Opinion statement

Catheter ablation is currently the most effective treatment option for ventricular arrhythmias. However, in some circumstances, classic radiofrequency ablation cannot effectively eliminate some deeply located intramural arrhythmias. Thus, novel mapping approaches can be supported by such advanced ablation techniques as enhanced unipolar radiofrequency ablation, bipolar radiofrequency ablation, alcohol ablation, stereotactic body radio-ablation, or pulsed-field ablation.

Introduction

Catheter ablation (CA) is a widely recognized therapy for ventricular arrhythmias (VAs), demonstrating success rates ranging from 47 to 90% [1]. The effectiveness varies based on factors such as the presence of ventricular tachycardia (VT) substrate and its etiology, the location of the arrhythmia’s origin, and whether multisite ablation is needed for intramural sources [2,3,4, 5•], and if the substrate progression is likely to occur [6]. Despite the relatively high effectiveness, CA may encounter limitations, often associated with anatomical challenges such as deep intramural arrhythmogenic foci or proximity to the coronary arteries and conduction system. In this article, we provide a brief overview addressing challenging substrates in ventricular arrhythmias (VAs) and explore techniques to enhance outcomes in cases resistant to conventional ablation methods.

Imaging

At the stage of pre-procedural planning, an accurate determination of the anatomical substrates for VA occurrence is important for successful ablation procedures. Recent findings in the integration of advanced imaging technologies have impacted an approach to mapping substrates located in the ventricular myocardium. Especially, the dedicated scar segmentation software has emerged as a promising option. Automatic Detection of Arrhythmogenic Substrate (ADAS) was created to outline the structure of the ventricles and incorporate this information into electroanatomical mapping systems [7]. Based on computed tomography (CT) or cardiac magnetic resonance (CMR), it allows the generation of ventricular scar maps. Another software—In-HEART—evaluates CMR or CT to imaging data for the development of three-dimensional cardiac models. The software conducts detailed segmentation of scars and anatomical structures such as wall thinning, epicardial fat, coronary arteries, or phrenic nerves which can provide additional benefit, not only during intraprocedural design of the ablation lesion set [8] but also can be helpful for appropriate determination of ablation target at the stage of pre-procedural planning. Intracardiac echocardiography (ICE) can be helpful for intraprocedural visualization of the left ventricular scar [9] but also can help to navigate the ablation catheter in real-time and can track any possible occurrence of CA-related complications at their early stage [10].

Mapping

Appropriate mapping techniques are particularly important for the assessment of the substrate’s electrophysiological characteristics. Such evaluation of the ventricular myocardial substrate is significantly influenced by the dimensions of the mapping electrodes. Microelectrode mapping can overcome some limitations associated with standard bipolar mapping performed using classic diagnostic or ablation catheters. Utilizing electrophysiological signals recorded using catheters equipped with microelectrodes enables the recording of electrograms of higher specificity in regions characterized by low bipolar voltage during sinus rhythm [11]. Enhancing sampling density through the use of microelectrodes improves resolution and increases the probability of capturing near-field electrical information [12]. Due to such features, microelectrode mapping surpasses standard bipolar mapping in its sensitivity to identify viable myocytes during sinus rhythm, potentially facilitating the recognition of proper targets for CA [11]. Nevertheless, classic endocardial mapping can be still limited if the substrate is located in the intramural area [13]. In such circumstances, direct mapping of the septal perforator veins can be useful, and this can be performed using small-diameter catheters equipped with microelectrodes [12] or insulated angioplasty guidewires [14]. If the appropriate early activation is determined this way, the ablation can be performed from the anatomically adjacent chambers.

Enhancing the efficacy of VT ablation strategies requires the identification of crucial ablation targets. Such presumed areas of scar frequently have their border zones close to relatively healthy myocardial tissue. Collision of multiple wavefronts arising from scar and nearby myocardium can have an influence on the ultimate signal formation [15], and this can impair the accuracy of mapping performed during sinus rhythm or regular ventricular pacing. Previous studies have shown that ventricular electrograms, which demonstrated decremental conduction using decrement evoked potentials (DEEP) during right ventricular apical pacing with an extra-stimulus, are more likely to participate in reentrant VT circuits than conventional substrate ablation targets [16]. This mapping technique enables the identification of the functional substrate critical to the VT circuit with high specificity [17]. Moreover, it has been shown to be more specific than late potential mapping for identifying the critical targets of VT ablation [16] and should be considered in cases with difficult substrates of VT.

Additionally, high-density (HD) mapping emerges as a promising approach for accurate detailing of substrates for VT. HD mapping catheters provide detailed and comprehensive electroanatomical information across a number of points with superior resolution, enabling more accurate discrimination of local abnormal electrograms [18]. This high-resolution mapping enhances the precision of substrate delineation and characterization of scar substrates [19] [20] frequently leading to more accurate ablation target delineation.

Alternative mapping sites in ventricular arrhythmias

Various mapping sites beyond the conventional right and left ventricular endocardial surface locations have been investigated for the identification of recurrent PVC/VT true origin, expanding the range of possibly successful ablation targets. For classic outflow tract arrhythmias, an important area of interest are cusps of the pulmonic valve. Recent studies suggest that occasionally a subset of arrhythmias with morphology suggestive of the right ventricular outflow tract (RVOT) originates from these cusps [21,22,23]. The efficacy of the “reversed U-curve” technique has been established for mapping and radiofrequency ablation of these arrhythmias, providing improved catheter stability and contact. Sporadically, this method is also advantageous for some arrhythmias arising from the left ventricular summit (LVS), particularly its more septal aspect, which is in close proximity to the RVOT and left pulmonic cusp [24, 25]. Additionally, more classic but detailed mapping of pulmonic cusp junctions may sometimes eliminate the necessity for using the reversed U-curve technique [26].

Coronary veins can appear as another key mapping site, particularly for OT VAs refractory to endocardial ablation. Mapping using ablation or diagnostic catheter can reveal the earliest activation in the great coronary vein (GCV) or anterior interventricular vein (AIV), which is suggestive of some LVS arrhythmias. While ablation within GCV/AIV is feasible, obstacles such as high impedance [27] and proximity to major coronary arteries [28] necessitate caution. The telescopic approach, involving stepwise catheter [29], guidewire advancement [30], and microcatheters in GCV/AIV and their branches [31], can be helpful if catheter positioning in the coronary veins is challenging. In cases of recurrence post-ablation within GCV/AIV, the use of low- or non-ionic coolant for irrigation is safe and may enhance radiofrequency power delivery both from the coronary vein and opposite endocardium [32,33,34].

Although infrequently required, epicardial access has been considered for specific LVS arrhythmias [35]. Assessments of percutaneous epicardial mapping indicate limited success, with only a small subset of patients benefiting from direct epicardial ablation due to challenges like proximity to major coronary vessels or the presence of epicardial fat [35]. These findings may suggest that the direct epicardial ablation of LVS arrhythmias has a limited role in this application; however, epicardial access is frequently necessary for the complete elimination of arrhythmogenic tissue in a spectrum of non-ischemic cardiomyopathies [36].

Advanced ablation strategies

It has been demonstrated that in cases when scar substrate is located septally or is located within the LVS area, acute ablation success may be more difficult to achieve [3] and sometimes can be even associated with increased long-term cardiovascular mortality [37•]. With a better understanding of the limitations of intramural substrate ablation in such areas, several newer ablative techniques are still being implemented, such as alcohol ablation [38]. Injecting ethanol through coronary vessels has been effective in immediate cell destruction and the elimination of clinical PVC/VT [39]. While initially delivered through coronary arteries [40], recent improvements have revitalized the method by introducing ethanol injection through coronary veins [41]. The Valderrabano group has innovated with a double-balloon technique to reduce ethanol dispersion, making ablation more focused on the targeted ablation area [42]. While the results are encouraging, the exact shape of the anticipated lesions created by injecting ethanol in the LVS area is still not completely determined.

Another advanced ablation technique involves delivering radiofrequency current using two ablation catheters in a bipolar fashion, where one catheter connects to the ground port instead of the dispersive patch [43]. This approach appeared effective for treating PVC/VTs from challenging locations such as the interventricular septum [44], LVS [45,46,47], or RVOT diverticulum [48]. Some obstacles may include non-uniform energy transfer due to impedance mismatch, which can be attenuated using a large tip ablation catheter in the GCV [49, 50]. The absence of intramural capture, facilitated by a microcatheter or wire, seems encouraging for assessing the completeness of lesions in real-time during bipolar ablation procedures [51]. Precautions are necessary for procedures closer to the His bundle [52] and coronary arteries [53, 54], especially when the target is more anteriorly located [55].

The conventional radiofrequency (RF) ablation system uses a unipolar current between the catheter tip and a dispersive patch on the patient’s skin. Relocating the dispersive patch, especially to the front of the chest, has been suggested to improve the creation of lesions in PVC/VT from the anterior aspect of the OT [56]. Studies indicate that changing the dispersive patch location and using additional dispersive electrodes may result in larger RF lesions and deeper lesion formation [57].

Radiotherapy

Recent advancements in non-invasive VT therapy options have introduced the use of stereotactic body radiation therapy (SBRT) as a novel ablation approach. SBRT, originally developed for oncological purposes, has been adapted to target arrhythmogenic substrates within the heart [58]. The precision of SBRT allows for the focused delivery of high-dose radiation targeted to a specific area of tissue [59], potentially abolishing the arrhythmogenic focus without the need for invasive catheterization. Early clinical trials have shown promising results in reducing the burden of refractory VT, particularly in patients where conventional catheter ablation techniques have previously failed [60]. The mechanism of action is believed to involve the induction of fibrosis within the targeted tissue, leading to the electrical elimination of the arrhythmogenic substrate [61•]. While the initial outcomes are encouraging, and the method seems to be safe, potential complications of cardiac radiotherapy, such as radio-induced coronary lesions [62], are still not completely investigated. Future promising and unique features of SBRT may include possible acceleration of conduction within slow-propagating zones of scar [63].

Pulsed-field ablation

Another novel technique in the spectrum of VA therapies is pulsed-field ablation (PFA), which offers a potentially safer and more precise alternative to traditional thermal ablation methods [64]. PFA uses ultra-short electrical pulses to induce irreversible electroporation, selectively targeting cardiac tissues responsible for arrhythmias while minimizing collateral damage to adjacent structures [65]. This specificity can be particularly advantageous in ventricular arrhythmia ablation, where the proximity to vital cardiac structures like the coronary arteries and the conduction system poses significant risks with thermal ablation techniques. Recent studies have demonstrated PFA’s efficacy in effectively eliminating arrhythmogenic foci with a substantially lower risk of complications such as steam pops or collateral tissue damage [66]. Furthermore, PFA’s ability to create more homogenous and transmural lesions [67] could potentially lead to improved long-term success rates in treating ventricular tachycardias, especially in substrates where conventional ablation has some limitations [68]. Pivotal VT ablation cases with PFA appeared successful [69, 70]; however, the durability of the lesions and long-term effectiveness still remain unknown. Given a possible risk of coronary arterial spasm, precautions such as systemic or intracoronary nitroglycerin administration should be performed preceding PFA applications in order to minimize such risk of high-voltage delivery into ventricles [71].

Conclusions

Catheter ablation of ventricular arrhythmias is highly successful, but failure may occur in case of anatomical obstacles such as intramural arrhythmia origin or proximity to the coronary arteries. In situations where standard ablation proves unsuccessful, innovative ablation techniques can serve as a backup strategy and may attain success, especially in cases with a difficult substrate of arrhythmia.