Primary Ablation of Ventricular Tachycardia: In Search of a Better Strategy

Over the last years, radiofrequency catheter ablation has been consistently demonstrated as an effective treatment for drug-refractory recurrent ventricular tachycardia (VT).^1-12 Significant advances in techniques and technologies for VT ablation, such as improvements in cardiac mapping systems,¹³ the introduction of percutaneous techniques for epicardial ablation,¹⁴ and open-irrigation ablation platforms,¹² have further advanced the field, increasing the number of patients referred for ablative treatment, with improved success rates. However, most of the published literature is largely limited to patients experiencing multiple episodes of VT refractory to antiarrhythmic drug therapy (i.e., secondary VT ablation),^{1,4,10,12,13,15} and only three studies have evaluated the role of catheter ablation earlier in the treatment of VT (i.e., primary VT ablation).^2,3,5 This article will summarize the available evidence on primary VT ablation, reviewing the techniques and results of such an ablation strategy.

Evidence-Based Indications and Results of Primary VT Ablation

Three randomized trials have evaluated the benefit of primary VT ablation compared to standard medical therapy in patients with ischemic cardiomyopathy.^2,3,5 In a small pilot randomized trial published in abstract form, Schreieck et al reported the results of early intervention with VT ablation on top of implantable cardioverter-defibrillator (ICD) placement (secondary prevention indication) versus ICD alone in a sample of 39 patients (19 randomized to ablation).⁵ After a mean follow-up of 11.3 ± 8.9 months, 47% of the ablated patients and 60% of controls had VT recurrence.⁵

The Substrate Mapping and Ablation in Sinus Rhythm to Halt Ventricular Tachycardia (SMASH-VT) trial was a multicenter prospective, unblinded, randomized trial that tested the hypothesis that catheter ablation would reduce the recurrence of sustained ventricular arrhythmias in patients undergoing ICD implantation for the secondary prevention of sudden cardiac death.³ Initially, only patients undergoing secondary prevention ICD implantation (within a six-month period from study enrollment) were eligible for randomization. Subsequently, enrollment criteria were extended to patients who had received an ICD for primary prophylaxis and received appropriate ICD therapy for a single event. Among key exclusion criteria were active treatment with antiarrhythmic drugs (class I or class III) and VT storm. Patients were randomized either to catheter ablation or medical therapy (no antiarrhythmic drugs). The primary study endpoint was survival free from any appropriate ICD therapy, defined as ICD shock or antitachycardia pacing. Freedom from any appropriate ICD shock, overall mortality, and VT storm were among the secondary endpoints analyzed. A total of 128 patients (64 in each group) underwent randomization, and at two-year follow-up, 12% of patients in the ablation group and 33% of those in the control group received an appropriate ICD intervention (hazard ratio [HR] = 0.35, 95% confidence interval [CI] 0.15 to 0.78, P = 0.007), which was driven by a significant decrease of ICD shocks (9% vs. 31%, HR = 0.27, 95% CI 0.11 to 0.67, P = 0.003). The predictors of appropriate ICD intervention in the catheter ablation group were assessed by means of a multiple Cox regression analysis in a subsequent study.¹⁶ The only variable associated with occurrence of appropriate ICD intervention at follow-up was the number of VT induced in the baseline electrophysiological study, while VT inducibility after ablation did not influence long-term clinical success.¹⁶

The multicenter Catheter Ablation of Stable Ventricular Tachycardia Before Defibrillator Implantation in Patients With Coronary Artery Disease (VTACH) trial was a prospective, unblinded, randomized controlled trial testing the hypothesis that early intervention with catheter ablation in patients with previous myocardial infarction, reduced left ventricular ejection fraction (i.e., ≤50%), and documented first episode of hemodynamically tolerated sustained VT undergoing secondary prevention ICD implantation, would reduce the rate of recurrent VT or ventricular fibrillation compared to standard medical therapy plus ICD implantation.² The primary endpoint was the time from ICD implantation to recurrence of any sustained VT or ventricular fibrillation. A total of 107 patients were randomized in a 1:1 ratio to catheter ablation with ICD implantation or ICD implantation only, and patients were followed up for at least one year. After a mean follow-up of 22.5 ± 9 months, patients allocated to catheter ablation had significantly longer time to arrhythmia recurrence compared to those randomized to ICD only (median 18.6 months vs. 5.9 months), and lower two-year arrhythmia recurrence rates (53% vs. 71%, HR = 0.61, 95% CI 0.37 to 0.99, P = 0.045).

Putting together the results of primary VT ablation trials, there is adequate evidence to support the early use of catheter ablation of VT on top of ICD therapy to decrease arrhythmia recurrence in patients with history of malignant ventricular arrhythmias. However, the long-term freedom from recurrent VT achievable with primary ablation is still suboptimal.

Evidence-Based Techniques for Primary VT Ablation

A substrate-based approach was implemented in the majority of patients included in clinical studies evaluating the role of primary VT ablation.^2,3,5 Schreieck et al reported a stepwise approach beginning with programmed ventricular stimulation to test inducibility of VTs. Therefore, the exit points of all documented or inducible VTs were defined by pace mapping in sinus rhythm, and radiofrequency applications using cooled-tip or large tip ablation catheters were delivered to target VT exit points along the scar border zone guided by electroanatomical voltage mapping (Carto^™, Biosense Webster, Inc., a Johnson & Johnson company, Diamond Bar, CA) or non-contact mapping (EnSite^™, St. Jude Medical, St. Paul, MN).

In the SMASH-VT trial, all the ablation procedures were performed with a substrate-based approach after VT(s) induction with programmed ventricular stimulation.³ A left ventricular voltage mapping was obtained with the Carto system, and pace mapping maneuvers were performed to reproduce the ECG morphology of the inducible VT. After identification of the putative VT exit sites, two ablation lines were performed: one from the VT exit site (site of optimal pace mapping) toward the center of the scar, and the other perpendicular to the first line along the border zone of the scar. A second strategy targeting late and fractionated potentials within the scar was employed in patients with severe left ventricular dysfunction. Entrainment mapping was done only in case of hemodynamically stable VT.

In the VTACH trial, the three-dimensional electroanatomical reconstruction of the left ventricle was done with either a contact mapping system (Carto) or non-contact system (EnSite).² Activation and entrainment mapping were performed in case of stable VT, while a substrate-based approach similar to the SMASH-VT approach was implemented in case of non-inducible or unstable VT.

In conclusion, a substrate-based approach limited to the ablation of clinical or inducible VT(s) exit sites is the strategy most commonly implemented in primary VT ablation studies. As mentioned, the long-term success rate of such an approach still appears unsatisfactory. For instance, more than a half of the patients allocated to catheter ablation in the VTACH trial had ventricular arrhythmia recurrence after two years of follow-up.

Primary VT Ablation Compared with Secondary VT Ablation: Implication for Further Research

Available data on primary VT ablation generate multiple areas of uncertainties, and further studies are necessary to evaluate the optimal ablation strategy to increase the procedural success rate. Of note, a comparison of success rates of primary versus secondary VT ablation studies does not disclose significant differences in terms of long-term freedom from arrhythmia recurrence (Figure 1).

These figures support the concept that future research should focus more on identifying new ablation techniques and strategies, rather than testing current techniques in broader patient populations. To this regard, preliminary data from our group suggest that extensive substrate-based ablation targeting all the potential arrhythmogenic areas within the scar (i.e., “homogenization of the scar”) may improve the long-term freedom from ventricular arrhythmia recurrence in patients with post-infarct high-burden ventricular arrhythmias.¹⁷ Such an approach has a strong pathophysiological rationale, based on the significant evolution of post-infarct substrates for VT in current patients treated with reperfusion therapies.¹⁸ In fact, the introduction of mechanical reperfusion therapies for acute myocardial infarction has led to a higher percentage of non-transmural necrosis, with heterogeneous infarct cores containing bundles of surviving myocytes and fibrotic tissue, surrounded by similarly complex border zones merging into normal myocardium.¹⁸ Further, the occurrence of the “no-reflow” phenomenon,¹⁹ of distal embolization of thrombotic material during mechanical reperfusion,²⁰ and varying degrees reperfusion-related myocardial injury have further increased the complexity of the substrate for post-infarction VT, generating multiple slow conduction channels within the dense scar, with VT exit points located in different areas, including the subendocardial scar, the border zone, or even in the mid-wall or subepicardial myocardial layers. As a result, the presence of multiple slow conduction channels within the scar and the possibility of mid-wall or epicardial VT exit sites provide the rationale for an extensive endo-epicardial scar homogenization to treat the current population of patients with post-infarction VT.¹⁷

Conclusions

Primary VT ablation through a substrate-based approach reduces the VT recurrence rate compared to medical therapy (no antiarrhythmic drugs) in patients with ischemic cardiomyopathy undergoing secondary prevention ICD implantation. However, the long-term freedom from arrhythmia recurrence is still suboptimal and similar to that reported in secondary VT ablation studies. Further studies testing novel ablation strategies and techniques are warranted to increase the procedural success rate.

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