Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Dutch Heart Foundation Introduction We recently optimized our ECG imaging (ECGi) method for the estimation of endo- and epicardial activation during sinus rhythm. In patients with arrhythmogenic cardiomyopathy, late gadolinium enhancement (LGE)-CMR can identify regional myocardial injury and the combination of structural and electrical information may provide valuable insight in disease progression and risk stratification. However, the effect of structural disease and local conduction delay on the ECGi estimation of ventricular activation has not been studied. Purpose Evaluate the relation between LGE-CMR and non-invasively estimated local conduction velocity (CV). Methods 8 pathogenic mutation carriers (PKP2/PLN) underwent LGE-CMR for clinical follow up and 67 lead body surface mapping. Subject specific triangulated surface heart/torso/lung meshes were created. ECGi activation sequences were used to determine local CV with the triangulation method. The LGE location was identified according to the AHA 17 segment model. Per segment, variation in CV was computed and local activation timing maps and CV maps were constructed. Results Isochronal crowding was observed in subjects in segments with LGE (figure, red boxes) and locally, conduction velocity decreased. Variation in conduction velocity per segment in subjects with extensive LGE presence (>9 segments) was higher 0.031±0.018 vs. 0.026±0.013 m/s/cm2 in subjects without. Conclusion Our preliminary results indicate the ability of the ECGi method to identify regions with higher variation in local CV. This increase in CV variability might be used to assess the vulnerability to cardiac arrhythmia. Analysis will be extended towards the RV and subsequently, more subjects will be included.

Background Noninvasive electrocardiographic imaging (ECGi) using the equivalent double layer (EDL) source model enables both epicardial and endocardial reconstruction of electroanatomical activation patterns during sinus rhythm. The EDL source model has been validated in torso-tank models and animal experiments, however validation in humans using invasive electroanatomical mapping is limited. Purpose Validation of EDL based ECGi using invasive electroanatomical mapping. Methods Ten patients referred for epicardial and endocardial electroanatomical mapping underwent 67 electrode body surface potential mapping (BSPM), cardiac CT imaging and 3D imaging of electrode positions. Anatomical models of the ventricles, lungs and thorax were created and supplemented with electrode positions. Invasive epicardial (4020±1514 contact points), right ventricle endocardial (724±113 contact points) and left ventricle endocardial (459±117 contact points) local activation timing (LAT) maps were compared to ECGi derived LAT maps. Results Included patients (mean age 48±21 years, 80% males) were diagnosed with either arrhythmogenic cardiomyopathy (N=4), dilated cardiomyopathy (N=1), symptomatic premature ventricular complexes (N=3) or myocarditis (N=2). Measured BSMP highly correlated with simulated BSPM (97±2%) with a relative difference of 24% ± 6%. Source models consisted of a mean of 2614±214 nodes with a mean distance between nodes of 8.3±1 mm. Overall, invasive LAT maps and ECGi derived LAT maps showed reasonable correlation for epicardial maps (49% ± 18%) and endocardial maps of the right ventricle (48% ± 27%). Endocardial left ventricular LAT maps showed less correlation (23% ± 28). The absolute difference between invasive and ECGi LAT maps was 16.7±14.2 ms for epicardial maps, 17.2±12.9 ms for right ventricle endocardial maps and 34.0±19.8 ms for left ventricle endocardial maps. Visual comparison showed corresponding areas of breakthrough and regions of latest activation in all cases (Figure). Quantitative comparison of these areas showed a mean absolute difference of 33±7mm or 19±10 ms for epicardial maps, 25±10 mm or 17±13 ms for right ventricle endocardial maps and 39±16 mm or 20±6 ms for left ventricular endocardial maps. Conclusion Overall agreement was observed between EDL based ECGi LAT maps and electroanatomical LAT maps. Future research will focus on further quantification of this agreement and improvement of ECGi mapping accuracy. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation and UCL Hospitals NIHR Biomedical Research Centre.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Dutch Heart Foundation Introduction Arrhythmogenic cardiomyopathy (ACM) is a heterogeneous progressive disease. Identification of patients at risk for malignant ventricular arrhythmias is challenging, making extensive cardiac follow-up necessary. CineECG provides insight in the average cardiac pathway of cardiac electrical activity. In previous studies, CineECG proved useful to detect disease progression. Objective Evaluate the applicability of CineECG to monitor disease progression in plakophilin-2 (PKP2) pathogenic mutation carriers. Methods To compute the CineECG, a 3D heart/torso model and 12 lead ECG is used. From 68 PKP2 pathogenic mutation carriers, all raw ECGs were extracted from the patient database. In pathogenic mutation carriers with definite ACM, the ECG ±2 years before (ECG1), at (ECG2) and ±2 years after (ECG3) diagnosis were selected. In pathogenic mutation carriers without definite ACM, the most recent ECG (ECG2) and the ECG ±2 years before (ECG1) were selected. CineECGs were computed for the QRS complex and the distance between CineECG location at end QRS was determined per subject for subsequent CineECGs. Results In 53 pathogenic mutation carriers ≥2 ECGs were available. 33 pathogenic mutation carriers were diagnosed with definite ACM of whom 4 had an ECG before, at and after diagnosis. Average distance between CineECG location at end QRS was 7.8±6.8 mm. In pathogenic mutation carriers with definite ACM, CineECG before and at diagnosis (figure, example 1&2) were different whereas CineECG at and after diagnosis did not always change. In pathogenic mutation carriers without definite ACM, in 14/19 changes in CineECG were observed (figure, example 3), whereas in the others (figure, example 4) not. Conclusion Our preliminary results show that CineECG provides additional insight in the changes of cardiac activation in ACM patients and may enable detection of disease progression. Further analysis will also include cardiac repolarization.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by the Dutch Heart Foundation Introduction Non-invasive mapping of ventricular activation using inverse electrocardiography (iECG) in patients with cardiomyopathy during sinus rhythm, may improve risk stratification for sudden cardiac death. However, iECG is complicated by multiple simultaneous endocardial activation waves (multi-wave) mediated by the His-Purkinje system, especially when the QRS complex is narrow. The activation estimation should be based on a realistic physiological model of the His-Purkinje system combining multiple waves initiated at His-Purkinje associated endocardial locations. Equivalent double layer based iECG provides an estimation of both the endocardial and epicardial surface. To improve accuracy, equivalent double layer based iECG was supplemented with electro-anatomical structures associated with the His-Purkinje system to test initial ventricular activation (Figure, Panel C). Multi-wave iECG local activation timing (LAT) maps and invasive LAT maps during sinus rhythm were quantitatively compared. Purpose Quantitative comparison of multi-wave iECG in His-Purkinje mediated cardiac activation using invasive activation maps in patients. Methods Thirteen patients referred for invasive electro-anatomical mapping (EAM) of the endocardial and epicardial surface were included. Prior to EAM, each subject underwent 64 electrode body surface potential mapping, cardiac computed tomography (CT) imaging, and 3D imaging of electrode positions. Anatomical models of the ventricles, lungs and thorax were created using CT images and supplemented with electrode positions (Figure, Panel A-B). Electro-anatomical structures associated with the His-Purkinje system were incorporated in ventricular anatomical models (Figure, Panel C) and multiple simultaneous activation waves were simulated. Invasive endocardial and epicardial LAT maps were quantitatively compared to iECG LAT maps. Invasive EAM LAT maps were quantitatively compared to estimated iECG LAT maps (Figure, Panel D) using inter-map correlation coefficients (CC, Pearson’s) and absolute differences (AD). Results Mean inter-map CC and AD were 0.54 ± 0.19 and 18 ± 7 ms respectively for the epicardial surface (n = 13). Similar to the RV endocardial surface (n = 10, CC = 0.50 ± 0.29, AD = 20 ± 8 ms) and the LV endocardial surface (n = 4, CC = 0.44 ± 0.26, AD = 25 ± 7 ms). Conclusion(s): Quantitative comparison of the multi-wave iECG method showed overall moderate performance. This novel iECG method provides a physiologically more realistic and more robust estimation of sinus rhythm and may serve as a tool for detection of electro-anatomical substrates and risk stratification. Compared to other available non-invasive ECG methods, multi-wave iECG captures His-Purkinje mediated ventricular activation better. This method might also be useful for the accurate detection and localization of structural conduction disorders. Abstract Figure. Multi-Wave inverse electrocardiography

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by the Dutch Heart Foundation Background Ventricular conduction disorders can induce arrhythmias and impair cardiac function. Bundle branch blocks are diagnosed by 12-lead ECG, but discrimination between complete bundle branch blocks, incomplete bundle branch blocks and normal tracings can be challenging. CineECG computes the mean temporo-spatial isochrone (mTSI) trajectory of activation waveforms in a 3D-heart model from 12-lead ECGs. This trajectory represents the mean trajectory of the ventricular electrical activation at any time interval directly related to ventricular anatomy. In Brugada patients, CineECG has localized the terminal components of ventricular depolarization to right ventricle outflow tract (RVOT). Also, for the localization of bundle branch blocks, the region of latest activation contains the most information. Using CineECG, subject specific anatomically related information about the location of bundle branch blocks is obtained. Purpose This study aimed at exploring whether CineECG can improve the discrimination between complete left/right bundle branch blocks (LBBB/RBBB), and incomplete RBBB (iRBBB). Methods We utilized 400 12-lead ECGs from the online Physionet-XL-PTB-Diagnostic ECG Database with a certified ECG diagnosis. The mTSI trajectory was calculated and projected into the anatomical 3D-heart model. Five CineECG classes were established: "Normal", "iRBBB", "RBBB", "LBBB" and "Undetermined", to which each tracing was allocated. We determined the accuracy of CineECG classification with the gold standard diagnosis. Results A total of 391 ECGs were analyzed (9 ECGs were excluded for noise) and 240/266 were correctly classified as "normal", 14/17 as "iRBBB", 55/55 as "RBBB", 51/51 as "LBBB" and 31 as "undetermined". Average mTSI trajectories were calculated according to ECG diagnosis (Figure). The terminal mTSI contained most information about the BBB localization, as that part directs to the site of latest activation (Figure, red arrow). Conclusion CineECG provided the anatomical localization of different BBBs and accurately differentiated between normal, LBBB and RBBB, and iRBBB. CineECG may aid clinical diagnostic work-up, potentially also contributing to the difficult discrimination between normal, iRBBB and Brugada patients. Abstract Figure. Average CineECG trajectories