Putting Novel Ablation Technologies to the Test

Till F. Althoff


Europace. 2023;25(4):1312-1314. 

Graphical abstract

Catheter ablation of atrial fibrillation has seen substantial advancements in the last decade, with novel technologies and approaches such as pulsed field ablation and high-power short-duration (HPSD) radiofrequency ablation (among others) having emerged more recently.[1] With different technologies entering the field at the same time, it remains a challenge to adequately test the safety and efficacy of each of them. In fact, despite being widely used in routine clinical practice already, sufficiently powered randomized trials are lacking for virtually all of the emerging technologies. One particular challenge is the fact that clinical efficacy endpoints depend not only on the ablation approach but also on a myriad of confounding factors, which is why very large sample sizes and tremendous efforts are required to perform adequately powered trials.

Against this background, assessment of ablation lesions could be a more convenient endpoint to test novel ablation approaches and technologies. Unlike clinical endpoints, assessment of ablation lesions is a very direct measure of ablation efficacy that mostly depends on the ablation technique itself with few confounding factors. Thus, the endpoint of lesion durability and continuity requires only a fraction of the sample size required for clinical endpoint studies. Although lesion assessment will not obviate the need to evaluate clinical outcome, lesion durability and continuity are key determinants of treatment effectiveness in terms of arrhythmia-free survival.[2] Moreover, such an approach will enable highly valuable mechanistic insights into lesion formation as well as the performance and specificities of distinct ablation approaches, which the investigation of clinical endpoints cannot provide.

Until recently, the only way to assess ablation lesions was invasive endocardial mapping. However, while quite a number of studies have systematically assessed lesion durability and continuity by endocardial mapping at 3 months post-ablation, ethical concerns may prohibit the performance of such highly invasive cardiac procedures merely for research purposes in many centres, and even if approved, few patients will be willing to undergo such procedure only for the sake of science.

In recent years, non-invasive assessment of ablation lesions by late gadolinium enhancement (LGE)-magnetic resonance imaging (MRI) has been established.[3] Gadolinium-based contrast agents diffuse freely into the interstitium, but cannot cross intact cell membranes and thus accumulate in the extracellular space resulting in signal enhancement in T1-weighted MRI sequences. Lesion assessment with LGE-MRI makes use of (i) the expansion of extracellular space and thus increased volume of distribution for the contrast agent that is associated with ablation-induced replacement fibrosis, as well as (ii) the prolonged washout owing to decreased capillary density within the myocardial fibrotic tissue. Of note, while all ablation methods aim to induce irreversible myocardial cell death, different energy sources (in particular thermal vs. non-thermal) may result in different extents of replacement fibrosis. It is also noteworthy that LGE is not specific for fibrotic tissue but can reflect other pathological processes associated with an expansion of the extracellular space such as inflammation and oedema formation, which impede definite lesion assessment, particularly in the acute post-ablation setting. This is why the correct timing of MR image acquisition is critical.[4] Late gadolinium enhancement-MRI is not only capable of detecting ablation-induced fibrosis but can accurately localize functional gaps as well.[4–6] Importantly, complete LGE lesions encircling the pulmonary veins without gaps have been shown to reliably rule out pulmonary vein reconnection after ablation.[7]

In this issue, Sciacca et al.[8] employed LGE-MRI to assess lesion formation after pulmonary vein isolation (PVI) with HPSD ablation. The concept of HPSD ablation aims to minimize conductive heating and increase resistive heating to deliver targeted energy to the atrial wall, while reducing the risk of collateral tissue damage.[1,9,10] Based on theoretical considerations and preclinical data, it has been proposed that, as a consequence of the increased ratio of resistive to conductive heating, HPSD ablation would result in a shallower lesion geometry with wider, more continuous, and less invasive lesions compared to conventional radiofrequency ablation.[11] However, clinical data on lesion geometry are lacking.

In an attempt to clarify these issues and to test the efficacy of HPSD ablation, the study by Sciacca et al.[8] included 60 consecutive patients to undergo PVI using a novel mode of temperature-controlled HPSD ablation (QMODE-plus, 90 W maximum power, 4 s per application, Biosense Webster). The study is among numerous other small-scale clinical studies of this specific HPSD ablation technology—all of them being insufficiently sized to yield conclusive results regarding clinical endpoints.[12,13] However, the study by Sciacca et al. is unique in employing LGE-MRI-based ablation lesion assessment as a direct measure of efficacy. LGE-MRI was systematically performed in 30 of the 60 patients at 3 months post-ablation—an optimal time point for lesion assessment with LGE-MRI.[4]

While acute procedural success, first-pass PVI rates, procedure times, and complication rates were consistent with previous reports on this technology, the study was clearly not powered for clinical endpoints.[12] However, the sample size is sufficient to allow for a valid assessment of lesion geometry and efficacy based on LGE-MRI. In the majority of the patients (66.7%), LGE-MRI detected 'complete' circumferential lesions, which the authors interpret as an indicator of good efficacy of the novel HPSD ablation approach. Two important aspects have to be considered, though. First, the authors' definition of 'complete' lesions tolerates gaps in the LGE lesion that may add up to 10% of the full circumference encircling ipsilateral pulmonary veins. Thus, while truly complete LGE lesion sets encircling the pulmonary veins without gaps are indicative of durable PVI with a positive predictive value of >95%,[7] the significance of 'complete' lesions according to the authors' quantitative definition is unknown. Second, a control group to put the proportion of patients with 'complete' lesions into perspective is lacking, rendering the data difficult (if not impossible) to interpret. In fact, it remains to be determined whether the reported proportion of patients with 'complete' LGE lesions is higher, lower, or equal to what would have been detected after ablation with conventional radiofrequency or other technologies. In principle, the same applies to the measured width of LGE lesions: in the absence of a control group, the ablation lesion parameters do not allow for a definite conclusion as to whether HPSD ablation results in a distinct lesion geometry. However, a comparison of the determined LGE lesion widths with previous reports on conventional ablation approaches could suggest that HPSD ablation may indeed result in wider lesions (although it has to be taken into account that distinct LGE-MRI post-processing methods result in a substantial variability and limited comparability of different studies).[14,15] Interestingly, the authors could link incomplete LGE lesion formation to lower contact forces during the corresponding radiofrequency applications. Although not surprising, this is an important finding and proof-of-concept, as in this particular ablation mode with automatic power regulation (according to tissue surface temperature) and fixed radiofrequency application times (4 s), contact force is one of the few operator-controlled variables.

Although in the absence of a reference control the results of this study are not fully conclusive, the authors must be congratulated for providing valuable insights into lesion formation after HPSD ablation. In fact, ablation lesion assessment with LGE-MRI may be a robust and efficient endpoint to test the efficacy of novel ablation approaches and technologies in the future.