Reply to Colli and Romero-Ferrer

Abstract

Colli et al., commenting on the electrophysiological efficacy of high-intensity focused ultrasound (HIFU), propose a revision of the acute conduction block theory, as a means to confirm effective pulmonary veins (PVs) isolation [1, 2]. Although this proposal could be original, albeit not supported by evidence, it is in contrast with the general agreement surrounding the end-points for atrial fibrillation (AF) ablation. In the areas of consensus on ablation techniques identified by the task force in the recently published Consensus Statement on AF catheter and surgical ablation [3], complete electrical isolation of all PVs should be the goal in every ablation strategy targeting the PVs and/or the PV antrum. So, if the PVs are targeted, electrical isolation should be the goal, and its achievement requires, at a minimum, the assessment and demonstration of conduction block across the PVs lesion. Likewise for surgical PVs, isolation entrance and/or exit block should be validated. Since such acute validation can overestimate success, the Consensus also suggests an extra period of 20 min following PV isolation, to identify and treat PVs reconduction initially masked by the inflammation process, which gives an apparent acute conduction block. The evidence supporting the correlation between complete electrical isolation and clinical efficacy of ablation is clear-cut, since the major predictor of arrhythmia recurrence after catheter ablations is the absence of PVs isolation, indicating restored PV conduction or ineffective PV disconnection. Such a direct cause– effect relationship between PV isolation and cure supports the central role of durable transmurality of the ablations in AF treatment [4]. Despite the penetration properties of HIFU ablations being extensively studied at histology, the results are reported in the very acute context and the conduction block has normally not been evaluated. Hence, inferences between histological transmurality and electrophysiological block in the long-term remain undocumented. Colli and Romero-Ferrer state that in their surgical experience, the freedom from recurrence after HIFU ablation (unpublished data) improves with time, suggesting a progressive increase of the ablation efficacy. They speculate that these results might be related to a putative alternative modality of delayed cell death caused by HIFU. However, a comprehensive study conducted on eight dogs undergoing PV HIFU ablations suggests that the mechanism of permanent injury is irreversible cell death, through coagulative necrosis due to rapid hyperthermal toxicity occurring within the focused zone [5]. Even if different forms of necrotic cell death can be distinguished, based on their initiating mechanisms, i.e. necrosis, necroptosis and secondary necrosis, the downstream cascade of events that occurs thereafter takes place in an invariant fashion, during the following few hours [6]. In conclusion, to the best of the authors’ knowledge, ablation lesions can only get worse with time. Based on current evidence, there is no described biological mechanism that may explain a delayed myocardial cell death where the triggering event occurs during the ablation and the outcome cannot be detected after 3 weeks, as performed in our study.