The ideal index to predict the site of origin of outflow tract ventricular arrhythmias. Are we there yet?

Accurate mapping is crucial for successful catheter ablation of outflow tract ventricular arrhythmias (OT-VAs). These procedures, however, can be demanding, requiring a substantial amount of effort and time. OT-VAs arise from various closely related structures within the outflow tract region. These include the right ventricular outflow tract (RVOT), as well as structures in the left ventricular outflow tract (LVOT), such as the aortic cusps, the aorto-mitral continuity, and the left ventricular summit. As the site of origin varies, so do the challenges in accurately mapping and effectively ablating OT-VAs, as well as the risks associated with catheter ablation. Therefore, meticulous effort is required to obtain comprehensive data on the precise site of origin of OT-VAs to ensure optimal ablation strategy and accurate risk assessment. Given the close anatomical proximity of the potential sites of origin, OT-VAs present similar ECG morphologies,1 prompting the development of several ECG indices to differentiate right from left OT-VAs. These include, among others, the transition zone index,2 the V2 transition ratio,3 the RV1-V3 transition ratio,4 the V2S/V3R index,5 and the R wave duration index.6 Since these indices are based on the 12-lead ECG morphology of OT-VAs, they offer a noninvasive preprocedural tool to guide ablation strategy. However, the generalizability of these indices can be questioned, as most of them have been derived from small patient cohorts. Additionally, their predictive accuracy can be variable, especially when transition occurs at V3, while others are affected by cardiac rotation.7 In this issue of the Journal of Cardiovascular Electrophysiology, Mi et al. investigated the use of the local ventricular activation time in the coronary sinus to predict the site of origin of OT-VAs. They studied 51 patients with OT-VAs and precordial transition ≤V3, in whom a decapolar catheter was placed deep in the coronary sinus. The authors measured the time interval from the earliest QRS onset to the local ventricular activation at 3 and 12 o'clock of the mitral annulus in the left anterior oblique view (QRS-MA interval). They found that a QRS-MA12 interval ≤10 ms and a QRS-MA3 interval ≤32 ms predicted an LVOT site of origin, with a sensitivity of 100% and 78% and a specificity of 77% and 100%, respectively. Additionally, a QRS-MA12 ≤ −24 ms predicted an epicardial LVOT site of origin, with 70% sensitivity and 89% specificity. Notably, QRS-MA intervals outperformed ECG indices in this cohort, demonstrating a higher area under the receiver operating characteristic curve. Furthermore, these findings were prospectively validated in a cohort of 17 patients with OT-VAs, yielding promising results. In the validation cohort, QRS-MA3 ≤ 32 ms, QRS-MA12 ≤ 10 ms, and QRS-MA12 ≤−24 ms showed a sensitivity of 100%, 100%, and 60%, respectively, and a specificity of 80%, 100%, and 100%, respectively. The study introduces a valuable new electrophysiological index for predicting the site of origin of OT-VAs. However, despite the fact that QRS-MA intervals demonstrated a good predictive accuracy, the proposed cut-off values were derived from a small cohort of patients, thus limiting generalization of the findings. Moreover, RVOT sites of origin were underrepresented in the study, accounting for only 25% of the total cohort. According to the authors, this may be explained by the fact that they systematically excluded patients ablated in both the RVOT and the LVOT. This is an additional factor to consider, as OT-VAs may arise from intramural sites between the RVOT and the LVOT with a preferential exit on either side,8 limiting the value of any binary prediction algorithm. Ablation in these cases is particularly challenging and comprehensive mapping is important.9 In addition to the above limitations, the clinical perspective of the MA-QRS intervals should also be considered. As highlighted earlier, preprocedural assessment of the OT-VA origin is crucial. While QRS-MA intervals might offer valuable intraprocedural guidance for mapping and ablation, they lack the ability to inform preprocedural ablation strategy and risk assessment. Nevertheless, electroanatomical mapping of the coronary sinus is a frequently employed technique, as it can rapidly direct the operator towards potential LVOT regions of interest, based on the pattern of earliest activation.10, 11 However, in the study of Mi et al., the coronary sinus catheter could not be advanced to the junction of the great cardiac and intraventricular vein in 6 out of the 81 attempted patients, who, consequently, were excluded from the final analysis. Anatomical structures such as valves and angulations of the great cardiac vein can render catheter advancement challenging and impede mapping of the coronary sinus and the cardiac veins.12 While the ideal scenario would involve a simple, highly accurate, and preprocedurally available index for the prediction of OT-VAs site of origin, such a tool remains elusive. In the absence of a perfect single index, a combined approach utilizing existing published indices and algorithms is recommended, along with a standardized and comprehensive procedural workflow to maximize ablation success. The QRS-MA intervals could serve as an additional tool within this approach; however, validation in future studies is required.