Author + information
- Received October 21, 2011
- Revision received December 15, 2011
- Accepted January 2, 2012
- Published online April 24, 2012.
- David S. Frankel, MD⁎,
- Stavros E. Mountantonakis, MD†,
- Erica S. Zado, PA-C⁎,
- Elad Anter, MD⁎,
- Rupa Bala, MD⁎,
- Joshua M. Cooper, MD⁎,
- Rajat Deo, MD⁎,
- Sanjay Dixit, MD⁎,
- Andrew E. Epstein, MD⁎,
- Fermin C. Garcia, MD⁎,
- Edward P. Gerstenfeld, MD⁎,
- Mathew D. Hutchinson, MD⁎,
- David Lin, MD⁎,
- Vickas V. Patel, MD, PhD⁎,
- Michael P. Riley, MD, PhD⁎,
- Melissa R. Robinson, MD⁎,
- Wendy S. Tzou, MD⁎,
- Ralph J. Verdino, MD⁎,
- David J. Callans, MD⁎ and
- Francis E. Marchlinski, MD⁎,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Francis E. Marchlinski, Hospital of the University of Pennsylvania, 9 Founders Pavilion 3400 Spruce Street, Philadelphia Pennsylvania 19104
Objectives The goal of this study was to evaluate the ability of noninvasive programmed stimulation (NIPS) after ventricular tachycardia (VT) ablation to identify patients at high risk of recurrence.
Background Optimal endpoints for VT ablation are not well defined.
Methods Of 200 consecutive patients with VT and structural heart disease undergoing ablation, 11 had clinical VT inducible at the end of ablation and 11 recurred spontaneously. Of the remaining 178 patients, 132 underwent NIPS through their implantable cardioverter-defibrillator 3.1 ± 2.1 days after ablation. At 2 drive cycle lengths, single, double, and triple right ventricular extrastimuli were delivered to refractoriness. Clinical VT was defined by comparison with 12-lead electrocardiograms and stored implantable cardioverter-defibrillator electrograms from spontaneous VT episodes. Patients were followed for 1 year.
Results Fifty-nine patients (44.7%) had no VT inducible at NIPS; 49 (37.1%) had inducible nonclinical VT only; and 24 (18.2%) had inducible clinical VT. Patients with inducible clinical VT at NIPS had markedly decreased 1-year VT-free survival compared to those in whom no VT was inducible (<30% vs. >80%; p = 0.001), including 33% recurring with VT storm. Patients with inducible nonclinical VT only, had intermediate 1-year VT-free survival (65%).
Conclusions When patients with VT and structural heart disease have no VT or nonclinical VT only inducible at the end of ablation or their condition is too unstable to undergo final programmed stimulation, NIPS should be considered in the following days to further define risk of recurrence. If clinical VT is inducible at NIPS, repeat ablation may be considered because recurrence over the following year is high.
Optimal endpoints for ablation of ventricular tachycardia (VT) in patients with structural heart disease are not well defined. Typically, acute success is defined by noninducibility with programmed stimulation at the end of ablation of: 1) all clinical VTs; 2) all VTs with cycle lengths greater than or equal to the clinical cycle lengths; or 3) all VTs. However, even when these endpoints are achieved, subsequent recurrence of VT is not uncommon (1–4). Therefore, new endpoints that can predict greater freedom from long-term VT recurrence are needed.
There are several reasons why programmed stimulation at the end of ablation may fail to predict VT recurrence. First, changes in antiarrhythmic drugs are frequently made after ablation, particularly related to dosing or discontinuation of amiodarone. Second, the induction of re-entrant arrhythmias with programmed stimulation is probabilistic, and reproducibility is far from perfect (5). Third, changes in autonomic tone and/or the use of general anesthesia may affect VT inducibility (6,7). Fourth, ablation lesions may either expand as a result of disruption of microcirculation, with consequent myocyte loss, or regress secondary to healing and resolution of edema (8,9). Fifth, the patient's condition may be too unstable to subject to rigorous programmed stimulation after a prolonged ablation procedure.
Noninvasive programmed stimulation (NIPS) can be performed via a patient's implantable cardioverter-defibrillator (ICD) in the week after ablation to overcome some of these limitations. We hypothesized that among those without clinical VT inducible at the end of ablation and without spontaneous VT recurrence, inducibility of clinical VT at NIPS would identify an additional subgroup of patients at high risk of long-term VT recurrence.
We studied consecutive patients with sustained VT and structural heart disease who were referred to the Hospital of the University of Pennsylvania for ablation between January 2008 and April 2010. Patients with idiopathic VT were excluded. All patients provided written informed consent, and all procedures conformed to the University of Pennsylvania Health System guidelines.
Electrophysiology study and ablation
Conscious sedation was used whenever possible. General anesthesia with an inhaled anesthetic, most commonly sevoflurane, was used when necessary for ventilation, oxygenation, or patient comfort. In addition, general anesthesia was typically used during epicardial mapping and ablation. Electroanatomic mapping (CARTO, Biosense Webster, Inc., Diamond Bar, California) was performed during sinus or paced rhythm to define areas of low voltage and abnormal electrograms, consistent with scar (10). Programmed stimulation was performed and induced VTs were compared with those occurring spontaneously. When a 12-lead electrocardiogram (ECG) of spontaneous VT was available (62% of cases), clinical VT was defined by match in all 12 ECG leads. When a 12-lead ECG of spontaneous VT was not available (38% of cases), clinical VT was defined by match in near-field and far-field ICD electrogram morphology, as well as cycle length within 30 ms, of stored electrograms from spontaneous VT episodes. Every spontaneously occurring VT was considered clinical; thus, a single patient could have multiple clinical VTs. Special attention was paid to elimination of clinical VT. In addition, all mappable VT and VT with cycle length >250 ms were also considered relevant and routinely targeted for ablation. When hemodynamically tolerated, entrainment mapping was used to define critical components of the VT circuit. If VT was not mappable, substrate modification was performed with linear and/or cluster lesions targeting sites identified by pacemapping and late potentials. Ablation was typically performed using an irrigated ablation catheter (Thermocool [Biosense Webster, Inc.] or Chilli [Boston Scientific, Boston, Massachusetts]) using powers up to 50 W with a goal 12- to 15-ohm impedance drop. Epicardial mapping and ablation were performed when 12-lead ECG of VT suggested an epicardial exit (11) and/or endocardial ablation failed to eliminate targeted VT. After ablation, programmed stimulation was repeated in patients who were medically stable, with up to 3 ventricular extrastimuli delivered from 2 sites at 2 pacing cycle lengths. Ablation was repeated in patients with inducible clinical VT at the end of the first ablation and in those with spontaneous recurrence before NIPS.
Noninvasive programmed stimulation
In the absence of clinical VT being inducible at the end of ablation or spontaneous VT recurrence, NIPS was typically performed within several days of ablation, before hospital discharge. In the fasting state, with intermittent boluses of propofol titrated to deep sedation, single, double, and then triple extrastimuli were delivered to refractoriness at drive trains of 600 and 400 ms, via the right ventricular ICD lead. In 3 patients who did not have ICDs, programmed stimulation was performed via a quadripolar catheter advanced through the femoral vein to the right ventricle. Response to NIPS was categorized as “clinical VT inducible” if any sustained, monomorphic VT was induced matching any of the spontaneous VT on 12-lead ECG or on ICD electrograms when 12-lead ECG of spontaneous VT was not available. Response was categorized as “nonclinical VT inducible” if only sustained monomorphic VT not matching any of the clinical VTs was induced. Finally, if no sustained monomorphic VT could be induced, the response was categorized as “no VT inducible.” Patients with inducible nonsustained monomorphic VT, polymorphic VT, or ventricular fibrillation only were included in the no VT inducible group. The NIPS results were used for prognostic purposes and to optimize ICD programming. Detection rates were adjusted to detect induced VTs. If antitachycardia pacing (ATP) was demonstrated to be effective at NIPS, then specific programming to incorporate effective ATP was performed. In the remaining patients in whom ATP was not effective at NIPS or could not be tested because of noninducibility, 1 or 2 bursts of ATP to attempt to terminate spontaneous episodes without delaying shocks was typically programmed. Additional ablation was not performed on the basis of NIPS results.
Patients were routinely evaluated at 4 to 8 weeks after ablation and then at 3- to 6-month intervals. For patients not followed at our institution, referring cardiologists were contacted and ICD interrogations reviewed to determine arrhythmia recurrence. Telephone interviews were performed at 6- to 12-month intervals with patients or family members to confirm the absence of arrhythmia symptoms. The Social Security Death Index was also queried.
Continuous variables are expressed as mean ± SD, and categorical variables are expressed as percentages. The Student t test and Pearson's chi-square test were used to compare continuous and dichotomous variables, respectively. We constructed Kaplan-Meier curves to illustrate 1-year survival free of VT and compared those with clinical VT inducible at NIPS to those with nonclinical VT inducible and those with no VT inducible, using a log-rank test. This analysis was repeated in the subgroup of patients with ischemic cardiomyopathy only and then with nonischemic cardiomyopathy only. Multivariate logistic regression was used to identify predictors of time to VT recurrence. Variables subjected to univariate screening included age, left ventricular ejection fraction, ischemic cardiomyopathy, prior ablation, VT storm (≥3 episodes of VT within 24 h), amiodarone pre-ablation, high-dose (≥400 mg daily) amiodarone pre-ablation, general anesthesia, clinical VT inducible and sustained, clinical VT hemodynamically tolerated, number of VTs targeted, epicardial ablation, no programmed stimulation at end of ablation, clinical VT inducible at end of ablation, nonclinical VT inducible at end of ablation, NIPS not performed, clinical VT inducible at NIPS, nonclinical VT inducible at NIPS, slow VT (cycle length >300 ms) inducible at NIPS, VT inducible with single or double extrastimuli, polymorphic VT or ventricular flutter inducible at NIPS, and amiodarone dose reduced after ablation. Variables showing marginal associations with recurrence on univariate testing (p < 0.10) were assessed in a multivariate model.
Analyses were performed using SPSS version 16.0 (SPSS Inc., Chicago, Illinois). We considered p values ≤0.05 to indicate statistical significance.
Baseline and procedural characteristics
Of 200 consecutive patients with VT and structural heart disease undergoing ablation between September 2008 and April 2010, a total of 167 underwent programmed stimulation at the end of ablation, with clinical VT inducible in 11 patients (Fig. 1). The remaining 33 patients were not sufficiently medically stable to undergo final programmed stimulation. Eleven patients exhibited recurrence of spontaneous VT in the days after ablation. Of the remaining 178 patients, 132 (74%) underwent NIPS a mean of 3.1 ± 2.1 days after ablation. Reasons for not performing NIPS included unstable medical condition (n = 26), death before NIPS (n = 6), and patient and/or treating physician preference (n = 14). Compared to those in whom NIPS was not performed, patients undergoing NIPS were more likely to have been placed under general anesthesia during ablation, more likely to undergo final programmed stimulation at the end of ablation, and less likely to have any VT inducible at the end of ablation (p = 0.01, 0.05, and 0.01, respectively) (Table 1).
No VT was inducible at NIPS in 59 (44.7%) patients. Nonclinical VT was inducible in 49 (37.1%) and clinical VT inducible in 24 (18.2%) patients. Patients with inducible clinical VT were more likely to be treated with amiodarone, more likely to be treated with high-dose amiodarone, and more likely to have their amiodarone dose reduced after ablation, compared to those in whom no VT was inducible (p = 0.01, 0.01, and 0.01, respectively) (Table 2). Of the 24 patients with clinical VT induced at NIPS, 6 did not undergo programmed stimulation at the end of ablation, 6 had nonclinical VT induced at the end of the ablation, and 12 had no VT induced.
All patients were followed for 1 year after ablation or until censoring at the time of death or heart transplantation. Among patients in whom clinical VT was inducible at NIPS, 21% died during follow-up, compared with 24% among those in whom nonclinical VT was inducible and 3% among those in whom no VT was inducible (p = 0.01 for comparison between clinical inducible VT and no inducible VT). One patient in the nonclinical VT-inducible group and one patient in the no VT-inducible group underwent left ventricular assist device implantation. One patient in the clinical VT-inducible group and one patient in the nonclinical VT-inducible group underwent heart transplantation.
Using univariate testing, lower left ventricular ejection fraction, no programmed stimulation at the end of ablation, inducible clinical VT at the end of ablation, NIPS not performed, inducible clinical VT at NIPS, inducible slow VT (cycle length >300 ms) at NIPS, and amiodarone dose reduced after ablation were all associated with worse 1-year VT-free survival (Table 3). In multivariate analysis, no programmed stimulation at the end of ablation, inducible clinical VT at the end of ablation, NIPS not performed, and inducible clinical VT at NIPS remained independently associated with VT recurrence (p = 0.03, 0.003, 0.02, and 0.03, respectively).
In Kaplan-Meier survival analysis, patients with inducible clinical VT at NIPS had markedly decreased 1-year VT-free survival (<30%, p = 0.001 for comparison to no VT inducible) (Fig. 2). Importantly, 67% of these patients experienced recurrences with ICD shocks and 33% with VT storm. In subgroup analysis, patients with ischemic cardiomyopathy and those with nonischemic cardiomyopathy had worse VT-free survival after induction of clinical VT at NIPS (p = 0.01 and 0.001, respectively, for comparison to no VT inducible). Patients with inducible nonclinical VT had a more modest decrease in 1- year VT-free survival, compared to those with no VT inducible at NIPS (65% vs. 85%; p = 0.01).
In our series of consecutive patients with structural heart disease undergoing VT ablation, inducibility of clinical VT at the end of ablation (n = 11) and spontaneous recurrence before NIPS (n = 11) both identified patients at high risk of 1-year VT recurrence. However, inducibility of clinical VT at NIPS (n = 24) identified an additional group of patients at high risk of recurrence, including ICD shocks and VT storm, who otherwise would not have been detected. We propose noninducibility of clinical VT at NIPS as an important endpoint for VT ablation, in addition to noninducibility of clinical VT at the end of ablation and lack of early spontaneous recurrence. The benefit of identifying additional patients at high risk of VT recurrence includes the potential to provide further treatment to avoid ICD shocks and the accompanying increase in mortality (12,13). Conversely, noninducibility of clinical VT at NIPS and—even more so— noninducibility of any VT at NIPS allows the clinician to provide additional reassurance to patients who may have been psychologically traumatized by frequent VT or ICD shocks before ablation.
Patients with clinical VT inducible at the end of ablation are known to be at high risk of future VT recurrence, and further ablation should be considered in this group when possible (14,15). However, some patients may be unable to tolerate detailed programmed stimulation at the conclusion of a lengthy ablation procedure. Furthermore, even when programmed stimulation can be performed at the end of ablation, noninducibility of clinical VT at that time may fail to identify all high-risk patients because of subsequent changes in antiarrhythmic medications, imperfect reproducibility of programmed stimulation, alterations in autonomic tone and/or degree of sedation/anesthesia, and ablation lesion maturation or regression. In support of this, the 18 patients in our series with clinical VT inducible at NIPS who underwent programmed stimulation at the end of ablation did not have clinical VT inducible at that time.
Those with clinical VT inducible at NIPS were more likely to be taking amiodarone before ablation and more likely to have their typically high dose of amiodarone decreased or even discontinued after ablation. Although reduction of the amiodarone dose is certainly an important goal of the ablation procedure, amiodarone, particularly at high doses, may suppress some of the VT during the ablation procedure, thereby leading to less extensive ablation, more residual substrate, and greater risk of recurrence during follow-up (16). It has been our clinical observation that even an extra 3 to 4 days without high-dose amiodarone may change the electrophysiologic milieu, and therefore every attempt is made to withdraw amiodarone in advance of the ablation procedure. Thus, NIPS before discharge seems particularly important when changes in antiarrhythmic medications are made after ablation and when the patient's condition is too unstable to undergo detailed programmed stimulation at the end of the ablation procedure.
Study strengths and limitations
Strengths of our study include a sizable, contemporary cohort of patients with a mix of cardiomyopathies and careful characterization, particularly with regard to antiarrhythmic medications and arrhythmia episodes. Several limitations are worth noting. First, not all patients underwent NIPS and differences exist between those who did and did not undergo NIPS as detailed earlier. Second, the distinction between clinical and nonclinical VT can be problematic as some patients do not have 12-lead electrocardiograms of spontaneous VT, and nonclinical VTs can subsequently occur spontaneously (17). Nevertheless, 12-lead ECGs of spontaneous VT episodes were available in the majority of cases, and when not, ICD electrograms were used to identify clinical VT, as described previously (18). Our study looked at inducibility of VT at NIPS at one point in time (i.e., before discharge from the hospital). It would be interesting to study inducibility over time, as VT substrate and antiarrhythmic milieu continue to evolve. With 22 variables undergoing univariate screening and 74 events in follow-up, the multivariate analysis could be considered overfitted. Lastly, our study is observational. A prospective study examining the impact of early ablation in those with inducible clinical VT at NIPS is needed to confirm the efficacy of this recommendation.
When patients with VT and structural heart disease have no inducible VT or inducible nonclinical VT only at the end of ablation or are too unstable to undergo final programmed stimulation, NIPS should be considered in the following days in the absence of spontaneous VT to further define the risk of arrhythmia recurrence. If clinical VT is inducible at NIPS, repeat ablation may be indicated because recurrence over the following year is high, including ICD shocks and VT storm. NIPS may be of particular importance after discontinuation or reduction of antiarrhythmic drug dose and when programmed stimulation cannot be performed at the end of ablation. Noninduciblity of clinical VT at NIPS allows the clinician to more confidently reassure patients that they are at low risk of recurrence.
Dr. Cooper has received modest honoarirum from Medtronic, St. Jude, Boston Scientific, Biotronik, and Spectranectics. Dr. Garcia is a speaker for and has received research support from Biosense Webster. Dr. Gerstenfeld has received research grants from Medtronic and Biosense Webster; and has received honoraria from Biosense Webster. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- antitachycardia pacing
- implantable cardioverter-defibrillator
- noninvasive programmed stimulation
- ventricular tachycardia
- Received October 21, 2011.
- Revision received December 15, 2011.
- Accepted January 2, 2012.
- American College of Cardiology Foundation
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