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Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): EACVI Research Grant Academy Van Leersum grant of the Academy Medical Sciences Fund (Royal Netherlands Academy of Arts & Sciences). Background Implantable cardiac defibrillator (ICD) implantation can protect against sudden cardiac death (SCD) after a myocardial infarction. However, relatively few patients with an ICD experience a life-threatening arrhythmic event. Imaging studies have proposed metrics based on 2D analysis of late gadolinium enhancement (LGE) characteristics to predict post-infarct malignant arrhythmias and improve SCD risk assessment. However, given the intrinsic 3D nature of the electrical pathways through the infarcted regions, 3D reconstructions of the scar substrate from LGE imaging may be required to fully characterize the pro-arrhythmic nature of the scar substrate. Aim To evaluate the accuracy of LGE based 3D metrics such as conduction corridors (regions of borderzone (BZ) surrounded by scar core) and 3D interface surfaces (boundaries between scar and myocardium) towards predicting ICD therapy. Methods ADAS LV and custom-made software was used to generate 3D patient-specific ventricular models in a prospective cohort of post-infarct patients (n=40) having undergone LGE imaging pre-ICD implantation. The extent of variation in scar-characteristics was evaluated in ADAS by quantifying the BZ, scar core, the number and weight of conduction corridors i.e. BZ surrounded by scar core. Custom-written scripts were used to calculate metrics describing the 3D topology of the scar substrate, specifically the interface area between myocardium and total enhancement (BZ+core), and the interface between BZ and core. These metrics were compared with ICD therapy during follow-up. Results Total corridors were comparable between both groups (6.53 ± 7.9 vs. 4.6 ± 4, p = .38). Corridor weight demonstrated a trend towards higher mass in the event group (2.7 ± 2.1g vs. 1.6 ± 1.4g, p = .06). Patients with an event (n=17) had higher myocardium-total enhancement interface (103.8±35.1cm2 vs. 77.4±33.7cm2, p=.021) and BZ-core interface (76±27.5cm2 vs. 55.2±27.6cm2, p=.024). Cox-regression demonstrated a significant independent association of myocardium-total enhancement interface with an event (HR 2.79; 1.44-5.44, p < .01). Kaplan-Meier analysis showed a significantly higher event rate in patients with an interface area between myocardium-total enhancement of more than 72cm2 (Figure 1A) and BZ-core more than 42.3cm2 (Figure 1B). Conclusion These results demonstrate that patients with appropriate device therapy had larger myocardium-total enhancement and BZ-core surface interface areas. Conceptually, the BZ-core interface could be considered to be related to the reentrant circuit path-length whilst the myocardium-total enhancement interface reflects the surfaces most-likely to initiate unidirectional block, both of which can be consider pro-arrhythmic substrates. These findings emphasize the importance of visualizing and thereby characterizing substrate as a 3D entity instead of the currently applied 2D approach to facilitate early identification of high-risk patients.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): EACVI, Netherlands Heart Institute. Background MRI late gadolinium enhancement (LGE) images can provide novel insights about critical pathways through scar but does not assess the vulnerability of these pathways for sustaining scar-mediated ventricular tachycardia (VT). Computational modelling can augment the insights from imaging derived metrics by providing the functional implications of structural anatomy of the substrate. However, current (monodomain) approaches are computationally expensive and may not, by design, extract all critical pathways. Aim This study evaluated the performance of a novel, reaction-Eikonal based, automated reentrant pathway finding algorithm (VITA) to assess the functional viability of critical circuits identified on LGE and non-invasively predict arrhythmic risk in both an ICD and post-ablation cohort recurrence. Methods ADAS LV and custom-made software was used to generate 3D patient-specific ventricular models in a prospective cohort of post-infarct ICD patients (cohort 1, n=40) and a retrospective cohort of 20 post-infarct VT-ablation patients (cohort 2). Our Virtual Induction and Treatment of Arrhythmias (VITA) framework was then applied to comprehensively probe the viability of the scar substrate to sustaining reentrant circuits. VITA metrics, related to the numbers of induced VTs and their corresponding round trip times (RTTs), were compared with appropriate ICD therapy (cohort 1) and VT-recurrence (cohort 2) during follow-up. Results Patients in both cohorts with an event had higher VITA metrics. In cohort 1 (ICD), VITA demonstrated significantly more inducible VTs (6.6±4.2 vs. 4.1±3.4, p = .044), longer mean RTT (116.2±50.9 ms vs. 76.9±42.6 ms, p = .012) and max RTT (194.4±105.1 ms vs. 109.6±78.7, p =.009) in the event group. In addition, Cox-regression demonstrated a significant independent association with an event: induced VTs (HR 1.67; CI 1.04–2.68, p = .03), mean RTT (HR 2.14; CI 1.11–4.12, p = .02), maximum RTT (HR 2.13; CI 1.19–3.81, p = .01). In cohort 2 (VT-ablation), total induced VTs (85±43 vs. 42±27, p = .01) and unique VTs (9±4 vs. 5±4, p = .04) were significantly higher in patients with- compared to patients without recurrence, and were predictive of recurrence with AUC of .820 and .770, respectively. Max RTT demonstrated a trend towards significance 293 ± 90 ms vs. 200 ± 114 ms (p = .06) for recurrence and non-recurrence, respectively. No differences were observed in mean RTT between the two groups. Conclusion VITA enabled quantitative assessment of pro-arrhythmic vulnerability of the substrate which related directly to patient outcomes. The number of induced VTs were the most robust measure of appropriate ICD therapy and post-ablation arrhythmia recurrence. The RTT metrics, related to viable circuit lengths through scar, demonstrated a significant independent association with appropriate ICD therapy. Future studies should investigate the clinical utility of a VITA-guided selection and treatment approach.

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Netherlands Heart Institute Fellowship, CVON PREDICT2 Young Talent Program Background MRI late gadolinium enhancement (LGE) images can provide novel insights about critical pathways through scar but does not assess the vulnerability of these pathways for sustaining scar-mediated ventricular tachycardia (VT). Computational modelling can augment the insights from imaging derived metrics by providing the functional implications of structural anatomy of the substrate. However, current (monodomain) approaches are computationally expensive and may not, by design, extract all critical pathways. Aim This study evaluated the performance of a novel, reaction-Eikonal based, automated reentrant pathway finding algorithm (VITA) to assess the functional viability of critical circuits identified on LGE and non-invasively predict arrhythmic risk in both an ICD and post-ablation cohort recurrence. Methods ADAS LV and custom-made software was used to generate 3D patient-specific ventricular models in a prospective cohort of post-infarct ICD patients (cohort 1, n=40) and a retrospective cohort of 20 post-infarct VT-ablation patients (cohort 2). Our Virtual Induction and Treatment of Arrhythmias (VITA) framework was then applied to comprehensively probe the viability of the scar substrate to sustaining reentrant circuits. VITA metrics, related to the numbers of induced VTs and their corresponding round trip times (RTTs), were compared with appropriate ICD therapy (cohort 1) and VT-recurrence (cohort 2) during follow-up. Results Patients in both cohorts with an event had higher VITA metrics. In cohort 1 (ICD), VITA demonstrated significantly more inducible VTs (6.6±4.2 vs. 4.1±3.4, p = .044), longer mean RTT (116.2±50.9 ms vs. 76.9±42.6 ms, p=.012) and max RTT (194.4±105.1 ms vs. 109.6±78.7, p =.009) in the event group. In addition, Cox-regression demonstrated a significant independent association with an event: induced VTs (HR 1.67; CI 1.04–2.68, p = .03), mean RTT (HR 2.14; CI 1.11–4.12, p = .02), maximum RTT (HR 2.13; CI 1.19–3.81, p = .01). In cohort 2 (VT-ablation), total induced VTs (85±43 vs. 42±27, p = .01) and unique VTs (9±4 vs. 5±4, p = .04) were significantly higher in patients with- compared to patients without recurrence, and were predictive of recurrence with AUC of .820 and .770, respectively. Max RTT demonstrated a trend towards significance 293 ± 90 ms vs. 200 ± 114 ms (p = .06) for recurrence and non-recurrence, respectively. No differences were observed in mean RTT between the two groups. Conclusion VITA enabled quantitative assessment of pro-arrhythmic vulnerability of the substrate which related directly to patient outcomes. The number of induced VTs were the most robust measure of appropriate ICD therapy and post-ablation arrhythmia recurrence. The RTT metrics, related to viable circuit lengths through scar, demonstrated a significant independent association with appropriate ICD therapy. Future studies should investigate the clinical utility of a VITA-guided selection and treatment approach.