Mind In Vitro Platforms: Versatile, Scalable, Robust, and Open Solutions to Interfacing with Living Neurons.

Motivated by the unexplored potential of in vitro neural systems for computing and by the corresponding need of versatile, scalable interfaces for multimodal interaction, an accurate, modular, fully customizable, and portable recording/stimulation solution that can be easily fabricated, robustly operated, and broadly disseminated is presented. This approach entails a reconfigurable platform that works across multiple industry standards and that enables a complete signal chain, from neural substrates sampled through micro-electrode arrays (MEAs) to data acquisition, downstream analysis, and cloud storage. Built-in modularity supports the seamless integration of electrical/optical stimulation and fluidic interfaces. Custom MEA fabrication leverages maskless photolithography, favoring the rapid prototyping of a variety of configurations, spatial topologies, and constitutive materials. Through a dedicated analysis and management software suite, the utility and robustness of this system are demonstrated across neural cultures and applications, including embryonic stem cell-derived and primary neurons, organotypic brain slices, 3D engineered tissue mimics, concurrent calcium imaging, and long-term recording. Overall, this technology, termed "mind in vitro" to underscore the computing inspiration, provides an end-to-end solution that can be widely deployed due to its affordable (>10× cost reduction) and open-source nature, catering to the expanding needs of both conventional and unconventional electrophysiology.

Periaortic ventricular tachycardia in structural heart disease: Evidence of localized reentrant mechanisms.

BACKGROUND: The mechanisms for scar-related ventricular tachycardia (VT) originating from the periaortic region remain incompletely characterized. OBJECTIVE: The purpose of this study was to map the circuits responsible for periaortic VT in high resolution. METHODS: Cases with periaortic VT (2016-2020) were analyzed to characterize the substrate and mechanisms with multielectrode mapping. Periaortic VT was defined as low-voltage and/or deceleration zones within 2 cm of the left ventriculoaortic junction with a corresponding critical site during VT. RESULTS: Forty-nine periaortic monomorphic VTs were analyzed in 30 patients (25% of all patients with nonischemic cardiomyopathy). Isolated periaortic substrate was observed in 27% of patients, with 73% having concomitant scar, most commonly in the mid-septum (47%). Deceleration zones were equally prevalent on the septal and lateral portions of the periaortic region (87% vs 73%; P = .19). During activation mapping of VT (tachycardia cycle length 392 ± 105 ms), localized reentrant patterns of activation (14 mm [10-17 mm] × 10 mm [7-14 mm]) were demonstrated in 63% and 37% of VTs showed centrifugal activation, consistent with a focal breakout pattern. Ninety-three percent of VTs fulfilled criteria for a reentrant mechanism. Sixty-five percent of reentrant circuits had endocardial activation gaps within the tachycardia cycle length (3-dimensional circuitry), which were associated with higher rates of recurrence as compared with 2-dimensional complete circuits at 1 year (73% vs 37%; P = .028). CONCLUSION: Periaortic VTs were observed in 25% of patients with nonischemic cardiomyopathy and scar-related VT. For the first time, localized reentry confined to this anatomically challenging region was demonstrated as the predominant mechanism by high-resolution circuit activation mapping.

High-Density Grid Catheter for Detailed Mapping of Sinus Rhythm and Scar-Related Ventricular Tachycardia: Comparison With a Linear Duodecapolar Catheter.

OBJECTIVES: This study aimed to evaluate the feasibility and accuracy of using a novel grid mapping catheter during scar-related ventricular tachycardia (VT) ablation. BACKGROUND: Ultra-high-density (UHD) mapping improves identification of local abnormal ventricular activities (LAVAs) and characterization of scar substrates. METHODS: Consecutive patients underwent endocardial and/or epicardial ablation guided by a HD grid mapping catheter. A linear duodecapolar catheter was used in the initial cases for systematic correlation. Isochronal late activation mapping was performed during sinus rhythm to identify deceleration zones, and activation mapping of VT was performed when tolerated. RESULTS: In 38 patients, 51 electroanatomic maps (left ventricle: 26, epicardium: 21, right ventricle: 4) were created using a grid catheter. LAVAs were identified in 98% of cases and deceleration zones were observed in 86%. High-frequency electrograms with diastolic activation were identified during 44 sustained monomorphic VTs, and the critical isthmus was colocalized to deceleration zones during sinus rhythm in 96% of cases. In 17 cases that underwent sequential mapping with both grid and linear catheters, the low voltage area detected using the grid (HD wave) was significantly smaller, with ratios of 0.61 (<0.5 mV) and 0.81 (<1.5 mV) relative to the duodecapolar catheter. CONCLUSIONS: VT ablation guided by a novel HD grid catheter is safe and feasible for clinical use in human scar-related VT via both endocardial and epicardial approaches. Automated selection of larger bipolar amplitudes among orthogonal pairs consistently displayed smaller low voltage areas than a previously validated linear catheter.

Targeted Ablation of Ventricular Tachycardia Guided by Wavefront Discontinuities During Sinus Rhythm: A New Functional Substrate Mapping Strategy.

BACKGROUND: Accurate and expedited identification of scar regions most prone to reentry is needed to guide ventricular tachycardia (VT) ablation. We aimed to prospectively assess outcomes of VT ablation guided primarily by the targeting of deceleration zones (DZ) identified by propagational analysis of ventricular activation during sinus rhythm. METHODS: Patients with scar-related VT were prospectively enrolled in the University of Chicago VT Ablation Registry between 2016 and 2018. Isochronal late activation maps annotated to the latest local electrogram deflection were created with high-density multielectrode mapping catheters. Targeted ablation of DZ (>3 isochrones within 1cm radius) was performed, prioritizing later activated regions with maximal isochronal crowding. When possible, activation mapping of VT was performed, and successful ablation sites were compared with DZ locations for mechanistic correlation. Patients were prospectively followed for VT recurrence and mortality. RESULTS: One hundred twenty patients (median age 65 years [59-71], 15% female, 50% nonischemic, median ejection fraction 31%) underwent 144 ablation procedures for scar-related VT. 57% of patients had previous ablation and epicardial access was employed in 59% of cases. High-density mapping during baseline rhythm was performed (2518 points [1615-3752] endocardial, 5049±2580 points epicardial) and identified an average of 2±1 DZ, which colocalized to successful termination sites in 95% of cases. The median total radiofrequency application duration was 29 min (21-38 min) to target DZ, representing ablation of 18% of the low-voltage area. At 12±10 months, 70% freedom from VT recurrence (80% in ischemic cardiomyopathy and 63% in nonischemic cardiomyopathy) was achieved. The overall survival rate was 87%. CONCLUSIONS: A novel voltage-independent high-density mapping display can identify the functional substrate for VT during sinus rhythm and guide targeted ablation, obviating the need for extensive radiofrequency delivery. Regions with isochronal crowding during the baseline rhythm were predictive of VT termination sites, providing mechanistic evidence that deceleration zones are highly arrhythmogenic, functioning as niduses for reentry.

Intermittent left bundle branch block: What is the mechanism?

We present an illustrative case of a patient with intermittent left bundle branch block (LBBB) that underwent electrophysiological study with detailed multielectrode recordings of the right and left septum. The case elucidates the nature and location of conduction block and provides further insight into the underlying mechanisms of LBBB.

Incidence and Clinical Significance of New-Onset Device-Detected Atrial Tachyarrhythmia: A Meta-Analysis.

BACKGROUND: Despite the clear association between atrial fibrillation and risk for thromboembolic events (TEs), the clinical significance of new-onset device-detected atrial tachyarrhythmia (DDAT) and TE remains disputed. We aimed to determine the risk of TE in patients with new-onset DDAT. METHODS AND RESULTS: The OVID Medline, Cochrane, and Scopus databases (inception to November 2016) were searched. Randomized controlled trials, prospective, or retrospective studies of pacemaker or defibrillator patients reporting incidence of DDAT were selected. Summary statistics were used for analysis. Of 4893 reports identified, 28 studies following 24 984 patients were included: average age 69.9 years, 34.7% women, mean study duration 21.8±18.6 months. New-onset DDAT was observed in 23% of patients. Among 9 studies (n=8181) reporting TE, the absolute incidence was 2.1%. TE risk was significantly greater among patients with new-onset DDAT (relative risk [RR], 2.88; 95% CI, 1.79-4.64; P<0.001). TE risk was correlated with DDAT duration, with an increased risk associated with DDAT ≥5 minutes (RR, 3.86; 95% CI, 2.04-7.30; P<0.001) compared with <1 minute (RR, 1.77; 95% CI, 1.15-2.74; P=0.01). Notably, the risk of TE was also increased in patients with adjudicated atrial electrograms (RR, 3.60; 95% CI, 2.06-6.30; P<0.001) compared with nonadjudicated electrograms (RR, 2.05; 95% CI, 1.06-3.97; P=0.03), even when lower mean thresholds for detection were used. CONCLUSIONS: New-onset DDAT is common, affecting close to one quarter of all patients with implanted pacemakers or defibrillators. Adjudication of atrial electrograms further identifies at-risk patients, even when relatively short detection thresholds are used.

Cybersecurity for Cardiac Implantable Electronic Devices: What Should You Know?

Medical devices have been targets of hacking for over a decade, and this cybersecurity issue has affected many types of medical devices. Lately, the potential for hacking of cardiac devices (pacemakers and defibrillators) claimed the attention of the media, patients, and health care providers. This is a burgeoning problem that our newly electronically connected world faces. In this paper from the Electrophysiology Section Council, we briefly discuss various aspects of this relatively new threat in light of recent incidents involving the potential for hacking of cardiac devices. We explore the possible risks for the patients and the effect of device reconfiguration in an attempt to thwart cybersecurity threats. We provide an outline of what can be done to improve cybersecurity from the standpoint of the manufacturer, government, professional societies, physician, and patient.

Characterization of Ventricular Tachycardia After Left Ventricular Assist Device Implantation as Destination Therapy: A Single-Center Ablation Experience.

OBJECTIVES: This study sought to report mechanisms of ventricular tachycardia (VT) and outcomes of VT ablation in patients with a left ventricular assist device (LVAD) as destination therapy. BACKGROUND: Continuous flow LVAD implantation plays a growing role in the management of end-stage heart failure, and VT is common. There are limited reports of VT ablation in patients with a destination LVAD. METHODS: Patients with a continuous-flow LVAD referred for VT ablation from 2010 to 2016 were analyzed retrospectively. Baseline patient characteristics, procedural data, and clinical follow-up were evaluated. Arrhythmia-free survival was assessed. RESULTS: Twenty-one patients (90% male, 62 ± 10 years) underwent catheter ablation of VT at a median of 191 days (interquartile range: 55 to 403 days) after LVAD implantation (15 HeartMate II, 6 HeartWare HVAD). Five patients (24%) had termination (n = 4) or slowing (n = 1) of VT with ablation near the apical inflow cannula, and 3 (14%) had bundle-branch re-entry. Freedom from recurrent VT among surviving patients was 64% at 1 year, with overall survival 67% at 1 year for patients without arrhythmia recurrence and 29% for patients with recurrence (p = 0.049). One patient had suspected pump thrombosis within 30 days of the ablation procedure, with no other major acute complications. CONCLUSIONS: In this relatively large, single-center experience of VT ablation in destination LVAD, freedom from recurrent VT and implantable cardioverter-defibrillator shocks was associated with improved 1-year survival. Bundle branch re-entry was more prevalent than anticipated, and cannula-adjacent VT was less common. This challenging population remains at risk for late pump thrombosis and mortality.

Pulmonary vein isolation with complex fractionated atrial electrogram ablation for paroxysmal and nonparoxysmal atrial fibrillation: A meta-analysis.

BACKGROUND: Pulmonary vein isolation (PVI) is recognized as a potentially curative treatment for atrial fibrillation (AF). Ablation of complex fractionated atrial electrograms (CFAEs) in addition to PVI has been advocated as a means to improve procedural outcomes, but the benefit remains unclear. OBJECTIVE: This study sought t synthesize the available data testing the incremental benefit of adding CFAE ablation to PVI. METHODS: We performed a meta-analysis of controlled studies comparing the effect of PVI with CFAE ablation vs. PVI alone in patients with paroxysmal and nonparoxysmal AF. RESULTS: Of the 481 reports identified, 8 studies met our inclusion criteria. There was a statistically significant increase in freedom from atrial tachyarrhythmia (AT) with the addition of CFAE ablation (relative risk [RR] 1.15, P = .03). In the 5 reports of nonparoxysmal AF (3 randomized controlled trials, 1 controlled clinical trial, and 1 trial using matched historical controls), addition of CFAE ablation resulted in a statistically significant increase in freedom from AT (n = 112 of 181 [62%] for PVI+CFAE vs. n = 84 of 179 [47%] for PVI alone; RR 1.32, P = .02). In trials of paroxysmal AF (3 randomized controlled trials and 1 trial using matched historical controls), addition of CFAE ablation did not result in a statistically significant increase in freedom from AT (n = 131 of 166 [79%] for PVI+CFAE vs. n = 122 of 164 [74%] for PVI alone; RR 1.04, P = .52). CONCLUSION: In these studies of patients with nonparoxysmal AF, addition of CFAE ablation to PVI results in greater improvement in freedom from AF. No additional benefit of this combined approach was observed in patients with paroxysmal AF.