## 3 Results
### EP Studies (EAM Mapping and Arrhythmia Inducibility Tests)  
Figure 8a-c illustrates examples of endocardial bipolar voltage maps, along with representative intracardiac electrograms (iEGMs), recorded following a retrograde aortic approach: (a) in the healthy control pig; (b) in pig #3; and (c) in pig #4, respectively. The healthy tissue (depicted in magenta) was defined by bipolar voltages with amplitude >1.5 mV, whereas small patches of fibrosis (depicted in dark red and green) had bipolar voltages <1.5 mV, as is typical for the clinical threshold that defines unexcitable fibrotic scars. Figure 8d,e illustrates the 3D segmented LGE images for pig #3 and pig #4 after registration with endocardial bipolar voltage maps from CARTO3. The LGE-CARTO3 registration was performed in ADAS 3D, using a rigid landmark-based approach with 8 fiducial markers and the endocardial surface (i.e., taking a 5% layer closest to the surface) of the myocardium defined from the 3D LGE images. Overall, both methods (LGE and CARTO3) revealed small patches of fibrosis scattered on the endocardial surface, especially on the anterior side of these two hearts. However, a precise geometrical correspondence between the locations of patches in the LGE shell vs. those in bipolar voltages cannot be found. This is due to the different spatial resolutions used, with the voxels in LGE images being of small size (1.4 mm \(\times\) 1.4 mm \(\times\) 1.4 mm) with the recorded bipolar voltage points several mm apart. The resulting slightly larger fibrotic patches defined by CARTO3 (compared to those seen in the LGE endocardial shells), were  
Figure 7: Results from the LGE-based evaluation of fibrosis density (calculated relative to the LV volume) for each animal, along with selected histopathological images denoting increased collagen deposition: (**a**) temporal evolution of LGE-defined fibrosis density from LGE images for each pig; (**b**) examples of Masson Trichrome stained samples from the control animal as well as from samples collected at 5 weeks and 9 weeks post-DOX, showing an increasing deposition of interstitial collagen and reactive fibrosis (in agreement with results obtained from MRI). The yellow scale-bar is 200 μm. likely due to the surface interpolation of the recording points. Furthermore, it is possible that there were a few very small fibrotic points that were missed by the contact catheter, but these likely appeared in the LGE-defined endocardial shell. Examples of wave analysis for QRS and QRS-T intervals for a few selected fibrosis points are included in Table 1. Note that the recorded iEGM waves were evaluated for reproducible morphological appearance within three consecutive QRS heart beats prior to the acquisition window, using the 12-lead ECGs as reference. The QRS-T intervals were clearly prolonged for the points of low voltage compared to those in the healthy pig. In addition, the QRS intervals for these points were slightly longer in pig #4, but fluctuated in pig #3. Figure 8: Examples of endocardial bipolar voltage maps, along with representative iEGM waves are presented for the healthy pig (**a**), pig #3 (**b**) and pig #4 (**c**). The location of low bipolar voltages in (**b,c**) agreed well with the with the corresponding location of LGE-defined fibrosis using the ADAS 3D software, as illustrated for pig #3 (**d**) and pig #4 (**e**). In both endocardial maps (i.e., from CARTO3 and segmented LGE shells), the fibrotic areas are indicated by red-green, while the healthy tissue is in magenta. Note that CARTO typically saves 2.5 s of recording prior to the moment a bipolar voltage is acquired to be projected on the anatomical shell. In Table 1, we presented the signal captured during the acquisition window, which was set before the QRS and T waves, within the time window of 400 ms during sinus rhythm. In evaluating iEGMs for reproducible morphological appearance in the regions of low voltage identified from registered segmented LGE and bipolar maps, we identified consistent morphological