Ventricular tachycardia (VT), which can lead to sudden cardiac death, occurs frequently in patients with myocardial infarction. Catheter-based radiofrequency ablation of cardiac tissue has achieved only modest efficacy, owing to the inaccurate identification of ablation targets by current electrical mapping techniques, which can lead to extensive lesions and to a prolonged, poorly tolerated procedure. Here we show that personalized virtual-heart technology based on cardiac imaging and computational modelling can identify optimal infarct-related VT ablation targets in retrospective animal (5 swine) and human studies (21 patients) and in a prospective feasibility study (5 patients). We first assessed in retrospective studies (one of which included a proportion of clinical images with artifacts) the capability of the technology to determine the minimum-size ablation targets for eradicating all VTs. In the prospective study, VT sites predicted by the technology were targeted directly, without relying on prior electrical mapping. The approach could improve infarct-related VT ablation guidance, where accurate identification of patient-specific optimal targets could be achieved on a personalized virtual heart prior to the clinical procedure.

Atrial fibrillation (AF) -the most common arrhythmia -significantly increases the risk of stroke and heart failure. Although catheter ablation can restore normal heart rhythms, patients with persistent AF who develop atrial fibrosis often undergo multiple failed ablations and thus increased procedural risks. Here, we present personalized computational modelling for the reliable predetermination of ablation targets, which are then used to guide the ablation procedure in patients with persistent AF and atrial fibrosis. We first show that a computational model of the atria of patients identifies fibrotic tissue that if ablated will not sustain AF. We then integrated the target-ablation sites in a clinical-mapping system, and tested its feasibility in 10 patients with persistent AF. The computational prediction of ablation targets avoids lengthy electrical mapping Reprints and permissions information is available at www.nature.com/reprints.Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Identification of optimal ablation sites in hearts with infarct-related ventricular tachycardia (VT) remains difficult to achieve with the current catheter-based mapping techniques. Limitations arise from the ambiguities in determining the reentrant pathways location(s). The goal of this study was to develop experimentally validated, individualized computer models of infarcted swine hearts, reconstructed from high-resolution ex-vivo MRI and to examine the accuracy of the reentrant circuit location prediction when models of the same hearts are instead reconstructed from low clinical-resolution MRI scans. To achieve this goal, we utilized retrospective data obtained from four pigs ~10 weeks post infarction that underwent VT induction via programmed stimulation and epicardial activation mapping via a multielectrode epicardial sock. After the experiment, high-resolution ex-vivo MRI with late gadolinium enhancement was acquired. The Hi-res images were downsampled into two lower resolutions (Med-res and Low-res) in order to replicate image quality obtainable in the clinic. The images were segmented and models were reconstructed from the three image stacks for each pig heart. VT induction similar to what was performed in the experiment was simulated. Results of the reconstructions showed that the geometry of the ventricles including the infarct could be accurately obtained from Med-res and Low-res images. Simulation results demonstrated that induced VTs in the Med-res and Low-res models were located close to those in Hi-res models. Importantly, all models, regardless of image resolution, accurately predicted the VT morphology and circuit location induced in the experiment. These results demonstrate that MRI-based computer models of hearts with ischemic cardiomyopathy could provide a unique opportunity to predict and analyze VT resulting for from specific infarct architecture, and thus may assist in clinical decisions to identify and ablate the reentrant circuit(s).

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, causing morbidity and mortality in millions worldwide. The atria of patients with persistent AF (PsAF) are characterized by the presence of extensive and distributed atrial fibrosis, which facilitates the formation of persistent reentrant drivers (RDs, i.e., spiral waves), which promote fibrillatory activity. Targeted catheter ablation of RD-harboring tissues has shown promise as a clinical treatment for PsAF, but the outcomes remain sub-par. Personalized computational modeling has been proposed as a means of non-invasively predicting optimal ablation targets in individual PsAF patients, but it remains unclear how RD localization dynamics are influenced by inter-patient variability in the spatial distribution of atrial fibrosis, action potential duration (APD), and conduction velocity (CV). Here, we conduct simulations in computational models of fibrotic atria derived from the clinical imaging of PsAF patients to characterize the sensitivity of RD locations to these three factors. We show that RDs consistently anchor to boundaries between fibrotic and non-fibrotic tissues, as delineated by late gadolinium-enhanced magnetic resonance imaging, but those changes in APD/CV can enhance or attenuate the likelihood that an RD will anchor to a specific site. These findings show that the level of uncertainty present in patient-specific atrial models reconstructed without any invasive measurements (i.e., incorporating each individual's unique distribution of fibrotic tissue from medical imaging alongside an average representation of AF-remodeled electrophysiology) is sufficiently high that a personalized ablation strategy based on targeting simulation-predicted RD trajectories alone may not produce the desired result.

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Many heart anatomy models have been developed to study the electrophysiological properties of the human heart. However, none of them includes the geometry of the whole human heart. In this study, an anatomically detailed mathematical model of the human heart was firstly reconstructed from the computed tomography images. In the reconstructed model, the atria consisted of atrial muscles, sinoatrial node, crista terminalis, pectinate muscles, Bachmann's bundle, intercaval bundles, and limbus of the fossa ovalis. The atrioventricular junction included the atrioventricular node and atrioventricular ring, and the ventricles had ventricular muscles, His bundle, bundle branches, and Purkinje network. The epicardial and endocardial myofiber orientations of the ventricles and one layer of atrial myofiber orientation were then measured. They were calculated using linear interpolation technique and minimum distance algorithm, respectively. To the best of our knowledge, this is the first anatomically-detailed human heart model with corresponding experimentally measured fibers orientation. In addition, the whole heart excitation propagation was simulated using a monodomain model. The simulated normal activation sequence agreed well with the published experimental findings.

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Patients with myocardial infarction have an abundance of conduction channels (CC); however, only a small subset of these CCs sustain ventricular tachycardia (VT). Identifying these critical CCs (CCCs) in the clinic so that they can be targeted by ablation remains a significant challenge. The objective of this study is to use a personalized virtual-heart approach to conduct a three-dimensional (3D) assessment of CCCs sustaining VTs of different morphologies in these patients, to investigate their 3D structural features, and to determine the optimal ablation strategy for each VT. To achieve these goals, ventricular models were constructed from contrast enhanced magnetic resonance imagings of six postinfarction patients. Rapid pacing induced VTs in each model. CCCs that sustained different VT morphologies were identified. CCCs' 3D structure and type and the resulting rotational electrical activity were examined. Ablation was performed at the optimal part of each CCC, aiming to terminate each VT with a minimal lesion size. Predicted ablation locations were compared to clinical. Analyzing the simulation results, we found that the observed VTs in each patient model were sustained by a limited number (2.7 5 1.2) of CCCs. Further, we identified three types of CCCs sustaining VTs: I-type and T-type channels, with all channel branches bounded by scar, and functional reentry channels, which were fully or partially bounded by conduction block surfaces. The different types of CCCs accounted for 43.8, 18.8, and 37.4% of all CCCs, respectively. The mean narrowest width of CCCs or a branch of CCC was 9.7 5 3.6 mm. Ablation of the narrowest part of each CCC was sufficient to terminate VT. Our results demonstrate that a personalized virtual-heart approach can determine the possible VT morphologies in each patient and identify the CCCs that sustain reentry. The approach can aid clinicians in identifying accurately the optimal VT ablation targets in postinfarction patients.