Comparison of Effective and Ineffective Target Sites That Demonstrate Concealed Entrainment in Patients With Coronary Artery Disease Undergoing Radiofrequency Ablation of Ventricular Tachycardia
Background Concealed entrainment has been useful in guiding catheter ablation of monomorphic ventricular tachycardia in patients with coronary artery disease. However, not all sites with concealed entrainment result in successful ablation of the targeted ventricular tachycardia. The purpose of this prospective study was to identify factors at sites that demonstrate concealed entrainment that differentiate effective from ineffective target sites.
Methods and Results In 14 consecutive patients with hemodynamically stable monomorphic ventricular tachycardia and coronary artery disease, radiofrequency ablation of 26 ventricular tachycardias was performed. Ablation was attempted at 46 sites that demonstrated concealed entrainment. Twenty-five of the targeted ventricular tachycardias (96%) were successfully ablated. The positive predictive value of concealed entrainment for successful ablation was 54%; it increased to 72% in the presence of a stimulus-QRS interval/ventricular tachycardia cycle length ratio of ≤70%, to 82% in the presence of a match of the stimulus-QRS and electrogram-QRS interval, and to 89% in the presence of isolated middiastolic potentials that could not be dissociated from ventricular tachycardia during entrainment.
Conclusions The positive predictive value of concealed entrainment for identification of successful ablation sites in patients with sustained ventricular tachycardia and coronary artery disease can be significantly enhanced by the presence of associated mapping criteria, particularly an isolated mid diastolic potential that cannot be dissociated from the tachycardia.
The phenomenon of concealed entrainment, also referred to as entrainment with concealed fusion,1 2 has been shown to identify a zone of slow conduction within the reentry circuit of ventricular tachycardia in patients with coronary artery disease.3 4 Although concealed entrainment may be useful in identifying sites for catheter ablation of ventricular tachycardia, radiofrequency energy applications at sites at which concealed entrainment is demonstrable are not always effective in the elimination of ventricular tachycardia.1 5 Therefore, the purpose of this prospective study was to compare effective and ineffective target sites at which concealed entrainment was present in patients with coronary artery disease who were undergoing catheter ablation of sustained, monomorphic ventricular tachycardia. The goal of the study was to identify variables that were predictive of a successful outcome, thereby improving the value of concealed entrainment as a guide for the identification of effective ablation sites.
The subjects of the present study were 14 consecutive patients with coronary artery disease and recurrent, hemodynamically stable, sustained monomorphic ventricular tachycardia who underwent a radiofrequency catheter ablation procedure at the University of Michigan Medical Center between December 1994 and December 1995 (Table 1⇓). There were 12 men and 2 women, and their mean age was 66±14 years (±SD). Each patient had a history of at least one myocardial infarction (anterior in 3, inferior in 5, and both in 6). Their mean left ventricular ejection fraction was 0.25±0.11.
Ten of the 14 patients had undergone implantation of an internal cardioverter-defibrillator before the ablation procedure. The indication for the ablation procedure consisted of incessant ventricular tachycardia in 7 patients; frequent internal cardioverter-defibrillator discharges (ranging from 120 shocks to 5 shocks within 2 days) in 5 patients; and recurrent, sustained monomorphic ventricular tachycardia associated with palpitations and lightheadedness in 2 patients. Before the ablation procedure, a mean of 1.6±0.8 antiarrhythmic drugs had failed to suppress spontaneous episodes of ventricular tachycardia. At the time of the ablation procedure, 10 patients were being treated with amiodarone, 2 with sotalol, 1 with quinidine, and 1 with procainamide.
The electrophysiology procedures were performed with the subjects in the fasting state after informed consent was obtained. An electrode catheter was inserted into a femoral vein and positioned in the right ventricle for programmed ventricular stimulation. Left ventricular mapping and ablation were performed with a 7F, quadripolar electrode catheter that had an interelectrode spacing of 2/5/2 mm, a deflectable tip, and a 4-mm distal electrode with a thermistor for monitoring temperature at the electrode-tissue interface (EP Technologies). The catheter was inserted into the left ventricle through a retrograde aortic approach from the femoral artery in 13 patients and through a transseptal approach in 1 patient who had aortic stenosis. A bolus of 5000 U of heparin was administered intravenously at the beginning of the procedure, followed by 1000 U/h heparin.
The intracardiac electrograms and leads V1, I, II, and III were displayed on an oscilloscope and recorded with a Mingograph 7 recorder (Siemens) at a paper speed of 100 mm/s. The left ventricular endocardial electrograms were recorded simultaneously at gain settings of 20 and 80 mm/mV at filter settings of 50 to 500 Hz. Pacing was performed with a programmable stimulator (Bloom Associates). In patients who did not have incessant ventricular tachycardia, right ventricular programmed stimulation was used to induce ventricular tachycardia with a stimulation protocol using four extrastimuli.6 Induced episodes of ventricular tachycardia were recorded on a 12-lead ECG. Left ventricular sites were paced during ventricular tachycardia using stimuli that had a pulse width of 2 ms and a current strength 1 to 2 mA higher than the capture threshold, up to 10 mA. If there was no reliable capture at an output of 10 mA, the pulse width was increased as necessary to a maximum of 9 ms. Sustained ventricular tachycardia was defined as ventricular tachycardia lasting ≥30 seconds or requiring termination because of loss of consciousness.
Pacing and Recording at Mapping Sites
In some studies, the response of ventricular tachycardia to pacing has been evaluated using unipolar pacing and either unipolar recordings from the distal electrode or bipolar recordings from the distal electrode pair.7 Although the unipolar technique eliminates a possible anodal contribution to depolarization and also has the advantage of allowing pacing and recording at the same location, the drawbacks are the sensing of far-field signals and the inability to record an undisturbed electrogram during or immediately after pacing. Therefore, in this study, bipolar pacing and recordings were used at mapping sites. To simultaneously pace and record in bipolar fashion at endocardial sites as close together as possible, electrodes 1 and 3 of the mapping catheter were used for bipolar pacing and electrodes 2 and 4 were used for recording.
Left ventricular mapping was performed during ventricular tachycardia. To identify sites at which there was concealed entrainment, pacing trains of 10 to 15 stimuli at cycle lengths 20 to 100 ms (3% to 22%) shorter than the ventricular tachycardia cycle length were introduced at all sites at which the local electrogram was abnormal (amplitude of ≤0.5 mV and duration of ≥60 ms),8 at which the local electrogram preceded the QRS complex by ≥40 ms, or at which an isolated middiastolic potential was present. Concealed entrainment was defined as acceleration of the ventricular tachycardia to the pacing cycle length, with no change in the QRS morphology in any of the 12 ECG leads during pacing at two or more pacing cycle lengths compared with the ventricular tachycardia; in addition, the stimulus-QRS interval was ≥60 ms, and there was resumption of ventricular tachycardia on the cessation of pacing (Fig 1A⇓). Whenever possible, concealed entrainment was confirmed by pacing at the same site during sinus rhythm to note whether there was a different QRS configuration than during pacing in the setting of ventricular tachycardia (Fig 1B⇓).
Delivery of Radiofrequency Energy
Radiofrequency energy was delivered during ventricular tachycardia at all sites at which concealed entrainment was present and not at any sites at which concealed entrainment was not present. Mapping of the entire left ventricle was not required before delivery of energy at a site at which concealed entrainment was demonstrated. The radiofrequency energy was delivered as a continuous, unmodulated sine wave at a frequency of 500 kHz (EP Technologies). The initial power setting was 10 W, and the power was titrated upward, as guided by temperature monitoring, to attain a temperature of 60°C. Once this end point was reached, the application of energy was continued for ≥20 seconds. If ventricular tachycardia did not terminate, the energy application was discontinued and mapping was continued at other sites; if ventricular tachycardia did terminate, the energy application was continued for a total of 60 seconds at the final power setting.
Programmed ventricular stimulation was then repeated to determine whether the targeted ventricular tachycardia or other ventricular tachycardias were still inducible. For the purposes of this study, an effective target site was defined as a site at which radiofrequency energy terminated ventricular tachycardia and prevented the reinduction of the targeted ventricular tachycardia using the entire programmed ventricular stimulation protocol. Ineffective target sites were defined as sites at which the application of radiofrequency energy did not terminate or prevent the reinduction of ventricular tachycardia despite an electrode/tissue interface temperature of ≥55°C.
Post Hoc Analysis of Mapping Data
After completion of the electrophysiology procedure, all target sites at which radiofrequency energy had been delivered were analyzed in regard to the following criteria. (1) Endocardial activation time: the timing of the local electrogram was measured relative to the earliest onset of the QRS complex in leads I, II, III, and V1. If an isolated middiastolic potential was present, the endocardial activation time was measured both including and excluding the middiastolic potential as part of the local electrogram. (2) An isolated middiastolic potential: this was defined as a low-amplitude, high-frequency diastolic potential separated from the preceding and subsequent ventricular electrograms by an isoelectric segment9 (Fig 2⇓). Isolated middiastolic potentials were subcategorized on the basis of whether they could or could not be dissociated from the ventricular tachycardia by pacing maneuvers. (3) The local electrogram-QRS interval during ventricular tachycardia was compared with the stimulus-QRS interval during entrainment (Fig 3⇓). When the electrogram-QRS interval is equal to the stimulus-QRS interval, this has been considered to be evidence that the pacing site lies within the reentry circuit.4 (4) The postpacing interval: this was defined as the interval from the last stimulus artifact of a pacing train that entrained the ventricular tachycardia to the electrogram of the first nonstimulated beat (Fig 4⇓). A postpacing interval that is within 30 ms of the ventricular tachycardia cycle length also has been considered to be evidence that the pacing site is within the reentry circuit.1 2
At each target site, the ratio of the stimulus-QRS interval to the ventricular tachycardia cycle length was determined and used as an indicator of the position of the mapping catheter relative to the common pathway of the reentry circuit. Sites at which the stimulus-QRS interval/ventricular tachycardia cycle length ratio was ≤0.7 were considered to lie within the common pathway of a figure-8 reentry circuit (Fig 3⇑), and sites at which the ratio was ≥0.7 were considered to lie outside the common pathway.2
After the ablation procedure, treatment was continued with the same antiarrhythmic medications with which the patients were being treated during the ablation procedure. In 6 patients, programmed ventricular stimulation was performed 5 to 7 days after the ablation procedure to confirm that the ventricular tachycardias that had been targeted were still not inducible. Two patients underwent internal cardioverter-defibrillator implantation: 1 because of a failed ablation attempt, and the other because of inducible ventricular tachycardia that was hemodynamically unstable. After discharge from the hospital, the patients were seen on an outpatient basis at 3- to 4-month intervals.
Continuous data are expressed as mean±1 SD. Statistical comparisons were performed using Student's t test, the Fisher exact test, or χ2 analysis, as appropriate. Correlations between continuous variables were determined by regression analysis. A value of P<.05 was considered to be statistically significant.
Ventricular Tachycardia Characteristics
A mean of 2.0±2.3 ventricular tachycardias were targeted for ablation in each patient, for a total of 26 different ventricular tachycardias among the 14 patients in this study (Table 1⇑). A single morphology of monomorphic ventricular tachycardia was targeted in 7 patients, and 2 to 10 ventricular tachycardias were targeted in the remaining 7 patients. The mean cycle length of the targeted ventricular tachycardias was 486±87 ms. Thirteen of the ventricular tachycardias had a right bundle-branch block configuration, and 13 had a left bundle-branch block configuration. In each of the 12 patients, at least 1 of the targeted ventricular tachycardias had been documented to occur spontaneously.
Results of Ablation
At least one site at which there was concealed entrainment could be demonstrated for each of the 26 ventricular tachycardias, and the total number of sites at which there was concealed entrainment was 46. Ablation of ventricular tachycardia was attempted at each of these 46 left ventricular sites. Twenty-five of the 26 targeted ventricular tachycardias (96%) were successfully ablated. All targeted ventricular tachycardias were successfully ablated in 13 of 14 patients (93%). The mean number of applications of radiofrequency energy was 2.1±1.1 per ventricular tachycardia and 3.6±2.6 per patient. The mean duration of fluoroscopy was 50±28 minutes (range, 16 to 143 minutes). A second ablation 2 to 4 days after the first procedure was required in 5 patients. The only complication occurred in patient 8, who developed high-degree atrioventricular block and required placement of a permanent pacemaker after an application of radiofrequency energy during ventricular tachycardia at the left ventricular basal septum.
Mapping Data at Ablation Sites
The mean stimulus-QRS interval during concealed entrainment was 256±138 ms, with a range of 60 to 590 ms. The mean endocardial activation time was −120±67 ms, with a range of 20 to −300 ms; the endocardial activation time was <−70 ms at 37 of the 46 sites (80%). An isolated middiastolic potential was present at 15 of the 46 target sites (33%); six of the isolated middiastolic potentials could be dissociated from the ventricular tachycardia, and the other nine could not. The electrogram-QRS interval was equal to the stimulus-QRS interval at 17 of the 46 sites (37%). The postpacing interval was within 30 ms of the ventricular tachycardia cycle length at 31 of the 46 sites (67%).
The ratio of the stimulus-QRS interval to the ventricular tachycardia cycle length was <0.7 (mean, 0.38±0.19) at 34 of the 46 ablation sites (74%) and >0.7 (mean, 0.86±0.13) at the remaining 12 sites (26%).
Comparison of Effective and Ineffective Target Sites
Among the 46 sites at which there was concealed entrainment, 25 sites (61%) were effective target sites and 21 were not. The effective and ineffective sites are compared in Table 2⇓.
The stimulus-QRS interval during concealed entrainment was significantly shorter at effective than at ineffective target sites (P<.01). The ratio of the stimulus-QRS interval to the ventricular tachycardia cycle length was significantly shorter at effective than at ineffective sites (P=.002; Fig 5⇓). At all except one of the effective sites, the stimulus-QRS interval/ventricular tachycardia cycle length ratio was <0.7. Other significant differences between the effective and ineffective sites included an earlier endocardial activation time (P<.05) and the more common occurrence of the electrogram-to-QRS interval being the same as the stimulus-QRS interval (P<.05) at the effective sites.
Isolated middiastolic potentials were equally distributed between effective and ineffective target sites. However, isolated middiastolic potentials that could not be dissociated from the ventricular tachycardia were more common at the effective than at the ineffective target sites (P<.05).
The prevalence of a postpacing interval that was within 30 ms of the ventricular tachycardia cycle length did not differ significantly between the effective and ineffective target sites.
Sensitivity, Specificity, and Positive and Negative Predictive Values
The sensitivity and specificity of the various mapping criteria for effective target sites are described in Table 3⇓.
The positive predictive value of concealed entrainment for the identification of an effective ablation site was 54% (Table 3⇑). The positive predictive value of concealed entrainment was increased to the greatest degree, to 89%, by association with an isolated middiastolic potential that could not be dissociated from the ventricular tachycardia. When combined with an electrogram-QRS interval equal to the stimulus-QRS interval, the positive predictive value of concealed entrainment was 82%, and when combined with a stimulus-QRS interval/ventricular tachycardia cycle length ratio of <0.7, it was 71%.
Because concealed entrainment was present at all ablation sites, the negative predictive value of concealed entrainment could not be determined in this study. The criterion in association with concealed entrainment that had the highest negative predictive value for the identification of an effective ablation site was a stimulus-QRS interval/ventricular tachycardia cycle length ratio of <0.7, which had a negative predictive value of 92%.
The 14 patients were followed for a mean of 8.7±6.7 months. Two patients died as a result of preexisting congestive heart failure or a malignancy at 3 and 11 months of follow-up, respectively. Among the 12 who had an internal cardioverter/defibrillator, there were no recurrences of incessant ventricular tachycardia or frequent internal cardioverter/defibrillator discharges; these patients experienced an average of none to seven discharges or antitachycardia pacing therapies per month. In the 2 patients who did not have an internal cardioverter/defibrillator, there were no recurrences of symptomatic ventricular tachycardia.
Concealed entrainment may identify sites within the zone of slow conduction or common pathway of the ventricular tachycardia reentry circuit in patients with coronary artery disease.1 2 3 4 5 However, the positive predictive value of concealed entrainment in identifying effective ablation sites in this series was only 54%, indicating that concealed entrainment may often identify sites that are not critical to the maintenance of reentry, such as a blind alley, alternate pathway, or inner loop.
The results of this study demonstrate that among the several other mapping criteria examined in this study in combination with concealed entrainment, three are helpful in increasing the probability of identifying an effective site for ablation of ventricular tachycardia. In combination with concealed entrainment, an isolated middiastolic potential that cannot be dissociated from ventricular tachycardia increases the positive predictive value for identifying an effective ablation site to ≈90%. If the electrogram-QRS interval is equal to the stimulus-QRS interval at a site at which there is concealed entrainment, the positive predictive value is ≈80%, and if the stimulus-QRS/ventricular tachycardia cycle length ratio is <0.7, the positive predictive value for successful ablation is ≈70%. Therefore, by searching for one of these three mapping criteria in association with concealed entrainment, the probability of successful ablation of ventricular tachycardia with a minimum number of radiofrequency energy applications can be significantly improved.
Of note is that concealed entrainment was demonstrable in each of the 26 ventricular tachycardias that were targeted for ablation in the 14 patients in this study. In contrast, in prior studies, concealed entrainment has been demonstrated in only 38% to 71% of patients with coronary artery disease and sustained monomorphic ventricular tachycardia.5 10 11 However, the patients in the present study were a selected group of patients and were not representative of the typical patient with coronary artery disease and sustained ventricular tachycardia. All of the patients in this study were being treated with an antiarrhythmic drug at the time of the ablation procedure; 50% of the patients had incessant ventricular tachycardia; all except 4 patients had already undergone implantation of an internal cardioverter-defibrillator; and the mean ventricular tachycardia cycle length was ≈500 ms, which is relatively long. It is possible that these factors facilitated the demonstration of concealed entrainment in these patients.
Isolated Middiastolic Potentials
A previous study demonstrated that isolated middiastolic potentials that cannot be dissociated from ventricular tachycardia are a reliable guide for DC ablation of ventricular tachycardia in patients with coronary artery disease, but pacing at the sites at which the isolated middiastolic potentials were recorded was not performed in that study.9 In the present study, the highest probability of successful ablation at sites at which there was concealed entrainment occurred when the site displayed an isolated middiastolic potential that could not be dissociated from the ventricular tachycardia.
It is likely that isolated middiastolic potentials that cannot be dissociated from ventricular tachycardia are generated in segments of the zone of slow conduction or common pathway, which are integral components of the reentry circuit.9 This would explain why this mapping criterion improves the positive predictive value of concealed entrainment for identifying an effective target site from ≈50% to ≈90%. However, because isolated middiastolic potentials were present at only a minority of effective target sites, their negative predictive value in combination with concealed entrainment is relatively low.
Electrogram-QRS Interval Equal to Stimulus-QRS Interval
The second most helpful mapping criterion for predicting a successful outcome at a site at which concealed entrainment was demonstrated was found to be an electrogram-QRS interval that was equal to the stimulus-QRS interval during concealed entrainment. This criterion was previously proposed to be helpful in differentiating a critical component of the zone of slow conduction from a blind alley or noncritical alternate pathway.4 Although this criterion increased the positive predictive value of concealed entrainment to ≈80%, it was not perfect in distinguishing effective from ineffective ablation sites.
Several factors may explain why the electrogram-QRS interval was not equal to the stimulus-QRS interval at all of the effective target sites in this study. One factor is likely to be the decremental conduction properties of the zone of slow conduction, which could account for a lengthening of the stimulus-QRS interval during pacing.5 12 13 Stimulus latency in an area of diseased tissue might also account for a delay in the stimulus-QRS interval compared with the electrogram-QRS interval. Finally, failure of the recording electrodes to detect low-amplitude depolarizations at the pacing site could account for a mismatch of the stimulus-QRS and electrogram-QRS intervals.14
Stimulus-QRS/Ventricular Tachycardia Cycle Length Ratio
On the basis of a computer model of a reentry circuit, Stevenson et al2 suggested that a stimulus-QRS/ventricular tachycardia cycle length ratio of >0.7 indicates that a pacing site lies outside the common pathway. Therefore, a ratio of ≤0.7 would be expected to improve the positive predictive value of concealed entrainment by eliminating the sites at which there is concealed entrainment but that do not lie within the common pathway. Accordingly, the negative predictive value of this criterion was 92%, indicating that ablation at sites with concealed entrainment at which the stimulus-QRS/ventricular tachycardia cycle length ratio is >0.7 is unlikely to be successful.
In this study, the combination of concealed entrainment and a stimulus-QRS/ventricular tachycardia cycle length ratio of ≤0.7 was associated with a relatively modest positive predictive value of ≈70%. It is possible that in some patients, even though a target site lies within the common pathway, ablation at that site is ineffective because the width of the common pathway is larger than the width of the lesion created by the radiofrequency energy.
Endocardial Activation Time
Although endocardial activation relative to the onset of the QRS complex occurred significantly earlier at effective than at ineffective target sites, this was the case only when isolated middiastolic potentials were considered to be part of the local electrogram. Considering only the continuous portion of the local electrogram, the endocardial activation time did not distinguish effective from ineffective sites. Therefore, although endocardial activation mapping has been useful in guiding surgical and catheter ablation of ventricular tachycardia,15 16 17 it appears to be of no incremental value at sites that demonstrate concealed entrainment.
Another mapping criterion that has been proposed to be helpful in identifying sites that are integral components of the reentry circuit is a postpacing interval that is within 30 ms of the ventricular tachycardia cycle length.1 2 However, in the present study, at sites that demonstrated concealed entrainment, this criterion was not helpful in distinguishing effective from ineffective ablation sites.
The failure of the postpacing interval to improve the predictive value of concealed entrainment may be due at least in part to the bipolar pacing technique used in this study. Because of a possible anodal contribution to local activation2 and because the local electrogram was not recorded from the same pair of electrodes used for pacing, errors may have been introduced into the comparisons of postpacing interval to the ventricular tachycardia cycle length. Additional errors may have been introduced by the decremental conduction properties of the zone of slow conduction that might cause a rate-dependent lengthening of the postpacing interval.5 12 13
A limitation of this study is that exhaustive mapping of the left ventricle was not performed before delivery of radiofrequency energy applications. To minimize the duration of the procedures and the risk of complications, ablation was attempted at any site at which concealed entrainment was demonstrated. Had complete mapping of the left ventricle been performed before ablation, additional sites with concealed entrainment may have been found, possibly altering the results of the study.
A second limitation is the possibility that some target sites were ineffective in ablating ventricular tachycardia not because of failure of the mapping criteria to identify a critical portion of the reentry circuit but rather because of inadequate heating or inadequate lesion size. To minimize this possibility, energy applications were guided by temperature monitoring, and a minimum temperature of 55°C was required before the conclusion was made that a target site was ineffective. However, although an electrode-tissue interface temperature of 55°C to 60°C is sufficient to ablate normal myocardium,18 19 20 it is unknown whether a higher temperature may be needed to ablate scarred or diseased myocardium.
Last, this study was designed to elucidate the predictive value only of concealed entrainment by itself or in combination with other mapping criteria. Therefore, this study does not provide any information on the predictive value of the various mapping criteria independent of their association with concealed entrainment.
The phenomenon of concealed entrainment is not specific to effective ventricular tachycardia ablation sites in patients with coronary artery disease, probably because concealed entrainment may occur at areas that have input into the zone of slow conduction or common pathway but are not critical components of the reentry circuit. Ancillary mapping criteria are useful in enhancing the positive predictive value of concealed entrainment to the 80% to 90% range, most notably, the presence of an isolated middiastolic potential that cannot be dissociated from the ventricular tachycardia and an electrogram-QRS interval that is equal to the stimulus-QRS interval. Furthermore, if the ratio of the stimulus-QRS interval to the ventricular tachycardia cycle length is >0.7, a successful ablation outcome is highly unlikely despite the presence of concealed entrainment. By evaluation of these mapping criteria at sites at which concealed entrainment is present, the number of radiofrequency energy applications needed to successfully ablate ventricular tachycardia in patients with coronary artery disease can be minimized.
- Received April 8, 1996.
- Revision received August 8, 1996.
- Accepted August 22, 1996.
- Copyright © 1997 by American Heart Association
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