a deflectable 4-mm tip (Webster, Mansfield, or EP Technologies) was inserted into a femoral artery and used for mapping and ablation in the left ventricle via a retrograde aortic approach during systemic heparinization. Pacing was performed with a programmable stimulator (Bloom Associates Ltd., Redding, PA, USA; Biotronik, Erlangen, Germany; or EP Med Systems, New Jersey). If the VT was not incessant, right ventricular programmed stimulation was performed using up to four extrastimuli. The same protocol was repeated at the end of the procedure. Left ventricular mapping was performed, and at sites with abnormal ventricular electrograms (amplitude ⱕ0.5mV, duration ⱖ133 ms, presence of isolated potentials),8,9 pacing trains of 8 to 15 stimuli were delivered at a cycle length 20 to 100 ms shorter than the VT cycle length. The pacing current was 1 to 2 mA greater than the capture threshold measured during sinus rhythm at sites with abnormal electrograms in the left ventricle. The pacing current subsequently was increased to a maximum of 10 mA at a pulse width of 2 ms, as needed to achieve capture when entrainment mapping was performed. The mean capture threshold at left ventricular sites with abnormal electrograms was 5.9 ⫾ 2.8 mA at a pulse duration of 2 ms. The first stimulus of the pacing train was synchronized to be simultaneous with either the QRS complex or the right
Figure 1 A: Episode of nonglobal capture with local capture resulting in ventricular tachycardia (VT) termination. Surface ECG leads V1, I, II, and III, and intracardiac recordings from poles 2 and 4 of the mapping catheter (Map 2/4) and the right ventricular apex (RVA) are shown. Two different gain settings (80 and 20 mm/mV) of the recordings from the mapping catheter are shown. The first pacing stimulus (S) terminates the VT without global capture. Local capture (arrow) after the first stimulus results in VT termination without global capture. The second stimulus results in a paced QRS complex during sinus rhythm. Radiofrequency ablation at this site resulted in successful ablation of this VT. B: Episode of nonglobal capture without local capture resulting in VT termination during left ventricular mapping. Surface ECG leads V1, I, II, and III, and intracardiac tracings from the right ventricular apex (RVA) and the recordings from poles 2/4 of the mapping catheter (Map) are displayed (gain settings of 20 and 80 mm/mV). The first pacing stimulus (S) from the mapping catheter terminates the VT without global capture. There is no local capture after the first pacing stimulus, as the local electrogram of the mapping catheter is unchanged. The second stimulus results in global capture during sinus rhythm. Radiofrequency ablation at this site resulted in successful ablation of this VT.
424 ventricular electrogram. In an attempt to cover most of the diastolic interval as well as electrical systole with pacing stimuli, the coupling interval of subsequent drive trains was progressively shortened by 10 to 20 ms until there was entrainment or capture without entrainment. If VT terminated during pacing with nonglobal capture, we determined whether or not the local electrogram was captured by the terminating stimulus (Figure 1). Repeated pacing trains were delivered after VT was reinduced, in an attempt to demonstrate concealed entrainment. If VT was terminated repeatedly by pacing with nonglobal capture, radiofrequency energy was delivered during VT at that site. If there was classic entrainment, the catheter was moved to another location. Electrodes 1/2 or 1/3 of the mapping catheter were used for bipolar pacing, and electrodes 1/2 and 2/4 were used for bipolar recording. The intracardiac electrograms and leads V1, I, II, and III were displayed on an oscilloscope and recorded at a paper speed of 100 mm/s. Left ventricular electrograms were recorded simultaneously at gain settings of 20 and 80 mm/mV, with filter settings of 30 to 500 Hz. The recordings were stored on optical diskette (Prucka, Bard, or EP Technologies).
Radiofrequency ablation Radiofrequency energy was applied at sites where concealed entrainment was present or where VT was terminated by pacing with nonglobal capture. The power was titrated automatically to maintain an electrode-tissue interface temperature of 60°C. Applications of energy were delivered during VT and continued for only 20 seconds if VT did not terminate. If the VT terminated during delivery of radiofrequency energy, the application was continued for 60 seconds. Programmed ventricular stimulation then was repeated to determine whether the ablated VT was still inducible. A successful outcome was defined as termination of the VT during an application of radiofrequency energy and the inability to reinduce the VT using a complete programmed stimulation protocol.
Data analysis We determined the prevalence of VT termination by pacing with nonglobal capture during mapping. Only sites where concealed entrainment could be identified as well as sites where VT was terminated by pacing with nonglobal capture (with or without demonstration of concealed entrainment) were analyzed. Other mapping criteria, including the stimulus-QRS interval, electrogram-QRS interval, prevalence of isolated potentials during VT, and prevalence of matching electrogram-QRS intervals and stimulus-QRS intervals, were documented. These mapping criteria have been described in detail in prior reports.10
Heart Rhythm, Vol 1, No 4, October 2004
Statistical analysis Continuous variables are expressed as mean ⫾ 1 SD. Comparisons were performed using Student’s t-test, Chisquare analysis, or Fisher’s exact test, as appropriate. P ⬍ .05 was considered statistically significant.
Results Termination of VT with nonglobal capture Overall, reproducible termination of VT by pacing with nonglobal capture occurred at 15 sites in 15 (24%) of 62 VTs, in 11 (32%) of 34 patients. At all of the sites where VT was terminated by pacing with nonglobal capture, there was global capture when pacing was performed during sinus rhythm at the same stimulus output. Concealed entrainment was present at 101 endocardial sites. Among these 101 sites, VT was terminated by pacing with nonglobal capture at 5 sites (10%) in 52 VTs. At 10 sites identified in 10 patients, VT was terminated by pacing with nonglobal capture, and concealed entrainment could not be tested for because of reproducible termination of VT by pacing. There was evidence of local capture by the stimulus that terminated VT at 2 of 15 sites. At the other 13 sites where there was termination of VT by pacing with nonglobal capture, there was no alteration of the local electrogram by the terminating stimulus (Figure 1). VT termination by pacing with nonglobal capture occurred in 11 patients during 15 different VTs, and 8 (73%) of these 11 patients were being treated with amiodarone. In comparison, among the 22 patients in whom termination of VT by pacing with nonglobal capture could not be demonstrated, 10 (45%) were being treated with amiodarone (P ⫽ .2).
Successful ablation sites Fifty-three (85%) of 62 VTs were successfully ablated. The specificity and positive predictive value of termination of VT by pacing with nonglobal capture for a successful ablation site were 100% each. The sensitivity and negative predictive values were 16% and 58%, respectively. Table 1 compares the sensitivity, specificity, and positive and negative predictive values of other mapping criteria.
Follow-up Mean follow-up was 12 ⫾ 8.4 months (range 1–26). In 3 of 29 patients, VTs that had a cycle length similar to that of the targeted VT recurred. This resulted in a repeat procedure in two of three patients and a change in the antiarrhythmic medications in one patient. In the remaining patients, neither change in the antiarrhythmic regimen nor revascularization procedures were done during the follow-up period.
Bogun et al Table 1
Ventricular Tachycardia
425
Comparison of mapping criteria
Variables
PPV
NPV
Sensitivity
Specificity
P value
N-G capture without CE (n ⫽ 10) N-G capture ⫾ CE (n ⫽ 15) S-QRS ⫽ EGM QRS (n ⫽ 37) IP-dissoc. (n ⫽ 23) SQRS/VTCL ⬍ 0.7 (n ⫽ 33)
100% 100% 84% 79% 56%
53% 56% 83% 67% 74%
24% 29% 84% 64% 83%
100% 100% 83% 81% 43%
0.001 ⬍0.001 ⬍0.001 ⬍0.001 0.01
P value indicates the ability of the mapping criterion to differentiate effective from ineffective sites. N-G capture ⫽ nonglobal capture; CE ⫽ concealed entrainment; S-QRS ⫽ stimulus-QRS interval; EGM-QRS ⫽ electrogram-QRS interval; IP-dissoc. ⫽ isolated potential that cannot be dissociated from VT; S-QRS/VTCL ⫽ stimulus-QRS interval/VT cycle length ratio; PPV ⫽ positive predictive value; NPV ⫽ negative predictive value.
Discussion Main findings This study demonstrates that termination of VT by pacing with nonglobal capture is demonstrable in approximately one third of patients with postinfarction VT, and that this criterion is very specific for identifying a critical component of the reentrant circuit, whether or not concealed entrainment can be demonstrated at the pacing site. In most instances, there was no evidence of local capture when VT was terminated by nonglobal capture.
Mapping criteria During entrainment mapping, the presence of concealed entrainment identifies a protected area that is within or connected to the reentrant circuit. However, not all sites with concealed entrainment are critical to the reentrant circuit, and the positive predictive value of concealed entrainment for an effective target site is only 50%. Prior studies have described the incremental value of mapping criteria other than concealed entrainment.10 The present study demonstrates that VT termination by pacing with nonglobal capture improves the positive predictive value of concealed entrainment for effective ablation sites from approximately 50% to 100%. Based on our results, termination of VT by pacing with nonglobal capture may be sufficient by itself to justify delivery of radiofrequency energy. We found VT termination with nonglobal capture to be the most specific mapping criterion for identification of critical areas of postinfarction VT reentrant circuits.
Possible mechanisms of arrhythmia termination Different electrophysiologic mechanisms may be responsible for the phenomenon of VT termination despite nonglobal capture.1,3,4 Local capture of the isthmus without global ventricular capture may terminate VT by resulting in block in both directions within the isthmus. This mechanism appears to be uncommon, as local capture was observed at only 2 of 15 sites where VT termination occurred.
Prior studies have demonstrated that an impulse delivered during the refractory period may prolong repolarization and refractoriness of tissue.3,4 In poorly coupled tissues with diminished excitability and complex anisotropy (such as scar), a nonexcitatory impulse also may induce postrepolarization refractoriness locally.11 This may explain how pacing stimuli may terminate VT in the absence of local capture. For VT to terminate due to prolongation of repolarization, a prerequisite would be for the tachycardia to have a long wavelength and a short excitable gap. Conversely, if the arrhythmia had a long excitable gap with slow conduction through the isthmus, a nonexcitatory impulse could induce postrepolarization refractoriness and conduction block by electrotonic inhibition.12 In this scenario, the head of the wavefront encounters refractory tissue within the isthmus, and the VT terminates. Poorly coupled tissues with diminished excitability would be a prerequisite for this mechanism to occur.
Prior studies Different terms have been used to describe VT termination during pacing with nonglobal capture. Subthreshold stimulation is one of these terms. It has been recognized that subthreshold stimulation delivered within the effective refractory period of the atrium or the ventricle prolongs the refractory period locally.3,4,13 Ruffy et al14 described this phenomenon for the first time in a postinfarction patient. Subthreshold stimulation subsequently was described in case reports as a criterion to identify critical sites of the reentrant circuit of postinfarction VT.1 Several reports stress that the stimuli must be delivered close to the site of origin of the VT in order to terminate the VT with subthreshold stimulation.1,15,16 However, no prior studies have systematically determined the prevalence of termination of VT by pacing with nonglobal capture and the value of nonglobal capture as a mapping criterion to guide radiofrequency ablation.
Study limitations The majority of the targeted VTs were hemodynamically stable; therefore, the results of this study cannot be extrap-
426 olated to unstable VTs. The sample size was small, and the results need to be confirmed in a larger series. VT termination with nonglobal capture might have been observed more frequently if the entire cycle length of the VT had been scanned with a pacing stimulus rather than using a fixed coupling interval. Finally, given the inherent limitations of extracellullar recordings, it is difficult to identify the exact mechanisms of VT termination by pacing with nonglobal capture.
Clinical implications The presence of nonglobal capture during pacing is of great clinical value because it predicts an effective ablation site with some certainty. The low sensitivity limits the applicability of nonglobal capture as the only mapping criteria. Further studies in which the entire cardiac cycle length is scanned with a subthreshold stimulus will be helpful in determining whether the sensitivity of this criterion can be improved.
References 1. Podczeck A, Borggrefe M, Martinez-Rubio A, Breithardt G. Termination of re-entrant ventricular tachycardia by subthreshold stimulus applied to the zone of slow conduction. Eur Heart J 1988;9:1146 – 1150. 2. Ruffy R. Termination of ventricular tachycardia by nonpropagated local depolarization: further observations on entrainment of ventricular tachycardia from an area of slow conduction. Pacing Clin Electrophysiol 1990;13:852– 858. 3. Windle JR, Miles WM, Zipes DP, Prystowsky EN. Subthreshold conditioning stimuli prolong human ventricular refractoriness. Am J Cardiol 1986;57:381–386. 4. Skale BT, Kallok MJ, Prystowsky EN, Gill RM, Zipes DP. Inhibition of premature ventricular extrastimuli by subthreshold conditioning stimuli. J Am Coll Cardiol 1985;6:133–140.
Heart Rhythm, Vol 1, No 4, October 2004 5. Shenasa M, Cardinal R, Kus T, Savard P, Fromer M, Page P. Termination of sustained ventricular tachycardia by ultrarapid subthreshold stimulation in humans. Circulation 1988;78(5 Pt 1):1135– 1143. 6. Garan H, Ruskin JN. Reproducible termination of ventricular tachycardia by a single extrastimulus within the reentry circuit during the ventricular effective refractory period. Am Heart J 1988;116(2 Pt 1): 546 –550. 7. Bogun F, Hohnloser SH, Bender B, Li YG, Groenefeld G, Pelosi F, Oral H, Knight B, Strickberger SA, Morady F. Mechanism of ventricular tachycardia termination by pacing at left ventricular sites in patients with coronary artery disease. J Interv Card Electrophysiol 2002;6:35– 41. 8. Josephson ME. Clinical cardiac electrophysiology: techniques and interpretations, 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 2002. 9. Josephson M. Clinical cardiac electrophysiology techniques and interpretations, 2nd edition. Philadelphia; Lea & Febiger, 1993: 427. 10. Bogun F, Bahu M, Knight B, Weiss R, Paladino W, Harvey M, Goyal R, Daoud E, Man K, Strickberger S, Morady F. Comparison of effective and ineffective target sites that demonstrate concealed entrainment in patients with coronary artery disease undergoing radiofrequency ablation of ventricular tachycardia. Circulation 1997;95:183–190. 11. Antzelevitch C. Electrotonus and reflection. In: Rosen MR, Wit AL, Janse MJ, eds. Cardiac electrophysiology: a textbook. Mount Kisco, NY: Futura Publishing Co., 1990:491–516. 12. Antzelevitch C, Moe GK. Electrotonic inhibition and summation of impulse conduction in mammalian Purkinje fibers. Am J Physiol 1983;245:H42–H53. 13. Prystowsky EN, Zipes DP. Inhibition in the human heart. Circulation 1983;68:707–713. 14. Ruffy R, Friday KJ, Southworth WF. Termination of ventricular tachycardia by single extrastimulation during the ventricular effective refractory period. Circulation 1983;67:457– 459. 15. Shenasa M, Fromer M, Borggrefe M, Breithardt G. Subthreshold electrical stimulation for termination and prevention of reentrant tachycardias. J Electrocardiol 1992;24(Suppl):25–31. 16. Shenasa M, Fromer M. Termination of sustained ventricular tachycardia by subthreshold electrical stimulation via epicardial patch electrodes (abstr). Circulation 1991;85:II-427.