BACKGROUND Recent advances have enabled noninvasive mapping of cardiac arrhythmias with electrocardiographic imaging and noninvasive delivery of precise ablative radiation with stereotactic body radiation therapy (SBRT). We combined these techniques to perform catheter-free, electrophysiology-guided, noninvasive cardiac radioablation for ventricular tachycardia. METHODS We targeted arrhythmogenic scar regions by combining anatomical imaging with noninvasive electrocardiographic imaging during ventricular tachycardia that was induced by means of an implantable cardioverter–defibrillator (ICD). SBRT simulation, planning, and treatments were performed with the use of standard techniques. Patients were treated with a single fraction of 25 Gy while awake. Efficacy was assessed by counting episodes of ventricular tachycardia, as recorded by ICDs. Safety was assessed by means of serial cardiac and thoracic imaging. RESULTS From April through November 2015, five patients with high-risk, refractory ventricular tachycardia underwent treatment. The mean noninvasive ablation time was 14 minutes (range, 11 to 18). During the 3 months before treatment, the patients had a combined history of 6577 episodes of ventricular tachycardia. During a 6-week postablation “blanking period” (when arrhythmias may occur owing to postablation inflammation), there were 680 episodes of ventricular tachycardia. After the 6-week blanking period, there were 4 episodes of ventricular tachycardia over the next 46 patient-months, for a reduction from baseline of 99.9%. A reduction in episodes of ventricular tachycardia occurred in all five patients. The mean left ventricular ejection fraction did not decrease with treatment. At 3 months, adjacent lung showed opacities consistent with mild inflammatory changes, which had resolved by 1 year. CONCLUSIONS In five patients with refractory ventricular tachycardia, noninvasive treatment with electrophysiology-guided cardiac radioablation markedly reduced the burden of ventricular tachycardia. (Funded by Barnes–Jewish Hospital Foundation and others.)

BACKGROUND-Case studies have suggested the efficacy of catheter-free, electrophysiologyguided noninvasive cardiac radioablation for ventricular tachycardia (VT) using stereotactic body radiation therapy (SBRT), though prospective data is lacking. METHODS-We conducted a prospective phase I/II trial of noninvasive cardiac radioablation in adults with treatment-refractory episodes of VT or cardiomyopathy related to premature ventricular contractions (PVCs). Arrhythmogenic scar regions were targeted by combining noninvasive anatomic and electrical cardiac imaging with a standard SBRT workflow followed by delivery of a single fraction of 25 Gray (Gy) to the target. The primary safety endpoint was treatment-related serious adverse events (SAE) in the first 90 days. The primary efficacy endpoint was any reduction in VT episodes (tracked by indwelling ICDs) or any reduction in PVC burden

Background-Various mechanisms of atrial fibrillation (AF) have been demonstrated experimentally. Invasive methods to study these mechanisms in humans have limitations, precluding continuous mapping of both atria with sufficient resolution. In this article, we present continuous biatrial epicardial activation sequences of AF in humans using noninvasive electrocardiographic imaging (ECGI). Methods and Results-In the testing phase, ECGI accuracy was evaluated by comparing ECGI with coregistered CARTO images during atrial pacing in 6 patients. Additionally, correlative observations from catheter mapping and ablation were compared with ECGI in 3 patients. In the study phase, ECGI maps during AF in 26 patients were analyzed for mechanisms and complexity. ECGI noninvasively imaged the low-amplitude signals of AF in a wide range of patients (97% procedural success). Spatial accuracy for determining initiation sites from pacing was 6 mm. Locations critical to maintenance of AF identified during catheter ablation were identified by ECGI; ablation near these sites restored sinus rhythm. In the study phase, the most common patterns of AF were multiple wavelets (92%), with pulmonary vein (69%) and non-pulmonary vein (62%) focal sites. Rotor activity was seen rarely (15%). AF complexity increased with longer clinical history of AF, although the degree of complexity of nonparoxysmal AF varied widely. Conclusions-ECGI

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Background-Ablation of complex arrhythmias would be greatly facilitated by more precise control of ablation catheters.A feasibility study was performed in animals to evaluate a novel magnetic guidance system (MGS) that generates a magnetic field to control the movement and position of a magnetic ablation catheter. Methods and Results-The MGS is composed of a digital biplanar fluoroscope within an array of superconducting electromagnets that surround the torso of the experimental animal and a computer control system that generates a composite magnetic field for directional catheter deflection. Magnetic catheter navigation was performed in dogs and pigs (20 to 30 kg). A 7F magnetic ablation catheter was used for intracardiac navigation and radiofrequency ablation. The performance of a standard 7F deflectable catheter was not affected by the MGS. The magnetic catheter was navigated successfully to 51 predefined targets throughout the heart in 6 animals. In 5 animals, the magnetic catheter, guided by a 3D computed tomogram, was successfully navigated to all pulmonary veins. Navigation accuracy was estimated as Ͻ1 mm displacement from the target. The magnetic catheter was used to ablate the atrioventricular node in 4 animals and to perform linear ablations across the endocardial surface underlying an epicardial multielectrode recording plaque in 4 animals. Conclusions-These results demonstrate that the MGS can navigate and stabilize an ablation catheter at endocardial targets. Linear or focal radiofrequency ablation with the magnetic catheter is not compromised by the magnetic field.

Sudden cardiac death due to ventricular tachycardia (VT) is a major health issue worldwide. Efforts to identify patients at risk, determine VT mechanisms, and effectively prevent and treat VT with a mechanism-based approach would benefit from continuous noninvasive imaging of the arrhythmia over the entire heart. This paper presents the first noninvasive images of human ventricular arrhythmias using electrocardiographic imaging (ECGI), highlighting the large diversity of human VT in terms of activation patterns, mechanisms, and sites of initiation. Based on comparison with catheter mapping, ECGI provided high spatial resolution; a property that overcomes a limitation of the body surface electrocardiogram, which provides only global information. The spatial resolution and ability to image the activation sequences over the entire ventricular surfaces in a single beat allowed us to make observations regarding VT initiation and continuation, and regarding relationships to ventricular substrates, including anatomical scars and abnormal electrophysiological substrate. The ability of ECGI to provide patient-specific physiologic insights, to map the VT activation sequence and to identify the location and depth of VT origin from a single beat has important clinical implications in treating patients with ventricular arrhythmias.

Background Brugada syndrome (BrS) is a highly arrhythmogenic cardiac disorder, associated with an increased incidence of sudden death. Its arrhythmogenic substrate in the intact human heart remains ill-defined. Methods and Results Using noninvasive ECG imaging (ECGI), we studied 25 BrS patients to characterize the electrophysiologic substrate, and 6 patients with right bundle branch block (RBBB) for comparison. Seven normal subjects provided control data. Abnormal substrate was observed exclusively in the right ventricular outflow tract (RVOT) with the following properties (compared to normal controls; p<0.005): (1)ST-segment elevation (STE) and inverted T-wave of unipolar electrograms (EGMs) (2.21±0.67 vs. 0 mV); (2)delayed RVOT activation (82±18 vs. 37±11 ms); (3)low amplitude (0.47±0.16 vs. 3.74±1.60 mV) and fractionated EGMs, suggesting slow discontinuous conduction; (4)prolonged recovery time (RT; 381±30 vs. 311±34 ms) and activation-recovery intervals (ARIs; 318±32 vs. 241±27 ms), indicating delayed repolarization; (5)steep repolarization gradients (ΔRT/Δx= 96±28 vs. 7±6 ms/cm, ΔARI/Δx= 105±24 vs. 7±5 ms/cm) at RVOT borders. With increased heart rate in 6 BrS patients, reduced STE and increased fractionation were observed. Unlike BrS, RBBB had delayed activation in the entire RV, without STE, fractionation, or repolarization abnormalities on EGMs. Conclusions The results indicate that both, slow discontinuous conduction and steep dispersion of repolarization are present in the RVOT of BrS patients. ECGI could differentiate between BrS and RBBB.

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