Incidence and predictors of mortality following ablation of ventricular tachycardia in patients with an implantable cardioverter-defibrillator
Article Outline
- Abstract
- Introduction
- Methods
- Electrophysiologic study and ablation of VT
- Clinical follow-up
- Statistical analysis
- Results
- Efficacy and safety of VT ablation associated with structural heart disease
- Clinical outcomes following ablation of VT
- Predictors of mortality after VT ablation
- Discussion
- Mortality in patients with VT and ICDs
- Prior investigation into mortality after VT ablation
- Safety and efficacy of VT ablation over time
- Potential for mortality risk modification with ablation of ventricular arrhythmias
- Study limitations
- Conclusion
- References
- Copyright
Background
Long-term outcomes following ablation of ventricular tachycardia (VT) have not been well described.
Objective
The purpose of this study was to identify the incidence and predictors of mortality following catheter ablation of VT in patients with an implantable cardioverter-defibrillator (ICD).
Methods
The cohort included in the analysis consisted of patients with ischemic or nonischemic cardiomyopathy undergoing electrophysiologic study and ablation of VT. Catheter ablation of VT involved the use of pacemapping, entrainment mapping (when possible), and substrate modification. Clinical recurrences, ICD therapy history, and mortality were recorded for all patients included in the cohort. Comparisons were made between those subjects who died over a 3-year follow-up period and those who survived.
Results
A total of 208 subjects underwent 327 VT ablations over the course of the study period. Sixty-seven deaths (75% of all deaths and 32% of the cohort) occurred within 3 years after VT ablation. After multivariable adjustment, clinical predictors of mortality included age, lower left ventricular ejection fraction, and presence of renal insufficiency. Procedural variables associated with reduced mortality following VT ablation included presence of hemodynamically tolerated VT, lack of inducibilty of any VT following ablation, and procedural date in the latter part of the study.
Conclusion
The survival rate after VT ablation has improved over time and may reflect improved mapping and ablation techniques, in addition to improved therapies for treatment of congestive heart failure. Tolerated VT and lack of inducible ventricular arrhythmias following VT ablation was associated with improved survival in this study, suggesting their value as a risk factor for subsequent mortality.
Keywords: Ablation, Mortality, Ventricular tachycardia
Abbreviations: CI, confidence interval, ICD, implantable cardioverter-defibrillator, VT, ventricular tachycardia
Introduction
Ablation of ventricular tachycardia (VT) remains palliative in many patients with structural heart disease and an implantable cardioverter-defibrillator (ICD). Typically, patients present with frequent therapies delivered by the ICD for VT or ventricular fibrillation refractory to antiarrhythmic medical therapy. Although mortality after VT ablation is known to be high,1, 2, 3, 4 detailed analysis of potential variables that may influence outcome has not been performed in a large cohort.
In addition, the safety and efficacy of VT ablation have not been fully characterized over the period of time that it has been developed. Recent improvements in mapping and ablation technology may have a substantial impact on clinical outcomes following catheter ablation. In tandem with these procedural improvements, advances in device and pharmacologic therapy for patients with congestive heart failure may reduce mortality in patients presenting with frequent episodes of VT.
The aim of this study was to characterize the incidence of mortality following ablation of VT associated with structural heart disease due to ischemic or nonischemic cardiomyopathy and identify variables associated with improved outcomes in a large cohort of patients from a single center.
Methods
Study population
The cohort of patients included in the analysis comprised all patients with ischemic or nonischemic left ventricular cardiomyopathy undergoing electrophysiologic study and ablation of VT at the University of Pennsylvania Health System from January 1999 to May 2005. Patients with other causes of VT, such as idiopathic VT or VT associated with isolated right ventricular cardiomyopathy or congenital heart disease, were excluded. All patients had a functioning ICD placed either prior to or immediately after ablation.
Electrophysiologic study and ablation of VT
Patients presented to the cardiac electrophysiology laboratory in the fasting state under sedation. Catheters were placed into position in the heart using fluoroscopic guidance and standard techniques. VT was induced with programmed electrical stimulation and identified as a clinical rhythm based on morphologic analysis of stored ICD electrograms and/or comparison to a recorded 12-lead ECG. When possible, electroanatomic mapping was performed during VT to ascertain voltage and activation characteristics of the chamber from which VT originated. If a clinical VT was unmappable due to hemodynamic instability, a sinus rhythm voltage map was created prior to programmed stimulation. Hemodynamically unstable VT(s) was then ablated using pacemapping and substrate modification as previously described.5
Following ablation, repeat programmed stimulation was performed to determine whether procedural success, defined as lack of inducibility of the clinically apparent VT as seen on stored electrograms, was achieved. Programmed stimulation consisted of an eight-beat drive train followed by at least double extrastimuli. Every attempt was made to complete a standard three-stimuli, two-site protocol (plus left ventricular stimulation, particularly if necessary for induction prior to ablation); this was not completed if induction of poorly tolerated rapid VT morphologies required repetitive cardioversion. If a nonclinical VT was induced with programmed stimulation, it was terminated with antitachycardia pacing or with cardioversion if it was not hemodynamically tolerated. All induced VTs that were within 50 ms of the tachycardia cycle length recorded by an ICD prior to therapy delivery were considered to be clinically relevant. Induction of VT with a cycle length ≤240 ms was considered to be nonclinical, unless evidence of this VT was recorded by ECG or stored ICD electrograms. In addition, any VT that was hemodynamically tolerated was mapped and ablated, whether or not this induced VT was considered to be clinically relevant. Procedural success was defined as failure to induce targeted clinical VT following ablation.
Clinical follow-up
Clinical recurrences, ICD therapy history, and mortality were recorded for all patients included in the cohort. Most patients were followed by our electrophysiology service, but many patients were referred from outside cardiologists so that routine device interrogation was impossible. In these situations, mortality data were obtained via periodical queries to the social security death index and telephone interview with either the patient or the patient's family members. Thirteen patients underwent orthotopic heart transplantation following ablation and therefore were excluded from our analysis. All subjects had at least 3 years of follow-up information obtained. The point of origin for follow-up for all patients was the time of first ablation of VT.
Statistical analysis
Results are expressed as mean ± SD. The Pearson Chi-square test was used to compare clinical characteristics between patients who survived 3 years after VT ablation to those who did not. Analysis of variance was used for continuous covariates. Multivariable logistic regression analysis was used to adjust for possible confounding. Variables included in the multivariable model were age, sex, left ventricular ejection fraction, type of catheter used, hemodynamic tolerability of VT, year in which VT ablation was performed, and history of hypertension, coronary disease, diabetes mellitus, or renal insufficiency. Statistical analyses were performed using the SPSS statistical software program (version 17.0, SPSS, Inc., Chicago, IL, USA). Statistical significance was defined as two-sided P <.05. The study was reviewed by the University of Pennsylvania Institutional Review Board.
Results
Clinical characteristics of the cohort
The cohort consisted of 208 patients identified after exclusion of subjects with a structurally normal heart, congenital heart disease, arrhythmogenic right ventricular cardiomyopathy, or subsequent heart transplantation. Of these patients, 144 had healed myocardial infarction and 64 had nonischemic dilated cardiomyopathy. One hundred thirty-three subjects (54.3%) presented only with VT that was not hemodynamically tolerated. Therefore, the ablation consisted of substrate modification and was performed during sinus rhythm in these individuals. Table 1 lists the clinical and electrophysiologic characteristics of the patients included in the cohort.
Table 1. Clinical characteristics of the cohort (N = 208)
| Age (years) | 63.6 ±13.1 |
| Left ventricular ejection fraction (%) | 28.6±14.0 |
| Morphologically distinct VTs targeted for ablation | 2.7±1.1 |
| Angiotensin-converting enzyme or angiotensin receptor blocker use | 126(60.6%) |
| Beta-blocker use | 146(70.2%) |
| Revascularized (% of patients with coronary disease) | 87(67.4%) |
| Biventricular pacing | 22(10.6%) |
| Diabetes mellitus | 23(11.1%) |
| Renal insufficiency (creatinine ≥1.5) | 61(29.3%) |
| Coronary heart disease | 144(69.2%) |
| Sex (male) | 187(89.9%) |
| Noninducible VT after ablation | 94(45.2%) |
| Hemodynamically tolerated VT at presentation | 95(45.7%) |
| VT ablation performed after January 1, 2003 | 88(42.3%) |
Efficacy and safety of VT ablation associated with structural heart disease
A total of 327 ablation procedures were performed during the study period (mean 1.5 sessions per patient, range 1–7). Lack of inducibility of the targeted clinical VT morphologies was achieved in 298 (91%) of 327 procedures. There were 7 (2.1%) major complications noted as a result of the VT ablation including 3 embolic strokes, and 4 pericardial effusions requiring drainage. In addition, there were 5 (1.5%) procedures that were aborted because of hemodynamic instability during the mapping and ablation of ventricular tachycardia despite restoration of sinus rhythm and 1 (0.3%) procedure aborted due to an adverse reaction to anesthesia. There were no immediate deaths at the time of ablation. Over the course of the study, use of a cooled-tip (either externally irrigated or closed-loop irrigation) ablation catheter increased from 11.5% in 1999 to 69.4% in 2005. Prior to 2003, cooled-tip ablation was used in 48% of cases versus 68% of cases after 2003.
Clinical outcomes following ablation of VT
A single ablation procedure was effective in 147 patients, and at least one repeat procedure was required for treatment of VT recurrence in 61 (29%) patients over the course of the study period. Over a mean follow-up duration of 51 ± 29 months, 89 (42.8%) deaths were observed. Ten (5%) patients died within 30 days after VT ablation. Sixty-seven deaths (75% of all deaths and 32% of the cohort) occurred within 3 years after VT ablation.
Predictors of mortality after VT ablation
Table 2 lists the unadjusted predictors of mortality at 3 years following ablation of VT. There was no difference in mortality with respect to etiology of cardiomyopathy. Patients who presented with hemodynamically tolerated VT had a lower mortality following ablation than did those with hemodynamically unstable VT (Figure 1). The adjusted odds ratio for 3-year mortality associated with hemodynamically tolerated VT ablation was 0.32 (95% confidence interval [CI] 0.15, 0.67; P <.01). A different rate of mortality in patients undergoing VT ablation after January 2003 compared to those undergoing ablation earlier than this date was observed (Figure 2). After adjustment for potential confounding, this association was significant 3 years after VT ablation (hazard ratio 0.78; 95% CI 0.66, 0.92; P <.01). In addition, there appeared to be a long-term survival benefit in those patients who did not have any inducible ventricular arrhythmias following VT ablation (hazard ratio for 3-year mortality 0.42; 95% CI 0.21, 0.85; P = .02). Figure 3 shows the different rates of mortality in patients who had inducible nonclinical VT with programmed stimulation versus those who did not over the course of the study. Other multivariate predictors of mortality after 3 years included renal insufficiency, age, and left ventricular ejection fraction (Table 3).
Table 2. Variables associated with 3-year mortality following VT ablation
| 3-Year survival | P value | ||
|---|---|---|---|
| Alive | Deceased | ||
| 141 | 67 | ||
| Age (years) | 61.4±13.5 | 71.1±8.2 | <.01 |
| Left ventricular ejection fraction (%) | 30.6±14.4 | 22.2±10.3 | <.01 |
| Morphologically distinct VTs targeted for ablation | 2.6±1.2 | 2.8±1.4 | .63 |
| Noninducible VT | 73(51.7) | 23(34.3) | .02 |
| Angiotensin-converting enzyme or angiotensin receptor blocker use | 85(60.3) | 41(61.2) | .47 |
| Beta-blocker use | 97(68.8) | 49(73.1) | .34 |
| Revascularized (% coronary artery disease) | 58(61.7) | 29(58.0) | .67 |
| Biventricular pacing | 18(12.8) | 8(11.9) | .88 |
| Diabetes mellitus | 18(12.8) | 7(10.4) | .65 |
| Renal insufficiency | 26(18.4) | 33(49.3) | <.01 |
| Coronary artery disease | 94(66.7) | 50(74.6) | .25 |
| Sex (male) | 126(89.4) | 59(88.1) | .82 |
| Radiofrequency ablation performed after January 1, 2003 | 79(56.0) | 28(41.7) | .04 |
| Tolerated VT | 74(52.4) | 22(32.8) | <.01 |
Figure 1.
Kaplan-Meier survival curve for different rates of mortality following ablation of hemodynamically tolerated versus not tolerated ventricular tachycardia (VT).
Figure 2.
Kaplan-Meier survival curve for different rates of mortality following radiofrequency ablation (RFA) before versus after January 2003. VT = ventricular tachycardia.
Figure 3.
Kaplan-Meier survival curve for different rates of mortality following ventricular tachycardia (VT) ablation in patients with versus those without inducible nonclinical VT following VT ablation.
Table 3. Adjusted odds ratios for variables associated with mortality following VT ablation
| 3-Year mortality HR (95% CI) | P value | |
|---|---|---|
| Age | 1.08(1.04,1.12) | <.01 |
| Renal insufficiency | 3.19(1.54,6.60) | <.01 |
| Left ventricular ejection fraction | 0.96(0.93,0.98) | <.01 |
| RFA after January 1, 2003 | 0.78(0.66,0.92) | <.01 |
| Noninducible after RFA | 0.42(0.21,0.85) | .02 |
| Tolerated VT | 0.32(0.15,0.67) | <.01 |
Discussion
Study results
The present study characterizes the clinical outcomes associated with VT ablation in a large cohort of consecutive patients undergoing the procedure over 6 years. During this time period, there was a notable decrease in mortality following the procedure. Patients who underwent VT ablation during the last half of the study period appeared to have a survival advantage compared to those who underwent VT ablation during the first half of the study period. In addition, a survival advantage was noted in those patients who presented with hemodynamically tolerated VT and in those who did not have an inducible ventricular arrhythmia with programmed stimulation following the procedure.
Mortality in patients with VT and ICDs
Patients with structural heart disease are known to be at risk for ventricular arrhythmias and sudden death. Even though the relatively recent use of the ICD for primary prevention of sudden death has reduced mortality in this group of patients, mortality approaches 15% on optimal medical therapy at 3 years.6, 7 Although the 3-year mortality observed in the present study was 32%, this population is different from those in primary prevention trials of ICDs and would be expected to have a higher mortality rate as seen in trials examining the use of the ICD for treatment of known ventricular arrhythmias. For example, in the Antiarrhythmics Versus Implantable Defibrillator (AVID) trial, the 3-year mortality in the group that received an ICD was 25%.8 This is similar to the results of the present study as well as other secondary prevention trials of ICDs.9, 10
In the present study, renal insufficiency, age, and reduced left ventricular ejection fraction all were associated with higher mortality after multivariable adjustment. This is consistent with prior studies examining risk factors associated with long-term mortality in patients with heart failure on optimal medical therapy.11, 12 Although univariate analyses suggest a survival benefit from revascularization, biventricular pacing, and beta-blocker use, after multivariable adjustment, these known beneficial interventions did not achieve a statistically significant association with reduced mortality. This lack of statistical significance likely reflects the lack of precision with multivariable analyses using the small number of exposed cases in our study as well as bias resulting from confounding by indication, as the cohort in this study included patients with and without dyssynchrony, low left ventricular ejection fraction, and heart failure.
Prior investigation into mortality after VT ablation
Several studies have reported mortality following VT ablation.1, 2, 3, 4, 13, 14, 15, 16 These studies were limited by a small number of subjects and/or limited follow-up duration. The present study differs from these previous investigations in that a larger cohort of patients with a longer follow-up duration is available for analysis. In addition, the present study includes all patients with structural heart disease, including those with clinical VT that is not hemodynamically tolerated, which constituted the majority of subjects. In prior studies that included only subjects with hemodynamically tolerated VT, the annualized mortality rate ranged from 3% to 15%.1, 13, 14, 16 These results differ substantially from studies that include subjects with VT that is not hemodynamically tolerated, in which the annualized mortality rate was 10% to 38%.2, 3, 4, 15 Our results are consistent with these prior studies, with an observed annualized mortality of 9% and 14% for subjects presenting with and without tolerated VT, respectively.
Safety and efficacy of VT ablation over time
Ablation of VT has evolved significantly over the study period. Initial VT ablations were performed using a 4-mm tip with limited power delivery. With the introduction of larger and irrigated-tip catheters, power delivery has been substantially enhanced.15, 17 With the increased power delivery, deeper lesions in myocardial scar may have led to improved outcomes by reducing recurrences. In addition, improvements in mapping and ablation techniques may have contributed to improved procedural outcomes.18 However, it is impossible to resolve whether the improved mortality observed in patients undergoing VT ablation in the latter half of the study is due to changes in technique or if this phenomenon is a reflection of improvements in the care given to patients with heart failure over this same period in time. During the study period, beta-blockers and angiotensin-converting enzyme inhibitors became standard of care, and cardiac resynchronization was introduced for patients with cardiac dyssynchrony. These therapeutic interventions also may explain the improved mortality observed during the same period in time.
Potential for mortality risk modification with ablation of ventricular arrhythmias
One of the interesting findings in the present study is the association of lack of inducible ventricular arrhythmias and reduced mortality. A potential explanation for this finding is that patients who continue to have inducible ventricular arrhythmias are at higher risk for developing new arrhythmias, which places them at risk for recurrent ICD shocks or use of antiarrhythmic therapy, both of which may increase the likelihood of progressive heart failure.7, 19 In addition, VT recurrence may be refractory to ICD therapy. Although ICDs are extremely effective devices, ICD failure can be due to inadequate defibrillation, postshock electromechanical dissociation, incessant VT, or VT occurrence at below the programmed rate detection.20 Lack of inducibility may signify protection from future arrhythmias that are not afforded to patients who continue to have inducible VT or ventricular fibrillation, thereby placing them at risk for future events. VT inducibility with programmed stimulation has been shown to lead to increased events following successful ablation of clinical VT.13, 21 Of course, inducibility may also reflect an increased scar burden or possibly other risk factors for nonarrhythmic causes of death. This would suggest that patients who do not have inducible ventricular arrhythmias are in some way healthier and protected from arrhythmic and nonarrhythmic modes of death. However, if lack of inducibility does result in a mortality benefit due to a direct reduction of arrhythmias in the future, it may become a procedural endpoint that would require further investigation to prove its utility in prolonging life in these patients.
Study limitations
The limitations inherent to observational research must be considered in this study. The present investigation is a retrospective cohort study evaluating clinical and electrophysiologic characteristics associated with mortality following ablation of VT. Although the cohort is relatively large for this procedure, a small number of outcomes were analyzed. For this reason, there is imprecision with multivariable analyses that could result in inaccuracies. This is especially true for any potential covariate that has a low incidence in the cohort or has a weak association with the outcome. Nonetheless, we believe that the statistical analyses performed in the present study allow for some understanding of mortality following ablation despite the limited number of cases.
Uncontrolled confounding could create bias toward a false association between date of first VT ablation and improved mortality. Patients treated later in the study period may have benefited from therapies that were not available to their counterparts in the earlier period of the study. The improved mortality seen for this as well as other analyses could merely be a reflection of this bias created from confounding. However, multivariable adjustment using covariates that may generate bias did not diminish these associations.
We used a standard mapping and ablation strategy for all VT ablations. Specifically, if an induced VT was hemodynamically tolerated, we constructed an activation map and used pacing maneuvers with resetting and entrainment of the tachycardia to identify critical areas of the VT circuit. If an induced VT was not hemodynamically tolerated, we performed the ablation in sinus rhythm using pacemapping to identify portions of the VT circuit within a defined area of scar. We are unable to compare these techniques beyond the comparison of hemodynamically tolerated versus not tolerated VTs ablated. In addition, we are unable to compare other mapping techniques that may be used in other laboratories, such as targeting late potentials within a scar independent of pacemap morphology and use of noncontact mapping, because we did not routinely use these techniques during the study period.
Finally, this study does not have a contemporary control group of patients with ICDs who did not undergo catheter ablation. Therefore, we are unable to conclude whether VT ablation itself can be associated with improved survival. However, this question is beyond the scope of the present study, so we are unable to conclude whether VT ablation itself can impact survival. Similarly, because we did not have a control group of subjects not undergoing ablation, we cannot deduce any potential impact in mortality related to VT ablation in the subgroups that we identified as having a higher risk for mortality following ablation.
Conclusion
Successful ablation of VT in patients with structural heart disease and an ICD is associated with a mortality rate similar to that seen in clinical trials of ICDs for primary and secondary prevention of sudden death. The survival rate after VT ablation has improved over time and may reflect improved mapping and ablation techniques in addition to improved therapies for treatment of congestive heart failure. Lack of inducible ventricular arrhythmias following VT ablation was associated with improved survival in this study, suggesting its value as a risk factor for subsequent mortality. Further investigation is required to evaluate the potential use of noninducibility after VT ablation as a procedural end-point to improve survival in this population.
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Drs. Marchlinski, Callans, and Gerstenfeld have received research funding support from St. Jude Medical and Biosense-Webster, Inc., manufacturers of ablation and mapping equipment. Drs. Marchlinski and Callans have received honoraria from Biosense-Webster.
PII: S1547-5271(09)01001-7
doi:10.1016/j.hrthm.2009.09.014
© 2010 Published by Elsevier Inc.
