Bivalent target-binding bioPROTACs induce potent degradation of oncogenic SHP2.

Targeted protein degradation is an emergent and rapidly evolving therapeutic strategy. In particular, biologics-based targeted degradation modalities (bioPROTACs) are relatively under explored compared to small molecules. Here, we investigate how target affinity, cellular localization, and valency of bioPROTACs impact efficacy of targeted degradation of the oncogenic phosphatase src-homology 2 containing protein tyrosine phosphatase-2 (SHP2). We identify bivalent recruitment of SHP2 by bioPROTACs as a broadly applicable strategy to improve potency. Moreover, we demonstrate that SHP2-targeted bioPROTACs can effectively counteract gain-of-function SHP2 mutants present in cancer, which are otherwise challenging to selectively target with small molecule constructs. Overall, this study demonstrates the utility of bioPROTACs for challenging targets, and further explicates design principles for therapeutic bioPROTACs.

Embodiment Is Related to Better Performance on a Brain-Computer Interface in Immersive Virtual Reality: A Pilot Study.

Electroencephalography (EEG)-based brain-computer interfaces (BCIs) for motor rehabilitation aim to "close the loop" between attempted motor commands and sensory feedback by providing supplemental information when individuals successfully achieve specific brain patterns. Existing EEG-based BCIs use various displays to provide feedback, ranging from displays considered more immersive (e.g., head-mounted display virtual reality (HMD-VR)) to displays considered less immersive (e.g., computer screens). However, it is not clear whether more immersive displays improve neurofeedback performance and whether there are individual performance differences in HMD-VR versus screen-based neurofeedback. In this pilot study, we compared neurofeedback performance in HMD-VR versus a computer screen in 12 healthy individuals and examined whether individual differences on two measures (i.e., presence, embodiment) were related to neurofeedback performance in either environment. We found that, while participants' performance on the BCI was similar between display conditions, the participants' reported levels of embodiment were significantly different. Specifically, participants experienced higher levels of embodiment in HMD-VR compared to a computer screen. We further found that reported levels of embodiment positively correlated with neurofeedback performance only in HMD-VR. Overall, these preliminary results suggest that embodiment may relate to better performance on EEG-based BCIs and that HMD-VR may increase embodiment compared to computer screens.

Bachmann's bundle and coronary sinus ostial pacing accentuate left atrial electrical dyssynchrony in an acute canine model.

INTRODUCTION: In patients with intraatrial conduction delay and sinus node (SN) dysfunction, pacing Bachmann's bundle (BBR) and coronary sinus ostium (CSO) has been suggested to achieve atrial resynchronization with potential beneficial impact on atrial fibrillation and diastolic heart failure. Clinical studies have not shown superiority of one approach. METHODS AND RESULTS: We studied electrical activation sequence in an open-chest acute canine model of normal atrial function in 8 mongrel dogs under general anesthesia. Bipolar plunge electrodes were distributed over the surface of the atria during unifocal pacing, and intracardiac activation sequence was observed. SN pacing resulted in near-simultaneous activation at midline sites (BBR and CSO); the left atrium (LA) was activated by anterior and posterior wavefronts simultaneously propagating septally to laterally and meeting at the low-lateral perimitral LA. Right atrial appendage (RAA) pacing created intra-RA conduction delay and delayed onset of LA activation. Pacing from RAA, CSO, and BBR resulted in nonsimultaneous activation at midline sites and produced an anteroposterior gradient of LA activation. This phenomenon was seen to the greatest degree with midline pacing and shifted the site of latest activation away from the low-lateral perimitral LA in all pacing configurations except SN pacing. CONCLUSION: Pacing-induced intra-LA activation dispersion is enhanced with midline atrial pacing, and secondarily shifts the site of latest activation away from the lateral mitral annulus. Measuring atrial activation times to the low-lateral perimitral LA can underestimate the degree of atrial dyssynchrony and be misinterpreted as atrial synchrony. Establishing clinical impact requires evaluation of human data.

Molecular Docking Improved with Human Spatial Perception Using Virtual Reality.

Adaptive steered molecular dynamics (ASMD) is a computational biophysics method in which an external force is applied to a selected set of atoms or a specific reaction coordinate to induce a particular molecular motion. Virtual reality (VR) based methods for protein-ligand docking are beneficial for visualizing on-the-fly interactive molecular dynamics and performing promising docking trajectories. In this paper, we propose a novel method to guide ASMD with optimal trajectories collected from human experiences using interactive molecular dynamics in virtual reality (iMD-VR). We also explain the benefits of using VR as a tool for expediting the process of ligand binding, outlining an experimental protocol that enables iMD-VR users to guide Amprenavir into and out of the binding pockets of HIV-1 protease and recreate their respective crystallographic binding poses within 5 minutes. Later, we discuss our analysis of the results from iMD-VR-assisted ASMD simulation and assess its performance compared to a standard ASMD simulation. From the accuracy point of view, our proposed method calculates higher Potential Mean Force (PMF) values consistently relative to a standard ASMD simulation with an almost twofold increase in all the experiments. Finally, we describe the novelty of the research and discuss results showcasing a faster and more effective convergence of the ligand to the protein's binding site as compared to a standard molecular dynamics simulation, proving the effectiveness of VR in the field of drug discovery. Future work includes the development of an artificial intelligence algorithm capable of predicting optimal binding trajectories for many protein-ligand pairs, as well as the required force needed to steer the ligand to follow the said trajectory.

A randomized, prospective trial evaluating surgeon preference in selection of absorbable suture material.

This study is the first double-blinded, randomized comparison of two absorbable sutures. To better understand product characteristics and surgeon preference, we conducted a study of two similar-appearing FDA-approved sutures, glyconate and poliglecaprone 25. Four dermatologic surgeons were enlisted. A total of 48 patients with 53 surgical sites were examined. One half of each surgical wound was closed with one type of suture and the other half with the other type. Each half was evaluated for product characteristics. There was no statistically significant difference in surgeon preference for glyconate versus poliglecaprone 25 (P=0.64). Of the cohort preferring poliglecaprone 25, there was a correlation with speed of closure (P=0.06). Of the surgeons that preferred glyconate, we found significantly better visibility (P=0.03), reduced suture breakage during knot tying (P=0.05), and correlation with better handling properties (P=0.06) associated with that preference. The data from this study will enable products to be designed towards these needs and allow surgeons to select sutures that more precisely fit their particular requirements.

Characterizing Recurrence Following Hybrid Ablation in Patients With Persistent Atrial Fibrillation.

PURPOSE: It is widely accepted that atrial fibrillation (AF) accounts for half of arrhythmia recurrences following endocardial catheter ablation of AF. An epicardial-endocardial approach (hybrid) has emerged as an alternative to endocardial ablation alone for the treatment of AF, yet recurrence after a hybrid procedure has not been well characterized. This retrospective study is aimed at characterizing recurrence following hybrid ablation for patients with persistent AF. METHODS: Patients with persistent AF (N=108) received both endocardial and epicardial ablation of the posterior left atrial wall using catheter ablation and a small midline surgical approach (hybrid). Presence of atrial flutter or AF was determined with ambulatory monitoring (n=22) or electrocardiogram analysis (n=86) at each follow-up visit. Recurrence mode was confirmed by electrophysiology study for those patients undergoing subsequent catheter ablation after hybrid ablation. RESULTS: Patients were followed for a mean ± standard deviation of 25 ± 14 months. Of patients who had a recurrence, 53% (n=33) were in atrial flutter and 47% (n=29) were in AF. Of those who had a recurrence with atrial flutter, 14 received repeat ablation for either left (n=11) or left/right (n=3) atrial flutter and 3 received AF ablation. Half of ablations for atrial flutter recurrence following the hybrid procedure involved the mitral isthmus. CONCLUSIONS: Atrial flutter accounts for about half of arrhythmia recurrences post-hybrid ablation. If catheter ablation of the mitral isthmus is considered during the hybrid procedure to prevent subsequent occurrence of perimitral flutter, bidirectional block must be performed to ensure a complete line of block.

Pacing lead implantation without live fluoroscopy: feasibility of acute success in the live canine model.

INTRODUCTION: Fluoroscopic visualization for transvenous pacing lead placement necessitates lead shielding to minimize radiation exposure. An electromagnetic (EM) navigation system that integrates real-time intracardiac tracking within an anatomic navigation environment may provide an effective alternative for lead delivery that obviates live fluoroscopy. We assessed feasibility of pacing lead implantation with electromagnetic tracking guided solely by radiographic virtual navigation and compared this to fluoroscopy-guided implants in a canine model. METHODS: Seven mongrel dogs with normal hearts were randomized to 47 pacing lead placements in the right atrium (RA) or right ventricle (RV) guided by single-plane fluoroscopy, or an experimental EM navigation system guided by registered fluoroscopic snapshots obtained before implant (EMN). Ability to achieve successful lead delivery acutely was assessed, and pacing parameters as well as fluoroscopy and implant times were measured. Means were compared using a paired t-test. RESULTS: All lead delivery attempts were acutely successful. One atrial lead dislodged with EMN, resulting in 46 successful pacing attempts. There was no statistical difference in pacing parameters and time for lead placement between the approaches (EMN vs fluoroscopic navigation [mean +/- SD]: RA threshold 1.15 V +/- 0.98 V vs 1.95 V +/- 0.98 V [P = NS], RV threshold 1.18 V +/- 0.58 V vs 1.42 V +/- 0.63 V [P = NS], implant time 4:38 +/- 2:37 minutes vs 4:44 +/- 2:38 minutes [P = NS]). No live fluoroscopy was required for EMN implants. CONCLUSION: Pacing lead placement with an EM system guided by preprocedural fluoroscopic views is feasible and comparable to fluoroscopic navigation, and avoids the use of live fluoroscopy.

Orientation Perception in Real and Virtual Environments.

Spatial perception in virtual environments has been a topic of intense research. Arguably, the majority of this work has focused on distance perception. However, orientation perception is also an important factor. In this paper, we systematically investigate allocentric orientation judgments in both real and virtual contexts over the course of four experiments. A pattern of sinusoidal judgment errors known to exist in 2D perspective displays is found to persist in immersive virtual environments. This pattern also manifests itself in a real world setting using two differing judgment methods. The findings suggest the presence of a radial anisotropy that persists across viewing contexts. Additionally, there is some evidence to suggest that observers have multiple strategies for processing orientations but further investigation is needed to fully describe this phenomenon. We also offer design suggestions for 3D user interfaces where users may perform orientation judgments.

Effects of video placement and spatial context presentation on path reconstruction tasks with contextualized videos.

Many interesting and promising prototypes for visualizing video data have been proposed, including those that combine videos with their spatial context (contextualized videos). However, relatively little work has investigated the fundamental design factors behind these prototypes in order to provide general design guidance. Focusing on real-time video data visualization, we evaluated two important design factors--video placement method and spatial context presentation method--through a user study. In addition, we evaluated the effect of spatial knowledge of the environment. Participants' performance was measured through path reconstruction tasks, where the participants followed a target through simulated surveillance videos and marked the target paths on the environment model. We found that embedding videos inside the model enabled realtime strategies and led to faster performance. With the help of contextualized videos, participants not familiar with the real environment achieved similar task performance to participants that worked in that environment. We discuss design implications and provide general design recommendations for traffic and security surveillance system interfaces.

Computed tomography-fluoroscopy image integration-guided catheter ablation of atrial fibrillation.

INTRODUCTION: This study examines the feasibility of atrial fibrillation (AF) ablation using registered three-dimensional computed tomography (CT) images of the left atrium with fluoroscopy. METHODS AND RESULTS: A total of 50 consecutive patients with symptomatic AF refractory to medical therapy (32 paroxysmal, 18 persistent, age 55 +/- 10 years) were randomized to undergo a catheter-based AF ablation procedure with or without the CT-fluoroscopy guidance system. All patients underwent preprocedural contrast-enhanced CT imaging and segmentation of the left atrium. For the CT-fluoroscopy group, circumferential lesions encompassing the pulmonary vein (PV) antrum and linear lesions along the roof of the left atrium between the superior PVs and the mitral isthmus were created on the CT image, which was registered with real-time fluoroscopy. The registered images were then used to navigate the ablation catheters to the sites of planned ablation. After the ablation sites were completed, any remaining PV potentials were isolated with electrophysiological guidance. In the control patients, the same technique was performed without using the CT-fluoro guidance system. CT scans were accurately registered to fluoroscopic images with minimal manual correction. Operators could navigate catheters on the registered images to preplanned, extraostial sites for ablation. CT-fluoroscopy guidance decreased procedure duration and fluoro times (P < 0.05). At a mean follow-up of 9 +/- 2 months, 21 patients (84%) in the CT-fluoro guidance group and 16 patients (64%) in the control group have had no recurrence of AF. CONCLUSION: CT-fluoroscopic-guided left atrial ablation is feasible and allows appropriate catheter manipulation in the left atrium.

Contextualized videos: combining videos with environment models to support situational understanding.

Multiple spatially-related videos are increasingly used in security, communication, and other applications. Since it can be difficult to understand the spatial relationships between multiple videos in complex environments (e.g. to predict a person's path through a building), some visualization techniques, such as video texture projection, have been used to aid spatial understanding. In this paper, we identify and begin to characterize an overall class of visualization techniques that combine video with 3D spatial context. This set of techniques, which we call contextualized videos, forms a design palette which must be well understood so that designers can select and use appropriate techniques that address the requirements of particular spatial video tasks. In this paper, we first identify user tasks in video surveillance that are likely to benefit from contextualized videos and discuss the video, model, and navigation related dimensions of the contextualized video design space. We then describe our contextualized video testbed which allows us to explore this design space and compose various video visualizations for evaluation. Finally, we describe the results of our process to identify promising design patterns through user selection of visualization features from the design space, followed by user interviews.

Comparative Effectiveness of Hybrid Ablation Versus Endocardial Catheter Ablation Alone in Patients With Persistent Atrial Fibrillation.

OBJECTIVES: The outcomes of hybrid ablation versus endocardial catheter ablation alone were evaluated in patients with persistent and long-standing persistent atrial fibrillation (AF). BACKGROUND: Variable outcomes exist following endocardial catheter ablation in medically refractory patients with persistent AF. A hybrid epicardial-endocardial approach has emerged as an alternative to endocardial ablation. METHODS: In 133 consecutive patients, 69 received endocardial ablation alone (pulmonary vein isolation and radiofrequency catheter ablation [endo group]) and 64 received endocardial catheter ablation and epicardial ablation (hybrid group). Recurrence was defined as any arrhythmia following the 3-month blanking period. RESULTS: Patients were followed for a median of 16 months. The hybrid and endo groups were similar in age (61 ± 10 years vs. 62 ± 8 years), body mass index (35 ± 6 kg/m2 vs. 35 ± 7 kg/m2), CHA2D2-VASc score (2 ± 1 vs. 2 ± 1), and ejection fraction (54 ± 11% vs. 53 ± 8%). The hybrid group had longer AF duration (median [interquartile range (IQR)] (12 months [IQR: 8 to 28 months] vs. 7 months [IQR: 5 to 12 months]; p < 0.001) and more previous ablations (58% vs. 25%; p < 0.001). Both groups had similar antiarrhythmic drug use at follow-up (55% vs. 48%). The hybrid group was less likely to have recurrence (37% vs. 58%; p = 0.013) and repeat ablation (9% vs. 26%; p = 0.012), and had an AF-free survival of 72% versus 51% (p = 0.01). CONCLUSIONS: Among patients with persistent AF, hybrid ablation is associated with less AF recurrence and fewer re-do ablations. Prospective large-scale randomized trials are needed to validate these results.

Registration of three-dimensional left atrial computed tomographic images with projection images obtained using fluoroscopy.

BACKGROUND: Anatomic structures such as the left atrium and the pulmonary veins (PVs) are not delineated by fluoroscopy because there is no contrast differentiation between them and the surrounding anatomy. Representation of an anatomic structure via a 3D model obtained from computed tomography (CT) imaging and subsequent projection of these images over the fluoroscopy system may help in navigation of the mapping and ablation catheter to the appropriate sites during electrophysiology procedures. METHODS AND RESULTS: In this feasibility study, in vitro experiments were performed with a plastic heart model (phantom) with 2 catheters or radiopaque platinum beads placed in the phantom at the time of CT imaging and fluoroscopy. Subsequently, 20 consecutive patients underwent contrast-enhanced, ECG-gated CT scanning. Left atrial volumes were generated from the reconstructed data at &75% of the R-R interval during the cardiac cycle. Similarly, the superior vena cava and the coronary sinus were also reconstructed from these images. During the electrophysiology procedure, digital records (cine sequences) were obtained. Using predetermined algorithms, both the phantom model and the patients' 3D left atrial models derived from the CT were registered with projection images of fluoroscopy. Registration was performed with a transformation that linked the superior vena cava and the coronary sinus from the CT model with a catheter placed inside the coronary sinus via the superior vena cava. Registration was successfully accomplished with the plastic phantom and in all 20 patients. Registration accuracy was assessed in the phantom by assessing the overlapping beads seen both in the CT and the fluoroscopy images. The mean registration error was 1.4 mm (range 0.9 to 2.3 mm). Accuracy of the registered images was assessed in patients with recordings from a basket catheter placed sequentially in the superior PVs and by injecting contrast into the PVs to assess overlapping of contrast-filled PVs with the corresponding vessels on the registered images. The images could be calibrated quite accurately. Any rotational error, which was usually minor, could be corrected by rotating the images as needed. CONCLUSIONS: Registration of 3D models of the left atrium and PVs with fluoroscopic images of the same is feasible and could enable appropriate navigation and localization of the mapping and ablation catheter during procedures such as atrial fibrillation ablation.

Registration of 3D computed tomographic images with interventional systems: implications for catheter ablation of atrial fibrillation.

Despite the great promise catheter ablation offers in the treatment of complex arrhythmias such as atrial fibrillation (AF), long procedure times and somewhat suboptimal results hinder the widespread use of this technique. As fluoroscopy does not provide contrast differentiation between the area of interest and the surrounding structures, there is a lack of proper intra procedure image guidance. Segmentation of anatomical structures such as the left atrium (LA) can be performed using images obtained with modalities such as computed tomography (CT). However, unlike the cardiac mapping systems, these imaging systems do not track catheters in real time. This review addresses the evolving concept of image registration to deliver therapy in cardiac arrhythmias.

Posterior left atrial-esophageal relationship throughout the cardiac cycle.

BACKGROUND: Radiofrequency energy delivered throughout the cardiac cycle has the potential to cause thermal injury to the esophagus if the anatomical relationship between the posterior left atrium and the esophagus changes during cardiac motion. OBJECTIVE: To assess the posterior left atrial-esophageal relationship throughout the cardiac cycle. METHODS: In this study, the anatomical relationship between the posterior left atrium and the esophagus was assessed throughout the cardiac cycle in 10 consecutive patients. All patients underwent contrast-enhanced, ECG-gated CT scanning. Left atrial volumes and the esophageal structure were generated from the reconstructed data at 10 phases of the cardiac cycle from 5% to 95% of the R-R interval. The posterior left atrial-esophageal anatomical relationship was measured at four levels, the superior pulmonary vein ostial site, and the upper, mid and lower left atrium. RESULTS: There were significant variations in the left atrial-esophageal relationship in the 10 patients. The relative movement between the esophagus and the posterior left atrium throughout the cardiac cycle in the anteroposterior and right-to-left orientations was 0.55 +/- 0.99 mm and 0.60 +/- 1.02 mm (95% confidence interval, 2.03 and 1.98 respectively). CONCLUSIONS: Under normal conditions, there is little change in the anatomical relationship between the posterior left atrium and the esophagus during the entire cardiac cycle. However, due to the interpatient variability at the esophageal location, identification of esophageal location may help prevent complications during catheter ablation procedures involving the left atrium.

Pulmonary vein isolation and linear lesions in atrial fibrillation ablation.

BACKGROUND: Various strategies have been used for atrial fibrillation (AF) ablation. It is unclear whether adding linear lesions to pulmonary vein (PV) isolation has significant advantages. OBJECTIVES: We assessed the clinical benefit of adding linear lesions in patients undergoing PV isolation for AF. METHODS: One hundred patients (63 male and 37 female; mean age of 59 +/- 11 years) with documented paroxysmal AF were included in the study. Patients were randomized into two groups. The first group underwent PV isolation alone. The second group underwent PV isolation and had two linear lesions created; one line between the superior PVs, and a second line from the left inferior PV to the mitral valve annulus. Patients' clinical progress after the ablation was evaluated and compared at 1, 3, and 9 months after their respective ablation procedures. RESULTS: The linear lesions group maintained sinus rhythm and had fewer symptoms than the lone PV isolation group (86 vs. 58%, respectively) (p < 0.05) at 1 month. At 9 months, when patients who reverted to AF underwent additional management to regain sinus rhythm (90 vs. 82%, respectively) (p = NS), there was no statistical difference between the groups regarding the use of antiarrhythmics, the need for electrical cardioversion, and subjective improvement. CONCLUSION: The addition of linear lesions to PV isolation more effectively achieved sinus rhythm initially and fewer patients required additional management to maintain their rhythm when compared to patients who underwent lone PV isolation. However, at 9 months, the overall results were similar in both groups.

Identifying the third dimension in 2D fluoroscopy to create 3D cardiac maps.

Three-dimensional cardiac mapping is important for optimal visualization of the heart during cardiac ablation for the treatment of certain arrhythmias. However, many hospitals and clinics worldwide cannot afford the high cost of the current mapping systems. We set out to determine if, using predefined algorithms, comparable 3D cardiac maps could be created by a new device that relies on data generated from single-plane fluoroscopy and patient recording and monitoring systems, without the need for costly equipment, infrastructure changes, or specialized catheters. The study included phantom and animal experiments to compare the prototype test device, Navik 3D, with the existing CARTO 3 System. The primary endpoint directly compared: (a) the 3D distance between the Navik 3D-simulated ablation location and the back-projected ground truth location of the pacing and mapping catheter electrode, and (b) the same distance for CARTO. The study's primary objective was considered met if the 95% confidence lower limit was greater than 0.75% for the Navik 3D-CARTO difference between the 2 distances, or less than or equal to 2 mm. Study results showed that the Navik 3D performance was equivalent to the CARTO system, and that accurate 3D cardiac maps can be created using data from equipment that already exists in all electrophysiology labs.

Feasibility and validation of registration of three-dimensional left atrial models derived from computed tomography with a noncontact cardiac mapping system.

OBJECTIVES: The purpose of this study was to determine the feasibility and assess the validity of registering three-dimensional (3D) models from computed tomographic (CT) images using a cardiac mapping system. BACKGROUND: Registration of 3D anatomic models with an interventional system could help identify and navigate mapping and ablation catheters over a complex structure such as the left atrium (LA). METHODS: ECG-gated, contrast-enhanced cardiac CT imaging was performed in 14 patients with atrial fibrillation. Segmentation was used to create 3D models of the LA. The 3D models were registered with the mapping system using a series of fiducial points. Registration was accomplished retrospectively in the first 10 patients, and catheter navigation was visualized from recorded data. In the final four patients, registration was accomplished in real time during electrophysiologic study. The mapping catheter position, as it was navigated inside the LA, was applied to the registered model in real time. For the validation study, temporary pacing leads were implanted in the LA of 10 dogs. Following this, CT scanning, segmentation, LA model importation, and registration was described previously. After registration, a mapping catheter was positioned at the site of each buried lead according to the registered model with no fluoroscopic guidance. A radiofrequency lesion was created at this location, and the dog was sacrificed, the heart removed and stained, and the distance between the buried lead and the lesion measured. RESULTS: During the feasibility study, the location of the catheter in the registered model correlated with fluoroscopy, angiography, and intracardiac electrograms. LA endocardial potentials during sinus rhythm and any premature atrial contractions also were successfully delineated over the registered models. In the validation study, the mean target registration error was 2.0 +/- 3.6 mm. CONCLUSIONS: Registration of CT-derived 3D models of the LA using a cardiac mapping system is feasible and accurate.

Catheter location, tracking, cardiac chamber geometry creation, and ablation using cutaneous patches.

OBJECTIVE: The ability to construct a three-dimensional (3-D) surface model of the endocardium and track the location of catheters within a cardiac chamber, using only cutaneous patches, would be a useful advancement in treating arrhythmias. We tested the feasibility of such a system, Ensite NavX (Endocardial Solutions, Inc., St. Paul, MN, USA), in patients undergoing catheter ablation for SVTs. METHODS: Sixteen patients with 20 arrhythmias undergoing ablation were selected. Skin electrode patches were placed on the chest to create a 3-D coordinate system. A low-amplitude, 5.7 kHz signal emitted from the patches was received by conventional catheters positioned in the heart. Catheter location was determined by measuring the field strength received by the catheters. Location points were successively acquired while catheters were moved throughout the chamber. This information was collected and processed by a workstation to create a detailed 3-D model of the endocardial surface. Anatomic landmarks were labeled on the model as the mapping catheter was navigated. 3-D cardiac chamber geometry reconstruction, landmark labeling, and real time catheter tracking were performed successfully in all patients. Up to six catheters, with a total of up to 26 intracardiac electrodes, were tracked simultaneously. RESULTS: Constructed geometries, including major vessels and valves, correlated closely with traditional anatomic models as well as intracardiac recordings and fluoroscopic images. CONCLUSIONS: Real-time catheter tracking and 3-D cardiac chamber model construction is feasible using cutaneous patches and conventional catheters. This approach may be useful in the treatment of patients with cardiac arrhythmias where ablation therapy is primarily anatomically based.