David E. Haines

Background Electrographic flow (EGF) mapping algorithms employing Horn-Schunck flow estimations can create temporospatial visualizations of atrial electrical wavefront propagations during atrial fibrillation (AF). Reproducible patterns of centrifugal EGF activation from discrete sites may represent sites of AF origin or sources. Our objectives were to assess the patterns and prevalence of AF sources using EGF mapping. Methods Unipolar electrograms were recorded for 1-minute with 64-pole basket catheters. Flow estimates were constructed by passing consecutive frames through an algorithm to learn and then compare typical wave direction patterns to describe flow-field evolution. During each 2-second segment, sites initiating centrifugal activation patterns were defined as AF sources. Maps of source location/activity duration were generated. Results The EGF method was applied to 405 prospective and retrospective patients with persistent or long-standing persistent AF. Mean age 62.5 years; mean LA size 54 mm; mean AF duration 4.6 years. EGF mapping found 6.6 ± 2.4 AF sources/patient (range 1 to 17). Distribution was 55% LA and 45% RA. Dominant sources (prevalence ≥20%) were demonstrated in 185 (45.7%) patients, but only 10.7% of all sources were dominant. While AF cycle length (CL) was not affected by source prevalence, CL variance significantly decreased as source prevalence increased. Conclusions Complex AF conduction patterns make ablation challenging, but EGF mapping enables detection and organization of time-dependent AF behaviors. Although many low prevalence sources are detected, they may not be clinically relevant, while higher prevalence sources seem to modulate AF. Recording durations of 1 minute facilitate source discrimination.

Background: Pulsed field ablation uses electrical pulses to cause nonthermal irreversible electroporation and induce cardiac cell death. Pulsed field ablation may have effectiveness comparable to traditional catheter ablation while preventing thermally mediated complications. Methods: The PULSED AF pivotal study (Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF) was a prospective, global, multicenter, nonrandomized, paired single-arm study in which patients with paroxysmal (n=150) or persistent (n=150) symptomatic atrial fibrillation (AF) refractory to class I or III antiarrhythmic drugs were treated with pulsed field ablation. All patients were monitored for 1 year using weekly and symptomatic transtelephonic monitoring; 3-, 6-, and 12-month ECGs; and 6- and 12-month 24-hour Holter monitoring. The primary effectiveness end point was freedom from a composite of acute procedural failure, arrhythmia recurrence, or antiarrhythmic escalation through 12 months, excluding a 3-month blanking period to allow recovery from the procedure. The primary safety end point was freedom from a composite of serious procedure- and device-related adverse events. Kaplan-Meier methods were used to evaluate the primary end points. Results: Pulsed field ablation was shown to be effective at 1 year in 66.2% (95% CI, 57.9 to 73.2) of patients with paroxysmal AF and 55.1% (95% CI, 46.7 to 62.7) of patients with persistent AF. The primary safety end point occurred in 1 patient (0.7%; 95% CI, 0.1 to 4.6) in both the paroxysmal and persistent AF cohorts. Conclusions: PULSED AF demonstrated a low rate of primary safety adverse events (0.7%) and provided effectiveness consistent with established ablation technologies using a novel irreversible electroporation energy to treat patients with AF. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04198701.

Ablation strategies remain poorly defined for persistent atrial fibrillation (AF) patients with recurrence despite intact pulmonary vein isolation (PVI). As the ability to perform durable PVI improves, the need for advanced mapping to identify extra-PV sources of AF becomes increasingly evident. Multiple mapping technologies attempt to localize these self-sustained triggers and/or drivers responsible for initiating and/or maintaining AF; however, current approaches suffer from technical limitations. Electrographic flow (EGF) mapping is a novel mapping method based on well-established principles of optical flow and fluid dynamics. It enables the full spatiotemporal reconstruction of organized wavefront propagation within the otherwise chaotic and disorganized electrical conduction of AF. Given the novelty of EGF mapping and relative unfamiliarity of most clinical electrophysiologists with the mathematical principles powering the EGF algorithm, this paper provides an in-depth explanation of the technical/mathematical foundations of EGF mapping and demonstrates clinical applications of EGF mapping data and analyses. Graphical abstract Starting with a 64-electrode basket catheter, unipolar EGMs are recorded and processed using an algorithm to visualize the electrographic flow and highlight the location of high prevalence AF “source” activity. The AF sources are agnostic to the specific mechanisms of source signal generation.

Background: Phrenic nerve palsy is a well-known complication of cardiac ablation, resulting from the application of direct thermal energy. Emerging pulsed field ablation (PFA) may reduce the risk of phrenic nerve injury but has not been well characterized. Methods: Accelerometers and continuous pacing were used during PFA deliveries in a porcine model. Acute dose response was established in a first experimental phase with ascending PFA intensity delivered to the phrenic nerve (n=12). In a second phase, nerves were targeted with a single ablation level to observe the effect of repetitive ablations on nerve function (n=4). A third chronic phase characterized assessed histopathology of nerves adjacent to ablated cardiac tissue (n=6). Results: Acutely, we observed a dose-dependent response in phrenic nerve function including reversible stunning (R ² =0.965, P <0.001). Furthermore, acute results demonstrated that phrenic nerve function responded to varying levels of PFA and catheter proximity placements, resulting in either: no effect, effect, or stunning. In the chronic study phase, successful isolation of superior vena cava at a dose not predicted to cause phrenic nerve dysfunction was associated with normal phrenic nerve function and normal phrenic nerve histopathology at 4 weeks. Conclusions: Proximity of the catheter to the phrenic nerve and the PFA dose level were critical for phrenic nerve response. Gross and histopathologic evaluation of phrenic nerves and diaphragms at a chronic time point yielded no injury. These results provide a basis for understanding the susceptibility and recovery of phrenic nerves in response to PFA and a need for appropriate caution in moving beyond animal models.

What is Different About Pulsed Field Ablation … Everything?David E. Haines, MDBeaumont Health System, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan, USAFunding: NoneDisclosures: Dr. Haines is a consultant for Ablacon, Inc., Affera, Inc., Biosense Webster, Inc., Boston Scientific Corporation, Inc., Medtronic, Inc., and Philips Healthcare, Inc. He has equity interest in Ablacon, Inc. and Affera, Inc.Corresponding author:David E. Haines, MD Director, Heart Rhythm Center Professor, Cardiovascular Medicine Oakland University William Beaumont School of Medicine 3601 West 13 Mile Road Royal Oak, MI 48073 248-898-4176 dhaines@beaumont.eduFrom the time of early preclinical reports of the efficacy, speed and safety of pulsed field ablation (PFA), the interventional electrophysiology community has been waiting in anxious anticipation for its clinical approval and release. As most people actively engaged in interventional electrophysiology know, PFA is the technology that creates myocardial lesions with trains of very high voltage pulses that are nanoseconds or microseconds in duration.1 This form of ablation is nonthermal, and cell injury/death is created by electroporation of the organelles and sarcolemmal membrane, with cell death occurring via apoptosis as well as other mechanisms.2 Because myocardial ablation is the result of an electrical field effect, electrode-tissue proximity is important but contact force is not. The physiological effect of acute PFA is striking in that there is immediate loss of electrical signal so that acute pulmonary vein isolation is achieved from a single shot catheter in under one second (figure 1). Preclinical animal studies have demonstrated effective chronic lesions that have been reliably transmural for atrial ablations.3 But the most compelling aspect of PFA is the apparent tissue selectivity of this energy form. At doses sufficient to create reliable transmural lesions in animals, there is little or no discernable injury to the esophagus, phrenic nerves, coronary arteries or distal pulmonary veins, in contrast to ablation with thermal techniques such as radiofrequency or cryoballoon ablation, where thermal collateral injury to contiguous structures can lead to substantial morbidity and death.4,5So, what is the catch? Is there any downside to PFA compared to other ablation technologies? The answer is that we do not know. Despite a substantial body of preclinical experience published to date, clinical outcomes with PFA are just starting to be reported. In this issue of theJournal , Neven et al describe the acute pathological effects of PFA in a swine model over the first 60 minutes and compare them to findings from chronic animals at 3 weeks and 3 months.6 For their study, they mostly employed a suction electrode for epicardial delivery (some lesions created with a circular catheter under blood) and delivered a single unipolar cathodal pulse of mostly 200 J (some dose ranging performed with chronic lesions between 30 – 200 J) at various sites on the right and left ventricles. Pathology on acute specimens was examined 0 to 60 minutes post ablation, and chronic specimens were examined after 3 weeks and 3 months. They reported that acute lesions showed contraction band necrosis and interstitial edema, and at >/= 3 weeks, there was sharply demarcated connective tissue that evolved into scar.What new insights have we gained from the present study that we can now apply to the burgeoning field of clinical PFA? Unfortunately, despite considerable effort put forth by these investigators, their results are not generalizable to the wider field of PFA. No study reporting outcomes using one proprietary PFA system will be necessarily applicable to results from a competing proprietary system. The field of catheter ablation has become accustomed to interchangeability of one RF generator or catheter for another. That is because the thermodynamics of electrical resistive heating of tissue is predictable, and there are limited operator parameters (power, time, contact force) and design parameters (electrode size, convective cooling) that affect tissue heating. The biological effects of hyperthermia are straightforward and reproducible; thus, it is possible for scientists and clinicians to compare experiences from one proprietary RFA system to another and draw some generalizable conclusions. 7 Not so with PFA. To paraphrase an old saying, “When you’ve seen one PFA system, you’ve seenone PFA system.” The operator-controlled parameters are familiar (energy level, catheter-tissue position), but the design parameter variations are dizzying and most importantly unknown to us . A precedent was set early in the development of this field that the PFA waveform was proprietary, and that the commercialized product was a “black box”. A few of the parameters that can be modulated by the manufacturer include pulse amplitude, pulse duration, unipolar/bipolar, monophasic/biphasic, interpulse delay, interphase delay, pulse train number, pulse train duration and more. For example, the waveform used by Neven et al. was a milliseconds duration, monophasic damped sine wave generated by an external defibrillator (Lifepak 9, Physio-Control, Inc; Redmond, WA) and delivered in a unipolar cathodal fashion to an indifferent dispersive skin electrode. In contrast, most PFA systems deliver pulses are nanoseconds to microseconds in duration with a range of variation of the other parameters listed above (figure 2). Thus, the outcomes from ablation with a proprietary PFA system cannot and should not be extrapolated to different proprietary systems that may have dramatically different waveforms that result in different procedural outcomes.One of the major unanswered questions in the field of PFA is what is the time course of clinical effect after energy delivery? The hope and anticipation has been that lesions created by PFA will...