Ventricular tachycardia functional substrate targeting: a standalone strategy for all?

This editorial refers to ‘Evoked delayed potential ablation for post-myocardial infarction ventricular tachycardia: results from a large prospective multicentre study’ by M. de Riva et al., https://doi.org/10.1093/europace/euaf003.

Technical advancements and the development of new technologies in ventricular tachycardia (VT) ablation have garnered significant scientific interest in recent years.^1–5 Over the past decade, substrate ablation has emerged as the predominant approach for treating VT. This method not only addresses the challenges associated with ablating non-inducible or non-tolerated VTs but has also proven superiority in terms of arrhythmia-free survival with respect to the strategy of targeting only clinical and mappable VTs.⁶ The reduced recurrence rate observed with substrate ablation can be attributed to its ability to eliminate not only the arrhythmogenic substrate responsible for the clinical VT but also the circuits that could be exploited by other re-entrant VTs in the future. In fact, the complete abolition of the arrhythmogenic substrate has been adopted as a procedural endpoint and stands as a critical predictor of long-term efficacy of the VT ablation procedure.^7,8

However, the targets of substrate-based ablation are still partially dependent on the operator and can sometimes be interpreted ambiguously. Two decades ago, Arenal et al.⁹ demonstrated that electrograms within the area of scar displaying isolated delayed components are associated with clinical VTs, and their ablation is effective for the treatment of unmappable VTs. In a seminar paper, Jaïs et al.¹⁰ gave a major contribution describing that sharp high-frequency low-amplitude electrograms called ‘local abnormal ventricular activities’ (LAVAs) can occur anytime during or after the far-field electrogram. Due to a poor coupling between the LAVA-generating myocardial bundles in the scar tissue and the remaining myocardium, the near-field abnormal electrogram frequently split further away from the far-field ventricular electrogram after a short-coupled extra-stimulus.

In patients with this substrate, it has gradually gained evidence the hypothesis that decremental conduction delay and unidirectional block are critical for initiating and maintaining re-entrant tachycardia, so that subsequent research has focused on identifying electrograms that exhibit slow and decremental conduction properties (Table 1). In a small observational study on six post-myocardial infarction (MI) patients, Jackson et al.¹⁵ firstly described that sites exhibiting conduction delay following short-coupled extra-stimulus were specific in identifying the critical part of the VT circuits. Acosta et al.¹¹ demonstrated that the use of a double ventricular extra-stimulus can reveal slow-conducting areas that might remain undetected during sinus rhythm mapping in patients undergoing VT substrate ablation and, for the first time, areas with decremental conduction properties were incorporated as targets in the ablation strategy, proving to significantly reduce VT inducibility and to improve long-term outcomes in terms of survival free from any VT.¹³ However, despite these significant advancements in the characterization of arrhythmogenic substrates, further progress is needed to accurately define the optimal ablation targets.

In this issue of the journal, de Riva et al.¹⁴ have reported on a multicentre, prospective study the evaluation of a VT substrate ablation approach based on targeting evoked delayed potentials (EDPs) in a population of 130 post-MI patients. EDPs were defined as low-voltage near-field electrograms that delayed more than 10 ms or blocked in response to a short-coupled right ventricular extra-stimulus. Mapping was focused on the infarcted areas, and the decremental response of the electrograms was analysed regardless of their voltage or morphology. Procedural data indicated favourable acute outcomes, as 76% of patients were non-inducible for VT following EDP-guided VT substrate ablation. Additionally, re-mapping post-ablation demonstrated EDPs elimination in 96% of patients. This ablation strategy demonstrated promising mid-term outcomes, with VT-free survival rates of 78% at 6 months and 72% at 12 months. However, it is important to note that up to 50% of patients were still on antiarrhythmic drugs at the time of the last follow-up. The most noteworthy aspect of this article is that it validates the reproducibility of the same EDP-based approach previously described in 2018, which was initially tested in a smaller single-centre cohort.⁸ The current study confirms those initial findings in a multicentre setting, including centres with varying levels of expertise in the proposed technique.

These results are indeed promising and provide further confirmation that sites with decremental properties should be targeted during substrate ablation procedures; however, the optimal approach for identifying and ablating these sites has yet to be fully established. In the regions with functional slow conduction properties, the conduction delay is significantly influenced by the activation front directionality and the coupling interval of the extra-stimulus.¹⁵ While de Riva et al. used a single extra-stimulus from the right ventricle with a coupling interval of 50 ms above the ventricular refractory period, other groups have employed a double or even a triple (needed in more than 10% of tested sites) ventricular extra-stimulus protocol^11,13 to further reveal local decremental properties. The ideal method must balance a comprehensive identification of slow conduction regions, minimizing unnecessary procedural time or unintentional VT induction, a topic that warrants further investigation. Additionally, the effects of ongoing antiarrhythmic drug use on these manoeuvres remain unexplored.

One of the most unresolved questions is how to handle late potentials that do not demonstrate additional conduction delay in response to short-coupled extra-stimulus. In the study by de Riva et al.,¹⁴ such sites were not included as ablation targets. The favourable acute and mid-term outcomes of the current study highlight the efficacy of an ablation approach that preserves local abnormal ventricular activities lacking functional slow conduction properties. Similarly, a prior small multicentre study (n = 20) proposed an ablation strategy focused on eliminating EDPs as an initial step, with additional RF ablation only if VT remained inducible.¹² In that study, 80% of patients were rendered non-inducible after EDP-based ablation, and the VT-free survival rate reached 75% at 6 months. In contrast, Acosta et al.¹³ incorporated ablation of regions with functional slow conduction properties as part of a substrate-modification strategy based on the scar dechannelling approach during sinus rhythm, that also considered late potentials without additional conduction delay as targets for ablation. This last method achieved remarkable VT-free survival rates, as outlined in Table 1. So far, it remains unclear whether EDP ablation should be integrated into a broader strategy that includes traditional late potential ablation or if EDP-only elimination may be enough as a standalone approach.

To date, no randomized trials testing the possible benefit of EDPs ablation have been conducted. Only three single-centre studies have compared the outcomes of this approach with historical control cohorts, showing only small improvements in both acute and long-term outcomes.^8,11,13

Additionally, as is common in this field of research, the current study exclusively involved post-MI patients. Only the cohort by Acosta et al.^11,13 included a significant proportion of patients with non-ischaemic arrhythmic substrates. Therefore, the magnitude of the benefit to be obtained from EDP-based ablation and its applicability across the full spectrum of patients with scar-related VT of varying origins remains unclear. Probably, near-field EDPs from non-ischaemic mid-myocardial scars would not be detected by endocardial or epicardial mapping in many cases.

Despite these limitations, this article represents a significant step forward in the spread of the technique to test for the presence of functional slow conduction, demonstrating its reproducibility and showing that a substrate ablation approach exclusively based on targeting sites with EDPs could be a reasonable standalone approach. However, substantial technique refinements remain to standardize the methodology to be used in any VT substrate and VT patient and to better understand how to integrate this approach into the broader substrate ablation armamentarium.

Conflict of interest: none declared.

Data availability

Not applicable.

References

Author notes