The response to high frequency stimulation (HFS) is used to locate putative sites of ganglionated plexuses (GPs), which are implicated in triggering atrial fibrillation (AF). To identify topological and immunohistochemical characteristics of presumed GP sites functionally identified by HFS. Sixty-three atrial sites were tested with HFS in four Langendorff-perfused porcine hearts. A 3.5 mm tip quadripolar ablation catheter was used to stimulate and deliver HFS to the left and right atrial epicardium, within the local atrial refractory period. Tissue samples from sites triggering atrial ectopy/AF (ET) sites and non-ET sites were stained with choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH), for quantification of parasympathetic and sympathetic nerves, respectively. The average cross-sectional area (CSA) of nerves was also calculated. Histomorphometry of six ET sites (9.5%) identified by HFS evoking at least a single atrial ectopic was compared with non-ET sites. All ET sites contained ChAT-immunoreactive (ChAT-IR) and/or TH-immunoreactive nerves (TH-IR). Nerve density was greater in ET sites compared to non-ET sites (nerves/cm²: 162.3 ± 110.9 vs. 69.65 ± 72.48; P = 0.047). Overall, TH-IR nerves had a larger CSA than ChAT-IR nerves (µm²: 11 196 ± 35 141 vs. 2070 ± 5841; P < 0.0001), but in ET sites, TH-IR nerves were smaller than in non-ET sites (µm²: 6021 ± 14 586 vs. 25 254 ± 61 499; P < 0.001). ET sites identified by HFS contained a higher density of smaller nerves than non-ET sites. The majority of these nerves were within the atrial myocardium. This has important clinical implications for devising an effective therapeutic strategy for targeting autonomic triggers of AF.

BACKGROUND: Conventional activation mapping of atrial fibrillation (AF) during clinical procedures is limited by low-amplitude, fractionated electrograms and cycle length variability. The Tau20-RETROmapping stimulator-recorder system (TauRhythm Therapies, United Kingdom) is an investigational device used to identify nonpulmonary vein AF drivers by real-time, high-density activation mapping of uniform wavefronts during AF. We validated the accuracy of the system and applied it to left atrial mapping for evidence of AF drivers. METHODS: Left atrial geometry was acquired using a 3-dimensional electroanatomic mapping system with high-density mapping catheters (CARTO 3 with Optrell, or EnSite X with HD Grid). Electrograms were recorded for 30 seconds at multiple left atrial sites. The Tau20-RETROmapping system generates activation maps of organized wavefronts. System performance was manually validated against randomly sampled local electrograms using a grid sweep of thresholds to identify Pareto-optimal parameters in sinus rhythm, atrial pacing, atrial tachycardia (AT), and AF. The system was then applied to identify putative driver activation patterns during persistent AF. RESULTS: We studied 24 patients undergoing pulmonary vein isolation for AF. Six patients presented in sinus rhythm or AT, in whom the system demonstrated a sensitivity of 100.0% (95% CI, 80.5%–100.0%) and a specificity of 100.0% (85.2%–100.0%). Eighteen patients were mapped in AF: the system had a sensitivity of 94.4% (86.2%–98.4%) and a specificity of 97.1% (89.9%–99.6%) when identifying organized AF wavefronts, and accurately identified the earliest activation in 89.6% (79.7%–95.7%) of waves. Stable propagation originating from the left atrial appendage (LAA) was observed in 3/18 patients, while 8/18 demonstrated competing propagation toward and away from the LAA. Conduction away from the LAA was detected along the anterior (8/18 patients), lateral (8/18 patients), and posterior (7/18 patients) walls. No propagation near the LAA was observed in 6/18 patients. CONCLUSIONS: The Tau20-RETROmapping system enables real-time activation mapping of AF, with the most convincing driver-like areas being identified around the LAA.

Background: We present a miniature (30 × 34 mm) 64-channel data acquisition headstage optimized for high-density surface electromyography. Methods: The headstage is made up of a multi-channel ASIC analogue front-end utilizing only MOS transistors, fabricated in 350 nm CMOS technology (IC die dimensions 6.9 × 1.8 mm), combined with an off-the-shelf multi-channel current-input ADC (DDC264, Texas Instruments). The ASIC analogue front-end employs MOS-based capacitors for both processing and AC-coupling. Results: The combination of these two sub-circuits enables the simultaneous recording of 64 channels at a typical sampling rate of 4 KHz with a maximum analogue bandwidth of 0.5–1500 Hz and a resolution of 20-bits. Typical input-referred-noise, determined by the analogue front-end, is 3.5 μV_RMS for a surface EMG bandwidth of interest of 20–500 Hz. This two-chip solution results in a power consumption of 5 mW per channel. Analogue performance variability of the custom ASIC was characterized across a dataset of 960-channels (15 dies) from two fabrication runs. Conclusions: This work practically demonstrates the viability of using both a MOS-only analogue front-end and commercially available off-shelf high-performance back-end hardware already developed for medical imaging applications to record high-density surface biosignals. The aforementioned techniques can be employed to reduce the size and cost for systems or wearable devices; facilitating the translation of high-density bio-acquisition setups from the research environment to more affordable commercial products.